Circulation (Circulation)

Publications in this journal

• Article: New Therapeutic Targets in Cardiology: Heart Failure and Arrhythmia: HCN Channels.

  François Roubille, Jean-Claude Tardif
  Circulation 05/2013; 127(19):1986-96.
• Article: Digital clubbing.

  John D Rutherford
  Circulation 05/2013; 127(19):1997-9.
• Article: Bayesian Methods for Evidence Evaluation: Are We There Yet?

  Steven N Goodman
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  ABSTRACT: "First they ignore you, then they laugh at you, then they fight you, then you win," a saying reportedly misattributed to Mahatma Ghandi(1), might apply to the use of Bayesian statistics in medical research. The idea that Bayesian approaches might be used to "affirm" findings derived from conventional methods, and thereby be regarded as more authoritative, is a dramatic turnabout from an era not very long ago when those embracing Bayesian ideas were considered barbarians at the gate. I remember my own initiation into the Bayesian fold, reading with a mixture of astonishment and subversive pleasure one of George Diamond's early pieces taking aim at conventional interpretations of large cardiovascular trials of the early 80's.(2) It is gratifying to see that the Bayesian approach, which saw negligible application in biomedical research in the 80's and began to get traction in the 90's, is now not just a respectable alternative to standard methods, but sometimes might be regarded as preferable. That said, it is premature to declare a "win," and the statistical lingua franca of biomedical research is still firmly frequentist, with P-values, confidence intervals and Type I and II errors dominating the journal landscape. It is helpful to use the thoughtful and thorough Bayesian exercise of Bittl et al.(3) to reflect on what Bayesian approaches give us, and what they don't.
  Circulation 05/2013;
• Article: High-Dose Statin Therapy in Patients with Stable Coronary Artery Disease: Treating the Right Patients Based on Individualized Prediction of Treatment Effect.

  Johannes A N Dorresteijn, S Matthijs Boekholdt, Yolanda van der Graaf, John J P Kastelein, John C Larosa, Terje R Pedersen, David A Demicco, Paul M Ridker, Nancy R Cook, Frank L J Visseren
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  ABSTRACT: BACKGROUND: Clinicians need to identify coronary artery disease patients for whom the benefits of high-dose versus usual-dose statin therapy outweigh potential harm. We therefore aimed to develop and validate a model for prediction of the incremental treatment effect of high-dose statins for individual patients in terms of reduction of 5-year absolute risk for myocardial infarction, stroke, coronary death or cardiac resuscitation. METHODS AND RESULTS: Based on data from the Treating to New Targets trial (TNT; n=10,001), a Cox proportional hazards model was developed comprising 13 easy-to-measure clinical predictors: age, sex, smoking, diabetes mellitus, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, history of myocardial infarction, coronary artery bypass grafting, congestive heart failure or abdominal aortic aneurysm, glomerular filtration rate, and treatment status (i.e. atorvastatin 80mg or 10mg). External validation in the Incremental Decrease in End Points Through Aggressive Lipid Lowering trial (IDEAL; n=8,888) confirmed adequate goodness-of-fit and calibration, but moderate discrimination (C-statistic 0.63; 95%CI 0.62-0.65). Still, among participants of both trials combined, the model identified a group of 11.7% whose predicted 5-year number needed to treat (NNT) was 25 or lower and a group of 41.9% whose predicted NNT was 50 or higher. A decision curve shows that making treatment decisions on the basis of predictions using our model may improve net benefit. CONCLUSIONS: Estimation of the incremental treatment effect of high-dose versus usual-dose statin therapy in individual coronary artery disease patients enables selection of high-risk patients that benefit most from more aggressive therapy. CLINICAL TRIAL REGISTRATION INFORMATION: www.clinicaltrials.gov. Identifiers: NCT00327691 and NCT00159835.
  Circulation 05/2013;
• Article: Impact of Onset-to-Reperfusion Time on Stroke Mortality: A Collaborative Pooled Analysis.

  Mikael Mazighi, Saqib A Chaudhry, Marc Ribo, Pooja Khatri, David Skoloudik, Maxim Mokin, Julien Labreuche, Elena Meseguer, Sharon D Yeatts, Adnan H Siddiqui, Joseph Broderick, Carlos A Molina, Adnan I Qureshi, Pierre Amarenco
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  ABSTRACT: Onset-to-reperfusion time has been reported to be associated with clinical prognosis. However, its impact on mortality remained to be assessed. Using a collaborative pooled analysis, we examined whether early mortality after successful endovascular treatment is time dependent. In a collaborative pooled analysis of 7 endovascular databases, we assessed the impact of onset-to-reperfusion time in large-artery occlusion (internal carotid artery or middle cerebral artery) on outcomes. Successful reperfusion was defined as complete or partial restoration of blood flow within 8 hours from symptom onset. Primary outcome was 90-day all-cause mortality. Secondary outcomes included 90-day favorable outcome (modified Rankin Scale score, 0-2), 90-day excellent outcome (modified Rankin Scale score, 0-1), and occurrence of any intracerebral hemorrhage within 24 to 36 hours after treatment. A total of 480 cases with successful reperfusion (median time, 285 minutes) contributed to the present pooled analysis (120 with internal carotid artery occlusion and 360 with isolated middle cerebral artery occlusion). Increasing onset-to-reperfusion time was associated with an increased rate of mortality and intracerebral hemorrhage and with a decreased rate of favorable and excellent outcomes, without heterogeneity across studies. The adjusted odds ratio for each 30-minute time increase was 1.21 (95% confidence interval, 1.09-1.34; P<0.001) for mortality, 0.79 (95% confidence interval, 0.72-0.87) for favorable outcome, 0.78 (95% confidence interval, 0.71-0.86) for excellent outcome, and 1.21 (95% confidence interval, 1.10-1.33) for intracerebral hemorrhage. Onset-to-reperfusion time affects mortality and favorable outcome and should be considered the main goal in acute stroke patient management.
  Circulation 05/2013; 127(19):1980-5.
• Article: Extreme right and left atrial enlargement in a patient with rheumatic valvular disease and mitral mechanical prosthesis.

  Alberto García-Lledó, Javier Balaguer
  Circulation 05/2013; 127(19):2000.
• Article: Radiating chest pain to the back.

  Mukesh Gopalakrishnan, Federico Silva-Palacios, Hany Demo, Paula Eryazici, Mercy Chandrasekaran, Sorin Danciu, Cesar J Herrera
  Circulation 05/2013; 127(19):e593-6.
• Article: Letter by llau and ferrandis regarding article, "bridging evidence-based practice and practice-based evidence in periprocedural anticoagulation".

  Juan V Llau, Raquel Ferrandis
  Circulation 05/2013; 127(19):e616.
• Article: Two Sides to Every Pro-Inflammatory Coin: New Insights into the Role of Dendritic Cells in the Regulation of T-Cell Driven Autoimmune Myocarditis.

  Gabriel K Griffin, Andrew H Lichtman
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  ABSTRACT: Myocarditis is a major cause of heart failure in young adults that is typically precipitated by cardiac infection with organisms such as Coxsackie B virus or the parasite Trypanosoma Cruzi(1). Myocarditis has a variety of clinical presentations but is often characterized by severe ventricular dysfunction and risk of fatal arrhythmia. Tissue injury during myocarditis is caused by direct infection of cardiomyoctes and immune-mediated responses to microbial antigens; in addition, autoimmune T cell and antibody responses to myocardial antigens can develop and persist even after the inciting infection has been cleared. The autoimmune component of myocarditis indicates a failure of self-tolerance mechanisms, and may be driven by molecular mimicry between microbial and myocardial self-antigens. Although there has been an emphasis on the role of autoantibodies in autoimmune myocarditis, such as those targeting the β1 adrenergic receptor or the αmyosin heavy chain αMHC), this may reflect the relative ease of their experimental detection as compared to assays of T cell activation by specific self-antigens. Nonetheless, the relevance of T cells is supported by the fact that lymphocytic infiltrates including CD4(+) helper T cells can be demonstrated in endocardial biopsy or autopsy sections taken from patients with myocarditis, and by the fact that many of the cardiac auto-antibodies in human myocarditis have undergone IgG class switching, which reflects T helper dependent B cell responses.
  Circulation 05/2013;
• Article: Innate Signalling Promotes Formation of Regulatory Nitric Oxide-Producing Dendritic Cells Limiting T Cell Expansion in Experimental Autoimmune Myocarditis.

  Gabriela Kania, Stefanie Siegert, Silvia Behnke, Rafael Prados-Rosales, Arturo Casadevall, Thomas F Lüscher, Sanjiv A Luther, Manfred Kopf, Urs Eriksson, Przemyslaw Blyszczuk
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  ABSTRACT: BACKGROUND: Activation of innate pattern recognition receptors promotes CD4(+) T cell-mediated autoimmune myocarditis and subsequent inflammatory cardiomyopathy. Mechanisms, which counter-regulate exaggerated heart-specific autoimmunity are poorly understood. METHODS AND RESULTS: Experimental Autoimmune Myocarditis (EAM) was induced in BALB/c mice by immunization with alpha-myosin heavy chain peptide (αMyHC) and complete Freund's adjuvant (CFA). Together with IFN-γ, heat-killed M. tuberculosis (Mtb(hk)), an essential component of CFA, converted CD11b(hi)CD11c(-) monocytes into TNFα- and nitric oxide synthase 2 (NOS2)-producing dendritic cells (TipDCs). Mtb(hk) stimulated NOS2 production via Toll-like receptor (TLR)2-mediated NF-κB activation. TipDCs limited antigen-specific T cell expansion through NOS2-dependent nitric oxide production. Moreover, TipDCs promoted NOS2 production in hematopoietic and stromal cells in a paracrine manner. Consequently, NOS2 production by both, radiosensitive hematopoietic and radioresistant stromal cells prevented exacerbation of autoimmune myocarditis in vivo. CONCLUSIONS: Innate TLR2 stimulation promotes formation of regulatory TipDCs, which confine autoreactive T cell responses in EAM via nitric oxide. Therefore, activation of innate pattern recognition receptors is not only critical for disease induction, but also for counter-regulatory mechanisms, protecting the heart from exaggerated autoimmunity.
  Circulation 05/2013;
• Article: Postoperative Troponin Screening: A Cardiac Cassandra?

  Joshua A Beckman
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  ABSTRACT: The cardiovascular management of the patient undergoing non-cardiac surgery has been in evolution for the last 35 years. Over this time frame, two secular trends have advanced in parallel but provided contrary practice implications for the care of the surgical patient. First, cardiovascular event rates have been dropping significantly over time. In 1977, Goldman and colleagues created a risk evaluation system that predicted a 22% rate of "life-threatening" cardiovascular events and more than 50% mortality in the highest risk group(1) in 1001 patients undergoing surgery. These rates of events have dropped each decade since significantly. Finks and colleagues reported 2 years ago a mere 2.8% national mortality rate for open abdominal aortic aneurysm repair; the exemplar of routine, high-risk surgery(2). These numbers were recapitulated world-wide for high-risk patients undergoing noncardiac surgery in the PeriOperative ISchemic Evaluation (POISE) trial(3). Improvements in surgical and anesthetic techniques, perioperative medical therapy, and intensive care have each participated in the significant improvement in outcomes.
  Circulation 05/2013;
• Article: Predictors of Mortality and Outcomes of Therapy in Low Flow Severe Aortic Stenosis: A PARTNER Trial Analysis.

  Howard C Herrmann, Philippe Pibarot, Irene Hueter, Zachary M Gertz, William J Stewart, Samir Kapadia, E Murat Tuczu, Vasilis Babaliaros, Vinod Thourani, Wilson Y Szeto, Joseph E Bavaria, Susheel Kodali, Rebecca T Hahn, Mathew Williams, D Craig Miller, Pamela S Douglas, Martin B Leon
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  ABSTRACT: BACKGROUND: The prognosis and treatment of patients with low flow (LF) severe aortic stenosis (AS) is controversial. METHODS AND RESULTS: The PARTNER trial randomized patients with severe AS to medical management (MM) vs transcatheter (TAVR) aortic valve replacement ("inoperable" cohort) and surgery (SAVR) vs TAVR (high risk cohort). Among 971 patients with evaluable echocardiograms (92%), LF (stroke volume index (SVI) ≤35 ml/m2) was observed in 530 (55%), LF and low ejection fraction (<50%, LEF) in 225 (23%), LF, LEF, and low mean gradient (<40 mmHg, LG) in 147 (15%). Two-year mortality was significantly higher in patients with LF compared with normal SVI (47% vs 34%, HR 1.5, 95%CI [1.25,1.89], p=0.006). In the inoperable cohort, patients with LF had higher mortality than those with normal flow, but both groups improved with TAVR (46% vs 76% with LF and 38% vs 53% with normal flow, p<0.001). In the high-risk cohort, there was no difference between TAVR and SAVR. In patients with paradoxical LF and LG (preserved EF), TAVR reduced 1-year mortality from 66% to 35% (HR 0.38, p=0.02). LF was an independent predictor of mortality in all patient cohorts (HR ~1.5), whereas EF and gradient were not. CONCLUSIONS: Low flow is common in severe AS and independently predicts mortality. Survival is improved with TAVR as compared to MM and similar with TAVR and SAVR. A measure of flow (SVI) should be included in the evaluation and therapeutic decision making of patients with severe AS. CLINICAL TRIAL REGISTRATION INFORMATION: clinicaltrial.gov. Identifier: NCT00530894.
  Circulation 05/2013;
• Article: Quantifying Options for Reducing Coronary Heart Disease Mortality By 2020.

  Mark D Huffman, Donald M Lloyd-Jones, Hongyan Ning, Darwin R Labarthe, Maria Guzman Castillo, Martin O'Flaherty, Earl S Ford, Simon Capewell
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  ABSTRACT: BACKGROUND: The AHA 2020 Strategic Impact Goal proposes a 20% improvement in cardiovascular health of all Americans. We aimed to estimate the potential reduction in coronary heart disease (CHD) deaths. METHODS AND RESULTS: We used data on 40,373 CVD-free adults from NHANES (1988-2010). We quantified recent trends for six metrics (total cholesterol [TC]; systolic blood pressure [SBP]; physical inactivity; smoking; diabetes; obesity) and generated linear projections to 2020. We projected the expected number of CHD deaths in 2020 if 2006 age- and sex-specific CHD death rates remained constant, which would result in approximately 480,000 CHD deaths in 2020 (12% increase). We used the previously validated IMPACT CHD model to project numbers of CHD deaths in 2020 under two different scenarios. A) Assuming a 20% improvement in each CVH metric, we project 365,000 CHD deaths in 2020, (range 327,000-403,000) a 24% decrease reflecting modest reductions in TC (-41,000), SBP (-36,000), physical inactivity (-12,000), smoking (-10,000), diabetes (-10,000), and obesity (-5,000). B) Assuming that recent risk factor trends continue to 2020, we project 335,000 CHD deaths (range 274,000-386,000), a 30% decrease reflecting improvements in TC, SBP, smoking and physical activity (~167,000 fewer deaths), offset by increases in diabetes and BMI (~24,000 more deaths). CONCLUSIONS: Two contrasting scenarios of change in CVH metrics could prevent 24-30% of the CHD deaths expected in 2020, though with differing impacts by age. Unfavorable continuing trends in obesity and diabetes would have substantial adverse effects. This analysis demonstrates the utility of modelling to inform health policy.
  Circulation 05/2013;
• Article: ACCF/AHA/SCAI 2013 Update of the Clinical Competence Statement on Coronary Artery Interventional Procedures: A Report of the American College of Cardiology Foundation/American Heart Association/American College of Physicians Task Force on Clinical Competence and Training (Writing Committee to Revise the 2007 Clinical Competence Statement on Cardiac Interventional Procedures).

  John G Harold, Theodore A Bass, Thomas M Bashore, Ralph G Brindis, John E Brush, James A Burke, Gregory J Dehmer, Yuri A Deychak, Hani Jneid, James G Jollis, [......], Glenn N Levine, James B McClurken, John C Messenger, Issam D Moussa, J Brent Muhlestein, Richard M Pomerantz, Timothy A Sanborn, Chittur A Sivaram, Christopher J White, Eric S Williams
  Circulation 05/2013;
• Article: Atorvastatin, Etidronate, or Both in Patients at High Risk for Atherosclerotic Aortic Plaques: A Randomized Controlled Trial.

  Tetsuya Kawahara, Masako Nishikawa, Chie Kawahara, Tetsuya Inazu, Kunio Sakai, Gen Suzuki
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  ABSTRACT: BACKGROUND: Statins are not effective in reducing atherosclerotic plaques of the abdominal aorta, and accumulating evidence suggests that bisphosphonates have the potential to induce the regression of atherosclerotic plaques of the abdominal aorta. METHODS AND RESULTS: A prospective, randomized, open-label, blinded-endpoint trial, involving 108 participants with hypercholesterolemia was conducted, participants received either 20 mg of atorvastatin daily, 400 mg of etidronate daily, or both drugs daily. The primary endpoint was the percent change in maximal vessel wall thickness of atherosclerotic plaques in the thoracic and abdominal aortas as measured by magnetic resonance imaging, following 12 months of treatment. In both the combination-therapy and atorvastatin groups, maximal vessel wall thickness of the thoracic aorta was reduced by 13.8% [95% confidence interval [CI] -16.4 to -11.3] and 12.3% [95% CI -14.9 to -9.7], respectively. These reduction rates were comparable between both groups (p=0.61). Meanwhile, in the etidronate group, maximal vessel wall thickness of the thoracic aorta remained unchanged (2.2% [95% CI -0.3 to 4.8%]). Conversely, maximal vessel wall thickness of the abdominal aorta was reduced more effectively in the combination-therapy group (-11.4%) than those achieved in the atorvastatin group (-0.9%; p<0.001) and the etidronate group (-5.5%; p=0.006). CONCLUSIONS: Atorvastatin plus etidronate combination-therapy for 12 months significantly reduced both thoracic and abdominal aortic plaques, while atorvastatin monotherapy reduced only thoracic aortic plaques, and etidronate monotherapy reduced only abdominal aortic plaques. The effectiveness of combination-therapy on reducing atherosclerotic plaques in the abdominal aorta was significantly greater than both atorvastatin and etidronate monotherapy. CLINICAL TRIAL REGISTRATION INFORMATION: http://www.umin.ac.jp/ctr/. Identifier: UMIN 000002635.
  Circulation 05/2013;
• Article: Should Bilateral Internal Thoracic Artery (BITA) Grafting Be Used In Elderly Patients Undergoing Coronary Artery Bypass Grafting?

  Benjamin Medalion, Rephael Mohr, Osnat Frid, Gideon Uretzky, Nachum Nesher, Yosef Paz, Amir Kramer, Dmitry Pevni
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  ABSTRACT: BACKGROUND: Although Bilateral Internal Thoracic Artery (BITA) grafting is associated with improved survival, the use of this technique in elderly is controversial due to their increased surgical risk and shorter life expectancy. The purpose of this study is to evaluate the effect of age on outcome of patients undergoing BITA grafting. METHODS AND RESULTS: Between 1996 and 2001, 1714 consecutive patients underwent skeletonized BITA grafting, of whom 748 were 65 years of age or younger, 688 were between 66 and 75 and 278 were 76 or older. Operative mortality of the three age groups (1.2%, 4.1% and 5.8%) was lower than the logistic Euroscore predicted mortality (3.9%, 6.5%, 9.3%, respectively, p<0.001). There was no significant difference between groups in occurrence of sternal infection (1.3%, 2.6% and 1.4% respectively, p=0.171). Mean follow-up was 11.5 years. Kaplan-Meier 10-year survival for patients ≤65, 66-75 and >75 years of age was 85%, 65% and 40%, respectively (p<0.001). They were better than the corresponding predicted Charlson Comorbidity Index survivals (68%, 37% and 20%, respectively, p<0.001 for all age groups), approaching survival of gender and age-matched general population (90%, 70% and 41%, respectively). Age 65 or younger (HR 0.232, 95% Ci 0.188-0.288) and 66-75 (HR 0.499, 95% Ci 0.414-0.602) were independent predictors of improved survival (Cox Model) CONCLUSIONS: BITA grafting should be considered in patients older than 65, due to the significant survival benefit obtained with this surgical technique without additional risk of sternal wound infection related to age.
  Circulation 05/2013;
• Article: Histopathology of Embolic Debris Captured During Transcatheter Aortic Valve Replacement.

  Nicolas M Van Mieghem, Marguerite E I Schipper, Elena Ladich, Elham Faqiri, Robert van der Boon, Abas Randjgari, Carl Schultz, Adriaan Moelker, Robert-Jan van Geuns, Fumiyuki Otsuka, Patrick W Serruys, Renu Virmani, Peter P de Jaegere
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  ABSTRACT: BACKGROUND: Recent Transcatheter Aortic Valve Replacement (TAVR) studies have raised concerns about adverse cerebrovascular events. The etiopathology of the embolized material is currently unknown. METHODS AND RESULTS: A total of 40 patients underwent TAVR with the use of a dual filter-based embolic protection device (Montage™ Dual Filter System, Claret Medical, Inc. Santa Rosa, CA, USA). Macroscopic material liberated during the TAVR procedure was captured in the device filter baskets in 30 (75%) patients and sent for histopathological analysis. The captured material varied in size from 0,15mm to 4,0mm. Amorphous calcified material (size 0.55 mm - 1.8 mm) was identified in five patients (17%). In eight patients (27%), the captured material (size 0.25mm - 4.0mm) contained valve tissue composed of loose connective tissue (collagen and elastic fibers) with focal areas of myxoid stroma, with or without coverage by endothelial cells and intermixed with fibrin. In another 13 (43%) patients collagenous tissue, which may represent elements of vessel wall and/or valve like structures were identified. In nine patients (30%) thrombotic material was intermixed with neutrophils (size 0.15 mm - 2.0 mm). Overall, thrombotic material was found in 52% of patients and tissue fragments compatible with aortic valve leaflet or aortic wall origin in 52% (21/40) of patients. CONCLUSIONS: Embolic debris travelling to the brain was captured in 75% of TAVR procedures where a filter-based embolic protection device was used. The debris consisted of fibrin, or amorphous calcium and connective tissue derived most likely from either the native aortic valve leaflets or aortic wall.
  Circulation 05/2013;
• Article: Letter by erdoes et Al regarding article, "cerebral embolization during transcatheter aortic valve implantation: a transcranial Doppler study".

  Gabor Erdoes, Stephan Windecker, Balthasar Eberle
  Circulation 05/2013; 127(18):e590.
• Article: Hampton's Hump and Palla's Sign in Pulmonary Embolism.

  Ricardo Ladeiras-Lopes, Ayres Neto, Cláudia Costa, Marta Sousa, Paula Ferreira, Vítor Paixão Dias, Vasco Gama Ribeiro
  Circulation 05/2013; 127(18):1914-5.