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We aimed to identify a simple metric accounting for peri-procedural hemoglobin changes, independent of blood product transfusion strategies, and assess its correlation with outcomes in patients undergoing left ventricular assist device (LVAD) implantation We included consecutive patients undergoing LVAD implantation at a single center between 10/1/2008 and 6/1/2014. The anemia stress index (ASI), defined as the sum of number of packed red blood cells transfused and the hemoglobin changes after LVAD implantation, was calculated for each patient at 24 h, discharge, and 3 months after LVAD implantation. Our cohort included 166 patients (80.1% males, mean age 56.3 ± 15.6 years) followed up for a median of 12.3 months. Increases in ASI per unit were associated with a higher hazard for all-cause mortality and early RV failure. The associations between the ASI and all-cause mortality persisted after multivariable adjustment, irrespective of when it was calculated (adjusted HR of 1.11, 95% CI 1.03–1.20 per unit increase in ASI). Similarly, ASI at 24 h after implant was associated with early RV failure despite multivariable adjustment (OR 1.09, 95% CI 1.05–1.14). We present a novel metric, the ASI, that is correlated with an increased risk for all-cause mortality and early RV failure in LVAD recipients.

The coronavirus-2019 (COVID-19) infection pandemic has affected the care of patients with heart failure (HF) who have contracted COVID-19 as well as those without COVID-19 who have been impacted by the restructuring of health care delivery. Patients with HF and other cardiovascular comorbidities are at risk for severe disease and complications of infection. Similarly, COVID-19 has been demonstrated to cause myocarditis and may be implicated in new-onset cardiomyopathy. During this pandemic, special considerations are needed for patients with advanced HF, including those supported by durable left ventricular assist devices (LVADs) and heart transplant recipients. The purpose of this review is to summarize emerging data regarding the development of HF secondary to COVID-19 infection in patients with advanced HF and the implications of the pandemic for care of uninfected patients with HF.

The liver is not the exclusive site of glucose production in humans in the postabsorptive state. Robust data support that the kidney is capable of gluconeogenesis and studies have demonstrated that renal glucose production can increase systemic glucose production. The kidney has a role in maintaining glucose body balance, not only as an organ for gluconeogenesis but by using glucose as a metabolic substrate. The kidneys reabsorb filtered glucose through the sodium‐glucose cotransporters sodium‐glucose cotransporter (SGLT) 1 and SGLT2, which are localized on the brush border membrane of the early proximal tubule with immune detection of their expression in the tubularized Bowman capsule. In patients with diabetes mellitus, the renal maximum glucose reabsorptive capacity, and the threshold for glucose passage into the urine, are higher and contribute to the hyperglycemic state. The administration of SGLT2 inhibitors to patients with diabetes mellitus enhances sodium and glucose excretion, leading to a reduction of the glycosuria threshold and tubular maximal transport of glucose. The net effects of SGLT2 inhibition are to drive a reduction in plasma glucose levels, improving insulin secretion and sensitivity. The benefit of SGLT2 inhibitors goes beyond glycemic control, since inhibition of renal glucose reabsorption affects blood pressure and improves the hemodynamic profile and the tubule glomerular feedback. This action acts to rebalance the dense macula response by restoring adenosine production and restraining renin‐angiotensin‐aldosterone activation. By improving renal and cardiovascular function, we explain the impressive reduction in adverse outcomes associated with heart failure supporting the current clinical perspective.

Heart failure (HF) is a global epidemic affecting millions of individuals worldwide. Although important progress has been made in the management of HF, this condition remains a common cause of morbidity and death. Since the publication of the previous sets of guidelines for the management of HF, new diagnostic and therapeutic options for HF have emerged. Now, both the ESC and the ACC/AHA/HFSA have simultaneously published an update of their guidelines incorporating, among others, recommendations for the use of new pharmacological therapies for the treatment of HF. For this Viewpoint article, we have asked the chairs of the ESC Task Force, the chairs of the ACC/AHA/HFSA Writing Committee, and an independent opinion leader in the field to offer their expert insight into the new guidelines, highlighting what is new, what the main differences are between the two sets of guidelines, and what steps should be taken to improve the guidelines in future updates.

Heart failure (HF) is the most common cause for hospitalization among patients aged ≥65 years, affecting ≈6 million Americans; at 40 years, American men and women have a 1 in 5 lifetime risk of developing HF.1 There are 2 distinct HF phenotypes: a syndrome with normal or near-normal left ventricular ejection fraction (LVEF) referred to as HF with preserved EF (HFpEF)2 and the phenotype associated with poor cardiac contractility or HF with reduced EF (HFrEF). HFrEF is frequently caused by coronary artery disease with a male predominance; evidence-based strategies have been established for more than a decade. In contrast, the precise clinical criteria for HFpEF are not universally agreed on, the syndrome disproportionally affects women in 2:1 ratio, and there are no proven treatments.3–5 There are some commonalities between HFrEF and HFpEF in addition to the classic symptoms of breathlessness, edema, and fatigue: older age, diabetes mellitus, and a history of valvular disease are risk factors that are predictive of both clinical phenotypes.6 Risk factors associated with HFpEF include female sex, especially women with diabetes mellitus,7 higher body mass index, smoking, hypertension, concentric LV hypertrophy (LVH), and atrial fibrillation (AF).6,8,9 Risk factors associated with HFrEF include male sex, higher total cholesterol and heart rate, eccentric LVH, coronary artery disease, and left bundle-branch block.6,9 A remarkable lack of consensus exists with respect to the phenotypic characteristics of HFpEF, as evidenced by the divergent definitions of the European Study Group on Diastolic Heart Failure,10 the Framingham Group,11 and the European Society of Cardiology,12 to name just a few (Table).13 All include symptoms or signs but vary in specificity and a requirement for objective data. The definition of preserved LVEF is also inconsistent …

Background— The long-term durability and prognostic significance of improvement in renal function after mechanical circulatory support (MCS) has yet to be characterized in a large multicenter population. The primary goals of this analysis were to describe serial post-MCS changes in estimated glomerular filtration rate (eGFR) and determine their association with all-cause mortality. Methods and Results— Adult patients enrolled in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) with serial creatinine levels available (n=3363) were studied. Early post-MCS, eGFR improved substantially (median improvement, 48.9%; P P P =0.002) and worsening in eGFR (adjusted HR, 1.63; 95% CI, 1.15–2.13; P =0.004). Conclusions— Post-MCS, early improvement in renal function is common but seems to be largely transient and not necessarily indicative of an improved prognosis. This pattern was observed with both pulsatile and continuous-flow devices. Additional research is necessary to better understand the mechanistic basis for these complex post-MCS changes in renal function and their associated survival disadvantage. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00119834.

There are an increasing number of elderly patients with end-stage heart failure. Destination mechanical circulatory support is often the only therapy available for these patients who are not transplant candidates. The outcomes after continuous flow left ventricular assist device (CF LVAD) implant in older patients remains unclear. We undertook this multi-institutional study to quantify short-term and midterm outcomes after CF LVAD implant in the elderly.We retrospectively analyzed all patients in the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) national registry that underwent implant of a CF LVAD (June 2006 to April 2012). Patients were divided into 2 cohorts based upon age (70 years [n = 4,439] and ≥ 70 years (n = 590]). Preoperative, intraoperative, and postoperative variables were analyzed. The primary endpoint, survival, was compared between cohorts.Patients age 70 and older were more hemodynamically stable pre-VAD implant as evidenced by INTERMACS profile and inotrope dependence. Perioperative outcomes, including median bypass time (89 vs 89 minutes) and length of stay (0.657 vs 0.657 months) were similar between cohorts (p = not significant). Kaplan-Meier analysis revealed a significant difference in 2-year survival between patients aged 70 years or greater (63%) and less than 70 (71%, p0.001). Multivariable Cox proportional hazard analysis revealed age as an independent predictor of mortality during follow-up (p0.001). Nonetheless, midterm cumulative survival in the older cohort was still reasonable (63% at 2 years).Multi-institutional analysis revealed advanced age as a predictor of increased mortality after CF LVAD implantation. Careful patient selection is critical in the elderly to optimize long-term outcomes after CF LVAD implantation.

ACC/AHA : American College of Cardiology/American Heart Association ACCF/AHA : American College of Cardiology Foundation/American Heart Association ACE : angiotensin-converting enzyme ACEI : angiotensin-converting enzyme inhibitor ACS : acute coronary syndrome AF : atrial fibrillation

Background— Soluble ST2 reflects activity of an interleukin-33–dependent cardioprotective signaling axis and is a diagnostic and prognostic marker in acute heart failure. The use of ST2 in chronic heart failure has not been well defined. Our objective was to determine whether plasma ST2 levels predict adverse outcomes in chronic heart failure in the context of current approaches. Methods and Results— We determined the association between ST2 level and risk of death or transplantation in a multicenter, prospective cohort of 1141 chronic heart failure outpatients. Adjusted Cox models, receiver operating characteristic analyses, and risk reclassification metrics were used to assess the value of ST2 in predicting risk beyond currently used factors. After a median of 2.8 years, 267 patients (23%) died or underwent heart transplantation. Patients in the highest ST2 tertile (ST2 >36.3 ng/mL) had a markedly increased risk of adverse outcomes compared with the lowest tertile (ST2 ≤22.3 ng/mL), with an unadjusted hazard ratio of 3.2 (95% confidence interval [CI], 2.2 to 4.7; P P =0.002). In receiver operating characteristic analyses, the area under the curve for ST2 was 0.75 (95% CI, 0.69 to 0.79), which was similar to N-terminal pro-B–type natriuretic peptide (NT-proBNP) (area under the curve, 0.77; 95% CI, 0.72 to 0.81; P =0.24 versus ST2) but lower than the Seattle Heart Failure Model (area under the curve, 0.81 (95% CI, 0.77 to 0.85; P =0.014 versus ST2). Addition of ST2 and NT-proBNP to the Seattle Heart Failure Model reclassified 14.9% of patients into more appropriate risk categories ( P =0.017). Conclusions— ST2 is a potent marker of risk in chronic heart failure and when used in combination with NT-proBNP offers moderate improvement in assessing prognosis beyond clinical risk scores.

SERCA2a deficiency is commonly seen in advanced heart failure (HF). This study is designed to investigate safety and biological effects of enzyme replacement using gene transfer in patients with advanced HF.A total of 9 patients with advanced HF (New York Heart Association [NYHA] Class III/IV, ejection fraction [EF]or = 30%, maximal oxygen uptake [VO2 max]16 mL.kg.min, with maximal pharmacological and device therapy) received a single intracoronary infusion of AAV1/SERCA2a in the open-label portion of this ongoing study. Doses administered ranged from 1.4 x 10(11) to 3 x 10(12) DNase resistant particles per patient. We present 6- to 12-month follow-up data for these patients. AAV1/SERCA2a demonstrated an acceptable safety profile in this advanced HF population. Of the 9 patients treated, several demonstrated improvements from baseline to month 6 across a number of parameters important in HF, including symptomatic (NYHA and Minnesota Living with Heart Failure Questionnaire, 5 patients), functional (6-minute walk test and VO2 max, 4 patients), biomarker (NT-ProBNP, 2 patients), and LV function/remodeling (EF and end-systolic volume, 5 patients). Of note, 2 patients who failed to improve had preexisting anti-AAV1 neutralizing antibodies.Quantitative evidence of biological activity across a number of parameters important for assessing HF status could be detected in several patients without preexisting neutralizing antibodies in this open-label study, although the number of patients in each cohort is too small to conduct statistical analyses. These findings support the initiation of the Phase 2 double-blind, placebo-controlled portion of this study.

Mechanical circulatory support (MCS) frequently is used to treat medically refractory end-stage heart failure. Initially designed to be a bridge to transplantation, MCS also has proven itself as a durable therapy for patients who are not transplant candidates. As outcomes for patients with MCS have improved, research interest in device development has flourished, with many new device types under investigation. In addition to improvement of MCS devices, investigational work continues to achieve appropriate patient selection and complication management.

See related editorials on pages 1245 and 1253. N early 5 million Americans have heart failure (HF) today, with an incidence approaching 10 per 1000 population in persons older than 65 years of age; approximately 50% of these patients are women (Figure 1). In 2000, 62.3% of all HF mortalities occurred among women; 20% of those patients died within 1 year of their diagnosis, and less than 15% of women survive more than 8 to 12 years after diagnosis. These results notwithstanding, the Framingham study recently noted that the age-adjusted rates of HF are higher among men, with no significant change in this rate over a 50-year period. Among women, the incidence of HF has decreased by 31% to 40% in the decades after 1950. HF is the reason for at least 20% of all hospital admissions in persons older than 65 years, and over the past decade, hospitalizations for HF have increased by 159%. Women who have been hospitalized with HF have less improvement in physical health status and perceive their quality of care to be lower than that of their male cohorts. Of the thousands of patients disabled from HF within 6 years of their diagnosis, 46% are adult women compared with only 22% of men. In 1997, an estimated $5501 was spent for every hospital-discharge diagnosis of HF, and another $1742 per month was required to care for each patient after discharge. Gender has been shown to be an important determinant of hospital length of stay, hospital charges, and mortality during hospitalization. The above statistics and countless other graphs, studies, and reports chronicle 2 very important issues: (1) the syndrome of HF has reached epidemic proportions in the United States and throughout the world, and (2) the disease appears to have different characteristics in men and women. It is reasonable to postulate that an elucidation of these sex-specific differences might suggest novel approaches to the prevention of this serious disorder. Moreover, additional insights into genderspecific pathophysiologic mechanisms that lead to HF might be used to develop unique therapies for this relentlessly lethal disease. This review, then, should be regarded as more than a politically expedient exercise but as one part of the larger battle to fight the syndrome of HF in all its forms. We would also like to acknowledge the newer literature on this subject since the outstanding review of Petrie and colleagues was published in 1999.

Objectives. The purpose of this study was to prospectively assess the effect of dynamic cardiomyoplasty in patients with symptomatic chronic heart failure. Background. Since the first procedure was performed in 1985, dynamic cardiomyoplasty has been developed for use in patients with chronic heart failure. The aging population in developed countries has made heart failure a growing public health concern. Heart transplantation is appropriate or available for only a small proportion of these patients because of limited donor supply. Effective alternatives to transplantation are needed. Methods. Eight centers in North and South America performed 68 cardiomyoplasty procedures between May 1991 and September 1993. Data were prospectively collected every 6 months and compared with preoperative values using paired t tests, chi-square tests and actuarial survival analyses. Results. Patients had a mean (±SD) age of 57 ± 1 years and were predominantly male (53 [78%] of 68). Heart failure etiology was classified as idiopathic in 47 (69%) of 68 patients and ischemic in 21 (31%). The in-hospital mortality rate was 12% (8 of 68), and the survival rate at 6 and 12 months was 75 ± 5% and 68 ± 6%, respectively. Objective improvements were seen at 6 months (n = 49) in left ventricular ejection fraction (23 ± 1% vs. 25 ± 1%, p = 0.05), stroke volume (50 ± 2 vs. 56 ± 3 ml/beat, p = 0.02) and left ventricular stroke work index (26 ± 1 vs. 30 ± 2 g/m2 per beat, p = 0.01). Improvements in mean New York Heart Association functional class (3 ± 0.04 vs. 1.8 ± 0.1, p = 0.0001) and activity of daily living score (59 ± 3 vs. 80 ± 2, p = 0.0001) were also observed. There were no significant changes at 6 months in peak oxygen consumption (15 ± 1 vs. 16 ± 1 ml/kg per min), cardiac index (2.26 ± 0.08 vs. 2.33 ± 0.08 liters/min per m2), pulmonary capillary wedge pressure (19 ± 2 vs. 18 ± 1 mm Hg) or heart rate (87 ± 2 vs. 82 ± 3 beats/min). Conclusions. These data suggest that dynamic cardiomyoplasty improves ventricular systolic function, reduces symptoms of heart failure and improves objective measures of quality of life in patients with congestive heart failure. This improvement occurred without changes in peak exercise capacity, ventricular filling pressure or actuarial survival.

In this landmark year for the U.S. healthcare system, during which the Affordable Care Act was signed into law, there have been many notable advances in the area of heart failure (HF) and heart transplantation. In addition to scientific discoveries reviewed here and the publication of important

[Figure][1] As communicated in these pages previously, the American Board of Internal Medicine (ABIM) began a change in governance in mid-2013, establishing the council and specialty boards separate from their board of directors [(1–3)][2]. The role of the board of directors is to focus

Background Although orthotopic heart transplantation has been an effective treatment for end-stage heart failure, the incidence of allograft failure has increased, necessitating treatment options. Cardiac retransplantation remains the only viable long-term solution for end-stage cardiac allograft failure. Given the limited number of available donor hearts, the long term results of this treatment option need to be evaluated. Methods 709 heart transplants were performed over a 20 year period at our institution. Repeat cardiac transplantation was performed in 15 patients (2.1%). A retrospective analysis was performed to determine the efficacy of cardiac retransplantation. Variables investigated included: 1 yr and 5 yr survival, length of hospitalization, post-operative complications, allograft failure, recipient and donor demographics, renal function, allograft ischemic time, UNOS listing status, blood group, allograft rejection, and hemodynamic function. Results Etiology of primary graft failure included transplant arteriopathy (n = 10), acute rejection (n = 3), hyperacute rejection (n = 1), and a post-transplant diagnosis of metastatic melanoma in the donor (n = 1). Mean age at retransplantation was 45.5 ± 9.7 years. 1 and 5 year survival for retransplantation were 86.6% and 71.4% respectively, as compared to 90.9% and 79.1% for primary transplantation. Mean ejection fraction was 67.3 ± 12.2% at a mean follow-up of 32.6 ± 18.5 mos post-retransplant; follow-up biopsy demonstrated either ISHLT grade 1A or 0 rejection (77.5 ± 95.7 mos post-transplant). Conclusion Cardiac retransplantation is an efficacious treatment strategy for cardiac allograft failure.

[Figure][1] ![Figure][1] This past month, the American College of Cardiology (ACC) and the American Heart Association (AHA), in collaboration with the National Heart, Lung, and Blood Institute (NHLBI) and other specialty societies, released 4 long-awaited guidelines focused on the