bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of coronary artery spasm in progression of organic coronary stenosis and acute myocardial infarction in a swine model. Importance of mode of onset and duration of coronary artery spasm.
Authors: Kuga T , Tagawa H , Tomoike H , Mitsuoka W , Egashira S , Ohara Y , Takeshita A , Nakamura M
Published: June 2012

BACKGROUND

Coronary spasm may play an important role in progression of organic coronary stenosis and myocardial infarction, but the mechanisms responsible for these complications are not known. This study aimed to examine whether the mode of onset and the duration of coronary spasm influenced progression of organic coronary stenosis and acute myocardial infarction in a swine model of coronary spasm.

METHODS AND RESULTS

Göttingen miniature pigs were subjected to cholesterol feeding, balloon-induced coronary arterial denudation, and x-ray irradiation. Five months later, coronary spasm was induced by intracoronary injection of serotonin. In 10 pigs, coronary spasm was provoked abruptly and maintained for 25 minutes by five repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes (group A, abrupt onset and short duration). In group B, coronary spasm was provoked gradually by intracoronary injections of serotonin at graded doses of 0.1, 0.3, and 0.6 microgram/kg every 5 minutes and was then maintained for 25 minutes in four pigs (group B1, gradual onset and short duration) and for 120 minutes in six pigs (group B2, gradual onset and long duration) by repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes. Intramural hemorrhage was noted histologically at the spastic site more frequently in group A with abrupt onset (nine of 10 pigs) than in group B with gradual onset (two of 10 pigs) (p < 0.01). Progression of organic coronary stenosis due to intramural hemorrhage was noted in seven pigs (six pigs in group A and one pig in group B), including three cases of total coronary occlusion. Evidence for the evolution of acute myocardial infarction (serial ECG findings, left ventriculograms, and histological findings) was noted in one pig (7%) of group A or B1 with short duration and in five of six pigs (83%) in group B2 with long duration (p < 0.01 versus group A and B1).

CONCLUSIONS

These results indicate that: 1) intramural hemorrhage was frequently induced by coronary spasm of abrupt but not of gradual onset, 2) intramural hemorrhage resulted in acute progression of coronary stenosis and sometimes resulted in persistent total coronary occlusion leading to acute myocardial infarction, and 3) prolonged coronary spasm resulted in acute myocardial infarction without progression of organic coronary stenosis.
Results of percutaneous transluminal coronary angioplasty in women. 1985-1986 National Heart, Lung, and Blood Institute's Coronary Angioplasty Registry.
Authors: Kelsey S F , James M , Holubkov A L , Holubkov R , Cowley M J , Detre K M
Published: June 2012

BACKGROUND

The National Heart, Lung, and Blood Institute (NHLBI) Percutaneous Transluminal Coronary Angioplasty (PTCA) 1978-1981 Registry cohort indicated that PTCA risk was higher and efficacy was lower in women. Data from the 1985-1986 PTCA Registry are used to address the question of whether compared with men, women still have a worse outcome after PTCA.

METHODS AND RESULTS

The 1985-1986 NHLBI PTCA Registry collected data on consecutive, first-PTCA cases at 16 centers. Initial results are reported for 2,136 patients, 546 of whom were women. Four-year follow-up status was available on 95% of the cohort. Although women were an average of 4.5 years older than the male patients and had more cardiovascular risk factors and more severe angina, their coronary artery disease as assessed by angiography was not more extensive. Rates of angiographic success on a per-lesion basis were similar for women and men (89% versus 88%), and the clinical success rates (79%) were the same. Women had more initial complications (29% versus 20%, p < 0.001) and a considerably higher procedural mortality rate (2.6% versus 0.3%, p < 0.001). For patients who survived the initial procedure, 4-year survival was similar for men and women. At 4 years, women had slightly fewer events (myocardial infarction, repeat PTCA, and/or coronary artery bypass grafting). Despite the higher proportion of women reporting the presence of angina and medication use at 4 years, the proportion reporting improvement in symptomatic status was similar to that of men.

CONCLUSIONS

Women undergoing PTCA have a higher procedural mortality risk than men; this is explained in part by their worse cardiovascular risk factor profile. Otherwise, the success rate and long-term prognosis after PTCA are excellent, and PTCA should be considered for women in need of revascularization.
Comparison of angioplasty and surgery for unoperated coarctation of the aorta.
Authors: Shaddy R E , Boucek M M , Sturtevant J E , Ruttenberg H D , Jaffe R B , Tani L Y , Judd V E , Veasy L G , McGough E C , Orsmond G S
Published: June 2012

BACKGROUND

The use of balloon coarctation angioplasty instead of surgery as treatment for unoperated coarctation of the aorta is controversial. The efficacy and complications of the two procedures have not been studied before in a prospective fashion.

METHODS AND RESULTS

Thirty-six patients were prospectively randomized to either angioplasty (20 patients) or surgery (16 patients). Immediate results and patient follow-up, including physical examination, angiograms, and magnetic resonance imaging, were compared between groups. Reduction in peak systolic pressure gradient across the coarctation was similar (86%) immediately after both balloon coarctation angioplasty and surgery. On follow-up, aneurysms were seen only in the angioplasty group (20%) and not in the surgery group (0%). No aneurysms have shown progression or required surgery. The incidence of other complications was similar in both groups, although two patients experienced neurological complications after surgery. Although not statistically different, the incidence of restenosis (peak systolic pressure gradient > or = 20 mm Hg) tended to be greater in the angioplasty group (25%) than in the surgery group (6%). Restenosis after angioplasty occurred more frequently in patients with an aortic isthmus/descending aorta diameter ratio < 0.65 and was associated with an immediate catheterization residual peak systolic pressure gradient across the coarctation > or = 12 mm Hg.

CONCLUSIONS

Immediate gradient reduction is similar after balloon coarctation angioplasty and surgical treatment of unoperated coarctation of the aorta. The risks of aneurysm formation and possibly restenosis after angioplasty are higher than after surgery, although the risks of other complications are similar. Balloon coarctation angioplasty may provide an effective initial alternative to surgical repair of unoperated coarctation of the aorta in children beyond infancy, particularly in patients with a well-developed isthmus. Further follow-up is necessary to determine the long-term risks of postangioplasty aneurysms.
Abnormal baroreceptor-mediated vasodilation of the peripheral circulation in congestive heart failure secondary to idiopathic dilated cardiomyopathy.
Authors: Wroblewski H , Kastrup J , Mortensen S A , Haunsø S
Published: June 2012

BACKGROUND

Peripheral edema is a major clinical problem in congestive heart failure (CHF). The function of the edema-protective baroreceptor-mediated and local nervous vasoconstrictor reflexes of the lower leg during orthostasis in moderate and severe CHF has largely been unexplored.

METHODS AND RESULTS

Baroreceptor-mediated and local nervous regulation of subcutaneous blood flow of the lower leg was studied in healthy subjects and in patients with moderate and severe CHF secondary to idiopathic dilated cardiomyopathy. Blood flow was measured by the local 133Xe washout method in the supine position and during 45 degrees head-up tilt. When the central baroreceptor reflex alone was activated, the changes in subcutaneous blood flow of the heart failure patients in both groups were significantly different from those of the eleven control subjects: blood flow increased 48 +/- 26% in 10 severe and 3 +/- 24% in nine moderate CHF patients compared with the decrease in blood flow of -36 +/- 15% observed in 11 control subjects (p < 0.0001 for both). A highly significant direct association was demonstrated between changes in blood flow and New York Heart Association functional class (p = 0.007) and the left ventricular ejection fraction (p = 0.01). Activation of the baroreceptor and local venoarteriolar axon reflexes simultaneously increased blood flow significantly (30 +/- 9%) in 14 patients with severe CHF, compared with the decrease found in 14 control subjects (-53 +/- 9%) and in the group of 14 patients with moderate CHF (-17 +/- 25%) (p < 0.0001 for both).

CONCLUSIONS

Patients with CHF secondary to idiopathic dilated cardiomyopathy have an abnormal baroreceptor-mediated vasodilation in subcutaneous tissue of the lower leg during the upright position, which increases with the severity of the disease. The hemodynamic consequence is capillary hypertension and hyperemia in the leg during the upright position that may contribute to the development of edema and to the initiation of structural changes (microangiopathy) demonstrated in the microcirculation.
Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion.
Authors: Przyklenk K , Bauer B , Ovize M , Kloner R A , Whittaker P
Published: June 2012

BACKGROUND

One or more brief episodes of coronary artery occlusion protect or "precondition" the myocardium perfused by that artery from a subsequent episode of sustained ischemia. We sought to determine whether ischemic preconditioning protects only those myocytes subjected to brief coronary occlusion or whether brief occlusions in one vascular bed also limit infarct size and/or attenuate contractile dysfunction in remote virgin myocardium subjected to subsequent sustained coronary occlusion.

METHODS AND RESULTS

In the preliminary limb of the study, six anesthetized dogs underwent four episodes of 5-minute circumflex branch occlusion plus 5-minute reperfusion, followed by 1 hour of sustained left anterior descending coronary artery occlusion and 4.5 hours of reflow. Subendocardial blood flow during left anterior descending coronary artery occlusion (measured by injection of radiolabeled microspheres) was 0.07 +/- 0.03 mL.min-1 x g tissue-1, similar to the value of 0.07 +/- 0.02 mL.min-1 x g-1 observed in a group of eight concurrent control dogs. However, infarct size (assessed by triphenyltetrazolium staining) in the circumflex preconditioned group averaged 4 +/- 1% of the myocardium at risk, significantly less (p < 0.05) than the value of 13 +/- 4% observed in the concurrent controls. An additional 18 dogs were then randomized to undergo either four episodes of circumflex branch occlusion (n = 8) or no intervention (n = 10) before 1 hour of left anterior descending coronary artery occlusion and 4.5 hours of reflow. Subendocardial blood flow averaged 0.08 +/- 0.02 versus 0.08 +/- 0.03 mL.min-1 x g-1 in the control versus circumflex preconditioned groups, yet infarct size was significantly smaller in circumflex preconditioned dogs than in the controls (6 +/- 2% versus 16 +/- 5% of the risk region; p < 0.05). At 4.5 hours following reperfusion, segment shortening in the left anterior descending coronary artery bed (assessed by sonomicrometry) averaged -21 +/- 19% of baseline in control animals versus 13 +/- 12% of baseline in the preconditioned group (p = NS). Circumflex preconditioning did not, however, have an independent beneficial effect on contractile function: Regression analysis revealed that the trend toward improved function in circumflex preconditioned dogs reflected the smaller infarct sizes in this group.

CONCLUSIONS

Brief episodes of ischemia in one vascular bed protect remote, virgin myocardium from subsequent sustained coronary artery occlusion in this canine model. These data imply that preconditioning may be mediated by factor(s) activated, produced, or transported throughout the heart during brief ischemia/reperfusion.
The renin-angiotensin system and volume overload-induced cardiac hypertrophy in rats. Effects of angiotensin converting enzyme inhibitor versus angiotensin II receptor blocker.
Authors: Ruzicka M , Yuan B , Harmsen E , Leenen F H
Published: June 2012

BACKGROUND

The degree of cardiac hypertrophy is not only load dependent: Among other factors, the renin-angiotensin system may play a role in the regulation of cardiac myocyte growth.

METHODS AND RESULTS

To evaluate the role of the renin-angiotensin system in volume overload-induced cardiac hypertrophy, we assessed: 1) the time course of changes in cardiac hemodynamics, cardiac anatomy, and plasma and cardiac renin activity in response to volume overload induced by two sizes of abdominal aortocaval shunt and 2) the effects of chronic treatment with an angiotensin converting enzyme inhibitor (ACEI) versus an angiotensin II receptor blocker on hemodynamics and cardiac hypertrophy. Drug treatment started 3 days before shunt surgery. An increase in left ventricular end-diastolic pressure (LVEDP) and the development of right ventricular (RV) and left ventricular (LV) eccentric hypertrophy in response to volume overload occurred within the first week after induction of the shunt. Plasma renin activity (PRA) and cardiac renin activity peaked shortly after induction of the shunt. During the chronic phase, LVEDP and PRA decreased somewhat but remained significantly elevated up to 7 weeks after shunt surgery. Cardiac renin activity returned toward normal within 4 weeks after surgery. Treatment with the ACEI enalapril caused only a modest decrease in LV internal diameter but did not affect increases in LV and RV weights in response to volume overload despite a major decrease in LVEDP after chronic treatment. In contrast, treatment with the angiotensin II receptor blocker losartan, which had similar effects on cardiac and peripheral hemodynamics, prevented dilation of the LV after 7 days and attenuated the dilation of the LV after 28 days. Moreover, increases in LV and RV weights were significantly attenuated by losartan.

CONCLUSIONS

The development of volume overload-induced cardiac hypertrophy is associated with significant increases in PRA and cardiac renin activity shortly after induction of an aortocaval shunt. Whereas the two blockers of the renin-angiotensin system decreased LVEDP to a similar extent, only the angiotensin II receptor blocker blunted the hypertrophic response of the heart to volume overload, which is indicative for other than hemodynamic determinants of the cardiac hypertrophic response. One trophic factor may be cardiac angiotensin II generated via an angiotensin II-forming enzyme resistant to ACEI and possibly activated by cardiac volume overload.
Prognostic value of an abnormal signal-averaged electrocardiogram in patients with nonischemic congestive cardiomyopathy.
Authors: Mancini D M , Wong K L , Simson M B
Published: June 2012

BACKGROUND

An abnormal signal-averaged ECG (SAECG) has predictive value for arrhythmic events in patients with coronary artery disease. The purpose of this study was to investigate whether an abnormal SAECG could provide prognostic information in patients with nonischemic dilated cardiomyopathy.

METHODS AND RESULTS

We prospectively obtained SAECGs in 114 patients with dilated nonischemic cardiomyopathy. Twelve-lead ECGs, left ventricular ejection fractions, hemodynamic measurements, and peak exercise oxygen consumption (VO2) also were measured. An SAECG was defined as abnormal by any one of the three following criteria: filtered QRS duration > 120 msec, root-mean-square voltage in the last 40 msec < 20 microV, or duration < 40 microV > 38 msec at 40 Hz. Sixty-six patients had a normal SAECG, 20 patients had an abnormal SAECG, and 28 patients had bundle branch block (BBB). Mean follow-up was 10 +/- 5 months. Age, ejection fraction, peak VO2, pulmonary capillary wedge pressure, and cardiac index were not statistically different among the three groups. Use of antiarrhythmic drugs was similar among the three groups, although patients with BBB had more implantable defibrillators (p < 0.05). The incidence of previous atrial arrhythmias was similar for the three groups. Patients with abnormal SAECG or BBB had more past episodes of sustained ventricular tachycardia and/or sudden death episodes (n = 9) than patients with normal SAECG (n = 1) (p < 0.01). Prospectively, none of the 66 patients with normal SAECG died suddenly or had sustained ventricular arrhythmias. Two deaths occurred from progressive heart failure, and three patients required urgent transplant. In the 20 patients with an abnormal SAECG, four patients had sustained ventricular tachycardia, five patients died suddenly, two patients died from progressive heart failure, and one patient required urgent transplant. In the patients with BBB, four patients had sustained ventricular tachycardia, and four patients required urgent transplant. One-year event-free survival, i.e., absence of ventricular tachycardia and/or death, was 95% in patients with normal SAECG, 88% in patients with BBB, and only 39% in patients with an abnormal SAECG (p < 0.001). Multivariate analysis demonstrated that SAECG and New York Heart Association classification were independent predictors of survival.

CONCLUSIONS

Patients with an abnormal SAECG had a statistically significant increase in sustained ventricular arrhythmias and/or death than did patients with a normal SAECG or BBB. This study demonstrates that an abnormal SAECG is a marker of past and future arrhythmic events in patients with nonischemic dilated cardiomyopathy. In contrast, patients with a dilated cardiomyopathy with a normal SAECG have an excellent prognosis with adverse outcome only from progressive heart failure.
Spontaneous occurrence of symptomatic paroxysmal atrial fibrillation and paroxysmal supraventricular tachycardia in untreated patients.
Authors: Clair W K , Wilkinson W E , McCarthy E A , Page R L , Pritchett E L
Published: June 2012

BACKGROUND

Ambulatory outpatients (n = 150) with a history of paroxysmal supraventricular arrhythmia were studied to establish the characteristics of the first recurrence of symptomatic tachycardia (time to first recurrence, heart rate during tachycardia, and observed rhythm that was regular versus irregular) when no antiarrhythmic drug was being taken. Baseline variables were examined to assess their impact on time to first recurrence: index arrhythmia (paroxysmal atrial fibrillation [n = 37] versus paroxysmal supraventricular tachycardia [n = 113]), age (mean +/- SD, 43.3 +/- 16.1 years), female sex (n = 71), or presence of other heart or lung disease (n = 53).

METHODS AND RESULTS

Transtelephonic monitoring of the ECG was used to document the rhythm during recurrences of symptomatic tachycardia. Time to first recurrence of symptomatic tachycardia and heart rate during tachycardia were measured, the observed rhythm was classified as irregular (consistent with paroxysmal atrial fibrillation) or regular (consistent with paroxysmal supraventricular tachycardia), and the hour of recurrence was recorded. Advancing age was significantly associated with a decreasing time to first recurrence (p < 0.001); the estimated increase in the hazard function was 25% with each 10 years of advancing age. After the effect of age was adjusted for, neither the classification of arrhythmia (p > 0.2), presence of other heart or lung disease (p > 0.8), nor sex (p > 0.9) was significantly associated with time to first recurrence. Among patients with paroxysmal supraventricular tachycardia, 6.5% had atrial fibrillation recorded at the next symptomatic arrhythmia; among patients with paroxysmal atrial fibrillation, 11.8% had a regular tachycardia recorded at the next symptomatic arrhythmia. There was a circadian pattern to the hour of occurrence of paroxysmal supraventricular tachycardia but not paroxysmal atrial fibrillation.

CONCLUSIONS

Age is more important than other clinical variables, including the ECG classification of a paroxysmal supraventricular arrhythmia in predicting the occurrence of symptomatic arrhythmias. Arrhythmias documented by ECG during symptoms are often different from the arrhythmia documented at the time of referral, which may confound interpretation of antiarrhythmic drug effects.
Positron emission tomography with 11C CGP-12177 to assess beta-adrenergic receptor concentration in idiopathic dilated cardiomyopathy.
Authors: Merlet P , Delforge J , Syrota A , Angevin E , Mazière B , Crouzel C , Valette H , Loisance D , Castaigne A , Randé J L
Published: June 2012

BACKGROUND

Positron emission tomography (PET) with 11C-labeled CGP-12177 (CGP) has been shown to have the potential to noninvasively measure beta-adrenergic receptor concentration in dog heart. The present study was undertaken to evaluate the clinical value of this technique.

METHODS AND RESULTS

Eight normal subjects and 10 patients with heart failure related to an idiopathic cardiomyopathy were studied. Estimation of beta-receptor concentration was based on a graphic method applied on myocardial PET time-concentration curves obtained after an intravenous injection of 11C-CGP followed 30 minutes later by a coinjection of labeled and unlabeled CGP. The clinical tolerance of these injections was good. Left ventricular concentration of beta-receptors was decreased in patients compared with controls (3.12 +/- 0.51 versus 6.60 +/- 1.18 pmol/mL, respectively; p < 0.001). This 53% decrease agrees with previous in vitro data. In eight of the 10 patients, the beta-receptor concentration obtained from PET was compared with the beta-receptor density determined on left ventricular endomyocardial biopsy samples by in vitro binding technique using 3H-CGP-12177. Results obtained with both techniques were correlated (r = 0.79, p = 0.019). Moreover, decreased beta-receptor concentration correlated with the beta-contractile responsiveness to intracoronary dobutamine infusion (r = 0.83, p = 0.003), indicating a direct link between changes in the receptor number and its biological function.

CONCLUSIONS

PET appears to be a safe and reliable method of assessing in vivo changes in the number of left ventricular beta-adrenergic receptor sites of patients with idiopathic cardiomyopathy.
Cardiotoxicity of human recombinant interleukin-2 in rats. A morphological study.
Authors: Zhang J , Yu Z X , Hilbert S L , Yamaguchi M , Chadwick D P , Herman E H , Ferrans V J
Published: June 2012

BACKGROUND

One of the side effects of interleukin 2 (IL-2) cancer immunotherapy in humans is the vascular leak syndrome, which is frequently associated with depression of myocardial function, myocarditis, and myocardial necrosis.

METHODS AND RESULTS

To investigate this cardiotoxicity, IL-2 (three doses of 5 x 10(5) Cetus units/day i.p.) was given to rats for 2, 3, or 5 days. Heart, lung, liver, spleen, and kidney tissues were studied by light and electron microscopy and with immunoperoxidase techniques. Cardiac changes consisted of focal lymphocytic and eosinophilic infiltration, myocyte vacuolization, myofibrillar loss, and necrosis. Ultrastructural alterations included swelling of endothelial cells, with dissociation of intercellular junctions, migration of lymphocytes into the interstitium, and interstitial hemorrhage and edema. Close contact between infiltrating lymphocytes, particularly large granular lymphocytes, and cardiac myocytes was often observed in areas of tissue damage. All lesions were more severe on day 5 than on days 2 and 3. Immunoperoxidase stains demonstrated asialo GM1 ganglioside antibody-positive, granular lymphocytes to be much more frequent in myocardium of IL-2-treated rats than in that of control rats.

CONCLUSIONS

Although we cannot exclude the possibility of a direct toxic effect of IL-2 on myocytes, our observations suggest that the myocardial damage produced by this agent is triggered by IL-2-activated lymphocytes that exert cytolytic effects, first on endothelial cells and then on cardiac myocytes, thus producing lesions that involve both the cardiac microcirculation and the muscle cells.
A randomized, prospective comparison of anterior and posterior approaches to radiofrequency catheter ablation of atrioventricular nodal reentry tachycardia.
Authors: Langberg J J , Leon A , Borganelli M , Kalbfleisch S J , el-Atassi R , Calkins H , Morady F
Published: June 2012

BACKGROUND

Two different techniques have been developed for radiofrequency catheter ablation of typical atrioventricular nodal reentry (AVNRT). Lesions made anteriorly near the apex of the triangle of Koch usually eliminate fast pathway function, whereas lesions made posteriorly near the ostium of the coronary sinus selectively affect slow pathway function. The current study compares the safety, efficacy, and electrophysiological effects of these two techniques in a prospective, randomized fashion.

METHODS AND RESULTS

Fifty consecutive patients with typical AVNRT were randomly assigned to receive radiofrequency lesions either anteriorly (n = 22) or posteriorly (n = 28). If the initial approach failed to eliminate inducibility of AVNRT after 1 hour or 10 applications of radiofrequency energy, the alternative ablation technique was used. Patients underwent repeat electrophysiological testing 48 hours and 3 months after ablation. The primary success rates of the anterior and posterior techniques were similar (55% versus 68%, p = NS). All of the patients who failed the initial approach were successfully treated by the alternative technique without developing high-grade atrioventricular block. One patient developed right bundle branch block during an anterior lesion, and another patient developed complete atrioventricular block as the result of a posterior lesion.

CONCLUSIONS

The posterior approach to radiofrequency catheter modification of the atrioventricular node is as effective as the anterior approach, and both techniques are associated with a low risk of complications. As long as AVNRT persists, it appears safe to cross over from one technique to the other.
Effect of picotamide on the clinical progression of peripheral vascular disease. A double-blind placebo-controlled study. The ADEP Group.
Authors: Balsano F , Violi F
Published: June 2012

BACKGROUND

Patients with peripheral vascular disease (PVD) undergo a clinical course that can be complicated by cardiovascular events occurring in several areas of the circulation.

METHODS AND RESULTS

In the present study we investigated the ability of picotamide, a substance that inhibits platelet thromboxane A2 (TxA2) synthase and antagonizes TxA2 receptors, to reduce cardiovascular complications in PVD patients. The study was double blind and placebo controlled. After a 1-month run-in period, 2,304 patients were randomly allocated to either placebo or picotamide (300 mg t.i.d.) and followed for 18 months. Major and minor events were analyzed. Results of an "intention-to-treat analysis" were that patients on picotamide suffered 45 major events (3.9%) and 77 minor events (6.7%), whereas those taking placebo suffered 52 major (4.5%) and 99 minor events (8.6%). There was borderline statistical difference between the two groups with respect to the sum of the major and minor events (risk reduction, 18.9%; p = 0.056, log-rank test). Results of an "on-treatment" analysis were that patients on picotamide suffered 40 major (3.8%) and 66 minor events (6.3%), whereas those taking placebo suffered 45 major (4.2%) and 95 minor events (8.9%). The sum of both major and minor events was 106 (10.1%) in the picotamide group and 140 (13.1%) in the placebo group. This difference was significant (risk reduction, 23%; p = 0.029, log-rank test).

CONCLUSIONS

The results of this study indicate that picotamide reduces cardiovascular complications in PVD patients. The apparently low effect of this drug in reducing major events suggests that further studies be made with picotamide in PVD patients who are at high risk of cardiovascular complications so as to further assess its clinical efficacy.
Shock occurrence and survival in 241 patients with implantable cardioverter-defibrillator therapy.
Authors: Grimm W , Flores B T , Marchlinski F E
Published: June 2012

BACKGROUND

The purpose of this study was to determine the influence of clinical characteristics on shock occurrence and survival in 241 patients with implantable cardioverter-defibrillator (ICD) therapy.

METHODS AND RESULTS

Two hundred forty-one consecutive patients underwent ICD implantation between November 1982 and November 1991 and were subsequently followed for 26 +/- 22 months (intention-to-treat analysis). Actuarial incidence of "appropriate" shocks was 13%, 42%, and 63%, and the incidence of any spontaneous shocks was 15%, 51%, and 76% at 1, 3, and 5 years of follow-up, respectively. Poor left ventricular function (ejection fraction < or = 30%) was associated with an earlier occurrence of both appropriate and any spontaneous ICD shocks (p = 0.001). Appropriate and any spontaneous shocks occurred significantly later in patients who presented with cardiac arrest and in patients in whom only ventricular fibrillation but no uniform ventricular tachycardia was induced during preoperative programmed stimulation. In addition, amiodarone treatment at implant was associated with later occurrence of any spontaneous shocks. Cumulative survival from all-cause mortality including perioperative mortality was 84%, 62%, and 57%, and survival from arrhythmic death was 97%, 89%, and 83% at 1, 3, and 5 years, respectively. Ejection fraction < or = 30% was the best predictor of both total arrhythmic death (p = 0.019) and total mortality (p = 0.003). Antiarrhythmic therapy with class 1 agents at implant was also associated with a higher total mortality during follow-up (p = 0.023) but not with total arrhythmic death. Age, sex, underlying heart disease, clinical presentation, and preoperative response to programmed stimulation did not predict long-term survival. In addition, survival curves were similar for patients with and without spontaneous shocks.

CONCLUSIONS

The majority of patients receive shocks during long-term follow-up. The occurrence of appropriate or any spontaneous shocks during follow-up is not associated with increased arrhythmic or total mortality consistent with effective prevention of sudden cardiac death with ICD therapy in this high-risk patient population. Although low ejection fraction is the strongest predictor of both shock occurrence and mortality during follow-up, no easy algorithm can be derived from the analyzed clinical characteristics to predict which patients will benefit most from ICD implantation.
A prospective randomized repeat-crossover comparison of antitachycardia pacing with low-energy cardioversion.
Authors: Bardy G H , Poole J E , Kudenchuk P J , Dolack G L , Kelso D , Mitchell R
Published: June 2012

BACKGROUND

Multiprogrammable antiarrhythmia devices can treat monomorphic ventricular tachycardia (VT) with autodecremental overdrive pacing and/or with low-energy cardioversion. These two methods provide the opportunity to decrease patient discomfort typically experienced with high-energy pulses. Although both therapies are known to be effective, controversy persists over their relative safety and efficacy.

METHODS AND RESULTS

The purpose of this study was to examine the safety and efficacy of autodecremental overdrive pacing and low-energy cardioversion in reproducibly terminating monomorphic VT in 24 patients with multiprogrammable antiarrhythmia devices. The protocol required that identical ECG morphology VT be reproducibly induced four times to assess the outcome of antitachycardia pacing and cardioversion twice for each patient in a randomized fashion. Each episode of VT was induced via the implanted device. Autodecremental overdrive pacing initially began with seven stimuli at 97% of the VT cycle length, decrementing by 10 msec per stimulus to a minimum coupling interval of 200 msec. If ineffective, autodecremental overdrive pacing was allowed to iterate three more times for a total of four pacing interventions. With each iteration, one stimulus was added to the pacing train. Similarly, with low-energy cardioversion, up to four therapeutic attempts were made, beginning with a 0.2-J pulse. If ineffective, pulse energy was increased to 0.4, 1.0, and finally 2.0 J. All interventions were automatic without human interference. VT (cycle length, 306 +/- 42 msec) was repeatedly terminated in 15 of 24 patients (63%) by autodecremental overdrive pacing and in 18 of 24 patients (75%) by low-energy cardioversion (p = 0.53). Eight of the 24 patients (33%) had their VT terminated repeatedly by both therapies. VT accelerated to faster VT or ventricular fibrillation by autodecremental overdrive pacing in four of 24 patients (17%) and by low-energy cardioversion in five of 24 (21%) (p = 0.88). Only one of the 24 patients (4%) accelerated with both therapies. No patient was unaffected by either therapy.

CONCLUSIONS

In the manner programmed, autodecremental overdrive pacing and low-energy cardioversion have similar efficacy and acceleration rates. Response to one therapy does not predict response to the other.
Implantable cardioverter-defibrillator therapy in the absence of significant symptoms. Rhythm diagnosis and management aided by stored electrogram analysis.
Authors: Hook B G , Callans D J , Kleiman R B , Flores B T , Marchlinski F E
Published: June 2012

BACKGROUND

This report describes the value of stored ventricular electrogram analysis in the diagnosis and management of patients experiencing minimal or no symptoms before implantable cardioverter-defibrillator (ICD) therapy.

METHODS AND RESULTS

The study population included 48 patients who received the Cadence Tiered Therapy Defibrillator System, an investigational third-generation ICD with ventricular electrogram storage capabilities. Criteria for arrhythmia diagnosis were based on analysis of the electrogram rate, RR interval variability, and morphology. Twenty-nine of the 48 patients (60%) experienced at least one episode of antitachycardia pacing or shock (one shock or more in 25 of 29 patients) that was preceded by minimal or no symptoms during a mean follow-up of 15.1 +/- 7.8 months. There were 194 tachycardia episodes registered by the device, including 101 for which ventricular electrograms were stored and available for analysis. Of the 101 stored electrograms, 74 were classified as ventricular tachycardia (VT), 24 as non-VT rhythms (atrial fibrillation, 13; supraventricular tachycardia, six; rate-sensing lead disruption, four; T wave oversensing, one), and only three as indeterminate rhythms. Based on the electrogram analysis, changes in tachycardia detection criteria and/or antiarrhythmic drug regimens were implemented and were associated with a reduction in the number of device responses for non-VT rhythms from 24 during the initial study period to three during 11.0 +/- 7.2 months of additional follow-up.

CONCLUSIONS

ICD responses in the absence of symptoms are relatively common in third-generation devices with antitachycardia pacing capabilities. Despite potential limitations such as the effect of bundle branch block on the electrogram morphology during supraventricular tachycardia, the availability of electrogram storage capabilities allowed a presumptive diagnosis of the events precipitating asymptomatic device responses. Device reprogramming based on analysis of stored electrograms was associated with a dramatic reduction in the incidence of ICD responses for non-VT rhythms.
Noninvasive measurement of rate of left ventricular relaxation by Doppler echocardiography. Validation with simultaneous cardiac catheterization.
Authors: Nishimura R A , Schwartz R S , Tajik A J , Holmes D R
Published: June 2012

BACKGROUND

The instantaneous pressure gradient between the left ventricle and left atrium during systole can be calculated from the mitral regurgitation Doppler velocity curve. The purpose of our study was to determine the accuracy of measuring the time constant of relaxation (TAU) derived from the Doppler mitral regurgitation signal by comparing it with simultaneous high-fidelity left ventricular pressure measurements in humans.

METHODS AND RESULTS

Twenty-five patients had continuous-wave Doppler mitral regurgitation recordings performed with simultaneous high-fidelity left ventricular pressure measurements. Fifteen of these patients had measurements of six to eight beats at various RR intervals. Doppler velocity curves were converted to left ventricular pressure curves by different methods through application of the modified Bernoulli equation at 3-msec intervals. The correlation between catheter-derived and Doppler-derived TAU was best when a zero asymptote and knowledge of the left ventricular end-diastolic pressure were used. A less optimal but acceptable method used the addition of 20 mm Hg to the Doppler-derived ventriculoatrial gradient. Use of a nonzero asymptote for calculation of TAU yielded poor correlation between catheter and Doppler measurements. The correlation of percentage change in Doppler-derived TAU plotted against percentage change in catheter-derived TAU was poor.

CONCLUSIONS

The descending limb of the Doppler-derived mitral regurgitation velocity signal can be used as a semiquantitative estimate of the rate of ventricular relaxation. This method requires knowledge of left atrial pressure and may not be sufficiently accurate for detecting small changes in the rate of relaxation on a beat-to-beat basis.
Heart rate variability from 24-hour electrocardiography and the 2-year risk for sudden death.
Authors: Algra A , Tijssen J G , Roelandt J R , Pool J , Lubsen J
Published: June 2012

BACKGROUND

Low heart rate variability has been implicated as a risk factor for sudden death. However, no large epidemiological studies using sudden death as an outcome event have been reported.

METHODS AND RESULTS

A total of 6,693 consecutive patients who underwent 24-hour ambulatory ECG were followed up for 2 years; of these, 245 patients died suddenly. Clinical data at the time of 24-hour ambulatory ECG were collected for all patients who died suddenly and for a random sample of 268 patients from the study cohort. In all patients in sinus rhythm with or without occasional supraventricular arrhythmias at the 24-hour ECG (193 patients who died suddenly and 230 patients from the sample), heart rate variability parameters were derived. Patients with low short-term RR interval variability (mean during 24 hours of per-minute standard deviations [SD] of RR intervals < 25 msec) had a 4.1-fold higher risk (95% confidence interval [CI], 2.6, 8.1) for sudden death than patients with high short-term variability (> or = 40 msec); after adjustment for age, evidence of cardiac dysfunction, and history of myocardial infarction, the relative risk was 2.6 (95% CI, 1.4, 5.1). The crude relative risk of long-term RR interval variability (SD during 24 hours of per-minute means of RR intervals < 8 msec) was 4.4 (95% CI, 2.6, 7.7); after adjustment for the same risk factors, it was 2.2 (95% CI, 1.2, 4.1). Patients with a minimum heart rate > or = 65 beats per minute had a double risk of sudden death compared with those with a minimum heart rate < 65 beats per minute (adjusted relative risk, 2.1; 95% CI, 1.3, 3.6).

CONCLUSIONS

These findings support the theory that patients with low parasympathetic activity (low short-term RR interval variability) have an increased risk for sudden death independent of other risk factors.
Atrioventricular nodal reentry. Clinical, electrophysiological, and therapeutic considerations.
Authors: Akhtar M , Jazayeri M R , Sra J , Blanck Z , Deshpande S , Dhala A
Published: June 2012

BACKGROUND

Atrioventricular (AV) nodal reentry is a relatively common cause of regular, narrow QRS tachycardia. The underlying basis for this arrhythmia is functional (and anatomic) duality of pathways in the region of the AV node, although the exact boundaries of the reentrant circuit have not been convincingly defined. During the more common type of AV nodal reentry (seen in approximately 90% of cases), a slow conducting pathway is used in the anterograde direction, and a fast pathway is operative in the retrograde direction. In the uncommon form, the direction of impulse propagation within the reentrant circuit is reversed. In this article, the clinical, ECG, and electrophysiological features of AV nodal reentry as well as approaches to therapy are discussed.

METHODS AND RESULTS

Clinical diagnosis may be made from the surface ECG. In the common type of AV nodal reentry, the P wave is obscured by the QRS or may be present in its terminal portion. The P wave in the uncommon form occurs late (i.e., in or after the T wave), producing a pattern of long RP and short PR. Both forms of AV nodal reentry are controllable with various therapeutic modalities. For acute termination, adenosine is probably the ideal agent. Prevention of recurrences can be achieved with several pharmacological agents, including beta-blockers, calcium channel blockers, and class Ia, Ic, and III antiarrhythmic agents. Curative therapy is now available with a variety of nonpharmacological methods. However, the most promising therapy at the present time is catheter modification of the AV node by ablation of either the fast or slow pathway, using radiofrequency energy. Ablation of the fast pathway carries a higher risk of second- or third-degree AV block. Slow pathway ablation, by providing a high rate of success and minimal risk of AV block, seems to be a more acceptable initial approach.

CONCLUSIONS

AV nodal reentry is a common cause of paroxysmal supraventricular tachycardia, and a precise diagnosis can be made with intracardiac electrophysiological evaluation. Although the arrhythmia responds to a variety of antiarrhythmic agents, curative therapy can now be offered with catheter modification of the AV node using radiofrequency energy. At the time of this writing, it seems that catheter modification of the AV node is rapidly becoming the therapy of initial choice in patients with symptomatic AV nodal reentrant tachycardia requiring treatment.
Myocardial glucose uptake in patients with insulin-dependent diabetes mellitus assessed quantitatively by dynamic positron emission tomography.
Authors: vom Dahl J , Herman W H , Hicks R J , Ortiz-Alonso F J , Lee K S , Allman K C , Wolfe E R , Kalff V , Schwaiger M
Published: June 2012

BACKGROUND

Animal studies have demonstrated reduced myocardial glucose utilization in the diabetic heart, suggesting abnormalities in glucose transport. This study was designed to evaluate myocardial glucose uptake as assessed by 2-fluoro-(fluorine-18)2-deoxy-D-glucose (FDG) and positron emission tomography (PET) in patients with insulin-dependent diabetes mellitus (IDDM) under standardized metabolic conditions.

METHODS AND RESULTS

A hyperinsulinemic-euglycemic clamp technique was used during PET data acquisition in nine healthy male volunteers and seven young male patients with a history of IDDM for less than 5 years. Oxidative metabolism was assessed with C-11 acetate, and glucose uptake was quantitatively measured with FDG using Patlak graphic analysis. Hemodynamic data and C-11 acetate kinetics were comparable. Myocardial glucose uptake averaged 0.44 +/- 0.12 mumol.g-1.min-1 in normal subjects and 0.43 +/- 0.16 mumol.g-1.min-1 in patients with IDDM (P = NS). Blood tracer clearance was also similar in both groups as determined by the ratio of peak blood tracer activity to the activity at 55 to 60 minutes after tracer injection. F-18 activity ratio between myocardium and blood pool averaged 7.2 +/- 3.4 in the normal heart and 7.5 +/- 3.0 in the diabetic heart (P = NS).

CONCLUSIONS

These data indicate that metabolic standardization and supplementation with insulin in young patients with IDDM is associated with myocardial glucose uptake similar to that observed in the normal heart. Chronic therapy with insulin may prevent the metabolic abnormalities observed in diabetic animal models.
Low-dose dobutamine echocardiography detects reversible dysfunction after thrombolytic therapy of acute myocardial infarction.
Authors: Smart S C , Sawada S , Ryan T , Segar D , Atherton L , Berkovitz K , Bourdillon P D , Feigenbaum H
Published: June 2012

BACKGROUND

Dysfunction after thrombolytic therapy of acute myocardial infarction (MI) may be reversible. Early after myocardial infarction, both reversible and irreversible injury may be manifested by regional wall motion abnormalities. Improved wall thickening during dobutamine infusion (dobutamine-responsive wall motion) may accurately identify reversibly injured segments.

METHODS AND RESULTS

To determine whether dobutamine-responsive wall motion accurately detects reversible postischemic dysfunction irrespective of infarct location, multistage (baseline, 4 and 12 micrograms.kg-1.min-1, and peak) dobutamine echocardiography (DE) was performed within 7 days of thrombolytic therapy. Resting echocardiography was repeated > or = 4 weeks after MI, and reversible dysfunction was defined as improved wall motion. The accuracy of dobutamine-responsive wall motion was compared with that of signs of early reperfusion, non-Q-wave MI, and peak creatine kinase (CK). Sixty-three patients underwent DE without complications. Follow-up echocardiograms were done in 51 (81%) of these patients, and wall motion improved in 22 (41%). Dobutamine-responsive wall motion during all stages of DE was very specific for reversible dysfunction (90% to 93%) but sensitive (86%) only when hemodynamics were not altered (low dose, 4 micrograms.kg-1.min-1). Non-Q-wave MI and a low peak CK (< 1000 IU/mL) were also specific (89% to 93%) but less sensitive (64% [P = .16] and 55% [P < .05], respectively). Signs of early reperfusion did not identify postischemic dysfunction. Low-dose dobutamine-responsive wall motion and non-Q-wave MI independently identified reversible dysfunction, but only dobutamine-responsive wall motion was sensitive in all infarct locations. Non-Q-wave MI was sensitive only in anterior infarction.

CONCLUSIONS

Multistage dobutamine echocardiography can be performed safely early after thrombolytic therapy. Low-dose dobutamine-responsive wall motion accurately detected reversible dysfunction in all infarct locations. Dobutamine-responsive wall motion and non-Q-wave infarction may be very useful for accurately identifying reversible dysfunction early after thrombolytic therapy for acute MI.