Congress Reports

September 5, 2005: In the second report from this satellite symposium, held at the European Society of Cardiology’s annual congress in Stockholm, Sweden, presentations focused on which treatment modalities really make a difference in the prevention of sudden death, and the importance of implantable cardioverter defibrillators (ICDs) and the effects of biventricular pacing when added on top of optimal medical management.BR/>Read the first report from this symposium by clicking here.

Effects of non-beta-blocking agents including amiodarone on sudden cardiac death
Professor John McMurray, Western Infirmary, Glasgow, Scotland, UK

ProfessorMcMurray reviewed the evidence that certain pharmacological agents are able to reduce the risk of sudden death. In particular he focused on patients with arterial disease (mainly coronary artery disease) and heart failure (HF). He began by stating that the benefits of angiotensin-converting enzyme (ACE) inhibitors in acute myocardial infarction (MI) and HF are well known but added that although evidence for reducing sudden death in HF is inconclusive, a meta-analysis of 15 trials investigating ACE inhibitors in acute MI has shown a 20% relative risk reduction for sudden death.

ProfessorMcMurray continued his presentation with a brief description of drugs that also target the renin-angiotensin system (RAS). The angiotensin-receptor blocker (ARB) candesartan has been shown to reduce the risk of sudden death by 20% in patients with HF and a low left ventricular ejection fraction.A further study has shown that the ARB valsartan reduces sudden death to a similar extent as the ACE inhibitor captopril.

Another treatment clearly shown to reduce sudden death in HF and MI is the aldosterone antagonist spironolactone. In RALES, spironolactone reduced the risk of sudden death by 29% and eplerenone rapidly reduced the risk of sudden death by 21%, even when administered on top of extensive secondary preventive treatment (including an ACE inhibitor and beta-blocker).

In continuing his presentation, Professor McMurray expressed surprise that he could find little evidence that antiplatelet or statin treatment reduce the risk of sudden death. He highlighted that the Swedish Angina Pectoris Aspirin Trial (SAPAT) had shown the addition of 75 mg aspirin to sotalol in comparison to sotalol plus placebo led to a trend of reduced sudden death but this trend was not statistically significant. Similarly, pravastatin was associated with a reduced mortality rate compared with placebo but in this trial no statistical analysis was carried out.

The anti-arrhythmic drug amiodarone is the only non-beta-blocking drug that has been shown to convincingly reduce the risk of sudden death, explained Dr McMurray. However, he showed that the effect of amiodarone on all-cause mortality is less convincing (approximately 13%) and that the reduction in sudden death observed (29%) has been shown only in a meta-analysis of individual trials.

In summarizing his presentation, Professor McMurray outlined that non-beta-blocking drugs can reduce the risk of sudden death in high-risk patients, which contributes to their effects on overall mortality. He added, however, that amiodarone reduces sudden death but has a less certain effect on all-cause mortality.

He concluded that most effective treatments for MI and HF that are able to reduce all-cause mortality probably reduce sudden death, although some are more effective than others. Furthermore, he stressed that these treatments almost certainly reduce sudden death indirectly through preventing coronary occlusion or by stabilizing electrically unstable myocardium (e.g. reducing ventricular dilation and fibrosis, improving autonomic function and preventing electrolyte abnormalities).

Optimal treatment of today - prophylactic medications and in certain patients combined with intracardiac defibrillator
Dr. Michael Bristow, University of Colorado Health Sciences Center, Denver, Colorado, USA

Dr. Michael Bristow began his presentation by explaining that drug development in the treatment of HF is slowing down but that mechanical devices are ably “filling the gap.” He continued by outlining that despite the favorable effects of beta-blockers and drugs that affect the RAS, sudden cardiac death remains a serious problem in patients with HF. He explained that the percentage of patients dying as a result of sudden death is inversely related to the severity of HF but the absolute number of patients dying suddenly increases as HF progresses. In essence, sudden death is a major problem throughout the spectrum of systolic dysfunction/HF and necessitates specific therapeutic targeting.

In the next section of his presentation, Dr. Bristow discussed the use of ICDs. These devices, with or without biventricular pacing, have been shown to specifically lower sudden death incidence in HF patients (decrease in mortality of approximately 30%). However, he explained that their effects are not uniform across the spectrum of HF and they are most useful in patients with chronic or less advanced HF. As HF progresses to New York Heart Association (NYHA) class III, pump failure deaths become as prevalent as sudden deaths and the impact of ICDs is much reduced. In NYHA class IV patients, pump failure deaths predominate and ICDs do not have a favorable impact on total mortality.

However, Dr. Bristow pointed out that the effectiveness of ICDs in more severe heart failure (NYHA class III and IV) is improved considerably when used in combination with a biventricular pacer, otherwise referred to as cardiac resynchronization therapy (CRT). The CRT devices organize ventricular contraction and increase pump volume, which leads to improved functional capacity and patient quality of life, and may also reverse contractile dysfunction. In NYHA class III patients, a CRT with a defibrillator (CRT-D) reduces sudden death markedly and has a very favorable impact on total mortality. In many cases (65% of patients), a CRT-D is able to convert NYHA class IV patients back to class III or even class II.

In summary, Dr. Bristow outlined that although NYHA class IIIb or IV HF can be a relative contraindication for an ICD, a CRT-D device has numerous beneficial effects. He concluded that in advanced HF, the pharmacologic/device therapeutic approach must incorporate strategies that address pump failure death specifically whereas in less advanced HF, therapy may be more selective in order to reduce the incidence of sudden death.

Read the first report from this symposium by clicking here.