Prophylactic implantable cardioverter-defibrillator therapy in patients with left ventricular systolic dysfunction: a pooled analysis of 10 primary prevention trials

Strategies to decrease sudden cardiac death in patients with left ventricular systolic dysfunction are evolving. Recent clinical trials have evaluated the role of prophylactic implantable cardioverter-defibrillators (ICDs) in patients with and without additional risk stratifiers. We pooled studies comparing treatment with and without ICDs from published data and presented abstracts, irrespective of QRS duration and etiology of systolic dysfunction. On the basis of the available clinical trials, implantation of an ICD for primary prevention of death provides a 7.9% absolute mortality reduction (p = 0.003) in patients with left ventricular (LV) systolic dysfunction who were receiving optimized medical therapy. This finding was not sensitive to the exclusion of any individual trial. The ICD is an effective primary preventative measure in patients who are at risk for death; however, the application of this therapy needs to be individualized for the patient, similar to drug therapies in LV systolic dysfunction. In health care settings without unlimited resources, optimal use of this therapy will require better risk stratification methods or lowering of the initial device cost.     

Beta-blocker therapy in patients with ventricular tachyarrhythmias in the setting of left ventricular dysfunction

Although several studies suggest beta blockers (BB) are effective in suppressing ventricular arrhythmias, less is known about their role in the treatment of patients with ventricular tachyarrhythmias associated with impaired left ventricular function. To assess the tolerance and efficacy of these agents, 32 patients presenting with either ventricular fibrillation (18) or sustained ventricular tachycardia (14) were studied during BB therapy. Left ventricular dysfunction (mean ejection fraction 29%) was present as a consequence of coronary artery disease (26) or cardiomyopathy (6). Baseline arrhythmia assessment revealed recurrent ventricular tachycardia in all patients. Antiarrhythmic drug therapy including BB was guided by programmed stimulation (10), exercise testing (8), ambulatory monitoring (12), or was given empirically (2). Beta blockers were well tolerated, as measured by exercise duration, which improved significantly, and by long-term maintenance, which continued in 23 of 32 (72%) patients. Over a mean follow-up of 668 days, patients treated with BB had a relatively low incidence of both sudden (3%) and nonsudden (9%) death. Thus, BB can be effective and well tolerated adjunct therapy in patients with a history of ventricular tachyarrhythmias in the setting of impaired left ventricular function.     

Cell therapy in patients with left ventricular dysfunction due to myocardial infarction

Objectives: The purpose of this study was to determine the impact of autologous transplantation of mononuclear bone marrow cells on myocardial function in patients with left ventricular (LV) dysfunction due to an acute myocardial infarction. Methods: The randomized study included 82 patients with a first acute myocardial infarction treated with a stent implantation. This presentation is a subanalysis of 47 patients with left ventricular dysfunction–EF (ejection fraction) ≤ 40%. Group H patients (n = 17) received higher number (100,000,000) of cells; Group L patients (n = 13) received lower number (10,000,000) of cells. The patients of control Group C (n = 17) were not treated with cells. The Doppler tissue imaging and single photon emission computed tomography were performed before cell transplantation and 3 months later. Results: At 3 months of follow‐up, the baseline EF of 35%, 36%, 35% in Groups H, L, and C increased by 6% (P < 0.01 vs. baseline), 5% (P < 0.01 vs. baseline), and 4% (P = NS vs. baseline), respectively, as assessed by single photon emission computed tomography (P = NS between groups). The baseline number of akinetic segments of 6.9, 7.0, and 6.2 in H, L, and C groups decreased by 1.7 (P < 0.01 vs. baseline), 1.5 (P < 0.01 vs. baseline), and 0.7 (P = NS vs. baseline, P = NS between groups), respectively, as demonstrated by echocardiography. Conclusion: In our study, the statistically important effect of transplantation of mononuclear bone marrow cells on myocardial function was not found. Only an insignificant trend toward the improvement of global LV EF fraction was found at 3‐month follow‐up.     

Driving and implantable cardioverter-defibrillator shocks for ventricular arrhythmias: results from the TOVA study.

OBJECTIVES: This study examined the risk of implantable cardioverter-defibrillator (ICD) shocks for ventricular tachycardia (VT) or ventricular fibrillation (VF) associated with driving. BACKGROUND: Concerns regarding VT/VF occurring during driving are the basis for driving restrictions in ICD patients; however, limited data are available to inform recommendations. METHODS: This study used a prospective nested case-crossover design to compare the risk of ICD shock for VT/VF both during and up to 60 min after an episode of driving as compared with that during other activities among 1,188 ICD patients enrolled in the TOVA (Triggers of Ventricular Arrhythmia) study. RESULTS: Over a median follow-up of 562 days, there were 193 ICD shocks for VT/VF with data on exposure to driving before ICD shock. The absolute risk of ICD shock for VT/VF within 1 h of driving was estimated to be 1 episode per 25,116 person-hours spent driving. The ICD shocks for VT/VF were twice as likely to occur within 1 h of driving a car as compared with other times (relative risk [RR] 2.24, 95% confidence interval [CI] 1.57 to 3.18). This risk was specific for shocks for VT/VF and occurred primarily during the 30-min period after driving (RR 4.46, 95% CI 2.92 to 6.82) rather than during the driving episode itself (RR 1.05, 95% CI 0.48 to 2.30). CONCLUSIONS: Although the risk of ICD shock for VT/VF was transiently increased in the 30-min period after driving, the risk was not elevated during driving and the absolute risk was low. These data provide reassurance that driving by ICD patients should not translate into an important rate of personal or public injury.     

Effect of cardiac resynchronization therapy on the incidence of ventricular arrhythmias in patients with an implantable cardioverter-defibrillator.

BACKGROUND: Cardiac resynchronization therapy (CRT) reduces mortality in selected patients with heart failure. However, this result may not be entirely related to the beneficial hemodynamic effects of CRT. OBJECTIVES: The purpose of this study was to assess retrospectively the effect of CRT on the incidence of appropriate therapy in patients with an implantable cardioverter-defibrillator (ICD). METHODS: Sixty-five patients (48 men and 17 women; mean age 58 +/- 13 years) with an ICD (31 biventricular, 34 dual-chamber) were included in the study. Clinical, ECG, and ICD stored data and electrograms were collected. RESULTS: Biventricular and dual-chamber ICDs were implanted in 31 and 34 patients, respectively, who had either ischemic (n = 36) or dilated cardiomyopathy (n = 29). Thirty-two (49%) patients received > or =1 appropriate ICD therapy during follow-up of 11 +/- 8 months. Thirty-five percent and 62% of patients with biventricular (n = 11) and dual-chamber ICDs (n = 21), respectively, received appropriate ICD therapy during the follow-up period (odds ratio = 0.340, P = .048). Stratifying the patients according to underlying heart disease and ejection fraction resulted in an adjusted odds ratio = 0.239 (P = .029). Comparing the rate of > or =1 appropriate ICD therapy between the two groups by Kaplan-Meier analysis and the log rank test resulted in P = .027. CONCLUSION: In this retrospective analysis, biventricular pacing was associated with a decreased incidence of sustained ventricular arrhythmias requiring ICD therapy. The antiarrhythmic effect of biventricular pacing could contribute to the reduction in mortality reported in recent large-scale clinical trials on CRT. However, further prospective studies are warranted to clarify this issue.     

Clinical outcome of patients with malignant ventricular tachyarrhythmias and a multiprogrammable implantable cardioverter-defibrillator implanted with or without thoracotomy: An international multicenter study

Objectives. The long-term efficacy and safety of a thirdgeneration implantable cardioverter-defibrillator implanted with thoracotomy and nonthoracotomy lead systems was evaluated in a multicenter international study.Background. The clinical impact of transvenous leads for nonthoracotomy implantation and pacing for bradyarrhythmias and tachyarrhythmias in implantable cardioverter-defibrillator systems is not well defined.Methods. The safety of the implantation procedure and clinical outcome of 1,221 patients with symptomatic and life-threatening ventricular tachyarrhythmias who underwent implantation of a third-generation cardioverter-defibrillator using either a thoracotomy approach with epicardial leads (616 patients) or a nonthoracotomy approach with endocardial leads (605 patients) in a nonrandomized manner was analyzed. The implantable cardioverter-defibrillator system permitted pacing, cardioversion, defibrillation, arrhythmia event memory and noninvasive tachycardia induction.Results. Successful implantation of an endocardial lead system was achieved in 665 (88.2%) of 686 patients and an epicardial system in 614 (99.7%) of 616 (p < 0.05). Perioperative 30-day mortality rate was 0.8% (1.8% including crossover) in endocardial implant recipients compared with 4.2% (p < 0.001) in epicardial implant recipients (3.6% without crossovers, p < 0.05, respectively). Implantation mortality risk was significantly lower for noathoracotomy systems irrespective of left ventricular ejection fraction or New York Heart Association functional class. Pacing therapies prevented need for cardioversion or defibrillation shocks in 89% of all ventricular tachycardia episodes and were comparably effective for both lead systems. Total survival rate at 2 years was significantly higher in endocardial (87.6%) than epicardial (81.9%) lead recipients (p < 0.001). Elimination of perioperative mortality from the analysis demonstrated comparable survival in both groups (p > 0.2).Conclusions. Third-generation cardioverter-defibrillators with monophasic waveforms can be successfully implanted with epicardial (99.7%) and endocardial (88.2%) lead systems. We conclude that endocardial leads should be the implant technique of first choice. Improved patient management and tolerance for device therapy is achieved with the addition of antitachycardia pacemaker capability in these systems.     

Arterial stiffness is associated with left ventricular dysfunction in patients with rheumatoid arthritis

Arterial stiffness (AS) has a detrimental effect on cardiovascular system particularly on left ventricle (LV). The aim of the study was to evaluate the impact of AS on LV functions in patients with rheumatoid arthritis (RA). Forty patients with RA and 25 age-sex matched control subjects (mean age 48.5?±?6.3 vs. 45.1?±?6.9 years, respectively, p?=?0.06) were enrolled in study. AS was assessed by carotid-femoral pulse wave velocity (CF-PWV) and heart rate corrected augmentation index (AIx@75) measured by applanation tonometry (SphygmoCor). LV function was evaluated using tissue Doppler-derived myocardial performance index (MPI) from lateral mitral annulus. CF-PWV (28.3?±?10.3 vs. 21.8?±?9.3 m/s, p?=?0.03), AIx@75 (10.2?±?2.3 vs. 9.2?±?1, %, p?=?0.01) and MPI (0.46?±?0.12 vs. 0.36?±?0.1, p?<?0.001) were significantly higher in patients with RA than in controls. LV MPI was found to be significantly positive correlated with CF-PWV, AIx@75, and ESR (r?=?0.360, p?=?0.005; r?=?0.334, p?=?0.009; r?=?0.293, p?=?0.023, respectively). Arterial stiffness parameters including CF-PWV and AIx@75 are associated with subclinical left ventricular dysfunction in patients with RA.     

Amiodarone-induced thyrotoxicosis: left ventricular dysfunction is associated with increased mortality

OBJECTIVE: Amiodarone-induced thyrotoxicosis (AIT) is a challenging management problem, since patients treated with amiodarone invariably have underlying heart disease. Consequently, thyrotoxicosis can significantly contribute to increased morbidity and mortality. The aim of this study was to compare the clinical outcome and hormone profiles of patients with AIT (n = 60) with those with Graves' thyrotoxicosis (n = 49) and toxic multinodular goitre (MNG, n = 40). DESIGN: A retrospective study of patients with AIT in a single institution was conducted. METHODS: Data from patients with AIT over 12 years were collected. RESULTS: Mean TSH levels were significantly suppressed in all three groups. However, there was no intergroup significant difference. Free thyroxine (T4) levels were significantly higher in AIT (45.6 +/- 3.5 pmol/l) and Graves' disease (44.6 +/- 4.0 pmol/l) compared with toxic MNG (31.5 +/- 5.1 pmol/l, P < 0.05). In contrast, free triiodothyronine (T3) levels were only significantly higher in Graves' disease (14.7 +/- 1.5 pmol/l, P = 0.002) compared with AIT (8.6 +/- 0.7 pmol/l) and toxic MNG (7.4 +/- 0.5 pmol/l). Six deaths occurred in the patients with AIT (10.0%, P < 0.01) and no deaths occurred in the other groups. Amiodarone treatment (P = 0.002) was the most significant predictor of death, whereas free T4, free T3 and age did not affect outcome. Within the amiodarone-treated group severe left ventricular dysfunction (P = 0.0001) was significantly associated with death. CONCLUSIONS: (i) AIT differs from other forms of thyrotoxicosis, and (ii) severe left ventricular dysfunction is associated with increased mortality in AIT.     

Effect of statin therapy on risk of ventricular arrhythmia among patients with coronary artery disease and an implantable cardioverter-defibrillator

Hydroxymethylglutaryl coenzyme-A reductase inhibitors, or statins, have been shown to decrease mortality rates in patients who have coronary artery disease. It has been postulated that part of the mortality benefit conferred by statins is due to a decrease in ventricular arrhythmias. We assessed the effect of statin therapy on recurrent ventricular arrhythmias in 281 patients who developed coronary artery disease after implantable cardioverter-defibrillator placement. Statin therapy was associated with a significant decrease in the risk of ventricular arrhythmia that would require implantable cardioverter-defibrillator therapy.     

CRT plus ICD in congestive heart failure. Use of cardiac resynchronization therapy and an implantable cardioverter-defibrillator in heart failure patients with abnormal left ventricular dysfunction

Cardiac resynchronization therapy (CRT) significantly improves functional status, exercise duration, left ventricular (LV) ejection fraction, death from progressive congestive heart failure (CHF), and hospitalization for CHF in patients with moderate-to-severe CHF, an abnormal LV ejection fraction, and a QRS duration on the electrocardiogram of 120 msec or more. In these patients, CRT reduces all-cause mortality, though not significantly. However, CRT plus. an implantable cardioverter-defibrillator (ICD) significantly reduces all-cause mortality. Compared with placebo, ICD therapy significantly reduced all-cause mortality by 33% in patients with class II or III CHF, an abnormal LV ejection fraction, and a QRS duration on the electrocardiogram of 120 msec or more.