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Cariporide minimizes adverse myocardial effects of epinephrine during resuscitation from ventricular fibrillation.

Epinephrine given during closed-chest resuscitation increases blood flow across the coronary and cerebral circuits. However, epinephrine worsens reperfusion arrhythmias and intensifies postresuscitation myocardial dysfunction. We investigated whether cariporide-a selective sodium-hydrogen exchanger isoform-1 inhibitor-could ameliorate such adverse effects without diminishing its vasopressor actions.</AbstractText>Randomized animal study.</AbstractText>University-based animal laboratory.</AbstractText>Twenty-four anesthetized male domestic pigs (29-43 kg).</AbstractText>Ventricular fibrillation was electrically induced and left untreated for 8 mins. Pigs were randomized to receive after 2 mins of chest compression a 3 mg/kg bolus of cariporide (n = 8), a 0.02 mg/kg bolus of epinephrine (n = 8), or a combination of cariporide and epinephrine (n = 8). Additional doses of epinephrine were given if the coronary perfusion pressure decreased below 15 mm Hg. Successfully resuscitated pigs were observed for 72 hrs.</AbstractText>The averaged coronary perfusion pressure was higher in the epinephrine (34 +/- 11 mm Hg, p = .001) and cariporide/epinephrine (35 +/- 10 mm Hg, p &lt; .001) groups compared with the cariporide group (15 +/- 6 mm Hg). All pigs in the epinephrine and cariporide/epinephrine groups but only six in the cariporide group were successfully resuscitated and survived 72 hrs. During the immediate postresuscitation period, four of eight pigs in the epinephrine group had episodes of recurrent ventricular fibrillation or pulseless ventricular tachycardia requiring additional electrical shocks (7.0 +/- 6.4) but none in the cariporide and cariporide/epinephrine groups (chi-square, p = .008). Myocardial dysfunction occurred early after return of spontaneous circulation but only in the epinephrine group.</AbstractText>The combined administration of cariporide and epinephrine prompted adequate pressor effects during chest compression and facilitated reestablishment of cardiac activity without episodes of recurrent ventricular fibrillation or transient myocardial dysfunction as with epinephrine alone.</AbstractText>

Effects of combined administration of vasopressin, epinephrine, and norepinephrine during cardiopulmonary resuscitation in pigs.

Synergistic effects of epinephrine and vasopressin may be of benefit during cardiopulmonary resuscitation. However, cerebral perfusion was decreased when epinephrine was combined with vasopressin compared with vasopressin alone. Although a combined infusion of norepinephrine and vasopressin improves hemodynamic variables compared with norepinephrine alone during sepsis, it is unknown whether norepinephrine in addition to vasopressin and epinephrine changes vital organ perfusion during cardiopulmonary resuscitation.</AbstractText>Prospective, randomized animal study.</AbstractText>: University hospital research laboratory.</AbstractText>Twenty-one domestic pigs.</AbstractText>After 4 mins of ventricular fibrillation and 3 mins of basic life support, the pigs were randomly assigned to receive either 200 microg/kg epinephrine, 0.4 units/kg vasopressin alone, or 45 microg/kg norepinephrine plus 45 microg/kg epinephrine plus 0.4 units/kg vasopressin before defibrillation.</AbstractText>Organ perfusion was determined by radiolabeled microspheres. Myocardial blood flow (mean +/- sem) before and 90 secs and 5 mins after drug administration was 8 +/- 2, 25 +/- 6, and 7 +/- 1 mL/min/100 g after high-dose epinephrine, 12 +/- 1, 75 +/- 7, and 60 +/- 10 mL/min/100 g after vasopressin, and 9 +/- 2, 95 +/- 26, and 46 +/- 15 mL/min/100 g after vasopressin/epinephrine/norepinephrine, respectively (p &lt; .05 at 90 secs and 5 mins vasopressin vs. epinephrine and vasopressin/epinephrine/norepinephrine vs. epinephrine). At the same time points, cerebral blood flow was 8 +/- 2, 23 +/- 3, and 17 +/- 3 mL/min/100 g after epinephrine, 11 +/- 3, 55 +/- 7, and 52 +/- 7 mL/min/100 g after vasopressin, and 11 +/- 4, 67 +/- 13, and 53 +/- 12 mL/min/100 g after vasopressin/epinephrine/norepinephrine, respectively (p &lt; .05 at 90 secs and 5 mins vasopressin vs. epinephrine and vasopressin/epinephrine/norepinephrine vs. epinephrine). Two of seven animals in the epinephrine group, four of seven animals in the vasopressin/epinephrine/norepinephrine group, and seven of seven animals in the vasopressin group could be successfully resuscitated (p &lt; .05 vasopressin vs. epinephrine).</AbstractText>Vasopressin with or without epinephrine and norepinephrine resulted in higher myocardial and cerebral perfusion than epinephrine alone, but there was no benefit in adding norepinephrine to vasopressin and epinephrine with regard to cardiac and cerebral blood flow during cardiopulmonary resuscitation.</AbstractText>

Diabetes mellitus is a strong, independent risk for atrial fibrillation and flutter in addition to other cardiovascular disease.

Diabetes mellitus (DM) is a major risk factor for atherosclerosis. There is a controversy in literature about correlation between DM and atrial fibrillation. The goal of this study was to evaluate DM as a risk factor for atrial fibrillation or flutter using a very large database.</AbstractText>Patient treatment files (PTF) containing discharge diagnoses were utilized using ICD-9 codes of inpatient treatment from Veterans Health Administration Hospitals (VAH). Patients with type II DM (ICD-9 code 250.0) (293,124) discharged from the VAH between 1990 and 2000. Non-matched controls without DM but with hypertension (552,624) were selected from the same PTF. By using multi-variate logistic regressions, the occurrence of atrial fibrillation, atrial flutter, CHF, CAD and LVH was compared.</AbstractText>Atrial fibrillations occurred in 43,674 (14.9%) DM patients vs. 57,077 (10.3%) in the control group (p&lt;0.0001). Atrial flutter occurred in 11,852 (4%) of DM patients vs. 13,554 (2.5%) of the control group (p&lt;0.0001). Using multi-variant analysis, DM remained independently associated with atrial fibrillation with an OR of 2.13, (95% CI: 2.10 to 2.16; p&lt;0.0001) and flutter (OR 2.20, CI: 2.15 to 2.26; p&lt;0.0001). Furthermore, CHF (OR 3.12, CI: 3.09 to 3.16; p&lt;0.0001), LVH (OR 1.85, CI: 1.77 to 1.92; p&lt;0.0001) and CAD (OR 2.39, CI: 2.34 to 2.44; p&lt;0.0001) were also independently associated with DM.</AbstractText>This is the first large-scale study finding DM as a strong, independent risk for the occurrence of atrial fibrillation and flutter and other cardiovascular disease.</AbstractText>

Ventricular fibrillation in acute myocardial infarction before and during primary PCI.

There are scarce and sometimes contradictory data about ventricular fibrillation (VF) during the acute phase of MI. In-hospital VF most often occurs with inferior MI, when treated with fibrinolytics. Out-of-hospital VF seems to be associated with anterior MI. We studied characteristics of patients with VF during reperfusion therapy by primary angioplasty (PCI) versus patients with VF before PCI.</AbstractText>From January 1995 until December 2001, we treated 2826 patients for acute MI and reviewed clinical records of all patients who developed VF and classified the patients according to the first episode of VF: either before or during the angioplasty procedure.</AbstractText>VF developed in 219 (8%) patients. Patients with VF during reperfusion therapy (n=74, 3%) were older (p=0.03), more frequently female (0.04), less often had heart failure (p=0.04), when compared with patient with VF before PCI (n=145, 5%). Patients with VF during PCI experienced more often preinfarction angina (p=0.009) and suffered more often from inferior MI (p=0.001), when compared with patients with VF before PCI.</AbstractText>Patients with early VF before reperfusion have different characteristics when compared with patients with VF during reperfusion. Infarct location is a major determinant of timing of VF, when both groups are compared (p&lt;0.001).</AbstractText>

Acceleration of functional reentry by rapid pacing in anisotropic cardiac monolayers: formation of multi-wave functional reentries.

Attempts to cardiovert tachycardia by rapid point pacing can sometimes result in transient or stable increase of the heart rate (acceleration), changed ECG morphology, and/or fibrillation. The goal of this study was to investigate the effect of rapid pacing on the dynamics of functional reentry in monolayer cultures of cardiac cells.</AbstractText>Fully confluent, uniformly anisotropic monolayers of neonatal rat ventricular myocytes were prepared using methods of microabrasion. Cells were paced by a point electrode at rest and during functional reentry, and membrane voltages were optically mapped.</AbstractText>Point pacing readily induced single loop anisotropic functional reentry with monomorphic optical pseudo-ECG (pECG) and average rotation period of 193+/-52 ms (n=71 monolayers). Attempts to cardiovert reentry by rapid pacing at rates 10-50% faster than the reentry rate were successful in 57/71 monolayers. In 14/71 monolayers, the number of rotating waves was stably increased by 1 to 4, yielding a 10-70% acceleration of pECG rate and change to a different monomorphic or polymorphic pECG. The resulting multi-wave functional reentries were classified based on the number and direction of their rotating waves. The higher the number of waves in the multi-wave reentry, the more accelerated was the rate of cell firing in the monolayer. Importantly, stable acceleration was only inducible in monolayers with relatively deep and broad conduction velocity restitution relationships. Reapplication of point pacing further accelerated, decelerated, or eventually terminated the reentrant activity.</AbstractText>These results suggest that stable multiplication of rotating waves in conjunction with a deep and broad conduction velocity restitution relationship is a possible mechanism for stable acceleration of functional reentry by rapid pacing.</AbstractText>

CRT-D therapy in patients with left ventricular dysfunction and atrial fibrillation.

The number of patients with atrial fibrillation and congestive heart failure has steadily increased in the United States. The presence of atrial fibrillation increases morbidity and mortality for patients with left ventricular dysfunction. The emergence of cardiac resynchronization therapy to improve symptoms and survival from congestive heart failure may provide benefits for those with atrial fibrillation; we review the pathophysiology of atrial fibrillation in the presence of left ventricular dysfunction and the promise of cardiac resynchronization therapy to improve symptoms for the for these patients.

Our search for the porcine mother rotor.

A single stationary mother rotor, located in the fastest activating region and giving rise to activation fronts that propagate throughout the remainder of the myocardium, has been hypothesized to be responsible for the maintenance of ventricular fibrillation (VF). Others have reported a mother rotor in guinea pigs and rabbits. We wanted to see if a mother rotor exists in a larger heart, that is, pigs. Epicardial mapping studies have demonstrated that VF wavefronts in pigs tend to propagate from the posterior basal LV to the anterior LV and on to the anterior RV, raising the possibility of a mother rotor in the posterior LV. However, no sustained reentry consistent with a mother rotor was found on the posterior LV epicardium, even though an intramural mapping study showed that the fastest activating transmural layer was near the epicardium. Many wavefronts in the posterior LV entered the mapped region from the posterior boundary of the mapping array, adjacent to the posterior descending coronary artery, raising the possibility that a mother rotor is located in the right ventricle or septum. Since a previous study has shown that the RV activates more slowly than the LV during VF, the more likely site for a mother rotor was the septum. However, we then performed a study in which we recorded from the right side of the septum and found that reentry was uncommon there also and that the activation rate was slower than the posterobasal LV. Many of the VF wavefronts in the septum passed from the posterior septum toward the anterior septum. This fact coupled with the fact that many wavefronts passed from the posterior LV free wall toward the anterior LV free wall point to the region where the posterior free wall intersects with the septum, the region where the posterior papillary muscle is located, as the possible site of a mother rotor. Indeed, a recent abstract by others reports that, after propranolol, a stable reentrant circuit is present on the endocardium at the insertion of the posterior papillary muscle into the LV free wall in pigs.

Prognostic impact of demographic factors and clinical features on the mode of death in high-risk patients after myocardial infarction--a combined analysis from multicenter trials.

Contemporary information is lacking on the effect of demographic features and clinical features on the specific mode of mortality after myocardial infarction (MI) in the thrombolytic era.</AbstractText>The aims of this study were (1) to examine the risk and trend of a different mode of mortality (i.e., all-cause, arrhythmic, and nonarrhythmic cardiac mortality) in high-risk patients post MI with reduced left ventricular ejection fraction (LVEF) or ventricular arrhythmias; and (2) to assess the predictive value of demographic and clinical variables in the prediction of specific modes of death in high-risk patients post MI in the thrombolytic era.</AbstractText>In all, 3,431 patients receiving placebo (2,700 men, median age 64 +/- 11 years) from the EMIAT, CAMIAT, SWORD, TRACE, and DIAMOND-MI studies, with LVEF &lt; 40% or ventricular arrhythmia were pooled. Risk factors for mortality among patients surviving &gt; or = 45 days after MI up to 2 years were examined using Cox regression. Short-term survival (from onset of MI to Day 44 after MI) was also examined for TRACE and DIAMOND-MI, in which patients were recruited within 2 weeks of MI.</AbstractText>After adjustment for treatment and study effects, age, previous MI/angina, increased heart rate, and higher New York Heart Association functional class increased the risk of all-cause, arrhythmic, and cardiac mortality. Male gender, history of hypertension, low baseline systolic blood pressure, and Q wave were predictive of all-cause and arrhythmic mortality, whereas diabetes was only predictive of all-cause mortality. Smoking habit and atrial fibrillation had no prognostic value. Similar parameters were also predictive of short-term mortality, but not identical.</AbstractText>Our study has shown that in high-risk patients post MI, who have been preselected using LVEF or frequent ventricular premature beats, demographic and clinical features are powerful predictors of mortality in the thrombolytic era. We propose that demographic and clinical factors should be considered when designing risk stratification or survival studies, or when identifying high-risk patients for prophylactic implantable cardiodefibrillator therapy.</AbstractText>

Successful treatment of electrical storm with oral quinidine in Brugada syndrome.

A patient implanted with a cardioverter-defibrillator for symptomatic Brugada syndrome was referred to our hospital 17 months later because of recurrent shocks due to ventricular fibrillation (VF). Isoprenaline was intravenously infused and prevented VF episodes, but VF recurred after every attempt of drug discontinuation. A total of 34 shocks were recorded over 25 days. Subsequently, we treated the patient with oral quinidine and the drug suppressed the electrical storm and prevented VF episodes during a follow-up period of 3 years. This case report, together with few others reported in the literature, suggests a role of oral quinidine in the treatment of electrical storm in Brugada syndrome.

[Right ventricular pacing: a resource or a threat?].

Early after the beginning of the pacemaker era, endocardial right ventricular apex has been the most extensively used site for cardiac pacing because it was easily accessible and reliable in a long-term perspective. However many data have demonstrated that this kind of pacing is suboptimal from a physiologic point of view because it causes several adverse effects such as altered ventricular contraction geometry, mitral regurgitation, perfusion alterations and interference with myocardial ion channels which determine a worsening of left ventricular function. Several strategies have been proposed to solve these problems (alternative pacing sites, specific algorithms able to reduce the percentage of ventricular pacing) which are still under evaluation. In this review we analyzed the effects of right apical ventricular pacing and its possible alternatives.

Implantable cardioverter-defibrillators in patients with hypertrophic cardiomyopathy -- dilemmas and difficulties.

The implantation of a cardioverter-defibrillator (ICD) is an established method of sudden cardiac death (SCD) prevention. The value of ICD therapy in secondary prevention of SCD is unquestionable. Precise identification of high-risk patients and ICD use for primary prevention of SCD, especially in patients with hypertrophic cardiomyopathy (HCM), remain controversial. Problems include the high prevalence of complications associated with ICD implantation and optimal selection of ICDs.</AbstractText>To estimate the frequency and type of complications after ICD implantations in HCM patients in a long-term follow-up.</AbstractText>The efficacy and safety of ICD therapy were estimated in 46 HCM patients with devices implanted for a secondary (n-18) or primary prevention (n-28) of SCD.</AbstractText>During the mean follow-up period of 28.2+/-26.1 months (from 2 to 68) appropriate ICD interventions occurred in 10 (55%) patients of the secondary prevention group and in 3 (10%) patients of the primary prevention group. Complications were documented in 15 (33%) patients. The most frequent were inappropriate ICD interventions recorded in 14 (30%) patients. The causes of these inappropriate ICD shocks were: T-wave oversensing (7 patients), atrial fibrillation with rapid ventricular rhythm (3 patients), lead failure (2 patients), and sinus tachycardia (2 patients). In two patients infections of the ICD pocket requiring removal of the system occurred. Displacement of the lead occurred in one patient. There were no significant differences in the prevalence of complications between the primary and secondary prevention groups or in the number of inappropriate interventions with respect to ICD type.</AbstractText>The high rate of appropriate ICD shocks provides proof of high ICD-based SCD prevention efficacy. There is a high rate of complications observed after ICD implantation with inappropriate interventions being the most frequent among them. This indicates that careful programming of the device as well as the use of a programme with T-wave oversensing prevention should be ensured.</AbstractText>

Comprehensive multidetector computed tomography assessment of severe cardiac contusion in a pediatric patient: correlation with echocardiography.

Multidetector computed tomography (MDCT) cardiac findings in an unconscious teenager after blunt chest trauma are presented. Multidetector computed tomography enabled accurate comprehensive evaluation of the coronary arteries, myocardial perfusion, and left ventricular function. This case illustrates the full capabilities of MDCT in the evaluation of cardiac contusion in a noncooperative pediatric patient.

Inappropriate discharges of intravenous implantable cardioverter defibrillators owing to lead failure.

We describe here the case of a 58-year-old female patient who experienced inappropriate shocks from her implantable cardioverter-defibrillator (ICD). Stored electrograms from her ICD showed high frequency noise preceding the shock. Although the pacing threshold was normal and lead fracture was not found in chest X-rays, pacing lead impedance decreased to 480 omega. Moreover, such high frequency noise was observed by electrogram telemetry, but not by routine evaluation every 3 months. ICD lead dysfunction was suspected, so we elected to replace the ICD lead system. At the time of the operation, lead impedance was 410 omega and pacing threshold was the same as it was at the time of the ICD implantation, and no lead insulation disturbances were observed in the generator pocket. However, manipulation of the lead system produced high frequency noise reproducibly. Since some of the ICD lead dysfunction initially was clinically silent at rest, dysfunction was difficult to detect before serious problems occurred. Therefore, more careful evaluation of the ICD lead system is needed during long-term follow-up of ICD implants.

New antiarrhythmic drugs for prevention of atrial fibrillation.

Enhanced understanding of the mechanisms underlying atrial fibrillation (AF) and advent of catheter-based therapy for AF has altered the approach to patients with this most common arrhythmia. However, despite the success of aggressive procedural techniques, pharmacologic therapy remains the first-line and mainstay approach in the treatment of AF. This review of new antiarrhythmic drug (AAD) therapy for AF provides an in-depth overview of recently available classic and new investigational drugs being considered for AF treatment. Currently available AADs are associated with less than satisfactory efficacy in preventing AF and a significant side effect profile, including ventricular proarrhythmia. Recent investigations have focused on development of new AADs that, hopefully, will be more effective and safer even in patients with structural heart disease. These new AADs include selective multi-ion channel and atrial specific blockers and agents that target the underlying etiologies and substrate alterations that lead to AF. Included among the latter new category are agents that suppress activation of the renin-angiotensin-aldosterone system or inflammation, which represent novel targets for drug therapy for AF. Finally, new selective A1 adenosine receptor agonists may offer the possibility of more specific and successful ventricular rate control during AF. There is considerable hope and interest that improved understanding of AF mechanisms ultimately will result in more effective and less dangerous pharmacologic therapy becoming available in the future.

Electrical and structural remodeling: role in the genesis and maintenance of atrial fibrillation.

Atrial fibrillation (AF) and congestive heart failure (CHF) are 2 frequently encountered conditions in clinical practice. Both lead to changes in atrial function and structure, an array of processes known as atrial remodeling. This review provides an overview of ionic, electrical, contractile, neurohumoral, and structural atrial changes responsible for initiation and maintenance of AF. In the last decade, many studies have evaluated atrial remodeling due to AF or CHF. Both conditions often coexist, which makes it difficult to distinguish the contribution of each. Because of atrial stretch in the setting of hypertension or CHF, atrial remodeling frequently occurs long before AF arises. Alternatively, AF may lead to electrical remodeling, that is, shortening of refractoriness due to the high atrial rate itself. In many experimental AF or rapid atrial pacing studies, the ventricular rate was uncontrolled. In those studies, atrial stretch due to CHF may have interfered with the high atrial rate to produce a mixed type of electrical and structural remodeling. Other studies have dissected the individual role of AF or atrial tachycardia from the role CHF plays in atrial remodeling. Atrial fibrillation itself does not lead to structural remodeling, whereas this is frequently produced by hypertension or CHF, even in the absence of AF. Primary and secondary prevention programs should tailor treatment to the various types of remodeling.

Analysis of current management of atrial fibrillation in the acute setting: GEFAUR-1 study.

Limited information relative to the management of atrial fibrillation in the emergency department (ED) daily practice is available. This study evaluates current management of atrial fibrillation in this setting to identify areas for practice improvement.</AbstractText>This was a prospective multicenter observational study carried out in 12 EDs. Adults in whom atrial fibrillation was demonstrated in an ECG obtained in the ED were included. Clinical variables and atrial fibrillation management in the ED were prospectively collected by the treating physicians using a standardized questionnaire. Patients with rapid ventricular response (&gt;100 beats/min) were considered eligible for rate control, and patients with recent-onset episodes (&lt;48 hours) were eligible for rhythm control.</AbstractText>Of 1,178 patients, 41% presented with a rapid ventricular response and 21% had recent-onset episodes. Rhythm control was attempted in 42% of eligible patients, with antiarrhythmic drugs in 88% of cases (I-C drugs in 44% of patients; amiodarone in 43% of patients). Overall effectiveness of pharmacologic cardioversion was 63% (amiodarone 54.5%, flecainide 93%), whereas electrocardioversion was effective in 87.5% of cases. Rate control was performed in 68.3% of eligible patients (overall effectiveness 47.8%); digoxin was used in 67% of cases (effectiveness 45%). Both strategies were selected in 4.5% of cases, whereas no treatment for atrial fibrillation was performed in 60% of patients.</AbstractText>In our ED population, rate-control effectiveness is poor and rhythm control is not attempted in most recent-onset episodes. Methods to improve rate-control effectiveness, the selection of patients for rhythm control, and the use of electrocardioversion appear warranted.</AbstractText>

Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial.

Despite previous randomised trials of early beta-blocker therapy in the emergency treatment of myocardial infarction (MI), uncertainty has persisted about the value of adding it to current standard interventions (eg, aspirin and fibrinolytic therapy), and the balance of potential benefits and hazards is still unclear in high-risk patients.</AbstractText>45,852 patients admitted to 1250 hospitals within 24 h of suspected acute MI onset were randomly allocated metoprolol (up to 15 mg intravenous then 200 mg oral daily; n=22,929) or matching placebo (n=22,923). 93% had ST-segment elevation or bundle branch block, and 7% had ST-segment depression. Treatment was to continue until discharge or up to 4 weeks in hospital (mean 15 days in survivors) and 89% completed it. The two prespecified co-primary outcomes were: (1) composite of death, reinfarction, or cardiac arrest; and (2) death from any cause during the scheduled treatment period. Comparisons were by intention to treat, and used the log-rank method. This study is registered with ClinicalTrials.gov, number NCT 00222573.</AbstractText>Neither of the co-primary outcomes was significantly reduced by allocation to metoprolol. For death, reinfarction, or cardiac arrest, 2166 (9.4%) patients allocated metoprolol had at least one such event compared with 2261 (9.9%) allocated placebo (odds ratio [OR] 0.96, 95% CI 0.90-1.01; p=0.1). For death alone, there were 1774 (7.7%) deaths in the metoprolol group versus 1797 (7.8%) in the placebo group (OR 0.99, 0.92-1.05; p=0.69). Allocation to metoprolol was associated with five fewer people having reinfarction (464 [2.0%] metoprolol vs 568 [2.5%] placebo; OR 0.82, 0.72-0.92; p=0.001) and five fewer having ventricular fibrillation (581 [2.5%] vs 698 [3.0%]; OR 0.83, 0.75-0.93; p=0.001) per 1000 treated. Overall, these reductions were counterbalanced by 11 more per 1000 developing cardiogenic shock (1141 [5.0%] vs 885 [3.9%]; OR 1.30, 1.19-1.41; p&lt;0.00001). This excess of cardiogenic shock was mainly during days 0-1 after admission, whereas the reductions in reinfarction and ventricular fibrillation emerged more gradually. Consequently, the overall effect on death, reinfarction, arrest, or shock was significantly adverse during days 0-1 and significantly beneficial thereafter. There was substantial net hazard in haemodynamically unstable patients, and moderate net benefit in those who were relatively stable (particularly after days 0-1).</AbstractText>The use of early beta-blocker therapy in acute MI reduces the risks of reinfarction and ventricular fibrillation, but increases the risk of cardiogenic shock, especially during the first day or so after admission. Consequently, it might generally be prudent to consider starting beta-blocker therapy in hospital only when the haemodynamic condition after MI has stabilised.</AbstractText>

Right ventricular fibrosis and conduction delay in a patient with clinical signs of Brugada syndrome: a combined electrophysiological, genetic, histopathologic, and computational study.

The mechanism of ECG changes and arrhythmogenesis in Brugada syndrome (BS) patients is unknown.</AbstractText>A BS patient without clinically detected cardiac structural abnormalities underwent cardiac transplantation for intolerable numbers of implantable cardioverter/defibrillator discharges. The patient's explanted heart was studied electrophysiologically and histopathologically. Whole-cell currents were measured in HEK293 cells expressing wild-type or mutated sodium channels from the patient. The right ventricular outflow tract (RVOT) endocardium showed activation slowing and was the origin of ventricular fibrillation without a transmural repolarization gradient. Conduction restitution was abnormal in the RVOT but normal in the left ventricle. Right ventricular hypertrophy and fibrosis with epicardial fatty infiltration were present. HEK293 cells expressing a G1935S mutation in the gene encoding the cardiac sodium channel exhibited enhanced slow inactivation compared with wild-type channels. Computer simulations demonstrated that conduction slowing in the RVOT might have been the cause of the ECG changes.</AbstractText>In this patient with BS, conduction slowing based on interstitial fibrosis, but not transmural repolarization differences, caused the ECG signs and was the origin of ventricular fibrillation.</AbstractText>

Prevention of fatal arrhythmias in high-risk subjects by fish oil n-3 fatty acid intake.

The long-chain n-3 fatty acids in fish have been demonstrated to have antiarrhythmic properties in experimental models and to prevent sudden cardiac death in a randomized trial of post-myocardial infarction patients. Therefore, we hypothesized that these n-3 fatty acids might prevent potentially fatal ventricular arrhythmias in high-risk patients.</AbstractText>Four hundred two patients with implanted cardioverter/defibrillators (ICDs) were randomly assigned to double-blind treatment with either a fish oil or an olive oil daily supplement for 12 months. The primary end point, time to first ICD event for ventricular tachycardia or fibrillation (VT or VF) confirmed by stored electrograms or death from any cause, was analyzed by intention to treat. Secondary analyses were performed for "probable" ventricular arrhythmias, "on-treatment" analyses for all subjects who had taken any of their oil supplements, and "on-treatment" analyses only of those subjects who were on treatment for at least 11 months. Compliance with double-blind treatment was similar in the 2 groups; however, the noncompliance rate was high (35% of all enrollees). In the primary analysis, assignment to treatment with the fish oil supplement showed a trend toward a prolonged time to the first ICD event (VT or VF) or of death from any cause (risk reduction of 28%; P=0.057). When therapies for probable episodes of VT or VF were included, the risk reduction became significant at 31%; P=0.033. For those who stayed on protocol for at least 11 months, the antiarrhythmic benefit of fish oil was improved for those with confirmed events (risk reduction of 38%; P=0.034).</AbstractText>Although significance was not achieved for the primary end point, this study provides evidence that for individuals at high risk of fatal ventricular arrhythmias, regular daily ingestion of fish oil fatty acids may significantly reduce potentially fatal ventricular arrhythmias.</AbstractText>

Increased risk of sudden and non-sudden cardiovascular death in patients with atrial fibrillation/flutter following acute myocardial infarction.

Atrial fibrillation (AF) is a common complication in patients with acute myocardial infarction and is associated with an increase in the risk of death. The excess mortality associated with AF complicating acute myocardial infarction has not been studied in detail. Observations indicate that AF facilitates induction of ventricular arrhythmias, which may increase the risk of sudden cardiovascular death (SCD). A close examination of the mode of death could potentially provide useful knowledge to guide further investigations and treatments.</AbstractText>We analysed the relation between AF/atrial flutter (AFL) and modes of death in 5983 consecutive patients discharged alive after an acute myocardial infarction screened in the TRAndolapril Cardiac Evaluation registry. This cohort of patients with an enzyme-verified acute myocardial infarction was admitted to 27 centres in 1990-92. Survival status was obtained 2 years after screening of the last patient. An independent endpoint committee assessed the modes of death. Left ventricular ejection fraction was determined in all the screened patients and information about presence or absence of AF/AFL was prospectively collected. Sustained or paroxysmal AF/AFL was observed in 1149 patients (19%) during hospitalization. During follow-up, 1659 patients (34%) died: 482 (50%) patients with AF/AFL and 1177 (30%) patients without AF/AFL, P&lt;0.001. SCD occurred in 536, non-SCD occurred in 725, and 398 died of non-cardiovascular causes (includes 142 unclassifiable cases). The adjusted risk ratio of AF/AFL for total mortality was 1.33 (95% CI: 1.19-1.49; P&lt;0.0001) and the risk ratio for SCD was 1.31 (95% CI: 1.07-1.60; P&lt;0.009). The adjusted risk ratio of AF/AFL for non-SCD was 1.43 (95% CI: 1.21-1.70; P&lt;0.0001).</AbstractText>The excess mortality observed in patients with AF/AFL following acute myocardial infarction is due to a significant increase in both SCD and non-SCD.</AbstractText>

The effectiveness and cost-effectiveness of dual-chamber pacemakers compared with single-chamber pacemakers for bradycardia due to atrioventricular block or sick sinus syndrome: systematic review and economic evaluation.

To estimate the effectiveness and cost-effectiveness of dual-chamber pacemakers versus single-chamber atrial or single-chamber ventricular pacemakers in the treatment of bradycardia due to sick sinus syndrome (SSS) or atrioventricular block (AVB).</AbstractText>Electronic databases and relevant Internet sites. Contact with device manufacturers and experts in the field.</AbstractText>A systematic review was carried out of randomised controlled trials (RCTs). The quality of selected studies was appraised using standard frameworks. Meta-analyses, using random effects models, were carried out where appropriate. Limited exploration of heterogeneity was possible. Critical appraisal of economic evaluations was carried out using two frameworks. A decision-analytic model was developed using a Markov approach, to estimate the cost-effectiveness of dual-chamber versus ventricular or atrial pacing over 5 and 10 years as cost per quality-adjusted life-year (QALY). Uncertainty was explored using one-way and probabilistic sensitivity analyses.</AbstractText>The searches retrieved a systematic review of effectiveness and cost-effectiveness published in 2002, four parallel group RCTs and 28 cross-over trials. Dual-chamber pacing was associated with lower rates of atrial fibrillation, particularly in SSS, than ventricular pacing, and prevents pacemaker syndrome. Higher rates of atrial fibrillation were seen with dual-chamber pacing than with atrial pacing. Complications occurred more frequently in dual-chamber pacemaker insertion. The cost of a dual-chamber system, over 5 years, including cost of complications and subsequent clinical events in the population, was estimated to be around 7400 pounds. The overall cost difference between single and dual systems is not large over this period: around 700 pounds more for dual-chamber devices. The cost-effectiveness of dual-chamber compared with ventricular pacing was estimated to be around 8500 pounds per QALY in AVB and 9500 pounds in SSS over 5 years, and around 5500 pounds per QALY in both populations over 10 years. Under more conservative assumptions, the cost-effectiveness of dual-chamber pacing is around 30,000 pounds per QALY. The probabilistic sensitivity analysis showed that, under the base-case assumptions, dual-chamber pacing is likely to be considered cost-effective at levels of willingness to pay that are generally considered acceptable by policy makers. In contrast, atrial pacing may be cost-effective compared with dual-chamber pacing.</AbstractText>Dual-chamber pacing results in small but potentially important benefits in populations with SSS and/or AVB compared with ventricular pacemakers. Pacemaker syndrome is a crucial factor in determining cost-effectiveness; however, difficulties in standardising diagnosis and measurement of severity make it difficult to quantify. Dual-chamber pacing is in common usage in the UK. Recipients are more likely to be younger. Insufficient evidence is currently available to inform policy on specific groups who may benefit most from pacing with dual-chamber devices. Further important research is underway. Outstanding research priorities include the economic evaluation of UKPACE studies of the classification, diagnosis and utility associated with pacemaker syndrome and evidence on the effectiveness of pacemakers in children.</AbstractText>

[A preliminary study on the role of anti-atrial fibrillation pacemaker in the prevention of atrial tachyarrhythmia].

To investigate the effect of anti-atrial fibrillation of Philos DDDR pacemaker on atrial tachyarrhythmia.</AbstractText>Thirty-eight patients with sick sinus syndrome and paroxysmal atrial fibrillation (AF) were implanted with Philos DDDR pacemaker. After implantation, auto-Mode-Switch (AMS) function was switched "on" and AF preventive algorithms were "off" in all cases. The number of AMS, atrial premature beats, heart rate and the percentage of atrial and ventricular pacing were recorded by pacemaker diagnostic function for one-month after procedure. AF preventive algorithms function with "middle" (approx 8 bpm) was then switched on and the same parameters as above from the database of pacemaker diagnostic function were collected for additional one month.</AbstractText>The symptoms of dizziness, dyspnoea, and palpitation in the majority of patients were dramatically improved regardless of whether the AF preventive algorithms function was switched "on" or "off" after pacemaker implantation. There were no significant clinical changes in most patients when AF preventive algorithms were "on". However, 5 cases (13.2%) had palpitations and short of breath. These symptoms were relieved by changing the algorithms from "middle to slight (approx 4 bpm)". When AF preventive algorithms were switched on, atrial premature beats were reduced significantly (P &lt; 0.05) with a dramatic increase in atrial pacing percentage and heart rate (P &lt; 0.05). However, there was no significant difference in AMS (P &gt; 0.05) between the two groups of AF preventive algorithms function switching "on" and "of", indicating that atrial tachyarrhythmias were not inhibited by anti-atrial fibrillation pacemaker.</AbstractText>This study suggested that atrial fibrillation and atrial tachycardia were not reduced by implantation of an anti-atrial fibrillation Philos DDDR pacemaker, although atrial premature beats decreased significantly with increasing atrial pacing percentage when AF preventive algorithms were in "middle" and "slight".</AbstractText>

[Efficacy and safety of the coronary intervention therapy to prevent electrical storm in patients with coronary artery disease but without myocardial infarction].

To study the efficacy and safety of the coronary interventional therapy to prevent electrical storm (ES) in patients with coronary artery diseases (CAD) but without myocardial infarction or ischemic cardiomyopathy.</AbstractText>Coronary angiography and stent implantation were performed in CAD patients with ES as major symptom, according to the standardized methods. Holter Electrocardiography was recorded regularly during follow-up.</AbstractText>Six patients, five male and one female, with mean age of 49.5 +/- 9.1 year-old, were hospitalized. In 2 patients with repetitive syncope, multiple episodes of ventricular tachycardia and/or ventricular fibrillation (VF) were documented by Holter recording. One patient developed VF during exercise test. Three patients experienced chest pain and multiple episodes of cardiac arrest. Before procedure, averaged 16.5 +/- 5.3 episodes of syncope or VF were documented in 6 patients. Coronary angiography revealed severe one or multi-vessel diseases. Total 8 stents, including 3 drug-eluting stents, were implanted in 6 patients. Symptom, ST-T changes and ES disappeared after coronary stenting. During 4 month to 6.5 year follow-up (mean 47.7 +/- 30.7 months), ES was not documented, no appropriated shock occurred in patients with implantable defibrillator for 6.5 years.</AbstractText>In CAD patients without myocardial infarction, coronary stenting can relieve the ischemic substrate of ES, hence prevents sudden death effectively.</AbstractText>

Mechanisms of disease: new mechanisms of antiarrhythmic actions.

Cardiac arrhythmias are a leading cause of morbidity and mortality in many developed countries. Despite intensive investigation, the cellular mechanisms for most cardiac arrhythmias have not been clearly established. As a consequence, drug therapy for most forms of atrial and ventricular arrhythmias remains largely empirical and ineffective, leading to the increased use of nonpharmacologic treatments. Clearly, new approaches to the prevention of cardiac arrhythmias are needed. Here we review the current experimental basis for several promising antiarrhythmic strategies, with a focus on those targeted against atrial and ventricular fibrillation. Although none of these strategies is yet ready for clinical application, they provide a basis for cautious optimism that effective pharmacologic therapy for fatal cardiac rhythm disturbances could be forthcoming.

Feasibility assessment of aortic valve area in patients with aortic stenosis using a pressure wire through a 4 French system and single femoral arterial access.

We sought to determine the safety, success and accuracy of using a pressure wire through a 4 French catheter with single arterial access to determine the aortic valve area in patients with aortic stenosis.</AbstractText>Conventional invasive techniques to assess aortic stenosis are associated with procedural risks secondary to bilateral femoral access or the sheath size and reduced accuracy using femoral sheath pressure to replace ascending aortic pressure.</AbstractText>Cardiac output was measured using a pulmonary artery catheter. With a 4 French catheter through single femoral access ascending aortic pressure and, with a pressure wire, left ventricular pressure were recorded simultaneously in four patients with aortic stenosis. Likewise, both pressures were recorded using the pullback method. Pressure gradients were determined by both methods and aortic valve area calculated with the Gorlin equation prior to correlation. Of note, patients with significant arrhythmias such as atrial fibrillation or frequent premature atrial or ventricular contractions were excluded to maintain accuracy of the pullback method.</AbstractText>All hemodynamic parameters were successfully obtained in all four patients. The correlation between pressure wire and pullback method was highly significant in this case series (n = 4, r = 0.983, p = 0.017). There were no complications.</AbstractText>The results suggest that the aortic valve area can be safely and accurately evaluated with a pressure wire using a 4 French system. This novel method could be the preferred method for patients with vascular access limitations.</AbstractText>

Chronic atrioventricular nodal vagal stimulation: first evidence for long-term ventricular rate control in canine atrial fibrillation model.

We have previously demonstrated that selective atrioventricular nodal (AVN) vagal stimulation (AVN-VS) can be used to control ventricular rate during atrial fibrillation (AF) in acute experiments. However, it is not known whether this approach could provide a long-term treatment in conscious animals. Thus, this study reports the first observations on the long-term efficacy and safety of this novel approach to control ventricular rate during AF in chronically instrumented dogs.</AbstractText>In 18 dogs, custom-made bipolar patch electrodes were sutured to the epicardial AVN fat pad for delivery of selective AVN-VS by a subcutaneously implanted nerve stimulator (pulse width 100 micros or 1 ms, frequency 20 or 160 Hz, amplitude 6 to 10 V). Fast-rate right atrial pacing (600 bpm) was used to induce and maintain AF. ECG, blood pressure, and body temperature were monitored telemetrically. One week after the induction of AF, AVN-VS was delivered and maintained for at least 5 weeks. It was found that AVN-VS had a consistent effect on ventricular rate slowing (on average 45+/-13 bpm) over the entire period of observation. Echocardiography showed improvement of cardiac indices with ventricular rate slowing. AVN-VS was well tolerated by the animals, causing no signs of distress or discomfort.</AbstractText>Beneficial long-term ventricular rate slowing during AF can be achieved by implantation of a nerve stimulator attached to the epicardial AVN fat pad. This novel concept is an attractive alternative to other methods of rate control and may be applicable in a selected group of patients.</AbstractText>

Reverse remodeling of the left cardiac chambers after catheter ablation after 1 year in a series of patients with isolated atrial fibrillation.

Isolated atrial fibrillation (AF) is associated with mild enlargement of the left atrium (LA) and left ventricular (LV) diastolic dysfunction. The impact of ablation of isolated AF on left chamber size and function is unclear, and whether diastolic dysfunction is the cause or the consequence of AF remains unknown. The objective of this prospective study was to evaluate the impact of sinus rhythm restoration by catheter ablation on LV diastolic dysfunction, LA morphology, and mechanical function.</AbstractText>Forty-eight patients with isolated AF were studied by serial echocardiographic studies at baseline and at 1-, 3-, 6-, 9-, and 12-month intervals after radiofrequency ablation. LA dimensions and mechanical function and LV systolic and diastolic functions were evaluated at each time interval. Diastolic function was assessed with conventional Doppler parameters and new indexes such as tissue Doppler imaging, mitral flow propagation velocity, and combined criteria. LV diastolic dysfunction was present in paroxysmal and chronic AF patients with a reduction of tissue Doppler imaging lateral early diastolic peak velocity in 37% (P&lt;0.001) and 48% (P&lt;0.01), respectively, compared with healthy control subjects. At the end of the follow-up, LA area decreased significantly by 18% (P&lt;0.001) in paroxysmal and 23% (P&lt;0.05) in chronic AF patients. Diastolic function improved significantly with an increase in lateral early diastolic peak velocity of 29% (P&lt;0.001) in paroxysmal AF and 46% (P&lt;0.05) in chronic AF patients. A significant increase in LV ejection fraction was also noted for both groups: 7.7% and 18.8%, respectively.</AbstractText>This study demonstrates reverse morphological remodeling of the LA and improvement of LV diastolic and systolic functions after restoration of sinus rhythm by ablation for isolated AF. Because patients with isolated AF have none of the traditional causes of LV diastolic dysfunction, our findings suggest that AF may be partly the cause rather than the consequence of diastolic dysfunction.</AbstractText>

QT interval prolongation and torsade de pointes associated with indapamide.

Direct blockade of the delayed rectifier repolarising potassium current is the major underlying mechanism of drug-induced QT interval prolongation. Indapamide is a well known blocker of the slow component of the delayed rectifier current leading to prolongation of cardiac repolarization. The case of an acquired long QT and torsade de pointes ventricular tachycardia in a woman with systemic lupus erythematosus and hypertension receiving prednisolone and indapamide, respectively, is described in the present report.

Antiarrhythmic drugs in patients with implantable cardioverter-defibrillators.

Antiarrhythmic drugs need to be initiated in up to 70% of patients with implantable cardioverter-defibrillators (ICDs) in order to treat atrial tachyarrhythmias, decrease the frequency of defibrillator shocks, and terminate ventricular arrhythmias along with antitachycardia pacing. trial fibrillation (AF) occurs in about 20% of patients with ICDs (the majority with congestive heart failure [CHF]). Antiarrhythmic drugs are initiated for this indication in 2-20% of the ICD population. Data from CHF-STAT (Congestive Heart Failure: Survival Trial of Antiarrhythmic Therapy; amiodarone vs placebo) and DIAMOND-AF (Danish Investigations of Arrhythmia and Mortality ON Dofetilide--rial Fibrillation; dofetilide vs placebo) support the approach that restoration and maintenance of sinus rhythm might be beneficial in CHF, even though no study has specifically addressed the CHF population with ICDs. Further clarification on potential benefits of rhythm control in CHF-associated AF will come from the AF-CHF (Atrial Fibrillation and Congestive Heart Failure) trial that is currently underway. The vast majority of patients with ICDs will have discharges of their devices during follow-up. Although class III antiarrhythmic drugs are widely considered to be effective for prophylaxis against frequent shocks, there are surprisingly few controlled studies that demonstrate this. In contrast to conflicting amiodarone data, sotalol has been found to be effective in preventing shocks from ICDs in prospective, randomized, placebo-controlled studies. A large study (SHIELD; SHock Inhibition Evaluation with azimiLiDe) has shown that azimilide significantly reduces ventricular tachyarrhythmia recurrence, thereby reducing the burden of symptomatic ventricular tachyarrhythmia. Other novel antiarrhythmic drugs, such as dofetilide or dronedarone, as well as different strategies (e.g. in the OPTIC [Optimal Pharmacological Therapy in Implantable Cardioverter] trial; beta-adrenoceptor antagonist therapy alone, amiodarone plus beta-adrenoceptor antagonist therapy, or sotalol alone) for the prevention of ICD shocks are under evaluation. The majority of antiarrhythmic drugs, including sotalol, dofetilide, and azimilide, have no effect on, or are even associated with a decrease in, defibrillation thresholds in humans. Amiodarone, in contrast, has been shown to be related to higher defibrillation thresholds at implant and during follow-up of monophasic devices. Potential cardiac (e.g. ventricular proarrhythmia, negative inotropic effect) and drug-specific non-cardiac adverse effects are a frequent cause for drug discontinuation and need to be considered when initiating and maintaining antiarrhythmic drug therapy. In conclusion, antiarrhythmic drugs are frequently used in ICD patients, the main indications being treatment of atrial tachyarrhythmias and prevention of ICD shocks. Despite potential adverse effects, antiarrhythmics can be administered safely, as long as ICD/drug interactions are appreciated. Controlled studies that will further define the role of concomitant antiarrhythmic drug utilization in patients with ICDs are underway.

Pharmacological management of atrial fibrillation following cardiac surgery.

Atrial fibrillation (AF) is the most common complication following coronary artery bypass graft surgery (CABG). Post-CABG AF occurs most commonly on the second postoperative day and declines in incidence thereafter. A number of risk factors have been found to be associated with a higher frequency of post-CABG AF. These risk factors include advanced age, a prior history of AF, hypertension, and heart failure. Postoperative complications--including low cardiac output, use of an intra-aortic balloon pump, pneumonia, and prolonged mechanical ventilation--are also associated with higher rates of post-CABG AF. Post-CABG AF increases the risk of stroke, and the length and cost of hospitalization. Prophylactic administration of conventional beta-adrenoceptor antagonists (beta-blockers) or sotalol produces a consistent and significant reduction in the incidence of post-CABG AF; however, results with prophylactic amiodarone or magnesium are less consistent. Termination of post-CABG AF, once it occurs, can be accomplished with a number of antiarrhythmic agents. Ibutilide has been the most widely studied agent for this indication. Sotalol is not indicated for cardioversion of AF and has not been studied in the post-CABG setting. Electrical cardioversion and biatrial pacing have also been used to terminate post-CABG AF. Ventricular rate is best controlled with beta-blockers and calcium channel antagonists. Esmolol has a rapid onset of action and is easily titrated to effect. Digoxin can control the ventricular rate, but has a slow onset of action. There are limited data available to guide decisions regarding the optimal management of post-CABG AF.

Defibrillation of German shepherds with inherited ventricular arrhythmias and sudden death.

To characterize defibrillation success in German shepherd (GS) dogs with inherited ventricular arrhythmias and sudden death.</AbstractText>Ventricular tachycardia (VT) degenerates to ventricular fibrillation (VF) as the cause of death in GS dogs. To test the hypothesis that GS dogs are more difficult to defibrillate than other dogs, we sought to compare defibrillation success of induced VF in affected GS dogs to a control group of beagles.</AbstractText>ECG and monophasic action potential (MAP) recordings were acquired during VF and transthoracic defibrillation in anesthetized GS dogs (n=13) and normal beagles (n=7). Shock efficacy, energy requirements, VF frequency and post-defibrillation rhythms were compared between the 2 groups.</AbstractText>First shock success of all episodes of VF was lower in GS dogs (10 of 18) than beagles (46 of 47) (p&lt;0.0001). However, when evaluated by dog, shock success was not different between GS and beagles (7 of 13 and 6 of 7, respectively; p=0.15). Multiple shock success (&lt;/=3 consecutive shocks) resulted in a poorer defibrillation success of all episodes of VF in GS dogs (15 of 18) as compared to beagles (47 of 47) (p&lt;0.02). Multiple shock success evaluated by dog was similar between GS (11 of 13) and beagles (7 of 7) (p=0.11).</AbstractText>Affected GS dogs had lower defibrillation success than beagles; however, defibrillation was possible in the majority of cases.</AbstractText>

A retrospective evaluation of transthoracic biphasic electrical cardioversion for atrial fibrillation in dogs.

To evaluate safety, efficacy, and clinical usefulness of biphasic transthoracic cardioversion for management of dogs with atrial fibrillation (AF).</AbstractText>In dogs AF is usually managed with heart rate control rather than by restoration of sinus rhythm (SR). However, restoration of SR has potential advantages of improving cardiac output and reducing ventricular filling pressures, and biphasic cardioversion provides an improved benefit/risk ratio compared to traditional monophasic cardioversion.</AbstractText><AbstractText Label="ANIMALS, MATERIALS AND METHODS" NlmCategory="METHODS">Retrospective analysis of data from 39 dogs with spontaneous AF managed with biphasic transthoracic cardioversion was done. Conversion characteristics, adverse effects, and duration of SR were evaluated. Effects of heart disease and pretreatment with amiodarone on success of cardioversion and on duration of SR were also evaluated.</AbstractText>Restoration of SR was achieved in 36 of 39 dogs (92.3%). Presence of heart disease or atrial enlargement had no effect on cardioversion characteristics or ability to restore SR. Median duration of SR following cardioversion and treatment with amiodarone was 120 days. Dogs with lone AF remained in SR longer than those with heart disease.</AbstractText>Biphasic cardioversion is safe and effective. Although duration of SR varied, a majority of dogs remained in SR long enough to benefit.</AbstractText>

Electric shock: Cardiac effects relative to non fatal injuries and post-mortem findings in fatal cases.

The documented cardiovascular effects of an electrical shock include acute myocardial necrosis, myocardial ischemia with or without necrosis, heart failure, arrhythmias, haemorrhagic pericarditis, acute hypertension with peripheral vasospasm and anomalous, non specific ECG alterations. Studies documenting the development of acute left ventricular failure and pulmonary oedema sustain that the observed ECG changes are secondary to myocardial injury. The cause of death of victims of instantly fatal electrical accidents is ventricular fibrillation, but it is not clear if this fibrillation is due to purely electrophysiological changes or to identifiable structural abnormalities in the heart. Little is known about the morphological changes in the heart, as differing anatomical alterations are described. Data from such studies may aid in a more accurate comprehension of clinical and morphological alterations of the heart and in the development of therapeutic strategies that could counterbalance such effects.

Factors influencing appropriate firing of the implanted defibrillator for ventricular tachycardia/fibrillation: findings from the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II).

The purpose of this study was to prospectively examine the role of clinical, laboratory, echocardiographic, and electrophysiological variables as predictors of appropriate initial implantable cardioverter-defibrillator (ICD) therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF) or death in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) population.</AbstractText>There is limited information regarding the determinants of appropriate ICD therapy in patients with reduced ventricular function after a myocardial infarction.</AbstractText>We used secondary analysis in one arm of a multicenter randomized clinical trial in patients with a previous myocardial infarction and reduced left ventricular function.</AbstractText>We analyzed baseline and follow-up data on 719 patients enrolled in the ICD arm of the MADIT-II study. Appropriate ICD therapy was observed in 169 subjects. Clinical, laboratory, echocardiographic, and electrophysiological variables, along with measures of clinical instability such as interim hospitalization for congestive heart failure (IH-CHF) and interim hospitalization for coronary events (IH-CE), were examined with proportional hazards models and Kaplan-Meier time-to-event curves before and after first interim hospitalization. Interim hospitalization-CHF, IH-CE, no beta-blockers, digitalis use, blood urea nitrogen (BUN) &gt;25, body mass index (BMI) &gt; or =30 kg/m2, and New York Heart Association functional class &gt;II were associated with increased risk for appropriate ICD therapy for VT, VF, or death. In a multivariate (stepwise selection) analysis, IH-CHF was associated with an increased risk for the end point of either VT or VF (hazard ratio [HR] 2.52, 95% confidence interval [CI] 1.69 to 3.74, p &lt; 0.001) and for the combined end point of VT, VF, or death (HR 2.97, 95% CI 2.15 to 4.09, p &lt; 0.001). Interim hospitalization-CE was associated with an increased risk for VT, VF, or death (HR 1.66, 95% CI 1.09 to 2.52, p = 0.02).</AbstractText>These results provide important mechanistic information, suggesting that worsening clinical condition and cardiac instability, as reflected by an IH-CHF or IH-CE, are subsequently associated with a significant increase in the risk for appropriate ICD therapy (for VT/VF) and death.</AbstractText>

Variable Unstressed Volume Keeps Normal Distributions of Canine Left Ventricular Contractility and Total Mechanical Energy under Atrial Fibrillation.

We have reported that the contractility index (E(max)) and the total mechanical energy (PVA) of arrhythmic beats of the left ventricle (LV) distribute normally in canine hearts under electrically induced atrial fibrillation (AF). Here, E(max) is the ventricular elastance as the slope of the end-systolic (ES) pressure-volume (P-V) relation (ESPVR), and PVA is the systolic P-V area as the sum of the external mechanical work within the P-V loop and the elastic potential energy under the ESPVR. To obtain E(max) and PVA, we had to assume the systolic unstressed volume (V(o)) as the V-axis intercept of the ESPVR to be constant despite the varying E(max), since there was no method to obtain V(o) directly in each arrhythmic beat. However, we know that in regular stable beats V(o) decreases by approximately 7 ml/100 g LV with approximately 100 times the increases in E(max) from ~0.2 mmHg/(ml/100 g LV) of almost arresting weak beats to approximately 20 mmHg/(ml/100 g LV) of strong beats with a highly enhanced contractility. In the present study, we investigated whether E(max) and PVA under AF could still distribute normally, despite such E(max)-dependent V(o) changes. The present analyses showed that the E(max) changes were only approximately 3 times at most from the weakest to the strongest arrhythmic beat under AF. These changes were not large enough to affect V(o) enough to distort the frequency distributions of E(max) and PVA from normality. We conclude that one could practically ignore the slight E(max) and PVA changes with the Emax-dependent V(o) changes under AF.

Differences in outcomes between patients treated with single- versus dual-chamber implantable cardioverter defibrillators: a substudy of the Multicenter Automatic Defibrillator Implantation Trial II.

We sought to evaluate the influence of single- versus dual-chamber implantable cardioverter defibrillators (ICDs) on the occurrence of heart failure and mortality as well as appropriate and inappropriate ICD therapy in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II).</AbstractText>In MADIT-II, ICD therapy in patients with a prior myocardial infarction and ejection fraction &lt; or =0.30 was associated with a 31% reduction in risk of mortality when compared to conventionally treated patients. An unexpected finding was an increased occurrence of hospitalization for heart failure in the ICD group.</AbstractText>Data from 717 patients randomized to ICD therapy with single- or dual-chamber pacing devices in MADIT-II were retrospectively analyzed. Endpoints selected for analysis included death from any cause, new or worsening heart failure requiring hospitalization, death or heart failure, appropriate therapy for ventricular tachycardia (VT) or ventricular fibrillation (VF), and inappropriate ICD therapy for atrial fibrillation or supraventricular tachycardia.</AbstractText>A total of 404 single-chamber ICDs (S-ICDs) and 313 dual-chamber ICDs (D-ICDs) were implanted. Patients receiving D-ICDs were at a higher risk at baseline than those receiving S-ICDs, with older age, higher NYHA class, more frequent prior CABG, wider QRS complex, more LBBB, higher BUN level, a history of more atrial arrhythmias requiring treatment, and a longer time interval from their index myocardial infarction to enrollment. While there was a trend toward an increase in adverse outcomes in the D-ICD group, no statistically significant differences in heart failure or mortality were observed between S-ICD versus D-ICD groups.</AbstractText>Patients with D-ICDs had a nonsignificant trend toward higher mortality and heart failure rates than patients with S-ICDs.</AbstractText>

A Latin American registry of implantable cardioverter defibrillators: the ICD-LABOR study.

Despite the progress that has been reached in emergency medical systems and resuscitation, sudden cardiac death (SCD) continues to be the major cause of the death, and remains a significant public health problem. In this publication we are reporting our Latin American experience in the secondary prevention of SCD, by means of an ongoing registry involving seven Latin American countries and 770 patients.</AbstractText>Every individual within the present registry to date has presented with antecedents of aborted sudden death or cardiac arrest due to ventricular tachycardia or ventricular fibrillation. Patients included have fulfilled the Class I indication for implantable cardioverter defibrillator (ICD) and they were implanted with a Biotronik ICD (all models). The study was not sponsored by Biotronik, nor did they have access to the data. A specific protocol was designed for implantation and follow-up of patients. The database was completely registered through the Internet and a personal password was assigned to each group of investigators. The primary end point was death from all causes. Secondary end points were SCD and death due to congestive heart failure (CHF).</AbstractText>The etiology of cardiac disease was found to be predominantly coronary artery disease (CAD) 39.7% (306 patients), followed by Chagas disease (ChD), 26.1% (201 patients), and idiopathic dilated cardiomyopathy (DCM), 17% (131 patients). Any remaining pathologies were included as miscellaneous 13.2% (101 patients). In 31 patients (4%) the etiology was unknown. The age did not differ within the principal pathologies, but was significantly older than the miscellaneous group (62.0 +/- 11.3 years vs 48.2 +/- 18.9 years, P &lt; 0.0001). The follow-up period was 27 +/- 25 months (1-113 months) for the whole group. The mortality in functional classes I-II was significantly lower than mortality for functional classes III-IV (relative risk 1.46, CI 95%, P &lt; 0.0001). Mean left ventricular ejection fraction (LVEF) for the whole group was 37.7 +/- 14.3%. Male LVEF was 36.1 +/- 14.1% and female LVEF was 42.2 +/- 13.8% P &lt; 0.0001. During the follow-up period, 130 deaths were reported (global mortality 16.9 +/- 9.7%), out of which 84 (64.6%) were attributed to cardiac causes (10.9 +/- 5.1% of the total population). The annual adjusted cardiac mortality was 5.2 +/- 1.72% (range 3.5-7.0%). Among cardiac deaths the most common cause was progressive heart failure, 48 patients (57%) including 3 patients with pulmonary embolism. The second main cause of cardiac death was SCD, 36 patients (43%), including 4 patients with electrical storm and 3 patients with electromechanical dissociation after multiple shock therapy treatments.</AbstractText>Despite the differences in terms of pathologies between the ICD-LABOR (Latin American bioelectronic ongoing registry) and randomized ICD trials, a parallel evolution in all cause mortality and cardiac mortality was observed. Independent risk factors for mortality included age &gt;70 years, male gender, NYHA III/IV, and ejection fraction &lt;0.30. The etiology of heart disease (Chagas vs Coronary Disease) was not found to be a risk factor.</AbstractText>

Effects of mobile telephones on the function of implantable cardioverter defibrillators.

We investigated whether mobile telephones affect the function of implantable cardioverter defibrillators (ICDs).</AbstractText>It is well known that electromagnetic fields can affect medical devices.</AbstractText>The study included 43 patients with ventricular tachycardia and/or fibrillation treated with transvenous pectoral ICDs. Testing was done under continuous electrocardiograph monitoring under supervision of an ICD programmer. Initially, each patient was tested during spontaneous rhythm. Then the ICD was programmed to a pace rhythm higher than the patient's heart rate, and the tests were repeated at paced rhythm. In 7 patients, tests were performed during the implantation procedure as well. In 3 of the patients, only a single defibrillation zone was active. The other 40 patients had one or more active ventricular tachycardia zones. Two mobile phones (both GSM 900 MHz) were positioned 50 cm away from the implanted device in opposite directions and switched on. Communication was established between these phones, two investigators had a 20-second conversation, and then the phones were switched off. The same procedure was repeated at 30, 20, and 10 cm away from the implantation site, respectively. Finally, the procedure was performed with the antennae of both phones touching the device pocket. In the above-mentioned 7 cases where testing was done during implantation of the ICD, a call was made from one phone to the other, ringing occurred for 5 seconds, and then two investigators conversed while the device was implanted.</AbstractText>There was no change in the function of the ICDs during any of the phone testing procedures. In 5 cases, artifacts were noted on the surface electrocardiographic (ECG) screen of the programmer during the tests, but no such changes were observed on the simultaneous intracardiac ECGs.</AbstractText>The results of the study suggest that mobile phones have no effects on ICD function.</AbstractText>

Noninvasive risk stratification of subjects with a Brugada-type electrocardiogram and no history of cardiac arrest.

Recent studies suggest that the Brugada-type electrocardiogram (ECG) is much more prevalent than the manifest Brugada syndrome. Although invasive electrophysiologic investigations have been proposed as a risk stratifier, their value is controversial, and alternative noninvasive techniques may be preferred. We sought a noninvasive strategy to detect a high-risk group in a long-term follow-up study of subjects with a Brugada-type ECG, and no history of cardiac arrest.</AbstractText>This study enrolled 124 consecutive subjects with a Brugada-type ECG. Prognostic indices included: age, sex, a family history of sudden death, syncopal episodes, a spontaneous coved-type ST-segment elevation, maximal magnitude of ST-segment elevation, a spontaneous change in ST segment, a mean QRS duration, maximal QT interval, QT dispersion, late potentials (LP) by signal-averaged ECG, and microvolt T-wave alternans.</AbstractText>Of the 124 subjects, 20 consenting subjects had an implantable defibrillator before follow-up. During a 40 +/- 19-month follow-up, 12 subjects (9.7%) reached one of the endpoints (sudden death or ventricular tachyarrhythmia). Of the 12 risk indices, a family history of sudden death, syncopal episodes, a spontaneous coved-type ST-segment elevation, a spontaneous change in ST segment, and LP had significant values. In multivariate analysis, a spontaneous change in ST segment had the most significance (a relative hazard, 9.2; P = 0.036). Combined assessment of this index and other significant indices obtained higher positive predictive values (43-71%).</AbstractText>A spontaneous change in ST segment is associated with the highest risk for subsequent events in subjects with a Brugada-type ECG. The presence of syncopal episodes, a history of familial sudden death, and/or LP may increase its value.</AbstractText>

Functional assessment of compound mutations in the KCNQ1 and KCNH2 genes associated with long QT syndrome.

Long QT syndrome (LQTS) is a cardiovascular disorder characterized by prolonged QTc time, syncope, or sudden death caused by torsades de pointes and ventricular fibrillation. We investigated the clinical and electrophysiologic phenotype of individual mutations and the compound mutations in a family in which different genotypes could be found.</AbstractText>The purpose of this study was to determine the impact of genotype-based diagnostic assessment in LQTS.</AbstractText>We used cascade screening and functional analyses to investigate the phenotype in a family with LQTS. The contributions of the compound mutations in the KCNQ1 and KCNH2 genes (KCNQ1 R591H, KCNH2 R328C) were analyzed by heterologous expression in Xenopus laevis oocytes using two-electrode voltage clamp and by confocal imaging.</AbstractText>KCNH2 R328C did not show any functional phenotype whereas KCNQ1 R591H resulted in severe reduction of current. Neither wild-type nor mutant channels affected each other functionally in coexpression experiments. Therefore, a direct interaction between KCNQ1 and KCNH2 was ruled out under these conditions.</AbstractText>Assessment of novel mutational findings in LQTS should include accurate genetic and functional analysis. Notably, appropriate studies are needed if two or more mutations in different genes are present in one proband. Our findings prompt reconsideration of the impact of compound mutations in LQTS families and reinforce the need for thorough functional evaluation of novel ion channel mutations before assignment of pathogenic status.</AbstractText>

Predictors of appropriate implantable defibrillator therapies in patients with arrhythmogenic right ventricular dysplasia.

Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited cardiomyopathy characterized by ventricular arrhythmias and sudden cardiac death. The risk factors for sudden death and indications for implantable cardioverter-defibrillator (ICD) placement in patients with ARVD are not well defined.</AbstractText>The purpose of this study was to determine which clinical and electrophysiologic variables best predict appropriate ICD therapies in patients with ARVD. Particular attention focused on whether the ICD was implanted for primary or second prevention.</AbstractText>We enrolled 67 patients (mean age 36 +/- 14 years) with definite or probable ARVD who had undergone ICD placement. Appropriate ICD therapies were recorded, and Kaplan-Meier analysis was used to compare the event-free survival time between patients based upon the indication for ICD placement (primary vs secondary prevention), results of electrophysiologic testing, and whether the patient had probable or definite ARVD.</AbstractText>Over a mean follow-up of 4.4 +/- 2.9 years, 40 (73%) of 55 patients who met task force criteria for ARVD and 4 (33%) of 12 patients with probable ARVD had appropriate ICD therapies for ventricular tachycardia/ventricular fibrillation (VT/VF; P = .027). Mean time to ICD therapy was 1.1 +/- 1.4 years. Eleven of 28 patients who received an ICD for primary prevention (39%) and 33 of 35 patients who received an ICD for secondary prevention (85%) experienced appropriate ICD therapies (P = .001). Electrophysiologic testing did not predict appropriate ICD interventions in patients who received an ICD for primary prevention. Fourteen patients (21%) received ICD therapy for life-threatening (VT/VF &gt;240 bpm) arrhythmias. There was no difference in the incidence of life-threatening arrhythmias in the primary and secondary prevention groups (P = .29).</AbstractText>Patients who meet task force criteria for ARVD are at high risk for sudden cardiac death and should undergo ICD placement for primary and secondary prevention, regardless of electrophysiologic testing results. Further research is needed to confirm that a low-risk subset of patients who may not require ICD placement can be identified.</AbstractText>

Prevalence of atrial fibrillation and associated factors in a population of long-term hemodialysis patients.

Hemodialysis (HD) is associated with cardiovascular structural modifications; moreover, during HD, rapid electrolytic changes occur. Both factors may favor the onset of atrial fibrillation.</AbstractText>To define the prevalence of atrial fibrillation and identify associated factors, 488 patients on long-term HD therapy (age, 66.6 +/- 13.4 years; men, 58.0%; duration of HD, 76.5 +/- 84.3 months) were studied.</AbstractText>Atrial fibrillation was reported in 27.0% of patients; paroxysmal in 3.5%, persistent in 9.6%, and permanent in 13.9%. Clinical and echocardiographic variables were considered: patients with atrial fibrillation were older (71.8 +/- 9.3 versus 64.7 +/- 14.2 years; P &lt; 0.01), and its prevalence increased with age. Patients with arrhythmia had a longer duration of dialysis therapy (93.2 +/- 100.5 versus 70.2 +/- 76.7 months; P = 0.02). Atrial fibrillation was associated significantly with ischemic heart disease (P &lt; 0.01), dilated cardiomyopathy (P &lt; 0.01), acute pulmonary edema (P &lt; 0.05), valvular disease (P &lt; 0.05), cerebrovascular accidents (P &lt; 0.05), and predialytic hyperkalemia (P &lt; 0.05). Patients with atrial fibrillation more frequently showed left atrial dilatation (59.8% versus 34.5%; P &lt; 0.0001), and in these subjects, left ventricular ejection fraction was significantly lower (53.9% versus 57.4%; P = 0.029). No association was found between arrhythmia and hypertension or diabetes. Multivariate analysis confirmed that patient age (P &lt; 0.001), duration of HD therapy (P = 0.001), and left atrial dilatation (P &lt; 0.001) were associated with atrial fibrillation.</AbstractText>Atrial fibrillation is much more frequent in HD patients than in the general population; age, duration of HD history, presence of some heart diseases, and left atrial dilatation are associated with the arrhythmia.</AbstractText>

Reliability of old and new ventricular fibrillation detection algorithms for automated external defibrillators.

A pivotal component in automated external defibrillators (AEDs) is the detection of ventricular fibrillation by means of appropriate detection algorithms. In scientific literature there exists a wide variety of methods and ideas for handling this task. These algorithms should have a high detection quality, be easily implementable, and work in real time in an AED. Testing of these algorithms should be done by using a large amount of annotated data under equal conditions.</AbstractText>For our investigation we simulated a continuous analysis by selecting the data in steps of one second without any preselection. We used the complete BIH-MIT arrhythmia database, the CU database, and the files 7001-8210 of the AHA database. All algorithms were tested under equal conditions.</AbstractText>For 5 well-known standard and 5 new ventricular fibrillation detection algorithms we calculated the sensitivity, specificity, and the area under their receiver operating characteristic. In addition, two QRS detection algorithms were included. These results are based on approximately 330,000 decisions (per algorithm).</AbstractText>Our values for sensitivity and specificity differ from earlier investigations since we used no preselection. The best algorithm is a new one, presented here for the first time.</AbstractText>

The novel antiarrhythmic drug dronedarone: comparison with amiodarone.

Dronedarone is a noniodinated benzofuran derivative that has been developed to overcome the limiting iodine-associated adverse effects of the commonly used antiarrhythmic drug, amiodarone. It displays a wide cellular electrophysiological spectrum largely similar to amiodarone, inhibiting the potassium currents I(Kr), I(Ks), I(KI), I(KACh), and I(sus), as well as sodium currents and L-type calcium currents in isolated cardiomyocytes. In addition, dronedarone exhibits antiadrenergic properties. In vivo, dronedarone has been shown to be more effective than amiodarone in several arrhythmia models, particularly in preventing ischemia- and reperfusion-induced ventricular fibrillation and in reducing mortality. However, an increased incidence of torsades de pointes with dronedarone in dogs shows that possible proarrhythmic effects of dronedarone require further evaluation. The clinical trails DAFNE, EURIDIS, and ADONIS indicated safety, antiarrhythmic efficacy and low proarrhythmic potential of the drug in low-risk patients. In contrast, the increased incidence of death in the dronedarone group of the discontinued ANDROMEDA trial raises safety concerns for patients with congestive heart failure and moderate to severe left ventricular dysfunction. Dronedarone appears to be effective in preventing relapses of atrial fibrillation and atrial flutter. Torsades de pointes, the most severe adverse effect associated with amiodarone, has not yet been reported in humans with dronedarone. Unlike amiodarone, dronedarone had little effect on thyroid function and hormone levels in animal models and had no significant effects on human thyroid function in clinical trials. In conclusion, dronedarone could be a useful drug for prevention of atrial fibrillation and atrial flutter relapses in low-risk patients. However, further experimental studies and long-term clinical trials are required to provide additional evidence of efficacy and safety of dronedarone.

[Variation in the plasma concentration of B-type natriuretic peptide in emergent paroxysmal atrial fibrillation, in acute pulmonary embolism, in acute coronary syndrome and in dilated cardiomyopathy].

Our research is based on the critical evaluation of plasma concentration variation of B-type natriuretic peptide (BNP)--in emergency--in paroxysmal atrial fibrillation, acute pulmonary edema, acute coronary syndrome and dilated cardiomyopathy. The aim of our research was to assess if the BNP concentration variation may be useful in the diagnosis and therapy. Peptide synthesis takes place mainly in the ventricular myocardium. We selected 102 patients: 27 control subjects, and 75 admitted to the emergency and reception department for dyspnea and/or precordialgia and/or palpitations. At the beginning they were considered as one group only, and then they were divided into groups according to the diagnosis: 20 with paroxysmal atrial fibrillation with reversion to sinus rhythm in the first week; 20 with acute pulmonary edema; 22 with acute coronary syndrome without electrocardiographic ST-segment changes; 13 with compensated dilated cardiomyopathy. Our research assessed that the BNP activation and secretion are evident especially in patients with heart failure and remains at the high level until the administration of an effective therapy and then they reach a balance with values higher than the standards, while in the paroxysmal atrial fibrillation and in acute coronary syndrome they rise and come back to the standard levels or even at lower levels after the disease solution. For this reason, BNP reiterated measurements allow to assess treatment efficacy, even at home, and to optimize the therapy. The main limit of BNP diagnostic role is in the need of knowing in advance the specific values for each patient. The BNP concentration evaluation in the acute phase is necessary to differentiate patients with dyspnea due to heart failure from those with pulmonary pathologies, while the BNP assessment in the acute coronary syndrome predicted exitus or heart failure manifestations.

Critical care providers' perceptions of the use of vasopressin in cardiac arrest.

Although published algorithms and guidelines list epinephrine and vasopressin as either/or choices for treatment of ventricular fibrillation and/or pulseless ventricular tachycardia, little is known about how critical care providers respond to this recommendation.</AbstractText>To assess the use of vasopressin as a first-line drug of choice for ventricular fibrillation and/or pulseless ventricular tachycardia and describe factors that may influence decision making for using vasopressin.</AbstractText>A convenience sample from 4 academic medical centers in the United States was recruited to complete a 20-item survey on demographic factors such as year of last Advanced Cardiac Life Support (ACLS) provider course, specialty certification, predominant practice responsibility, and beliefs related to the use of vasopressin for cardiac arrest. Descriptive statistics, Pearson correlation analysis, and logistic regression were used to analyze the data.</AbstractText>A total of 214 critical care providers (80% registered nurses) completed the survey. Year of last ACLS course (r=-0.188, P=.006) was a significant demographic factor, and behavioral beliefs (attitude about using vasopressin) had the strongest relationship (r=0.687, P&lt;.001) and were the best predictor for intentions to use or recommend the use of vasopressin (beta=0.589, P&lt;.001).</AbstractText>Despite the recommendation for vasopressin as an agent equivalent to epinephrine for treatment of ventricular fibrillation and/or pulseless ventricular tachycardia, 63% of respondents used epinephrine as a first-line drug of choice. More research is needed to address the classification system for interpreting the quality of evidence that may influence practice.</AbstractText>

Discordant repolarization alternans-induced atrial fibrillation is suppressed by verapamil.

Ventricular alternans of repolarization produces serious ventricular arrhythmias in experimental models. The present study investigated the role of alternans of atrial repolarization in patients with atrial fibrillation (AF).</AbstractText>Electrophysiological studies were performed in 19 patients without structural heart disease. Monophasic action potentials (MAP) were recorded with 2 Franz catheters during steady state pacing, starting at a cycle length (CL) of 400 ms with subsequent decrements of 10 ms. Duration from the onset of upstroke to 90% repolarization of the MAP were measured. If discordant alternans (DA) was present during pacing, verapamil was administrated, and MAP measurements were repeated. Rapid pacing resulted in concordant alternans to DA in 13 of 19 (68%) patients. AF was initiated after the induction of DA in 8 of 13 patients (p=0.012). Verapamil treatment resulted in a significant decrease in the longest pacing CL at which DA was induced (207+/-19 vs 178+/-17 ms, p&lt;0.0001).</AbstractText>Rapid atrial pacing induced DA and was associated with initiation of AF. Furthermore, induction of DA was suppressed by verapamil. Reducing the spatiotemporal repolarization heterogeneity may be how the calcium-channel blockade prevents initiation of AF.</AbstractText>

Multicenter survey on the validity of the CD-ROM guideline for antiarrhythmic drug therapy produced by the Japanese Circulation Society and the Japanese Society on Electrocardiology: preliminary report of the survey of the Japanese guideline for Arrhythmia Management By Individual Therapy (J-GAMBIT).

A multicenter investigational survey (Japanese Guideline for Arrhythmia Management By Individual Therapy) was conducted to evaluate the validity of using CD-ROM guidelines vs physician choice for the selection of antiarrhythmic drugs.</AbstractText>Patients with paroxysmal atrial fibrillation (PAF, n=274) or premature ventricular contractions (PVC, n=216) were enrolled. The rate of concordance for drug selection between the treating physician and the CD-ROM was 216 of 274 patients (78.8%) with PAF. Of these, 168 (61.3%) were concordant for first-line agents and the remaining 48 (17.5%) were concordant for second-line agents. The concordance for the treatment of PVC was 154/216 cases (71.3%). Of these, 106 (49.1%) were concordant for first-line agents and the remaining 48 (22.2%) were concordant for second-line agents. Nonconcordance for PAF therapy was more likely to occur for patients with underlying heart disease (p&lt;0.05), depressed cardiac function (p&lt;0.001), and with more frequent ECG abnormalities and renal dysfunction. These differences were not seen in patients with PVC.</AbstractText>The CD-ROM guidelines appear to be valid in the selection of antiarrhythmic drugs for both PAF and PVC, but their usefulness is influenced by the patient's clinical characteristics.</AbstractText>

Global dynamic coupling of activation and repolarization in the human ventricle.

The ability to determine spatial and dynamic changes in ventricular repolarization may help to understand arrhythmogenic mechanisms in humans. We hypothesized that noncontact mapping could be used to investigate global activation-repolarization coupling in the human ventricle during steady state and premature extrastimulation.</AbstractText>Activation-recovery intervals (ARIs) determined from reconstructed unipolar electrograms by the Ensite system were analyzed during sinus rhythm, constant pacing, spontaneous ventricular ectopic beats, and premature stimulation at intermediate and short coupling intervals in the left or right ventricle of 13 patients (6 female; mean age, 48 years) without structural myocardial disease. ARIs were measured from 32 sites in each ventricle with the use of a method validated with monophasic action potential recordings and unipolar contact electrograms. Global T-wave distribution was displayed on a 3-dimensional geometry of the ventricle, with polarities opposite to the direction of activation during steady state and premature stimulation. There was a significant inverse correlation between activation times and ARIs during sinus rhythm, ventricular ectopy, and premature stimulation (r=0.72, slope=-0.76, P&lt;0.001). Premature stimuli at short coupling intervals flattened the regression slope compared with sinus rhythm (-0.61 versus -0.81; P=0.05), but the global pattern of repolarization was preserved. In comparison to our method, the Wyatt method of ARI measurement failed to demonstrate significant coupling between activation and repolarization (r=0.34, slope=0.19).</AbstractText>Global, dynamic repolarization mapping of the human ventricle is feasible. An inverse coupling of activation and repolarization during steady state and premature stimulation may preserve electric stability in the normal ventricle.</AbstractText>

Myocardial protection with intermittent cross-clamp fibrillation: does preconditioning play a role?

Previously, we showed intermittent cross-clamp fibrillation afforded equivalent protection to cardioplegia. This study examined whether protection induced by intermittent cross-clamp fibrillation involves an ischemic preconditioning mechanism.</AbstractText>Isolated Langendorff-perfused rat hearts were subjected to three different studies to determine: Study 1, whether a single intermittent cross-clamp fibrillation episode (10 min) and reperfusion (10 min) before prolonged ischemia acts as a preconditioning trigger for protection; Study 2, whether cardioprotection induced by intermittent cross-clamp fibrillation alone (no prolonged ischemia) involves a preconditioning mechanism; Study 3, whether intermittent cross-clamp fibrillation cardioprotection can be prevented by targeting putative components of the preconditioning mechanism (protein kinase C or the mitochondrial ATP-sensitive potassium (K(ATP)) channel). Hearts were reperfused (60 min) and recovery of function (left ventricular developed pressure measured using an intraventricular balloon) and myocardial injury (creatine kinase leakage) were measured.</AbstractText>In Study 1, recovery of function in the single intermittent cross-clamp fibrillation hearts was 61+/-3% (mean+/-SEM) (p&lt;0.05) compared to 41+/-2% in control group; glibenclamide (a non-specific ATP-sensitive potassium (K(ATP))-channel blocker) prevented this preconditioning protection (37+/-4%). In Study 2, recovery of function in intermittent cross-clamp fibrillation hearts (62+/-3%) was significantly (p&lt;0.05) higher than intermittent cross-clamp fibrillation hearts treated with glibenclamide (33+/-2%) and ischemia hearts (30+/-5%). In Study 3, protection by intermittent cross-clamp fibrillation (60+/-3%; p&lt;0.05) was attenuated by protein kinase C inhibition (chelerythrine, 34+/-3%) and mitochondrial K(ATP)-channel blockade (5-hydroxydecanoate, 27+/-4%) to levels not significantly different from that of ischemia hearts (25+/-4%).</AbstractText>The cardioprotective efficacy of intermittent cross-clamp fibrillation was attenuated by protein kinase C inhibition or K(ATP)-channel blockade. Involvement of these putative preconditioning cascade components in association with cardioprotection induced by intermittent cross-clamp fibrillation, suggests a role for the ischemic preconditioning mechanism.</AbstractText>

Levosimendan improves postresuscitation outcomes in a rat model of CPR.

In this study we sought to determine whether a calcium sensitizer, levosimendan, would have a more favorable effect on postresuscitation myocardial function and, consequently, postresuscitation survival than beta-adrenergic dobutamine. The extreme decrease in survival before hospital discharge of resuscitated victims is attributed, in part, to postresuscitation myocardial failure, and dobutamine has been recommended for the management of postresuscitation myocardial failure. We studied a total of 15 animals. Ventricular fibrillation was induced in Sprague-Dawley rats weighing 450 to 550 g. Cardiopulmonary resuscitation (CPR), including chest compressions and mechanical ventilation, was begun after 8 minutes of untreated cardiac arrest. Electrical defibrillation was attempted after 6 minutes of CPR. Each animal was resuscitated. Animals were randomized to undergo treatment with levosimendan, dobutamine, or saline-solution placebo. These agents were administered 10 minutes after the return of spontaneous circulation. Levosimendan was administered in a loading dose of 12 microg kg(-1) over a 10-minute period, followed by infusion of 0.3 microg kg(-1) min(-1) over the next 230 minutes. Dobutamine was continuously infused at a dosage of 3 microg kg(-1) min(-1). Saline-solution placebo was administered in the same volume and over the same amount of time as levosimendan. Levosimendan and dobutamine produced comparable increases in cardiac output and rate of left-ventricular pressure increase. However, administration of levosimendan resulted in lower heart rates and lesser increases in left ventricular diastolic pressure compared with both dobutamine and placebo. The duration of postresuscitation survival was significantly greater with levosimendan (16 +/- 2 hours), intermediate with dobutamine (11 +/- 2 hours) and least with saline-solution placebo (8 +/- 1 hour). Levosimendan and dobutamine both improved postresuscitation myocardial function. However, levosimendan produced more favorable postresuscitation myocardial function and increased the duration of postresuscitation survival.

Evaluation and course of an unusual case of arrhythmogenic right ventricular dysplasia.

We report a case of a 42-year-old Caucasian man who presented with isolated right ventricular failure and atrial fibrillation without ventricular arrhythmia. In this report, we describe accurate evaluation by MR imaging confirmed by histopathologic findings as well as imaging progression of this unusual case of arrhythmogenic right ventricular dysplasia.

Atrial fibrillation following cardiac surgery.

Atrial tachyarrhythmias, usually atrial fibrillation or atrial flutter, are the most common complications of cardiac surgery. Atrial tachyarrhythmias are associated with patient discomfort/anxiety, hemodynamic deterioration, cognitive impairment, thromboembolic events (including stroke), exposure to the risks of antiarrhythmic treatments, longer hospital stays and increased costs. Many approaches to the prevention of postoperative atrial tachyarrhythmias have been studied. Of these, studies using perioperative beta-blocking agents or amiodarone provide level A evidence of efficacy and, in properly selected patients, have shown a high degree of safety. Less convincing, level B evidence exists for the use of postoperative temporary atrial pacing and for perioperative intravenous magnesium treatment. The treatment of postoperative atrial tachyarrhythmias is similar to those occurring in other settings and includes excluding other potential causes of atrial tachyarrhythmias, antithrombotic or anticoagulation therapy, control of the ventricular response rate and consideration of restoring/maintaining sinus rhythm. The selection of therapies to achieve these goals should consider the sympathetic nervous system discharge state of the postoperative environment and the natural history of postoperative atrial fibrillation, which includes spontaneous resolution of the arrhythmogenic tendency after approximately six weeks. The Canadian Cardiovascular Society Consensus Conference recommendations for the prevention of atrial tachyarrhythmias after cardiac surgery and for the treatment of atrial tachyarrhythmias that occur after cardiac surgery are presented along with evidence that supports these recommendations.

Pacing for the prevention of atrial fibrillation.

Multiple randomized clinical trials have demonstrated that atrial or dual-chamber pacing prevents paroxysmal and permanent atrial fibrillation (AF) in patients with symptomatic bradycardia as the primary indication for cardiac pacing. The benefit of atrial pacing for the prevention of AF is observed predominantly in patients with sinus node dysfunction. Emerging evidence also suggests that the risk of AF is directly linked to the proportion of time that ventricular pacing occurs. Consequently, pacemakers should be programmed to minimize the amount of ventricular pacing in patients with intrinsic atrioventricular conduction. Temporary atrial pacing following heart surgery may be of benefit for the prevention of perioperative AF. Atrial pacing has not been shown to prevent AF in patients without symptomatic bradycardia. In addition, selective pacing algorithms designed to prevent AF have minimal or no incremental benefits for the prevention of AF. At present, the role of selective atrial lead site(s) for the prevention of AF remains uncertain.

Pharmacological and nonpharmacological methods for rate control.

In many patients with atrial fibrillation, the most appropriate strategy is 'rate control', designed to slow down the rapid ventricular rates often seen with atrial fibrillation. Based on the hypothesis that symptoms, especially palpitations and exercise intolerance, are due to rapid ventricular rates with activity, optimum rate control usually requires reducing ventricular rates at rest and during activity. Beta-blockers and nondihydropyridine calcium channel blockers are likely more effective than digoxin alone, and the adequacy of rate control is best assessed with heart rate measurement during activity or with ambulatory electrocardiographic monitoring. Taking a patient's symptoms into account, reasonable target ventricular rates are less than 80 beats/min at rest and less than 100 beats/min, on average, over 24 h.

Drug therapy for termination of atrial fibrillation and maintenance of sinus rhythm.

Antiarrhythmic drug therapy to maintain sinus rhythm has not been demonstrated in randomized clinical trials to improve prognosis or prevent thromboembolic complications in patients with atrial fibrillation (AF). Therefore, drug therapy to restore and maintain sinus rhythm should be limited to those patients who have a greater symptomatic burden of AF. Patients with AF may be completely unaware of their arrhythmia or may present with palpitations, poor exercise tolerance or symptoms of congestive heart failure. In general, younger patients with paroxysmal arrhythmia and patients with decreased left ventricular compliance tend to be more symptomatic. The present article outlines the mechanisms of action of antiarrhythmic drugs in AF. Drugs that are recommended and frequently used to convert AF and maintain sinus rhythm are reviewed, and the toxicity of antiarrhythmic drug toxicity is discussed.

[A case report of idiopathic thrombocytosis in 27-year-old man treated for myocardial infarction].

We present the case of 27-year-old male, physical training teacher in whom the first clinical sign of idiopathic thrombocytosis was myocardial infarction. The infarct was complicated by heart arrest caused by ventricular fibrillation. Streptolysis (streptokinase) was used in treatment. Thrombocytosis 842 G/l was observed in blood tests at admission. To estimate its cause the bone marrow biopsy and trepanobiopsy of hip bone were performed. Tests were performed to exclude the secondary cause of thrombocytosis. The coronarography did not show relevant stenoses of coronary arteries. The results let diagnose myocardial infarction in a patient with essential thrombocytosis.

Granulocyte colony-stimulating factor-induced blood stem cell mobilisation in patients with chronic heart failure--Feasibility, safety and effects on exercise tolerance and cardiac function.

Bone marrow-derived stem cells may contribute to the regeneration of non-haematopoietic organs. In order to test whether an increase in circulating stem cell numbers improves impaired myocardial function we treated 16 male patients with chronic heart failure due to dilated (DCM; n = 7) or ischaemic cardiomyopathy (ICM; n = 9) with the stem cell mobilising cytokine granulocyte colony-stimulating factor (G-CSF; four 10-day treatment periods interrupted by treatment-free intervals of equal length). Safety and efficacy analyses were performed at regular intervals. Peak CD34+ cell counts remained constant from cycle to cycle. Cardiac side effects in ICM patients included occasional episodes of dyspnea or angina and one episode of fatal ventricular fibrillation. Nine (4 DCM, 5 ICM) of 12 patients receiving four full G-CSF cycles experienced an improvement by one New York Heart Association (NYHA) class and a statistically significant increase in six-minute walking distance. By contrast, none of 8 ICM historical controls had a change in NYHA class during a similar time period. Statistically significant changes in echocardiographic parameters were not recorded. Sequential administration of G-CSF is feasible and possibly effective in improving physical performance in patients with chronic heart failure. Patients with ICM may be at risk of increased angina and arrhythmias.

QT dispersion in sarcoidosis.

QT dispersion (QTd) is the maximal interlead difference in QT interval on surface 12-lead ECG. An increase in QTd is found in various cardiac diseases. Sarcoidosis augments inhomogeneity in ventricular repolarization by sarcoid granuloma, which significantly correlates with ventricular fibrillation. Changes in QTd in the course of sarcoidosis have not been investigated previously.</AbstractText>The study included 35 patients with systemic sarcoidosis. The diagnosis of systemic sarcoidosis was made by biopsy. Thallium scintigraphy was performed in all patients with systemic sarcoidosis. Cardiac sarcoidosis was diagnosed in 16 patients based on abnormal thallium scintigraphy and normal coronary arteriography results. QTd, corrected QTd (cQTd), maximum QT (QTmax), maximum corrected QT (cQTmax), minimum QT, and minimum corrected QT intervals were measured. Twenty-four healthy subjects represented the control group for QT interval analysis.</AbstractText>In the cardiac sarcoidosis group, mean QTd (+/- SD) was significantly greater than in the noncardiac sarcoidosis group and control group (49.50 +/- 10.86 ms, 28.14 +/- 11.02 ms, and 27.08 +/- 10.41 ms, respectively; p &lt; 0.001). cQTd was significantly greater in the cardiac sarcoidosis group than in the noncardiac sarcoidosis group and control group (53.17 +/- 10.44 ms, 30.61 +/- 10.94 ms, and 29.01 +/- 10.52 ms, respectively; p &lt; 0.001). QTmax (440 +/- 15.01 ms, 409 +/- 14.86 ms, and 410 +/- 13.21 ms; p &lt; 0.001) and cQTmax (449 +/- 16.31 ms, 417 +/- 12.51 ms, and 418 +/- 11.76, respectively; p &lt; 0.001) were also significantly greater in patients with cardiac sarcoidosis. In a limited follow-up group (11 cardiac and 9 noncardiac sarcoidosis patients), the incidence of premature ventricular contraction (PVC) on ECG was greater in the cardiac sarcoidosis group than in the noncardiac sarcoidosis group (36% and 0%, respectively; p &lt; 0.05). A medium correlation existed between QTd and PVC (r = 0.331, p &lt; 0.05).</AbstractText>QTd, cQTd, QTmax, and cQTmax are prolonged in patients with cardiac sarcoidosis compared to the patients with noncardiac sarcoidosis and control subjects. The incidence of PVC on ECG was greater in the cardiac sarcoidosis group than in the noncardiac sarcoidosis group.</AbstractText>

Atrial pacemaker complex preserved radiofrequency maze procedure reducing the incidence of sick sinus syndrome in patients with atrial fibrillation.

The Cox maze III procedure can effectively restore sinus rhythm in most patients with permanent atrial fibrillation (AF). However, previous studies have shown that the maze procedure results in significant sinus node dysfunction, and, consequently, a considerable number of patients required postoperative pacemaker implantation.</AbstractText>This study investigates the hypothesis that the modification of the Cox III maze procedure, to avoid injuring the sinus node and the atrial physiologic pacemaker complex, will reduce the incidence of sick sinus syndrome following surgery.</AbstractText>This study investigated 71 patients with permanent AF and mitral valve disease who were undergoing concomitant open-heart surgery. Most atrial incisions in the Cox maze III procedure were replaced with radiofrequency ablation, and the intercaval counterablation was moved posterolaterally to avoid injury to the sinus node and atrial pacemaker complex. At a mean (+/- SD) follow-up time of 46.5 +/- 24 months, 59 patients (83.1%) regained sinus rhythm without receiving antiarrhythmic drug therapy or undergoing electrical cardioversion. The transmitral atrial wave was observed in 44 patients (62%), and the transtricuspid atrial wave was also observed in 53 patients (74.6%). Late sinus node dysfunction developed in only two patients (2.8%), who received permanent pacemaker implantation.</AbstractText>This modified radiofrequency maze procedure produces few patients with sick sinus syndrome and effectively restores sinus rhythm and atrial transport function in most patients with permanent AF undergoing concomitant open-heart surgery.</AbstractText>

Left atrial dysfunction in patients with atrial fibrillation after successful rhythm control for &gt; 3 months.

Large-scale clinical trials have demonstrated that patients with atrial fibrillation (AF), when treated with a rhythm-control strategy, are still at risk for embolic events. We hypothesized that left atrial (LA) dysfunction persisted even after successful maintenance of sinus rhythm for &gt; 3 months.</AbstractText>A total of 93 patients with AF and satisfactory rhythm control for &gt; 3 months were included. Satisfactory rhythm control was defined as being free of AF based on patient-reported symptoms, monthly ECG follow-up, and ambulatory Holter ECG if needed. Among the 93 patients, 25 patients had sustained AF that was terminated by electrical or pharmacologic cardioversion, while 68 patients had paroxysmal AF under good medical control. Clinical data were obtained, and transthoracic and transesophageal echocardiography were performed after satisfactory rhythm control for &gt; 3 months.</AbstractText>Among the 93 patients, 34 patients (37%) had LA dysfunction, defined as LA appendage (LAA) peak emptying velocity &lt; 40 cm/s or spontaneous echo contrast and/or thrombus in the LA or LAA. When compared to the other 59 patients without LA dysfunction, they had larger LA dimension (40 +/- 6 mm vs 36 +/- 8 mm [+/- SD], p = 0.018) but did not differ significantly regarding the left ventricular (LV) chamber size, LV ejection fraction, mitral or tricuspid inflow, and ratio of the amplitude of the waves created by early diastolic filling and atrial contraction. We also analyzed the relationship between LA function and clinical risk factors for stroke, including hypertension, diabetes mellitus, coronary artery disease, age &gt; 65 years, and prior cerebral vascular accident. LA dysfunction was found in 10 of 17 patients (59%) with three or more risk factors. The odds ratio for having LA dysfunction was 3.1 (p = 0.04; 95% confidence interval, 1.1 to 9.1) when compared with patients with less than three risk factors.</AbstractText>LA dysfunction was present in more than one third of AF patients after satisfactory rhythm control for &gt; 3 months. Patients with higher burden (three or more) of clinical risk factors were more likely to have impaired LA function.</AbstractText>

Sleep-disordered breathing occurs frequently in stable outpatients with congestive heart failure.

Sleep-disordered breathing (SDB) has a potential role in the pathogenesis of congestive heart failure (CHF). High rates of central sleep apnea (CSA) are found in patients with severe CHF, and equal proportions of obstructive sleep apnea (OSA) and CSA in are found CHF patients referred to sleep clinics. The prevalence, type, and severity of SDB in unselected stable outpatients with CHF are unknown.</AbstractText>To determine the frequency and type of SDB in stable CHF outpatients and to examine the relationship between indexes of SDB and impaired cardiac function.</AbstractText>Fifty-three of 87 eligible outpatients (left ventricular ejection fraction [LVEF] &lt; 45%) were predominantly male (77%), with an average age of 60.1 +/- 9.8 years, mean body mass index of 27.9 +/- 5.3 kg/m2, and mean LVEF of 34.0 +/- 8.5% (+/- SD).</AbstractText>Polysomnography, clinical questionnaire, echocardiography, urinary catecholamines, and amino-terminal fragment of pro-brain natriuretic peptide (NT-BNP).</AbstractText>SDB (apnea-hypopnea index &gt;10 events/h) was demonstrated in 36 patients (68%) including two subgroups: OSA (n = 28, 53%) and CSA (n = 8, 15%). SDB was associated with atrial fibrillation (0% vs 28%, p = 0.02), more severe oxyhemoglobin desaturation (percentage of time with oxygen saturation &lt; 90%: 0.4% vs 7.9%, p = 0.003), sleep disruption (p = 0.003), and higher urinary noradrenaline levels (p = 0.013) in OSA patients and CSA patients, respectively. Subjective sleepiness (Epworth sleepiness scale, 7.5 vs 8.5; p = 0.11), indexes of impaired cardiac function including Minnesota Living With Heart Failure Questionnaire scores, shuttle walk distance, and NT-BNP levels were not related to the presence of SDB (p &gt; 0.05). CSA patients had lower LVEF (p = 0.0013).</AbstractText>SDB is very common in stable outpatients with CHF, and in our sample OSA predominates. Atrial fibrillation and severe left ventricular impairment increased the likelihood of SDB (particularly CSA), whereas symptom severity, subjective daytime sleepiness, exercise capacity, and NT-BNP levels did not. If specific therapy for SDB such as continuous positive airway pressure can be shown to improve major cardiovascular end points, these results support screening of clinically stable CHF patients.</AbstractText>

Ventricular arrhythmia in the X-linked cardiomyopathy Barth syndrome.

Barth syndrome is an X-linked disorder characterized by dilated cardiomyopathy, cyclic neutropenia, skeletal myopathy, abnormal mitochondria, and growth deficiency. The primary defect is a mutation in the TAZ gene on the X chromosome at Xq28, resulting in abnormal phospholipid biosynthesis and cardiolipin deficiency. To date, there has been no systematic evaluation of the cardiac phenotype. We report five cases of cardiac arrest and/or placement of an internal cardiac defibrillator with documented ventricular arrhythmia. We suggest that ventricular arrhythmia is part of the primary phenotype of the disorder and that patients should be screened accordingly.

Sudden cardiac death: what is inside our genes?

Although sudden cardiac death in youths is generally rare, it is estimated that 10% to 20% of these deaths occur in previously healthy infants, children, adolescents and young adults without any findings on autopsy and with devastating consequences on the family. The majority of these deaths are caused by inherited arrhythmia syndromes, the so-called 'channelopathies'. In the present paper, the recent advances in the clinical and genetic background of long QT syndrome, short QT syndrome, catecholaminergic polymorphic ventricular tachycardia, Brugada syndrome and the overlapping phenotypes are reviewed, and the recently established connections between these syndromes and idiopathic ventricular fibrillation and sudden infant death syndrome are discussed.

Effects of diltiazem on hemodynamic variables and ventricular function in healthy horses.

Quinidine is effective for treatment of atrial fibrillation (AF) in horses, but often accelerates ventricular response rate. Diltiazem effectively controls heart rate response to AF in other species. This investigation determined the effects of diltiazem on cardiac rate and rhythm, left ventricular (LV) function, central hemodynamics, and peripheral blood flow in normal, standing, nonsedated horses. A dose-finding study was performed. Afterward, 8 healthy horses were treated with diltiazem IV every 30 minutes to achieve cumulative dosages of 0 (saline control), 1, 1.5, and 2 mg/kg. Plasma diltiazem concentration, heart rate and rhythm (by electrocardiography), LV function and central hemodynamics (by cardiac catheterization), LV dimensions (by echocardiography), and forelimb blood flow (by Doppler sonography) were determined during each treatment period. Diltiazem plasma concentrations between 390 and 910 ng/mL were achieved, with considerable variation among horses. Cardiac effects of diltiazem included intermittent depression of the sinus and atrioventricular (AV) nodes and mild impairment of systolic and diastolic LV function. Vascular effects of diltiazem included arterial vasodilatation, increased limb blood flow, and decreased systemic vascular resistance. Baroreceptor reflex-mediated sympathetic activation increased sinus node rate and presumably blunted the depressive effects of diltiazem on myocardial and nodal tissues. Two horses developed transient high-grade sinus arrest with severe systemic hypotension. Diltiazem appears relatively safe in healthy horses, but dosage may be limited by hypotension from vasodilatation and direct suppression of sinus node discharge. Because of its inhibitory effects on AV nodal conduction, diltiazem may prove useful for heart rate control in horses with AF.

[Characterization of premature ventricular contraction initiating ventricular fibrillation].

The aim of this study is to characterize the electrocardiographic features of premature ventricular contractions (PVC) from different anatomical region that trigger ventricular fibrillation (VF).</AbstractText>36 consecutives patients (20 males, 42+/-14 yrs) undergoing VF ablation from 7 centres were studied (22 with idiopathic VF, 4 associated with a long QT syndrome, 3 with Brugada syndrome, 4 with ischaemic cardiomyopathy and 3 associated with other substrate). Mapping of these PVC showed 2 different origins, which were then confirmed by ablation: right ventricular outflow tract (RVOT) (22%) and peripheral Purkinje network (81%). One patient had PVC from both origins (Brugada). RVOT PVC were frequent but had triggered only 5+/-5 episodes of VF for 26+/-33 months. Purkinje PVC were more likely to be present during electrical storm with 18+/-28 episodes of VF for 33+/-45 months. Right Purkinje PVC have a left bundle branch block with superior axis morphology whereas left Purkinje ones have a right bundle branch block. The axis of activation showed variation from inferior to superior depending on the area of origin from the Purkinje network and the exit site to the myocardium. However Purkinje PVC were characterized by short QRS duration (126+/-18 vs 145+/-13ms for RVOT PVC; p=0.05). In addition the coupling interval was significantly shorter compared to RVOT PVC (292+/-45 vs 358+/-37ms respectively; p=0.005).</AbstractText>PVC initiating VF demonstrate specific electrocardiographic features that facilitate determination of their origin. Ablation of these typical PVC is feasible in order to reduce ICD shock.</AbstractText>

Diurnal variation in QT dispersion in patients with chronic heart failure.

QT dispersion is defined as the difference in QT interval among the different leads of the standard 12-lead electrocardiogram and reflects inhomogeneity of myocardial repolarization. Dispersion of repolarization is an important electrophysiologic feature that is considered fundamental for the initiation of ventricular fibrillation. However, no data exist regarding the diurnal variation of QT dispersion measured from simultaneous 12-lead recording in chronic heart failure patients. The aim of this study was to identify diurnal variation in QT dispersion in patients with chronic heart failure. QT dispersion was measured in the 12-lead standard electrocardiogram in 11 patients with chronic heart failure. QT dispersion in these patients was increased in the afternoon compared to the morning. It is concluded that QT dispersion has a clear diurnal variation in patients with chronic heart failure. These findings have potentially significant implications for therapy and prevention of sudden cardiac death in patients with chronic heart failure.

Functional and prognostic implications of left ventricular contractile reserve in patients with asymptomatic severe mitral regurgitation.

To evaluate contractile reserve (CR) determined by exercise echocardiography in predicting clinical outcome and left ventricular (LV) function in asymptomatic severe mitral regurgitation (MR).</AbstractText>Cohort study.</AbstractText>Regional cardiac centre.</AbstractText>LV volumes and ejection fraction (EF) were measured at rest and after stress in 71 patients with isolated MR. During follow up (mean (SD) 3 (1) years), EF and functional capacity were serially assessed and cardiac events (cardiac death, heart failure, and new atrial fibrillation) were documented.</AbstractText>CR was present in 45 patients (CR+) and absent in 26 patients (CR-). Age, resting LV dimensions, EF, and MR severity were similar in both groups. Mitral surgery was performed in 19 of 45 (42%) CR+ patients and 22 of 26 (85%) CR- patients. In patients undergoing surgery, CR was an independent predictor of follow up EF (p = 0.006) and postoperative LV dysfunction (EF &lt; 50%) persisted in five patients, all in the CR- group. Event-free survival was lower in surgically treated patients without CR (p = 0.03). In medically treated patients, follow up EF was preserved in those with intact CR but progressively deteriorated in patients without CR, in whom functional capacity also deteriorated.</AbstractText>Evaluation of CR by exercise echocardiography may be useful for risk stratification and may help to optimise the timing of surgery in asymptomatic severe MR.</AbstractText>

The impact of beta-adrenoreceptor gene polymorphisms on survival in patients with congestive heart failure.

Discordant results have been published regarding a possible association between beta-adrenoreceptor (betaAR) gene polymorphisms and survival in patients with congestive heart failure (CHF). The aim of the study was to analyze the impact of five functional betaAR gene polymorphisms in patients with stable CHF.</AbstractText>We prospectively studied 444 consecutive patients with CHF related to left ventricular systolic dysfunction. The beta1ARSer49Gly, beta1ARGly389Arg, beta2AR Arg16Gly, beta2AR Gln27Glu and beta2AR Thr164Ile polymorphisms were determined. Patients underwent echocardiography, radionuclide angiography and a cardiopulmonary exercise test.</AbstractText>Mean age was 56.6+/-11.9 years old, left ventricular ejection fraction (LVEF) was 32+/-12%, and peak VO2 was 15.5+/-4.9 ml/min/kg or 63+/-18% of maximal predicted VO2. Most of the patients (95%) were receiving angiotensin converting enzyme inhibitors and 91% beta-blockers. There was no statistically significant differences between baseline characteristics among beta1AR and beta2AR genotypes. During a median follow-up period of 1232 days, there were 110 cardiac-related deaths and five urgent transplantations. Independent predictors of survival were percent (%) of maximal predicted VO2 (p&lt;0.0001), age (p&lt;0.0001), LVEF (p=0.004), creatinine (p=0.02) and atrial fibrillation (p=0.04). No betaAR polymorphisms were associated with survival. However, patients with the combined beta2ARGly16Gly/beta2ARGln27Gln genotype, who express receptors highly sensitive to down-regulation, had a significantly lower survival rate than patients with other genotypes but only in univariate analysis.</AbstractText>In this prospective study, we found no association between five functional betaAR polymorphisms and survival in patients with stable CHF. However, we demonstrated, only in univariate analysis, a possible association between the combined beta2ARGly16Gly/beta2ARGln27Gln genotype and survival.</AbstractText>

Effects of KR-32570, a new sodium hydrogen exchanger inhibitor, on myocardial infarction and arrhythmias induced by ischemia and reperfusion.

The present study was performed to evaluate the cardioprotective effects of [5-(2-methoxy-5-chloro-5-phenyl)furan-2-ylcarbonyl]guanidine (KR-32570) in rat and dog models of coronary artery occlusion and reperfusion. In addition, we sought to clarify the efficacy of KR-32570 on reperfusion-induced fatal ventricular arrhythmia. In anesthetized rats subjected to 45-min coronary occlusion and 90-min reperfusion, KR-32570 (i.v. bolus) dose-dependently reduced myocardial infarct size from 58.0% to 50.7%, 35.3%, 33.5% and 27.0% for 0.03, 0.1, 0.3 and 1.0 mg/kg, respectively (P&lt;0.05). In anesthetized beagle dogs that underwent 1.2-h occlusion followed by 3.0-h reperfusion, KR-32570 (3 mg/kg, i.v. bolus) markedly decreased infarct size from 28.9% in vehicle-treated group to 8.0% (P&lt;0.05), and reduced the reperfusion-induced release in creatine kinase isoenzyme MB, lactate dehydrogenase, Troponin-I and glutamic-oxaloacetic transaminase. KR-32570 dose-dependently decreased the incidence of premature ventricular contraction, ventricular tachycardia or ventricular fibrillation induced by ischemia and reperfusion in rats. Similar results were obtained in dogs with reperfusion-induced arrhythmia. In separate experiments to assess the effects of timing of treatment, KR-32570 given 10 min before or at reperfusion in rat models also significantly reduced the myocardial infarct size (40.9% and 46.1%, respectively) compared with vehicle-treated group. In all studies, KR-32570 caused no significant changes in any hemodynamic profiles. Taken together, these results indicate that KR-32570 significantly reduced the myocardial infarction and incidence of arrhythmias induced by ischemia and reperfusion in rats and dogs, without affecting hemodynamic profiles. Thus, it could be potentially useful in the prevention and treatment of myocardial injuries and lethal ventricular arrhythmias.

Discovery of gradient pattern in dominant frequency maps during fibrillation: implication of rotor drift and epicardial conduction velocity changes.

Dominant frequency (DF) maps for mapping epicardial activations of ventricular fibrillation (VF) have been studied mainly using fast Fourier transform (FFT). Small and discrete DF domains exhibited in these DF maps have undermined the hypothesis of mother rotor for VF maintenance. We applied continuous Fourier transform (CFT) to generate high-precision DF maps and studied characteristics of these high-precision DF maps. Optical epicardial activations were recorded in isolated rabbit hearts (n=10). Continuous Fourier transform of 1-second segments was performed in VF (n=188) and ventricular tachycardia (n=189) at 0.1 Hz precisions. Banded gradient patterns of gradual change in DF values were observed in 136 of 188 VF segments, but not in ventricular tachycardia. These gradients were not observed when FFT was used. Gradients were observed along the conduction path of reentrant-like waves with decreasing DF values along the path. Spectra in the gradients did not exhibit bimodal spectra as is usually observed in traditional DF domain boundaries. Time-space plots revealed clear association between gradient pattern and epicardial conduction velocity changes. Prior simulation studies predicted a gradient in activation rate during rotor drift. This gradient pattern has been observed for the first time experimentally by only using CFT, but not FFT. High-precision DF videos indicated the existence of gradient movement from one spatial location to another, smoothly instead of randomly disappearing from one location and appearing in another. The discovery of associated pseudoconduction velocity changes, and gradient patterns might suggest that dominant rotor (mother rotor) drifting plays a maintenance role only detectable by CFT and not FFT.

Short QT syndrome. Genotype-phenotype correlations.

The short QT syndrome is a new congenital entity associated with familial atrial fibrillation and/or sudden death or syncope. Three different gain-of-function mutations in genes encoding for cardiac potassium channels (KCNH2, KCNQ1, and KCNJ2) have been identified up to now to cause short QT syndrome. The syndrome is characterized electrocardiographically by a shortened QTc interval less than 300 to 320 milliseconds and a lack of adaptation during increasing heart rates. During programmed electrical stimulation, atrial and ventricular effective refractory periods are shortened, and in a high percentage, ventricular tachyarrhythmias are inducible. Sudden cardiac death occurs in all age groups and even in newborns. Therapy for choice seems to be the implantable cardioverter-defibrillator because of the high incidence of sudden death. However, ICD therapy may be associated with an increased risk of inappropriate therapies for T wave oversensing, which, however, can be resolved by reprogramming ICD detection algorithms. The impact of sotalol, ibutilide, flecainide, and quinidine on QT prolongation has been evaluated. But only quinidine effectively suppressed gain-of-function in IKr, along with prolongation of the QT interval. Furthermore, in patients with a mutation in HERG (SQT1), quinidine rendered ventricular tachyarrhythmias noninducible and restored the QT interval/heart rate relationship toward a reference range. It may serve as an adjunct to ICD therapy or as possible alternative treatment especially for children and newborns.

Ischemia-induced arrhythmia: the role of connexins, gap junctions, and attendant changes in impulse propagation.

Sudden cardiac death accounts for more than half of all cardiovascular deaths in the US, and a large proportion of these deaths are attributed to ischemia-induced ventricular fibrillation. As such, the mechanisms underlying the initiation and maintenance of these lethal rhythms are of significant clinical and scientific interest. In large animal hearts, regional ischemia induces two phases of ventricular arrhythmia. The first phase (1A) occurs between 5 and 7 min after arrest of perfusion. This phase is associated with membrane depolarization, a mild intracellular and extracellular acidification and a small membrane depolarization. A second phase (1B) of ventricular arrhythmia occurs between 20 and 30 minutes after arrest of perfusion. This phase occurs at a time when ischemia-induced K+ and pH changes are relatively stable. The arrhythmia is presumed to relate to the process of cell-to-cell electrical uncoupling because a rapid increase of tissue impedance precedes the onset of the arrhythmia. Of note is that tissue resistance is primarily determined by the conductance properties of the gap junctions accounting for cell-to-cell coupling. Impulse propagation in heart is determined by active and passive membrane properties. An important passive cable property that is modulated by ischemia is intercellular resistance and is determined primarily by gap junctional conductance. As such changes in Impulse propagation during myocardial ischemia are determined by contemporaneous changes in active and passive membrane properties. Cellular K loss, intracellular and extracellular acidosis and membrane depolarization are important factors decreasing excitatory currents, while the collapse of the extracellular compartment and cell-to-cell electrical uncoupling increase the resistance to current flow. The time-course of cellular coupling is closely linked to a number of physiological processes including depletion of ATP, and accumulation of intracellular Ca2+. Hence, interventions such as ischemic preconditioning attenuate the effect of subsequent ischemia, delay the onset of cell-to-cell electrical uncoupling and likewise delay the onset of ischemia-induced arrhythmia.

ST-segment elevation in the early repolarization syndrome, idiopathic ventricular fibrillation, and the Brugada syndrome: cellular and clinical linkage.

ST-segment elevation in a structurally normal heart is associated with an electrocardiographic (ECG) J wave, which can be observed in the early repolarization syndrome (ERS), idiopathic ventricular fibrillation (VF), and the Brugada syndrome. Animal studies have demonstrated that the J wave is the consequence of a transmural voltage gradient resulting from an Ito-mediated action potential notch (spike and dome) in epicardium but not endocardium. Ito-mediated spike and dome morphology predisposes loss or depression of the dome in epicardium, leading to ST-segment elevation. Despite the fact that 3 clinical syndromes share many common ECG features, their clinical consequences are remarkably different. The ERS is a benign ECG finding characterized by a distinct J wave and ST segment in left precordial leads V4 through V6. In contrast, idiopathic VF and the Brugada syndrome, characterized by a J wave and ST-segment elevation in the inferior and right precordial leads, respectively, are the leading causes for sudden cardiac death in young Southeast Asian males. The underlying mechanism for such a difference in clinical consequences among these syndromes is due to a difference in Ito density and Ito-mediated epicardial spike and dome. When Ito is prominent, complete loss of the dome may occur due to either a decrease in inward currents or an increase in outward currents, leading to phase 2 reentry capable of initiating VF as in idiopathic VF and the Brugada syndrome. When Ito is relatively small as in the ERS, partial depression of the dome occurs without the development of phase 2 reentry.

Acquired forms of the Brugada syndrome.

The Brugada syndrome is characterized by ST-segment elevation in the right precordial leads (V1 through V3) and an episode of ventricular fibrillation in the absence of structural heart disease. SCN5A, the gene encoding the alpha subunit of the sodium channel, is the only gene thus far linked to the Brugada syndrome but is identified in only 18% to 30% of patients with clinically diagnosed Brugada syndrome. On the other hand, experimental studies have suggested that an intrinsically prominent transient outward current-mediated action potential (AP) notch and a subsequent loss of the AP dome in the epicardium but not in the endocardium of the right ventricular outflow tract give rise to a transmural voltage gradient, resulting in ST-segment elevation and phase 2 reentry-induced ventricular fibrillation. Therefore, any intervention that increases outward currents (eg, transient outward current, adenosine triphosphate-sensitive potassium current, delayed modifier potassium current) or decreases inward currents (eg, L-type calcium current, fast sodium current) at the end of phase 1 of the AP can accentuate or unmask ST-segment elevation, similar to that found in the Brugada syndrome, thus producing acquired forms of the Brugada syndrome. In this review, several drugs in addition to sodium-channel blockers and conditions that induce transient ST-segment elevation such as that in the Brugada syndrome, developing acquired forms of the Brugada syndrome, are discussed.

Similarities between Brugada syndrome and ischemia-induced ST-segment elevation. Clinical correlation and synergy.

Vasospastic angina (VSA) and Brugada syndrome (BS) are classified into different categories of cardiac disease, but both can be causes of sudden cardiac death from ventricular fibrillation (VF). The coexistence of VSA and BS in the same patient is possible, and this raises several questions: (1) what is the incidence of the coexistence of BS and VSA in the same patient? (2) is susceptibility to VF enhanced by the coexistence of the 2 diseases? and (3) is there any possibility of Ca-antagonists being used for the treatment of VSA-aggravated BS? In our institution, VSA coexisted in 5 of the 38 patients with BS (13.1%). Anginal episodes were confirmed clinically in 4 of the 5 patients, and syncope attack occurred after the symptom of chest pain in 2 patients. However, VF did not develop during the coronary vasospasm in any of the patients. Treatment with Ca-antagonist was effective for VSA, and neither aggravation of Brugada-type electrocardiographic abnormality nor an increase in the incidence of syncope attack was observed. Although the coexistence of BS and VSA in the same patient is not rare, neither enhanced susceptibility to VF nor the proarrhythmic effect of Ca-antagonist has been confirmed in our experience. However, careful attention is required in such patients because the influence of myocardial ischemia and/or the effect of Ca-antagonist may be different in each patient with BS.

Unnecessary interruptions of cardiac massage during simulated cardiac arrests.

Cardiopulmonary resuscitation should not be interrupted until the return of spontaneous circulation or the decision to withhold further treatment. There are no data on how consistent in-hospital cardiopulmonary resuscitation is performed. Accordingly, the aim of the present study was to identify length and type of unnecessary interruptions in simulated cardiac arrests.</AbstractText>The study was carried out in a patient simulator. A scenario of cardiac arrest due to ventricular fibrillation was used. Resuscitation teams consisted of three nurses, a resident and a staff physician. Using videotapes recorded during simulations, the activities of the teams were coded in 5-s intervals. Unnecessary interruptions were defined as any interruptions in cardiac massage of 10 s or more that were not caused by defibrillation or endotracheal intubation.</AbstractText>Twelve teams were studied. The total time of possible cardiac massage was 414 +/- 125 s. In each team at least one unnecessary interruption occurred (range 1-5). Interruptions mounted up to 65 +/- 40 s (range 20-155) or 16 +/- 10% (range 5-41) of the total time of possible cardiac massage. Failure to swiftly resume cardiac massage after an unsuccessful defibrillation accounted for 14 of 39 episodes and for 44 +/- 40% of the time of unnecessary interruptions. The debriefings revealed that participants had generally not noticed the unnecessary interruptions during the simulation.</AbstractText>The present study identified a significant amount of unnecessary interruptions in cardiac massage. These interruptions were not noticed by the health-care workers involved.</AbstractText>

[Acute chloroquine intoxication--rare, but always serious: case reports and literature review].

Chloroquine is a derivative of 4-aminoquinoline, which is used in the malaria prophylaxis and treatment and the therapy of some connective tissue diseases. Its narrow therapeutic index causes that the medicine is relatively toxic, especially in the case of an overdose or an acute intoxication. In the recent study two cases of the acute chloroquine poisoning, hospitalized in the Toxicology Department in Krak&#xf3;w, were described and one of them was fatal. The first case was 16-year-old girl who ingested 5 g of chloroquine phosphate in the suicidal attempt. After about 2 hours general seizures appeared followed by ventricular fibrillation and cardiac arrest. After near 2-hour-lasted reanimation procedures she was resuscitated, but 14 hours later another cardiac arrest appeared because of the bradyasystole. Despite the institution of advanced reanimation methods including external pacemaker and electrostimulation, spontaneous circulation did not return and the patient was declared dead. Postmortem toxicological examination of blood, vitreous humour, bile and liver revealed extremely high concentrations of chloroquine (252.15 mg/l in blood). The second case was the 15-year-old girl who ingested 7.5 g of chloroquine phosphate. She developed significant hypotension requiring intravenous infusions of fluids and catecholamines and respiratory distress positively treated with endotracheal intubation and mechanical ventilation. In both cases a considerable hypokalemia and prolonged QTc interval were observed. According to the literature, a clinical picture, diagnosis and recommended therapy of an acute chloroquine poisoning were reviewed.

Improved survival after in-hospital cardiac arrest outside critical care areas.

The in-hospital Utstein Guidelines may be used to evaluate resuscitation strategies. This study utilized the Utstein template prospectively to examine changes in outcome and outcome-related factors after resuscitation outside critical care areas over a 10-year period.</AbstractText>Sein&#xe4;joki Central Hospital (460 beds) is a secondary hospital in Finland with acute care activities. In 1993, the in-hospital cardiac arrest management was remodelled; an intensive care unit-based resuscitation team was formed and prospective data collection began (modified according to the Utstein Guidelines in 1997). An analysis of resuscitation attempts outside critical care areas between 1993 and 2002 was performed. To monitor developments, the patients were divided into two groups (first period, 1993-97; second period, 1998-2002). Variables independently associated with survival were identified using multiple logistic regression analysis.</AbstractText>During the 10-year period, resuscitation was attempted in 183 patients. Survival to discharge was 6% during the first period and 16% during the second (P = 0.048). The corresponding figures for survival at 1 year from the event were 3% and 10% (P = 0.064). Independent predictors of survival were ventricular fibrillation or ventricular tachycardia as the initial rhythm [odds ratio (OR), 9.8; confidence interval (CI), 3.2-30.3] and cardiac arrest occurring during the second period (OR, 3.3; CI, 1.1-10.1).</AbstractText>Prospective Utstein style data collection proved to be a valuable tool for the evaluation of management and outcome following in-hospital cardiac arrest. Increased survival was seen over 10 years outside critical care areas. Organizational changes, including cardiopulmonary resuscitation training for ward personnel and standardized resuscitation management, may have contributed to this change.</AbstractText>

Right heart failure due to loss of right ventricular capture in a patient with atrioventricular junction ablation and biventricular pacing.

We describe the case of a patient with atrioventricular (AV) junction ablation and chronic biventricular pacing in which intermittent dysfunction of the right ventricular (RV) lead resulted in left ventricular (LV) stimulation alone and onset of severe right heart failure. Restoration of biventricular pacing by increasing device output and then performing lead revision resolved the issue. This case provides evidence that LV pacing alone in patients with AV junction ablation may lead to severe right heart failure, most likely as a result of iatrogenic mechanical dyssynchrony within the RV. Thus, probably this pacing mode should be avoided in pacemaker-dependent patients with heart failure.

Severe left ventricular systolic dysfunction increases atrial fibrillation after ablation of atrial flutter.

Atrial fibrillation (Afib) that occurs after a successful atrial flutter (AFL) ablation may negate the potential benefits of the ablation. Afib occurs more often when severe left ventricular systolic dysfunction (LVSD) is present. We hypothesized that even after a successful AFL ablation, the incidence of postablation Afib is increased when severe LVSD is present.</AbstractText>Ninety consecutive patients with LVSD who underwent ablation for AFL at Montefiore Medical Center from August 2001 to January 2005 were classified according to the severity of LVSD. Group 1 (n = 36) consisted of patients with EF &lt; or = 35%, and group 2 (n = 54) consisted of patients with EF 36-55%. There were no statistically significant differences in baseline patient characteristics between the two groups.</AbstractText>During a mean follow up of 350 days, Afib occurred in 31% (n = 11; 8 with prior history of AFib) in group 1, and 7.4% (n = 4; all with prior history of Afib) in group 2. Cumulative probability of remaining Afib-free in group 1 versus group 2 was 75% versus 96% at 365 days, and 69% versus 91% at 600 days (P = 0.01). A prior history of Afib did not interact with EF when analyzed with a logistic regression analysis.</AbstractText>After an AFL ablation, the incidence of Afib is increased, and the probability of remaining free of Afib is decreased, when severe LVSD is present, independent of a prior history of Afib. This finding may have implications for optimal patient selection for AFL ablation, and the use of adjunctive therapies.</AbstractText>

Clinical results of an advanced SVT detection enhancement algorithm.

Supraventricular tachycardia (SVT) has many characteristics that are similar to ventricular tachycardia (VT). This presents a significant challenge for the SVT-detection algorithms of an implantable cardioverter defibrillator (ICD). A newly developed ICD, which utilizes a Vector Timing and Correlation algorithm as well as interval-based conventional SVT discrimination algorithms (Rhythm ID), was evaluated in this study.</AbstractText>This study was a prospective, multicenter trial that evaluated 96 patients implanted with an ICD at 21 U.S. centers. All patients were followed at 2 weeks, 1 month, and every 3 months post implant. A manual Rhythm ID reference vector was acquired prior to any arrhythmia induction. During testing, atrial tachyarrhythmias were induced first, followed by ventricular arrhythmia induction. Induced and spontaneous SVT and VT/ventricular fibrillation (VF) episodes recorded during the trial were annotated by physician investigators.</AbstractText>The mean age of the patients implanted with an ICD was 67.3 +/- 10.8 years. Eighty-one percent of patients were male. The primary cardiovascular disease was coronary artery disease, and the primary tachyarrhythmia was monomorphic VT. Implementation of the Rhythm ID algorithm did not affect the VT/VF detection time. There were a total of 370 ventricular tachyarrhythmias (277 induced and 93 spontaneous) and 441 SVT episodes (168 induced and 273 spontaneous). Sensitivity for ventricular tachyarrhythmias was 100%, and specificity for SVT was 92% (94% and 91% for induced and spontaneous SVT, respectively). All patients had a successful manual Rhythm ID acquisition prior to atrial tachyarrhythmia induction. At the 1-month follow-up, the Rhythm ID references were updated automatically an average of 167.8 +/- 122.7 times. Stored Rhythm ID references correlated to patients' normally conducted rhythm 100% at 2 weeks, and 98% at 1 month.</AbstractText>The Rhythm ID algorithm achieved 100% sensitivity for VT/VF, and 92% specificity for SVT. The manual and automatic Rhythm ID update algorithms successfully acquired references, and the updated references were highly accurate.</AbstractText>

Chronotropic incompetence in patients with an implantable cardioverter defibrillator: prevalence and predicting factors.

Chronotropic incompetence (CI), which has not been systematically examined in the ICD patient population, may have implications for device programming. A total of 123 ICD patients were classified into three groups: single-chamber ICD with sinus rhythm, dual-chamber ICD with sinus rhythm, and single-chamber ICD with permanent atrial fibrillation. Heart rate response, maximum oxygen uptake, and oxygen uptake at the anaerobic threshold were measured during treadmill exercise testing. In addition, clinical variables such as antiarrhythmic drug therapy, underlying heart disease, and left-ventricular (LV) ejection fraction were recorded. Of the patients studied, 38% were chronotropically incompetent (47/123). Significant predictors of CI were as follows: presence of a coronary disease (P = 0.036), prior cardiac surgery (P = 0.037), chronic drug therapy with beta-blockers (P = 0.032), administration of amiodarone (P = 0.025), and a combination of these two forms of treatment (P = 0.01). Spiroergometry revealed reduced exercise capacity (P = 0.041) and lessened VO2max (P = 0.034) among chronotropically incompetent patients. A large percentage of ICD patients demonstrates CI with subsequently reduced physical stress tolerance. In light of the DAVID study, we believe that a closer examination of rate-adaptive modes for ICD patients is warranted under enhanced conditions: (1) optimized AV interval programming; (2) utilization of new algorithms to reduce ventricular pacing in combination with rate-adaptive atrial pacing, with the goal of addressing CI while minimizing ventricular pacing; and (3) an optimized upper heart-rate limit.

Targeting the renin-angiotensin-aldosterone-system in atrial fibrillation: a shift from electrical to structural therapy?

Despite its increasing incidence and prevalence, treatment options in atrial fibrillation (AF) are far from ideal and often limited. After decades of focus on the electrical aspects of AF with unsatisfactory results, recent research is focusing increasingly on the atrial structural remodelling that underlies the development of AF in different pathological conditions, such as hypertension, heart failure, diabetes mellitus and coronary artery disease. The aim of this review is to provide a comprehensive overview of the role of the renin-angiotensin-aldosterone-system in AF and to highlight the clinical evidence on renin-angiotensin-aldosterone-system blockade as a therapeutic option in AF.

Ventricular fibrillation induced by carotid sinus massage without preceding bradycardia.

Carotid sinus massage is widely used to detect carotid sinus hypersensitivity in patients presenting with syncope. Although generally safe, the risks associated with the procedure may not be fully appreciated by either the patient or the attending medical staff. We present the case of a patient who developed ventricular fibrillation during carotid sinus massage, not explained by preceding bradycardia or concomitant predisposing heart disease, and which highlights the need for ready availability of resuscitation equipment during this procedure.

Transoesophageal left ventricular pacing in heart failure patients with permanent right ventricular pacing.

Previous studies of biventricular (BV) pacing for treatment of heart failure (HF) patients with left bundle branch block (LBBB) evaluated responders to BV pacing with acute transvenous left ventricular (LV) pacing and arterial pulse pressure (PP). The aim of this study was to assess transoesophageal LV pacing in evaluation of the haemodynamic response with a view to upgrading responders from permanent right ventricular (RV) pacing to BV pacing.</AbstractText>Ten HF patients (age 62+/-8 years; one female, nine males) in NYHA III, LV ejection fraction 24+/-9% and permanent RV pacing by means of an implanted pacemaker or ICD were tested using transoesophageal LV pacing and PP. Permanently RV-paced HF patients were analysed with transoesophageal atrial sensed LV pacing in VAT mode with a different AV delay (n = 6) and with transoesophageal LV pacing in V00 mode during atrial fibrillation (n = 4). In five responders, PP was higher during transoesophageal LV pacing than PP during RV pacing (74+/-42 versus 57+/-31 mmHg, P = 0.015). Responders were upgraded by means of an LV lead via the coronary sinus in the posterior (n = 1) or posterolateral (n = 4) walls and after attaining a high LV pacing threshold with an epicardial LV lead on the anterior (n = 1) or anterolateral (n = 1) walls. NYHA class improved from 3 to 2+/-0.3 (P = 0.003) during 204+/-120 days follow-up and cardiac output increased from 4.4+/-1.5 to 5.6+/-1.7 l/min (P = 0.027) when comparing BV pacing and optimal AV delay with RV pacing. In five nonresponders, PP was not higher during transoesophageal LV pacing than during RV pacing.</AbstractText>Transoesophageal LV pacing may be a useful technique to detect responders to BV pacing in permanently RV-paced HF patients.</AbstractText>

Defibrillation efficacy testing: long-term follow-up and mortality.

Extensive defibrillation threshold testing is no longer necessary to perform as devices have become more effective. We assessed the lowest effective defibrillation (LED) level at implantation and before hospital discharge and related this to outcome.</AbstractText>One hundred and twenty-seven consecutive patients with biphasic shock and active can devices were studied at intraoperative and predischarge testing. A subgroup of 67 patients had &gt; or = 3 VF inductions at implant. Improvement was defined when LED decreased by &gt; or = 3 J. The LED was significantly higher at implantation compared with predischarge (P &lt; 0.001). Improvement was seen in 73/127 patients (58%). In the group with &gt; or = 3 VF inductions, an implantation LED &gt; 9 J was related to a lower LVEF (P &lt; 0.01); 34/67 patients (51%) had improvement in LED. During follow-up, 18/127 patients died, four received heart transplantation. No different outcome was observed in patients with and without improvement. However, for those with &gt; or = 3 VF inductions, an independent predictor of mortality was implantation LED &gt; 9 J without improvement on the second test. Safety margin &lt; 10 J was not related to mortality.</AbstractText>Repeated defibrillation efficacy testing before hospital discharge may confirm that a relatively high defibrillation energy is required. This is related to a higher mortality in long-term follow-up.</AbstractText>

Short QT interval syndrome: a case report.

Twelve-lead electrocardiograms revealed fine atrial fibrillation and a short QT interval (SQTI) (&lt;300 milliseconds) with an average ventricular rate of 54/min in a 20-year-old male presented with exertional dyspnea. His echocardiographic evaluation revealed interatrial septal aneurysm and slightly dilated pulmonary artery. An electrophysiologic study revealed atrial fibrillation with a very high frequency, short ventricular effective refractory period (130 milliseconds) and ventricular fibrillation inducible with 3 short coupled extrastimuli. Signs were consistent with the rare SQTI syndrome. Although SQTI syndrome is associated with increased risk for sudden cardiac death, the patient was free of arrhythmia symptoms and denied any syncope or presyncope. Family history was also negative for sudden cardiac death and for any symptom suggestive of arrhythmia. The patient refused implantable defibrillator and was treated with anticoagulation and quinidine therapy.

On the mechanisms for the conversion of ventricular fibrillation to tachycardia by perfusion with ruthenium red.

We have recently demonstrated that during pacing-induced sustained ventricular fibrillation (VF), perfusion of the heart with either ruthenium red (RR) or Ru 360, blockers of the mitochondrial Ca2+ uniporter, resulted in the reversible conversion of VF to ventricular tachycardia (VT). Here, we aimed at elucidating the electrophysiological mechanisms for the RR-induced conversion of VF to VT. The experiments were performed using Langendorff-perfused isolated rat hearts in which left ventricular pressure and left ventricular intracellular action potential were recorded. Perfusion with either RR or Ru 360 resulted in decreases in the action potential duration (APD), refractory period, and slope of APD restitution curves. These changes were antagonized by cotreatment with S(-)-Bay K8644. In addition, perfusion with verapamil produced the decreases in APD at 90% repolarization, refractory period and slope of APD restitution curves similar to the RR or Ru 360 perfusion. Such electrophysiological changes may be responsible for the reversible conversion of sustained VF to VT caused by perfusion with RR or Ru 360.

An unusual electrocardiogram artifact: what is its source?

A diabetic female presented with nausea and vomiting. Her electrocardiogram showed sinus rhythm with two artifactual spikes, not synchronized with the cardiac rhythm. The patient had an implanted gastric electrical stimulation system for treating her diabetic gastroparesis. Recent DC shock for ventricular fibrillation during coronary angiography caused malfunction of the gastric pacemaker.

Is it safe to perform cardiac catheterizations on adults with congenital heart disease in a pediatric catheterization laboratory?

To determine the complication rate during the catheterization in adults with congenital heart disease (CHD) in a pediatric catheterization laboratory (PCL).</AbstractText>An increasing number of patients with CHD are surviving into adulthood, with diagnostic and interventional cardiac catheterization being essential for the management of their disease. The complication rate during the catheterization of adults with CHD has not been reported.</AbstractText>A retrospective chart review was performed on all adult patients (&gt;18 years) with CHD who underwent diagnostic or interventional catheterization in our PCL within the past 8.5 years.</AbstractText>A total of 576 procedures were performed on 436 adult patients (median age 26 years). Complex heart disease was present in 387/576 (67%) procedures. An isolated atrial septal defect or patent foramen ovale was present in 115/576 (20%) procedures, and 51/576 (9%) procedures were performed on patients with structurally normal hearts with arrhythmias. Interventional catheterization was performed in 378/576 (66%) procedures. There were complications during 61/576 (10.6%) procedures; 19 were considered major and 42 minor. Major complications were death (1), ventricular fibrillation (1), hypotension requiring inotropes (7), atrial flutter (3), retroperitoneal hematoma, pneumothorax, hemothorax, aortic dissection, renal failure, myocardial ischemia and stent malposition (1 each). The most common minor complications were vascular entry site hematomas and hypotension not requiring inotropes. Procedures performed on patients &gt; or = 45 years of age had a 19% occurrence of complications overall compared with 9% occurrence rate in patients of age &lt; 45 years (P &lt; 0.01).</AbstractText>The complication rate during the catheterization of adults with CHD in a PCL is similar to the complication rate of children with CHD undergoing cardiac catheterization. The older subset of patients are more likely to encounter complications overall. The encountered complications could be handled effectively in the PCL. With screening in place, it is safe to perform cardiac catheterization on most adults with CHD in a PCL.</AbstractText>Copyright 2005 Wiley-Liss, Inc.</CopyrightInformation>

Complement activation-related cardiac anaphylaxis in pigs: role of C5a anaphylatoxin and adenosine in liposome-induced abnormalities in ECG and heart function.

Cardiac anaphylaxis is a severe, life-threatening manifestation of acute hypersensitivity reactions to allergens and drugs. Earlier studies highlighted an amplifying effect of locally applied C5a on the process; however, the role of systemic complement (C) activation with C5a liberation in blood has not been explored to date. In the present study, we used the porcine liposome-induced cardiopulmonary distress model for 1) characterizing and quantifying peripheral C activation-related cardiac dysfunction; 2) exploring the role of C5a in cardiac abnormalities and therapeutic potential of C blockage by soluble C receptor type 1 (sCR1) and an anti-C5a antibody (GS1); and 3) elucidating the role of adenosine and adenosine receptors in paradoxical bradycardia, one of the symptoms observed in this model. Pigs were injected intravenously with different liposomes [Doxil and multilamellar vesicles (MLV)], zymosan, recombinant human (rhu) C5a, and adenosine, and the ensuing hemodynamic and cardiac changes (hypotension, tachy- or bradycardia, arrhythmias, ST-T changes, ventricular fibrillation, and arrest) were quantified by ranking on an arbitrary scale [cardiac abnormality score (CAS)]. There was significant correlation between CAS and C5a production by liposomes in vitro, and the liposome-induced cardiac abnormalities were partially or fully reproduced with zymosan, rhuC5a, adenosine, and the selective adenosine A1 receptor agonist cyclopentyl-adenosine. The use of C nonactivator liposomes or pretreatment of pigs with sCR1 or GS1 attenuated the abnormalities. The selective A1 blocker cyclopentyl-xanthine inhibited bradycardia without influencing hypotension, whereas the A(2) blocker 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-ylamino]ethyl)phenol (ZM-24135) had no such effect. These data suggest that 1) systemic C activation can underlie cardiac anaphylaxis, 2) C5a plays a causal role in the reaction, 3) adenosine action via A1 receptors may explain paradoxical bradycardia, and 4) inhibition of C5a formation or action or of A1-receptor function may alleviate the acute cardiotoxicity of liposomal drugs and other intravenous agents that activate C.

Effects of glucose-insulin-potassium infusion on ST-elevation myocardial infarction in patients treated with thrombolytic therapy.

The role of glucose-insulin-potassium (GIK) infusion in the management of acute myocardial infarction is not well established. This prospective, randomized study comprised 120 patients who had ST-elevation myocardial infarction that was treated within 12 hours from symptom onset with a high dose of GIK (25% glucose, 50 IU of soluble insulin per liter, and 80 mmol of potassium chloride per liter at 1 ml/kg/hour over 24 hours) as adjunct to thrombolytic therapy (1.5 MU of streptokinase/30 to 60 minutes; GIK group) or thrombolytic therapy alone (control group). The primary end point of the study was the rate of major adverse cardiac events (MACEs) at 1 month, defined as a composite of cardiac death, reinfarction, serious arrhythmias (ventricular fibrillation and/or tachycardia), and severe heart failure. The secondary end points were the rate of MACEs at 1 year and improvement in left ventricular systolic function. The incidence of MACEs at 1 month was significantly lower in the GIK group (10% vs 32.5%, relative risk 0.24, 95% confidence interval 0.09 to 0.63, p = 0.0043). Patients in the GIK group had significant decreases in ventricular tachycardia and/or fibrillation (1.3% vs 15.0%, p = 0.003) and severe heart failure (3% vs 12.5%, p = 0.031). The rate of MACEs at 1 year was also significantly lower in the GIK group (13% vs 40.0%, relative risk 0.22, 95% confidence interval 0.09 to 0.55, p = 0.0012). After 1 year, there was a significant improvement in left ventricular ejection fraction in the GIK group (from 48 +/- 8% to 51 +/- 10%, p &lt;0.01), which was not observed in the control group. In conclusion, high-dose GIK, used as an adjunct to thrombolytic therapy, was safe and improved clinical outcome at 1 month. The beneficial effect of GIK infusion was maintained up to 1 year.

[Use of transesophageal pacing for documentation of older children with accessory pathway].

In case of an accessory pathway, children are exposed to severe cardiac events including sudden death. Radiofrequency ablation is a standardized procedure, which can be applied to a significant number of children although complications can still potentially occur. In this context, transesophageal evaluation of the accessory pathway evaluation can be discussed.</AbstractText>Among 140 procedures performed in 19 years, 70 were done for accessory pathway evaluation. The preexcitation was overt in 59 children older than 5 years, which form the basis in this study.</AbstractText>Anterograde refractory period was determined in 88% cases and was found&lt;220 ms in 12 cases justifying an ablation procedure. Conversely, in case of a long refractory period (&gt;250 ms), the ablation procedure was not performed in 8 asymptomatic cases and was postponed in 11/20 mildly symptomatic children. Transesophageal electrophysiologic study seems legitimate in asymptomatic or mildly symptomatic children.</AbstractText>This technique is probably less useful in case of an overt preexcitation and recurrent reciprocating tachycardia requiring long-term antiarrythmic treatment. In this case, endocavitary electrophysiological study eventually followed by an ablation procedure seems the best option.</AbstractText>

Brugada syndrome and neurally mediated susceptibility.

The risk of sudden death in patients with Brugada syndrome (BS) is still unclear. Moreover, particular clinical conditions may have a confounding effect on the diagnostic and therapeutic approach. We report the case of a 27-year-old man with a clinical history of suspected neurally mediated syncope and typical ECG features of BS. The tilt table test showed a type I, mixed, positive response. The electrophysiological study (EPS) disclosed a peculiar ventricular irritability with the induction of a life-threatening arrhythmia. After the implantation of a cardioverter-defibrillator an episode of ventricular fibrillation during sleep at night was correctly identified and treated by the device. The association between neurally mediated susceptibility and the typical ECG abnormalities of BS is not an unexpected event in young subjects. The misjudgment of the pathophysiological mechanism of syncopal episodes may lead, on one hand, to overlook the risk of sudden death and, on the other, to pursue inappropriate therapeutic measures. The application of a tailored diagnostic work-up based on currently available guidelines may be useful to overcome the clinical and therapeutic dilemma.

Initial energy for biphasic external electrical cardioversion of atrial fibrillation.

No international guidelines indicate the initial energy in biphasic external electrical cardioversion of atrial fibrillation (AF) actually. The aim of this study was to determine this value in order to find a reasonable compromise between the necessity of limiting tissue damage and of quickly restoring sinus rhythm as well.</AbstractText>Fifty-six consecutive patients with AF candidate to external electrical cardioversion were treated using adhesive anterior-posterior paddles and biphasic wave defibrillator Lifepack 12, with steps of 50 J. After 6 hours troponin I levels were measured.</AbstractText>Thirty-four patients were cardioverted by 50 J (group A), 18 by 100 J (group B) and 3 by 150 J (group C). One patient was not cardioverted (success rate 98%). No significant differences were noted between groups A and B with regard to age, sex, weight, height, thoracic circumference, body mass index, body surface area, impedance, NYHA class, left ventricular ejection fraction, left atrial diameter, causes of heart disease, antiarrhythmic medications, and duration of current AF episode. No increase of troponin I levels occurred.</AbstractText>An initial shock of 100 J in the biphasic external elective cardioversion of AF is a valid and highly effective option. An initial shock of 50 J was effective in 61% of our population, and it is probably appropriated in patients with a lower weight and body mass index.</AbstractText>

Atrial fibrillation in heart failure: high mortality risk even if ventricular function is preserved.

The purpose of this study was to determine if patients with atrial fibrillation (AF) and heart failure (HF) have a better prognosis when systolic function is preserved as compared with those with depressed systolic function.</AbstractText>Data from consecutive patients presenting to the emergency department at Brigham and Women's Hospital from January 1997 to December 2002 who had a diagnosis of AF and HF and a measure of ejection fraction (EF) were reviewed. Vital status was determined from the Social Security Death Index.</AbstractText>Of 478 patients (mean age 74 +/- 13 years; 47% women), EF was preserved (&gt; 50%) in 46%. Those with preserved left ventricular (LV) function were older (76 vs 72 years, P &lt; .0020), included more women (62 vs 35%, P &lt; .0001), more likely to have a history of hypertension and pulmonary disease and less likely to have had a prior myocardial infarction. At 5 years, mortality was similar between the preserved and depressed EF groups (50% vs 48%, P = .74). In multivariable analysis, age &gt; 75 years, history of cancer, cerebrovascular disease, aortic valve disease, serum creatinine &gt; 2.0 mg/dL, and serum sodium &lt; 130 mmol/L were associated with increased mortality. Therapy with beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blocker were associated with lower mortality.</AbstractText>Patients who present to the emergency department with AF, HF, and preserved LVEF have a similarly high mortality as compared with those with depressed LVEF. Further study is needed to assess the impact of therapies and clarify the reasons for the poor prognosis.</AbstractText>

[Cardiac consequences of clinical dysthyroidism. Pathophysiological, clinical, and epidemiologic data].

Thyroid hormones affect the vascular system, including the diastolic and systolic functioning of the heart. Resting heart rate increases early in hyperthyroidism (cardiac contractility expands due to improved ventricular loading and decreased systemic vascular resistance). Paradoxically, these hemodynamic alterations progressively reduce cardiac performance on effort (changes in diastolic, then systolic functioning) and finally at rest (modification in ventricular loading following tachycardia or atrial fibrillation), especially in cases of underlying heart disease (in the elderly). Hypothyroidism has an inverse hemodynamic effect and is less noisy, usually limited to relative bradycardia. The morbidity and mortality associated with hypothyroidism are apparently related to the atherogenic and prothrombotic vascular modifications that follow thyroid hormone deficiency, whereas heart failure and particularly atrial fibrillation and its thromboembolic complications are the primary consequences of hyperthyroidism. In both cases, return to normal thyroid levels corrects the cardiac abnormalities caused by the dysthyroidism. Dysthyroidism (hypo- or hyperthyroidism) occurs in 10 to 20% of the patients treated with amiodarone for arrhythmia. Because of its potential seriousness, some clinical or laboratory tests are necessary before initiating treatment, and specific clinical surveillance should be scheduled, including laboratory tests.

Survival after spontaneous coronary artery dissection presenting with ventricular fibrillation arrest.

Spontaneous coronary artery dissection (SCAD) is a rarely documented etiology of myocardial infarction and sudden cardiac death (SCD). We present a case of a 37-year-old non-pregnant female who presented with a left anterior descending artery (LAD) dissection complicated by ventricular fibrillation arrest. After early diagnostic catheterization and medical management, our patient experienced a complete recovery, returning to her pre-SCD status without limitation. This case is unique in that the SCAD did not occur in the context of previously described associations. Also, this is only the second reported case of a patient with SCAD who survived documented SCD. Our case suggests that medical management is a reasonable option in patients with single-vessel non-left main/proximal LAD artery SCAD.

Pacemaker selection: time for a rethinking of complex pacing systems?

Evidence from randomized trials indicates that the clinical benefits of dual-chamber (DDD) pacing are modest: (i) no significant differences exist between physiological pacing and single-chamber pacing in mortality and stroke; (ii) ventricular desynchronization resulting from chronic right-ventricular pacing in DDD mode, induces a significantly increased incidence of atrial fibrillation (AF) and heart failure hospitalizations; (iii) AF pacing prevention and therapy algorithms have shown a modest to minimal or absent efficacy; (iv) the widespread use of physiological pacemakers is not an economically attractive strategy. Thus, these data provide a reliable body of evidence on which to make more rationale clinical decisions for individual patients and policy decisions for health costs saving. The cheaper single-chamber AAI(R) or VVI(R) has been shown to satisfy both conditions in most cases of sinus node disease and AV block.