Basic science of cardiac resynchronization therapy: molecular and electrophysiological mechanisms.
Basic science of cardiac resynchronization therapy: molecular and electrophysiological mechanisms.
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DOI：
10.1161/circep.111.962746
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发表时间：
2012-06-01
期刊：
影响因子：
--
通讯作者：
Tomaselli GF
中科院分区：
文献类型：
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作者：
Cho H;Barth AS;Tomaselli GF
Electromechanical dyssynchrony can markedly worsen heart failure (HF) morbidity and mortality, independent of traditional risk factors. 1–4 Depending on the metric used, current estimates of the prevalence of dyssynchrony vary from 25–30% in patients with HF (based on QRS widening) up to 60%, based on tissue Doppler or MRI measures of dyssynchronous contraction of the left ventricle (LV). 5, 6 Cardiac resynchronization therapy (CRT) or biventricular pacing has emerged as a promising option to treat patients with HF and dyssynchronous contraction. 7–9 The past few decades have seen the rise of pharmacotherapy, primarily through agents that antagonize the effect of excessive concentrations of circulating neurohormones, yet, HF-related morbidity and mortality remain high. 3–6 Biventricular stimulation has been demonstrated to improve contractile performance in patients with mechanical dyssynchrony acutely and chronically while also prolonging long-term survival—something not yet achieved by drug therapy. 10 Although the clinical and mechanical effectiveness of CRT are well described, 30% of patients do not benefit from CRT and clinical criteria to identify CRT nonresponders remain elusive8, 11, 12 Currently, the most widely used predictor of reverse remodeling is the presence of marked mechanical dyssynchrony before CRT, as indexed by the width of the QRS. 13 Mechanical dyssynchrony seems important, yet imaging-based measures have not predicted response well14 and even improvement in dyssynchrony after initiation of CRT only weakly predicts chronic response. 15 Limited understanding of the molecular mechanisms underlying reverse cardiac remodeling induced by CRT has hampered the selection of potential responders. In this review, we focus on the electrophysiological aspects and molecular networks underlying the benefits of CRT. We will review how CRT homogenizes regional differences in stress kinase signaling and electric remodeling and then review its global effect on myocyte function and its broader impact on the cardiac ventricular transcriptome. A comprehensive understanding of the molecular features of dyssynchronous contraction in the failing heart (DHF) and its reversibility by biventricular pacing promises to identify sets of biological markers for the selection of patients who will benefit most from CRT and, in a more general sense, to advance our knowledge of HF-associated pathophysiological processes.
