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INSIDE THIS ISSUE

Inside This Issue

	Quarterly Focus Issue: Heart Rhythm Disorders

Top Quarterly Focus Issue: Heart... Hypertension Congenital Heart Disease

Joseph D. Mishkin, Sherry J. Saxonhouse, Gregory W. Woo, Thomas A. Burkart, William M. Miles, Jamie B. Conti, Richard S. Schofield, Samuel F. Sears, Juan M. Aranda, Jr

An estimated 20% to 35% of heart failure (HF) patients who receive an implantable cardioverter-defibrillator (ICD) for primary prevention will experience an appropriate shock within 1 to 3 years, and 33% will experience an inappropriate shock. An ICD shock is associated with a 2- to 5-fold increase in mortality, with the most common cause being progressive HF. This review by Mishkin and colleagues describes an evidence-based, multidisciplinary strategy for evaluating and managing HF patients who receive an ICD shock. Interventions addressed include pharmacologic and device-based strategies such as adding amiodarone, titrating HF medications, adjusting ICD sensitivity, and employing antitachycardia pacing.

Viewpoint.   The Early ICD Paradox

2001

Jeffrey J. Goldberger, Rod Passman

The risk of sudden cardiac death (SCD) is highest early after a myocardial infarction and progressively declines over time; however, early implantable cardioverter-defibrillator (ICD) placement has failed to improve outcomes in several clinical trials. Goldberger and Passman explore this acute myocardial infarction (MI)–sudden cardiac death paradox in a Viewpoint paper. They offer 3 potential explanations: 1) these cases of SCD may not be due to arrhythmias; 2) ejection fraction may not be an adequate risk stratifier in this population; and 3) the act of device implantation and testing may be deleterious and thereby offset any potential benefits. Further investigation is needed to delineate the actual causes of death in the early post-MI period and to determine which interventions would be of benefit.

Clinical Research.   Different Risk Factors for Sudden Cardiac Arrest in Men and Women
2006

Sumeet S. Chugh, Audrey Uy-Evanado, Carmen Teodorescu, Kyndaron Reinier, Ronald Mariani, Karen Gunson, Jonathan Jui

Chugh and colleagues noted that there are significant sex-based differences in the prevalence of sudden cardiac arrest (SCA) and used the Ore-SUDS (Oregon Sudden Unexpected Death Study) to explore if the risk factors for SCA in men and women are the same. All cases meeting criteria for SCA in the Portland, Oregon, metropolitan area were ascertained using multiple sources, and medical records were reviewed. Over 1,500 adult SCA cases were identified (women 36% vs. men 64%). Women were older and were significantly less likely to have severe left ventricular dysfunction or previously recognized coronary artery disease. These findings indicate that fewer women with SCA would have been eligible for prophylactic implantable cardioverter-defibrillator placement, which suggests the need for other methods of SCA risk stratification.

Clinical Research.   Improved Transtelephonic Pacemaker Interrogation May Improve Outcomes

2012

George H. Crossley, Jane Chen, Wassim Choucair, Todd J. Cohen, Douglas C. Gohn, W. Ben Johnson, Eleanor E. Kennedy, Luc R. Mongeon, Gerald A. Serwer, Hongyan Qiao, Bruce L. Wilkoff, for the PREFER Study Investigators

Currently, pacemakers are fully interrogated in person at 6- to 12-month intervals, and some models transmit telephonically limited information, such as a current rhythm strip, more frequently. Crossley and colleagues compared this standard of care with newer remote monitoring technology that enables full device interrogation including reviewing stored electrograms. The primary end point was the time to first diagnosis of a clinically actionable event, and this occurred earlier in the Remote arm (6 months) than in the Control arm (8 months). Two percent of the events in the Control arm and 66% of the events in the Remote arm were identified remotely. The ability to review stored events when pacemakers are interrogated remotely can lead to earlier diagnoses of status changes, such as paroxysmal atrial fibrillation, that may require a change in treatment.

Editorial Comment: Mark H. Schoenfeld, p. 2020

Clinical Research.   Risk of Developing AF Is Not Affected by Antihypertensive Class
2023

L. Julian Haywood, Charles E. Ford, Richard S. Crow, Barry R. Davis, Barry M. Massie, Paula T. Einhorn, Angela Williard, for the ALLHAT Collaborative Research Group

This subanalysis of the ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) examined the incidence of new-onset atrial fibrillation or atrial flutter (AF/AFL) in subjects who were randomly assigned to amlodipine, lisinopril, doxazosin, or chlorthalidone. New-onset AF/AFL, which occurred in 2.0% of patients, did not differ by antihypertensive treatment assignment or by assignment to pravastatin versus usual care. There was a nearly 2.5-fold increase in mortality risk when AF/AFL was present at baseline or developed during the trial. In this high-risk hypertensive population, pre-existing and new-onset AF/AFL were both associated with increased mortality, but these results do not offer guidance on medical interventions to reduce the risk of developing AF/AFL.

Clinical Research.   CHADS₂ Score Predicts Risk of Left Atrial Appendage Thrombus

2032

Sarinya Puwanant, Brandon C. Varr, Kevin Shrestha, Sarah K. Hussain, W. H. Wilson Tang, Ruvin S. Gabriel, Oussama M. Wazni, Mandeep Bhargava, Walid I. Saliba, James D. Thomas, Bruce D. Lindsay, Allan L. Klein

Puwanant and colleagues sought to determine if patients with a low CHADS₂ score require a routine screening transesophageal echocardiogram (TEE) before pulmonary vein isolation (PVI). Pre-PVI TEEs from over 1,000 atrial fibrillation (AF) patients were reviewed. The prevalence of LA/LAA thrombus, sludge, and spontaneous echo contrast was 0.6%, 1.5%, and 35%, respectively. The prevalence of left atrial/left atrial appendage (LA/LAA) thrombus/sludge increased with ascending CHADS₂ score. No patient with a CHADS₂ score of 0 had LA/LAA sludge/thrombus. The prevalence of LA/LAA sludge/thrombus in patients with AF undergoing a pre-PVI screening TEE is very low (<2%) and increases significantly with higher CHADS₂ scores, suggesting that patients with CHADS₂ of 0, who met the study entry criteria, may not require pre-PVI TEE.

Editorial Comment: Bradley P. Knight, p. 2040

Clinical Research.   Frequency of Atrial Arrhythmias After Heart or Lung Transplants
2043

José Dizon, Kimberly Chen, Matthew Bacchetta, Michael Argenziano, Donna Mancini, Angelo Biviano, Joshua Sonett, Hasan Garan

Dizon and colleagues compared the incidence of atrial arrhythmias after double-lung or heart transplant surgeries because both create a type of pulmonary vein isolation (PVI) caused by the suture lines. In the heart transplant group, 4.6% had atrial fibrillation (AF) compared with 19% in the lung transplant group, which was similar to a group of control patients undergoing coronary artery bypass grafting. The heart transplant patients who developed AF were more likely to have myocardial dysfunction and graft rejection than those who did not. These findings suggest that cardiac autonomic denervation may have a protective effect against atrial fibrillation in the post-operative setting, but that the PVI caused by the atriotomies during double-lung transplant procedures is not protective.

Editorial Comment: Sanjay Dixit, p. 2049

Clinical Research.   Location of Mutations Affects Outcomes in Type 2 LQTS

2052

Wataru Shimizu, Arthur J. Moss, Arthur A. M. Wilde, Jeffrey A. Towbin, Michael J. Ackerman, Craig T. January, David J. Tester, Wojciech Zareba, Jennifer L. Robinson, Ming Qi, G. Michael Vincent, Elizabeth S. Kaufman, Nynke Hofman, Takashi Noda, Shiro Kamakura, Yoshihiro Miyamoto, Samit Shah, Vinit Amin, Ilan Goldenberg, Mark L. Andrews, Scott McNitt

Shimizu and colleagues reviewed the effect of the location, coding type, and topology of KCNH2(hERG) mutations on clinical phenotype in patients with type 2 long QT syndrome (LQTS). Over 800 subjects with 162 different mutations were studied. For patients with missense mutations, the transmembrane pore and N-terminus regions were associated with increased risk compared with the C-terminus region and the transmembrane nonpore region. However, for nonmissense mutations the location seemed less important. A significantly higher risk was found in subjects with mutations located in -helical domains than in those with mutations in β-sheet domains or other locations.

Editorial Comment: Koonlawee Nademanee, p. 2063

Clinical Research.   A New Strategy for Identifying Mutations Associated With Catecholaminergic Polymorphic Ventricular Tachycardia
2065

Argelia Medeiros-Domingo, Zahurul A. Bhuiyan, David J. Tester, Nynke Hofman, Hennie Bikker, J. Peter van Tintelen, Marcel M. A. M. Mannens, Arthur A. M. Wilde, Michael J. Ackerman

Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) is believed to be caused by gain of function mutations in the cardiac ryanodine receptor encoded by RYR2. Most RYR2 mutational analyses to date have targeted 3 domains encoded by <40% of the translated exons. Medeiros-Domingo and colleagues performed a mutational analysis of all RYR2 exons on patients with either a clinical diagnosis of CPVT or a high suspicion for this disorder. Nearly one-half of subjects were found to have RYR2 mutations, and these mutations were found in 13 exons that are not typically analyzed. These results suggest that a strategy of RYR2 screening that includes 16 exons would identify an RYR2 mutation in two-thirds of patients with CPVT1.

Clinical Research.   Ganglionated Plexi May Be the Link Between Sleep Apnea and AF
2075

Muhammad Ghias, Benjamin J. Scherlag, Zhibing Lu, Guodong Niu, Annerie Moers, Warren M. Jackman, Ralph Lazzara, Sunny S. Po

Ghias and colleagues designed an experimental model to simulate sleep apnea-induced atrial fibrillation (AF) by temporarily halting respirations in anesthesized, intubated dogs. Obstructive apnea was induced by turning off the respirator during end expiration. Programmed pacing was then performed with S1-S2 5 to 10 ms earlier than the atrial refractory period. Neural activity was monitored from the ganglionated plexi (GP) adjacent to the right pulmonary veins. During apnea, this S1-S2 protocol induced AF in 9 of 10 dogs, and GP activity increased prior to AF onset. In a second series of studies, ablating the GP prevented the induction of AF. This experimental model of apnea links the risk of AF with activity in the GP.

Editorial Comment: Samuel J. Asirvatham, Suraj Kapa, p. 2084

	Hypertension

Top Quarterly Focus Issue: Heart... Hypertension Congenital Heart Disease

 
Hypertension.   Earlier Reflection Wave Unlikely to Cause Aging Related Hypertension

2087

Arun J. Baksi, Thomas A. Treibel, Justin E. Davies, Nearchos Hadjiloizou, Rodney A. Foale, Kim H. Parker, Darrel P. Francis, Jamil Mayet, Alun D. Hughes

The arterial pressure waveform is divided into 2 components: an initial rise due to left ventricular ejection and a secondary rise caused by reflected waves. The rise in blood pressure with aging has been attributed to an increased magnitude and an earlier return of the reflected waves. Baksi and colleagues performed a meta-analysis of studies have that examined the relationship between these waves and aging. They report that in subjects of all ages, reflection times were well within systole and there was only a small tendency for younger subjects to have later reflection. This difference amounted to only 0.7 ms per year; at this rate of change, arrival of wave reflection during diastole would only occur at an age of –221 years. These findings challenge the current consensus view that a shift in timing of wave reflection from diastole to systole causes aging-related hypertension.

	Congenital Heart Disease

Top Quarterly Focus Issue: Heart... Hypertension Congenital Heart Disease

 
Congenital Heart Disease.   Anemia Is Associated With Increased Mortality in ACHD

2093

Konstantinos Dimopoulos, Gerhard-Paul Diller, Georgios Giannakoulas, Ricardo Petraco, Aikaterini Chamaidi, Evaggelia Karaoli, Michael Mullen, Lorna Swan, Massimo F. Piepoli, Philip A. Poole-Wilson, Darrel P. Francis, Michael A. Gatzoulis

Dimopoulos and colleagues investigated the relationship between anemia and functional capacity and mortality in adults with congenital heart disease (ACHD). Over 800 patients with ACHD, which was noncyanotic, had at least 1 measurement of hemoglobin; anemia was defined as a hemoglobin concentration <13 g/dl in males and <12 g/dl in females. The prevalence of anemia was 13% and was highest in patients with congenitally-corrected transposition of the great arteries and Ebstein's anomaly. Anemic patients had a 3-fold higher mortality risk, which persisted after propensity score adjustment. These results suggest that screening for anemia should be a part of the routine assessment of ACHD patients.

Related Articles

Appropriate Evaluation and Treatment of Heart Failure Patients After Implantable Cardioverter-Defibrillator Discharge: Time to Go Beyond the Initial Shock

Joseph D. Mishkin, Sherry J. Saxonhouse, Gregory W. Woo, Thomas A. Burkart, William M. Miles, Jamie B. Conti, Richard S. Schofield, Samuel F. Sears, and Juan M. Aranda, Jr
J. Am. Coll. Cardiol. 2009 54: 1993-2000. [Abstract] [Full Text] [PDF]

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