What is treatment success in cardiac resynchronization therapy?

Cardiac resynchronization therapy (CRT) is an established treatment for symptomatic patients with heart failure, a prolonged QRS duration, and impaired left ventricular (LV) function. Identification of ‘responders’ and ‘non-responders’ to CRT has attracted considerable attention. The response to CRT can be measured in terms of symptomatic response or clinical outcome, or both. Alternatively, the response to CRT can be measured in terms of changes in surrogate measures of outcome, such as LV volumes, LV ejection fraction, invasive measures of cardiac performance, peak oxygen uptake, and neurohormones. This review explores whether these measures can be used in assessing the symptomatic and prognostic response to CRT. The role of these parameters to the management of individual patients is also discussed

A polymorphism within a conserved β(1)-adrenergic receptor motif alters cardiac function and β-blocker response in human heart failure

Heterogeneity of heart failure (HF) phenotypes indicates contributions from underlying common polymorphisms. We considered polymorphisms in the β(1)-adrenergic receptor (β(1)AR), a β-blocker target, as candidate pharmacogenomic loci. Transfected cells, genotyped human nonfailing and failing ventricles, and a clinical trial were used to ascertain phenotype and mechanism. In nonfailing and failing isolated ventricles, β(1)-Arg-389 had respective 2.8 ± 0.3- and 4.3 ± 2.1-fold greater agonist-promoted contractility vs. β(1)-Gly-389, defining enhanced physiologic coupling under relevant conditions of endogenous expression and HF. The β-blocker bucindolol was an inverse agonist in failing Arg, but not Gly, ventricles, without partial agonist activity at either receptor; carvedilol was a genotype-independent neutral antagonist. In transfected cells, bucindolol antagonized agonist-stimulated cAMP, with a greater absolute decrease observed for Arg-389 (435 ± 80 vs. 115 ± 23 fmol per well). Potential pathophysiologic correlates were assessed in a placebo-controlled trial of bucindolol in 1,040 HF patients. No outcome was associated with genotype in the placebo group, indicating little impact on the natural course of HF. However, the Arg-389 homozygotes treated with bucindolol had an age-, sex-, and race-adjusted 38% reduction in mortality (P = 0.03) and 34% reduction in mortality or hospitalization (P = 0.004) vs. placebo. In contrast, Gly-389 carriers had no clinical response to bucindolol compared with placebo. Those with Arg-389 and high baseline norepinephrine levels trended toward improved survival, but no advantage with this allele and exaggerated sympatholysis was identified. We conclude that β(1)AR-389 variation alters signaling in multiple models and affects the β-blocker therapeutic response in HF and, thus, might be used to individualize treatment of the syndrome

Preoperative evaluation of patients with, or at risk of, coronary artery disease undergoing non-cardiac surgery

The increasing number of patients with coronary artery disease undergoing major non-cardiac surgery justifies guidelines concerning preoperative evaluation, stress testing, coronary angiography, and revascularization. A review of the recent literature shows that stress testing should be limited to patients with suspicion of a myocardium at risk of ischaemia, and coronary angiography to situations where revascularization can improve long-term survival. Recent data have shown that any event in the coronary circulation, be it new ischaemia, infarction, or revascularization, induces a high-risk period of 6 weeks, and an intermediate-risk period of 3 months. A 3-month minimum delay is therefore indicated before performing non-cardiac surgery after myocardial infarction or revascularization. However, this delay may be too long if an urgent surgical procedure is requested, as for instance with rapidly spreading tumours, impending aneurysm rupture, infections requiring drainage, or bone fractures. It is then appropriate to use perioperative beta-block, which reduces the cardiac complication rate in patients with, or at risk of, coronary artery disease. The objective of this review is to offer a comprehensive algorithm to help clinicians in the preoperative assessment of patients undergoing non-cardiac surgery

ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM)

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