Link between change in cognition and left ventricular function following cardiac resynchronization therapy.

PURPOSE: In patients with heart failure, reduced cardiac ejection fraction has been associated with impaired cognition. Improving cardiac function may have beneficial effects on cognition; however, no controlled intervention studies have examined this possibility. Cardiac resynchronization therapy (CRT) is one intervention that has been shown to increase cardiac function. The goals of the current study were to (1) evaluate neuropsychological performance before and 3 months after crt and (2) examine follow-up neuropsychological performance of patients classified on the basis of extent of improved left ventricular ejection fraction (LVEF). METHODS: Twenty-seven patients with moderate to severe heart failure completed a neuropsychological assessment, 6-minute walk test, and transthoracic echocardiography before and 3 months after CRT. Patients were classified on the basis of improvement in LVEF. Results of a multivariate analysis of variance revealed a significant effect of improvement in LVEF on change in cognition (Wilks Λ, P = .031). RESULTS: Patients with improved LVEF demonstrated significant increases on measures of executive functioning (F = 8.57, P = .007) and visuospatial function (F = 7.52, P = .011) and less decline on global cognition (F = 5.73, P = .024) than those without LVEF improvement. CONCLUSIONS: Findings provide preliminary evidence that improved LVEF in response to CRT is associated with enhanced cognitive outcomes within 3 months of CRT. Patients with improved LVEF showed better outcomes on measures of executive functioning, global cognition, and visuospatial functioning. Future, controlled, large-scale trials will be necessary to determine whether there is an underlying causal relationship linking increase in LVEF and cognition.

Left ventricular ejection fraction for sudden death risk stratification and guiding implantable cardioverter-defibrillators implantation.

Current guidelines for use of implantable cardioverter-defibrillators (ICDs) for primary prevention of sudden death in patients with coronary disease and nonischemic dilated cardiomyopathy are based primarily on ejection fraction (EF) <30%-35%. The origin of this is based on EF as the common variable in several randomized clinical trials evaluating the ability of ICDs to reduce mortality. However, although low EF identifies one patient population at relatively increased risk for sudden death, there are a number of limitations to use of EF as the primary indication for ICD. Patients with low EF are not uniform with regard to other prognostic markers, and not all are at high risk for sudden death. Conversely, although patients with EF >35% as a group are at lower risk for sudden death, these patients are not uniform with regard to other prognostic variables. A variety of tests, including measures of reduced repolarization reserve and measures of altered sympathetic/parasympathetic balance, have identified patients with EF >35% at relatively high risk for sudden death. One explanation for this "disconnect" is that there is no evidence of any direct mechanistic link between low EF and mechanisms responsible for ventricular tachyarrhythmias.

Effects of cardiac resynchronization therapy on health-related quality of life in older adults with heart failure.

The aim of the study was to examine changes in health-related quality of life among older adults undergoing cardiac resynchronization therapy (CRT), a pacemaker based intervention for heart failure. Twenty-one patients (mean age = 68; SD = 8) completed measures of cardiovascular health and quality of life prior to and 3-months post-CRT. Following the intervention, patients reported improvements in their perception of their physical functioning (t = 2.8, p < 0.01) and feelings of vitality (t = 2.9, p < 0.01) on the MOS SF-36 Health Survey. Patients improved on objective clinical measures of exercise capacity, cardiac ejection fraction, and ventricular dyssynchrony. Younger patients reported greater improvements in physical functioning and decreases in pain. Higher baseline body mass index was associated with less improvement in physical functioning. Finally, patients with nonischemic heart failure reported greater improvements on multiple subscales of the SF-36 than patients with ischemic heart failure. This preliminary study documented improvements in health-related quality of life following CRT. The findings highlight that specific patient characteristics may be associated with quality of life changes. Future studies will benefit from including quality of life measures that assess multiple health-related domains.

True bipolar defibrillator leads have increased sensing latency and threshold compared with the integrated bipolar configuration.

BACKGROUND: Dual-coil implantable defibrillator (ICD) leads with true bipolar pacing and sensing (quadripolar leads) have been introduced to provide improved sensing characteristics without sacrificing defibrillation efficacy. Electrode configuration has been shown to have little effect on the amplitude or slew rate of the intracardiac electrogram, but does have an effect on the duration of the sensed electrogram. Closer spacing of the electrodes and smaller surface area of the anode may, therefore, result in a different latency of sensing relative to the onset of the QRS complex. METHODS: We tested the difference in ventricular sensing latency between integrated bipolar and true bipolar electrode configurations in 40 patients undergoing ICD implantation for standard indications (Medtronic Sprint Quattro lead in 26 and St. Jude Riata in 16). In addition, we compared R wave amplitude, pacing threshold, impedance, and slew rate. RESULTS: Sensing latency was significantly longer in the true bipolar configuration (Medtronic Sprint Quattro 45.2 +/- 14.7 msec in the true bipolar configuration, vs 37.4 +/- 18.2 msec in the integrated bipolar configuration, and St. Jude Riata, 43.5 +/- 9.8 msec true bipolar, vs 33.8 +/- 10.1 msec integrated bipolar, P < 0.01). There was no difference in R wave amplitude or slew rate. Pacing threshold and impedance were also greater in the true bipolar configuration than in the integrated bipolar configuration. CONCLUSION: The true bipolar configuration has a longer sensing latency than the integrated bipolar configuration. In some patients, this may require a longer programmed AV delay to avoid ventricular pseudofusion.

Optimising the use of beta-adrenoceptor antagonists in coronary artery disease.

beta-Adrenoceptor antagonists (beta-blockers) provide multiple benefits to patients with coronary artery disease. The 2001 American Heart Association and American College of Cardiology (AHA/ACC) guidelines for secondary prevention of myocardial infarction (MI) recommend initiating beta-adrenoceptor blockade in all post-MI patients and continuing therapy indefinitely. Atenolol and metoprolol have been shown to decrease vascular mortality in the acute-MI period. In the post-MI period timolol provided a 39% reduction in mortality in the Norwegian Multicenter Study group and propranolol was associated with a 26% reduction in mortality in BHAT (Beta-blocker Heart Attack Trial). beta-Adrenoceptor antagonist therapy results in reduction of myocardial oxygen demand and is therefore also effective for the treatment of angina pectoris. In CAST (Cardiac Arrhythmia Suppression Trial) beta-adrenoceptor antagonist therapy was associated with a significant reduction in arrhythmic death or cardiac arrest. In the post-MI amiodarone trials EMIAT (European Myocardial Infarct Amiodarone Trial) and CAMIAT (Canadian Amiodarone Myocardial Infarction Trial) there was a mortality benefit and decreased arrhythmic death in patients who received both amiodarone and beta-adrenoceptor antagonist therapy, compared with patients receiving amiodarone therapy alone. In the post-MI defibrillator (implantable cardioverter defibrillator [ICD]) trials, AVID (Antiarrhythmic Versus Implantable Defibrillator) and MUSTT (Multicenter Unsustained Tachycardia Trial), beta-adrenoceptor antagonist therapy was independently associated with improved overall survival. The exception was the ICD patients in MUSTT, and the benefit was attenuated in the amiodarone and ICD patients in AVID.AHA/ACC guidelines recommend the use of beta-adrenoceptor antagonists in all patients with symptomatic left ventricular dysfunction, based on several large, controlled heart failure trials. Extended-release metoprolol succinate reduced all-cause mortality by 34% in MERIT-HF (Metoprolol Controlled-Release/Extended-Release Randomized Intervention Trial in Heart Failure). Bisoprolol was associated with a 34% mortality benefit in CIBIS-II (Cardiac Insufficiency Bisoprolol Study II) and carvedilol was associated with a 35% mortality reduction in the COPERNICUS (Carvedilol Prospective Randomized Cumulative Survival) trial. beta-Adrenoceptor antagonists reduce perioperative mortality in patients undergoing cardiac as well as non-cardiac surgery; however, they remain underutilised. Contraindications to beta-adrenoceptor antagonist therapy include severe bradycardia, high-grade atrioventricular block, marked sinus node dysfunction and acute exacerbations of heart failure. Many of the perceived adverse effects of beta-adrenoceptor antagonists have not been substantiated by large clinical trials.beta-Adrenoceptor antagonists differ with regard to receptor selectivity, receptor affinity, lipophilicity and intrinsic sympathomimetic activity. Beneficial properties of beta-adrenoceptor antagonists may not always be extrapolated as a class effect, and patient selection and drug preparations should follow trial guidelines. The beneficial effects of beta-adrenoceptor antagonists are clearly proven in cardiac patients and those at risk for cardiac disease. They are indicated for heart failure and proven beneficial in patients undergoing cardiac and non-cardiac surgery. These benefits appear to be consistent across most patient subgroups. beta-Adrenoceptor antagonists are generally well tolerated, yet significant morbidity and mortality result from their continued underutilisation.

Primary prevention of sudden cardiac death: trials in patients with coronary artery disease.

Over the past decade, four randomized, controlled trials have evaluated therapies for prevention of sudden cardiac death in patients with coronary disease. Three of the four trials have shown significant reductions in mortality with implanted defibrillators. Two studies failed to demonstrate any benefit from pharmacologic antiarrhythmic therapy. The results of these studies in similar patient populations have erased any doubt regarding the ability of implanted defibrillators to reduce the risk of sudden death in patients with coronary disease. Our major challenge at this time is understanding how best to utilize this therapy in order to bring the benefit to the maximum number of patients while minimizing expense.

Management of arrhythmias in heart failure.

Arrhythmias continue to contribute significantly to morbidity and mortality in heart failure. Implantable defibrillators have assumed an increasingly important role in preventing sudden death and are recommended for patients who have been resuscitated from cardiac arrest, have unexplained syncope, or exhibit inducible ventricular tachycardia in the setting of prior myocardial infarction. The extension of survival conferred by implantable defibrillators is likely to be limited in patients with advanced heart failure. Ongoing trials will help define the use of these devices in heart failure populations, in whom atrial fibrillation is common and rate control and anticoagulation are of major importance. Among pharmaceutical options, amiodarone and dofetilide are the major agents for maintenance of sinus rhythm. The complexity of coexistent heart failure and arrhythmia management warrants close collaboration between heart failure and arrhythmia specialists.

Effect of beta-blocking therapy on outcome in the Multicenter UnSustained Tachycardia Trial (MUSTT).

BACKGROUND: Beta-blockers are known to reduce total mortality and sudden death in survivors of recent myocardial infarction. The effects of these agents in patients at high risk for sudden death with remote infarction are not clear. METHODS AND RESULTS: We analyzed the effect of beta-blockers on outcomes in 2096 patients with coronary artery disease, ejection fraction < or =40%, and spontaneous nonsustained ventricular tachycardia enrolled in the Multicenter UnSustained Tachycardia Trial (MUSTT). Forty-five percent of 702 patients with inducible sustained ventricular tachyarrhythmia and 35% of 1394 patients without inducible tachycardia were discharged from hospital receiving beta-blockers. Patients treated with beta-blockers were younger and had higher ejection fractions, higher rates of recent angina, and more recent infarction. beta-Blockers were associated with decreased total mortality for the entire study population (5-year mortality 50% with beta-blockers versus 66% without beta-blockers; adjusted P=0.0001). The mortality benefit associated with beta-blockers was present in patients with and without inducible tachycardia, except those treated with implantable defibrillators. There was no significant effect of beta-blocker therapy on the rate of arrhythmic death or cardiac arrest (adjusted P=0.2344). CONCLUSIONS: beta-Blocking agents have beneficial effects on survival of patients having characteristics of those enrolled in the MUSTT trial. These effects do not appear to be due to a specific antiarrhythmic effect of beta-blockers. The beneficial effects of beta-blockers were demonstrable in all patients except those treated with implantable defibrillators.

Management of the non-inducible patient.

Management of the patient without inducible arrhythmias is dictated by the clinical setting in which the arrhythmias occur. Decisions must be based on whether the patient is being treated for symptomatic arrhythmias, or is undergoing evaluation of risk for potentially lethal arrhythmias. The management is influenced by the anatomic substrate, as well as the clinical presentation. As with all diagnostic tests, the significance of the electrophysiology study depends on the clinical context, and this type of test reflects but one mechanism for tachycardia. Finally, it is critical to remember that the results of published clinical trials can be used to guide management decisions, only when the same stimulation protocol utilized in the trials is employed, and the patient has the same characteristics as those enrolled in the trial.

Management of arrhythmias in heart failure.

Arrhythmias often complicate the management of heart failure and contribute to mortality and morbidity. Implantable cardioverter defibrillators are the best protection from death caused by ventricular arrhythmias, but their benefit will probably be less in heart failure populations than has been observed in trials that have not focused on heart failure populations. Implantable cardioverter defibrillators are first-line therapy for high-risk patients who have been resuscitated from sustained ventricular tachycardia or ventricular fibrillation, who have inducible ventricular tachycardia in the setting of previous myocardial infarction, or who have unexplained syncope. Amiodarone is the major pharmacologic option for treatment of symptomatic arrhythmias. In selecting therapy, the severity of heart failure and cause of heart failure are important considerations. Atrial fibrillation occurs with increasing frequency as the severity of heart failure increases. Anticoagulation and rate control are important. Attempted maintenance of sinus rhythm with amiodarone or dofetilide is a reasonable consideration for selected patients, although the benefit of treatment strategies that seek to maintain sinus rhythm has not been demonstrated. Ongoing trials will provide further guidance for arrhythmia management.

Upgrade of permanent pacemakers and single chamber implantable cardioverter defibrillators to pectoral dual chamber implantable cardioverter defibrillators: indications, surgical approach, and long-term clinical results.

The aim of this study was to describe the indications for upgrade of pacemakers (PMs) or single chamber (VVIR) ICDs to dual chamber (DDDR) ICDs, surgical approach, hardware hybridization, and clinical outcome. Patients with preexisting PMs or VVIR ICDs may develop indications for ICD therapy or dual chamber pacing, respectively, that can be served by DDDR ICDs that incorporate preexisting transvenous leads. Fifty-seven patients underwent upgrade from PMs (29/57) or VVIR ICDs (28/57) to pectoral DDDR ICDs. Preexisting transvenous atrial and/or ventricular leads suitable for continued use were incorporated into new DDDR ICDs in 88.5% and 100% of PM and VVIR ICD upgrades, respectively. Acceptable DFTs were achieved in 56 (98.2%) of 57 patients. Appropriate VT/VF therapies were registered among 33.3% of patients during follow-up. No shocks due to lead noise were observed in any patient with hybridized transvenous leads. Atrial far-field R wave (FFRW) oversensing occurred in 24% of DDDR ICD systems incorporating a preexisting atrial lead. FFRW was overcome by programming reduced atrial sensitivity without interfering with the normal ICD system performance in all instances. Upgrade of PMs and VVIR ICDs to pectoral DDDR ICDs is safe and technically feasible in most patients. Preexisting transvenous leads can be successfully incorporated into new DDDR ICDs, simplifying the surgical procedure, minimizing transvenous hardware, and eliminating the possibility of hazardous pacemaker-ICD interactions.