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Katelyn W Sylvester,1 Judy WM Cheng,1,3 Mandeep R Mehra2,41Department of Pharmacy, 2Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA; 3Massachusetts College of Pharmacy and Health Sciences, Boston, MA, 4Harvard Medical School, Boston MA, USAAbstract: Low dose aspirin therapy plays a fundamental role in both the primary and secondary prevention of cardiovascular events. Although the evidence using low dose aspirin for secondary prevention is well-established, the decision to use aspirin for primary prevention is based on an evaluation of the patient’s risk of cardiovascular events compared to their risk of adverse events, such as bleeding. In addition to the risk of bleeding associated with long term aspirin administration, upper gastrointestinal side effects, such as dyspepsia often lead to discontinuation of therapy, which places patients at an increased risk for cardiovascular events. One option to mitigate adverse events and increase adherence is the addition of esomeprazole to the medication regimen. This review article provides an evaluation of the literature on the concomitant use of aspirin and esomeprazole available through February 2013. The efficacy, safety, tolerability, cost effectiveness, and patient quality of life of this regimen is discussed. A summary of the pharmacokinetic and pharmacodynamic interactions between aspirin and esomeprazole, as well as other commonly used cardiovascular medications are also reviewed. The addition of esomeprazole to low dose aspirin therapy in patients at high risk of developing gastric ulcers for the prevention of cardiovascular disease, significantly reduced their risk of ulcer development. Pharmacokinetic and pharmacodynamic studies suggested that esomeprazole did not affect the pharmacokinetic parameters or the antiplatelet effects of aspirin. Therefore, for those patients who are at a high risk of developing a gastrointestinal ulcer, the benefit of adding esomeprazole likely outweighs the risks of longer term proton pump inhibitor use, and the combination can be recommended. Administering the two agents separately may also be more economical. On the other hand, for those patients at lower risk of developing a gastrointestinal ulcer, both the additional risk and cost make the inclusion of a proton pump inhibitor unwarranted.Keywords: aspirin, esomeprazole, proton pump inhibitors, cardiovascular event prevention

UnlabelledThe mycophenolate mofetil (MMF) trial involved 650 heart transplant patients from 28 centers who received MMF or azathioprine (AZA), both in combination with cyclosporine and corticosteroids. Baseline and 1-year intravascular ultrasound (IVUS) were performed in 196 patients (102 MMF and 94 AZA) with no differences between groups in IVUS results analyzed by morphometric analysis (average of 10 evenly spaced sites, without matching sites between studies). Baseline to first-year IVUS data can also be analyzed by site-to-site analysis (matching sites between studies), which has been reported to be more clinically relevant. Therefore, we used site-to-site analysis to reanalyze the multicenter MMF IVUS data.ResultsIVUS images were reviewed and interpretable in 190 patients (99 MMF and 91 AZA) from the multicenter randomized trial. The AZA group compared to the MMF group had a larger number of patients with first-year maximal intimal thickness (MIT)>or=0.3 mm (43% vs. 23%, p=0.005), a greater decrease in the mean lumen area (p=0.02) and a decrease in the mean vessel area (the area actually increased in the MMF group, p=0.03).ConclusionMMF-treated heart transplant patients compared to AZA-treated patients, both concurrently on cyclosporine and corticosteroids, in this study have significantly less progression of first-year intimal thickening.

Background: Clinical guidelines recommend implantable cardioverter-defibrillators (ICDs) for selected patients with chronic left ventricular dysfunction (LVD) to improve survival, yet ICD treatment rates for eligible patients with LVD or heart failure (HF) in cardiology practices remain poorly studied.Objective: This study sought to determine patient and practice characteristics associated with ICD use in the outpatient setting.Methods: IMPROVE HF (Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting), a prospective cohort study, is designed to characterize management of HF with reduced left ventricular ejection fraction (LVEF < or =35%). Baseline data were collected for 15,381 patients attending 167 outpatient cardiology practices located in the U.S.Results: By current guidelines, 7,221 patients met eligibility for ICD implantation (+/- cardiac resynchronization therapy [CRT]), of whom 3,659 (50.7%) received either ICD (63.8%) or CRT with defibrillator (36.2%). Individual practice conformity for guideline-recommended ICD use ranged from 0% to 100% (27.3% to 74.6% at the 10th and 90th percentiles, respectively). Adjusted analyses revealed lack of adherence for ICD use most notably with advancing age (odds ratio: 0.87; 95% confidence interval: 0.82 to 0.93 per 10 years), black race (odds ratio: 0.75; 95% confidence interval: 0.60 to 0.94), and lack of insurance (odds ratio: 0.45; 95% confidence interval: 0.26 to 0.78). Characteristics of increased adherence included male sex, ischemic disease, atrial fibrillation, and wider QRS. Practices in the Northeast U.S. were more likely to adhere to guidelines (P <.001), as were those with a dedicated HF clinic (P = .004) and electrophysiologists on staff (P <.001).Conclusion: Although a number of patient and practice characteristics are associated with guideline-based ICD use, there is significant unexplained variation in the use of ICD therapy for sudden death prophylaxis across cardiology practices. [ABSTRACT FROM AUTHOR]

The advent of neurohormonal blockade in heart failure (HF) has been an overwhelming success, but current evidence points to a ceiling effect as newer neurohormonal targets are exploited in an incremental manner. This has lead us to question whether the neurohormonal model of HF can be sustained by simply stacking multiple neurohormonal or cytokine blockers together as treatment. A unifying theme in some of these disparate trials relates to either a lack of efficacy or, more importantly, adversity resulting in regression of already achieved benefits. It is our contention that the available evidence has uncovered the remarkable complexity of interaction within the context of the neurohormonal construct. As we stand at a crossroad in HF and begin to fervently pursue non-neurohormonal therapeutic targets, we must also direct attention at navigating the multifaceted labyrinth of the neurohormonal model that has led to the current imbroglio. [ABSTRACT FROM AUTHOR]

Stress tests are a valuable tool for detecting CAD and for assessing prognosis, functional capacity, and response to therapy in patients with known disease. Here's how to choose the one that's right for your patients. [ABSTRACT FROM AUTHOR]

If you've always assumed that beta-blockers are dangers in heart failure, it's time to update your thinking. Recent studies demonstrate compellingly that for carefully selected patients, these agents can reverse ventricular remodeling, improve symptoms, and lengthen survival. [ABSTRACT FROM AUTHOR]

In coronary patients with "relatively normal" lipid values and hyperhomocystinemia (levels > or =15 micromol/L), significant 12% reductions in homocysteine levels occurred after cardiac rehabilitation and exercise training. This benefit from cardiac rehabilitation and exercise training may lead to 20% to 30% reductions in overall coronary artery disease risk. [ABSTRACT FROM AUTHOR]

Chronic heart failure (CHF) remains the only cardiovascular disease with an increasing hospitalization burden and an ongoing drain on health care expenditures. The prevalence of CHF increases with advancing life span, with diastolic heart failure predominating in the elderly population. Primary prevention of coronary artery disease and risk factor management via aggressive blood pressure control are central in preventing new occurrences of left ventricular dysfunction. Optimal therapy for CHF involves identification and correction of potentially reversible precipitants, target-dose titration of medical therapy, and management of hospitalizations for decompensation. The etiological phenotype, absolute decrease in left ventricular ejection fraction and a widening of QRS duration on electrocardiography, is commonly used to identify patients at increased risk of progression of heart failure and sudden death who may benefit from prophylactic implantable cardioverter-defibrillator placement with or without cardiac resynchronization therapy. Patients who transition to advanced stages of disease despite optimal traditional medical and device therapy may be candidates for hemodynamically directed approaches such as a left ventricular assist device; in selected cases, listing for cardiac transplant may be warranted. [ABSTRACT FROM AUTHOR]

Little has been published about sexual function in chronic heart failure (CHF) and knowledge among clinicians in this regard is sparse. To review data regarding sexual function and dysfunction in patients with CHF, 2 of the authors (S.A.M. and P.A.U.) independently conducted a literature search using the MEDLINE database. English-language articles and cited bibliographies published between January 1996 and November 2006 were reviewed. Search terms included heart failure or CHF or ventricular dysfunction or heart disease in conjunction with sexual activity, erectile dysfunction, impotence, or sex. Articles were selected for inclusion if they had a primary focus on CHF and sexual function or dysfunction. Critical reviews of the literature, observational studies using self-reported patient surveys, and prospective, blinded, randomized, placebo-controlled trials were included. Articles were not excluded on the basis of patient sample size but were excluded if the article concerned a broad aspect of cardiovascular disease rather than CHF. When properly screened and treated, most patients with CHF can safely engage in sexual activity and be treated for erectile dysfunction with sildenafil, provided that they do not have active ischemia and do not require treatment with nitrates. Clinicians should know the physiological requirements of sexual activity and the impact CHF has on sexual performance. Fear of a cardiac event during intercourse can interfere with patients' ability to perform and enjoy sex, and so it is important that the physician be able to counsel patients with CHF about sexual activity. [ABSTRACT FROM AUTHOR]

The National Heart, Lung, and Blood Institute (NHLBI) convened a Working Group (WG) on August 5 to 6, 2010 in Bethesda, Maryland to discuss future directions of research in heart transplantation (HT). The WG was composed of researchers with expertise in the basic science, clinical science, and epidemiological aspects of advanced heart failure and HT. These experts were asked to identify the highest priority research gaps in the field and make recommendations for future research strategies. The WG was also asked to include approaches that capitalize on current scientific opportunities and focus on areas that required unique NHLBI leadership. Finally, the WG was charged with developing recommendations that would have short- and long-term impact on the field of HT. The WG participants reviewed key areas in HT and identified the most urgent knowledge gaps. These gaps were then organized into the following 4 specific research directions: 1) enhanced phenotypic characterization of the pre-transplant population; 2) donor-recipient optimization strategies; 3) individualized immunosuppression therapy; and, 4) investigations of immune and non-immune factors affecting late cardiac allograft outcomes. Finally, because the HT population is relatively small compared with other patient groups, the WG strongly urged concerted efforts to enroll every transplant recipient into a clinical study and to increase collaborative networks to optimize research in this field. [ABSTRACT FROM AUTHOR]

This study sought to characterize mechanical activation in pulmonary arterial hypertension (PAH) using 2-dimensional echocardiography with tissue Doppler imaging. Whether pathologic alterations of the right ventricle in PAH affect interventricular dyssynchrony due to changes in mechanical activation of the septum and the right ventricle is unclear. We studied 20 patients with PAH (14 women, mean age 55 +/- 16 years) and 20 healthy controls (15 women, mean age 41 +/- 11 years) that underwent tissue Doppler imaging between July 2006 and May 2007. PAH was associated with accelerated right ventricular (RV) (p <0.0001) and septal (p = 0.022) activation times, but no differences were found in lateral wall activation times between groups (p = 0.35). Measures of ventricular dyssynchrony indicated that patients with PAH had significantly lower RV-lateral wall delays (patients 3.2 +/- 66.2 ms vs controls 56.7 +/- 52.0 ms, p = 0.007), reflecting a faster activation of the right ventricle relative to the lateral wall than controls. In conclusion, PAH is associated with interventricular dyssynchrony manifested by accelerated RV free wall and septal activation times. Whether such dyssynchrony should serve as a therapeutic target remains to be determined. [ABSTRACT FROM AUTHOR]

Myocarditis is a well-recognized cardiac manifestation of human immunodeficiency virus (HIV) infection, and alterations in the immune system likely play an important role in the pathogenesis of heart muscle disease in HIV-infected patients. Highly active antiretroviral therapy (HAART) has greatly improved survival in HIV patients but not without uncovering new and unique manifestations of disease. Immune reconstitution inflammatory syndrome is a collection of inflammatory disorders in which a pathologic inflammatory response and clinical deterioration occur during recovery of the immune system after HAART. To our knowledge, a correlation between immune reconstitution inflammatory syndrome and HIV-associated myocarditis has not been described previously. We report a case of acute myocarditis presenting with refractory ventricular arrhythmias in a patient with AIDS who experienced rapid immune recovery with the initiation of HAART. The case underscores the importance of recognizing this potential complication of AIDS treatment and calls for renewed vigilance concerning cardiac manifestations of HIV, especially during the immune reconstitution phase. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the test-retest reliability of intraventricular dyssynchrony (IVD) assessment by tissue Doppler imaging (TDI) echocardiography. Limited response rates to cardiac resynchronization may improve with TDI screening for appropriate recipients. However, the clinical applicability of TDI will depend on the reliability of the test. Repeat TDI was prospectively performed (11 +/- 11 days apart) in 15 patients with QRS intervals >120 ms and left ventricular ejection fractions <35% and 25 normal controls using the same machine, sonographer, and blinded readers for the 2 tests. There was no change in clinical status or treatment between tests. Established and clinically feasible criteria for IVD were evaluated. These were based on differences of TDI-derived activation time between 2, 4, or 12 left ventricular segments. Reliability was assessed by linear correlation and Bland-Altman analysis for quantified measures, along with percentage agreement and kappa statistics for IVD diagnosis. Despite good intrareader (r = 0.98, p <0.0001) and interreader (2 segments: r = 0.96, p <0.0001; 4 segments: r = 0.85, p <0.0001) reliability, test-retest correlations were uniformly modest for the 2-segment (r = 0.26, p = 0.11), 4-segment (r = 0.36, p = 0.021), and 12-segment (r = 0.50, p = 0.0009) measures. Test-retest agreement for IVD diagnosis by either criterion was equally limited (2 segments: 83%, kappa = 0.27; 4 segments: 75%, kappa = 0.47; 12 segments: 68%, kappa = 0.35). Bland-Altman analysis demonstrated wide confidence intervals, exceeding the diagnostic cutoff values for the respective criteria. In conclusion, the accurate assessment of IVD by TDI may be limited by poor test-retest reliability. [ABSTRACT FROM AUTHOR]

Competing Interests: Disclosures IN reports relationships with CARMAT SA, including consultant, investigator, advisory board member; with Fineheart SA as consultant, investigator, advisory board member; with LeviticusCardio as advisory board member, board member, stock holder; with Abbott as consultantand receiver of institutional support, ZT reports relationships with Abbott as consultant and receiver of institutional support and institutional support from Fineheart. MRM reports consulting fees from Abbott (paid to his institution), Natera, Paragonix, Moderna, NupulseCV, Fineheart, Transmedics, Leviticus, Cadrenal, and Second Heart Assist. The study was designed by Dr. Mehra with lead PI Dr. Netuka and was conducted solely at the Institute for Clinical and Experimental Medicine, Prague, Czech Republic, as a single-center study. These details are provided on the Clinical Trials registration website, where the complete study protocol is available at https://clinicaltrials.gov/study/NCT04974684).

Long-term outcomes of patients with advanced heart failure treated with durable left ventricular assist devices (LVADs) have been augmented due to improved durability and hemocompatibility on the backbone of pump engineering enhancements. The incidence of hemocompatibility-related adverse events (pump thrombosis, stroke and nonsurgical bleeding events) are device specific and vary by type of engineered pump. A fully magnetically levitated rotor containing LVAD in concert with use of antithrombotic therapy has successfully overcome an increased risk of pump thrombosis and stroke-risk, albeit with only modest reduction in bleeding events. Modifications to antithrombotic strategies have focused on reduced-dose vitamin K antagonist use or use of direct oral anticoagulants with demonstration of safety and progress in reduction of mucosal bleeding episodes with elimination of antiplatelet agents. This review outlines the current landscape of advances in anticoagulation management in LVAD patients, highlighting the need for ongoing research and cautious application of emerging therapies and technologies., Competing Interests: Disclosures Dr. Cikes reports investigator-initiated research grants to institutions: Novartis, Abbott, Pfizer; Clinical Study Contracts with institutions: Novo Nordisk, CorVia; advisory role, speaker honoraria, travel grants: Abbott, Abiomed, Amgen, Amicus Therapeutics, AstraZeneca, Bayer, Boehringer-Ingelheim, Bristol Meyers Squibb, GE Healthcare, Krka Pharma, Novartis, NovoNordisk, Pfizer, Pulsify Medical, Roche, Swixx, Takeda, Teva Pharmaceutical Industries, Viatris. Dr. Yuzefpolskaya reports consulting fees and research grant support from Abbott. Dr. Gustafsson reports research grants from Pfizer and the Novo Nordisk Foundation; advisory board honoraria from Bayer, Pfizer, Abbott, Ionis, and Alnylam; and speakers fees from AstraZeneca, Novartis, and Orion Pharma. Dr. Mehra reports payments made to his institution from Abbott for consulting; consulting fees from Mesoblast, Janssen, Moderna, Paragonix, Natera, and the Baim Institute for Clinical Research, Second Heart Assist, and Cadrenal; advisory board member for Transmedics, NuPulseCV, Leviticus, and FineHeart., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: The HeartMate 3 (Abbott) left ventricular assist device provides substantial improvement in long-term morbidity and mortality in patients with advanced heart failure. The Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy study compares thoracotomy-based implantation clinical outcomes with standard median sternotomy., Methods: We conducted a prospective, multicenter, single-arm study in patients eligible for HeartMate 3 implantation with thoracotomy-based surgical technique (bilateral thoracotomy or partial upper sternotomy with left thoracotomy). The composite primary end point was survival free of disabling stroke (modified Rankin score >3), or reoperation to remove or replace a malfunctioning device, or conversion to median sternotomy at 6-months postimplant (elective transplants were treated as a success). The primary end point (noninferiority, -15% margin) was assessed with >90% power compared with a propensity score-matched cohort (ratio 1:2) derived from the Multi-Center Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3 continued access protocol., Results: The study enrolled 102 patients between December 2020 and July 2022 in the thoracotomy-based arm at 23 North American centers. Follow-up concluded in December 2022. In the Implantation of the HeartMate 3 in Subjects With Heart Failure Using Surgical Techniques Other Than Full Median Sternotomy study group, noninferiority criteria was met (absolute between-group difference, -1.2%; Farrington Manning lower 1-sided 95% CI, -9.3%; P < .0025) and event-free survival was not different (85.0% vs 86.2%; hazard ratio, 1.01; 95% CI, 0.58-2.10). Length of stay with thoracotomy-based implant was longer (median, 20 vs 17 days; P = .03). No differences were observed for blood product utilization, adverse events (including right heart failure), functional status, and quality of life between cohorts., Conclusions: Thoracotomy-based implantation of the HeartMate 3 left ventricular assist device is noninferior to implantation via standard full sternotomy. This study supports thoracotomy-based implantation as an additional standard for surgical implantation of the HeartMate 3 left ventricular assist device., Competing Interests: Conflict of Interest Statement Dr Gosev reports consulting for Abbott. Dr Pham reports consulting for Abbott, Abiomed, and Medtronic. Dr Itoh reports speaker honoraria from Abbott and Abiomed. Dr Kotkar is a speaker (nonfinancial) for Abiomed and 3M. Dr Naka reports consulting for Abbott, Biomet-Zimmer, Cryolife, and receiving speaker’s fees for Nipro Co. Dr Peltz reports research support from Bridge to Life Ltd and Paragonix Inc. Dr Silvestry reports consulting for Abbott, Abiomed, Medtronic, and data and safety monitoring board participation for Carmat. Dr Leacche reports consulting for Abbott and advisory board participation for Abiomed. Dr Rao reports consulting for Abbott, Medtronic, and Gore. Dr Sun reports consulting for Abbott. Dr Tedford reports consulting for Abbott, Medtronic, Aria CV Inc, Alleviant, Acorai, Acceleron, Cytokinetics, Itamar, Edwards LifeSciences, Eidos Therapeutics, Lexicon Pharmaceuticals, Gradient, and United Therapeutics. He is the national co-principal investigator for the RIGHT-FLOW clinical trial (Edwards), serves on steering committees for Merck, and a research advisory board for Abiomed. He also does hemodynamic core lab work for Merck. Dr Mokadam reports consulting for Abbott, Medtronic, SynCardia, Carmat, and Xylocor. Drs McNutt and Crandall are employees of Abbott. Dr Mehra reports payment made to institution from Abbott for consulting; consulting fees from Mesoblast, Janssen, Moderna, and Paragonix, and Baim Institute for clinical research; he is an advisory board member for Transmedics, NuPulseCV, Leviticus, and FineHeart. Dr Salerno reports consulting for Abbott. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling manuscripts for which they may have a conflict of interest. The editors and reviewers of this article reported no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)