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INSIDE THIS ISSUE

Inside This Issue

	Quarterly Focus Issue: Heart Rhythm Disorders

Top Quarterly Focus Issue: Heart... Interventional Cardiology Valvular Heart Disease Viewpoint

Robert J. Myerburg, Vivek Reddy, Agustin Castellanos

Myerburg and colleagues review the literature regarding the indications for implantable cardioverter-defibrillators (ICDs). These indications come from randomized clinical trials, observational data, and expert opinion. The authors note that the randomized trials are limited by inadequate stratification designs due to high costs. Chief among these limitations is the varying cut-points used for ejection fraction (EF) as an enrollment criteria; if this had been treated as a continuous variable, the relationship between the risk of sudden cardiac death and EF would be clearer. The indications for ICD are reviewed for a variety of indications from myocarditis to long QT syndrome. The paper ends with a suggestion that the research and health care delivery arms of the health care enterprise should cooperate in research design and funding.

State-of-the-Art Paper.   The Effects of RV Apical Pacing on Ventricular Function
764

Laurens F. Tops, Martin J. Schalij, Jeroen J. Bax

Tops and colleagues review the increasing indirect evidence, derived from large pacing mode selection trials and observational studies, that conventional right ventricle (RV) apical pacing may have detrimental effects on left ventricular function. These detrimental effects appear to be related to the abnormal electrical and mechanical activation pattern of the ventricles (or ventricular dyssynchrony). Upgrading from RV pacing to cardiac resynchronization therapy (CRT) may reduce the deleterious effects of RV pacing. The available alternative strategies are discussed, including the utility of CRT or alternative RV pacing sites such as the RV outflow tract.

Year in Cardiology Series.   Clinical Cardiac Electrophysiology
777

Gregory M. Marcus, Edmund Keung, Melvin M. Scheinman

Marcus and colleagues review the most relevant publications from the last year related to electrophysiology. Among the highlights is a study of rate versus rhythm control in patients with atrial fibrillation and heart failure, which found no significant outcome differences between the 2 groups. Important new drug developments in the treatment of atrial fibrillation, including vernakalant and dronedarone, are discussed. Important new insights into the genetic mechanisms of atrial fibrillation are presented as well as new gene discoveries for patients with various genetic arrhythmia disorders. The risk associated with implantable cardioverter-defibrillator shocks and overall mortality is discussed. Finally, the implications of various T-wave alternans trials are explored.

Clinical Research.   AF CL Can Identify Those With Permanent AF Who May Benefit From Ablation
788

Seiichiro Matsuo, Nicolas Lellouche, Matthew Wright, Michela Bevilacqua, Sébastien Knecht, Isabelle Nault, Kang-Teng Lim, Leonardo Arantes, Mark D. O'Neill, Pyotr G. Platonov, Jonas Carlson, Frederic Sacher, Méelèze Hocini, Pierre Jaïs, Michel Haïssaguerre

Matsuo and colleagues investigated if certain pre-procedural clinical variables could predict procedural and clinical success of catheter ablation in patients with persistent atrial fibrillation (AF). Persistent AF was terminated in 84% by ablation. The surface electrocardiogram (ECG) AF cycle length (CL) was the only independent predictor of AF termination. In multivariate analysis, the surface ECG AF CL and the AF duration predicted clinical success of freedom from AF. The surface ECG AF CL is a clinically useful pre-ablation tool to predict patients in whom sinus rhythm is more likely to be restored, and maintained, by catheter ablation.

Editorial Comment: David J. Wilber, p. 796

Clinical Research.   VT Originating From the Epicardium in Patients With Nonischemic Cardiomyopathy

799

Oscar Cano, Mathew Hutchinson, David Lin, Fermin Garcia, Erica Zado, Rupa Bala, Michael Riley, Joshua Cooper, Sanjay Dixit, Edward Gerstenfeld, David Callans, Francis E. Marchlinski

This paper by Cano and colleagues describes their experience in evaluating and treating patients with nonischemic cardiomyopathy (NICM) and suspected epicardial ventricular tachycardia (VT). Twenty-two patients underwent detailed endocardial and epicardial bipolar voltage maps and VT ablation. Confluent low-voltage areas, consistent with scar, were present in the epicardium in 82% and 54% of the endocardial maps. The epicardial low-voltage areas also showed wide (>80 ms), split, and/or late electrograms. During follow-up, 78% of the patients with epicardial VT were free from recurrence after ablation. This is the first study to characterize the epicardial electroanatomical substrate in patients with NICM.

Editorial Comment: Kalyanam Shivkumar, Roderick Tung, p. 809

Clinical Research.   Polymorphism in KCNE1 Causes LQTS in Some Patients
812

Yukiko Nishio, Takeru Makiyama, Hideki Itoh, Tomoko Sakaguchi, Seiko Ohno, Yin-Zhi Gong, Satoshi Yamamoto, Tomoya Ozawa, Wei-Guang Ding, Futoshi Toyoda, Mihoko Kawamura, Masaharu Akao, Hiroshi Matsuura, Takeshi Kimura, Toru Kita, Minoru Horie

KCNE1 encodes the beta-subunit of cardiac voltage-gated K⁺ channels. D85N, a KCNE1 polymorphism in the c-terminal, is known to be a functional variant associated with drug-induced long QT syndrome (LQTS) in previous studies. In this study, Nishio and colleagues performed genetic screening in LQTS probands and in healthy control patients along with biophysical assays for the D85N variant in mammalian cells. The allele frequency for D85N carriers was 0.81% in healthy people and 3.9% in those with LQTS. In a heterologous expression study with Chinese hamster ovarian cells, KCNE1-D85N showed significant loss-of-function effects on both KCNQ1- and KCNH2-encoded channel currents. The KCNE1-D85N polymorphism is a functional variant that can produce an LQTS phenotype by interacting with KCNH2 and KCNQ1.

Editorial Comment: Elizabeth S. Kaufman, p. 820

Clinical Research.   ECG Changes After ICD Testing May Identify High-Risk Patients

822

Larisa G. Tereshchenko, Mitchell N. Faddis, Barry J. Fetics, Karl E. Zelik, Igor R. Efimov, Ronald D. Berger

Tereshchenko and colleagues studied near field (NF) bipolar right ventricular (RV) electrograms (EGMs) during induced ventricular fibrillation (VF) and 10 s after rescue implantable cardioverter-defibrillator (ICD) shock to see if these EGMs predicted the subsequent risk of death or hospitalization due to heart failure. A local injury current (LIC) on NF RV EGM was defined as a deviation of EGM potential 1 mV or 15% of the preceding R-wave amplitude. LIC was observed in approximately one-third of patients. After adjustment for baseline prognostic factors, patients with LIC were more likely to die or be hospitalized (hazard ratio: 2.7). The authors propose a "triple-hit" hypothesis to explain the genesis of LIC on the NF RV EGM: 1) cardiac myocytes are fragile due to an underlying condition; 2) mechanical injury occurs due to lead placement; and 3) a rescue ICD shock elicits LIC, especially if the first 2 "hits" are present.

Editorial Comment: Richard K. Shepard, Kenneth A. Ellenbogen, p. 829

Clinical Research.   High Risk for Subsequent Events for Infants With LQTS and History of ACA

832

Carla Spazzolini, Jamie Mullally, Arthur J. Moss, Peter J. Schwartz, Scott McNitt, Gregory Ouellet, Thomas Fugate, Ilan Goldenberg, Christian Jons, Wojciech Zareba, Jennifer L. Robinson, Michael J. Ackerman, Jesaia Benhorin, Lia Crotti, Elizabeth S. Kaufman, Emanuela H. Locati, Ming Qi, Carlo Napolitano, Silvia G. Priori, Jeffrey A. Towbin, G. Michael Vincent

This study evaluated the clinical and prognostic aspects of long QT syndrome (LQTS)-related cardiac events that occur in the first year of life. The study population consisted of over 3,000 patients with a corrected QT interval >450 ms enrolled in the International LQTS Registry, including 20 patients with sudden cardiac death (SCD), 16 patients with aborted cardiac arrest (ACA), and 34 patients with syncope. ACA before age 1 year was associated with a hazard ratio of 23.4 for another ACA or SCD before age 10 years. Patients with LQTS who experience ACA during the first year of life are at very high risk for subsequent ACA or death.

Editorial Comment: John Triedman, p. 838

Clinical Research.   Sympathetic Activation Leads to an Increase in QT Variability, a Risk Factor for SCD
840

Gianfranco Piccirillo, Damiano Magrì, Masahiro Ogawa, Juan Song, Voon J. Chong, Seongwook Han, Boyoung Joung, Eue-Keun Choi, Samuel Hwang, Lan S. Chen, Shien-Fong Lin, Peng-Sheng Chen

Piccirillo and colleagues investigated the relationship between the nervous system and the risk of sudden cardiac death (SCD) in a canine model of nonischemic cardiomyopathy. Three electrodes along with a pacemaker were implanted in canines. One electrode monitored integrated left stellate-ganglion nervous activity (iSGNA), another integrated vagus nerve activity (iVNA), and the third recorded a surface electrocardiogram (ECG). After measurements were obtained, rapid pacing was used to cause a tachycardia-induced cardiomyopathy. Sample recordings were then divided into periods of high or low sympathetic activity based on the iSGNA data. In the high sympathetic activity subgroup, QT variability index (QTVI) increased from baseline to congestive heart failure (CHF), but was unchanged during low sympathetic activity. The baseline QTVI correlated inversely with iVNA, but during CHF, the QTVI correlated directly with iSGNA. These results confirm that sympathetic activation is associated with an increase in the QT interval and QTVI in subjects with myocardial dysfunction.

Editorial Comment: Ronald D. Berger, p. 851

	Interventional Cardiology

Top Quarterly Focus Issue: Heart... Interventional Cardiology Valvular Heart Disease Viewpoint

 
Interventional Cardiology.   No Significant Differences Between PES and SES for Left Main Stenting

853

Jong-Young Lee, Duk-Woo Park, Sung-Cheol Yun, Seung-Whan Lee, Young-Hak Kim, Cheol Whan Lee, Myeong-Ki Hong, Seong-Wook Park, Seung-Jung Park

Lee and colleagues evaluated the long-term clinical outcomes after implantation of sirolimus-eluting stents (SES) or paclitaxel-eluting stents (PES) among patients with unprotected left main coronary artery (LMCA) disease. Over 850 consecutive patients with unprotected LMCA stenosis were treated with SES (80%) or PES (20%), with the choice based on operator discretion. Baseline clinical and angiographic characteristics were similar in the 2 groups. During 3 years of follow-up, there were comparable adjusted rates of death, myocardial infarction, target vessel revascularization, and stent thrombosis. In patients with unprotected LMCA disease undergoing drug-eluting stent implantation, SES and PES have similar long-term clinical outcomes.

	Valvular Heart Disease

Top Quarterly Focus Issue: Heart... Interventional Cardiology Valvular Heart Disease Viewpoint

 
Valvular Heart Disease.   Failure of Guideline Adherence for Intervention in Patients With Severe Mitral Regurgitation
860

David S. Bach, Mazen Awais, Hitinder S. Gurm, Sarah Kohnstamm

Bach and colleagues evaluated the incidence with which adult patients with significant mitral regurgitation (MR) do not undergo surgical intervention despite guideline indications for surgery. Three hundred patients were retrospectively identified who had moderate-to-severe or severe MR on echocardiographic imaging during 2005. Mitral surgery was performed in 16% of patients with functional MR, mostly due to heart failure or during another cardiac surgical procedure. Mitral surgery was performed in 53% of patients with organic MR. Using American College of Cardiology/American Heart Association guidelines, 1 or more indication for intervention was present in 74% of unoperated patients, most often New York Heart Association functional class II to III symptoms or ejection fraction <60%. Surgical intervention may occur in only 50% of patients with organic MR despite guideline indications for intervention in the majority.

	Viewpoint

Top Quarterly Focus Issue: Heart... Interventional Cardiology Valvular Heart Disease Viewpoint

 
Cardiomyopathy.   Myocardial Ischemia is an Important Component of HCM

866

Martin S. Maron, Iacopo Olivotto, Barry J. Maron, Sanjay K. Prasad, Franco Cecchi, James E. Udelson, Paolo G. Camici

Maron and colleagues review the literature linking myocardial ischemia and hypertrophic cardiomyopathy (HCM). Autopsy studies have found that the intramural coronary arterioles have thickened intimal and/or medial layers, which impinge luminal cross-sectional area. Positron emission tomography studies have demonstrated a blunted increase of myocardial blood flow (MBF) after dipyridamole infusion. Stress cardiac magnetic resonance imaging (CMR) with late gadolinium enhancement (LGE) has also demonstrated that MBF is reduced in relation to the magnitude of wall thickness, especially in segments with LGE (i.e., fibrosis). These CMR observations suggest an association between ischemia, fibrosis, and left ventricular remodeling, linking abnormal MBF due to microvascular dysfunction to ischemia-mediated myocyte death, and ultimately replacement fibrosis.

Related Articles

Indications for Implantable Cardioverter-Defibrillators Based on Evidence and Judgment

Robert J. Myerburg, Vivek Reddy, and Agustin Castellanos
J. Am. Coll. Cardiol. 2009 54: 747-763. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Search for Related Content Related Collections Related Articles