Justin Ghosh

Clinical trials update and cumulative meta‐analyses from the American College of Cardiology: WATCH, SCD‐HeFT, DINAMIT, CASINO, INSPIRE, STRATUS‐US, RIO‐Lipids and cardiac resynchronisation therapy in heart failure

This article continues a series of reports on recent research developments in the field of heart failure. Key presentations made at the American College of Cardiology meeting, held in New Orleans, Louisiana, USA in March 2004 are reported. These new data have been added to existing data in cumulative meta‐analyses. The WATCH study randomised 1587 patients with heart failure and left ventricular systolic dysfunction to warfarin, aspirin or clopidogrel. The study showed no difference between the effects of these agents on mortality or myocardial infarction, but hospitalisations for heart failure were higher on aspirin (22.2%) compared to warfarin (16.1%). The SCD‐HeFT study showed that ICD therapy reduced all‐cause mortality at 5 years by 23% in patients with predominantly NYHA class II heart failure and left ventricular systolic dysfunction, but amiodarone was ineffective. The DINAMIT study showed that ICD therapy was not beneficial in patients with left ventricular dysfunction after a recent MI, even in those with risk factors for arrhythmic death. In CASINO, levosimendan improved survival compared with dobutamine or placebo in patients with decompensated heart failure. INSPIRE showed that SPECT imaging can be used to assess risk early after acute MI safely and accurately. Rimonabant was shown to be safe and effective in treating the combined cardiovascular risk factors of smoking and obesity. An overview of new developments in cardiac resynchronisation therapy (CRT) in heart failure is also reported.

Cardiac resynchronisation for patients with heart failure due to left ventricular systolic dysfunction — a systematic review and meta-analysis

Randomised controlled trials generally suggest that cardiac resynchronisation improves outcomes in patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony. Our objective was to provide a valid synthesis of the effects of CRT on mortality, major morbidity, quality of life and implantation success rates.

Prognostic value of systolic mitral annular velocity measured with Doppler tissue imaging in patients with chronic heart failure caused by left ventricular systolic dysfunction

Objective: To assess the prognostic value of various conventional and novel echocardiographic indices in patients with chronic heart failure (CHF) caused by left ventricular (LV) systolic dysfunction. Methods: 185 patients with a mean (SD) age of 67 (11) years with CHF and LV ejection fraction < 45% despite optimal pharmacological treatment were prospectively enrolled. The patients underwent two dimensional echocardiography with tissue harmonic imaging to assess global LV systolic function and obtain volumetric data. Transmitral flow was assessed with conventional pulse wave Doppler. Systolic (Sm), early, and late diastolic mitral annular velocities were measured with the use of colour coded Doppler tissue imaging. Results: During a median follow up of 32 months (range 24–38 months in survivors), 34 patients died and one underwent heart transplantation. Sm velocity (hazard ratio (HR) 0.648, 95% confidence interval (CI) 0.463 to 0.907, p u200a=u200a 0.011), diastolic arterial pressure (HR 0.965, 95% CI 0.938 to 0.993, p u200a=u200a 0.015), serum creatinine (HR 1.006, 95% CI 1.001 to 1.011, p u200a=u200a 0.023), LV ejection fraction (HR 0.945, 95% CI 0.899 to 0.992, p u200a=u200a 0.024), age (HR 1.035, 95% CI 1.000 to 1.071, p u200a=u200a 0.052), LV end systolic volume index (HR 1.009, 95% CI 0.999 to 1.019, p u200a=u200a 0.067), and restrictive pattern of transmitral flow (HR 0.543, 95% CI 0.278 to 1.061, p u200a=u200a 0.074) predicted the outcome of death or transplantation on univariate analysis. On multivariate analysis, only Sm velocity (HR 0.648, 95% CI 0.460 to 0.912, p u200a=u200a 0.013) and diastolic arterial pressure (HR 0.966, 95% CI 0.938 to 0.994, p u200a=u200a 0.016) emerged as independent predictors of outcome. Conclusions: In patients with CHF and LV systolic dysfunction despite optimal pharmacological treatment, the strongest independent echocardiographic predictor of prognosis was Sm velocity measured with quantitative colour coded Doppler tissue imaging.

Multi-chamber pacing: a perfect solution for cardiac mechanical dyssynchrony?

See doi:10.1016/S1095-668X(02)00475-Xfor the article to which this editorial refers. nnWhen the heart fails, it becomes less efficient, as myocardial energy consumption rises without a corresponding increase in cardiac output. There are many possible reasons for this decline in cardiac efficiency (Fig. 1). Recently, because of the potential value of multi-site pacing, interest has focused on mechanical dyssynchrony, which encompasses a complex array of problems that often coexist in varying degrees along with ‘functional’ mitral regurgitation.1–3nnnn Fig. 1 nSome mechanisms of heart failure causation and progression (usually multiple mechanisms operating simultaneously conspire to cause progression of heart failure).nnnnIt is likely that mechanical dyssynchrony is common, although precisely how common is unclear, and will depend on the definition and the tools used to measure it. The presence and severity of cardiac dyssynchrony can be assessed directly using imaging techniques or indirectly by measuring time-intervals from a standard 12-lead echocardiography (ECG). ECG is the current method of choice owing to its wide availability, high temporal resolution and its ability to assess flow across the valves, although diagnostic criteria for cardiac dyssynchrony are still being refined.4 In the meantime, studies on relatively small numbers of patients have suggested that patients who have a QRS width ≥150ms very often have evidence of major inter- and intra-ventricular dyssynchrony on imaging.5 A high, but as yet uncertain, proportion of patients with QRS 120–150ms will also fulfil current echocardiographic criteria for ventricular dyssynchrony.6,7 Approximately, one in every four patients with heart failure secondary to left ventricular systolic dysfunction (LVSD) will have a QRS width >120ms on their surface ECG.8 The PR interval may be a useful marker for atrio-ventricular dyssynchrony,1 but <5% of patients with heart failure and LVSD will have a PR interval ≥220ms.8–11nnMechanical dyssynchrony and the possibility of …

Can cardiac-resynchronization therapy reduce mortality in patients suffering from advanced chronic heart failure?

Can cardiac-resynchronization therapy reduce mortality in patients suffering from advanced chronic heart failure?

Outcomes Related to First-Degree Atrioventricular Block and Therapeutic Implications in Patients With Heart Failure

The prevalence of first-degree atrioventricular block in the general population is approximately 4%, and it is associated with an increased risk of atrial fibrillation. Cardiac pacing for any indication in patients with first-degree heart block is associated with worse outcomes compared with patients with normal atrioventricular conduction. Among patients withxa0heart failure, first-degree atrioventricular block is present in anywhere between 15% and 51%. Data from cardiac resynchronization therapy studies have shown that first-degree atrioventricular block is associated with an increased risk of mortality and heart failure hospitalization. Recent studies suggest that optimization of atrioventricular delay in patients with cardiac resynchronization therapy is an important target for therapy; however, the optimal method for atrioventricular resynchronization remains unknown. Understanding the role of first-degree atrioventricular block in the treatment of patients with heart failure will improve medical and device therapy.

Applying evidence-based device care in cardiovascular patients: which patient with heart failure and what device?

In terms of engineering, clinical understanding and application, device therapy remains in its infancy. In clinical trials, implantable cardiac defibrillators (ICDs) have greatly reduced the rate of sudden death and had a modest impact on mortality in a relatively broad range of patients. They do not generally improve symptoms and may make them worse. Cardiac resynchronisation therapy (CRT) devices have been used more selectively - probably far too selectively - and have shown substantial improvement in symptoms and a large reduction in mortality both by reducing sudden death and death due to heart failure. These effects are not explained solely by improved ventricular function, and the clinical response to therapy has so far not been predicted well by any method of assessing cardiac function or dyssynchrony. Reduction in brady-arrhythmia-triggered sudden death may be an underestimated benefit of biventricular pacing. In recent trials, heart failure patients implanted with a device have had a remarkably low mortality. This forces the clinical community to contemplate universal device use for patients with heart failure, except in those who have irremediable, life-limiting, non-cardiac disease. For most patients this should be CRT or a combination of CRT and an ICD (CRT-D).

Cardiac resynchronization therapy with or without an implantable defibrillator: only indicated when everything else has failed?

Cardiac resynchronization therapy (CRT) is potentially an important new treatment for patients with heart failure due to left ventricular systolic dysfunction and cardiac dyssynchrony. There is growing evidence that CRT can improve symptoms although it is possible that similar benefits could be obtained by skillful manipulation of pharmacological therapy. There is also preliminary but inconclusive evidence to suggest that CRT alone or in synergy with an implantable cardiac defibrillator (ICD) may reduce morbidity and mortality. However, fashion is in danger of overtaking facts and it is important to ensure that benefits are not only statistically proven but clinically meaningful and cost-effective. Optimal timing of intervention and patient selection will be essential to ensure that treatment is deployed efficiently. If CRT with or without ICD becomes part of mainstream therapy for heart failure this will have far-reaching consequences for heart failure management. Implantation is a skilled and often time-consuming procedure. Long-term management of both CRT and ICD is likely to provide challenges in terms of lead technology, pacing thresholds and device management. Heart failure physicians will have to learn new skills and collaborate more closely with electrophysiologists. Such developments, in addition to the need for complex pharmacological interventions will accelerate the move away from general practice and towards specialist care for this most common of malignant diseases. If CRT does reduce mortality, it will graduate from an adjunctive therapy which could be used to an essential one that should be used as part of routine therapy for appropriate patients. Currently, CRT is a symptomatic therapy for patients with severe heart failure resistant to intensive pharmacological therapy delivered by a heart failure specialist.

Cardiac resynchronization therapy: redefining the role of device therapy in heart failure

That cardiac dyssynchrony can contribute to a decline in cardiac efficiency has been recognized in one form or another for at least 50 years. Although revascularization and β-blockers can improve cardiac synchrony, there was little interest in or awareness of this clinical entity until the advent of specific, highly effective therapy using atriobiventricular pacing, often described as cardiac resynchronization therapy. Over the last few years, significant advances in cardiac resynchronization therapy technology and the publication of large-scale clinical trials using cardiac resynchronization therapy devices in patients with heart failure have led to the widespread use of these devices. This review will briefly describe the complex nature of cardiac dyssynchrony, what is known about its epidemiology, the effects of cardiac resynchronization therapy, appropriate patient selection, practical aspects, such as implantation and monitoring, and some still unanswered questions.