Journal of the American College of Cardiology

Summaries of Key Journal Articles

2012-02-07

Effects of Radiation Exposure From Cardiac Imaging: How Good Are the Data?

Andrew J. Einstein — 2012-02-07

Concerns about medical exposure to ionizing radiation have become heightened in recent years as a result of rapid growth in procedure volumes and the high radiation doses incurred from some procedures. This paper summarizes the evidence base undergirding concerns about radiation exposure in cardiac imaging. After classifying radiation effects, explaining terminology used to quantify the radiation received by patients, and describing typical doses from cardiac imaging procedures, this paper will address the major epidemiological studies having bearing on radiation effects at doses comparable to those received by patients undergoing cardiac imaging. These include studies of atomic bomb survivors, nuclear industry workers, and children exposed in utero to x-rays, all of which have evidenced increased cancer risks at low doses. Additional higher-dose epidemiological studies of cohorts exposed to radiation in the context of medical treatment are described and found to be generally compatible with these cardiac dose–level studies, albeit with exceptions. Using risk projection models developed by the U.S. National Academies that incorporate these data and reflect several evidence-based assumptions, cancer risk from cardiac imaging can be estimated and compared with the benefits from imaging. Several ongoing epidemiological studies will provide better understanding of radiation-associated cancer risks.

Sex-Related Differences in Clinical Presentation and Outcome of Transcatheter Aortic Valve Implantation for Severe Aortic Stenosis

2012-02-07

Objectives: The purpose of this study was to clarify the impact of sex-related differences in transcatheter aortic valve implantation (TAVI) for high-risk patients with severe aortic stenosis. Background: Although TAVI is becoming a mature technique, the impact of sex differences remains unclear. Methods: The TAVI patients were included prospectively in a dedicated database from October 2006. The proportion of women (n = 131) was similar to that of men (n = 129). The Edwards valve (85.4%) and CoreValve (14.6%) were used through the transfemoral (65.0%), subclavian (3.1%), or transapical (31.9%) approach. All events were defined according to Valve Academic Research Consortium criteria. Results: Age was similar (83.1 ± 6.3 years), but women had less coronary and peripheral disease, less previous cardiac surgery, higher ejection fraction, and lower EuroSCORE (European System for Cardiac Operative Risk Evaluation [22.3 ± 9.0% vs. 26.2 ± 13.0%, p = 0.005]). Minimal femoral size (7.74 ± 1.03 mm vs. 8.55 ± 1.34 mm, p < 0.001), annulus size (20.9 ± 1.4 vs. 22.9 ± 1.7 mm, p < 0.001), and valve size (23.9 ± 1.6 mm vs. 26.3 ± 1.5 mm, p < 0.001) were smaller in women. Device success was similar (90.8% vs. 88.4%, p = 0.516) despite more frequent iliac complications (9.0% vs. 2.5%, p = 0.030). Residual mean aortic pressure gradient (11.6 ± 4.9 vs. 10.9 ± 4.9, p = 0.279) was also similar. The 1-year survival rate was higher for women, 76% (95% confidence interval: 72% to 80%), than for men, 65% (95% confidence interval: 60% to 69%); and male sex (hazard ratio: 1.62, 95% confidence interval: 1.03 to 2.53, p = 0.037) was identified as a predictor of midterm mortality by Cox regression analysis. Conclusions: Female sex is associated with better baseline clinical characteristics and improved survival, and is identified as a predictor of midterm survival after TAVI.

Meta-Analysis of Statin Effects in Women Versus Men

2012-02-07

Objectives: The aim of this study was to evaluate the effect of statins in decreasing cardiovascular events in women and men. Background: Published data reviews have suggested that statins might not be as effective in women as in men in decreasing cardiovascular events. Methods: Published data searches and contacts with investigators identified 18 randomized clinical trials of statins with sex-specific outcomes (N = 141,235, 40,275 women, 21,468 cardiovascular events). Odds ratios (ORs) and 95% confidence intervals (CIs) for cardiovascular events were calculated for women and men separately with random effects meta-analyses. Results: The cardiovascular event rate was lower among those randomized to statin intervention than in those randomized to control (low-dose statin in 4 studies, placebo in 11 studies, usual care in 3 studies) and similar in women and men (OR: 0.81, 95% CI: 0.75 to 0.89; p < 0.0001, and OR: 0.77, 95% CI: 0.71 to 0.83, p < 0.0001, respectively). The benefit of statins was statistically significant in both sexes, regardless of the type of control, baseline risk, or type of endpoint and in both primary and secondary prevention. All-cause mortality was also lower with statin therapy both in women and men without significant interaction by sex (p for interaction = 0.4457). Conclusions: Statin therapy is associated with significant decreases in cardiovascular events and in all-cause mortality in women and men. Statin therapy should be used in appropriate patients without regard to sex.

Controversy and Consensus About Statin Use: It Is Not About the Sex⁎

Lori Mosca — 2012-02-07

If statistics is a science of probability then Sir William Osler expressed the limitations of its applications when he articulated “Medicine is a science of uncertainty and an art of probability” (). Despite widespread consensus about statin use for the secondary prevention of cardiovascular disease (CVD) in both sexes, there has been substantial debate with regard to the use of statins for primary prevention among women. Much of the discourse has centered on the fact that women have not participated in primary prevention trials to that extent that men have; therefore, less-definitive conclusions can be drawn about the likelihood of benefits and risks among women. The short-term absolute risk of a future cardiovascular event among women is substantially lower than men in a primary prevention population, further amplifying the challenge of under-representation of women in primary prevention trials. The potential for pooling individual studies to provide a more precise single estimate of a treatment effect was recognized over 100 years ago by the statistician Karl Pearson as a method to reduce error in drawing conclusions based on small group sizes ().

Ursodeoxycholic Acid in Patients With Chronic Heart Failure: A Double-Blind, Randomized, Placebo-Controlled, Crossover Trial

2012-02-07

Objectives: This study sought to assess the effects of ursodeoxycholic acid (UDCA) on endothelial function and inflammatory markers in patients with chronic heart failure (CHF). Background: Endothelial dysfunction is commonly observed in patients with CHF, and it contributes to the limitation in exercise capacity that accompanies this condition. Bacterial lipopolysaccharide may trigger proinflammatory cytokine release and promote further endothelial dysfunction. UDCA, a bile acid used in the treatment of cholestatic liver disease, has anti-inflammatory and cytoprotective properties and may contribute to the formation of mixed micelles around lipopolysaccharide. These properties may help to improve peripheral blood flow in patients with CHF. Methods: We performed a prospective, single-center, double-blind, randomized, placebo-controlled crossover study of UDCA in 17 clinically stable male patients with CHF (New York Heart Association functional class II/III, left ventricular ejection fraction <45%). Patients received in random order 500 mg UDCA twice daily for 4 weeks and placebo for another 4 weeks. The primary endpoint was post-ischemic peak peripheral arm blood flow as assessed by strain-gauge plethysmography. Results: Sixteen patients completed the study. UDCA was well tolerated in all patients. Compared with placebo, UDCA improved peak post-ischemic blood flow in the arm (+18%, p = 0.038), and a trend for improved peak post-ischemic blood flow in the leg was found (+17%, p = 0.079). Liver function improved: compared with placebo, levels of γ-glutamyl transferase, aspartate transaminase, and soluble tumor necrosis factor α receptor 1 were lower after treatment with UDCA than after placebo (all p < 0.05). There was no change in 6-min walk test or New York Heart Association functional class, and levels of tumor necrosis factor α and interleukin-6 were unchanged or increased compared with placebo. Conclusions: UDCA is well tolerated in patients with CHF. UDCA improves peripheral blood flow and is associated with improved markers of liver function. (Ursodeoxycholic Acid in Chronic Heart Failure; NCT00285597)

Bile Salts for the Treatment of Heart Failure: Out on a Limb for a Gut Feeling?⁎

James M. McCabe, John R. Teerlink — 2012-02-07

In 1984, Warren and Marshall () presented indirect evidence of a putative microbial etiology for peptic ulcer disease. In the decades to follow, >37,000 scholarly articles have been published on Helicobacter pylori (). Unlike the discovery of the role of H pylori in peptic ulcer disease, enthusiasm for infectious causes of all manner of cardiovascular disease has been largely unsubstantiated (). Nevertheless, the robust relationship between inflammation and cardiovascular events lends biological plausibility to the possible association between infectious processes and cardiovascular disease, particularly heart failure (). Tumor necrosis factor (TNF)-α, interleukin (IL)-6, and other inflammatory cytokines have been recognized as correlates of heart failure disease progression and severity, as well as predictors of mortality. These cytokines are believed to be important mediators in the pathogenesis of many manifestations of heart failure, including myocardial remodeling and vascular dysfunction. Despite the compelling data supporting their central role, targeting abrogation of specific proinflammatory cytokines, specifically TNF-α, as a therapeutic strategy in chronic heart failure has largely been disappointing ().

Atrial Conduction Slows Immediately Before the Onset of Human Atrial Fibrillation: A Bi-Atrial Contact Mapping Study of Transitions to Atrial Fibrillation

2012-02-07

Objectives: The aim of this study was to determine whether onset sites of human atrial fibrillation (AF) exhibit conduction slowing, reduced amplitude, and/or prolonged duration of signals (i.e., fractionation) immediately before AF onset. Background: Few studies have identified functional determinants of AF initiation. Because conduction slowing is required for reentry, we hypothesized that AF from pulmonary vein triggers might initiate at sites exhibiting rate-dependent slowing in conduction velocity (CV restitution) or local slowing evidenced by signal fractionation. Methods: In 28 patients with AF (left atrial size 43 ± 5 mm; n = 13 persistent) and 3 control subjects (no AF) at electrophysiological study, we measured bi-atrial conduction time (CT) electrogram fractionation at 64 or 128 electrodes with baskets in left (n = 17) or both (n = 14) atria during superior pulmonary vein pacing at cycle lengths (CL) accelerating from 500 ms (120 beats/min) to AF onset. Results: Atrial fibrillation initiated in 19 of 28 AF patients and no control subjects. During rate acceleration, conduction slowed in 23 of 28 AF patients (vs. no control subjects, p = 0.01) at the site of AF initiation (15 of 19) or latest activated site (20 of 28). The CT lengthened from 79 ± 23 ms to 107 ± 39 ms (p < 0.001) on acceleration, in a spectrum from persistent AF (greatest slowing) to control subjects (least slowing; p < 0.05). Three patterns of CV restitution were observed: 1) broad (gradual CT prolongation, 37% patients); 2) steep (abrupt prolongation, at CL 266 ± 62 ms, 42%); and 3) flat (no prolongation, 21% AF patients, all control subjects). The AF initiation was more prevalent in patients with CV restitution (17 of 23 vs. 2 of 8; p = 0.03) and immediately followed abrupt re-orientation of the activation vector in patients with broad but not steep CV restitution (p < 0.01). Patients with broad CV restitution had larger atria (p = 0.03) and were more likely to have persistent AF (p = 0.04). Notably, neither amplitude nor duration (fractionation) of the atrial signal at the AF initiation site were rate-dependent (both p = NS). Conclusions: Acceleration-dependent slowing of atrial conduction (CV restitution) precedes AF initiation, whereas absence of CV restitution identifies inability to induce AF. Conduction restitution, but not fractionated electrograms, may thus track the functional milieu enabling AF initiation and has implications for guiding AF ablation and pharmacological therapy.

Incidence of and Risk Factors for Sudden Cardiac Death in Children With Dilated Cardiomyopathy: A Report From the Pediatric Cardiomyopathy Registry

2012-02-07

Objectives: The purpose of this study was to establish the incidence of and risk factors for sudden cardiac death (SCD) in pediatric dilated cardiomyopathy (DCM). Background: The incidence of SCD in children with DCM is unknown. The ability to predict patients at high risk of SCD will help to define who may benefit most from implantable cardioverter-defibrillators. Methods: The cohort was 1,803 children in the PCMR (Pediatric Cardiomyopathy Registry) with a diagnosis of DCM from 1990 to 2009. Cumulative incidence competing-risks event rates were estimated. We achieved risk stratification using Classification and Regression Tree methodology. Results: The 5-year incidence rates were 29% for heart transplantation, 12.1% non-SCD, 4.0% death from unknown cause, and 2.4% for SCD. Of 280 deaths, 35 were SCD, and the cause was unknown for 56. The 5-year incidence rate for SCD incorporating a subset of the unknown deaths is 3%. Patients receiving antiarrhythmic medication were at higher risk of SCD (hazard ratio: 3.0, 95% confidence interval: 1.1 to 8.3, p = 0.025). A risk stratification model based on most recent echocardiographic values had 86% sensitivity and 57% specificity. Thirty of 35 SCDs occurred in patients who met all these criteria: left ventricular (LV) end-systolic dimension z-score >2.6, age at diagnosis younger than 14.3 years, and the LV posterior wall thickness to end-diastolic dimension ratio <0.14. Sex, ethnicity, cause of DCM, and family history were not associated with SCD. Conclusions: The 5-year incidence rate of SCD in children with DCM is 3%. A risk stratification rule (86% sensitivity) included age at diagnosis younger than 14.3 years, LV dilation, and LV posterior wall thinning. Patients who consistently meet these criteria should be considered for implantable cardioverter-defibrillator placement. (Pediatric Cardiomyopathy Registry; NCT00005391)

In Vivo Detection of Oxidation-Specific Epitopes in Atherosclerotic Lesions Using Biocompatible Manganese Molecular Magnetic Imaging Probes

2012-02-07

Objectives: This study sought to evaluate the in vivo magnetic resonance imaging (MRI) efficacy of manganese [Mn(II)] molecular imaging probes targeted to oxidation-specific epitopes (OSE). Background: OSE are critical in the initiation, progression, and destabilization of atherosclerotic plaques. Gadolinium [Gd(III)]-based MRI agents can be associated with systemic toxicity. Mn is an endogenous, biocompatible, paramagnetic metal ion that has poor MR efficacy when chelated, but strong efficacy when released within cells. Methods: Multimodal Mn micelles were generated to contain rhodamine for confocal microscopy and conjugated with either the murine monoclonal IgG antibody MDA2 targeted to malondialdehyde (MDA)-lysine epitopes or the human single-chain Fv antibody fragment IK17 targeted to MDA-like epitopes (“targeted micelles”). Micelle formulations were characterized in vitro and in vivo, and their MR efficacy (9.4-T) evaluated in apolipoprotein-deficient (apoE−/−) and low-density lipoprotein receptor negative (LDLR−/−) mice (0.05 mmol Mn/kg dose) (total of 120 mice for all experiments). In vivo competitive inhibition studies were performed to evaluate target specificity. Untargeted, MDA2-Gd, and IK17-Gd micelles (0.075 mmol Gd/kg) were included as controls. Results: In vitro studies demonstrated that targeted Mn micelles accumulate in macrophages when pre-exposed to MDA-LDL with ∼10× increase in longitudinal relativity. Following intravenous injection, strong MR signal enhancement was observed 48 to 72 h after administration of targeted Mn micelles, with colocalization within intraplaque macrophages. Co-injection of free MDA2 with the MDA2-Mn micelles resulted in full suppression of MR signal in the arterial wall, confirming target specificity. Similar MR efficacy was noted in apoE−/− and LDLR−/− mice with aortic atherosclerosis. No significant differences in MR efficacy were noted between targeted Mn and Gd micelles. Conclusions: This study demonstrates that biocompatible multimodal Mn-based molecular imaging probes detect OSE within atherosclerotic plaques and may facilitate clinical translation of noninvasive imaging of human atherosclerosis.

Stent in the Heart

Go Watanabe, Hiroshi Ohtake, Shigeyuki Tomita, Shojiro Yamaguchi, Kenji Iino — 2012-02-07

A 56-year-old man who was admitted with acute myocardial infarction developed severe heart failure following stent placement in the left anterior descending artery. Ventricular septal perforation (VSP) was diagnosed. Conventional septal closure was considered high risk due to severe heart and multiple organ failure. We decided to place a stent graft in the left ventricle to exclude the VSP (A and B). The stent was placed retrograde from the ascending aorta through the aortic valve into the left ventricle, and the tip was stabilized to the apex. After stent placement, right ventricular free-wall bulging decreased markedly. Cardiac catheterization showed reduction of shunting to 20%. Three years after the procedure, no increase in shunting was observed. Chest radiograph and computed tomography showed no pulmonary coronary and a stent in the heart (C and D). This is the first report, to our knowledge, of placing a stent in the left ventricle to close VSP after acute myocardial infarction. Please see accompanying Online Videos 1, 2, 3, and 4

Thrombotic Obstruction of Mechanical Prosthetic Valve in Mitral Position: The Old “X-Ray” Fights the New 3-Dimensional Transesophageal Echocardiography

2012-02-07

A 34-year-old man with recent mitral valve replacement (Sorin Bicarbon prosthesis, Milan, Italy) was referred as the result of an abnormal color flow signal localized in only 1 hemidisc with a significantly increased gradient across the prosthesis during routine transthoracic echocardiography (A). He was asymptomatic, and oral anticoagulation was not adequate.

President's Page: A Transformational Troika

David R. Holmes, Michael J. Mack — 2012-02-07

Irrespective of the field, be it religion (the 3 main Abrahamic religions, Hinduism, or Buddhism), philosophy (Hegel's dialectic), physics (baryon), chemistry (atomic constituents), or anatomy (human light perception), the underlying structure of 3's has been accorded considerable attention.

Differences in Treatment Patterns and Outcomes Between Hispanics and Non-Hispanic Whites Treated for ST-Segment Elevation Myocardial Infarction: Results From the NCDR ACTION Registry–GWTG

2012-02-07

To the Editor: Ethnic disparities in contemporary ST-segment elevation myocardial infarction (STEMI) management have not been well characterized (). The National Cardiovascular Data Registry Acute Coronary Treatment and Intervention Outcome Network–Get With The Guidelines Registry (ACTION Registry–GWTG) is the largest national database including consecutive acute coronary syndrome patients from all U.S. geographic regions and therefore provides a unique opportunity to compare contemporary treatment patterns and outcomes between Hispanic and non-Hispanic white STEMI patients.

Intracardiac Electrogram and Ischemia Alert

2012-02-07

In an elegant study, Fischell et al. () employed an implantable intracardiac ischemia detection device for continuous surveillance for ST-segmental shifts as a warning system. During a median follow-up of 1.5 years, shifts exceeding 3 SDs were an accurate marker for thrombotic coronary occlusion, allowing for a median alert-to-door time of <20 min for patients at high risk of recurrent coronary syndromes who typically present with 2- to 3-h delays. The feasibility of such a strategy was earlier established clinically with temporary balloon occlusion during a coronary intervention procedure (), and experimentally with acute or subacute coronary occlusion in ambulatory porcine models (). We present an anecdotal case that underscores superior efficacy of an intracardiac electrocardiogram.

Inside This Issue

2012-02-07

553 Andrew J. Einstein