When Right May Not Be Right

Cardiac resynchronization therapy (CRT) in appropriately selected patients has been shown to improve cardiac function, heart failure symptoms, and survival. 1,2 On the basis of results of large, randomized trials, current American Heart Association/American College of Cardiology/Heart Rhythm Society guidelines recommend consideration of CRT in patients with cardiomyopathy on optimal medical therapy with left ventricular ejection fraction 35%, New York Heart Association class III or IV symptoms, and QRS duration 120 ms. 3 The idea of resynchronization therapy was derived from the seminal observations that intraventricular conduction abnormalities, extensively characterized in patients with left bundle-branch block (LBBB), adversely affect left ventricular mechanics. LBBB produces predictable changes in the left ventricular activation sequence.4,5 Abnormal activation of the interventricular septum and markedly delayed activation of the lateral left ventricle are typically seen in patients with LBBB. However, left ventricular activation patterns may be highly variable and more complex in patients with underlying cardiomyopathy.6 Delayed, dyssynchronous electromechanical activation in these segments leads to increased cardiac work, less efficient cardiac contraction, and lower cardiac output. 7 Electric (and mechanical) preactivation of the late-activating left ventricular region with CRT has been accepted to be prerequisite for successful clinical response. 8 Although remarkable symptomatic improvement is seen in many patients, up to 30% of subjects who participated in CRT trials failed to respond to therapy or may have worsened.2 Several clinical features have been identified that carry adverse clinical prognosis and predict less response to CRT therapy (Table). Despite extensive efforts, preimplant identification of nonresponders remains a significant problem and erodes the overall clinical (and cost) effectiveness of CRT therapy.