Journal of the American College of Cardiology Current Issue

Inside This Issue

Tue, 28 May 2013 00:00:00 GMT

Platelet Function Tests in Clinical Cardiology Unfulfilled Expectations

Gorog DA, Fuster V. — Tue, 28 May 2013 00:00:00 GMT

This review is a critical evaluation of publications in the past decade on the usefulness of platelet function tests (PFTs) in clinical cardiology, in aiding diagnosis, predicting risk, and monitoring therapy. The ideal PFT should: 1) detect baseline platelet hyperreactivity; 2) allow individualization of antiplatelet medication; 3) predict thrombotic risk; and 4) predict bleeding risk. The practicalities of clinical cardiology demand rapid, accurate, and reliable tests that are simple to operate at the bedside and available 24 h a day, 7 days a week. Point-of-care PFTs most widely evaluated clinically include PFA-100 and VerifyNow. None of these tests can reliably detect platelet hyperreactivity and thus identify a prothrombotic state. Identification of antiplatelet nonresponsiveness or hyporesponsiveness is highly test specific, and does not allow individualization of therapy. The power of PFTs in predicting thrombotic events for a given individual is variable and often modest, and alteration of antithrombotic treatment on the basis of the results of PFTs has not been shown to alter clinical outcome. PFTs in current mainstream use cannot reliably assess bleeding risk. These tests have been in use for over a decade, but the hopes raised by PFTs in clinical practice remain unfulfilled. Although physiologically relevant measurement of platelet function now is more important than ever, a critical reappraisal of available techniques in light of clinical requirements is needed. The use of native blood, global stimulus instead of individual agonists, contribution of thrombin generation by activated platelets to the test results, and establishment of a PFT therapeutic range for each antiplatelet drug should be considered and is discussed.

Impact of Baseline Heart Failure Burden on Post-Implantable Cardioverter-Defibrillator Mortality Among Medicare Beneficiaries

Chen C, Stevenson L, Stewart GC, et al. — Tue, 28 May 2013 00:00:00 GMT

Objectives

This study sought to assess the impact of baseline heart failure (HF) burden on survival with primary implantable cardioverter-defibrillator (ICD) among Medicare recipients.

Background

Survival after primary ICD implantation may differ between trial and Medicare populations.

Methods

Linking data from the CMS (Centers for Medicare and Medicaid Services) ICD registry and the Medicare files (2005 to 2009), we identified primary ICD recipients age ≥66 years with ejection fraction ≤35%. Number of previous HF hospitalizations (prev-HF-hosp) and length of hospitalization prior to implantation were used to define HF burden. Crude all-cause mortality was estimated. Adjusted hazard ratios (HR) were derived from Cox models.

Results

Of 66,974 ICD recipients (73% men, 88% white, mean age 75 years), 11,876 died (average follow-up = 1.4 years), with 3-year mortality of 31%. Among patients with no prev-HF-hosp, 3-year mortality was 27% compared with 63% in those with ≥3 prev-HF-hosp (adjusted HR: 1.8). Among patients with same-day implantation, 3-year mortality was 25% compared with 53% in those with >1-week hospitalization days prior to implantation (adjusted HR: 1.9). Mortality at 3-year follow-up among the 31,685 ICD recipients with no prev-HF-hosp and same-day implantation (low HF burden) was similar to that in trials (22%).

Conclusions

Nearly one-third of Medicare ICD recipients died within 3 years, reflecting a population with more advanced age and disease than seen in trial populations for primary prevention ICD. Nearly one-half of Medicare recipients had a low HF burden and had a survival similar to trial ICD recipients. Future research is warranted to understand the effectiveness of primary ICD implantation among Medicare beneficiaries with heavy HF burdens.

Interplay Between Right Ventricular Function and Cardiac Resynchronization Therapy An Analysis of the CARE-HF Trial (Cardiac Resynchronization–Heart Failure)

Damy T, Ghio S, Rigby AS, et al. — Tue, 28 May 2013 00:00:00 GMT

Objectives

The aim of this study was to investigate the impact of cardiac resynchronization therapy (CRT) on right ventricular (RV) function and the influence of RV dysfunction on the echocardiographic and clinical response to CRT among patients enrolled in the CARE-HF (Cardiac Resynchronization-Heart Failure) trial.

Background

Cardiac resynchronization therapy prolongs survival in appropriately selected patients with heart failure but the benefit might be diminished in patients with RV dysfunction.

Methods

Of 813 patients enrolled in the CARE-HF study, 688 had tricuspid plane systolic excursion (TAPSE) measured at baseline, and 345 of these were assigned to CRT. Their median (interquartile range) age was 66 (58 to 71) years, left ventricular (LV) ejection fraction was 24% (21% to 28%), and TAPSE was 19 (16 to 22) mm. Baseline LV function and size and QRS duration were similar among TAPSE tertiles, but those in the worst tertile (TAPSE <17.4 mm) were more likely to have ischemic heart disease.

Results

Overall, CRT improved LV but not RV structure and function with little evidence of an interaction with TAPSE. During a median (interquartile range) follow-up of 748 (582 to 950) days, 213 deaths occurred. Patients with lower TAPSE had a higher mortality, regardless of assigned treatment (p < 0.001). Greater inter-ventricular mechanical delay, New York Heart Association functional class, mitral regurgitation, and N-terminal pro–B-type natriuretic peptide, lower TAPSE, and assignment to the control group were independently associated with higher mortality. Reduction in mortality with CRT was similar in each tertile of TAPSE.

Conclusions

Right ventricular dysfunction is a powerful determinant of prognosis among candidates for CRT, regardless of treatment assigned, but did not diminish the prognostic benefits of CRT among patients enrolled in the CARE-HF trial. (Care-HF CArdiac Resynchronization in Heart Failure; NCT00170300)

Is Electricity Useful When the Pump Is Failing? More Data Urgently Needed ⁎ ⁎

Lampert R. — Tue, 28 May 2013 00:00:00 GMT

The benefit of prophylactic implantation of an implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy (CRT) ICD (CRT-D) in improving mortality in patients with heart failure has been firmly established by multiple randomized controlled trials (RCT) (1,2,3,4). However, it has also been well documented that patients receiving ICDs in the “real world” are older and sicker, with higher prevalences of diabetes, hypertension, and atrial fibrillation than are those enrolled in the landmark RCTs (1,3,5). It is an inherent limitation of RCTs that strict entry criteria limit “real-world” generalizability (6), and attempting to understand whether the findings of the RCTs can be extrapolated to these sicker patients is an important endeavor. Several previous studies of varying design have suggested that overall the benefit of the ICD for primary prevention of sudden cardiac death in patients in the real world is similar to that in the trials. Using administrative data from the Medicare database, Groeneveld et al. (7) compared 7,125 ICD recipients to a propensity-score matched group, finding a hazard ratio (HR) for mortality of 0.62 with the ICD. In a population-based study, Parkash et al. (8) compared outcomes between all patients receiving an ICD in Nova Scotia and comparable patients in a province-wide database. They found a dramatic survival benefit from the ICD, with an unadjusted HR for mortality of 0.46, going to 0.55 to 0.59 after multivariable and propensity analyses. In the most rigorous study to date of real-world benefit, Al-Khatib et al. (9) used patient-level data to compare mortality between ICD recipients in the NCDR (National Cardiovascular Data Registry) meeting criteria for MADIT-II (Multicenter Automatic Defibrillator Implantation Trial II) (3) or SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) (1) and the participants in those trials, looking at both ICD recipients and those randomized to standard-of-care medical therapy. Despite the fact that the NCDR patients were older and had greater comorbidities, the mortality in the NCDR patients was similar to ICD recipients in the trials, and significantly better than that in the trial control groups (HR: 0.73; 95% confidence interval [CI]: 0.59 to 0.92; p = 0.007 for the MADIT-II comparison, and HR: 0.82; 95% CI, 0.7 to 0.96; p = 0.01 for the SCD-HeFT comparison).

Nuisance Bleeding With Prolonged Dual Antiplatelet Therapy After Acute Myocardial Infarction and its Impact on Health Status

Amin AP, Bachuwar A, Reid KJ, et al. — Tue, 28 May 2013 00:00:00 GMT

Objectives

The purpose of this study was to examine the incidence of nuisance bleeding after AMI and its impact on QOL.

Background

Prolonged dual antiplatelet therapy (DAPT) is recommended after acute myocardial infarction (AMI) to reduce ischemic events, but it is associated with increased rates of major and minor bleeding. The incidence of even lesser degrees of post-discharge “nuisance” bleeding with DAPT and its impact on quality of life (QOL) are unknown.

Methods

Data from the 24-center TRIUMPH (Translational Research Investigating Underlying Disparities in Acute Myocardial Infarction Patients' Health Status) study of 3,560 patients, who were interviewed at 1, 6, and 12 months after AMI, were used to investigate the incidence of nuisance bleeding (defined as Bleeding Academic Research Consortium type 1). Baseline characteristics associated with “nuisance” bleeding and its association with QOL, as measured by the EuroQol 5 Dimension visual analog scale, and subsequent re-hospitalization were examined.

Results

Nuisance (Bleeding Academic Research Consortium type 1) bleeding occurred in 1,335 patients (37.5%) over the 12 months after AMI. After adjusting for baseline bleeding and mortality risk, ongoing DAPT was the strongest predictor of nuisance bleeding (rate ratio [RR]: 1.44, 95% confidence interval [CI]: 1.17 to 1.76 at 1 month; RR: 1.89, 95% CI: 1.35 to 2.65 at 6 months; and RR: 1.39, 95% CI: 1.08 to 1.79 at 12 months; p < 0.01 for all comparisons). Nuisance bleeding at 1 month was independently associated with a decrement in QOL at 1 month (−2.81 points on EuroQol 5 Dimension visual analog scale; 95% CI: 1.09 to 5.64) and nonsignificantly toward higher re-hospitalization (hazard ratio: 1.20; 95% CI: 0.95 to 1.52).

Conclusions

Nuisance bleeding is common in the year after AMI, associated with ongoing use of DAPT, and independently associated with worse QOL. Improved selection of patients for prolonged DAPT may help minimize the incidence and adverse consequences of nuisance bleeding.

Oxidation-Specific Biomarkers and Risk of Peripheral Artery Disease

Bertoia ML, Pai JK, Lee J, et al. — Tue, 28 May 2013 00:00:00 GMT

Objectives

The goal of this study was to examine the prospective association between oxidation-specific biomarkers, primarily oxidized phospholipids (OxPL) on apolipoprotein B-100–containing lipoproteins (OxPL/apoB) and lipoprotein (a) [Lp(a)], and risk of peripheral artery disease (PAD). We examined, as secondary analyses, indirect measures of oxidized lipoproteins, including autoantibodies to malondialdehyde-modified low-density lipoprotein (MDA-LDL) and apolipoprotein B-100 immune complexes (ApoB-IC).

Background

Biomarkers to predict the development of PAD are lacking. OxPL circulate in plasma, are transported by Lp(a), and deposit in the vascular wall and induce local inflammation.

Methods

The study population included 2 parallel nested case-control studies of 143 men within the Health Professionals Follow-up Study (1994 to 2008) and 144 women within the Nurses' Health Study (1990 to 2010) with incident confirmed cases of clinically significant PAD, matched 1:3 to control subjects.

Results

Levels of OxPL/apoB were positively associated with risk of PAD in men and women: pooled relative risk: 1.37, 95% confidence interval: 1.19 to 1.58 for each 1-SD increase after adjusting age, smoking, fasting status, month of blood draw, lipids, body mass index, and other cardiovascular disease risk factors. Lp(a) was similarly associated with risk of PAD (pooled adjusted relative risk: 1.36; 95% confidence interval: 1.18 to 1.57 for each 1-SD increase). Autoantibodies to MDA-LDL and ApoB-IC were not consistently associated with risk of PAD.

Conclusions

OxPL/apoB were positively associated with risk of PAD in men and women. The major lipoprotein carrier of OxPL, Lp(a), was also associated with risk of PAD, reinforcing the key role of OxPL in the pathophysiology of atherosclerosis mediated by Lp(a).

Prevalence and Predictors of Gaps in Care Among Adult Congenital Heart Disease Patients HEART-ACHD (The Health, Education, and Access Research Trial)

Gurvitz M, Valente A, Broberg C, et al. — Tue, 28 May 2013 00:00:00 GMT

Objectives

The goal of this project was to quantify the prevalence of gaps in cardiology care, identify predictors of gaps, and assess barriers to care among adult congenital heart disease (adult CHD) patients.

Background

Adult CHD patients risk interruptions in care that are associated with undesired outcomes.

Methods

Patients (18 years of age and older) with their first presentation to an adult CHD clinic completed a survey regarding gaps in, and barriers to, care.

Results

Among 12 adult CHD centers, 922 subjects (54% female) were recruited. A >3-year gap in cardiology care was identified in 42%, with 8% having gaps longer than a decade. Mean age at the first gap was 19.9 years. The majority of respondents had more than high school education and knew their heart condition. The most common reasons for gaps included feeling well, being unaware that follow-up was required, and complete absence from medical care. Disease complexity was predictive of a gap in care with 59% of mild, 42% of moderate, and 26% of severe disease subjects reporting gaps (p < 0.0001). Clinic location significantly predicted gaps (p < 0.0001), whereas sex, race, and education level did not. Common reasons for returning to care were new symptoms, referral from provider, and desire to prevent problems.

Conclusions

Adult CHD patients have gaps in cardiology care; the first lapse commonly occurred at age ∼19 years, a time when transition to adult services is contemplated. Gaps were more common among subjects with mild and moderate diagnoses and at particular locations. These results provide a framework for developing strategies to decrease gaps and address barriers to care in the adult CHD population.

Rapid-Rate Nonsustained Ventricular Tachycardia Found on Implantable Cardioverter-Defibrillator Interrogation Relationship to Outcomes in the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial)

Chen J, Johnson G, Hellkamp AS, et al. — Tue, 28 May 2013 00:00:00 GMT

Objectives

The aim of this study was to examine rapid-rate nonsustained ventricular tachycardia (RR-NSVT) during routine implantable cardioverter-defibrillator (ICD) evaluation in patients with heart failure and its relationship to outcomes.

Background

The clinical implications of RR-NSVT identified during routine ICD interrogation are unclear. In this study, the occurrence of RR-NSVT and its association with ICD shocks and mortality in SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) were examined.

Methods

The 811 patients who received ICDs in SCD-HeFT constituted the study population. The occurrence of RR-NSVT and its association with ICD shocks and mortality in SCD-HeFT were examined.

Results

RR-NSVT was documented on ICD interrogation in 186 of 811 patients (22.9%). The mean duration of RR-NSVT was 26.4 ± 9.1 beats (7.5 ± 2.6 s), with a mean cycle length of 259 ± 32 ms. Polymorphic RR-NSVT accounted for 56% of episodes. Compared with patients without RR-NSVT, those with RR-NSVT were less likely to be taking beta-blockers, statins, or aspirin at enrollment. After adjusting for other known predictors of mortality in SCD-HeFT, RR-NSVT was independently associated with appropriate ICD shocks (hazard ratio: 4.25; 95% confidence interval: 2.94 to 6.14; p < 0.0001), with all-cause mortality (hazard ratio: 2.40; 95% confidence interval: 1.62 to 3.54; p < 0.0001), and with a composite of all-cause mortality and appropriate ICD shocks (hazard ratio: 3.03; 95% confidence interval: 2.21 to 4.15; p < 0.0001).

Conclusions

RR-NSVT identified on routine ICD interrogation should be considered an important clinical event. RR-NSVT during ICD interrogation is associated with appropriate ICD shocks and all-cause mortality. The clinical evaluation of patients with RR-NSVT should include intensification of medical therapy, particularly beta-blockers, or other appropriate clinical interventions. (Sudden Cardiac Death in Heart Failure Trial [SCD-HeFT]; NCT00000609)

The Softer Side of Bleeding ⁎ ⁎

Dauerman HL. — Tue, 28 May 2013 00:00:00 GMT

Bleeding after coronary intervention and acute coronary syndromes is to be avoided (1). The association between in-hospital and 30-day bleeding with 1-year morbidity and mortality is consistent across multiple study designs (2); assessment of a patient's risk for in-hospital bleeding is a Class I guideline in the context of coronary interventional procedures (3). We also have standardized definitions of bleeding via the Bleeding Academic Research Consortium (BARC) and can anticipate a clearer picture of bleeding risk across future clinical trials (4). Rates of bleeding complications have steadily improved and are now at their lowest levels in decades (5). Has the bleeding pendulum swung to the extreme where we can now go back to focusing on development of drugs, devices, and pathways with a primary concern of antithrombotic efficacy? In this issue of the Journal, Amin et al. (6) remind us that the bleeding story is not yet fully elucidated.

Noninvasive Renal Sympathetic Denervation by Extracorporeal High-Intensity Focused Ultrasound in a Pre-Clinical Canine Model

Wang Q, Guo R, Rong S, et al. — Tue, 28 May 2013 00:00:00 GMT

Objectives

This study investigated the feasibility of noninvasive renal sympathetic denervation (RSD) by using the novel approach of extracorporeal high-intensity focused ultrasound (HIFU).

Background

Catheter-based RSD has achieved promising clinical outcomes.

Methods

Under the guidance of Doppler flow imaging, therapeutic ablations (250 W × 2 s) were performed by using extracorporeal HIFU on the bilateral renal nerves (36.3 ± 2.8 HIFU emissions in each animal) in a mean 27.4-min procedure in 18 healthy canines of the ablation group. Similar procedures without acoustic energy treatment were conducted in 5 canines of the sham group. The animals were killed on day 6 or 28. Blood pressure (BP), plasma noradrenaline (NA) level, and renal function were determined on days 0, 6, and 28. Pathological examinations were performed on all retrieved samples.

Results

All of the animals survived the treatment. After ablation, BP and NA significantly decreased compared with the baseline values (BP changed −15.9/−13.6 mmHg, NA changed −55.4% [p < 0.001] 28 days after ablation]) and compared with the sham group on days 6 and 28. Ablation lesions around the renal artery adventitia were observed on day 6. A histological examination revealed the disruption of nerve fibers, necrosis of Schwann cells and neurons, and apparent denervation on day 28. No procedure-related complications were observed.

Conclusions

Effective RSD was successfully achieved by using the extracorporeal HIFU method in canines. Thus, noninvasive HIFU may be further explored as an important and novel strategy for RSD.

Extensive Xanthomas and Severe Subclinical Atherosclerosis in Homozygous Familial Hypercholesterolemia

Rocha VZ, Chacra AM, Salgado W, et al. — Tue, 28 May 2013 00:00:00 GMT

An asymptomatic 20-year-old man presented with a history of high plasma cholesterol levels and gigantic tendinous xanthomas over the extensor tendons of his metacarpophalangeal joints and patellas (A to C). Laboratory tests showed total cholesterol of 785 mg/dl, low-density lipoprotein cholesterol (LDL) of 710 mg/dl, triglycerides (TG) of 221 mg/dl, and high-density lipoprotein cholesterol (HDL) of 31 mg/dl. The 320-detector coronary angiotomography revealed a plaque in the proximal left anterior descending (LAD) coronary artery causing severe stenosis (D, upper arrow), a moderate plaque in the ventricular posterior coronary artery, and aortic calcification (E, arrow). Angiography showed a plaque involving the proximal/medium LAD coronary artery and 80% stenosis (F). Angioplasty of the LAD coronary artery with 2 drug-eluting stents was performed without incident (G). On a statin and ezetimibe, his laboratory tests showed total cholesterol of 341 mg/dl, LDL of 300 mg/dl, TG of 66 mg/dl, and HDL of 28 mg/dl. Genotyping revealed a homozygotic mutation (A540T) in exon 11 of the LDL receptor gene.

Multilevel Obstruction in the Left Heart During Pregnancy

Bashir A, Thorne S, Steeds RP. — Tue, 28 May 2013 00:00:00 GMT

A 29-year-old woman presented 21 weeks into her first pregnancy with an episode of pulmonary edema. Transthoracic echocardiography suggested severe mitral stenosis (A, Online Video 1) due to a parachute mitral valve with single functioning papillary muscle (B, Online Video 2). Transesophageal echocardiography confirmed that the mitral valve could not be treated percutaneously but it also identified a bicuspid aortic valve without evidence of a subaortic ridge (C,Online Video 3). Cardiac magnetic resonance imaging identified the single functioning papillary muscle in a short-axis cine image (D, Online Video 4) and an aortic coarctation with a tight isthmus in the proximal descending aorta (E, Online Video 5). Complete Shone complex consists of a supravalvular mitral membrane, parachute mitral valve, subaortic stenosis, and coarctation of the aorta, but partial forms are more commonly diagnosed in adults when only 2 or 3 obstructive lesions are present.

Fish Oil and Post-Operative Atrial Fibrillation A Meta-Analysis of Randomized Controlled Trials

Mozaffarian D, Wu JY, de Oliveira Otto MC, et al. — Tue, 28 May 2013 00:00:00 GMT

Post-operative atrial fibrillation (PoAF) is among the most common complications of cardiac surgery and substantially increases morbidity and healthcare costs. Despite decades of surgical, anesthetic, and medical advances, rates of PoAF remain largely unchanged. Experiments and animal models suggest that perioperative fish oil (omega-3 fatty acids) may reduce PoAF (1). We recently reported in a large, multinational randomized trial that perioperative fish oil did not reduce PoAF (2). Yet several other trials have evaluated this question, with mixed results. Most of these trials were small, and some were open label (i.e., neither double blind nor placebo controlled).

Improving Quality of Life and Functional Capacity in Atrial Fibrillation and Congestive Heart Failure

Shelton RJ, Cleland JF. — Tue, 28 May 2013 00:00:00 GMT

We read with interest the paper by Suman-Horduna et al. (1) published in the January 2013 issue of the Journal. The investigators analyzed important quality-of-life data from a substantial substudy (n = 749) of a landmark trial (2), comparing rate control to rhythm control for patients with paroxysmal (∼30%) or persistent atrial fibrillation (AF) and congestive heart failure (CHF). Overall, each strategy was associated with similar improvements in symptoms and quality of life, but results were confounded by the high proportion of patients with paroxysmal AF (29.6%) assigned to rate control who remained in sinus rhythm (i.e., crossed over to rhythm control) and by patients assigned to rhythm control who remained in AF (22.4%) (i.e., in whom rhythm control failed).

Niacin Therapy Lives for Another Day—Maybe?

Lavie CJ, DiNicolantonio JJ, Milani RV, et al. — Tue, 28 May 2013 00:00:00 GMT

Being enthusiastic regarding the importance of high-density lipoprotein cholesterol (HDL-C) and the potential for HDL-C–raising therapies (1,2,3), we were disappointed in the outcomes of the early cholesterol ester transport protein inhibition trial with torcetrapib (4) as well as the recent AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial (5) with extended-release (ER) niacin. Although AIM-HIGH was the largest and most publicized niacin trial in decades, disappointing results may partly be due to limitations in the trial, including higher doses of simvastatin and greater use of ezetimibe (22% vs. 10%) in the statin-only compared with the statin/niacin arm, as well as the fact that the statin-only group actually received up to 200 mg of immediate-release niacin, and did have an increase in HDL-C (+9.8%) and a reduction in triglycerides (TGs) (−8.1%) and low-density lipoprotein cholesterol (LDL-C) (−5.5%) at 2 years. Also, the trial was stopped after only 36 months, which may have been too short term to notice benefits in patients with baseline LDL-C levels of only 71 mg/dl, realizing that the original Lipid Research Clinic–Coronary Prevention Trial with cholestyramine (6) and the 4S (Scandinavian Simvastatin Survival Study) with simvastatin (7) included patients with markedly higher levels of LDL-C (upper 190s mg/dl), and significant benefits were not noted until well after 3 years in these trials. Nevertheless, despite including AIM-HIGH in their meta-analysis, Lavigne and Karas's analysis (8) of 11 trials in 9,959 subjects in the recent issue of the Journal still reported reductions in major cardiovascular disease and coronary heart disease events of 34% (p = 0.007) and 25% (p = 0.02), respectively, with niacin therapy, potentially partly salvaging niacin's reputation as an effective preventive therapy in addition to its documented effects in raising HDL-C, and lowering TGs and LDL-C.

Reply

Suman-Horduna I, Roy D, Talajic M, et al. — Tue, 28 May 2013 00:00:00 GMT

We thank Drs. Shelton and Cleland for their interest in our study (1) and for their thoughtful comments. We agree with their general statements regarding limitations of antiarrhythmic agents and the need to develop and rigorously test more effective rhythm control strategies. However, a few subtle inaccuracies merit clarification. First, recurrence of atrial fibrillation in patients randomized to rhythm control is not synonymous with crossover, as implied. Recurrences (and adverse effects) are intrinsic to any rhythm control strategy, including approaches centered on catheter ablation. Rather, in randomized trials, crossover refers to a deliberate investigator-approved change in treatment arm. Second, although large-scale crossover in randomized trials remains a vexing problem, its primary impact on intention-to-treat analyses is to decrease statistical power. The suggestion that unidirectional crossover (i.e., from rhythm to rate control but not vice versa) produces less biased estimates than bidirectional crossover is fallacious. Under certain conditions, the reverse may be true. Third, insinuating that the CAFÉ-II (Chronic Atrial Fibrillation and Heart Failure) trial (2), however, important, was subject to less confounding than the AF-CHF (Atrial Fibrillation and Congestive Heart Failure) trial (3) is unfounded, if only by virtue of the much larger (N = 1,376 vs. 61) sample's enhanced ability to balance unknown or unmeasured influential factors, produce normal sample distributions, yield more precise standard errors, and provide greater statistical power.

2013 ACCF/ACR/ASE/ASNC/SCCT/SCMR Appropriate Utilization of Cardiovascular Imaging in Heart Failure A Joint Report of the American College of Radiology Appropriateness Criteria Committee and the American College of Cardiology Foundation Appropriate Use Criteria Task Force

Patel MR, White RD, Abbara S, et al. — Tue, 28 May 2013 00:00:00 GMT

2013 Appropriate Utilization of Cardiovascular Imaging A Methodology for the Development of Joint Criteria for the Appropriate Utilization of Cardiovascular Imaging by the American College of Cardiology Foundation and American College of Radiology

Carr J, Hendel RC, White RD, et al. — Tue, 28 May 2013 00:00:00 GMT