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Comparison of the effectiveness of intravenous diltiazem and metoprolol in the management of rapid ventricular rate in atrial fibrillation.

To compare the effectiveness of intravenous (IV) diltiazem and metoprolol in the management of rapid ventricular rate in atrial fibrillation (AF).</AbstractText>This prospective, randomised study was conducted in the Emergency Department of the Uludag University Medical Faculty Hospital, Bursa, Turkey. Forty AF patients with a ventricular rate &gt; or = 120/minute and systolic blood pressure &gt; or = 95 mm Hg were included and randomised to receive IV diltiazem 0.25 mg/kg (maximum 25 mg) or metoprolol 0.15 mg/kg (maximum 10 mg) over 2 minutes. Blood pressures and heart rate were measured at 2, 5, 10, 15, and 20 minutes. Successful treatment was defined as fall in ventricular rate to below 100/minute or decrease in ventricular rate by 20% or return to sinus rhythm.</AbstractText>Between January 2000 and July 2002, 40 patients (18 men, 22 women) met the inclusion criteria. Of these 20 (8 men, 12 women; mean age 60.2 years, range 31-82) received diltiazem and 20 (10 men, 10 women; mean age 64.0 years, range 31-82) received metoprolol. The success rate at 20 minutes for diltiazem and metoprolol was 90% (n = 18) and 80% (n = 16), respectively. The success rate at 2 minutes was higher in the diltiazem group. The percentage decrease in ventricular rate was higher in the diltiazem group at each time interval. None of the patients had hypotension.</AbstractText>Both diltiazem and metoprolol were safe and effective for the management of rapid ventricular rate in AF. However, the rate control effect began earlier and the percentage decrease in ventricular rate was higher with diltiazem than with metoprolol.</AbstractText>

Psychological stress preceding idiopathic ventricular fibrillation.

Emotional stress is well established as a trigger of sudden death in the context of coronary heart disease (CHD), but its role in patients experiencing cardiac arrest with apparently normal hearts is unknown. This study sought to determine the role of psychosocial stress as a precipitant of cardiac arrest in patients with apparently normal hearts, so-called idiopathic ventricular fibrillation (IVF).</AbstractText>We interviewed 25 IVF survivors (12 men, 13 women) and 25 matched comparison patients regarding life events during the 6 months and 24 hours preceding the cardiac event. The comparison group consisted of patients with an acute myocardial infarction or angina pectoris requiring angioplasty but without cardiac arrest. Judges independently rated written summaries of these interviews for psychosocial stress at each time point on a three-point scale (low, moderate, severe).</AbstractText>During the 6 months before the cardiac event, 20 patients sustaining IVF had severe/moderate stress and five had low stress, whereas 10 comparison patients had severe/moderate stress and 15 had low stress (Fisher exact p = .008). During the preceding 24 hours, nine patients with IVF had severe/moderate stress and 16 had low stress, whereas two comparison patients had severe/moderate stress and 22 had low stress (Fisher exact p = .04) (one silent myocardial infarction could not be precisely dated).</AbstractText>These data suggest that psychosocial stress is playing a role in otherwise unexplained cardiac arrest.</AbstractText>

Cellular mechanisms underlying the development of catecholaminergic ventricular tachycardia.<Pagination><StartPage>2727</StartPage><EndPage>2733</EndPage><MedlinePgn>2727-33</MedlinePgn></Pagination><Abstract><AbstractText Label="BACKGROUND" NlmCategory="BACKGROUND">Mutations in the ryanodine 2 receptor (RyR2) gene have been identified in patients with catecholaminergic polymorphic ventricular tachycardia. We examined the cellular basis for the ECG features and arrhythmia mechanisms using low-dose caffeine to mimic the defective calcium homeostasis encountered under these conditions.</AbstractText><AbstractText Label="METHODS AND RESULTS" NlmCategory="RESULTS">A transmural ECG and action potentials were recorded simultaneously from epicardial, M, and endocardial cells in arterially perfused canine ventricular wedge preparations. Caffeine alone produced no change (10 to 100 micromol/L) or a slight abbreviation (300 micromol/L) of the QT interval and no change in transmural dispersion of repolarization. Isoproterenol (100 nmol/L) alone induced sustained monomorphic ventricular tachycardia (VT) that originated in the epicardium in 3 of 14 wedge preparations. Isoproterenol in the presence of caffeine (100 to 300 micromol/L) induced epicardial VT in 9 of 16 wedge preparations. Delayed afterdepolarization-induced triggered beats that originated in the epicardium were associated with an increased Tpeak-Tend interval and transmural dispersion of repolarization. Bidirectional VT developed in 11 of 16 wedge preparations as a consequence of alternation in the origin of ectopic activity between endocardial, M, and epicardial regions. Single extrastimuli delivered during sustained epicardial VT induced a rapid polymorphic VT/ventricular fibrillation (VF) in 3 of 9 wedges. Spontaneous polymorphic VT was observed in 3 of 16 preparations. Propranolol (1.0 micromol/L) or verapamil (1.0 micromol/L) completely suppressed ectopic activity that arose from the epicardium and prevented induction of polymorphic VT.</AbstractText><AbstractText Label="CONCLUSIONS" NlmCategory="CONCLUSIONS">Our data suggest delayed afterdepolarization-induced extrasystolic activity serves to trigger catecholamine-induced VT/VF under conditions of defective calcium handling. Epicardial origin of the ectopic beats increases transmural dispersion of repolarization, thus providing the substrate for the development of reentrant tachyarrhythmias that underlie rapid polymorphic VT/VF.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Nam</LastName><ForeName>Gi-Byoung</ForeName><Initials>GB</Initials><AffiliationInfo><Affiliation>Masonic Medical Research Laboratory, 2150 Bleecker St, Utica, NY 13501-1787, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Burashnikov</LastName><ForeName>Alexander</ForeName><Initials>A</Initials></Author><Author ValidYN="Y"><LastName>Antzelevitch</LastName><ForeName>Charles</ForeName><Initials>C</Initials></Author></AuthorList><Language>eng</Language><GrantList CompleteYN="Y"><Grant><GrantID>R01 HL047678</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant><Grant><GrantID>HL47678</GrantID><Acronym>HL</Acronym><Agency>NHLBI NIH HHS</Agency><Country>United States</Country></Grant></GrantList><PublicationTypeList><PublicationType UI="D016428">Journal Article</PublicationType><PublicationType UI="D052061">Research Support, N.I.H., Extramural</PublicationType><PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType><PublicationType UI="D013487">Research Support, U.S. Gov't, P.H.S.</PublicationType></PublicationTypeList><ArticleDate DateType="Electronic"><Year>2005</Year><Month>05</Month><Day>23</Day></ArticleDate></Article><MedlineJournalInfo><Country>United States</Country><MedlineTA>Circulation</MedlineTA><NlmUniqueID>0147763</NlmUniqueID><ISSNLinking>0009-7322</ISSNLinking></MedlineJournalInfo><ChemicalList><Chemical><RegistryNumber>0</RegistryNumber><NameOfSubstance UI="D002395">Catecholamines</NameOfSubstance></Chemical><Chemical><RegistryNumber>3G6A5W338E</RegistryNumber><NameOfSubstance UI="D002110">Caffeine</NameOfSubstance></Chemical><Chemical><RegistryNumber>L628TT009W</RegistryNumber><NameOfSubstance UI="D007545">Isoproterenol</NameOfSubstance></Chemical><Chemical><RegistryNumber>SY7Q814VUP</RegistryNumber><NameOfSubstance UI="D002118">Calcium</NameOfSubstance></Chemical></ChemicalList><CitationSubset>IM</CitationSubset><MeshHeadingList><MeshHeading><DescriptorName UI="D000200" MajorTopicYN="N">Action Potentials</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D000818" MajorTopicYN="N">Animals</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D002110" MajorTopicYN="N">Caffeine</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration &amp; dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002118" MajorTopicYN="N">Calcium</DescriptorName><QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D002395" MajorTopicYN="N">Catecholamines</DescriptorName><QualifierName UI="Q000502" MajorTopicYN="Y">physiology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D004195" MajorTopicYN="N">Disease Models, Animal</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004285" MajorTopicYN="N">Dogs</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004305" MajorTopicYN="N">Dose-Response Relationship, Drug</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004562" MajorTopicYN="N">Electrocardiography</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D004699" MajorTopicYN="N">Endocardium</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D007545" MajorTopicYN="N">Isoproterenol</DescriptorName><QualifierName UI="Q000008" MajorTopicYN="N">administration &amp; dosage</QualifierName><QualifierName UI="Q000494" MajorTopicYN="N">pharmacology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D008954" MajorTopicYN="N">Models, Biological</DescriptorName></MeshHeading><MeshHeading><DescriptorName UI="D010496" MajorTopicYN="N">Pericardium</DescriptorName><QualifierName UI="Q000503" MajorTopicYN="N">physiopathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D017180" MajorTopicYN="N">Tachycardia, Ventricular</DescriptorName><QualifierName UI="Q000209" MajorTopicYN="Y">etiology</QualifierName><QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName></MeshHeading><MeshHeading><DescriptorName UI="D018879" MajorTopicYN="N">Ventricular Premature Complexes</DescriptorName></MeshHeading></MeshHeadingList></MedlineCitation><PubmedData><History><PubMedPubDate PubStatus="pubmed"><Year>2005</Year><Month>5</Month><Day>25</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="medline"><Year>2006</Year><Month>1</Month><Day>25</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate><PubMedPubDate PubStatus="entrez"><Year>2005</Year><Month>5</Month><Day>25</Day><Hour>9</Hour><Minute>0</Minute></PubMedPubDate></History><PublicationStatus>ppublish</PublicationStatus><ArticleIdList><ArticleId IdType="pubmed">15911700</ArticleId><ArticleId IdType="mid">NIHMS10280</ArticleId><ArticleId IdType="pmc">PMC1474839</ArticleId><ArticleId IdType="doi">10.1161/CIRCULATIONAHA.104.479295</ArticleId><ArticleId IdType="pii">CIRCULATIONAHA.104.479295</ArticleId></ArticleIdList><ReferenceList><Reference><Citation>Leenhardt A, Lucet V, Denjoy I, et al. 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Atrial fibrillation (AF) is one of the most widely spread type of arrhythmias and is characterized by the high rate of disability and mortality among the patients of cardiological profile. Despite the significant achievements in heart rhythm disorders management, selection of the optimal tactics for AF treatment still remains a difficult task. Strategy for retrieval and maintenance of sinus rhythm with paroxysmal and persistent forms of AF is a priority among the patients under 65 with the absence of manifested structural changes of cardiac muscle. In the case of AF with severe symptoms, carrying out of efforts to retrieve sinus rhythm by means of pharmacological or electric cardioversions is possible. Permanent AF is characterized by unsuccessful efforts of retrieval and maintenance of sinus rhythm and requires effective monitoring of ventricular contractures and antithrombotic therapy.

New quantitative methods for evaluation of dynamic changes in QT interval on 24 hour Holter ECG recordings: QT interval in idiopathic ventricular fibrillation and long QT syndrome.

To introduce a nomogram of the normal QT interval at various heart rates measured from 24 hour Holter ECG recordings in healthy subjects with respect to age and sex and to use the nomogram to characterise dynamic changes in QT interval in patients with idiopathic ventricular fibrillation (IVF) and the long QT syndrome (LQT).</AbstractText>The study group consisted of 422 subjects: 249 healthy men ranging in age from 21-88 years (mean (SD) 47 (20) years) and 173 healthy women ranging in age from 21-85 years (47 (19) years). In addition, seven men with IVF ranging in age from 33-53 years (43 (9) years) and five women with LQT ranging in age from 20-55 years (37 (14) years) were studied. For each subject, QT interval and heart rate were determined automatically from 24 hour Holter ECG digital data-namely, QT interval was measured from signal averaged ECG waves obtained by averaging consecutive sinus beats during each 15 second period over 24 hours. Data were grouped and averaged at an interval of 5 beats/min for heart rates ranging from 46-120 beats/min.</AbstractText>In healthy subjects aged &lt; 50 years and &gt; or = 50 years QT intervals were longer in women than in men. QT intervals were longer in both men and women aged &gt; or = 50 years than in ages &lt; 50 years. From these findings a nomogram of QT interval at varying heart rates adjusted for age (younger group aged &lt; 50 years or older group aged &gt; or = 50 years) and sex was determined. In patients with IVF, QT intervals were significantly shorter at slower heart rates than normal values obtained from the nomogram. In patients with LQT, QT intervals were significantly longer at both faster and slower heart rates than normal values.</AbstractText>The nomogram of QT interval at varying heart rates adjusted for sex and age could be used to assess dynamic changes of QT interval of various pathological conditions. For example, patients with IVF had shorter QT interval at slower heart rates, a finding suggestive of arrhythmogenicity of this specific syndrome at night. Patients with LQT had prolonged QT interval at specific heart rate ranges depending on their genotype.</AbstractText>

Knockout of the neural and heart expressed gene HF-1b results in apical deficits of ventricular structure and activation.

Knockout of the neural and cardiac expressed transcription factor HF-1b causes electrophysiological abnormalities including fatal ventricular arrhythmias that occur with increasing frequency around the 4th week of postnatal life. This study addresses factors that may contribute to conduction disturbance in the ventricle of the HF-1b knockout mouse. Disruptions to gap junctional connexin40 (Cx40) have been reported in distal (i.e., apically located), but not proximal His-Purkinje conduction tissues of the HF-1b knockout mouse. This abnormality in myocardial Cx40 led us to address whether 4-week-old HF-1b knockout postnates display other disruptions to ventricular structure and function.</AbstractText>Western blotting and immunoconfocal quantification of Cx43 and coronary arteriole density and function were undertaken in the ventricle. Electrical activation was described by optical mapping.</AbstractText>Western blotting and immunoconfocal microscopy indicated that overall levels of Cx43 (p&lt;0.001) and percent of Cx43 localized in intercalated disks (p&lt;0.001) were significantly decreased in the ventricular myocardium of knockouts relative to wildtype littermate controls. Analysis of the reduction in Cx43 level by basal and apical territories revealed that the decrease was most pronounced in the lower, apical half of the ventricle of knockouts relative to controls (p&lt;0.001). Myocyte size also showed a significant decrease in the knockout, that was more marked within the apical half of the ventricle (p&lt;0.05). Optical recordings of ventricular activation indicated apically localized sectors of slowed conduction in knockout ventricles not occurring in controls that could be correlated directly to tissues showing reduced Cx43. These discrete sectors of abnormal conduction in the knockout heart were resolved following point stimulation of the ventricular epicardium and thus were not explained by dysfunction of the His-Purkinje system. To further probe base-to-apex abnormalities in the HF-1b knockout ventricle, we analyzed coronary arterial structure and function. These analyses indicated that relative to controls, the apical ventricular territory of the HF-1b knockout had reductions in the density of small resistance vessels (p&lt;0.01) and deficits in arterial function as assayed by bead perfusion (p&lt;0.01).</AbstractText>The HF-1b knockout ventricle displays abnormalities in Cx43 level, myocyte size, activation spread and coronary arterial structure and function. These abnormalities tend to be more pronounced in the apical territory of the ventricle and seem likely to be factors contributing to the pathological disturbance of cardiac conduction that characterizes the heart of the HF-1b knockout mouse.</AbstractText>

Endothelin receptor--a blockade decreases ventricular arrhythmias after myocardial infarction in rats.

Endothelin-1 (ET-1) production increases during acute myocardial infarction (MI) and may contribute to the genesis of ventricular tachycardia (VT) and ventricular fibrillation (VF). However, the antiarrhythmic effects of ET-1 receptor blockade, examined shortly after MI, have been debated. In the present study, we examined the effects of such treatment on VT/VF during the first 24 h post-MI.</AbstractText>Thirty-five Wistar rats (223+/-22 g) were randomly allocated to either the ET-1 receptor-A (ETA) antagonist BQ-123 (0.4 mg/kg, BQ-123 group, n=17), or normal saline (control group, n=18) and were subjected to coronary artery ligation. A single-lead electrocardiogram was continuously recorded for 24 h post-MI, using an implanted telemetry system, and episodes of VT/VF were analyzed. Monophasic action potential (MAP) recordings were obtained from the left (LV) and right (RV) ventricular epicardium at baseline, 5 min after treatment and 24 h post-MI.</AbstractText>There were 15.94+/-19.35 episodes/h/rat of VT/VF in the control group and 1.66+/-2.22 in the BQ-123 group (p=0.010), resulting in a lower (p=0.030) arrhythmic mortality in treated animals. The mean episode duration was 7.40+/-7.16 s for the control group and 2.30+/-1.37 s for the BQ-123 group (p=0.011). The maximum decrease in VT/VF was observed during the 1st, 5th and 6th hours post-MI. In the control group, LV MAP duration increased 24 h post-MI, displaying an increased beat-to-beat variation, but remained unchanged in the BQ-123 group.</AbstractText>Acute ETA blockade reduces the incidence of VT/V F during the first 24-h post-MI in the rat, through a decrease in the dispersion of repolarization.</AbstractText>

Nitric oxide involvement in the delayed antiarrhythmic effect of treadmill exercise in dogs.

We have shown previously that a single period of treadmill exercise in dogs protects the heart against the severe ventricular arrhythmias that arise when a major (anterior descending) branch of the left coronary artery is occluded following anaesthesia 24 h later. This protection is aminoguanidine sensitive, suggesting a role for nitric oxide (NO) in this exercise-induced delayed antiarrhythmic effect. The present study has further examined the possible role of NO as a mediator and/or as a trigger using the selective induced (iNOS) inhibitor S-(2-aminoethyl)-methyl-isothiourea (AEST) and the specific but not selective nitric oxide synthase inhibitor N(omega)-nitro-L-arginine-methyl-ester (L-NAME). Exercise markedly reduced the severity of ischaemia and reperfusion-induced ventricular arrhythmias 24 h later. Thus, only one of the dogs (8%) so exercised fibrillated on occlusion (contrast 46% in the control, non-exercised dogs; P&lt;0.05) and the marked changes in the inhomogeneity of electrical activation that occur in the ischaemic region following occlusion were much reduced (P&lt;0.05 compared to controls). This delayed exercise-induced cardioprotection was significantly attenuated by the nitric oxide synthase (NOS) inhibitors L-NAME, given prior to the exercise protocol and by AEST given prior to the coronary artery occlusion. For example, survival from the ischaemia-reperfusion insult was 54% in the exercise dogs, 0% in the controls and 14% in those dogs given a NOS inhibitor. We conclude that nitric oxide (NO) is both the trigger and the mediator of this delayed protection against ischaemia and reperfusion-induced arrhythmias.

Late pulmonary valve implantation after repair of tetralogy of Fallot.

Ten cases of elective late pulmonary valve implantation after repair of tetralogy of Fallot were reviewed. The interval after initial repair ranged from 1.5 to 43 years (mean, 20.0 +/- 12.3 years). There was no hospital mortality or late death during a mean follow-up of 12.5 months. Preoperatively, 9 patients were in New York Heart Association functional class III-IV; after pulmonary valve implantation, all 10 patients were in class I-II (average improvement, 1.7 classes). Left ventricular ejection fraction improved significantly (from 62.1% +/- 4.7% to 70.2% +/- 4.9%), as did fractional shortening (from 34.0% +/- 5.0% to 40.0% +/- 4.2%). Right ventricular diameter decreased significantly (from 32.3 +/- 7.5 to 24.4 +/- 5.4 mm). QRS duration decreased significantly (155.2 +/- 27.1 vs. 140.0 +/- 21.2 msec), but there was no significant difference in QT interval (460.9 +/- 29.6 vs. 451.9 +/- 50.6 msec). Hospital stay was 4-7 days. One patient had preoperative ventricular fibrillation requiring resuscitation and an implantable cardiac defibrillator; another needed a defibrillator at the time of pulmonary valve implantation, because of ventricular arrhythmias. It was concluded that late pulmonary valve implantation after tetralogy of Fallot repair had significant benefits and carried low operative risk.

Teaching principles of cardiovascular function in a medical student laboratory.

We describe an animal laboratory using anesthetized swine to demonstrate the regulation of arterial blood pressure to second-year medical students at Saint Louis University School of Medicine (St. Louis, MO). The laboratory is designed to illustrate basic pharmacological and physiological concepts learned in the classroom. The specific learning objectives covered in this lab include maintenance of anesthesia, basic surgical technique including cannulation of blood vessels, understanding the measurement and significance of basic physiological parameters, premortem examination of in situ heart and lungs, direct cardiac massage and induction of ventricular fibrillation, understanding the fundamentals of the baroreceptor reflex, and cardiovascular responses to various pharmacological agents. Pharmacologic agents used include epinephrine, norepinephrine, isoproterenol, atropine, prazosin, propranolol, acetylcholine, nitroprusside, and angiotensin II. The laboratory demonstration has proven effective in reinforcing the fundamental principles of cardiovascular physiology and autonomic pharmacology. By the completion of this experiment, students are expected to be able to: 1) describe the basics of maintenance of anesthesia in a live animal; 2) describe basic surgical technique; 3) observe the procedure for proper cannulation of blood vessels; 4) describe the proper method of controlling hemorrhage from a bleeding source; 5) describe the measurement and recording of four physiological parameters: mean arterial pressure from a pressure transducer, heart rate from an ECG, hindquarters resistance from Doppler measurement of femoral arterial blood flow, and cardiac contractility by calculating dP/dt from left ventricular pressure measured with a Millar transducer; 6) perform a premortem exam of the heart and lungs and appreciate the in situ cardiothoracic anatomy of the living animal; 7) assist in the induction of ventricular fibrillation and perform direct cardiac massage; 8) characterize the autonomic responses activated by the baroreceptor reflex; 9) describe the effects of the adrenergic agonists epinephrine, norepinephrine, and isoproterenol on cardiovascular parameters and construct a dose response curve for each agent; 10) describe the effects of the adrenergic antagonists propranolol and prazosin on cardiovascular parameters and explain how they affect cardiovascular responses to adrenergic agonists; 11) describe the difference between endothelium-dependent and endothelium-independent vasodilation using acetylcholine, nitroprusside, and atropine; 12) observe the pressor response of angiotensin II and describe why this response is not blocked by pretreatment with prazosin; and 13) participate in the collection and analysis of experimental data and the presentation of results.

Does atrial fibrillation in elderly patients with chronic heart failure limit the efficacy of carvedilol? Suggestions from an observational study.

No clinical investigation provided any information about a possible influence of atrial fibrillation on the response to beta-blocker therapy in elderly patients with chronic heart failure (CHF). The aim of this study was to observe carvedilol effects in a cohort of patients &gt; 70 years of age with CHF due to left ventricular dysfunction and with chronic atrial fibrillation.</AbstractText>An observational, 12-month prospective clinical and echocardiographic study was carried out on 240 patients &gt; 70 years of age with heart failure due to systolic dysfunction, 64 of whom with atrial fibrillation.</AbstractText>After 1 year of beta-blocker treatment, patients with atrial fibrillation and those in sinus rhythm showed similar benefits, in terms of symptomatic improvement (deltaNYHA -0.44 if atrial fibrillation vs -0.57 if sinus rhythm, p = NS), reduction of events (death + hospitalizations -38 vs -15%), recovery of cardiac function (left ventricular ejection fraction delta +8.8 vs +9.4%, p = NS; left ventricular end-diastolic volume delta -17.2 vs -12.5 ml, p = NS), and reduction in mitral regurgitation (delta -042 vs -0.57, p = NS). No difference was found between the two study groups regarding left ventricular end-diastolic volume reduction (12% in atrial fibrillation patients and 18% in sinus rhythm patients, p = NS) and prevalence of the "reverse remodeling" phenomenon (22 and 21%, respectively, p = NS).</AbstractText>In CHF patients &gt; 70 years of age, beta-adrenergic blockade was shown to be equally effective in improving symptoms and left ventricular geometry and function in patients with atrial fibrillation or in sinus rhythm, without any adjunctive sign of long-term clinical deterioration.</AbstractText>

Adrenal adenoma presenting with ventricular fibrillation.

We report the case of a 58-year-old man who presented with ventricular fibrillation. The serum potassium level was 1.8 mEq/L after successful cardioversion. Coronary angiography showed a normal heart with no structural defects, but 12-lead electrocardiography showed indications of left ventricular hypertrophy, which was confirmed by echocardiography. Laboratory examinations showed a suppressed renin level and an elevated serum aldosterone level. Computed tomography then revealed a right adrenal mass. The patient was treated with surgical resection of the adenoma. This case emphasizes the importance of meticulous search for secondary causes of hypertension, before the occurrence of serious complications.

Effects of a novel cyclohexane dicarboximide derivative, ST-6, on reperfusion-induced arrhythmia in rats.

The present study was designed to determine whether a novel cyclohexane dicarboximide derivative, ST-6, 2-[4-[4-(chlorophenyl)-4-hydroxy-1-piperidinyl]butyl]hexahydro-1H-isoindol-1,3(2H)-dione, prevents reperfusion-induced ventricular arrhythmias. Pentobarbital-anesthetized rats were subjected to left coronary artery occlusion for 4 min followed by 4-min reperfusion, and the incidence of their ventricular arrhythmias was examined. The coronary occlusion of control rats induced ventricular tachycardia and fibrillation, eventually leading to sudden death. The intravenous injection of 0.1 to 2 mg/kg ST-6 prior to the occlusion resulted in a dose-dependent suppression of the ventricular arrhythmias. The suppression of ventricular fibrillation was also observed on the intraperitoneal and intradoudenal administration of 2 to 10 mg/kg ST-6 15 min prior to coronary occlusion. Antiarrhythmic effects of this agent (0.5 mg/kg per min) were compared with those of other antiarrhythmic agents including lidocaine (0.1 mg/kg per min), sematilide (0.3 mg/kg per min), and diltiazem (0.5 mg/kg per min) by administrating the agents from 1 min after the coronary occlusion to the end of 4-min reperfusion. Antiarrhythmic effects of ST-6 were similar in degree to those of lidocaine and diltiazem, whereas no significant prevention by sematilide was seen. The results suggest that ST-6 may be capable of suppressing reperfusion-induced arrhythmias following oral or intravenous administration.

The importance of increased interatrial septal thickness in patients with atrial fibrillation: a transesophageal echocardiographic study.

Histological studies in animal models have showed that extensive atrial fibrosis or fatty deposition as a result of loss of atrial cardiomyocytes increases the propensity to develop atrial fibrillation (AF). Although several reports have suggested that AF in humans may be a consequence of these mechanisms, no study has correlated the presence of AF with interatrial septal thickness (IAST).</AbstractText>Accordingly, we conducted a prospective analysis in 150 consecutive patients referred for transesophageal echocardiography (TEE) for numerous medical reasons. A total of 105 patients (mean age 62 +/- 14 years) who met inclusion and exclusion criteria were included for analysis. Pertinent demographics, echocardiographic chamber dimensions, left ventricular ejection fraction (LVEF), color flow, and spectral Doppler analysis, as well as IAST measured in both systole (S) and diastole (D) were obtained.</AbstractText>When patients with a documented history of AF were compared to patients without documented AF, no statistical difference was noted in terms of patients' height, weight, IVS thickness, or LVEF. Patients with AF had a significantly larger left and right atrial dimensions (P &lt; 0.001), lower left atrial appendage emptying velocities (P &lt; 0.002), and pulmonary vein systolic Doppler signal (P &lt; 0.01). The IAST in systole in patients with AF was 0.75 +/- 0.27 cm versus 0.60 +/- 0.16 cm in patients without AF (P &lt; 0.006) while the IAST in diastole was 0.61 +/- 0.22 cm versus 0.49 +/- 0.12 cm, respectively (P &lt; 0.009). However, no statistical difference was noted between IAST in either systole (P &lt; 0.8) or diastole (P &lt; 0.8) among patients with AF based on the duration of this arrhythmia.</AbstractText>The results of this prospective TEE study show a statistically significant increase in IAST with the presence of AF independent of patient's age, height, weight, and the degree of IVS thickness. In addition, since no significant valvular abnormalities or compromise in left ventricular systolic function were present, the increase in IAST in patients with AF then suggest possible changes in the material properties of the atrial wall, easily identified by TEE on the interatrial septum, either as a cause or as a result of AF. Since no correlation was found between the degree of IAST and the duration of AF, the presence of IAST not only might identify patients with a higher propensity to have or develop this atrial arrhythmia; but also be a surrogate marker of changes within the components of the atrial wall in AF.</AbstractText>

Stunning of the left atrium after conversion of atrial fibrillation: predictor for maintenance of sinus rhythm?

Recurrence of atrial fibrillation (AF) after cardioversion (CV) to sinus rhythm (SR) is determined by various clinical and echocardiographic parameters. The aim of this study was to determine the value of mitral inflow A-wave velocity, performed at 24 hours after CV in estimation of AF recurrence. The study group consisted of 187 consecutive patients with nonvalvular atrial fibrillation, who had been cardioverted to SR from 1998 to 2000. Transthoracic echocardiography was performed in all cases recruited for the study 24 hours after CV. Left atrial (LA) diameter, left ventricular ejection fraction, and mitral inflow A-wave velocity were measured. The patients were evaluated in five groups according to their recurrence time (&lt;30 days, 31-90 days, 91-180 days, 181-365 days, and &gt;365 days). Maintenance of SR was determined to have a negative linear correlation with age (r =-0.97, P = 0.006), LA diameter (r =-0.93, P = 0.02), and AF duration (r =-0.93, P = 0.02), while having a positive linear correlation with mitral inflow A-wave velocity (r = 0.96, P = 0.008). In the maintenance of sinus rhythm, age, LA diameter, and AF duration were not affected from the method of CV, while mitral inflow A-wave velocity was found to be affected with the method of CV. No relationship was determined between mitral inflow A-wave velocity and the maintenance of sinus rhythm in those performed electrical cardioversion, while frequency of recurrence was found to be higher in those with slow mitral inflow A-wave velocity who were performed pharmacological cardioversion (r = 0.89, P = 0.004). In conclusion, age, duration of AF, LA diameter, and the mitral inflow A-wave velocity can be used to predict the maintenance of SR after CV.

Lone atrial fibrillation associated with creatine monohydrate supplementation.

Atrial fibrillation in young patients without structural heart disease is rare. Therefore, when the arrhythmia is present in this population, reversible causes must be identified and resolved. Thyroid disorders, illicit drug or stimulant use, and acute alcohol intoxication are among these causes. We report the case of a 30-year-old Caucasian man who came to the emergency department in atrial fibrillation with rapid ventricular response. His medical history was unremarkable, except for minor fractures of the fingers and foot. Thyroid-stimulating hormone, magnesium, and potassium levels were within normal limits, urine drug screen was negative, and alcohol use was denied. However, when the patient was questioned about use of herbal products and supplements, the use of creatine monohydrate was revealed. The patient was admitted to the hospital, anticoagulated with unfractionated heparin, and given intravenous diltiazem for rate control and intravenous amiodarone for rate and rhythm control. When discharged less than 24 hours later, he was receiving metoprolol and aspirin, with follow-up plans for echocardiography and nuclear imaging to assess perfusion. Exogenous creatine is used by athletes to theoretically improve exercise performance. Vegetarians may also take creatine to replace what they are not consuming from meat, fish, and other animal products. Previous anecdotal reports have linked creatine to the development of arrhythmia. Clinicians must be diligent when interviewing patients about their drug therapy histories and include questions about their use of herbal products and dietary supplements. In addition, it is important to report adverse effects associated with frequently consumed supplements and herbal products to the Food and Drug Administration and in the literature.

Predictability of O2 consumption from contractility and mechanical energy of absolute arrhythmic beats in canine heart.

Left ventricular (LV) O2 consumption (V(O2)) per minute is measurable for both regular and arrhythmic beats. LV V(O2) per beat can then be obtained as V(O2) per minute minute divided by heart rate per minute minute for regular beats, but not for arrhythmic beats. We have established that V(O2) of a regular stable beat is predictable by V(O2) = a PVA + b E(max) + c, where PVA is the systolic pressure-volume area as a measure of the total mechanical energy of an individual contraction and E(max) is the end-systolic maximum elastance as an index of ventricular contractility of the contraction. Furthermore, a is the O2 cost of PVA, b is the O2 cost of E(max), and c is the basal metabolic V(O2) per beat. We considered it theoretically reasonable to expect that the same formula could also predict LV V(O2) of individual arrhythmic beats from their respective PVA and E(max) with the same a, b, and c. We therefore applied this formula to the PVA - Emax data of individual arrhythmic beats under electrically induced atrial fibrillation (AF) in six canine in situ hearts. We found that the predicted V(O2) of individual arrhythmic beats highly correlated linearly with either their V(O2) (r = 0.96 +/- 0.01) or E(max) (0.97 +/- 0.03) while both also highly correlated linearly with each other (0.88 +/- 0.04). This suggests that the above formula may be used to predict LV Vo2 of absolute arrhythmic beats from their Emax and PVA under AF.

Brugada syndrome: report of the second consensus conference.

Since its introduction as a clinical entity in 1992, the Brugada syndrome has progressed from being a rare disease to one that is second only to automobile accidents as a cause of death among young adults in some countries. Electrocardiographically characterized by a distinct ST-segment elevation in the right precordial leads, the syndrome is associated with a high risk for sudden cardiac death in young and otherwise healthy adults, and less frequently in infants and children. Patients with a spontaneously appearing Brugada ECG have a high risk for sudden arrhythmic death secondary to ventricular tachycardia/fibrillation. The ECG manifestations of Brugada syndrome are often dynamic or concealed and may be unmasked or modulated by sodium channel blockers, a febrile state, vagotonic agents, alpha-adrenergic agonists, beta-adrenergic blockers, tricyclic or tetracyclic antidepressants, a combination of glucose and insulin, hypo- and hyperkalemia, hypercalcemia, and alcohol and cocaine toxicity. In recent years, an exponential rise in the number of reported cases and a striking proliferation of articles defining the clinical, genetic, cellular, ionic, and molecular aspects of the disease have occurred. The report of the first consensus conference, published in 2002, focused on diagnostic criteria. The present report, which emanated from the second consensus conference held in September 2003, elaborates further on the diagnostic criteria and examines risk stratification schemes and device and pharmacological approaches to therapy on the basis of the available clinical and basic science data.

Repolarization dynamics in patients with idiopathic ventricular fibrillation: pharmacological therapy with bepridil and disopyramide.

The electrocardiographic parameters relating occurrence of ventricular fibrillation (VF) episodes in patients with idiopathic VF (IVF) are still unknown. The aim of this study was to clarify efficacy of pharmacological therapy in patients with IVF with respect to repolarization dynamics. The study group consisted of 8 men (age 43.6 +/- 9.1 years) with IVF (Brugada type 5 patients, prominent J wave in the inferior leads 3 patients) who had documented spontaneous episodes of VF, 7 of whom had implantable cardioverter defibrillators. The relation between QT and RR interval was analyzed from 24-hour Holter ECG using an automatic analyzing system before and after pharmacological therapy (bepridil 5 and disopyramide 3). From QT-RR linear regression lines, QT intervals were determined at RR intervals of 0.6 second [QT(0.6)], 1.0 second [QT(1.0)], and 1.2 seconds [QT(1.2)]. Pharmacological therapy increased the slope of QT-RR regression line from 0.105 +/- 0.020 to 0.144 +/- 0.037 (P &lt; 0.05). Accordingly, QT(1.0) and QT(1.2) became longer after drug therapy [QT(1.0), 0.382 +/- 0.016 seconds vs 0.414 +/- 0.016 seconds (P &lt; 0.01); QT(1.2), 0.403 +/- 0.017 seconds vs 0.442 +/- 0.021 seconds (P &lt; 0.01)]. However, QT(0.6) did not change after drug administration. Before drug therapy the average episodes of VF were 5.5 +/- 5.8 (range 1 to 17) during the observation period of 19.3 +/- 17.6 months (range 6 to 60 months). After drug therapy, 6 patients had no episode of VF for 24 to 120 months (66.0 +/- 38.5 months). Two patients had a single episode of VF for 12- and 96-month follow-ups. Pharmacological therapy decreased the frequency of VF episodes in association with prolongation of QT intervals at slower heart rates. Not only J wave and ST elevation but also shorter QT intervals at slower heart rates may represent an electrophysiological substrate for development of VF episodes in these specific IVF patients.

[Protective effects of losartan against myocardial ischemic reperfusion in intact canine].

To evaluate the protective effect of losartan, an angiotensin II type 1 (AT1) receptor antagonist, against myocardial ischemic reperfusion in intact canine.</AbstractText>Sixteen dogs were divided into model group(n=8) with left anterior descending coronary artery occlusion for 30 min followed by reperfusion for 30 min and losartan group (n=8) with 5 mg/(kg x d) intragastric losartan administration for 2 weeks before the ischemic-reperfusion model establishment. Monophasic action potential recording technique was employed to observe the incidence of early after depolarization (EAD) and reperfusion arrhythmias.</AbstractText>In the model group, 5 dogs (62.5%) developed EAD and reperfusion arrhythmia while 3 (37.5%) developed the symptoms in losartan group, showing significant difference between the two groups (P&lt;0.05). No ventricular tachycardia or ventricular fibrillation was observed in losartan group (P&lt;0.01).</AbstractText>Losartan can suppress the occurrence of EAD during reperfusion following myocardial ischemia to reduce the incidence of reperfusion arrhythmias, suggesting its protective effect against myocardial ischemic injury.</AbstractText>

Effects of ventricular rate and regularity on the velocity and magnitude of left atrial appendage flow in atrial fibrillation.

To prospectively determine whether ventricular rate and regularity are significant determinants of the velocity and magnitude of left atrial appendage (LAA) flow.</AbstractText>12 patients with atrial fibrillation (AF), high degree atrioventricular block, and indwelling permanent pacemakers were studied.</AbstractText>Cardiology department of a tertiary referral centre.</AbstractText>Pacing was triggered by an external programmable transcutaneous device. Patients were paced at 60, 120, and 150 beats/min in both regular and irregular rhythm. LAA flow velocity and magnitude were assessed with transoesophageal Doppler echocardiography.</AbstractText>Peak and mean LAA inflow and outflow velocity, and time-velocity interval (TVI) of LAA flow.</AbstractText>Increasing ventricular rate was associated with significantly lower peak inflow (p &lt; 0.01), peak outflow (p &lt; 0.05), mean inflow (p &lt; 0.01), and mean outflow (p &lt; 0.05) velocities and with a lower TVI of LAA filling and emptying velocities (p &lt; 0.01). This effect was noted at rates of 60 beats/min compared with both 120 and 150 beats/min. At a pacing rate of 120 beats/min there was a significantly higher total TVI when pacing at a regular than at an irregular rhythm (40.16 (14.6) cm v 30.74 (10.9) cm, p &lt; 0.05).</AbstractText>In this study, LAA filling velocities in patients in AF were significantly influenced by paced ventricular rate and to a much lesser extent ventricular rhythm. These results suggest that rapid ventricular rates may predispose to stasis in the LAA in AF.</AbstractText>

Effects of congestive heart failure on plasma von Willebrand factor and soluble P-selectin concentrations in patients with non-valvar atrial fibrillation.

To examine further the relations of plasma von Willebrand factor (vWf, an index of endothelial damage and dysfunction) and soluble P-selectin (sP-sel, an index of platelet activation) concentrations to the presence and onset of clinical congestive heart failure (CHF) and the degree of left ventricular (LV) dysfunction in patients taking part in the SPAF (stroke prevention in atrial fibrillation) study.</AbstractText>Plasma concentrations of vWf and sP-sel were measured by enzyme linked immunosorbent assay (ELISA) in 1321 participants in the SPAF III study and related to the presence and onset of clinical CHF, as well as echocardiographic findings. Of the 1321 patients with atrial fibrillation (AF), 331 (25%) had a documented history of clinical heart failure, of which 168 cases were related to a new or recurrent episode of acute decompensated heart failure occurring within the preceding three months.</AbstractText>Mean plasma vWf was higher among patients with AF and CHF (154 (29) v 144 (31) IU/dl, p &lt; 0.001), particularly those with acute or recent decompensated symptoms. Patients with severe LV dysfunction on two dimensional echocardiography and low fractional shortening also had significantly higher vWf concentrations than those with no LV dysfunction. CHF patients with clinical features--with (156 (28) IU/dl) and without (152 (31) IU/dl) LV dysfunction--also had higher mean vWf concentrations than patients with asymptomatic LV dysfunction (146 (31) IU/dl, p &lt; 0.001). The presence of mitral regurgitation in CHF was associated with lower vWf concentrations. Plasma sP-sel concentrations were not affected by presence, onset, or severity of heart failure.</AbstractText>CHF may contribute to hypercoagulability and thrombotic risk in AF through increased endothelial damage and dysfunction. Patients with acute or recent decompensated features have the highest degree of endothelial damage and dysfunction. The presence of CHF clinical features was an important determinant of plasma vWf concentrations.</AbstractText>

Increased risk of heart failure as a consequence of perioperative myocardial injury after coronary artery bypass grafting.

To analyse the relation between perioperative myocardial injury (PMI) and the risk of subsequent heart failure after coronary artery bypass grafting (CABG).</AbstractText>Clinical data were documented prospectively in all patients and stored in a computer. All hospital readmissions were identified and the registered primary diagnoses were analysed. Survival information on all patients was obtained by use of combined registers. The study was carried out at the cardiac surgical referral centre of University Hospital, Uppsala, Sweden.</AbstractText>7493 patients discharged alive after primary CABG between 1987 and 1996 were followed up until the first hospital readmission for heart failure, death, or 31 December 1996 was reached.</AbstractText>Hospital readmission for heart failure or late mortality.</AbstractText>Of the patients studied 576 (7.7%) were readmitted for heart failure. Actuarial freedom from readmission for heart failure after four years was 93%, and after seven years, 89%. Of the 576 patients, 114 (20%) had had PMI, which increased the risk of heart failure independently (hazard ratio (HR) 2.3, 95% confidence interval (CI) 1.8 to 2.8). Increased age, female sex, diabetes, previous myocardial infarction, dyspnoea, preoperative atrial fibrillation, left ventricular dysfunction, and triple vessel disease were independent risk factors for heart failure. The use of an internal mammary artery decreased the risk. PMI implied increased mortality (HR 1.4, 95% CI 1.1 to 1.8). Late mortality was greatly increased in patients readmitted for heart failure.</AbstractText>PMI increased the risk of heart failure and late death after CABG, and heart failure had a notable adverse effect on late survival.</AbstractText>

Specific therapy based on the genotype and cellular mechanism in inherited cardiac arrhythmias. Long QT syndrome and Brugada syndrome.

Seven forms of congenital long QT syndrome (LQTS) caused by mutations in ion channel genes have been identified. Genotype-phenotype correlation in clinical and experimental studies involving arterially-perfused canine left ventricular wedges suggest that beta-blockers are protective in LQT1, less so in LQT2, but not protective in LQT3. A class IB sodium channel blocker, mexiletine, is most effective in abbreviating QT interval in LQT3, but effectively reduces transmural dispersion of repolarization (TDR) and prevents the development of Torsade de Pointes (TdP) in all 3 models, suggesting its potential as an adjunctive therapy in LQT1 and LQT2. High concentrations of intravenous nicorandil, a potassium channel opener, have been shown to be capable of decreasing QT and TDR, and preventing TdP in LQT1 and LQT2 but not in LQT3. The calcium channel blocker, verapamil, has also been suggested as adjunctive therapy for LQT1, LQT2 and possibly LQT3. Experimental data using right ventricular wedge preparations suggest that a prominent transient outward current (I(to))-mediated action potential (AP) notch and a loss of AP dome in epicardium, but not in endocardium, give rise to a transmural voltage gradient, resulting in ST segment elevation and the induction of ventricular fibrillation (VF), characteristics of the Brugada syndrome. Since the maintenance of the AP dome is determined by the balance of currents active at the end of phase 1 of the AP, any intervention that reduces the outward current or boosts inward current at the end of phase 1 may normalize the ST segment elevation and suppress VF. Such interventions are candidates for pharmacological therapy of the Brugada syndrome. The infusion of isoproterenol, a beta-adrenergic stimulant, strongly augments L-type calcium current (I(Ca-L)), and is the first choice for suppressing electrical storms associated with Brugada syndrome. Quinidine, by virtue of its actions to block I(to), has been proposed as adjunctive therapy, with an implantable cardioverter defibrillator as backup. Oral denopamine, atropine or cilostazol all increase ICa-L, and for this reason may be effective in reducing episodes of VF.

Bedside risk stratification after acute myocardial infarction: prospective evaluation of the use of heart rate and left ventricular function.

This study evaluated the predictive power of heart rate (HR) assessed from the standard 12-lead electrocardiogram (ECG) or from Holter recordings for future mortality and arrhythmic events in survivors of acute myocardial infarction (AMI).</AbstractText>Data from 432 consecutive survivors of AMI (343 men, 89 women; mean [SD] age, 58 [11] years) were analyzed. Heart rate was assessed from a standard 12-lead ECG and from 24-hour Holter recordings obtained at hospital discharge. In addition, left ventricular ejection fraction (LVEF) was noninvasively determined. The study end point was prospectively defined as a composite end point comprising mortality and arrhythmic events (ie, sudden death, resuscitated ventricular fibrillation, sustained ventricular tachycardia). Patients were followed for an average (SD) of 41 (25) months.</AbstractText>Patient age, LVEF, and HR were univariate risk predictors of event-free survival. Multivariate analysis by means of a stepwise regression analysis revealed LVEF ( chi2 11.4, P = .0007), age ( chi 2 9.2, P = .02), and HR assessed from the standard 12-lead ECG ( chi2 7.1, P = .008) as independent risk parameters.</AbstractText>Bedside risk stratification of survivors of AMI is feasible using simple parameters such as age, LVEF, and HR.</AbstractText>

A teenager with angiographically normal epicardial coronary arteries and acute myocardial infarction after butane inhalation.

The most common cause of death among volatile substance abusers is sudden cardiac death. To the best of our knowledge, butane-induced myocardial infarction is a rare presentation among teenagers. We report on a 14-year-old male student who sustained cardiopulmonary arrest after sniffing seven canisters of butane. He was found to have extensive anterior myocardial infarction complicated by ventricular fibrillation. Cardiac catheterization revealed patent coronary arteries with severe anterolateral and apical left ventricular wall hypokinesia. We assume that cardiac complications after butane inhalations may partly be secondary to intense coronary artery spasm on the basis of the clinical and laboratory findings. This assumption may have major therapeutic implications in this patient population.

Performance of first responders in simulated cardiac arrests.

Survival of in-hospital cardiac arrests depends more on first responders than on cardiac arrest teams. The objective of this study was to determine the adherence to algorithms of cardiopulmonary resuscitation of first responders in simulated cardiac arrests in intensive care. A second objective was to assess the effect of the early vs. late availability of a physician on the performance of nurse-based teams acting as first responders.</AbstractText>Prospective study.</AbstractText>Patient simulator in a tertiary level intensive care unit.</AbstractText>A total of 20 teams consisting of three registered nurses and one resident each.</AbstractText>A simulated witnessed cardiac arrest due to ventricular fibrillation occurred in the presence of one nurse while the remaining two nurses could be called to help. Depending on the time of the residents' arrival, teams were classified as "early" (median arrival 50 secs after the onset of the arrest) or "late" (median arrival 150 secs after the onset of the arrest).</AbstractText>In all teams, the recognition of the arrest and the calling for help occurred in a timely fashion. However, a median of 85 secs (interquartile range [IQ], 130 secs) elapsed until the start of cardiac massage and 100 secs (IQ, 45 secs) to the first defibrillation. Once commenced, cardiac massage and mask ventilation were carried out during 61% (IQ, 33%) and 77% (IQ, 23%) of the possible time only. Delays and interruptions were generally not recalled by the participants. Compared with teams with late arriving residents, teams with early arriving residents administered more countershocks: 4.5 (IQ, 2) vs. 3.5 (IQ, 1.5; p = .026).</AbstractText>First responders in intensive care often failed to build a team structure that ensured timely, effective, monitored, and ongoing team activity. The early availability of a physician increased the number of countershocks administered. Self-reporting is unsuitable to reliably assess the quality of cardiopulmonary resuscitation.</AbstractText>

The effect of magnesium sulfate on action potential duration and cardiac arrhythmias.

To evaluate the electrophysiologic and antiarrhythmic effects, Mg was infused at 15 mg/h (n = 5) or an equal volume of saline (1.2 mL/h) (n = 5) and electrocardiogram and action potential duration (APD) recorded every 15 minutes. Rats were anesthetized with 70 mg/kg pentobarbital intraperitoneally. Mg increased QT 15 +/- 6% on average compared with 1 +/- 4 for saline P &lt; 0.01. Mg increased QT, 0, 0, 6 +/- 4, 13 +/- 5, 16 +/- 4, 23 +/- 5, 29 +/- 8, and 32 +/- 5% over baseline after a 2 hours infusion (P &lt; 0.01). APD increased by 0, 6 +/- 3, 8 +/- 8, 14 +/- 4, 16 +/- 12, 21 +/- 4, 25 +/- 5% change from baseline (P &lt; 0.05). The mean percentage of increase was 12 +/- 8 for the Mg group and 1 +/- 3 for the saline group (P &lt; 0.05). The JT interval also increased after Mg (P &lt; 0.01). After Mg loading, coronary occlusion of the left anterior descending coronary artery was performed. Ventricular premature contractions (VPCs), ventricular tachycardia (VT), and ventricular fibrillation (VF) were frequent in the saline control group, with 2 dying in VF; with only scattered VPCs and short runs of nonsustained VT in the Mg group. The results of these findings indicate that infusion of MgSO4 can prolong the QRS, QT, and JT intervals in the rat and these changes correlate well with arrhythmia suppression.

Bidirectional ventricular tachycardia and fibrillation elicited in a knock-in mouse model carrier of a mutation in the cardiac ryanodine receptor.

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by adrenergically mediated polymorphic ventricular tachycardia leading to syncope and sudden cardiac death. The autosomal dominant form of CPVT is caused by mutations in the RyR2 gene encoding the cardiac isoform of the ryanodine receptor. In vitro functional characterization of mutant RyR2 channels showed altered behavior on adrenergic stimulation and caffeine administration with enhanced calcium release from the sarcoplasmic reticulum. As of today no experimental evidence is available to demonstrate that RyR2 mutations can reproduce the arrhythmias observed in CPVT patients. We developed a conditional knock-in mouse model carrier of the R4496C mutation, the mouse equivalent to the R4497C mutations identified in CPVT families, to evaluate if the animals would develop a CPVT phenotype and if beta blockers would prevent arrhythmias. Twenty-six mice (12 wild-type (WT) and 14RyR(R4496C)) underwent exercise stress testing followed by epinephrine administration: none of the WT developed ventricular tachycardia (VT) versus 5/14 RyR(R4496C) mice (P=0.02). Twenty-one mice (8 WT, 8 RyR(R4496C), and 5 RyR(R4496C) pretreated with beta-blockers) received epinephrine and caffeine: 4/8 (50%) RyR(R4496C) mice but none of the WT developed VT (P=0.02); 4/5 RyR(R4496C) mice pretreated with propranolol developed VT (P=0.56 nonsignificant versus RyR(R4496C) mice). These data provide the first experimental demonstration that the R4496C RyR2 mutation predisposes the murine heart to VT and VF in response caffeine and/or adrenergic stimulation. Furthermore, the results show that analogous to what is observed in patients, beta adrenergic stimulation seems ineffective in preventing life-threatening arrhythmias.

[The value of BNP determination in general practice].

The natriuretic peptides BNP and NT-proBNP are synthesized and released dependent of wall tension in the atria and ventricles. The determination of these peptides in a rapid test makes two markers available that closely correlate with the severity of heart failure. Systolic as well as diastolic left ventricular dysfunction are recorded, but a clear differentiation cannot be made by marker determination. Particularly important is the high negative predictive value and the certainty with which heart failure can be excluded when the plasma level is normal. Besides the diagnostic assistance, natriuretic peptides have a high and above all independent value to assess the prognosis of heart failure, acute coronary syndromes and partially of atrial fibrillation. It is possibile to optimize the therapy of heart failure according to the plasma level.

Erythropoietin just before reperfusion reduces both lethal arrhythmias and infarct size via the phosphatidylinositol-3 kinase-dependent pathway in canine hearts.

Although recent studies suggest that erythropoietin (EPO) may reduce multiple features of the myocardial ischemia/reperfusion injury, the cellular mechanisms and the clinical implications of EPO-induced cardioprotection are still unclear. Thus, in this study, we clarified dose-dependent effects of EPO administered just before reperfusion on infarct size and the incidence of ventricular fibrillation and evaluated the involvement of the phosphatidylinositol-3 (PI3) kinase in the in vivo canine model. The canine left anterior descending coronary artery was occluded for 90 min followed by 6 h of reperfusion. A single intravenous administration of EPO just before reperfusion significantly reduced infarct size (high dose (1,000 IU/kg): 7.7 +/- 1.6%, low dose (100 IU/kg): 22.1 +/- 2.4%, control: 40.0 +/- 3.6%) in a dose-dependent manner. Furthermore, the high, but not low, dose of EPO administered as a single injection significantly reduced the incidence of ventricular fibrillation during reperfusion (high dose: 0%, low dose: 40.0%, control: 50.0%). An intracoronary administration of a PI3 kinase inhibitor, wortmannin, blunted the infarct size-limiting and anti-arrhythmic effects of EPO. Low and high doses of EPO equally induced Akt phosphorylation and decreased the equivalent number of TUNEL-positive cells in the ischemic myocardium of dogs. These effects of EPO were abolished by the treatment with wortmannin. In conclusion, EPO administered just before reperfusion reduced infarct size and the incidence of ventricular fibrillation via the PI3 kinase-dependent pathway in canine hearts. EPO administration can be a realistic strategy for the treatment of acute myocardial infarction.

B-type natriuretic peptide in organic mitral regurgitation: determinants and impact on outcome.

B-type natriuretic peptide (BNP) activation observed in cardiac diseases is a predictor of poor outcome; however, in organic mitral regurgitation (MR), BNP determinants and prognostic value are unknown.</AbstractText>We prospectively enrolled 124 patients with chronic organic MR (aged 63+/-15 years, 60% males) in whom we measured BNP level and simultaneously quantified MR degree, left ventricular (LV) remodeling, and left atrial (LA) volumes and analyzed long-term outcome. Baseline BNP level (54+/-67 pg/mL, median 31 pg/mL) was associated univariately with multiple clinical and echocardiographic characteristics, but in multivariate analysis, independent determinants of BNP, beyond age and sex (both P&lt; or =0.01), were LV end-systolic volume index, LA volume, atrial fibrillation, and symptoms (all P&lt;0.02). Conversely, MR degree was not independently associated with BNP. During follow-up, patients with high versus low BNP (&gt; or =31 versus &lt;31 pg/mL) displayed lower survival rates (at 5 years, 72+/-10% versus 95+/-5%, P=0.03) and higher rates of the combined end point of death and heart failure (at 5 years, 42+/-10% versus 16+/-7%, P=0.03). In multivariate analysis, with adjustment for age, sex, functional class, MR severity, and ejection fraction, BNP was independently predictive of mortality (hazard ratio per 10 pg/mL, 1.23 [95% CI 1.07 to 1.48], P=0.004) and of death or heart failure (hazard ratio per 10 pg/mL, 1.09 [95% CI 1.001 to 1.19], P=0.04).</AbstractText>BNP activation in organic MR reflects primarily ventricular and atrial consequences rather than degree of MR. Higher BNP level in patients with organic MR independently predicts adverse events under conservative management. Therefore, BNP activation in organic MR is an emerging biomarker of severity of MR consequences and of poor clinical outcome, and its assessment should be considered in the clinical evaluation and risk stratification of patients with MR.</AbstractText>

[Safety of new anti-arrhythmic drugs].

The majority of new antiarrhythmic drugs are still undergoing clinical trials and are not yet available on the French market. The studies of efficacy are mainly targeted on the treatment of atrial fibrillation. Intravenous ibutilide prolongs the duration of the action potential by stimulating sodium exchange during phase 2 of the action potential. Used for terminating episodes of atrial flutter and fibrillation, ibutilide has been shown to have a low proarrhythmic effect. Dofetilide is a pure I(Kr) current antagonist and is given orally. The molecule prolongs the duration of the atrial and ventricular action potentials. The amplitude of this effect is inversely related to the heart rate. No effect has been observed on the mortality rate in the post-infarct period. Adjusting the dosage with respect to renal function has reduced the occurrence of torsades de pointe from 4.8 to 2.9%. Azimilide is an I(Kr) and I(Ks) current blocker and its efficacy decreases at rapid heart rates. After oral administration, azimilide does not appear to have a deleterious effect in patients with a history of myocardial infarction and left ventricular dysfunction. The risk of torsades de pointe is less than 1%. Cases of neutropaenia have been reported. Dronedarone is an amiodarone analogue without iodine. The molecule prolongs atrial and ventricular action potentials and its efficacy is maintained at high heart rates. This drug had deleterious effects when given to patients with coronary artery disease and left ventricular dysfunction. Gastrointestinal side effects may be observed at high dosage. The great advantages of dronedarone are the absence of thyroid complications and of pro-arrhythmic effects.

[Automobile driving and implantable defibrillators].

The consequences of implanting an automatic cardioverter defibrillator (ICD) on vehicle driving in France are poorly known. This retrospective study examined the behaviour at the wheel of ICD recipients who were recommended to abstain from driving for 3 to 6 months after device implantation. The study population included 98 patients (mean age = 59.5 +/- 14.8 years) followed for a mean of 24. +/- 23.9 months, who underwent ICD implant for ventricular tachycardia (65% of patients ventricular fibrillation (15%), syncope (8%), as part of a research protocol of myocardial cell transplantation 6%, or for primary prevention (5%). The underlying heart disease was ischemic in 59% of patients dilated cardiomyopathy in 11%,hypertrophic cardiomyopathy in 8%, valvular in 6%. Brugada syndrome in 4%, right ventricular arrhythmogenic cardiomyopathy in 2%, and miscellaneous disorders in 9% of patients. Five patients died without post mortem interrogation of the ICD. Only 28% of drivers remembered, and 13% observed, the recommended driving limitations. However, 45% (the oldest) claimed to drive prudently. During follow-up, 47% of patients received an ICD shock. Their mean it ventricular ejection fraction was 34 +/- 14%, versus 43 +/- 18% in patients who received no ICD therapy (p = 0.015). Syncope occurred in 16% who received ICD shocks. Shocks were delivered during driving in 6 patients, without consequent accident. Despite their non-observance of recommended driving limitations. ICD recipients suffered few traffic accidents. Legislation in France should reproduce the guidelines issued by European professional societies and enacted by the British laws.

Atrial and ventricular volume and function in persistent and permanent atrial fibrillation, a magnetic resonance imaging study.

Left atrial size is independently related to cardiovascular morbidity and mortality, and atrial fibrillation (AF) is strongly associated with atrial size. Our aims were to report atrial and ventricular dimensions in patients with AF evaluated with magnetic resonance imaging (MRI), and to assess the inter-study reproducibility of the measurements. Nineteen healthy volunteers, 19 patients with permanent AF, and 58 patients with persistent AF had cardiac dimensions evaluated by 6-mm cinematographic breath-hold MRI scans using a 1.5 Tesla Siemens Vision Magnetom scanner with a phased array chest coil. Intraobserver variability and inter-study reproducibility of the cardiac volumes and ejection fractions (EF) gave acceptable Bland-Altman plots, good correlations (R2: 0.80-0.99), and low reproducibility coefficients. The mean atrial volumes were similar in the two groups with AF [systolic vol. index (SVI): 75.9-80.3 mL/m2; diastolic vol. index (DVI): 77.4-82.1 mL/m2] and significantly different from the healthy volunteers (SVI: 30.3 mL/m2; DVI: 62.3 mL/m2; p &lt; 0.0001). Mean left ventricular (LV) volumes and EF were significantly different in permanent AF (SVI: 34.2 mL/m2; DVI: 68.3 mL/m2; EF: 50.8%) compared to persistent AF [SVI: 44.0 mL/m2 (p = 0.02); DVI: 77.2 mL/m2 (p = 0.03); EF: 44.9% (p = 0.02)], and closer to the normal values (SVI: 22.4 mL/m2; DVI: 66.5 mL/m2; EF: 67.0%). MRI is a highly reproducible method for measurement of atrial and ventricular dimensions in healthy volunteers and in patients with AF. Our results suggest that atrial dilatation appears within the first months of AF and stays more or less unchanged thereafter. The LV appears to dilate early as a response to AF, but later seems to adapt.

Livers from non-heart-beating donors tolerate short periods of warm ischemia.

In contrast with kidneys, transplantation of livers originating from non-heart-beating donors remains rare, mainly because warm ischemia causes a higher rate of potentially lethal primary graft nonfunction. Little is known on the tolerance of liver grafts to warm ischemia. No techniques are available to assess the viability of ischemic livers before implantation. Therefore, experimental models are needed to address these questions before non-heart-beating liver transplantation can be more widely applied. This study aims to develop a reproducible large animal model of liver transplantation using non-heart-beating donors and, in this model, to define the tolerance of the liver to warm ischemia.</AbstractText>Pigs weighing 25to 30 kg are used. In donors, cardiac arrest is caused by ventricular fibrillation. After increasing lengths of warm ischemia (0, 15, 30, 45, and 60 min), the liver is flushed in situ with 4 degrees C histidine tryptophan ketoglutarate preservation solution and procured. The liver is transplanted after a 4-hour cold storage period.</AbstractText>Control livers (no warm ischemia) and livers exposed to 15 minutes of warm ischemia function normally after transplantation, whereas all livers submitted to 60 minutes of warm ischemia display primary nonfunction and cause recipient death. Graft function and survival are occasionally observed after 30 and 45 minutes of warm ischemia.</AbstractText>A reproducible model of non-heart-beating liver transplantation is described. We found that the liver tolerates 15 minutes of warm ischemia. This preclinical model is a valid tool to develop techniques to predict the quality of ischemic livers before implantation and to design interventional strategies to improve the tolerance of the liver to warm ischemia.</AbstractText>

Acute exercise increases the ventricular arrhythmia threshold via the intrinsic adenosine receptor system in conscious hypertensive rats.

Coronary artery occlusion-induced tachyarrhythmias that culminate in ventricular fibrillation are the leading cause of death in developed countries. The intrinsic adenosine receptor system protects the heart from an ischemic insult. Thus the increased functional demands made on the heart during exercise may produce protective adaptations mediated by endogenous adenosine. Therefore, we tested the hypothesis that a single bout of dynamic exercise increases the ventricular arrhythmia threshold (VAT) induced by coronary artery occlusion in conscious hypertensive rats via the intrinsic adenosine receptor system. To test this hypothesis, we recorded the VAT before and on an alternate day after a single bout of dynamic treadmill exercise (12 m/min, 10% grade for 40 min). A single bout of dynamic exercise significantly reduced postexercise arterial pressure (Delta-24 +/- 4 mmHg) and increased VAT (Delta+1.95 +/- 0.31 min). Adenosine receptor blockade with the nonselective adenosine receptor antagonists theophylline or aminophylline (10 mg/kg) attenuated the cardioprotective effects of a single bout of dynamic exercise. Results suggest that strategies that increase myocardial ATP requirements leading to adenosine production provide protection against coronary artery occlusion.

Pacing with capture verification in candidates for resynchronisation therapy: a feasibility study.

Devices for cardiac resynchronisation therapy (CRT) deliver energy into 3 output channels. Such a burden can significantly reduce device longevity. Autocapture has been shown to improve pacemaker longevity and safety of right ventricular pacing in clinical studies. The aim of this study was to investigate the application of Autocapture during biventricular pacing (BIV) to decrease the energy cost of CRT.</AbstractText>During implantation of BIV devices, an acute study was performed to test the hypothesis that the evoked response (ER) elicited by each delivered stimulus is correctly detected and measured either on the right ventricular (RV) channel during BIV pacing with the left ventricular (LV) channel pacing first, or in the LV channel with the RV channel pacing first. A reliable measurement of ER is the critical requirement for the correct performance of Autocapture.</AbstractText>ER amplitude in the right ventricle during BIV pacing was not significantly decreased compared with RV pacing in the VVI mode (16.36+/-5.27 mV vs 17.09+/-6.12 mV). ER amplitude in the left ventricle during BIV pacing was not significantly decreased compared with LV pacing in the VVI mode (12.4+/-8.95 mV vs 12.25+/-8.97 mV). Three patients in atrial fibrillation had a DDDR pacemaker with the LV lead connected to the atrial port, and received BIV pacing with Autocapture turned on in the RV channel. Autocapture performance in the long term, as assessed by the trend of RV threshold over 20+/-8 months, showed that LV depolarisation was never sensed as an ER on the RV channel.</AbstractText>Our observations support the feasibility and safety of capture verification during BIV pacing on the ventricular channel paced secondly, which could increase the longevity of CRT devices, and decrease the costs of this new therapy for heart failure patients.</AbstractText>

Atrial fibrillation triggered by postinfarction ventricular premature beats in a patient with Wolff-Parkinson-White syndrome.

The mechanism by which atrial fibrillation is initiated in patients with accessory pathways is not fully understood. Retrograde conduction of ventricular premature beats to the atrium, causing the arrhythmia, is a very rare cause. We report a patient with Wolff-Parkinson-White syndrome (WPW), without previous tachycardias, who presented multiple episodes of paroxysmal atrial fibrillation after having a myocardial infarction. During the electrophysiological (EP) study the patient presented two spontaneous episodes of atrial fibrillation initiated by ventricular premature beats conducted to the atria through the accessory pathway. After successful catheter ablation of the accessory pathway the patient did not present arrhythmia recurrences.

A novel missense mutation in the SCN5A gene associated with Brugada syndrome bidirectionally affecting blocking actions of antiarrhythmic drugs.

Brugada syndrome is an inherited cardiac disorder caused by mutations in the SCN5A gene encoding the cardiac sodium channel alpha subunit, which can lead ventricular fibrillation and sudden death. Inattentive use of antiarrhythmic drugs potentially triggers fatal cardiac arrhythmias through further reduction of sodium current (I(Na)). We studied the molecular mechanism underlying a case of Brugada syndrome that showed no response to a class Ic antiarrhythmic drug. Molecular genetic studies of a patient with Brugada syndrome identified a novel mutation in SCN5A, which causes substitution of serine for asparagine (N406S) in S6 of domain I (IS6). The provocation test with pilsicainide, a class Ic antiarrhythmic drug, failed to exacerbate ST-segment elevation in this case. Electrophysiological analyses of the N406S-mutant channel expressed together with the beta1 subunit in HEK293 cells showed that the voltage dependence of activation was positively shifted by 16 mV and that intermediate inactivation was enhanced. Whereas tonic block by pilsicainide was not changed in the N406S channel, use-dependent block by pilsicainide was almost completely abolished, consistent with the clinical findings of the negative provocation test. In contrast, the N406S channel showed stronger use-dependent block by quinidine than the wild-type channel. We demonstrate a novel Brugada mutation N406S, which is associated with the discordant effects on blocking actions of antiarrhythmic drugs as well as the multiple channel gating defects. We emphasis that an antiarrhythmic drug may exert unpredicted effects in patients with channel mutations.

Long-term incidence of malignant ventricular arrhythmia and shock therapy in patients with primary defibrillator implantation does not differ from event rates in patients treated for survived cardiac arrest.

Recent trials have demonstrated benefit of prophylactic defibrillator (ICD) implantation compared to conventional treatment in high-risk patients. However, many patients have rare or no sustained arrhythmias following implantation. Our study addresses the question, whether patients with prophylactic defibrillator implantation have a lower risk for life-threatening ventricular tachycardia (VT) or ventricular fibrillation (VF) compared to sudden cardiac death (SCD) survivors.</AbstractText>Over 7 years we enrolled 245 patients. Occurrence of spontaneous sustained VT/VF resulting in adequate ICD treatment was the endpoint. Incidence, type, and treatment of sustained arrhythmia in 43 previously asymptomatic ICD recipients (group B) were compared to data of 202 survivors of imminent SCD (group A). All patients had severely impaired left ventricular ejection fraction (&lt;45%). Group B patients had long runs (&gt;6 cycles, &lt;30 s) of VT during Holter monitoring and inducible sustained arrhythmia. Incidence of rapid VT and VF (cycle length &lt;240 ms/heart rate &gt;250 bpm) after 4 years (35% in both groups, P = ns) and adequate defibrillator therapies (57% vs 55%, P = ns) were similar in both groups after univariate and multivariate analysis. Cumulative mortality tended to be lower in group B compared to group A, but the difference was not statistically significant.</AbstractText>During long-term follow-up, incidence of sustained rapid ventricular arrhythmia in prophylactically treated patients is as high as that of SCD survivors. Benefit from defibrillator implantation for primary prevention (group B) appears to be comparable to that for survived cardiac arrest (group A).</AbstractText>

Increased intensity of anticoagulation may reduce risk of thrombus during atrial fibrillation ablation procedures in patients with spontaneous echo contrast.

A 10% incidence of left atrial (LA) thrombus formation has been detected using intracardiac echocardiography (ICE) imaging monitoring during LA ablation for atrial fibrillation (AF). The aim of this study was to determine if the intensity of anticoagulation reduces LA thrombus formation during pulmonary vein isolation procedure in patients with AF and spontaneous echo contrast (SEC).</AbstractText>We studied 511 patients (age 56 +/- 10 years) undergoing pulmonary vein ostial isolation/ablation using radiofrequency energy. SEC was detected in 179 of 511 patients with ICE imaging before dual transseptal catheterization. All patients were anticoagulated with heparin to achieve activated clotting time (ACT) 250-300 seconds (group I) or &gt;300 seconds (group II) confirmed at 30-minute intervals. SEC was detected in 49/294 (16.7%) patients in group I versus 130/217 (59.9%) in group II (P &lt; 0.0001). LA thrombus was observed in 33/294 (11.2%) patients in group I versus 6/217 (2.8%) in group II (P &lt; 0.05). For those patients with SEC, LA thrombus was observed in 22/49 (44.9%) in group I versus 2/61 (4.6%) in group II (P &lt; 0.0001). There were no significant differences in age, number of unsuccessful drugs, persistent AF, left ventricular ejection fraction, and LA diameter between the two groups. No clinical embolic event was observed with withdrawal of LA thrombus to the RA.</AbstractText>ICE-diagnosed SEC before transseptal catheterization identifies an increased risk of LA thrombus. Increased intensity of heparin anticoagulation (ACT &gt;300 seconds) during LA ablation for AF may prevent LA thrombus formation especially in patients with SEC.</AbstractText>

Catheter ablation of atrial fibrillation versus atrioventricular junction ablation plus pacing therapy for elderly patients with medically refractory paroxysmal atrial fibrillation.

Catheter ablation of atrial fibrillation (AF) has become another nonpharmacologic therapeutic option for medically refractory paroxysmal AF. Whether this method is better than atrioventricular (AV) junction ablation plus pacing therapy is unknown. The purpose of this study was to compare the very long-term (longer than 4 years) clinical outcomes of the 2 methods in elderly patients (&gt;65 years old) with medically refractory paroxysmal AF.</AbstractText>From January 1995 to December 2001, 71 elderly patients with medically refractory paroxysmal AF were included; group 1 included 32 patients with successful AV junction ablation plus pacing therapy and group 2, 37 patients with successful catheter ablation of AF.</AbstractText>After a mean follow-up of more than 52 months, the AF was better controlled in the group 1 patients than group 2 (100% vs 81%, P = 0.013), however, they had a significantly higher incidence of persistent AF (69% vs 8%, P &lt; 0.001) and heart failure (53% vs 24%, P = 0.001). Furthermore, the incidence of ischemic stroke and cardiac death was similar between the 2 groups. Compared with the preablation values, a significant increase in the NYHA functional class (1.7 +/- 0.9 vs 1.4 +/- 0.7, P = 0.01) and significant decrease in the left ventricular ejection fraction (44 +/- 8% vs 51 +/- 10%, P = 0.01) were noted in the group 1 patients, but not in the group 2 patients.</AbstractText>Although AV junction ablation plus pacing therapy better controlled the AF in elderly patients with medically refractory paroxysmal AF, that method was associated with a higher incidence of persistent AF and heart failure than catheter ablation of AF in the very long-term follow-up.</AbstractText>

Vascular dementia. Advances in nosology, diagnosis, treatment and prevention.

Ischemic or hemorrhagic cerebrovascular disease (CVD) produces injury of brain regions important for executive function, behavior, and memory leading to decline in cognitive functions and vascular dementia (VaD). Cardiovascular disease may cause VaD from hypoperfusion of susceptible brain areas. CVD may worsen degenerative dementias such as Alzheimer disease (AD). Currently, the global diagnostic category for cognitive impairment of vascular origin is vascular cognitive disorder (VCD). VCD ranges from vascular cognitive impairment (VCI) to VaD. The term VCI is limited to cases of cognitive impairment of vascular etiology, without dementia; VCI is equivalent to vascular mild cognitive impairment (MCI). Risk factors for VaD include age, hypertension, diabetes, smoking, cardiovascular disease (coronary heart disease, congestive heart failure, peripheral vascular disease), atrial fibrillation, left ventricular hypertrophy, hyperhomocysteinemia, orthostatic hypotension, cardiac arrhythmias, hyperfibrinogenemia, sleep apnea, infection, and high C-reactive protein. Research on biomarkers revealed increased CSF-NFL levels in VaD, whereas CSF-tau was normal. CSF-TNF-alpha, VEGF, and TGF-beta were increased in both AD and VaD. VaD shows low CSF acetylcholinesterase levels. This condition responds to acetylcholinesterase inhibitors, confirming the central role of cholinergic deficit in its pathogenesis. Evidence strongly suggests that control of vascular risk factors, in particular hypertension, could prevent VaD.

The Italian Implantable Cardioverter-Defibrillator Registry. A survey of the national activity during the years 2001-2003.

In recent years several trials demonstrated the efficacy of implantable cardioverter-defibrillator (ICD) therapy for sudden cardiac death prevention and total mortality reduction in particular high-risk groups of patients. The aim of this review was to report the main epidemiological data and the most important clinical characteristics of patients enrolled in the Italian ICD Registry in the years 2001-2003.</AbstractText>The Italian ICD Registry--official member of the Italian Association of Arrhythmology and Cardiac Pacing (AIAC)--collects 85% of the data concerning the national ICD implantation activity, based on the European Implantable Defibrillator form (EURID). Data are validated for quality of information and uniqueness at the moment of data entry and in successive steps at the time of the annual analysis.</AbstractText>The number of ICDs implanted in Italy has been continuing to increase during the last years according to the general trend in European and non-European countries: 2400 in the year 2001, 3934 in the year 2002, and 5318 in the year 2003. The number of ICDs per million of inhabitants in Italy was 42.1 in the year 2001 (+11.8% with respect to 2000), 69.0 in the year 2002 (+63.9% with respect to 2001), and 93.3 in the year 2003 (+35.2% with respect to 2002). The number of implanting centers increased progressively from 273 in the year 2001 to 304 in the year 2002, and 340 in the year 2003. The median age of patients treated with ICD implantation was 67 years in the years 2001-2002, 68 years in the year 2003. The prevalence of male patients was significantly higher (79.3% in 2001, 82.3% in 2002, and 81.4% in 2003). The main indication was syncope (25.5, 29.3, and 32.9% in the years 2001, 2002, and 2003, respectively), followed by palpitations (17.7, 18.5, and 16.4% in the years 2001, 2002, and 2003, respectively), and cardiac arrest (10.0, 13.1, and 16.5% in the years 2001, 2002, and 2003, respectively). The use of ICD in patients considered at risk but without history of sustained ventricular tachycardia had a 3-fold increase during the 3 years, from 6.4% in 2001 to 18.2% in 2003. Ventricular tachycardia was the main arrhythmia in 50.4 to 55.0% of cases, ventricular fibrillation in 13.5 to 18.1%, both in 4.1 to 6.5%. The vast majority of patients presented at the enrolment either a mild or severe reduction in ejection fraction (30 to 50%, &lt; 30%). Amiodarone was administered alone or in combination with antiarrhythmics in 29.7 to 40.0% of patients. Single-chamber ICDs were implanted in the years 2002 and 2003 in 45.7 and 39.2% of patients, dual-chamber ICDs in 34.9 and 32.4%, biventricular ICDs in 19.4 and 28.4%, respectively.</AbstractText>The ICD implantation rate in Italy increased significantly in the period 2001-2003, similarly to the trend in the other western countries and following the publication of controlled studies in the field of primary and secondary prevention of sudden cardiac death. The Italian ICD Registry showed during the last 3 years an important increase in prophylactic ICD utilization. A sophisticated ICD, including dual-chamber pacing or cardiac resynchronization therapy, was chosen in a high percentage of patients.</AbstractText>

Surgical ablation of arrhythmias.

The surgical approach was the earliest therapeutic ablation of hyperkinetic arrhythmias. Following the progressive improvements in electrophysiological mapping and operative techniques, new surgical approaches have been developed for the treatment of those arrhythmias related to ectopic phenomena or reentry mechanisms. These procedures have been proven to be highly effective but the associated morbidity and mortality were unacceptably high. More recent and advanced techniques of transcatheter ablation have revolutionized the treatment of these arrhythmias and now represent the treatment of choice in the majority of cases. However, the significant reduction in the operative risk and the improvement in patient outcome with respect to the past, thanks to a better patient selection and to advances in the surgical and myocardial protection techniques, make do that the surgical approach to some forms of arrhythmias is still valid, especially in those cases requiring associated surgery: atrial tachyarrhythmias in patients with congenital heart disease, post-ischemic ventricular tachycardias in patients who necessitate myocardial revascularization, and/or ventricular remodeling and chronic or paroxysmal atrial fibrillation in patients who require cardiac surgery. New techniques such as radiofrequency, microwaves and cryoablation guarantee the creation of linear and transmural lesions with minimum damage to the cardiac structures and appear very interesting as they are surgically simple and associated with shorter procedure times and less complications. The possibility of performing the ablative procedure completely on the epicardial surface may open the way for atrial fibrillation surgery on a totally beating heart and for procedures that are ever less invasive thus enabling treatment of patients without associated surgical indications.

Atrial tachyarrhythmia prevention and treatment by means of special pacing algorithms.

Pacing prevention algorithms have been introduced in order to maximize the benefits of atrial pacing in atrial fibrillation prevention. It has been demonstrated that algorithms actually keep overdrive atrial pacing, reduce atrial premature contractions, and prevent short-long atrial cycle phenomenon, with good patient tolerance. However, clinical studies showed inconsistent benefits on clinical endpoints such as atrial fibrillation burden. Factors which may be responsible for neutral results include an already high atrial pacing percentage in conventional DDDR, non-optimal atrial pacing site, deleterious effects of high percentages of apical ventricular pacing. Atrial antitachycardia pacing (ATP) therapies are effective in treating spontaneous atrial tachyarrhythmias, mainly when delivered early after arrhythmia onset and/or on slower tachycardias. Effective ATP therapies may reduce atrial fibrillation burden, but conflicting evidence does exist as regards this issue, probably because current clinical studies may be underpowered to detect such an efficacy. Wide application of atrial ATP may reduce the need for hospitalizations and electrical cardioversions and favorably impact on quality of life. Consistent monitoring of atrial and ventricular rhythm as well as that of ATP effectiveness may be extremely useful for optimizing device programming and pharmacological therapy.

Non-invasive sudden death risk stratification.

Most sudden cardiac deaths are caused by fatal ventricular arrhythmias (ventricular tachycardia [VT] and fibrillation) in patients with and without known structural heart diseases. Given the large number of patients potentially at risk for developing ventricular arrhythmias, any strategy for treating them prophylactically requires efficient and effective risk stratification. Both non-invasive and invasive testing may be used for prognostic evaluation of patients with heart diseases. The optimal way to use them in the risk stratification for sudden cardiac death will depend in part on the goals of screening. At present risk markers perform better at identifying low-risk patients who may not need an implantable cardioverter-defibrillator (ICD), because all tests have a high negative predictive accuracy. In our opinion an electrophysiological test should not be performed and an ICD should not be implanted in post-myocardial infarction patients with moderate left ventricular dysfunction (left ventricular ejection fraction 30-40%) with a preserved autonomic balance and without non-sustained VT. In MADIT II-like patients electrophysiological testing does not seem necessary and an ICD could not be implanted only in patients with a negative T-wave alternans test. Most of the data available refer to patients with ischemic cardiomyopathy but the preliminary data on T-wave alternans suggest its usefulness in patients with non-ischemic cardiomyopathy too, although a large definitive study has not yet been completed in this important population.

Non-antiarrhythmic drugs for the prevention of cardiac arrhythmias.

It is noteworthy that drugs having a significant impact in preventing arrhythmias (atrial or ventricular) are those with no direct specific antiarrhythmic electrophysiologic properties. Specifically, drugs able to interfere with the renin-angiotensin system and the n-3 fatty acids seem to play a relevant role as antiarrhythmics, even if they do not act in the typical manner. Angiotensin-converting enzyme (ACE) inhibitors decrease the incidence of arrhythmias in patients with decreased left ventricular function. The main reduction is linked to a decrease of ventricular arrhythmias, while several studies have suggested that ACE-inhibitors may also decrease the burden of atrial fibrillation. Furthermore, many of angiotensin receptor blockers and spironolactone have been shown to have antiarrhythmic properties. n-3 polyunsaturated fatty acids (PUFAs) are known to be antiarrhythmic as well. Their effects on the fast voltage-dependent sodium current I(NA), inhibition of I(Ca2+) and the K+ channel modulation explain their antiarrhythmic properties. For these reasons the renin-angiotensin system blockade and the n-3 PUFA intake may provide simple and safe protection from cardiac arrhythmias.

Dual site right atrial pacing can improve the impact of standard dual chamber pacing on atrial and ventricular mechanical function in patients with symptomatic atrial fibrillation: further observations from the dual site atrial pacing for prevention of atrial fibrillation trial.

The effects of atrial pacing mode on atrial and ventricular function in patients with atrial fibrillation (AF) and bradycardia have not been evaluated. We evaluated atrial and ventricular function during randomization to support pacing (SP), high right atrial pacing (HRA), and dual site right atrial pacing (DAP).</AbstractText>Seventy-nine patients (66 +/- 12 yr, 46 male) with standard pacing indications and symptomatic AF were randomized to each of three pacing modes (DAP, HRA, SP) for 6 months in a crossover design. Echocardiographic studies were performed at enrollment and the end of each mode. Paired comparisons of atrial and ventricular function parameters were performed between each pacing mode and baseline.</AbstractText>HRA pacing in DDDR mode resulted in increased left ventricular (LV) end systolic volume (78 +/- 42 vs. 60 +/- 31 ml, p = 0.001) and reduced LV ejection fraction (44 +/- 14 vs. 50 +/- 11%, p = 0.007) compared to baseline. These parameters did not change during DAP. DAP resulted in increased peak A wave velocity (75 +/- 19 vs. 63 +/- 23 cm/s, p = 0.003) and atrial filling fraction compared to baseline (0.47 +/- 0.15 vs. 0.38 +/- 0.13, p = 0.005). Atrial and ventricular function were similar between control and SP.</AbstractText>DAP, but not HRA or SP, improved left atrial (LA) function in patients with AF and bradycardia. HRA pacing in DDDR mode resulted in LA dilatation and deterioration of LV function which was not observed with DAP.</AbstractText>

[Long QT syndrome and Brugada syndrome. Drugs, ablation or ICD?].

Long QT syndrome and Brugada syndrome are potentially fatal inherited arrhythmogenic diseases. Thanks to the contribution of molecular genetics, the genetic bases, pathogenesis, and genotype-phenotype correlation of both diseases have been progressively unveiled and shown to have an extremely high degree of genetic heterogeneity. The clinical manifestation of the diseases is also highly variable. Symptomatic patients experience ventricular tachyarrhythmias which may lead to recurrent syncope and/or sudden cardiac death. In long QT syndrome patients with syncope, therapy with beta-blockers has proven effective. When, despite beta-blocker treatment, arrhythmia-related symptoms continue to occur, an implantable cardioverter defibrillator is indicated. Such a device should also be implanted in resuscitated patients. In symptomatic patients with Brugada syndrome, the implantable cardioverter defibrillator is the only life-saving option. In asymptomatic patients with a Brugada ECG pattern, risk stratification has become of utmost importance in order to discover which patients really need definitive treatment.

[Interventional treatment in hypertrophic cardiomyopathy].

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease phenotypically expressed in the general population at about 0.2%. Annual mortality rate is about 1% in unselected patients, 3-6% in patients with severe symptoms, and 17% following resuscitation from ventricular tachycardia (VT)/ventricular fibrillation (VF). 50-80% of deaths are sudden. Beneath effective treatment in severe symptoms of heart failure (most common in midlife and beyond) the prevention of sudden death (most common in young patients) continues to be a major challenge. The highest risk has been associated with any of the following markers: 1. prior cardiac arrest or spontaneous sustained VTs, 2. a family history of premature HCM-related death, 3. extreme left ventricular hypertrophy (&gt; or = 30 mm), 4. syncope, 5. multiple bursts of nonsustained VTs, 6. hypotensive blood pressure response to exercise, and 7. marked septal scarring (hyperenhancement in magnetic resonance imaging). Treatment options in patients with drug-refractory symptoms or increased risk of sudden death are surgical myectomy, transcoronary ablation of septal hypertrophy (TASH), dual-chamber pacing, ablation of atrial fibrillation (or the AV node), and the implantable cardioverter defibrillator (ICD). 1. Surgical myectomy effectively improves symptoms, hemodynamics and probably prognosis. Long-term results are well known, but patients' preference and the number of experienced surgical centers are fading. Randomized studies are missing. 2. TASH induces quite similar improvements in symptoms and hemodynamics. It is remarkably evaluated for a postprocedural follow-up of up to 10 years, and it is the preferred mode of treatment in patients. However, information on long-term prognosis, rhythmogenic effects and randomized studies are missing. For the prevention of sudden death, TASH has to be combined with an ICD. 3. Dual-chamber pacing was evaluated in randomized crossover studies, but symptomatic and hemodynamic improvements and patients' preference are substantially lower than for TASH. 4. The ICD has the potential to alter prognosis in secondary (class I indication) and primary prevention. HCM patients should undergo a risk stratification assessment. Prophylactic implants base on a clinical profile with two or more risk markers (sometimes one risk marker). 5. Ablation of atrial fibrillation or the AV node is indicated to improve symptoms in patients with fast ventricular rates despite medical treatment. For the prevention of sudden death, it has to be combined with an ICD.

Successful defibrillation immediately after the intravascular injection of ropivacaine.

To report successful resuscitation of ventricular fibrillation induced by accidental intravascular injection of ropivacaine.</AbstractText>A 15-yr-old healthy girl weighing 59 kg was scheduled for transposition of the tibial tuberosity under combined sciatic/three-in-one block. No premedication was given. In the induction room, an iv infusion was started, along with electrocardiogram monitoring, non-invasive blood-pressure measurement and pulse-oximetry. The sciatic nerve was found with the use of a nerve stimulator at the first attempt by the classical approach of Labat. Aspiration for blood was negative and the injection of ropivacaine 0.75% without epinephrine started. Convulsions, followed within seconds by ventricular fibrillation occurred at the end of the injection of 18 mL ropivacaine 0.75%. Oxygen was administered by face mask ventilation and immediate defibrillation was successful on the second attempt (2 x 200 joules). Within two minutes convulsions stopped and normal cardiac rhythm returned. Propofol and sufentanil were injected and a laryngeal mask inserted to start general anesthesia for surgery. Postoperatively no evidence of sciatic block could be demonstrated. The patient did not remember the event and was discharged the following day with no residual effects.</AbstractText>This case report shows that ventricular fibrillation after unintentional intravascular injection of ropivacaine can be treated successfully when one is prepared and cardiac life support measures are taken immediately.</AbstractText>

Reducing ventilation frequency during cardiopulmonary resuscitation in a porcine model of cardiac arrest.

American Heart Association/American College of Cardiology guidelines recommend a compression-to-ventilation ratio (C/V ratio) of 15:2 during cardiopulmonary resuscitation (CPR) for out-of-the-hospital cardiac arrest. Recent data have shown that frequent ventilations are unnecessary and may be harmful during CPR, since each positive-pressure ventilation increases intrathoracic pressure and may increase intracranial pressure and decrease venous blood return to the right heart and thereby decrease both the cerebral and coronary perfusion pressures.</AbstractText>We hypothesized that reducing the ventilation rate by increasing the C/V ratio from 15:2 to 15:1 will increase vital-organ perfusion pressures without compromising oxygenation and acid-base balance.</AbstractText>Direct-current ventricular fibrillation was induced in 8 pigs. After 4 min of untreated ventricular fibrillation without ventilation, all animals received 4 min of standard CPR with a C/V ratio of 15:2. Animals were then randomized to either (A) a C/V ratio of 15:1 and then 15:2, or (B) a C/V ratio of 15:2 and then 15:1, for 3 min each. During CPR, ventilations were delivered with an automatic transport ventilator, with 100% oxygen. Right atrial pressure, intratracheal pressure (a surrogate for intrathoracic pressure), aortic pressure, and intracranial pressure were measured. Coronary perfusion pressure was calculated as diastolic aortic pressure minus right atrial pressure. Cerebral perfusion pressure was calculated as mean aortic pressure minus mean intracranial pressure. Arterial blood gas values were obtained at the end of each intervention. A paired t test was used for statistical analysis, and a p value &lt; 0.05 was considered significant.</AbstractText>The mean +/- SEM values over 1 min with either 15:2 or 15:1 C/V ratios were as follows: intratracheal pressure 0.93 +/- 0.3 mm Hg versus 0.3 +/- 0.28 mm Hg, p = 0.006; coronary perfusion pressure 10.1 +/- 4.5 mm Hg versus 19.3 +/- 3.2 mm Hg, p = 0.007; intracranial pressure 25.4 +/- 2.7 mm Hg versus 25.7 +/- 2.7 mm Hg, p = NS; mean arterial pressure 33.1 +/- 3.7 mm Hg versus 40.2 +/- 3.6 mm Hg, p = 0.007; cerebral perfusion pressure 7.7 +/- 6.2 mm Hg versus 14.5 +/- 5.5 mm Hg, p = 0.008. Minute area intratracheal pressure was 55 +/- 17 mm Hg . s versus 22.3 +/- 10 mm Hg . s, p &lt; 0.001. End-tidal CO(2) with 15:2 versus 15:1 was 24 +/- 3.6 mm Hg versus 29 +/- 2.5 mm Hg, respectively, p = 0.001. Arterial blood gas values were not significantly changed with 15:2 versus 15:1 C/V ratios: pH 7.28 +/- 0.03 versus 7.3 +/- 0.03; P(aCO(2)) 37.7 +/- 2.9 mm Hg versus 37.6 +/- 3.5 mm Hg; and P(aO(2)) 274 +/- 36 mm Hg versus 303 +/- 51 mm Hg.</AbstractText>In a porcine model of ventricular fibrillation cardiac arrest, reducing the ventilation frequency during CPR by increasing the C/V ratio from 15:2 to 15:1 resulted in improved vital-organ perfusion pressures, higher end-tidal CO(2) levels, and no change in arterial oxygen content or acid-base balance.</AbstractText>

Variable electrocardiographic effects of short-term quinidine sulfate administration in Brugada syndrome.

Quinidine, a class I antiarrhythmic agent with blocking property of transient outward current, is a possible candidate for the suppression of ventricular fibrillation in patients with Brugada syndrome; although there is a concern that its ability to these effects may be proarrhythmic. Therefore, we evaluated the effect of quinidine sulfate on ST-segment elevation in Brugada syndrome. In 8 patients with Brugada syndrome, the magnitude of ST-elevation at the J-point (ST(J)), and the ST-segment configuration in leads V1-V3, were compared before and on day 2 after the initiation of quinidine administration. In 3 patients, quinidine attenuated ST(J) by &gt; or = 0.1 mV. Of these 3 patients, ST-segment elevation was normalized in 2 patients, while the ST-segment configuration was unchanged in another. In another 3 patients, quinidine augmented ST(J) by &gt; or = 0.1 mV without any change of ST-segment configuration, and the augmentation was returned to baseline after the discontinuation of quinidine. Quinidine exhibited no effect on the ST-segment in the remaining 2 patients. The favorable effects of quinidine on the ST-segment tended to be more pronounced in patients with prominent ST-elevation at baseline. In 1 patient, quinidine was effective in eliminating both ST-segment elevation and repetitive tachyarrhythmia episodes. In conclusion, the effects of quinidine on ST-segment elevation were variable. Quinidine may potentially augment the ST-segment elevation in some patients with Brugada syndrome.

Carvedilol's antiarrhythmic properties: therapeutic implications in patients with left ventricular dysfunction.

Carvedilol is a beta- and alpha-adrenergic-blocking drug with clinically important antiarrhythmic properties. It possesses anti-ischemic and antioxidant activity and inhibits a number of cationic channels in the cardiomyocyte, including the HERG-associated potassium channel, the L-type calcium channel, and the rapid-depolarizing sodium channel. The electrophysiologic properties of carvedilol include moderate prolongation of action potential duration and effective refractory period; slowing of atrioventricular conduction; and reducing the dispersion of refractoriness. Experimentally, carvedilol reduces complex and repetitive ventricular ectopy induced by ischemia and reperfusion. In patients, carvedilol is effective in controlling the ventricular rate response in atrial fibrillation (AF), with and without digitalis, and is useful in maintaining sinus rhythm after cardioversion, with and without amiodarone. In patients with AF and heart failure (HF), carvedilol reduces mortality risk and improves left ventricular (LV) function. Large-scale clinical trials have demonstrated that combined carvedilol and angiotensin-converting enzyme inhibitor therapy significantly reduces sudden cardiac death, mortality, and ventricular arrhythmia in patients with LV dysfunction (LVD) due to chronic HF or following myocardial infarction (MI). Despite intensive neurohormonal blockade, mortality rates remain relatively high in patients with post-MI and nonischemic LVD. Recent trials of implantable cardioverter-defibrillators added to pharmacologic therapy, especially beta blockers, have shown a further reduction in arrhythmic deaths in these patients.

Atrial fibrillation in elderly patients after cardiac surgery: postoperative hemodynamics and low postoperative serum triiodothyronine.

The purpose of this study was to evaluate serum triiodothyronine levels as a trigger of postoperative atrial fibrillation (AF) in elderly patients undergoing cardiac surgery and to study the possible association of serum triiodothyronine levels with preoperative and postoperative hemodynamics.</AbstractText>Prospective study.</AbstractText>University hospital.</AbstractText>Forty-six consecutive nonemergency patients 65 years or older undergoing cardiac surgery during 1999 to 2000 in Tampere University Hospital, Tampere, Finland.</AbstractText>Free serum T3 concentration was used as a measure of serum triiodothyronine levels. Samples were taken preoperatively, on the fourth postoperative day, and at the 3-month follow-up. The hemodynamic state of the patients was estimated by whole-body impedance cardiography preoperatively, during the intensive care unit period, daily until the fourth postoperative day, and at the 3-month follow-up.</AbstractText>AF occurred in 43% of the patients. The patients in the AF group had significantly more grafts (3.9 v 3.1, p = 0.02), and there was a small difference in age between the AF and non-AF groups (73 years v 69 years, p = 0.06). The free T3 concentration on the fourth postoperative day was significantly lower in the AF group (3.5 nmol/L v 4.6 nmol/L, p = 0.04). In logistic regression analysis, the independent predictors of AF were age, number of grafts, and serum free T3 concentration on the fourth postoperative day. In the group with low T3 concentration, the cardiac index was lower (1.4 v 1.8, p = 0.05) and the systemic vascular resistance index was higher (4,064 v 2,969, p = 0.04) but only immediately after the operation. Although the AF mostly appeared during the second to fourth postoperative days, there were no longer any differences in the hemodynamic state at that time.</AbstractText>In a group of elderly patients undergoing cardiac surgery, there was a strong association between a postoperative decrease of serum triiodothyronine levels and atrial fibrillation. The decrease of serum triiodothyronine levels was related to the changes of hemodynamic parameters only in the immediate postoperative period.</AbstractText>

Digitalis in heart failure! Still applicable?

In patients with heart failure and atrial fibrillation cardiac glycosides, generally in combination with beta-blockers, are indicated to control ventricular rate. In systolic heart failure and sinus rhythm, however, the use of digitalis continues to be debated. There are special concerns that cardiac glycosides might lead to an increased mortality rate in women. Retrospective analyses, however, do not indicate any sex-based differences in the effectiveness of cardiac glycosides. Beneficial effects of cardiac glycosides in heart failure seem to be related to the attenuation of sympathetic activation and neurohumoral alterations, which is already obtained at low digoxin serum concentrations, while high serum levels are associated with increased mortality. Therefore, in patients with sinus rhythm who remain symptomatic under an optimized therapy with ACE inhibitors, beta-blockers and diuretics in addition to digitalis should be considered regardless of the gender. However, target serum digoxin concentrations should be low in a range of 0.5 to 0.8 ng/ml.

Impact of preoperative and postoperative atrial fibrillation on outcome after mitral valvuloplasty for nonischemic mitral regurgitation.

We sought to determine the impact of preoperative or postoperative atrial fibrillation on survival, stroke, and cardiac function after mitral valvuloplasty for mitral regurgitation.</AbstractText>Between 1991 and 2003, 1026 patients with nonischemic/noncardiomyopathy mitral valve regurgitation underwent mitral valve plasty in 3 centers; 663 patients remained in sinus rhythm (group A), and 363 patients had atrial fibrillation or flutter preoperatively (group B) with concomitant maze procedures (group BM, n = 163) or without maze procedures (group BN, n = 200).</AbstractText>Eight-year freedom from cardiovascular-related death was better in group A (99.3%) than group B (BM: 96.9%, BN: 81.6%) ( P &lt; .001) and also better in group BM than group BN ( P = .007). The adjusted hazard ratio of group B versus group A for preoperative differences was 5.1 (95% confidence interval: 1.8-14.8). Eight-year freedom from stroke was better in group A (99.2%) than group B (BM: 98.2%, BN: 82.6%) ( P &lt; .001) and also better in group BM than group BN ( P &lt; .001). Patients with preoperative atrial fibrillation had larger left atria and left ventricular systolic dimensions. The adjunct maze procedure improved left ventricular systolic dimensions over mitral repair alone (group A vs B: P = .359; group BM vs BN: P = .001).</AbstractText>Preoperative permanent/persistent atrial fibrillation was associated with a dilated left atrium and reduced left ventricular function in patients with mitral regurgitation. Including the maze procedure with mitral repair improved survival, late cardiac function, and freedom from late stroke.</AbstractText>

Sex differences in outcome after ventricular fibrillation in out-of-hospital cardiac arrest.

Previous studies have shown that early defibrillation programs improve survival after an out-of-hospital cardiac arrest (OHCA). Reports also suggest that women fare worse than men do after cardiovascular events, but there is no population-based study of sex differences after an OHCA with early defibrillation. We, therefore, compared the short- and long-term survival and quality-of-life (QOL) in women and men after an OHCA.</AbstractText>All patients with a ventricular fibrillation (VF) OHCA who received early defibrillation in Olmstead County, Minnesota between November 1990 and December 2000 were included. Using medical records and the cardiac arrest database, the short- and long-term survival and QOL based on a SF-36 survey of each sex were compared. Adjusted QOL scores were obtained by using age- and sex-specific norms from a sample of the general U.S. population; an adjusted score of 50 (normalized mean) was considered normal.</AbstractText>Thirty-seven female and 163 male patients presented with a VF OHCA and early defibrillation. Survival to hospital admission was significantly better for women than men [30 female survivors to admission (81%), 112 male (69%), p = 0.04]. Paradoxically, survival to discharge among those admitted was worse for women [13 female survivors to discharge (43%), 66 male (61%), p = 0.04]. The average length of follow-up was 4.8+/-3.0 years. The 5-year expected survival was 83% in women and 78% in men (p = 0.48). There was no difference in call-to-shock time (6+/-2, 6+/-2 min, p = 0.6) or whether the arrest was witnessed (86, 82%, p = 0.64). There was no statistical difference between women and men in age (64+/-17, 65+/-14 years), ejection fraction (40+/-17, 40+/-18%), diabetes (17, 29%, p = 0.16), hypertension (23, 28%, p = 0.58) or known CAD (27, 48%, p = 0.06). Adjusted QOL scores were similar between women and men in terms of pain (52+/-9, 52+/-10) vitality (47+/-11, 40+/-9), general health (49+/-9, 44+/-7), social function (51+/-10, 51+/-8), and mental health (50+/-10, 49+/-6).</AbstractText>Women are more likely to survive to hospital admission following an OHCA. However, admitted women less likely to survive their hospital stay. Long-term survival and QOL are equally favorable in both sexes.</AbstractText>

The prevalence of atrial fibrillation among acute medical admissions in Kuwait.

To establish the prevalence of atrial fibrillation (AF) among acute medical admissions to the Adan Hospital, Kuwait, and to evaluate the clinical features of the patients.</AbstractText>Of 2,833 acute medical admissions to the Adan Hospital from January 1 to May 31, 2003, 120 patients with AF were included in the study. The patients were divided into paroxysmal or persistent (PPAF), and chronic atrial fibrillation (CAF). The prevalence of stroke and clinical features of the CAF patients with and without strokes were studied. All the patients with AF underwent echocardiography to evaluate left ventricular ejection fraction (LVEF) and left atrial dimension (LAD).</AbstractText>The prevalence of AF in the study period was 4.24%, of which 68.3% had CAF and 31.7% had PPAF. The prevalence of heart failure, ischemic heart disease, systemic hypertension, and diabetes mellitus was 27.5, 55.8, 65.8, and 53.3%, respectively. Patients with CAF were older and had a higher prevalence of heart failure compared to PPAF patients. Of the patients with CAF, 26.8% had at least one episode of stroke. The CAF patients had lower LVEF and larger LAD than PPAF patients. Stroke patients with CAF had lower LVEF and larger LAD as compared to those without stroke.</AbstractText>Atrial fibrillation is a common admission diagnosis in our hospital. Patients with AF commonly suffer from heart failure, hypertension, diabetes mellitus, and ischemic heart disease. There was a high prevalence of stroke among CAF patients.</AbstractText>

Right atrial pacing impairs cardiac function during resynchronization therapy: acute effects of DDD pacing compared to VDD pacing.

We aimed to compare the hemodynamic effects of right-atrial-paced (DDD) and right-atrial-sensed (VDD) biventricular paced rhythm on cardiac resynchronization therapy (CRT).</AbstractText>Cardiac resynchronization therapy improves hemodynamics in patients with severe heart failure and left ventricular (LV) dyssynchrony. However, the impact of active right atrial pacing on resynchronization therapy is unknown.</AbstractText>Seventeen CRT patients were studied 10 months (range: 1 to 46 months) after implantation. At baseline, the programmed atrioventricular delay was optimized by timing LV contraction properly at the end of atrial contraction. In both modes the acute hemodynamic effects were assessed by multiple Doppler echocardiographic parameters.</AbstractText>Compared to DDD pacing, VDD pacing resulted in much better improvement of intraventricular dyssynchrony assessed by the septal-to-posterior wall motion delay (VDD 106 +/- 83 ms vs. DDD 145 +/- 95 ms; p = 0.001), whereas the interventricular mechanical delay (difference between onset of pulmonary and aortic outflow) did not differ (VDD 20 +/- 21 ms vs. DDD 18 +/- 17 ms; p = NS). Furthermore, VDD pacing significantly prolonged the rate-corrected LV filling period (VDD 458 +/- 123 ms vs. DDD 371 +/- 94 ms; p = 0.0001) and improved the myocardial performance index (VDD 0.60 +/- 0.18 vs. DDD 0.71 +/- 0.23; p &lt; 0.01).</AbstractText>Our findings suggest that avoidance of right atrial pacing results in a higher degree of LV resynchronization, in a substantial prolongation of the LV filling period, and in an improved myocardial performance. Thus, the VDD mode seems to be superior to the DDD mode in CRT patients.</AbstractText>

Effects of left ventricular assist device therapy on ventricular arrhythmias.

In a retrospective study, we sought to evaluate the effect of left ventricular assist device (LVAD) therapy on ventricular tachyarrhythmias in patients with advanced congestive heart failure.</AbstractText>Despite the increasing use of LVAD as a bridge to cardiac transplantation, our knowledge regarding its effect on ventricular arrhythmias is currently limited to small series. Little is known about the prevalence, predictors, and clinical consequences of ventricular arrhythmias in LVAD recipients.</AbstractText>We reviewed the pre- and post-LVAD course of the last 100 consecutive adult patients to receive a HeartMate LVAD (Thoratec Laboratories Corp., Pleasanton, California) at our institution. All ventricular arrhythmias sustained for at least 30 s or requiring defibrillation were analyzed. All documented pre- and post-LVAD sustained ventricular arrhythmias were classified either as monomorphic ventricular tachycardia (MVT) or polymorphic ventricular tachycardia (PVT)/ventricular fibrillation (VF).</AbstractText>Our population had an average age of 51 years, had predominately ischemic cardiomyopathy (63%), and a mean left ventricular ejection fraction of 20 +/- 10%. New-onset MVT was observed in 18 patients who did not have MVT before LVAD placement. After LVAD, new-onset MVT was 4.5 times more likely than elimination of previously present MVT (p = 0.001), whereas the effect of LVAD on incidence of PVT/VF was not significant. In a multivariate Cox proportional hazards regression analysis, serum electrolyte abnormality was an independent predictor of post-LVAD ventricular arrhythmias. Preoperative MVT did not predict postoperative MVT.</AbstractText>After LVAD placement, there is a significant rise in the incidence of de novo MVT. By contrast, the incidence of PVT/VF was unaffected by LVAD placement.</AbstractText>

Coronary-subclavian steal syndrome. A case report.

Coronary-subclavian steal is an unusual clinical syndrome after successful internal mammary-coronary artery bypass grafting. Proximal subclavian artery (SA) stenosis is present and atherosclerotic disease is the underlying pathophysiologic mechanism in the majority of cases. The authors report a case of a sixty-two-year old man with angina and ventricular fibrillation soon after myocardial revascularization with left internal mammary artery (LIMA) to left anterior descending coronary (LAD). Dobutamine stress echocardiography showed ischemia in the anterior myocardial territory with patent LIMA-LAD bypass in the angiographic evaluation. This procedure showed occlusion of the proximal SA with reversal of flow in the LIMA. The best therapeutic approach was discussed and a carotid-subclavian bypass was performed with restoration of antegrade blood flow and reversal of the clinical setting.

Hypertensive heart disease.

Hypertensive heart disease encompasses anatomical changes and altered physiology of heart muscle, coronary arteries, and great vessels. Left ventricular hypertrophy is not only a target organ response to increased afterload, but is also the most potent cardiovascular risk factor. Regression of hypertrophy reduces morbidity and mortality. Heart failure may be present in the absence of a reduction of myocardial contractility. Ischemic heart disease occurs in the absence of epicardial coronary disease. Left atrial size and atrial fibrillation are associated. Potentially lethal ventricular arrhythmias and sudden cardiac death are more common in hypertensive patients. The relationship of aortic root size to blood pressure is weaker than expected; however, the relationship to aortic dissection is stronger. Careful attention and treatment of left ventricular hypertrophy, heart failure, ischemic heart disease, and atrial fibrillation will improve survival.

Changes in left atrial size in patients with persistent atrial fibrillation: a prospective echocardiographic study with a 5-year follow-up period.

Atrial fibrillation (AF) is a common arrhythmia, occurring in 0.4% of the general population. AF has been shown to be associated with left atrial enlargement, which is considered both a cause and a consequence of the arrhythmia. The aim of the study was to determine the influence of AF on changes in echocardiographically determined left atrial (LA) size, during 5 year follow-up period, in a population with well-controlled hypertension, free from structural heart disease, except mild left ventricle thickening, and with an absence of other potential causes of atrial enlargement. The study group, comprised of 81 patients with persistent AF, with underlying hypertensive heart disease, consecutively referred for elective direct current cardioversion. The mean age of the study population was 59.3+/-8.4 years (ranged from 43 to 80), a mean AF duration was 8.8+/-8.7 months (ranged from 1 to 30 months). The patients underwent two-dimensional echocardiography to determine left atrial size, before and 5 years after cardioversion. Twenty out of eighty-one cardioverted patients maintained sinus rhythm 5 years after cardioversion (25%). In this group anteroposterior LA dimension and LA volume decreased from a mean (+/-S.D.) 49.7+/-4.5 to 46.8+/-4.8 mm (-6%, p &lt; 0.05) and from 103.6+/-28.8 to 91.1+/-18.3 cm2 (-9.2%, p &lt; 0.05), respectively. Left ventricle ejection fraction increased from 52.8+/-6.3% to 60.0+/-4.0% (p &lt; 0.05) and clinical stage improved in patients who maintained sinus rhythm through 5 years. In contrast, in the AF group, anteroposterior LA dimension and LA volume increased from 46.6+/-4.3 to 48.1+/-5.6 mm, and from 91.3+/-20 to 103+/-34 cm2 (by an average 3.3% and 14.3%, respectively), at the end of study. When divided into two groups: Imid R:II and III NYHA class, in AF patients LA volume increased by an 21.4% in the III NYHA class and 7.3% in the Imid R:II NYHA class. Left ventricular ejection fraction did not change between the two echocardiographic studies in the AF group (44.9+/-14.3% vs. 44.6+/-12.9%, Ns). In conclusion, it has been proved that AF occurring in patients with hypertensive heart disease causes a slow and progressive increase in LA size especially in patients in functional III NYHA class, and that the maintenance of sinus rhythm partially reverts the process of LA enlargement in patients with well-controlled hypertension, a history of AF and successfully treated for AF.

[Sudden cardiac death in familial hypertrophic cardiomyopathy. Identification of high-risk patients].

Hypertrophic cardiomyopathy (HCM) is a relatively frequent, genetically determined primary cardiomyopathy, characterized by most often asymmetric hypertrophy of the ventricular septum with or without systolic obstruction of the left ventricular outflow tract. HCM is a genetically heterogeneous disease, with 12 different disease-causing genes beeing indentified to date. Histologically the disease is characterized by hypertophy and disarray of myofibrils as well as by an increase in myocardial fibrosis. Clinically, these changes may lead to palpitations, dyspnoe on exertion, and/or angina pectoris. However, they also lead to an increased propensity to the development of severe ventricular tachyarrhythmias and sudden cardiac death. The incidence of sudden death is significantly increased in HCM, particularly in affected young subjects. Risk stratification in HCM should include a complete clinical-cardiological evaluation that should also consider new diagnostic features, e. g. MR imaging. Major risk factors for sudden cardiac death include a survived cardiac arrest (ventricular fibrillation), non-sustained and sustained ventricular tachycardia, a history of premature familial sudden death, unexplained syncope, an abnormal blood pressure response on exercise, and left ventricular thickness greater than or equal to 3 cm. Ideally, risk stratification should also include genetic testing, since some gene mutations seem to be associated with a higher risk for sudden cardiac death than others. However, genetic testing in HCM in not yet available on a routine basis. The implantation of a cardioverter/defibrillator is first-line therapy in patients with documented ventricular tachycardia/fibrillation or patients who have survived sudden cardiac death. These devices also play an important role in the primary prevention of sudden cardiac death in HCM. Algorithms and scores are available to estimate the risk of sudden death, however, the decision to implant a cardioverter/defibrillator remains an individual decision in every single patient.

Cardiac Arrest Resuscitation Evaluation in Los Angeles: CARE-LA.

We determine survival for out-of-hospital cardiac arrests in Los Angeles using the Utstein method and compare these data with that reported for other urban and suburban areas.</AbstractText>This was a prospective observational cohort study of adult patients in Los Angeles presenting with nontraumatic, out-of-hospital cardiac arrest and with attempted out-of-hospital resuscitative efforts between July 1, 2000, and July 1, 2001. Entry criteria, time intervals, and nodal events conformed to Utstein template recommendations. The single target endpoint was neurologically intact survival at hospital discharge.</AbstractText>Of 2,021 consecutive cardiac arrest patients on whom resuscitation was attempted, 1,700 (84%) met entry criteria as a primary cardiac event. Overall, neurologically intact survival was 1.4% (99% confidence interval [CI] 0.8% to 2.4%) Three patients were lost to follow-up. Survival from bystander-witnessed ventricular fibrillation was 6.1% (99% CI 3.3% to 11.0%). Absolute survival differences from witnessed ventricular fibrillation was higher but not statistically different than that from Chicago (-3%; 99% CI -8% to 2%) and New York City (-2%; 99% CI -6% to 3%). The rate of bystander cardiopulmonary resuscitation (CPR) for our population was 28%, for which the overall survival rate was 2.1%. The survival rate for patients with witnessed arrests and bystander CPR was 3.2%. Among patients with no bystander CPR, the survival rate was 1.0%.</AbstractText>Survival from out-of-hospital cardiac arrest in Los Angeles was low but similar to that reported for New York and Chicago. This low survival rate may be due to population density, low bystander CPR rates, and traffic congestion delaying emergency response.</AbstractText>

Management of atrial fibrillation in patients with chronic obstructive pulmonary disease.

Atrial fibrillation is the cardiac arrhythmia encountered most often in clinical practice. It is triggered by many conditions such as thyroid dysfunction, cardiac disease, alcohol, and pulmonary disease. Patients with chronic obstructive pulmonary disease (COPD) are susceptible to many insults that can lead to an acute deterioration superimposed on chronic disease. Changes in blood gases, abnormalities in pulmonary functions, and hemodynamic changes resulting from pulmonary hypertension can lead to the development of atrial fibrillation. Atrial fibrillation and COPD frequently coexist and complicate treatment of both conditions. The treatment of COPD exacerbation may include beta-adrenergic agonist and theophylline, which can precipitate atrial fibrillation with rapid ventricular response. Pharmacologic and electrical cardioversion may be ineffective in the management of atrial fibrillation in patients with COPD until respiratory decompensation has been corrected. This article focuses on the management of atrial fibrillation in patients with COPD.

The influence of ethnicity on warfarin dosage requirement.

The optimal dose of warfarin varies among individuals, and the prediction of a maintenance dose is difficult. Ethnicity has been reported to influence warfarin dosing.</AbstractText>To quantitate the influence of ethnicity on warfarin dose requirement.</AbstractText>We conducted a retrospective cohort study at a university anticoagulation clinic to evaluate the influence of ethnicity on warfarin dose. Inclusion criteria included age &gt; or = 18 years, target international normalized ratio (INR) 2-3, and warfarin management within the clinic for &gt; or = 3 months with a minimum of 5 clinic visits. We collected clinical and demographic data including age, gender, weight, ethnicity, disease states, concomitant medications, indication, weekly warfarin dosage, and INR. To assess potential confounders, multivariate, repeated-measures regression analysis was used to identify and adjust for variables that may influence the maintenance dose of warfarin.</AbstractText>Of the 345 patients who met the inclusion criteria, 27% were Asian American, 6% Hispanic, 54% white, and 14% African American. The adjusted mean (95% CI) weekly warfarin doses for patients with an INR goal of 2 to 3 were Asian Americans 24 mg (21 to 27), Hispanics 31 mg (25 to 37), whites 36 mg (34 to 39), and African Americans 43 mg (39 to 47) (p &lt; 0.001). Additional factors found to influence warfarin dose requirement included age, weight, concomitant use of amiodarone, and diagnosis of venous thromboembolism.</AbstractText>Warfarin dose requirements vary across ethnic groups even when adjusted for confounding factors, suggesting that genetic variation contributes to interpatient variability.</AbstractText>

Pulmonary haemodynamics at rest and during exercise in patients with significant pulmonary vein stenosis after radiofrequency catheter ablation for drug resistant atrial fibrillation.

Iatrogenic pulmonary vein (PV) stenosis after radiofrequency catheter ablation for atrial fibrillation (AF) is a new pathology in cardiology. The effects of PV stenosis on the pulmonary circulation are not yet known. We provide long-term follow-up data in patients with significant PV stenosis including magnetic resonance imaging (MRI) and Swan Ganz (SG) right heart catheterization.</AbstractText>One hundred and seventeen patients had MRI 12-24 months after the AF ablation procedure. Eleven patients (58+/-7 years, nine males) with significant stenosis (n=9) or occlusion of the proximal PV (n=5) at this follow-up were re-examined using MRI and SG right heart catheterization at rest and during exercise (follow-up time since PV ablation 50+/-15 months). None of these underwent previous PV angioplasty. When compared with prior MRI studies, no significant changes were noted. At rest, no patient had pulmonary hypertension. At 100 W, seven patients had elevated pulmonary artery pressures, three of them probably caused, in part, by left ventricular dysfunction.</AbstractText>Significant stenosis/occlusions of one or two PV do not create pulmonary hypertension at rest during long-term follow-up. However, seven of the 11 patients develop pulmonary hypertension during exercise. All three patients with stenosis/occlusions of two PV were affected.</AbstractText>

Endocardial radiofrequency ablation during mitral valve surgery: effect on cardiac rhythm, atrial size, and function.

Restoration of sinus rhythm is thought to lead to a reduction in left atrial size and to recovery of atrial contraction. We aimed to investigate changes in atrial size and function in patients undergoing radiofrequency ablation for atrial fibrillation during mitral valve surgery.</AbstractText>In a prospective study, 70 patients (64 +/- 10 years) with mitral valve disease and atrial fibrillation underwent mitral surgery and left atrial endocardial radiofrequency ablation. Evaluation was achieved before surgery, at 7 days, 5 months, and 22 months after surgery. Maximal right and left atrial areas, left atrial diameter, and volume were measured. Atrial filling fraction (ventricular filling related to atrial contraction to total ventricular filling ratio) was used as an index of atrial contraction.</AbstractText>At the end of follow-up (22 +/- 10 months) most patients (91%) were in sinus rhythm. Actuarial freedom from atrial fibrillation recurrence was 62.5% after 2 years. Atrial size decreased, with a significant improvement in right (36 +/- 15 vs 10 +/- 20% preoperatively, p &lt; 0.0001) and left (25 +/- 12 vs 7 +/- 14%, p &lt; 0.0001) atrial filling fraction. Despite similar preoperative atrial size, at the end of follow-up atrial fibrillation recurrence was associated with a higher left atrial volume than in patients free of recurrence (41 +/- 14 vs 32 +/- 9 mL/m2, p = 0.004). Independent predictors of atrial fibrillation recurrence were previous mitral procedure (p = 0.029), left ventricular ejection fraction (p = 0.033), and mitral rheumatic lesion (p = 0.034).</AbstractText>Left atrial radiofrequency ablation for atrial fibrillation during mitral surgery is an effective procedure restoring sinus rhythm. Right and left atrial size was significantly reduced, with a recovery in atrial contraction.</AbstractText>

[Surgical treatment of active infective endocarditis].

To summarize the recent experience of surgical management of the active infective endocarditis (IE) disease in Fuwai Hospital.</AbstractText>From October 1, 1996 to December 31, 2003, 54 patients with active IE underwent heart operation in Fuwai Hospital. There were 41 males, 13 females, with an average age of 35 years old and an average weight 58 kg. Of the cases, 23 had congenital anomalies of the heart, and 1 had rheumatic valvulitis. Streptococci were found in 20 patients, staphylococci in 3, enterococci in 1, enterococcus in 2 and G(+) cocci in 1. Pre-operative cardiac classification (NYHA): class I was in 6 cases, class II in 12 cases, class III in 7 cases and class IV in 29 cases. Systemic embolization occurred in 23 cases and pulmonary infarction in 2 cases. Emergent operations were performed in 27 cases because of heart failure (8 cases), embolism (4 cases), aggressive infection (3 cases), heart failure plus embolism (2 cases), heart failure with aggressive infection (4 cases), aggressive infection with embolism (2 cases) and all the three factors (4 cases). The operations included aortic valve replacement (25 cases), aortic and mitral valves replacement (15 cases), mitral valve replacement (6 cases), mitral valve repair (3 cases), pulmonic valve replacement (1 case) and intracardiac shunt repair (4 cases).</AbstractText>The operative mortality was 17% (5 operative death and 4 lost in following-up after being discharged). All of operative deaths were due to infection. Fourteen patients had operative complications. The morbidity included peri-prosthetic leakage (8 cases), prosthetic IE (5 cases), residual intracardiac shunt (2 cases), complete heart block (2 cases), myocardial infarction, ventricular fibrillation, pulmonary trunk stenosis, and mitral regurgitation (1 case in each). Post-operative cardiac classification (NYHA): class I was in 41 cases, class II in 3 cases, class III in 1 case. Two patients were re-operated because of peri-prosthetic leakage, and then they were cured. Re-operation was also performed in other 3 patients. Unrelated late sudden death occurred in 1 patient and hemiplegia caused by anticoagulant intracranial hemorrhage in another patient.</AbstractText>Acceptable results can be achieved with active surgical intervention in active patients with IE.</AbstractText>

Molecular predictors of drug-induced prolongation of the QT interval.

One of the most common causes of drug withdrawal from the market is the prolongation of the QT interval associated with polymorphic ventricular tachycardia or torsade de pointes (TdP) that can degenerate into ventricular fibrillation and sudden cardiac death. Cardiac and non-cardiac drugs prolong the QT interval and cause TdP by blocking cardiac K+ channels in general, and selectively blocking the rapidly activating delayed rectifier channel IKr. Co-assembly of HERG (human-ether-a-go-go-related gene) alpha-subunits and MiRP1 (MinK-related peptide 1) beta-subunits recapitulate the behavior of native human IKr, and the majority of mutations of HERG and MiRP1 decrease the repolarizing current, delay ventricular repolarization and prolong the QT. Thus, drug-induced QT prolongation and TdP might represent an iatrogenic reproduction of the congenital long-QT syndrome (LQTS). Current evidence suggests that 5 to 10% of persons in whom TdP develops on exposure to QT-interval prolonging drugs harbor mutations associated with the LQTS and can therefore be viewed as having a subclinical form of the congenital syndrome. This clinical observation is entirely consistent with the concept of reduced repolarization reserve arising from a mutation in an ion-channel gene, which predisposes the carrier to drug-induced TdP. This review centers on the possible molecular mechanisms underlying drug-induced QT prolongation and TdP, the description of specific drugs and risk factors facilitating the development of TdP, and the recommendations for preventing and treating this potentially fatal arrhythmia.

Phase 2 ventricular arrhythmias in acute myocardial infarction: a neglected target for therapeutic antiarrhythmic drug development and for safety pharmacology evaluation.

Ventricular fibrillation (VF), a cause of sudden cardiac death (SCD) in the setting of acute myocardial infarction (MI), remains a major therapeutic challenge. In humans, VF may occur within minutes or hours after the onset of chest pain, so its precise timing in relation to the onset of ischaemia is variable. Moreover, because VF usually occurs unobserved, out of hospital, and is usually lethal in the absence of intervention, its precise timing of onset is actually unknown in most patients. In animal models, the timing of susceptibility to VF is much better characterised. It occurs in two distinct phases. Early VF (defined as phase 1 VF, with possible subphases 1a and 1b in some animal species) occurs during the first 30 min of ischaemia when most myocardial injury is still reversible. Late VF, defined as phase 2 VF, occurs when myocardial necrosis is becoming established (after more than 90 min of ischaemia). Although much is known about the mechanisms and pharmacology of phase 1 VF, little is known about phase 2 VF. By reviewing a range of different types of data we have outlined the likely mechanisms and clinical relevance of phase 2 VF, and have evaluated possible future directions to help evolve a strategy for its suppression by drugs. The possibility that a proarrhythmic effect on phase 2 VF contributes to the adverse cardiac effects of certain cardiac and noncardiac drugs is also discussed in relation to the emerging field of safety pharmacology. It is concluded that suppression of phase 2 as well as phase 1 VF will almost certainly be necessary if drugs of the future are to achieve what drugs of the past and present have failed to achieve: full protection against SCD. Likewise, safety will require avoidance of exacerbation of phase 2 as well as phase 1 VF.

Xenon attenuates cerebral damage after ischemia in pigs.

Cerebral blood flow may be compromised in a variety of anesthetic procedures, and ischemic cerebral complications represent the leading cause of morbidity after cardiac operations. With the growing importance of neuroprotective strategies, the current study was designed to determine whether xenon would attenuate cardiac arrest-induced brain injury in pigs.</AbstractText>Twenty-four pigs (aged 12-16 weeks) were investigated in a randomized design. General hemodynamics, intracranial pressure, brain tissue oxygenation, and cerebral microdialysis parameters were investigated. The animals were assigned to two groups to receive anesthesia with either xenon (75%) in oxygen (25%) or total intravenous anesthesia combined with air in oxygen (25%) ventilation 15 min before cardiac arrest. After induction (t0) of cardiac arrest of 4 min, cardiopulmonary resuscitation was performed for 1 min, and the induced ventricular fibrillation was terminated by electrical defibrillation. The investigation time was 240 min.</AbstractText>Approximately 60 s after cardiac arrest, brain tissue oxygenation decreased to a critical level of less than 5 mmHg, paralleled by a decrease in electroencephalographic activity. Glycerol as a damage marker increased significantly (&gt; 200 m; P &lt; 0.05), with a peak 90 min after cardiac arrest in both groups. Glycerol concentrations during reperfusion were significantly lower and normalized faster in the xenon group as compared with the total intravenous anesthesia group.</AbstractText>Although the primary ischemic lesion in this model was similar in both groups, the cerebral microdialysis data show that xenon induces a differential neurochemical benefit in cerebral cell damage and metabolism as compared with total intravenous anesthesia in vivo during cerebral reperfusion after cardiac arrest in a pig model.</AbstractText>

Defective cardiac ryanodine receptor regulation during atrial fibrillation.

Ca2+ leak from the sarcoplasmic reticulum (SR) may play an important role in triggering and/or maintaining atrial arrhythmias, including atrial fibrillation (AF). Protein kinase A (PKA) hyperphosphorylation of the cardiac ryanodine receptor (RyR2) resulting in dissociation of the channel-stabilizing subunit calstabin2 (FK506-binding protein or FKBP12.6) causes SR Ca2+ leak in failing hearts and can trigger fatal ventricular arrhythmias. Little is known about the role of RyR2 dysfunction in AF, however.</AbstractText>Left and right atrial tissue was obtained from dogs with AF induced by rapid right atrial pacing (n=6 for left atrial, n=4 for right atrial) and sham instrumented controls (n=6 for left atrial, n=4 for right atrial). Right atrial tissue was also collected from humans with AF (n=10) and sinus rhythm (n=10) and normal cardiac function. PKA phosphorylation of immunoprecipitated RyR2 was determined by back-phosphorylation and by immunoblotting with a phosphospecific antibody. The amount of calstabin2 bound to RyR2 was determined by coimmunoprecipitation. RyR2 channel currents were measured in planar lipid bilayers. Atrial tissue from both the AF dogs and humans with chronic AF showed a significant increase in PKA phosphorylation of RyR2, with a corresponding decrease in calstabin2 binding to the channel. Channels isolated from dogs with AF exhibited increased open probability under conditions simulating diastole compared with channels from control hearts, suggesting that these AF channels could predispose to a diastolic SR Ca2+ leak.</AbstractText>SR Ca2+ leak due to RyR2 PKA hyperphosphorylation may play a role in initiation and/or maintenance of AF.</AbstractText>

Near-miss SIDS due to Brugada syndrome.

A 19 day old infant was successfully resuscitated from ventricular fibrillation. The 12 lead ECG was normal, with a normal QT interval, and remains so over three years follow up. DNA analysis revealed a missense mutation (R1193Q) in the SCN5A gene, previously linked with familial sudden unexpected nocturnal death syndrome, also known as Brugada syndrome.

Improved defibrillation efficacy with an ascending ramp waveform in humans.

The purpose of this study was to compare an ascending ramp waveform (RAMP) with a standard, clinically available biphasic truncated exponential waveform (BTE) for defibrillation in humans.</AbstractText>In animal studies, RAMP had a lower defibrillation threshold (DFT) than BTE.</AbstractText>We studied 63 patients at implantable cardioverter-defibrillator placement using a dual-coil lead and left pectoral active can. The subjects were divided into two groups, one with a 12-ms ascending first phase and one with a 7-ms ascending first phase. Phase 2 of RAMP for both groups was a truncated exponential decay with 65% tilt and reversed polarity. The BTE had a 50% tilt in each phase. DFT and upper limit of vulnerability (ULV) were measured for both waveforms using a binary search protocol.</AbstractText>The patient population was 77% male, with a mean age of 63 +/- 10 years and ejection fraction of 33 +/- 13%. Delivered energy at DFT was lower with the 7-ms RAMP vs BTE (5.4 +/- 2.6 J vs 6.5 +/- 3.4 J; P &lt; .01) but unchanged with the 12-ms RAMP (7.4 +/- 4.5 J vs 7.1 +/- 4.9 J). Maximal voltage at DFT was significantly lower with either RAMP compared to BTE (P &lt; .01). There was a strong correlation between ULV and DFT for both RAMP and BTE (P &lt; .01).</AbstractText>The 7-ms ascending ramp waveform significantly reduced delivered energy (18%) and voltage (24%) at DFT, whereas the 12-ms RAMP reduced only DFT voltage. This is the first report of a waveform that is superior to a BTE for defibrillation in humans. ULV correlates with DFT for RAMP, supporting the use of ULV testing for implantation of devices.</AbstractText>

The inward rectifier current (IK1) controls cardiac excitability and is involved in arrhythmogenesis.

The cardiac inwardly rectifying potassium current (I(K1)) stabilizes the resting membrane potential and is responsible for shaping the initial depolarization and final repolarization of the action potential. The inwardly rectifying potassium channel (Kir2.x) subfamily members primarily mediate cardiac I(K1), but other inward rectifiers, including the acetylcholine-sensitive (Kir3.x) and ATP-sensitive (Kir6.x) inward rectifiers, also may modulate cardiac excitability. Studies suggest I(K1) plays a role in ventricular arrhythmias, highlighted by the recently described Andersen's syndrome and studies in the guinea pig heart model of ventricular fibrillation. This article describes the salient properties of cardiac I(K1) and discusses the role of this current in the cardiac action potential and in underlying regional differences in cardiac excitability. The mechanism of channel block, assembly, and structure are reviewed. The article discusses the role of I(K1) in ventricular fibrillation and speculates on modulation of I(K1) as a preventative antiarrhythmic mechanism.

Double SCN5A mutation underlying asymptomatic Brugada syndrome.

The purpose of this study was to identify risk markers in patients with Brugada syndrome.</AbstractText>Patients with Brugada syndrome who experience syncope or aborted sudden death are at high risk for recurrent lethal arrhythmias. The prognosis and therapeutic approaches in asymptomatic individuals with a Brugada-type ECG (asymptomatic Brugada syndrome) are controversial.</AbstractText>We genetically screened 30 asymptomatic probands (29 men and 1 woman; mean age 47.1 years) exhibiting a spontaneous Brugada-type ECG. Family members of patients with Brugada syndrome were excluded from the study.</AbstractText>Twenty-nine of 30 patients (96.7%) remained symptom-free for at least 3 years. One patient (case 1) with a family history of sudden death died suddenly during sleep. Ventricular fibrillation was induced by programmed electrical stimulation in 14 of 18 subjects (78%), but none of these 18 subjects developed spontaneous ventricular arrhythmias. Genetic screening failed to identify SCN5A mutations in most cases but demonstrated a novel double missense mutation (K1527R and A1569P) located on the same allele in another asymptomatic subject (case 2). Heterologously expressed mutant Na channels exhibited a negative shift of steady-state inactivation (9.2 mV) and enhanced slow inactivation, suggesting this individual harbors a subclinical channel dysfunction compatible with symptomatic Brugada syndrome.</AbstractText>Asymptomatic individuals with a Brugada-type ECG generally have a better prognosis than their symptomatic counterparts, but a subgroup of these individuals may have a poor prognosis. Severe Na channel dysfunction as a result of SCN5A mutations may not be sufficient to cause symptoms or arrhythmias in patients with Brugada syndrome, suggesting unknown factors or modifier genes influence arrhythmogenesis.</AbstractText>

Heart failure hospitalization is more common in pacemaker patients with sinus node dysfunction and a prolonged paced QRS duration.

The purpose of this study was to determine whether a prolonged paced QRS duration increases the risk of cardiac dysfunction.</AbstractText>Right ventricular apical pacing mimics left bundle branch block, results in a prolonged QRS duration of variable duration, and causes ventricular desynchronization.</AbstractText>In the Mode Selection Trial (MOST), QRS duration was measured in patients who had at least one paced ventricular complex recorded on 12-lead ECG within 3 months of enrollment (early) and after 9 months (late). Clinical endpoints including heart failure hospitalization, mortality, and atrial fibrillation were analyzed. A total of 1,026 patients were included in the analysis. Median age was 75 years (25th, 75th percentiles = 69, 80) and median ejection fraction prior to implant was 55% (45, 60). The cumulative percent ventricular pacing (DDDR and VVIR) was 81% over a median follow-up of 33 months. During period, 123 patients had heart failure hospitalization, 197 died, and 261 patients had atrial fibrillation.</AbstractText>Cox proportional hazards models demonstrated that paced QRS duration was a strong predictor of heart failure hospitalization (hazard ratio 1.15; 95% confidence interval 1.07,1.23) for each 10-ms increase in paced QRS duration (P = .001). The increased risk was unaffected by adjustment for other known predictors of heart failure hospitalization in the study. Paced QRS duration was not significant for mortality (P = .41) or atrial fibrillation (P = .20) when baseline QRS duration and other predictors were included.</AbstractText>Paced QRS duration is a significant, independent predictor of heart failure hospitalization in patients with sinus node dysfunction. A very long paced QRS duration is associated with increased heart failure hospitalization.</AbstractText>

T-wave alternans phase following ventricular extrasystoles predicts arrhythmia-free survival.

The purpose of this study was to assess the value of T-wave alternans (TWA) following ventricular extrasystoles in predicting arrhythmia-free survival.</AbstractText>Stratifying risk for sudden death in patients with coronary disease and moderate left ventricular (LV) dysfunction remains a challenge. We hypothesized that, in such patients, a discontinuity in beat-to-beat T-wave alternation (TWA phase reversal) following single ventricular extrasystoles reflects transiently exaggerated repolarization dispersion, and predicts spontaneous ventricular arrhythmias.</AbstractText>We studied 59 patients with ischemic LV dysfunction (mean LV ejection fraction 38.7 +/- 5.3%) and nonsustained ventricular tachycardia undergoing programmed stimulation. TWA was computed spectrally from the ECG during ventricular pacing, and TWA phase reversal was reflected by a discontinuity in T-wave oscillation after single ventricular extrasystoles.</AbstractText>Patients induced into ventricular arrhythmias (n = 36) had greater TWA magnitude (V(alt): 6.60 +/- 6.46 microV vs 2.61 +/- 1.97 microV; P = .001) and more frequent TWA phase reversal (62.1% vs 44.4%; P = .02) than those who were not (n = 23). During a mean follow-up of 36 +/- 12 months, positive TWA (V(alt) &gt; or =1.9 microV) and TWA phase reversal both (P &lt; .05) predicted events (all-cause mortality, ventricular tachycardia, ventricular fibrillation). Univariate predictors of arrhythmia-free survival were TWA phase reversal (P &lt; .005), positive TWA (P &lt; .05), age (P = .008), and LV mass index (P = .043). On multivariate analysis, only TWA phase reversal and age predicted events; if TWA phase was excluded, only positive TWA and age predicted events.</AbstractText>Phase reversal in TWA following ventricular extrasystoles predicts spontaneous ventricular arrhythmias and all-cause mortality in patients with moderate ischemic LV dysfunction and was a better predictor than positive TWA or programmed ventricular stimulation.</AbstractText>

Relationship between atrial tachyarrhythmias and symptoms.

The purpose of this study was to correlate patient-reported symptoms of atrial fibrillation with the underlying rhythm.</AbstractText>The reliability of patient-reported symptoms as a marker of atrial fibrillation recurrence has not been well studied.</AbstractText>This prospective multicenter trial correlated the recurrence of atrial tachyarrhythmias with symptoms in patients with a history of atrial fibrillation and a standard indication for permanent pacing. Pacemaker-detected atrial tachyarrhythmia events were correlated with symptoms. Patients logged symptomatic events into the device's memory via an external manual activator. Patients were followed for 12 months and were contacted weekly to ensure compliance with activator usage. Episodes were classified as symptomatic atrial tachyarrhythmia, asymptomatic atrial tachyarrhythmia, or symptomatic nonatrial tachyarrhythmia depending on concordance between patient symptoms and the rhythm.</AbstractText>Forty-eight patients underwent implantation of a DDDRP pacemaker and were followed for 12 +/- 2 months. A median of 25.0 (4.0-55.8) symptomatic events attributed to atrial fibrillation. A median of 1.0 (0.0-10.0) symptomatic atrial tachyarrhythmia episodes were documented during follow-up. Symptoms related to atrial fibrillation were reported in 6% of atrial tachyarrhythmia episodes identified by the pacemaker. The probability that symptoms were associated with an atrial tachyarrhythmia (positive predictive value) was 17%. The ventricular rate between symptomatic and asymptomatic atrial tachyarrhythmia events was not significantly different.</AbstractText>Among patients with symptomatic bradycardia and a history of atrial fibrillation, symptoms of atrial fibrillation often were not associated with documented atrial tachyarrhythmias, and more than 90% of atrial tachyarrhythmias were clinically silent.</AbstractText>

One conversion of ventricular fibrillation is adequate for implantable cardioverter-defibrillator implant: an analysis from the Low Energy Safety Study (LESS).

The purpose of this study was to analyze defibrillation conversion data from the Low Energy Safety Study (LESS) to determine how implant criteria that use fewer inductions of ventricular fibrillation (VF) correlate with outcome and, in particular, to assess the reliability of using a single VF induction and test shock at 14 J.</AbstractText>A safety margin of 10 J has become standard for implantation of an implantable cardioverter-defibrillator (ICD), but the specifics and rigor of the implant test sequence are not standardized.</AbstractText>In LESS, 611 ICD recipients completed a rigorous VF induction test scheme that began at 14 J and continued until the energy that succeeded three times without a failure was determined (DFT++). The data were analyzed to determine how well the outcome of the first 14-J shock and various other combinations of first and/or second shocks predicted a rigorous gold standard of DFT++ &lt; or =21 J (i.e., three successes at &lt; or =21 J).</AbstractText>The positive predictive accuracy for the 91% of patients in whom the first 14-J shock succeeded was virtually identical to the positive predictive accuracy for the commonly used criteria of two successes at &lt; or =17 J (99.1% vs 99.0%, P = .69), and slightly higher than the positive predictive accuracy for two successes at &lt; or =21 J (98.8%, P = .51). A single success at 17 J or 21 J had a somewhat lower positive predictive accuracy of 98.2% (P = .17). Eliminating VF induction testing would have resulted in a significantly lower positive predictive accuracy of 97.1% (P = .01).</AbstractText>A single conversion success at 14 J on the first VF induction provides similar positive predictive accuracy as two successes at 17 J or 21 J. Using this criterion, 91% of patients meet implant criteria with a single induction of ventricular fibrillation.</AbstractText>

Spontaneous onset of ventricular fibrillation in Brugada syndrome with J wave and ST-segment elevation in the inferior leads.

We report the case of a 52-year-old man with variant Brugada syndrome who was successfully resuscitated from ventricular fibrillation (VF). Resting ECG showed J wave and ST-segment elevation in the inferior leads but no coved or saddleback ST-segment elevation in the right precordial leads. Pilsicainide infusion provoked coved-type ST-segment elevation in the right precordial leads and mild ST-segment elevation 80 ms after the J point in the inferior leads. During an emergency, 12-lead ECG showed that spontaneous onset of VF was preceded by left bundle branch block and superior axis-type ventricular extrasystoles. The present case provides additional information on the site of origin of VF in patients with Brugada syndrome.

Spatial QRS-T angle predicts cardiac death in a clinical population.

<AbstractText Label="OBJECTIVES/BACKGROUND" NlmCategory="OBJECTIVE">The purpose of this study was to validate the prognostic value of computer-derived measurements of the spatial alignment of ventricular depolarization and repolarization from the standard 12-lead ECG in a general medical population.</AbstractText>Analyses were performed on the first ECG digitally recorded from 46,573 consecutive patients since 1987. QRS and T vector were synthesized by deriving XYZ leads from the 12 leads using the inverse Dower weighting matrix. Subset analyses were considered in patients with and those without standard ECG diagnoses (i.e., atrial fibrillation, Q waves, left ventricular hypertrophy, prolonged QRS duration). The main outcome measure was cardiovascular mortality.</AbstractText>During a mean follow-up of 6 years, 4,127 cardiovascular deaths occurred. After adjusting for age, heart rate, and gender in a Cox regression analysis, spatial QRS-T angle was the most significant predictor of cardiovascular mortality, outperforming all other ECG measurements and diagnostic statements. In the subset with ECGs free of any standard diagnoses, annual cardiovascular mortality was 0.8% for normal (0-50 degrees ), 2.3% for borderline (50-100 degrees ), and 5.1% for abnormal (100-180 degrees ) QRS-T angle groups. The borderline and abnormal angle groups had 1.5- and 1.9-fold higher risk, respectively, relative to the normal QRS-T angle group after adjustment for age, gender, and heart rate. Similar results were found when patients with standard ECG diagnosis were included or compared.</AbstractText>Spatial QRS-T angle is a significant and independent predictor of cardiovascular mortality that provides greater prognostic discrimination than any of the commonly utilized ECG diagnostic classifications.</AbstractText>

Clinical predictors of atrial defibrillation thresholds with a dual-coil, active pectoral lead system.

The purpose of this study was to identify clinical predictors of atrial defibrillation thresholds (DFTs) with standard implantable cardioverter-defibrillator (ICD) leads.</AbstractText>Atrial defibrillation can be achieved with active pectoral, dual-coil transvenous ICD lead systems. If clinical predictors of atrial defibrillation efficacy with these lead systems were identified, they could be used to predict which patients may require more complex lead systems for atrial defibrillation, such as a coronary sinus electrode.</AbstractText>This was a prospective study of 135 consecutive patients undergoing initial ICD implant for standard indications. The lead system evaluated was a transvenous defibrillation lead with coils in the superior vena cava (SVC) and right ventricular apex (RV), and a left pectoral pulse generator emulator (CAN). The shocking pathway was RV--&gt;SVC+CAN. Atrial DFT was measured using a step-up protocol. Clinical and echocardiographic parameters were evaluated as predictors of atrial DFT and multiple linear regression was performed.</AbstractText>Mean atrial DFT was 4.6 +/- 3.8 J. Atrial DFT was &lt; or =3 J in 70 patients (52%) and &lt; or = 10 J in 97% of patients. The highest atrial DFT was 20 J (one patient). Left atrial size (r = 0.21, P = .01) and left ventricular end-diastolic diameter (r = 0.19, P = .02) were independent predictors of atrial DFT. However, these two predictors accounted for only 6% of the variability in atrial DFT.</AbstractText>Clinical parameters are of limited use in predicting atrial DFT with a dual-coil, active pectoral ICD lead system. Because the RV--&gt; SVC + CAN shocking pathway provides reliable atrial and ventricular defibrillation, this configuration should be preferred for combined atrial and ventricular ICDs.</AbstractText>

Systematic evaluation of the determinants of defibrillation efficacy.

We studied the effect of varying shock capacitance, shock impedance, and pulse duration on defibrillation efficacy in a randomized, crossover manner for biphasic shocks.</AbstractText>The relationship between the electrical determinants of defibrillation efficacy is incompletely understood.</AbstractText>Biphasic shocks were delivered to 12 dogs through epicardial patches (to vary impedance) after 15 seconds of ventricular fibrillation using one of 100- or 155-muF capacitors at each of four pulse durations (2.5, 5, 10, 20 ms), in a balanced random order. There were two impedance groups: six with higher impedance (mean 97 +/- 15 Omega, range 80-120) and six with lower impedance (mean 39 +/- 3 Omega, range 34-44). Voltage requirements were estimated as the average of three defibrillation threshold (DFT) tests.</AbstractText>Shock capacitance, resistance, and pulse duration all had significant effects upon the minimum voltage DFT (P = .0065, P = .0066, and P = .0001, respectively). The tilt associated with the lowest voltage and current requirement for each of the four capacitance/resistance combinations varied widely, between 34 +/- 5% and 63 +/- 3%, depending on capacitance and impedance. The optimal pulse duration associated with minimum DFT lies between 5.11 and 5.34 ms.</AbstractText>Defibrillation voltage requirements for biphasic shocks are affected by pulse duration, capacitance and impedance, but not "tilt."</AbstractText>

Effect of rate and rhythm control on left ventricular function and cardiac dimensions in patients with persistent atrial fibrillation: results from the RAte Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study.

The purpose of this study was to evaluate left ventricular function and atrial and ventricular diameters in patients with persistent atrial fibrillation (AF) treated with rate or rhythm control.</AbstractText>Restoration of sinus rhythm in patients with persistent AF may improve left ventricular function and reduce atrial dimensions. Adequate rate control in AF may preserve ventricular function.</AbstractText>In 335 patients included in the RAte Control versus Electrical Cardioversion for Persistent Atrial Fibrillation (RACE) study, echocardiography was performed at baseline and 1- and 2-year follow-up. Echocardiography was compared between patients randomized to rate control (n = 160) and rhythm control (n = 175). In the rhythm control group, echocardiography was compared between patients with AF versus sinus rhythm at study end. Multivariate analysis was performed to determine parameters related to improvement of left ventricular function and increase of atrial diameters.</AbstractText>Fractional shortening improved significantly under rate and rhythm control (31 +/- 10% at baseline to 33 +/- 9% at 2 years, and from 30 +/- 10% to 34 +/- 9%; both P &lt; .05, respectively). Under rate control, left and right atrial size increased significantly compared to baseline. Under rhythm control, only left atrial size increased. Multivariate analysis revealed that only sinus rhythm at study end was associated with an increase of fractional shortening. AF at study end, hypertension, and no use of angiotensin-converting enzyme inhibitors were independently associated with increase in atrial size.</AbstractText>Routine rate control prevents deterioration of left ventricular function. Maintenance of sinus rhythm is associated with improvement of left ventricular function and reduction of atrial sizes.</AbstractText>

Inhibition of angiotensin II signaling and recurrence of atrial fibrillation in AFFIRM.

We investigated whether inhibition of endogenous angiotensin II signaling reduces the recurrence rate of atrial fibrillation (AF) in patients enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study.</AbstractText>Structural and electrical remodeling contribute to AF. Previous experimental studies have implicated the angiotensin II signaling pathway in this process, and recent clinical evidence supports a beneficial effect of inhibiting angiotensin II activity.</AbstractText>Using the AFFIRM database, we retrospectively identified a cohort of patients randomized to the rhythm-control arm who were in sinus rhythm. Exposure to angiotensin II receptor blockers or angiotensin-converting enzyme inhibitors (ANGI) was determined, and the time to first recurrence of AF was compared between ANGI users and nonusers.</AbstractText>The study cohort included 732 patients not taking ANGI through the initial 2-month follow-up and 421 patients taking ANGI during this time. Patients in the ANGI group more likely had hypertension, diabetes, coronary artery disease, and congestive heart failure compared to patients not taking ANGI. Risk of AF recurrence in the ANGI treatment group did not differ from the risk observed in patients not taking the drugs (hazard ratio [HR] = 0.91, 95% confidence interval [CI] = 0.77-1.09). However, in patients with congestive heart failure or impaired left ventricular function, ANGI use was associated with a lower risk of AF recurrence.</AbstractText>This analysis provides evidence that ANGI use may be beneficial in some patient subgroups with AF and underscores the need for randomized clinical trials defining more fully the role of angiotensin II inhibition in treating AF.</AbstractText>

Activation sequences following failed atrial defibrillation.

The purposes of this study were to examine the first activations following atrial defibrillation shocks to help understand how and where atrial fibrillation (AF) relapsed following failed shocks and to assess the difference in postshock activation between failed and successful shocks.</AbstractText>While many studies have investigated the mechanism of ventricular defibrillation, much less is known about the mechanisms of AF.</AbstractText>Sustained AF was induced electrically after pericardial infusion of methylcholine in 10 sheep. Biphasic subthreshold shocks were delivered to three configurations: right atrium to distal coronary sinus (RA-CS), sequential shocks with RA-CS as the first pathway followed by proximal CS to superior vena cava as the second pathway (Sequential), and right ventricle to superior vena cava plus can (V-triad). In eight sheep, global atrial mapping was performed with 504 electrodes spaced 3 to 4 mm apart.</AbstractText>Earliest postshock activations mostly arose from the left atrium for V-triad but arose from either atrium for RA-CS and Sequential. Preshock AF cycle lengths were significantly shorter at the earliest activation sites than at seven of eight other sites globally distributed over both atria. In all type B successful episodes in which one or more rapid activations occurred after the shock and in 50 of the 72 failed episodes analyzed, activation fronts spread away from the earliest site in a focal pattern, and discrete nonfragmented activation complexes were present in the first derivatives of the electrograms. In the other 22 failed episodes, earliest activation fronts spread in a nonfocal pattern, and earliest postshock electrogram derivatives were fractionated. To better interpret the activation pattern in the fragmented regions, a 504 electrode plaque with 1.5-mm electrode spacing was placed on the right atrial appendage in two additional sheep. In 11 of 108 failed episodes, earliest postshock activation appeared inside the plaque and spread in a focal pattern with nonfragmented electrogram derivatives in 10 episodes and in a reentrant pattern with fragmented electrogram derivatives in the other.</AbstractText>(1) The electrode configuration influenced the location of earliest postshock activation. (2) Earliest postshock activation occurred where the preshock AF cycle length was short. (3) Earliest activations following all type B successful and most failed episodes were not fragmented and spread in a focal pattern. (4) The region of earliest postshock activation in the failed episodes without a focal postshock activation pattern exhibited regions of fragmented electrogram derivatives that may represent conduction block and possibly reentry.</AbstractText>

Novel pore mutation in SCN5A manifests as a spectrum of phenotypes ranging from atrial flutter, conduction disease, and Brugada syndrome to sudden cardiac death.

The purpose of this study was to determine the clinical and biophysical characteristics of a novel SCN5A mutation.</AbstractText>Brugada syndrome and isolated cardiac conduction defect have been linked to SCN5A mutations.</AbstractText>Eleven members of a western European family underwent electrophysiologic investigations and mutation analysis of the SCN5A gene. Wild-type and mutant SCN5A channels were expressed in HEK293 cells, and whole cell currents were studied using patch clamp procedures.</AbstractText>A novel mutation, R376H, in the first pore segment of SCN5A variably causes Brugada syndrome and/or conduction disease in a single family. Biophysical analysis demonstrated a significant current reduction for the mutant, a pathophysiologic profile consistent with Brugada syndrome and isolated cardiac conduction defect. Among 11 family members, 9 were carriers of the mutation. The proband's initial presentation was a saddleback Brugada ECG, atrial flutter, and diffuse conduction disturbances. He had no inducible ventricular arrhythmias but experienced sudden cardiac death. His brother was affected by atrial flutter and had a clear conduction disorder, but he did not display baseline or evocable ECG signs of Brugada syndrome. He received an implantable cardioverter-defibrillator that delivered one appropriate shock after 1 year of follow-up. The phenotype in the family members was highly variable and ranged from noninducible and inducible asymptomatic carriers of the mutations to isolated conduction disease and to symptomatic Brugada syndrome.</AbstractText>We describe the functional characterization of a novel SCN5A pore mutation, R376H, with variable clinical expression in the same family. Differentiating between electrophysiologic entities (Brugada syndrome-isolated cardiac conduction defect) is more challenging. Recognition of factors modifying the clinical presentation may be important for clinical decision making.</AbstractText>

Spectrum and prevalence of cardiac sodium channel variants among black, white, Asian, and Hispanic individuals: implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testing.

The purpose of this study was to determine the prevalence and spectrum of nonsynonymous polymorphisms (amino acid variants) in the cardiac sodium channel among healthy subjects.</AbstractText>Pathogenic mutations in the cardiac sodium channel gene, SCN5A, cause approximately 15 to 20% of Brugada syndrome (BrS1), 5 to 10% of long QT syndrome (LQT3), and 2 to 5% of sudden infant death syndrome.</AbstractText>Using single-stranded conformation polymorphism, denaturing high-performance liquid chromatography, and/or direct DNA sequencing, mutational analysis of the protein-encoding exons of SCN5A was performed on 829 unrelated, anonymous healthy subjects: 319 black, 295 white, 112 Asian, and 103 Hispanic.</AbstractText>In addition to the four known common polymorphisms (R34C, H558R, S1103Y, and R1193Q), four relatively ethnic-specific polymorphisms were identified: R481W, S524Y, P1090L, and V1951L. Overall, 39 distinct missense variants (28 novel) were elucidated. Nineteen variants (49%) were found only in the black cohort. Only seven variants (18%) localized to transmembrane-spanning domains. Four variants (F1293S, R1512W, and V1951L cited previously as BrS1-causing mutations and S1787N previously published as a possible LQT3-causing mutation) were identified in this healthy cohort.</AbstractText>This study provides the first comprehensive determination of the prevalence and spectrum of cardiac sodium channel variants in healthy subjects from four distinct ethnic groups. This compendium of SCN5A variants is critical for proper interpretation of SCN5A genetic testing and provides an essential hit list of targets for future functional studies to determine whether or not any of these variants mediate genetic susceptibility for arrhythmias in the setting of either drugs or disease.</AbstractText>

Is idiopathic ventricular fibrillation a short QT syndrome? Comparison of QT intervals of patients with idiopathic ventricular fibrillation and healthy controls.

The purpose of this study was to determine if patients with idiopathic ventricular fibrillation (VF) have shorter QT intervals than comparable healthy controls.</AbstractText>The upper limit of the normal QT is well defined. Less is known about the lower limit of the normal QT. Patients with the recently described "short QT syndrome" have characteristics resembling those of patients with idiopathic VF.</AbstractText>The ECGs of 28 consecutive patients with idiopathic VF (17 men and 11 women, age 31 +/- 17 years) were compared to those of 270 age- and gender- matched healthy controls. Based on published literature, we defined "short QT" as QTc &lt; or = 360 ms for males and &lt; or = 370 ms for females.</AbstractText>Despite significant overlapping, the QTc of males with idiopathic VF was shorter than the QTc of healthy males (371 +/- 22 ms vs 385 +/- 19 ms, P = .034). Short QT intervals were found more frequently among males with idiopathic VF (35% vs 10%, P = .003). No such differences were apparent among women. Short QTc intervals were more commonly seen during bradycardia. However, the correlation between short QT and a history of VF was independent of heart rate.</AbstractText>"Short" QTc values are commonly seen in male patients with idiopathic VF. However, "short" QTc values are not rare among healthy adults, especially at slow heart rates. Further studies are needed to define when a given QT is really "too short."</AbstractText>

Randomized controlled study of detection enhancements versus rate-only detection to prevent inappropriate therapy in a dual-chamber implantable cardioverter-defibrillator.

The purpose of this study was to compare rate-only detection to enhanced detection in a dual-chamber implantable cardioverter-defibrillator (ICD), to discriminate ventricular tachycardia from supraventricular tachycardia.</AbstractText>ICDs are highly effective in treating ventricular tachycardia (VT) or ventricular fibrillation (VF). However, they frequently deliver inappropriate therapy during supraventricular tachycardia (SVT).</AbstractText>We conducted a randomized clinical trial of detection enhancements in a dual-chamber ICD compared to control (rate-only) detection to discriminate VT from SVT. Detection enhancements included a specific standardized protocol identical for all patients for programming rate stability, sudden onset, atrial-to-ventricular relationship (sudden onset = 9% and rate stability = 10 ms; V &gt; A "on"), and "sustained rate duration" (3 minutes). The primary endpoint was the time to first inappropriate therapy classified by a blinded events committee.</AbstractText>One hundred forty-nine patients had a history of sustained VT or VF. Mean age (+/- SD) was 60 +/- 13 years; 83% were male, and mean ejection fraction was 35 +/- 15%. Control (n = 70) and "enhanced" (n = 79) groups did not differ with regard to age, sex, ejection fraction, or primary arrhythmia. The proportion of patients free of inappropriate therapy over time was significantly higher in the enhanced versus the control group (hazard ratio = 0.47, P = .011). High-energy shocks were reduced from 0.58 +/- 4.23 shocks/patient/month in the control group to 0.04 +/- 0.15 shocks/patient/month in the enhanced group (P = .0425). No patient programmed per protocol failed to receive therapy for VT detected by the ICD (422 VT episodes).</AbstractText>Standardized programming in a dual-chamber ICD leads to a significant and clinically important reduction in inappropriate therapies compared to rate-only detection and does not compromise safety with respect to appropriate treatment of VT.</AbstractText>

Frank-Starling mechanism contributes modestly to ventricular performance during atrial fibrillation.

The aim of this study was to assess whether Frank-Starling mechanism has an independent effect on left ventricular (LV) performance in atrial fibrillation (AF).</AbstractText>Ventricular performance in AF depends on variable contractility through the interval-force mechanism based on the ratio of preceding and pre-preceding RR intervals (RR(p)/RR(pp)). The impact of end-diastolic volume (EDV) variability, through the Frank-Starling mechanism, is not well understood.</AbstractText>We induced AF in 16 open chest dogs. RR intervals, LV pressure, LV volume, and aortic flow were collected for &gt;400 beats during rapid AF (ventricular cycle length 292 +/- 66 ms). In six of the dogs, additional data were collected while average ventricular cycle length was prolonged from 258 +/- 34 ms to 445 +/- 80 ms by selective vagal nerve stimulation of the AV node.</AbstractText>The relations of maximal LV power (LVPower) and peak LV pressure derivative (dP/dt) versus RR(p)/RR(pp) were fitted to the equation y = A * (1 - EXP (RR(p)/RR(pp)min - RR(p)/RR(pp))/C) and the residuals (RES) of these relations were analyzed. LVPower and dP/dt strongly correlated with RR(p)/RR(pp) (r(2) = 0.67 +/- 0.12 and 0.66 +/- 0.12, P &lt; .0001 for all correlations). Importantly, RES-LVPower and RES-dP/dt showed linear correlation with EDV (r(2) = 0.20 +/- 0.14 and r(2) = 0.24 +/- 0.17, P &lt; .01 for all correlations). In the six dogs with slowed average ventricular rate, the slope of both residual relationships (RES-LVPower vs EDV and RES- dP/dt vs EDV) decreased (P &lt; .03 for both).</AbstractText>The Frank-Starling mechanism contributes to ventricular performance in AF independently of the interval-force effects of the beat-to-beat variability in cardiac contractility. The Frank-Starling mechanism is sensitive to the average ventricular rate.</AbstractText>

Achieving regular slow rhythm during atrial fibrillation without atrioventricular nodal ablation: selective vagal stimulation plus ventricular pacing.

The aim of this study was to achieve regular slow ventricular rhythm during atrial fibrillation (AF) without destroying the AV node (AVN).</AbstractText>Recent experimental and clinical studies have demonstrated that selective AVN vagal stimulation (AVN-VS) can be used to slow ventricular rate during AF; however, an irregular rhythm remains. Alternatively, ventricular on-demand (VVI) pacing achieves rate regularization but at rates faster than the already fast intrinsic rate during AF. We hypothesized that AVN-VS combined with VVI pacing would achieve slow, regular rhythm during AF without requiring AVN ablation.</AbstractText>AF was induced in eight dogs. AVN-VS was applied to the epicardial fat pad that projects vagal nerve fibers to the AVN. A computer-controlled algorithm adjusted AVN-VS intensity to achieve three levels of mean ventricular RR interval: 75%, 100%, or 125% of the spontaneous sinus cycle length. At each of the three levels, concomitant VVI pacing was delivered at a constant cycle length equal to the corresponding target. Hemodynamic measurements were performed during the study to elucidate the advantages of the proposed method.</AbstractText>AF resulted in rapid, irregular ventricular rates (RR = 287 +/- 36 ms, or 56% of sinus cycle length). AVN-VS achieved average ventricular rate slowing to the three target levels in all dogs (RR increased to 381 +/- 41, 508 +/- 54, and 632 +/- 68 ms, respectively). At each of the three target rate levels, AVN-VS combined with VVI pacing fully eliminated rate irregularities. The regular slow ventricular rhythms during AF were associated with significant hemodynamic improvement.</AbstractText>A novel approach combining AVN-VS with VVI pacing results in a regular, slow ventricular rhythm during AF that does not necessitate AVN ablation. Rate regularization achieved by this approach was associated with pronounced hemodynamic benefits during AF.</AbstractText>

Optical mapping of the functional reentrant circuit of ventricular tachycardia in acute myocardial infarction.

We used optical mapping to characterize the reentrant circuit of ventricular tachycardia (VT) during acute myocardial infarction (MI) in isolated canine left ventricular preparations.</AbstractText>The nature of the reentrant circuit that underlies VT during acute MI is not well understood.</AbstractText>Using optical mapping in isolated canine left ventricular preparations, we characterized the reentrant circuit of monomorphic VT (mean cycle length 245.3 +/- 15.6 ms, n = 7) induced by programmed stimulation during acute MI.</AbstractText>Optical mapping during VT revealed a functional reentrant circuit consisting of four components: (1) a protected isthmus located between the infarction area and the functional line of block; (2) an entrance site located at one end of the isthmus; (3) an exit site located at the other end of the isthmus; and (4) an outer loop consisting of nonischemic normal tissue, connecting the exit and entrance sites. Rate-dependent slow conduction within the border zone was associated with significant changes (n = 6) in action potential amplitude (99.1 +/- 0.4 vs 71.4 +/- 0.6 mV, P &lt; .01), maximal diastolic potential (-80.6 +/- 0.2 vs -65.4 +/- 0.6 mV, P &lt; .05), action potential duration at 90% repolarization (APD(90); 188.4 +/- 1.0 vs 164.3 +/- 3.1 ms, P &lt; .05), and dV/dt (302.4 +/- 7.9 vs 168.5 +/- 3.6 V/s, P &lt; .05). Compared to preparations with no inducible VT (n = 7), formation of a functional line of block was the key mechanism for initiation of functional reentry in preparations with VT. When comparing preparations with sustained and nonsustained VT, preservation of slow conduction over the isthmus was the key component for maintenance of sustained VT.</AbstractText>The reentrant circuit of monomorphic VT in the setting of acute MI involved both the infarction border zone and nonischemic normal tissue. The underlying mechanism is related to the presence of rate-dependent slow conduction and the development of a functional line of block in the border zone.</AbstractText>

Intracellular calcium cycling, early afterdepolarizations, and reentry in simulated long QT syndrome.

The purpose of this study was to investigate interactions between early afterdepolarizations (EADs) and reentry in long QT (LQT) syndromes.</AbstractText>EADs, a characteristic feature of congenital and acquired LQT syndromes, are classically bradycardia dependent. Mechanisms by which they promote tachyarrhythmias such as torsades de pointes and ventricular fibrillation are not fully understood. Recent evidence suggests that EADs also may occur at rapid heart rates as a sequela of spontaneous sarcoplasmic reticulum (SR) Ca(2+) release related to intracellular Ca(2+) overload. Here, we performed computer simulations to explore the arrhythmogenic consequences of this phenomenon.</AbstractText>We used a modified version of the Luo-Rudy dynamic model in one-dimensional and two-dimensional cardiac tissue with the time-dependent K(+) currents I(Kr) or I(Ks) reduced by 50% to simulate acquired and congenital LQT syndromes.</AbstractText>(1) Spontaneous SR Ca(2+) release prolonged action potential duration but did not induce overt EADs unless K(+) current density was reduced to simulate acquired and congenital LQT syndromes. (2) In simulated LQT syndromes, EADs were capable of both terminating and reinitiating one-dimensional reentry. (3) A similar phenomenon in simulated 2D tissue led to reinitiation of spiral wave reentry that otherwise would have self-terminated. (4) Reentry reinitiation occurred only when the L-type Ca(2+) current and SR Ca(i) cycling were potentiated to simulate moderate sympathetic stimulation, consistent with the known arrhythmogenic effects of sympathetic activation (and protection by beta-blockers) in LQT syndromes.</AbstractText>These computer simulations suggest that EADs related to spontaneous SR Ca(2+) release can enhance arrhythmogenesis in LQT syndromes by reinitiating reentry.</AbstractText>

Seasonal variation of mortality in the Antiarrhythmics Versus Implantable Defibrillators (AVID) study registry.

We postulated that the pattern of death would be nonrandom with respect to temporal variables.</AbstractText>Previous studies have demonstrated increased sudden death is associated with periods of relative stress, and overall mortality is associated with temporal variables.</AbstractText>In the Antiarrhythmics Versus Implantable Defibrillators (AVID) registry, vital status was obtained for 4,450 patients (who had a recent episode of sustained ventricular arrhythmias or unexplained syncope and inducible ventricular tachycardia) through the National Death Index Service as of December 31, 1997 (follow-up 25.5 +/- 13.7 months).</AbstractText>Mortality was not associated with the day of the week or with holidays but was associated with season (P = .033). Seasonal variation was present both in northern and southern sites. Mortality was higher during the winter months compared to the remaining months (111.2% in winter vs 96.5% in other months, P = .036). In addition, increased mortality was associated with a high-risk season variable defined (prior to evaluation of treatment arm associations) as spring in the north and winter in the south (P &lt; .001). The hazard ratio for death associated with this "high-risk season" measured 1.25 (P = .001) compared to the other seasons in each region. A test of interaction between "high-risk" season and implantable cardioverter-defibrillator (ICD) status suggested that the group with ICDs experienced reduced mortality during the "high-risk season" compared to the group without ICDs (P = .047).</AbstractText>Mortality was higher in the winter months and in the respective regional "high-risk" seasons. Furthermore, seasonal variation in mortality may have been due to variation in sudden arrhythmic death, and associated increases in mortality were reduced by ICD therapy.</AbstractText>