Card Fail Research Articles

COUNTERPOINT: the Seductive Trap of Relying on Exaggerated Effects in Short-Term Heart Failure Trials to Predict Benefits and Risks in Patients With Long-Term Disease

COUNTERPOINT: the Seductive Trap of Relying on Exaggerated Effects in Short-Term Heart Failure Trials to Predict Benefits and Risks in Patients With Long-Term Disease

EE3 Cost Estimation of Published Heart Failure and Edema Events in Hyperkalemic Patients on Patiromer and Sodium Zirconium Cyclosilicate

Risk of real-world hospitalizations for heart failure (HHF), and edema hospitalizations or emergency department (ED) visits (edema events) were previously directly compared by Zhuo et al (J Card Fail 2022;28:1414–23) for patients on patiromer (PAT) or sodium zirconium cyclosilicate (SZC), and showed consistent numerical differences across all endpoints favoring PAT. Statistical significance was achieved on the secondary endpoint of edema events and in a subgroup of patients who did not have HF prior to index HHF event. These numeric differences warrant further investigation as they may have economic and/or clinical importance.

Genetic Testing for Cardiomyopathies in Japan: Embarking on a Journey of Discovery

Our understanding of the genetic contributions to heart muscle disorders has grown tremendously over the past 4 decades. The impact of genotype on cardiomyopathy diagnosis, prognosis, and treatment is well-recognized, although there remains considerable heterogeneity in approach to cardiomyopathy evaluation, access to genetic testing, availability of molecular-based therapies, and representation of diverse populations in genetic databases across the world. In this issue of the Journal of Cardiac Failure, Kubo and Kitaoka 1 Kubo T, Kitaoka H. Genetic testing for cardiomyopathy in Japan 2022: current status and issues of precision medicine. J Card Fail. Google Scholar provide insight into these issues through their appraisal of the current state of genetic evaluation of cardiomyopathies in Japan.

Voluntary Reporting of Guideline-Directed Medical Therapy Use Rates in the Public Domain: A Challenge to the Heart Failure Community

Achieving target or maximally tolerated doses of Guideline Directed Medical Therapy (GDMT) is associated with decreased morbidity and mortality in patients with heart failure and reduced ejection fraction (HFrEF). 1 Greene SJ Butler J Hellkamp AS Spertus JA Vaduganathan M Devore AD Albert NM Patterson JH Thomas L Williams FB Hernandez AF Fonarow GC. Comparative Effectiveness of Dosing of Medical Therapy for Heart Failure: From the CHAMP-HF Registry. J Card Fail. 2022; 28: 370-384 Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar However, in a contemporary cohort of outpatients with HFrEF, the percentage of patients achieving target doses of GDMT was woefully low, with <1% of patients achieved target doses of three foundational components of GDMT (ACE/ARB/ARNI, beta-blocker, and MRA) at one-year follow-up. 2 Greene SJ Fonarow GC DeVore AD Sharma PP Vaduganathan M Albert NM Duffy CI Hill CL McCague K Patterson JH Spertus JA Thomas L Williams FB Hernandez AF Butler J. Titration of Medical Therapy for Heart Failure With Reduced Ejection Fraction. J Am Coll Cardiol. 2019; 73: 2365-2383 Crossref PubMed Scopus (216) Google Scholar

A New Norm for Early-Career Advanced Heart Failure Clinicians

The path to become an advanced heart failure and transplant cardiologist (AHFTC) is long and arduous. In the final year of postgraduate training, fellows are expected to rapidly acquire inpatient and outpatient expertise in heart failure, pulmonary hypertension, mechanical circulatory support, and heart transplantation in addition to numerous other competencies that are now expected in the skillset of an AHFTC. Moreover, trainees must cement a new, foundational knowledge base regarding the ethical, social, and economic implications of limited resource stewardship and cardiovascular health inequities.( 1 Jessup M Drazner MH Book W Cleveland JC Dauber I Farkas S et al. 2017 ACC/AHA/HFSA/ISHLT/ACP Advanced Training Statement on Advanced Heart Failure and Transplant Cardiology (Revision of the ACCF/AHA/ACP/HFSA/ISHLT 2010 Clinical Competence Statement on Management of Patients With Advanced Heart Failure and Cardiac Transplant): A Report of the ACC Competency Management Committee. Circ Heart Fail. 2017; 10 PubMed Google Scholar ) The challenges that early career cardiologists face have been well-documented ( 2 Tong CW Ahmad T Brittain EL Bunch TJ Damp JB Dardas T et al. Challenges facing early career academic cardiologists. J Am Coll Cardiol. 2014 Jun 3; 63: 2199-2208 Crossref PubMed Scopus (44) Google Scholar ), but for nearly three years, the coronavirus disease 2019 (COVID-19) pandemic has additionally and irrevocably impacted this particularly vulnerable time in junior AHFTCs’ careers (Figure 1). We were frequently “redeployed” as bedside COVID-19 clinicians, working long hours under, at times, hazardous conditions. The first year of the pandemic truncated the typical AHFT training experience by nearly 25% as trainees were reassigned from their native training programs to other patient care roles, and since then, nearly every aspect of medical education and healthcare delivery has been transformed. Enforcing historical training and fellow-to-faculty transition models amidst this persistent disruption has meant that AHFT graduates may be underprepared for independent practice, where we must confront new challenges in clinical decision making; adapt to new institutions, cultures, and workflows; build practices, relationships, referral bases; maintain productivity; and launch research, administrative, and teaching careers. More training may be beneficial to bolster these skills, though asking trainees to prolong fellowship is likely to result in further decline in interest in AHFT cardiology.( 3 Chuzi S Reza N. Cultivating Interest in Heart Failure Careers: Can We Reverse the Current Trend?: Cultivating Interest in Heart Failure Careers. J Card Fail. 2021 Jul; 27: 819-821 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar )

THE DANGER OF DIGOXIN: TOXICITY WITHIN THE "THERAPEUTIC” RANGE

THE DANGER OF DIGOXIN: TOXICITY WITHIN THE "THERAPEUTIC” RANGE

Can We Stop Reflexively Discontinuing Mineralocorticoid Antagonists for Patients With Heart Failure and Hyperkalemia?

The importance of promptly introducing low doses of multiple classes of guideline-directed medical therapy (GDMT) in patients with symptomatic heart failure is underscored in the recent heart failure guidelines. 1 Heidenreich PA Bozkurt B Aguilar D et al. 2022 AHA/ACC/HFSA guideline for the management of heart failure. J Card Fail. 2022; 28: e1-e167https://doi.org/10.1016/j.cardfail.2022.02.010 Abstract Full Text Full Text PDF PubMed Scopus (8) Google Scholar Concerns purported to foster the underuse of GDMT include inadequate patient and laboratory follow-up, patient nonadherence, medication-related expenses, polypharmacy, and the perceived risk of hyperkalemia (Fig. 1). 2 Greene SJ Butler J Albert NM et al. Medical therapy for heart failure with reduced ejection fraction. J Am Coll Cardiol. 2018; 72: 351-366https://doi.org/10.1016/j.jacc.2018.04.070 Crossref PubMed Scopus (412) Google Scholar Such trepidations commonly lead to avoidance or premature discontinuation of mineralocorticoid antagonists (MRAs). Observational data show that a single episode of hyperkalemia is cited as justification for cessation of MRAs in approximately 30% of patients; severe hyperkalemia (K+ ≥ 6 mmol/L) occurs in only one-quarter of those patients, but is commonly labeled as medication intolerance. 3 Trevisan M Fu EL Xu Y et al. Stopping mineralocorticoid receptor antagonists after hyperkalaemia: trial emulation in data from routine care. Eur J Heart Fail. 2021; 23: 1698-1707https://doi.org/10.1002/ejhf.2287 Crossref PubMed Scopus (10) Google Scholar MRA discontinuation decreases the incidence of recurrent hyperkalemia but confers a 10%–30% increased downstream risk of mortality and cardiovascular events. 3 Trevisan M Fu EL Xu Y et al. Stopping mineralocorticoid receptor antagonists after hyperkalaemia: trial emulation in data from routine care. Eur J Heart Fail. 2021; 23: 1698-1707https://doi.org/10.1002/ejhf.2287 Crossref PubMed Scopus (10) Google Scholar ,4 Siddiqi Tariq J Usman Muhammad S Abid M et al. Is stopping mineralocorticoid receptor antagonists after hyperkalemia associated with increased mortality in heart failure? A systematic review and meta-analysis. J Am Coll Cardiol. 2022; 79: 406https://doi.org/10.1016/S0735-1097(22)01397-3 Crossref Google Scholar Thus, patients are frequently deprived of life-saving therapies owing to hyperkalemia concerns. In this article, we present evidence supporting MRA continuation in the setting of mild hyperkalemia, suggest mitigation strategies and interventions for moderate to severe hyperkalemia, and expand on new and future options that may help attenuate the overall risk of hyperkalemia and its complications.

Impaired SARS-CoV-2 mRNA Vaccine Antibody Response in Chronic Medical Conditions: A Real-World Analysis

Impaired SARS-CoV-2 mRNA Vaccine Antibody Response in Chronic Medical Conditions: A Real-World Analysis

Role and Contribution of the General Heart Failure Cardiologist: Further Expansion of the Multidisciplinary Heart Failure Approach

Never before has the field of heart failure seen such accelerated advancements in medical and device therapies. The expansion of knowledge, albeit progressively over the last 5 decades with more rapid recent advances, provides heart failure specialists with a multitude of treatment options supported by a strong foundation of evidence. Nonetheless, the concurrent increasing prevalence of heart failure challenges the cardiology workforce to provide adequate care. Recently, the Journal of Cardiac Failure featured an article by Chuzi and Reza 1 Chuzi S Reza N Cultivating interest in heart failure careers: can we reverse the current trend? Cultivating interest in heart failure careers. J Card Fail. 2021; 27: 819-821 Abstract Full Text Full Text PDF PubMed Scopus (2) Google Scholar highlighting the need to cultivate interest in heart failure careers, rightfully suggesting the need to strengthen the advanced heart failure workforce. However, as it stands, heart failure is still an all-consuming cardiovascular disease, advancing much faster than the advanced heart failure workforce can handle. In addition, many advanced heart failure and transplant training programs remained unfilled to date. Thus, the need for dedicated specialized training to achieve the demanding competencies of heart failure may require further strategic development of training programs to manage preventive, early, and symptomatic heart failure stages.

MANAGING HEART FAILURE WITH REDUCED EJECTION FRACTION: WHAT TO KNOW?

The estimated population of congestive heart failure (CHF) patients in Pakistan is 28 millions.1 Besides epidemics of type 2 diabetes mellitus and coronary heart disease, South Asian countries are also be at an increased risk of heart failure at earlier ages than other racial/ethnic groups.2 Heart failure sub classified into three categories:&#x0D; &#x0D; With preserved ejection fraction (LVEF&gt;50%),&#x0D; Mid-range ejection fraction (LVEF41-49%),&#x0D; Reduced ejection fraction (LVEF&lt;40%).3&#x0D; &#x0D; According to studies in United States of American (USA) and United Kingdom (UK)4,5 heart failure with reduced ejection fraction (HFrEF) prevalence has increased due to ageing population, improved survival from myocardial infarction and high prevalence of co-morbid conditions like diabetes and obesity. With increasing number of young patients (&lt;40 years) with acute myocardial infarction (AMI) 12%6 in our population, prevalence of heart failure with predisposing factors need to be explored.&#x0D; Other than diagnosing and work up of these patients, the most challenging part is the pharmacological treatment by therapeutic agents proven to reduce morbidity and mortality in HRrEF. Registries have shown under-usage of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), angiotensin receptor-neprilysin inhibitor (ARNI), Beta-blockers and mineralocorticoid receptor antagonists (MRA) in such patients.7 Reason of not acheving the outcomes were due to not attaining the target levels of drugs dosages.8&#x0D; With recommendations from new guidelines new novel drug therapies i.e. sodium-glucose cotransporter-2 (SGLT2) inhibitors, most debatable questions from the physicians are keeping in view the hemodynamic status and kidney function. Questions coming to the Physicians minds include;9&#x0D; &#x0D; Should all guideline directed medical therapies be started together or stage wise?&#x0D; Which drugs should be titrated first?&#x0D; How quick can one up-titrate B-blockers and ARNI?&#x0D; At what level of kidney impairment should one stop ACE/ARB/ARNI/SGLT2 inhibitors?&#x0D; When should one refer these patients for cardiac resynchronization therapy device (CRTD) or Heart Transplantation?&#x0D; When should one repeat transesophageal echocardiography (TEE)?&#x0D; &#x0D; Physicians need to have clear answers and stance on the above queries.&#x0D; HFrEF is a major public health concern in our population especially with early onset of ischemic heart disease (IHD). Awareness, education and up to date knowledge regarding early diagnosis, work up and adjustments of drugs in such patients with proper follow up is important to reduce the ever rising morbidity and mortality in our population.&#x0D; &#x0D; References&#x0D; &#x0D; Sheikh SA. Heart failure in Pakistan: A demographic survey. J Card Fail. 2006;12(8):S157.&#x0D; Martinez-Amezcua P, Haque W, Khera R, Kanaya AM, Sattar N, Lam CS, et al. The upcoming epidemic of heart failure in South Asia. Circ Heart Fail. 2020;13(10):e007218.&#x0D; Yancy CW, Jessup M, Bozkurt B, Butler J, Casey Jr DE, Colvin MM, et al. 2017 ACC/AHA/HFSA focused update of the 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Failure Society of America. J Am Coll Cardiol. 2017;70(6):776-803.&#x0D; Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics—2020 update: a report from the American Heart Association. Circulation. 2020;141(9):e139-596.&#x0D; Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, et al. Heart disease and stroke statistics—2015 update: a report from the American Heart Association. Ccirculation. 2015;131(4):e29-322.&#x0D; Batra MK, Rizvi NH, Sial JA, Saghir T, Karim M. Angiographic Characteristics and in Hospital Outcome of Young Patients, Age Up to 40 Versus More Than 40 Years Undergoing Primary Percutaneous Coronary Intervention. J Pak Med Assoc. 2019;69(9):1308-12.&#x0D; Greene SJ, Butler J, Albert NM, DeVore AD, Sharma PP, Duffy CI, et al. Medical therapy for heart failure with reduced ejection fraction: the CHAMP-HF registry. J Am Coll Cardiol. 2018;72(4):351-66.&#x0D; Konstam MA, Neaton JD, Dickstein K, Drexler H, Komajda M, Martinez FA, et al. Effects of high-dose versus low-dose losartan on clinical outcomes in patients with heart failure (HEAAL study): a randomised, double-blind trial. Lancet. 2009;374(9704):1840-8.&#x0D; Murphy SP, Ibrahim NE, Januzzi JL. Heart failure with reduced ejection fraction: a review. JAMA. 2020;324(5):488-504.&#x0D;

MARKEDLY ELEVATED TROPONIN WITH COVID-19 PNEUMONIA WITHOUT ACUTE CORONARY SYNDROME

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: COVID infection can present with diverse manifestations. We present an interesting case of very high troponin elevation in patient with COVID infection without obvious reason for troponin elevation. CASE PRESENTATION: A 66-year-old man with history of HTN, DM2, CAD (CABG in 2009, percutaneous vascularization of RCA with multiple DES in 2018), NSTEMI- 1 year ago, PVD, status post left BKA, ESRD on HD presented with 1 week of watery diarrhea after being tested positive for COVID. He denied chest pain, had minimal SOB. He received first dose of COVID vaccine 2 weeks prior. Vital signs: afebrile, BP 145/68 mmhg, HR 75 beats/min, RR 20/min, oxygen saturation 90% on RA and 96% on 3L of O2 via NC. PE: R- IJ permanent catheter, L- BKA, lungs clear. Labs: COVID PCR assay (+), D dimer 359 D-DU ng/ml, LDH 330 U/l, ferritin 3207 ng/ml, CRP quant 87 ml/l, SARS-CoV-2 Ig G (RBD) 1.14 S/CO, SARS-COV-2 IgM (Beckman) 2.56. troponin (AccuTnI) 13.46 ng/ml, CPK normal, Cr 7.5 (at the baseline), EKG - sinus rhythm, left axis deviation, negative T waves in lateral leads and ST depression up to 1 m in anterior leads, no changes from old EKG, CXR - Increased b/l pulmonary opacities compatible with atypical/viral pneumonia. The most recent ECHO 1 year ago – mild LV dysfunction with thin and akinetic inferior and basal posterior walls, LVEF 50%. Patient was already on aspirin, plavix, statin and that treatment was continued during hospital course. COVID pneumonia was treated with dexamethasone and convalescent plasma versus placebo (VA Cures- 1 Trial). His hospital stay was uneventful, he remained hemodynamically stable and asymptomatic and was discharged home DISCUSSION: Our patient has known history of CAD and ESRD which are well known cause for elevated troponin. However his Cr level was at his baseline and his previous troponin levels were never this high even when he had NSTEMI, it was only 1.44 ng/ml. During this admission with Covid infection his troponin level was as high as 13.46 ng/ml and trended down to 4.15 ng/ml on discharge, his baseline level of troponin is 0.03-0.88 ng/ml. Reasons for such a high level of troponin can be due to Type II MI or myocarditis. In the settings of COVID infection it has been suggested that troponemia can be due to microvascular damage occurring in the heart with perfusion defects, vessel hyperpermeability, vasospasm and high cytokine levels may represent the key player of myocardial injury (1). Our patient did not have a very severe form of COVID pneumonia that required intubation in fact, he was saturating well on minimal oxygen requirements. He remained asymptomatic with no new interval EKG changes or any other signs of acute coronary syndrome (ACS). CONCLUSIONS: Serum Troponin can be significantly elevated in the setting of COVID infection and in the absence of ACS. REFERENCE #1: Reference #1: Tersalvi G, Vicenzi M, Calabretta D, Biasco L, Pedrazzini G, Winterton D. Elevated Troponin in Patients With Coronavirus Disease 2019: Possible Mechanisms. J Card Fail. 2020;26(6):470-475. doi:10.1016/j.cardfail.2020.04.009 DISCLOSURES: no disclosure on file for Moses Bachan;no disclosure on file for Zinobia Khan;No relevant relationships by Dileep Kumar, source=Web Response No relevant relationships by Mirjana Petrovic Elbaz, source=Web Response

Safety and Efficacy of Veverimer in Acidotic Patients With CKD and Heart Failure

Safety and Efficacy of Veverimer in Acidotic Patients With CKD and Heart Failure

Biomarker Testing Considerations in the Evaluation and Management of Patients With Heart Failure: Perspectives From the International Federation of Clinical Chemistry and Laboratory Medicine Committee

The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Committee on Clinical Applications of Cardiac Bio-Markers (C-CB) agree on the objective evidence that laboratory biomarkers can provide in the diagnosis of HF and support natriuretic peptides (NP; with b-type NP [BNP] and N-terminal pro-BNP [NT-proBNP] predominantly available from clinical laboratories) as the most well-documented and suitable biomarkers in this regard. We also believe it is important to highlight analytical issues that may affect the clinical interpretation of cardiac biomarkers, including the NPs. 1 Bozkurt B Coats AJ Tsutsui H Abdelhamid M Adamopoulos S Albert N et al. Universal definition and classification of heart failure: a report of the Heart Failure Society of America, Heart Failure Association of the European Society of Cardiology, Japanese Heart Failure Society and Writing Committee of the Universal Definition of Heart Failure. J Card Fail. 2021 Mar 1; (S1071-9164(21)00050-6)https://doi.org/10.1016/j.cardfail.2021.01.022 Google Scholar , 2 Mentz RJ Lala A. The universal definition of heart failure: perspectives from diverse stakeholders. J Card Fail. 2021; 27: 386 Google Scholar , 3 Wu AHB Christenson RH Greene DN Jaffe AS Kavsak PA Ordonez-Llanos J et al. Clinical laboratory practice recommendations for the use of cardiac troponin in acute coronary syndrome: expert opinion from the Academy of the American Association for Clinical Chemistry and the Task Force on Clinical Applications of Cardiac Bio-Markers of the International Federation of Clinical Chemistry and Laboratory Medicine. Clin Chem. 2018; 64: 645-655 Google Scholar , 4 Kavsak PA Lam CSP Saenger AK Jaffe AS Collinson P Pulkki K et al. Educational recommendations on selected analytical and clinical aspects of natriuretic peptides with a focus on heart failure: a report from the IFCC Committee on Clinical Applications of Cardiac Bio-Markers. Clin Chem. 2019; 65: 1221-1227 Google Scholar Accordingly, we have listed herein the first 5 of the 10 most current laboratory recommendations that clinicians should be cognizant of when ordering NP tests. 4 Kavsak PA Lam CSP Saenger AK Jaffe AS Collinson P Pulkki K et al. Educational recommendations on selected analytical and clinical aspects of natriuretic peptides with a focus on heart failure: a report from the IFCC Committee on Clinical Applications of Cardiac Bio-Markers. Clin Chem. 2019; 65: 1221-1227 Google Scholar Our aim is to highlight analytic issues of clinical relevance and provide recommendations to help clinicians optimally use NP values with respect to the universal definition of heart failure. To this end, we have listed the recommendations with corresponding text in the universal definition of heart failure to further clarify these important aspects.

Modified technique for left ventricular assist device insertion in the setting of apical calcification.

Modified technique for left ventricular assist device insertion in the setting of apical calcification.

Navigating Early Careers in Heart Failure in the Era of Novel Coronavirus Disease-2019

Navigating Early Careers in Heart Failure in the Era of Novel Coronavirus Disease-2019

Beta-Blockers for Primary Therapy of Heart Failure With Preserved Ejection Fraction: An Idea Whose Time Has Gone?

The beneficial effects of beta-blockers (BBs) in heart failure (HF) with reduced ejection fraction (HFrEF), including large (∼60%) reductions in mortality even on top of other mortality-reducing agents, are well established. However, there is uncertainty regarding the potential benefits and risks of BB for patients with HF with preserved ejection fraction (HFpEF), with a considerable amount of data suggesting lack of benefit or even worsening. In this issue of the Journal, Nambiar et al. provide additional valuable data regarding this important question. 1 Nambiar L. Silverman D. VanBuren P. et al. Beta-blocker cessation in stable outpatients with heart failure with a preserved ejection fraction. J Card Fail. 2019; (S1071-9164:30616-5) Abstract Full Text Full Text PDF PubMed Google Scholar

Academy of Nutrition and Dietetics Evidence-Based Practice Guideline for the Management of Heart Failure in Adults

Academy of Nutrition and Dietetics Evidence-Based Practice Guideline for the Management of Heart Failure in Adults

30-Year-Old Man With Outside-of-Hospital Cardiac Arrest

30-Year-Old Man With Outside-of-Hospital Cardiac Arrest

6 CardioMEMS for Effective Management of Heart Failure: Reducing Healthcare Utilization and 30 Day Readmissions

Heart failure (HF) affects over 5 million Americans and is associated with frequent, costly acute care hospitalizations and penalties for high 30-day readmission rates. Although current guidelines emphasize the importance of implementing systems to coordinate and deliver effective care, HF admission rates have increased, while readmission rates have remained essentially unchanged in the past decade. Early recognition of a HF episode is paramount in preventing a readmission. Research from the Champion Trial (J Card Fail. 2011 Jan;17(1):3-10. http://dx.doi.org/10.1016/j.cardfail.2010.08.002) demonstrates that pulmonary artery pressures more accurately reflect volume status changes in the heart failure patient than traditional methods of weight monitoring and physical assessment. These changes in volume status are also shown to precede a change in weight or symptom development by 1-3 weeks. The CardioMEMS Heart Failure Monitoring System is a permanently implantable pulmonary artery sensor device designed to transmit daily pulmonary artery (PA) pressure measurements from the patient’s home to a website available to the healthcare team. Monitoring PA pressure provides tangible data to help guide HF management in an outpatient setting.

Restriction therapy in acute heart failure is not shown to be effective

A critical appraisal and clinical application of Travers B, O’Loughlin C, Murphy NF, et al. Fluid restriction in the management of decompensated heart failure: no impact on time to clinical stability. J Card Fail. 2007;13(2):128-132. doi: 10.1016/j.cardfail.2006.10.012