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Hammam D Zmily1, Suleiman Daifallah2, Jalal K Ghali31Wayne State University/Detroit Medical Center, Detroit, MI, USA; 2John D Dingell VA Medical Center, Detroit, MI, USA; 3Detroit Medical Center, Detroit, MI, USAAbstract: Tolvaptan is the first FDA-approved oral V2 receptor antagonist for the treatment of euvolemic and hypervolemic hyponatremia, in patients with conditions associated with free water excess such as heart failure, cirrhosis, and the syndrome of inappropriate antidiuretic hormone secretion. Tolvaptan inhibits the binding of arginine vasopressin to the V2 receptors on the collecting ducts of the kidneys resulting in aquaresis, the electrolytes sparing excretion of water. This article reviews the accumulated experience with tolvaptan and all the major clinical trials that were conducted to study its safety and efficacy and concludes by summarizing clinicians’ views of its current application in clinical practice.Keywords: arginine vasopressin antagonist, tolvaptan, heart failure, hyponatremia

Background: Limited information is available on the risk and impact of renal dysfunction on the response to beta-blockade and mode of death in systolic heart failure (HF).Methods and Results: Renal function was estimated with glomerular filtration rate (eGFR) using the simplified Modification of Diet in Renal Disease (MDRD) equation. Patients from the Metoprolol CR/XL Controlled Randomized Intervention Trial in Chronic HF (MERIT-HF) were divided into 3 renal function subgroups (MDRD formula): eGFR(MDRD) > 60 (n = 2496), eGFR(MDRD) 45 to 60 (n = 976), and eGFR(MDRD) < 45 mL/min per 1.73 m(2) body surface area (n = 493). Hazard ratio (HR) was estimated with Cox proportional hazards models adjusted for prespecified risk factors. Placebo patients with eGFR < 45 had significantly higher risk than those with eGFR > 60: HR for all-cause mortality, 1.90 (95% confidence interval [CI], 1.28 to 2.81) comparing placebo patients with eGFR < 45 and eGFR > 60, and for the combined end point of all-cause mortality/hospitalization for worsening HF (time to first event): HR, 1.91 (95% CI, 1.44 to 2.53). No significant increase in risk with deceased renal function was observed for those randomized to metoprolol controlled release (CR)/extended release (XL) due to a highly significant decrease in risk on metoprolol CR/XL in those with eGFR < 45. For total mortality, metoprolol CR/XL vs placebo: HR, 0.41 (95% CI. 0.25 to 0.68; P < .001) in those with eGFR < 45 compared with HR, 0.71 (95% CI, 0.54 to 0.95; P < .021) for those with eGFR > 60; corresponding data for the combined end point was HR, 0.44 (95% CI, 0.31 to 0.63; P < .0001) and HR, 0.75 (0.62 to 0.92; P = .005, respectively; P = .095 for interaction by treatment for total mortality; P = .011 for combined end point). Metoprolol CR/XL was well tolerated in all 3 renal function subgroups.Conclusions: Renal function as estimated by eGFR was a powerful predictor of death and hospitalizations from worsening HF. Metoprolol CR/XL was at least as effective in reducing death and hospitalizations for worsening HF in patients with eGFR < 45 as in those with eGFR > 60. [ABSTRACT FROM AUTHOR]

BACKGROUND: To investigate if treatment with an aldosterone antagonist affects the outcomes of treatment by fixed dose combination of isosorbide dinitrate/hydralazine (FDC I/H) or placebo in black heart failure (HF) patients treated with contemporary HF medications. In the African-American Heart Failure Trial (A-HeFT), FDC I/H was effective in reducing mortality and improving event-free survival. The beneficial effects of aldosterone antagonist (spironolactone [SP]), however have not been adequately assessed in black patients with or without the use of FDC I/H. METHODS AND RESULTS: A retrospective analysis was performed in A-HeFT data base (n = 1050) to determine the effect of using SP (39% of patients) on outcomes. Baseline comparisons were done by 2-sample t-test or Fisher's exact test. Kaplan-Meier survival analyses were used for comparing between and within groups for outcomes. SP had no effect on mortality, event-free survival, or first HF hospitalization in the overall A-HeFT population. However, SP decreased mortality risk in the FDC I/H group by 59% (P = .03), and a favorable trend was noted on event-free survival and first HF hospitalization. In contrast, the use of SP was not associated with a decrease in mortality or HF hospitalizations in the placebo group. CONCLUSIONS: This study suggests that in black patients with systolic heart failure on standard therapy of beta-blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor antagonists, the beneficial effects of aldosterone antagonists require a background therapy of FDC I/H. [ABSTRACT FROM AUTHOR]

Objective: To evaluate attainment of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III low-density lipoprotein cholesterol (LDL-C) goal of less than 100 mg/dL with statin treatments in managed care patients at high risk for coronary heart disease.Patients and Methods: In a randomized, open-label, multicenter trial (SOLAR [Satisfying Optimal LDL-C ATP III goals with Rosuvastatin]) performed at 145 US clinical centers from June 5, 2002 to July 12, 2004, high-risk men and women in a managed care population received typical starting doses of rosuvastatin (10 mg/d), atorvastatin (10 mg/d), or simvastatin (20 mg/d) for 6 weeks. Those who did not meet the LDL-C target of less than 100 mg/dL at 6 weeks had their dose titrated (doubled), and all patients were followed up for another 6 weeks.Results: A total of 1632 patients were randomized to 1 of the 3 treatment regimens. After 6 weeks, 65% of patients taking rosuvastatin reached the LDL-C target of less than 100 mg/dL vs 41% with atorvastatin and 39% with simvastatin (P<.001 vs rosuvastatin for both). After 12 weeks, 76% of patients taking rosuvastatin reached the LDL-C target of less than 100 mg/dL vs 58% with atorvastatin and 53% with simvastatin (P<.001 vs rosuvastatin for both). Reductions in the LDL-C level, total cholesterol level, non-high-density lipoprotein cholesterol (non-HDL-C) level, and non-HDL-C/HDL-C ratio were significantly greater with rosuvastatin at both 6 and 12 weeks compared with the other statins. Adverse events were similar in type and frequency in all treatment groups, and only 3% of all patients discontinued treatment because of adverse events. No myopathy was observed, no clinically important impact on renal function was attributed to study medications, and clinically important increases in serum transaminases were rare.Conclusion: In a managed care population, 10 mg of rosuvastatin treatment resulted in more patients reaching the NCEP ATP III LDL-C goal compared with 10 mg of atorvastatin and 20 mg of simvastatin, potentially reducing the need for titration visits. [ABSTRACT FROM AUTHOR]

BACKGROUND: The impact of gender differences has not been well described in patients hospitalized with acute decompensated heart failure (ADHF). METHODS AND RESULTS: Through review of medical records, data on characteristics, treatments, and outcomes were analyzed on 105,388 patient records according to gender. Women accounted for 52% of these admissions and were older than men (74.5 versus 70.1 years,) and more commonly had preserved left ventricular function (51% versus 28%). Based on history, women were less likely to have coronary artery disease (51% versus 64%) and its risk factors, but more commonly had hypertension (76% versus 70%). Both genders received similar intravenous diuretic regimens, but fewer women received vasoactive therapy (24% vs 31%). Evidence-based oral therapies were underused in both genders. Women consistently received less procedure-oriented therapy. Mean length of stay (women 5.9, men 5.8 days) and the risk-adjusted in-hospital mortality (adjusted odds ratio 0.974 [0.910-1.042], P = .4390) were similar in both genders. CONCLUSION: More women than men are hospitalized with ADHF. Heart failure with preserved left ventricular function predominates in women. Though women are treated less aggressively, treatment gaps exists in both sexes. Despite these differences, length of stay and in-hospital mortality rates are similar. [ABSTRACT FROM AUTHOR]

Objectives: We sought to determine whether hormone replacement therapy (HRT) is associated with an improved prognosis in women with advanced heart failure (HF) and systolic dysfunction.Background: There are about two million postmenopausal women in the U.S. with HF. However, limited data are available to assess the effects of HRT on survival in this large group of patients.Methods: A retrospective analysis of women age 50 years and over entered into the Beta-Blocker Evaluation of Survival Trial (BEST) was conducted using Cox regression analysis comparing survival in HRT users and non-users after correcting for baseline variables known to predict survival in women with HF and systolic dysfunction.Results: In 493 women age 50 years and older, HRT was associated with a significant reduction in mortality-21% mortality in HRT users and 34% in non-users (p = 0.025). Multivariate analysis demonstrated a hazard ratio for mortality of 0.6 (95% confidence interval = 0.36 to 0.97) (p = 0.039) for HRT users. The benefits of HRT were noted only in women with a nonischemic etiology of HF (n = 237).Conclusions: Hormone replacement therapy is associated with a marked improvement in survival in postmenopausal women with advanced HF. A prospective, randomized trial of HRT should be performed in this large group of patients. [ABSTRACT FROM AUTHOR]

Objectives: This was a retrospective analysis to determine the effect of diabetes on outcome in patients with advanced heart failure (HF), and to determine the effect of beta-blockade in patients with HF with and without diabetes mellitus.Background: In chronic HF the impact on clinical outcomes and therapeutic response of the prevalent comorbid condition diabetes mellitus has not been extensively investigated.Methods: We assessed the impact of diabetes on prognosis and effectiveness of beta-blocker therapy with bucindolol in patients with HF enrolled in the Beta-Blocker Evaluation of Survival Trial (BEST). We conducted a retrospective analysis to examine the prognosis of patients with advanced HF with and without diabetes, and the effect of beta-blocker therapy on mortality and HF progression or myocardial infarction (MI). The database was the 2,708 patients with advanced HF (36% with diabetes and 64% without diabetes) who were randomized to the beta-blocker bucindolol or placebo in BEST and followed for mortality, hospitalization, and MI for an average of two years.Results: Patients with diabetes had more severe chronic HF and more coronary risk factors than patients without diabetes. Diabetes was independently associated with increased mortality in patients with ischemic cardiomyopathy (adjusted hazard ratio 1.33, 95% confidence interval 1.12 to 1.58, p = 0.001), but not in those with a nonischemic etiology (adjusted hazard ratio 0.98, 95% confidence interval 0.74 to 1.30, p = 0.89). Compared with patients without diabetes, in diabetic patients beta-blocker therapy was at least as effective in reducing death or HF hospitalizations, total hospitalizations, HF hospitalizations, and MI. Ventricular function and physiologic responses to beta-blockade were similar in patients with and without diabetes.Conclusions: Diabetes worsens prognosis in patients with advanced HF, but this worsening appears to be limited to patients with ischemic cardiomyopathy. In advanced HF beta-blockade is effective in reducing major clinical end points in patients with and without diabetes. [ABSTRACT FROM AUTHOR]

Background: Black adults show heightened cardiovascular risk compared with other groups despite comparable or lower coronary artery calcium (CAC) scores, indicating potential cardiovascular risk underestimation by CAC. Abdominal aortic calcification (AAC), preceding CAC, may predict cardiovascular events better in Black adults who are prone to early atherosclerotic cardiovascular disease and excess events at low CAC scores., Methods: We included 2551 participants from the JHS (Jackson Heart Study) visit 2 examination (2005-2008) without cardiovascular disease, followed through 2016. Cox regression estimated hazard ratios for incident cardiovascular events defined as a composite of myocardial infarction, stroke, heart failure, and all-cause mortality. The predictive value of CAC and AAC, when added to the American College of Cardiology/American Heart Association cardiovascular risk algorithm (pool cohort equation), was assessed., Results: Mean age was 57±10 years; 66% were women. Over a follow-up period of 12.6 years, 287 (11.3%) cardiovascular events and 360 (14.1%) mortality cases were observed. Adjusting for demographic and clinical variables, each 2-fold increase in CAC and AAC was associated with cardiovascular events (CAC: hazard ratio, 1.10 [95% CI, 1.06-1.13]; AAC: hazard ratio, 1.10 [95% CI, 1.06-1.13]) and all-cause mortality CAC: hazard ratio, 1.04 [95% CI, 1.01-1.08]; AAC: hazard ratio, 1.05 [95% CI, 1.01-1.08]). The incremental value of CAC (0.17 [95% CI, 0.08-0.23]) and AAC (0.15 [95% CI, 0.07-0.29]) to the pool cohort equation by net reclassification index was comparable. Notably, 45% of participants with 0 CAC showed some degree of AAC. Each 2-fold increase in AAC was associated with an increased risk of cardiovascular events (hazard ratio, 1.07 [95% CI, 1.01-1.19]) but not all-cause mortality among participants with 0 CAC., Conclusions: AAC is comparable to CAC in predicting cardiovascular events and all-cause mortality among Black adults, potentially valuable when CAC is absent.

Background: Heart failure and diabetes are comorbidities that disproportionately contribute to high morbidity and mortality among Blacks. Further compounding the racial and ethnic disparities in COVID-19 health outcomes, Blacks with cardiometabolic diseases are at high risk of experiencing serious complications or mortality from COVID-19. This study aimed to assess how Blacks with heart failure and diabetes navigated chronic care management during the COVID-19 pandemic., Methods: A mixed methods study including in-depth interviews and surveys with adults diagnosed with heart failure and diabetes (n = 17) was conducted in 2021-2022. Verbatim transcripts were analyzed using a thematic analysis approach., Results: Participants reported that while the pandemic initially caused delays in access to health services, shifts to telemedicine allowed for continued care despite preferences for in-person appointments. Various sources of information were used in different ways to make decisions on how to best reduce health risks due to COVID-19, but individuals and institutions affiliated with science and medicine, or who promoted information from these sources, were considered to be the most trusted sources of information among those who relied on outside guidance when making health-related decisions. Individuals' self-awareness of their own high-risk status and perceived control over their exposure levels to the virus informed what COVID-19 prevention and mitigation strategies people used., Conclusion: Information backed by scientific data was an important health communication tool that alongside other factors, such as fear of mortality due to COVID-19, encouraged individuals to get vaccinated and adopt other COVID-19 prevention and mitigation behaviors., (© 2024. The Author(s).)

Background: We aim to determine the added value of carotid intima-media thickness (cIMT) in stroke risk assessment for hypertensive Black adults., Methods: We examined 1,647 participants with hypertension without a history of cardiovascular (CV) disease, from the Jackson Heart Study. Cox regression analysis estimated hazard ratios (HRs) for incident stroke per standard deviation increase in cIMT and quartiles while adjusting for baseline variables. We then evaluated the predictive capacity of cIMT when added to the pool cohort equations (PCEs)., Results: The mean age at baseline was 57 ± 10 years. Each standard deviation increase in cIMT (0.17 mm) was associated with approximately 30% higher risk of stroke (HR 1.27, 95% confidence interval: 1.08-1.49). Notably, cIMT proved valuable in identifying residual stroke risk among participants with well-controlled blood pressure, showing up to a 56% increase in the odds of stroke for each 0.17 mm increase in cIMT among those with systolic blood pressure <120 mm Hg. Additionally, the addition of cIMT to the PCE resulted in the reclassification of 58% of low to borderline risk participants with stroke to a higher-risk category and 28% without stroke to a lower-risk category, leading to a significant net reclassification improvement of 0.22 (0.10-0.30)., Conclusions: In this community-based cohort of middle-aged Black adults with hypertension and no history of CV disease at baseline, cIMT is significantly associated with incident stroke and enhances stroke risk stratification., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Journal of Hypertension, Ltd. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Postural tachycardia syndrome (POTS) is a disorder characterized by a constellation of symptoms including lightheadedness, fatigue, and palpitations when upright, associated with an increase in the heart rate (HR) of > 30 beats per minute when changing from a lying down to standing position or head-up tilt position and not associated with orthostatic hypotension. The causes as well as the management of POTS are not quite fully understood., Areas Covered: We performed a literature review on the diagnosis and management of POTS, and this article includes an overview of novel pharmacotherapeutic options for the treatment of (POTS), although an effective treatment has not been established., Expert Opinion: POTS is a clinical syndrome characterized by a constellation of symptoms that are nonspecific. No single etiology or unified hypothesis could be identified. In fact, multiple pathophysiological mechanisms have been proposed, and none of the suggested medications have been approved by the FDA for this indication. Further understanding of the autonomic nervous system and its adjustment to standing position is needed to provide better management strategies.

Background Although there has been a decrease in the incidence of ST-segment-elevation myocardial infarction (STEMI) in the United States, this trend might be stagnant or increasing in young women. We assessed the trends, characteristics, and outcomes of STEMI in women aged 18 to 55 years. Methods and Results We identified 177 602 women aged 18 to 55 with the primary diagnosis of STEMI from the National Inpatient Sample during years 2008 to 2019. We performed trend analyses to assess hospitalization rates, cardiovascular disease (CVD) risk factor profile, and in-hospital outcomes stratified by three age subgroups (18-34, 35-44, and 45-55 years). We found STEMI hospitalization rates were decreased in the overall study cohort from 52 per 100 000 hospitalizations in 2008 to 36 per 100 000 in 2019. This was driven by decreased proportion of hospitalizations in women aged 45 to 55 years (74.2% to-71.7%; P <0.001). Proportion of STEMI hospitalizationincreased in women aged 18-34 (4.7%-5.5%; P <0.001) and 35-44 years (21.2%-22.7%; P <0.001). The prevalence of traditional and non-traditional female-specific or female-predominant CVD risk factors increased in all age subgroups. The adjusted odds of in-hospital mortality in the overall study cohort and age subgroups were unchanged throughout the study period. Additionally, we observed an increase in the adjusted odds of cardiogenic shock, acute stroke, and acute kidney injury in the overall cohort over the study period. Conclusions STEMI hospitalizations are increasing among women aged <45 years, and in-hospital mortality has not changed over the past 12 years in women aged <55 years. Future studies on the optimization of risk assessment and management of STEMI in young women are urgently needed.

Heart failure with reduced ejection fraction (HFrEF) is defined as the presence of typical symptoms of heart failure (HF) and a left ventricular ejection fraction ≤ 40%. HFrEF patients constitute approximately 50% of all patients with clinical HF. Despite breakthrough discoveries and advances in the pharmacologic management of HF, HFrEF patients continue to pose a significant economic burden due to a progressive disease characterized by recurrent hospitalizations and need for advanced therapy. Although there are effective, guideline-directed medical therapies for patients with HFrEF, a significant proportion of these patients are either not on appropriate medications' combination or on optimal tolerable medications' doses. Since the morbidity and mortality benefits of some of the pharmacologic therapies are dose-dependent, optimal medical therapy is required to impact the burden of disease, quality of life, prognosis, and to curb health care expenditure. In this review, we summarize landmark trials that have impacted the management of HF and we review contemporary pharmacologic management of patients with HFrEF. We also provide insight on general considerations in the management of HFrEF in specific populations. We searched PubMed, Scopus, Medline and Cochrane library for relevant articles published until April 2019 using the following key words "heart failure", "management", "treatment", "device therapy", "reduced ejection fraction", "guidelines", "guideline directed medical therapy", "trials" either by itself or in combination. We also utilized the cardiology trials portal to identify trials related to heart failure. We reviewed guidelines, full articles, review articles and clinical trials and focused on the pharmacologic management of HFrEF., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Objective: The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women., Background: PPCM is a major cause of maternal morbidity and mortality, and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis., Methods: The Investigation of Pregnancy-Associated Cardiomyopathy (IPAC) study enrolled 100 women presenting with a left ventricular ejection fraction of <0.45 within 2 months of delivery. Peripheral T-cell subsets, natural killer (NK) cells, and cellular activation markers were assessed by flow cytometry in PPCM women early (<6 wk), 2 months, and 6 months postpartum and compared with those of HP women and women with non-pregnancy-associated recent-onset cardiomyopathy (ROCM)., Results: Entry NK cell levels (CD3-CD56+CD16+; reported as % of CD3- cells) were significantly (P < .0003) reduced in PPCM (6.6 ± 4.9% of CD3- cells) compared to HP (11.9 ± 5%). Of T-cell subtypes, CD3+CD4-CD8-CD38+ cells differed significantly (P < .004) between PPCM (24.5 ± 12.5% of CD3+CD4-CD8- cells) and HP (12.5 ± 6.4%). PPCM patients demonstrated a rapid recovery of NK and CD3+CD4-CD8-CD38+ cell levels. However, black women had a delayed recovery of NK cells. A similar reduction of NK cells was observed in women with ROCM., Conclusions: Compared with HP control women, early postpartum PPCM women show significantly reduced NK cells, and higher CD3+CD4-CD8-CD38+ cells, which both normalize over time postpartum. The mechanistic role of NK cells and "double negative" (CD4-CD8-) T regulatory cells in PPCM requires further investigation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The growing popularity of medical and recreational consumption of cannabis, especially among the youth, raises immediate concerns regarding its safety and long-terms effects. The cardiovascular effects of cannabis are not well known. Cannabis consumption has been shown to cause arrhythmia including ventricular tachycardia, and potentially sudden death, and to increase the risk of myocardial infarction (MI). These effects appear to be compounded by cigarette smoking and precipitated by excessive physical activity, especially during the first few hours of consumption. Cannabinoids, or the active compounds of cannabis, have been shown to have heterogeneous effects on central and peripheral circulation. Acute cannabis consumption has been shown to cause an increase in blood pressure, specifically systolic blood pressure (SBP), and orthostatic hypotension. Cannabis use has been reported to increase risk of ischemic stroke, particularly in the healthy young patients. The endocannabinoid system (ECS) is currently considered as a promising therapeutic target in the management of several disease conditions. Synthetic cannabinoids (SCs) are being increasingly investigated for their therapeutic effects; however, the value of their benefits over possible complications remains controversial. Despite the considerable research in this field, the benefits of cannabis and its synthetic derivatives remains questionable even in the face of an increasingly tolerating attitude towards recreational consumption and promotion of the therapeutic complications. More efforts are needed to increase awareness among the public, especially youth, about the cardiovascular risks associated with cannabis use and to disseminate the accumulated knowledge regarding its ill effects., Competing Interests: Conflicts of Interest: The authors have no conflicts of interest to declare.

Aims: Many patients with heart failure and reduced EF remain at high risk for hospitalization despite evidence-based therapy. Digoxin may decrease hospitalization; however, uncertainty persists concerning its proper administration and effect on mortality. This study investigated whether using dose response concepts to re-evaluate the relationship between serum digoxin concentration and key mortality outcomes in patients with reduced EF in the Digitalis Investigation Group trial would help clarify efficacy and safety., Methods and Results: Multivariable Cox proportional hazards modelling and propensity score adjustment assessed the relationship between serum digoxin concentration (≥0.5 ng/mL) as a continuous variable and mortality outcomes. In patients treated with digoxin, a significant linear association was found between serum concentration and all-cause mortality [adjusted hazard ratio (HR) 1.25, 95% confidence interval (CI) 1.14-1.38, P < 0.001 per 0.5 ng/mL increase in serum concentration]. Based on this relationship, a bidirectional association was found between digoxin therapy and all-cause mortality when compared with placebo. The lowest serum concentrations (0.5-0.7 ng/mL) were associated with the lowest risk of all-cause mortality (adjusted HR 0.77, 95% CI 0.67-0.89, P < 0.001) while high serum concentrations (1.6-2.0 ng/mL) were associated with increased mortality (adjusted HR 1.33, 95% CI 1.12-1.58, P = 0.001). Consistent with this finding, lower serum concentrations (0.5-0.7 ng/mL) were associated with reduced death from worsening heart failure and a neutral effect on cardiovascular death not due to worsening heart failure., Conclusion: These findings favour targeting serum concentrations from 0.5 to 0.7 ng/mL when dosing digoxin in patients with heart failure and reduced EF., (© 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology.)

Introduction: Postpericardiotomy syndrome (PPS) is an inflammatory process, affecting 15% to 20% of patients, after surgery involving pleura, pericardium, or both. The role of electrocardiogram (ECG) in diagnosing PPS is uncertain because ECG is rarely normal (especially after cardiac surgery). We report a case of PPS that presented initially with localized ST-segment elevation and also discuss proposed mechanisms., Clinical Case: A 60-year-old White man presented to the emergency department (ED) after having chest pain, shortness of breath, and palpitation for approximately 2 hours. Patient had known coronary artery disease, status postcoronary artery bypass graft a month earlier with a graft to right coronary artery, and 2 grafts to marginal arteries. In the ED, ECG revealed localized ST-segment elevations in leads II, III, and aVF. Coronary angiography did not reveal significant coronary artery stenosis, and all the grafts were found to be patent. Following ECG showed PR depression along with diffuse ST elevation consistent with pericarditis. Patient was started on nonsteroidal anti-inflammatory drugs and colchicine with significant improvement of his symptoms in a few days., Discussion: In our patient, injury or surgical manipulation to the area perfused by right coronary artery might have initiated a process, initially localized to the inferior wall with subsequent diffuse involvement of the entire pericardium. The presentation of our patient shortly after the development of chest pain and availability of 2 ECGs a few minutes apart may have shed light on the pathophysiology of PPS., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Few guidelines exist regarding authorship on manuscripts resulting from large multicenter trials. The HF-ACTION investigators devised a system to address assignment of authorship on trial publications and tested the outcomes in the course of conducting the large, multicenter, National Heart, Lung, and Blood Institute-funded trial (n = 2,331; 82 clinical sites; 3 countries). The HF-ACTION Authorship and Publication (HAP) scoring system was designed to enhance rate of dissemination, recognize investigator contributions to the successful conduct of the trial, and harness individual expertise in manuscript generation., Methods: The HAP score was generated by assigning points based on investigators' participation in trial enrollment, follow-up, and adherence, as well as participation in committees and other trial activity. Overall publication rates, publication rates by author, publication rates by site, and correlation between site publication and HAP score using a Poisson regression model were examined., Results: Fifty peer-reviewed, original manuscripts were published within 6.5 years after conclusion of study enrollment. In total, 137 different authors were named in at least 1 publication. Forty-five (55%) of the 82 sites had an author named to at least 1 article. A Poisson regression model examining incident rate ratios revealed that a higher HAP score resulted in a higher incidence of a manuscript, with a 100-point increase in site score corresponding to an approximately 32% increase in the incidence of a published article., Conclusions: Given the success in publishing a large number of manuscripts and widely distributing authorship, regular use of a transparent, objective authorship assignment system for publishing results from multicenter trials may be recommended to optimize fairness and dissemination of trial results., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Chloride depletion alkalosis (CDA) is often seen as a consequence of diuresis in heart failure (HF) but its prognostic significance remains unknown. The purpose of this study was to evaluate the prognostic role of CDA in decompensated HF (DHF)., Methods: A retrospective cohort analysis was performed on 674 patients who were admitted with DHF. Patients were assigned to 2 groups based on the change in serum bicarbonate (median = 3 mmol/l) after diuresis, which was calculated by computing the difference in the admission and discharge serum bicarbonate: the CDA group (a change in serum bicarbonate ≥3 mmol/l) and the non-CDA group (change in serum bicarbonate <3 mmol/l). The primary end points were inhospital mortality and the composite end point of all-cause 30-day mortality and hospital readmission for HF., Results: In a multivariable logistic regression model, the CDA group, i.e. 374 patients, had a lower inhospital mortality than the non-CDA group, i.e. 300 patients (OR 0.11, 95% CI 0.03-0.38; p = 0.0005) after adjusting for other covariates. There was no statistically significant difference in the combined end point of all-cause 30-day mortality and readmission between the 2 groups (OR 1.26, 95% CI 0.74-2.12; p = 0.39)., Conclusion: The presence of CDA during hospitalization for DHF was independently associated with a better inhospital survival rate., (© 2015 S. Karger AG, Basel.)

Digoxin improves exercise tolerance and reduces hospitalizations in patients with systolic heart failure, but its use has declined progressively for the past two decades. The Digitalis Investigation Group trial showed that digoxin reduced hospitalizations but had a neutral effect on total mortality. There was evidence that mortality caused by worsening heart failure was less, but there was also a signal suggesting an increase in other cardiac (presumed arrhythmic) death. Use of digoxin has declined substantially and recent guideline recommendations have significantly de-emphasized the importance of this drug in the management of heart failure. Two developments suggest that re-evaluation of the contemporary role of digoxin in the management of heart failure with reduced ejection fraction is warranted. First, heart failure remains progressive, characterized by chronic debility, exercise intolerance, and frequent and costly hospitalizations, despite evidence-based drug and device therapies that prolong survival. Health economics have made reducing hospitalizations in patients with heart failure a major priority. Second, a strong association has emerged between serum concentration and the safety and efficacy of digoxin, which indicates a change in our approach to dosing this agent is needed. Experimental and clinical results suggest that optimizing therapeutic benefit and avoiding harm means dosing to achieve low serum digoxin concentrations (0.5-0.9 ng/mL). Digoxin is an inexpensive agent and the totality of evidence indicates that it reduces hospitalizations and improves symptoms safely when dosed to achieve low serum concentrations. These findings suggest digoxin should have a more prominent therapeutic role in patients with heart failure and reduced ejection fraction., (© 2014 The Authors. European Journal of Heart Failure © 2014 European Society of Cardiology.)