Search

Objectives Two trials (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation Trial and Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation Trial) were published in 2018 evaluating the effectiveness and safety of transcatheter repair for patients with heart failure with significant functional mitral regurgitation, which yielded different results. This article reviews the strength of the evidence, differences in trial designs, ethical and implementation implications, and delineates future research needs to help guide the appropriate dissemination of transcatheter repair for functional patients with mitral regurgitation. Methods The National Heart, Lung, and Blood Institute convened a workshop of interdisciplinary experts to address these objectives. Results Transcatheter repair of functional mitral regurgitation can provide significant benefits in terms of heart failure hospitalizations, survival, and quality of life when appropriate heart failure candidates with moderate to severe or severe mitral regurgitation while on optimal guideline-directed medical therapy can be identified. Key ingredients for success are preoperative evaluation and management and postoperative care by an interdisciplinary heart team. Conclusions Given the discordance observed between trials, ongoing innovation in patient management, and potential expansion of indications for use, the evidence base must be expanded to optimize appropriate implementation of this complex therapy. This will require more complete capture of outcome data in real-world settings for all eligible candidates whether or not they receive this therapy. Inevitably, the indications for use of this therapy will expand, as will the devices and therapeutic approaches for this population, necessitating the study of comparative effectiveness through randomized trials or observational studies. Moreover, given the substantial variations in care delivery, conducting implementation research to delineate characteristics of the optimal care model would be of benefit.

Objectives The authors used cardiopulmonary exercise testing (CPET) to define unexplained dyspnea in patients with post-acute sequelae of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection (PASC). We assessed participants for criteria to diagnose myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Background Approximately 20% of patients who recover from coronavirus disease (COVID) remain symptomatic. This syndrome is named PASC. Its etiology is unclear. Dyspnea is a frequent symptom. Methods The authors performed CPET and symptom assessment for ME/CFS in 41 patients with PASC 8.9 ± 3.3 months after COVID. All patients had normal pulmonary function tests, chest X-ray, and chest computed tomography scans. Peak oxygen consumption (peak VO2), slope of minute ventilation to CO2 production (VE/VCO2 slope), and end tidal pressure of CO2 (PetCO2) were measured. Ventilatory patterns were reviewed with dysfunctional breathing defined as rapid erratic breathing. Results Eighteen men and 23 women (average age: 45 ± 13 years) were studied. Left ventricular ejection fraction was 59% ± 9%. Peak VO2 averaged 20.3 ± 7 mL/kg/min (77% ± 21% predicted VO2). VE/VCO2 slope was 30 ± 7. PetCO2 at rest was 33.5 ± 4.5 mm Hg. Twenty-four patients (58.5%) had a peak VO2 55 (n = 3) or dysfunctional breathing (n = 12). For the whole cohort, 88% of patients (n = 36) had ventilatory abnormalities with dysfunctional breathing (n = 26), increased VE/VCO2 (n = 17), and/or hypocapnia PetCO2, Central Illustration

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a medically unexplained illness characterized by severe fatigue limiting normal daily activities for at least 6 months accompanied by problems with unrefreshing sleep, exacerbation of symptoms following physical or mental efforts (postexertional malaise [PEM]), and either cognitive reports or physiological evidence of orthostatic intolerance in the form of either orthostatic tachycardia and/or hypocapnia. Although rarely considered to have cardiac dysfunction, ME/CFS patients frequently have reduced stroke volume with a significant inverse relation between cardiac output and PEM severity. Magnetic resonance imaging of ME/CFS patients compared with normal control subjects found significantly reduced stroke, end-systolic, and end-diastolic volumes together with reduced end-diastolic wall mass. Another cardiovascular abnormality is reduced nocturnal blood pressure assessed by 24-hour monitoring. Autonomic dysfunction is also frequently observed with postural orthostatic tachycardia and/or hypocapnia. Two consecutive cardiopulmonary stress tests may provide metabolic data substantiating PEM.

Objectives The goal of this study was to evaluate the effect of empagliflozin, in addition to optimal medical treatment, on epicardial adipose tissue (EAT), interstitial myocardial fibrosis, and aortic stiffness in nondiabetic patients with heart failure with reduced ejection fraction (HFrEF). Background Several randomized clinical trials have established the benefits of the inhibitors of the sodium-glucose cotransporter-2 receptor (SGLT2-i) in HFrEF, independent of their hypoglycemic effects. The mechanisms of the benefits of SGLT2-i in HFrEF have not been well defined. Methods This study was a secondary analysis of patients enrolled in the EMPA-TROPISM [ATRU-4] (Are the cardiac benefits of Empagliflozin independent of its hypoglycemic activity?) clinical trial. It was a double-blind, placebo-controlled randomized clinical trial investigating the effect of empagliflozin in nondiabetic patients with HFrEF. Patients underwent cardiac magnetic resonance at baseline and after 6 months. Interstitial myocardial fibrosis was calculated by using T1 mapping (extracellular volume). Aortic stiffness was calculated by using pulsed wave velocity, and EAT was measured from the cine sequences. Results Empagliflozin is associated with significant reductions in EAT volume (–5.14 mL; 95% CI: –8.36 to –1.92) compared with placebo (–0.75 mL; 95% CI: –3.57 to 2.06; P Conclusions Empagliflozin significantly improved adiposity, interstitial myocardial fibrosis, aortic stiffness, and inflammatory markers in nondiabetic patients with HFrEF. These results shed new light on the mechanisms of action of the benefits of SGLT2-i. (Are the “Cardiac Benefits” of Empagliflozin Independent of Its Hypoglycemic Activity [ATRU-4] [EMPA-TROPISM]; NCT03485222 )

Objectives This study sought to determine cardiopulmonary exercise (CPX) predictors of the combined outcome of durable mechanical circulatory support (MCS), transplantation, or death at 1 year among patients with ambulatory advanced heart failure (HF). Background Optimal CPX predictors of outcomes in contemporary ambulatory advanced HF patients are unclear. Methods REVIVAL (Registry Evaluation of Vital Information for ventricular assist devices [VADs] in Ambulatory Life) enrolled 400 systolic HF patients, INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profiles 4-7. CPX was performed by 273 subjects 2 ± 1 months after study enrollment. Discriminative power of maximal (peak oxygen consumption [peak V O 2]; V O 2 pulse, circulatory power [CP]; peak systolic blood pressure • peak V O 2], peak end-tidal pressure C O 2 [PEtC O 2], and peak Borg scale score) and submaximal CPX parameters (ventilatory efficiency [VE/VC O 2 slope]; V O 2 at anaerobic threshold [V O 2AT]; and oxygen uptake efficiency slope [OUES]) to predict the composite outcome were assessed by univariate and multivariate Cox regression and Harrell’s concordance statistic. Results At 1 year, there were 39 events (6 transplants, 15 deaths, 18 MCS implantations). Peak V O 2, V O 2AT, OUES, peak PEtCO2, and CP were higher in the no-event group (all p Conclusions Among patients with ambulatory advanced HF, the strongest maximal and submaximal CPX predictor of MCS implantation, transplantation, or death at 1 year were CP and VE/VCO2, respectively. The patient-reported measure of exercise effort (Borg scale score) contributed substantially to the prediction of outcomes, a surprising and novel finding that warrants further investigation. (Registry Evaluation of Vital Information for VADs in Ambulatory Life [REVIVAL]; NCT01369407 )

A 56-year-old man underwent cardiac transplantation in April 2018. His post-operative course was uncomplicated and he had normal allograft function. On December 2019 he was admitted for fever and diarrhea and was found to have cytomegalovirus infection. A few weeks later, he presented with Guillain-Barré Syndrome. (Level of Difficulty: Advanced.), Graphical abstract

Large clinical trials established the benefits of sodium-glucose cotransporter 2 inhibitors in patients with diabetes and with heart failure with reduced ejection fraction (HFrEF). The early and significant improvement in clinical outcomes is likely explained by effects beyond a reduction in hyperglycemia.The purpose of this study was to assess the effect of empagliflozin on left ventricular (LV) function and volumes, functional capacity, and quality of life (QoL) in nondiabetic HFrEF patients.In this double-blind, placebo-controlled trial, nondiabetic HFrEF patients (n = 84) were randomized to empagliflozin 10 mg daily or placebo for 6 months. The primary endpoint was change in LV end-diastolic and -systolic volume assessed by cardiac magnetic resonance. Secondary endpoints included changes in LV mass, LV ejection fraction, peak oxygen consumption in the cardiopulmonary exercise test, 6-min walk test, and quality of life.Empagliflozin was associated with a significant reduction of LV end-diastolic volume (-25.1 ± 26.0 ml vs. -1.5 ± 25.4 ml for empagliflozin vs. placebo, respectively; p 0.001) and LV end-systolic volume (-26.6 ± 20.5 ml vs. -0.5 ± 21.9 ml for empagliflozin vs. placebo; p 0.001). Empagliflozin was associated with reductions in LV mass (-17.8 ± 31.9 g vs. 4.1 ± 13.4 g, for empagliflozin vs. placebo, respectively; p 0.001) and LV sphericity, and improvements in LV ejection fraction (6.0 ± 4.2 vs. -0.1 ± 3.9; p 0.001). Patients who received empagliflozin had significant improvements in peak OEmpagliflozin administration to nondiabetic HFrEF patients significantly improves LV volumes, LV mass, LV systolic function, functional capacity, and quality of life when compared with placebo. Our observations strongly support a role for sodium-glucose cotransporter 2 inhibitors in the treatment of HFrEF patients independently of their glycemic status. (Are the "Cardiac Benefits" of Empagliflozin Independent of Its Hypoglycemic Activity? [ATRU-4] [EMPA-TROPISM]; NCT03485222).

Aims Readmission after hospitalization for acute decompensated heart failure (HF) remains a major public health problem. Use of remote dielectric sensing (ReDS) to measure lung water volume allows for an objective assessment of volume status and may guide medical optimization for HF. We hypothesized that the use of ReDS would lower 30 day readmission in patients referred to rapid follow‐up (RFU) clinic after HF discharge. Methods and results We conducted a retrospective analysis of the use of ReDS for patients scheduled for RFU within 10 days post‐discharge for HF at Mount Sinai Hospital between 1 July 2017 and 31 July 2018. Diuretics were adjusted using a pre‐specified algorithm. The association between use of ReDS and 30 day readmission was evaluated. A total of 220 patients were included. Mean age was 62.9 ± 14.7 years, and 36.4% were female. ReDS was performed in 80 (36.4%) and led to medication adjustment in 52 (65%). Use of ReDS was associated with a lower rate of 30 day cardiovascular readmission [2.6% vs. 11.8%, hazard ratio (HR): 0.21; 95% confidence interval (CI): 0.05–0.89; P = 0.04] and a trend towards lower all‐cause readmission (6.5% vs. 14.1%, HR: 0.43; 95% CI: 0.16–1.15; P = 0.09) as compared with patients without a ReDS assessment. Conclusions ReDS‐guided HF therapy during RFU after HF hospitalization may be associated with lower risk of 30 day readmission.

Highlights • First, this case underscores the rapidity of deterioration in COVID-19 patients once hypoxia starts. • Second, COVID-19 must be considered in hospitalized patients even when they are asymptomatic. • Lastly it emphasizes the importance of early advanced care planning, Importance : As the Coronavirus disease 2019 (COVID-19) pandemic accelerates, our hospitals have become overwhelmed. Objective : To describe detection of COVID-19 in asymptomatic hospitalized individuals awaiting advanced therapies for HF and the management of complications of COVID-19. Design : We present a unique case report of hospital-acquired COVID-19 in a patient on temporary mechanical circulatory support. Main Outcome : Despite intensive care and monitoring, he developed rapid progression of hypoxic respiratory failure which led to his death. Conclusion : This case highlights various considerations for a patient with temporary MCS. It illustrates the high risk for development of COVID-19 for vulnerable hospitalized patients.

As health systems worldwide grapple with the coronavirus disease-2019 (COVID-19) pandemic, patients with durable LVAD support represent a unique population at risk for the disease. This paper outlines the case of such a patient who developed COVID-19 complicated by a “cytokine storm” with severe acute respiratory distress syndrome and myocardial injury and describes the challenges that arose during management.

Background Increased psychosocial risk portends poor outcomes following heart transplantation. The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a validated, psychosocial risk assessment tool that helps stratify candidates for transplantation. We assessed the impact of psychosocial factors as measured by the SIPAT on clinical outcomes following left ventricular assist device (LVAD) implantation at our institution. Methods and Results A total of 115 individuals (mean age: 57 years, 75.6% men) who underwent LVAD implantation, for either bridge-to-transplant (63%) or destination therapy, from 2014 to 2016 were included for analysis. Correlations between SIPAT scores, baseline characteristics, and post-LVAD outcomes were assessed through a retrospective correlational design. At 1 year post-LVAD, the higher risk SIPAT group had more emergency department visits, urgent clinic visits, and readmissions in univariate analysis (rate ratio 1.7 [95% confidence interval (CI) 1.0–2.7, P = .035]). After multivariate analysis, this association retained near-statistical significance (rate ratio 1.6 [95% CI 1.0–2.8, P = .051]). There was also a trend toward more device-associated infections (rate ratio 2.1 [95% CI 0.96–4.4, P = .064]). There was no difference in incidence of other adverse events or 1-year mortality between the 2 groups. Conclusions Higher psychosocial risk per SIPAT in patients undergoing LVAD implantation is associated with more emergency room visits, urgent visits and readmissions over 1 year, but not LVAD-related complications or mortality. Use of the SIPAT tool may help identify patients at higher risk for hospitalization and/or urgent care beyond traditional factors, but should not preclude LVAD implantation.

Background: Heart failure (HF) constitutes a growing burden for public health and the US health care system. While the prevalence of HF is increasing, differences in health care utilization and expenditures within various sociodemographic groups remain poorly defined. Methods: We used the Medical Expenditure Panel Survey to assess annual health care utilization and expenditures from 2012 to 2017. Health care utilization was based on the annual frequency of various health care encounters. Annual total and out-of-pocket expenditures were evaluated for hospital inpatient stays, emergency room visits, outpatient visits, office-based medical provider visits, prescribed medicines, dental visits, home health aid visits, and other medical expenses. We performed univariable and multivariable regression analysis based on patient characteristics including sociodemographic and comorbidity variables. Results: Our results showed that total health care expenditures among patients with HF were $21 177 (95% CI, $18 819–$24 736) per year as compared with $5652 (95% CI, $5469–$5837) in those without HF ( P Conclusions: Our findings of increased health care utilization and expenditures based on sex, age, increasing number of comorbidities, wealthier income status, and increased education attainment level may be used for efforts aimed at better distributing health care resources to improve health outcomes in HF.

Background COVID-19 continues to inflict significant morbidity and mortality, particularly on patients with preexisting health conditions. The clinical course, outcomes, and significance of immunosuppression regimen in heart transplant recipients with COVID-19 remains unclear. Methods We included the first 99 heart transplant recipients at participating centers with COVID-19 and followed patients until resolution. We collected baseline information, symptoms, laboratory studies, vital signs, and outcomes for included patients. The association of immunosuppression regimens at baseline with severe disease were compared using logistic regression , adjusting for age and time since transplant. Results The median age was 60 years, 25% were female, and 44% were white. The median time post-transplant to infection was 5.6 years. Overall, 15% died, 64% required hospital admission, and 7% remained asymptomatic. During the course of illness, only 57% of patients had a fever, and gastrointestinal symptoms were common. Tachypnea , oxygen requirement, elevated creatinine and inflammatory markers were predictive of severe course. Age ≥ 60 was associated with higher risk of death and the use of the combination of calcineurin inhibitor , antimetabolite , and prednisone was associated with more severe disease compared to the combination of calcineurin inhibitor and antimetabolite alone (adjusted OR = 7.3, 95% CI 1.8-36.2). Among hospitalized patients, 30% were treated for secondary infection, acute kidney injury was common and 17% required new renal replacement therapy . Conclusions We present the largest study to date of heart transplant patients with COVID-19 showing common atypical presentations and a high case fatality rate of 24% among hospitalized patients and 16% among symptomatic patients.

Left ventricular assist device (LVAD)-specific infections (LSIs) are common in patients on LVAD support awaiting heart transplant (HT), yet their impact on post-HT outcomes is not completely understood. We hypothesized that LSIs would result in vasoplegia and negatively affect post-HT 30-day and 1-year outcomes. LSI was defined as driveline, pump, or pocket infection. The short-term outcome was a composite of acute renal failure, allograft rejection, and mortality at 30 days after HT. The long-term outcome was a composite of allograft rejection and death within 1 year after HT. We performed a retrospective analysis of 111 HT recipients bridged with durable LVAD support at our institution from May 2012 to August 2019. Of these, 63 patients had LSIs, with 94% of the infections being driveline infections. Vasoplegia was more prevalent in the LSI group but not significantly (7 vs 2 persons, p = 0.3). There was no difference in the composite end point of acute renal failure, rejection, or death at 30 days (30% vs 25%, p = 0.55) or 1-year end point of rejection and death (38% vs 40%, p = 0.87) in patients with LSI versus those without LSI. In conclusion, LSIs were common in patients on LVAD who underwent HT in our single-center contemporary cohort. However, LSI was not associated with adverse outcomes at 30 days or at 1 year after HT.

Background: SGLT2 inhibitors (SGLT2i) improve prognosis in HFrEF patients. We recently demonstrated in a porcine model of non-diabetic HFrEF that empagliflozin (EMPA) ameliorates adverse cardiac remodeling and improves LV systolic function. However, the effect of EMPA on left atrial (LA) dilatation has not yet been studied Hypothesis:: Empagliflozin ameliorates left atrial dilatation in non-diabetic HFrEF patients Methods: The EMPATROPISM clinical trial investigated the efficacy and safety of EMPA in non-diabetic HFrEF patients. 84 patients were randomized to EMPA 10mg daily for 6 months or placebo on top of optimal medical treatment, and were evaluated with cardiac magnetic resonance (CMR). LA Volumes were quantified by CMR using the Simpson method (the number of slices in the usual short axis SSFP cine sequence was increased to cover both LV and the whole of LA. The primary endpoint was change in LVEDV. Prespecified secondary endpoints were changes in maximal and minimal LA volumes (ΔMax LA Vol and ΔMin LA Vol) at the end of 6 months between both arms Results: 80 patients completed the follow up period. There were no differences at baseline in LVEDV (220±75 vs 209±68mL for EMPA vs placebo, p=0.5) or LVEF (36±8 vs 37±8%, p=0.7). There were no differences at baseline in both groups in either maximal or minimal LA volume (Table). In the primary endpoint, EMPA-treated patients showed decrease in LVEDV and increase in LVEF (ΔLVEDV -25±25 vs -1±25mL, p Conclusions: In HFrEF patients without diabetes, treatment with empagliflozin ameliorates left atrial dilatation. As LA volume is a surrogate for chronic filling pressures, this reduced LA volume suggest improved diastolic function with EMPA

Background: SGLT2 inhibitors (SGLT2i) improve prognosis in HFrEF patients. We recently demonstrated in a porcine model of non-diabetic HFrEF that empagliflozin (EMPA) ameliorates adverse cardiac remodeling and improves LV systolic function. However, the effect of EMPA on interstitial myocardial fibrosis (IMF) and aortic stiffness has not yet been studied Hypothesis: Empagliflozin ameliorates IMF and aortic stiffness in non-diabetic HFrEF patients Methods: The EMPATROPISM clinical trial (NCT 03485222) investigated the efficacy and safety of EMPA in non-diabetic HFrEF patients. 84 patients were randomized to EMPA 10mg daily for 6 months or placebo on top of optimal medical treatment, and were evaluated with cardiac magnetic resonance (CMR). IMF was assessed by CMR using extracellular volume (ECV) by T1 mapping. Aortic stiffness was quantified by pulse wave velocity (PWV) by CMR. The primary endpoint was change in LVEDV. Prespecified secondary endpoints were changes in ECV (ΔECV) and PWV (ΔPWV) at 6 months between both arms Results: 80 patients completed the follow up period. There were no differences at baseline in LVEDV (220±75 vs 209±68mL for EMPA vs placebo, p=0.5) or LVEF (36±8 vs 37±8%, p=0.7). There were no differences at baseline in both groups in either ECV or PWV (Table). In the primary endpoint, EMPA-treated patients showed decrease in LVEDV and increase in LVEF (ΔLVEDV -25±25 vs -1±25mL, p Conclusions: In HFrEF patients without diabetes, treatment with empagliflozin ameliorates IMF and aortic stiffness. This may explain the benefits of SGLT2i in HFrEF even in the absence of diabetes

Background Myocardial injury is frequent among patients hospitalized with coronavirus disease-2019 (COVID-19) and is associated with a poor prognosis. However, the mechanisms of myocardial...

Background Patients with pre-existing heart failure (HF) are likely at higher risk for adverse outcomes in coronavirus disease-2019 (COVID-19), but data on this population are sparse. Objectives This study described the clinical profile and associated outcomes among patients with HF hospitalized with COVID-19. Methods This study conducted a retrospective analysis of 6,439 patients admitted for COVID-19 at 1 of 5 Mount Sinai Health System hospitals in New York City between February 27 and June 26, 2020. Clinical characteristics and outcomes (length of stay, need for intensive care unit, mechanical ventilation, and in-hospital mortality) were captured from electronic health records. For patients identified as having a history of HF by International Classification of Diseases-9th and/or 10th Revisions codes, manual chart abstraction informed etiology, functional class, and left ventricular ejection fraction (LVEF). Results Mean age was 63.5 years, and 45% were women. Compared with patients without HF, those with previous HF experienced longer length of stay (8 days vs. 6 days; p, Central Illustration

T cells are implicated in the pathogenesis of cardiac allograft vasculopathy (CAV), yet their clonality, specificity, and function are incompletely defined. Here we used T cell receptor β chain (TCRB) sequencing to study the T cell repertoire in the coronary artery, endomyocardium, and peripheral blood at the time of retransplant in four cases of CAV and compared it to the immunoglobulin heavy chain variable region (IGHV) repertoire from the same samples. High-dimensional flow cytometry coupled with single-cell PCR was also used to define the T cell phenotype. Extensive overlap was observed between intragraft and blood TCRBs in all cases, a finding supported by robust quantitative diversity metrics. In contrast, blood and graft IGHV repertoires from the same samples showed minimal overlap. Coronary infiltrates included CD4+ and CD8+ memory T cells expressing inflammatory (IFNγ, TNFα) and profibrotic (TGFβ) cytokines. These were distinguishable from the peripheral blood based on memory, activation, and tissue residency markers (CD45RO, CTLA-4, and CD69). Importantly, high-frequency rearrangements were traced back to endomyocardial biopsies (2-6 years prior). Comparison with four HLA-mismatched blood donors revealed a repertoire of shared TCRBs, including a subset of recently described cross-reactive sequences. These findings provide supportive evidence for an active local intragraft bystander T cell response in late-stage CAV.

BACKGROUND Orthotopic heart transplantation (OHT) recipients may be particularly vulnerable to coronavirus disease 2019 (COVID-19). OHT during the pandemic presents unique challenges in terms of feasibility and safety. METHODS Chart review was performed for consecutive OHT recipients with COVID-19 and waitlisted patients who underwent OHT from March 1, 2020 to May 15, 2020. RESULTS Of the approximately 400 OHT recipients followed at our institution, 22 acquired COVID-19. Clinical characteristics included median age 59 (range, 49–71) years, 14 (63.6%) were male, and median time from OHT to infection was 4.6 (2.5–20.6) years. Symptoms included fever (68.2%), gastrointestinal complaints (55%), and cough (46%). COVID-19 was severe or critical in 5 (23%). All patients had elevated inflammatory biomarkers. Immunosuppression was modified in 85% of patients. Most (n = 16, 86.4%) were hospitalized, 18% required intubation, and 14% required vasopressor support. Five patients (23%) expired. None of the patients requiring intubation survived. Five patients underwent OHT during the pandemic. They were all males, ranging from 30 to 59 years of age. Two were transplanted at United Network of Organ Sharing Status 1 or 2, 1 at Status 3, and 2 at Status 4. All were successfully discharged and are alive without allograft dysfunction or rejection. One contracted mild COVID-19 after the index hospitalization. CONCLUSION OHT recipients with COVID-19 appear to have outcomes similar to the general population hospitalized with COVID-19. OHT during the pandemic is feasible when appropriate precautions are taken. Further study is needed to guide immunosuppression management in OHT recipients affected by COVID-19.

The degree of myocardial injury, as reflected by troponin elevation, and associated outcomes among U.S. hospitalized patients with coronavirus disease-2019 (COVID-19) are unknown.The purpose of this study was to describe the degree of myocardial injury and associated outcomes in a large hospitalized cohort with laboratory-confirmed COVID-19.Patients with COVID-19 admitted to 1 of 5 Mount Sinai Health System hospitals in New York City between February 27, 2020, and April 12, 2020, with troponin-I (normal value 0.03 ng/ml) measured within 24 h of admission were included (n = 2,736). Demographics, medical histories, admission laboratory results, and outcomes were captured from the hospitals' electronic health records.The median age was 66.4 years, with 59.6% men. Cardiovascular disease (CVD), including coronary artery disease, atrial fibrillation, and heart failure, was more prevalent in patients with higher troponin concentrations, as were hypertension and diabetes. A total of 506 (18.5%) patients died during hospitalization. In all, 985 (36%) patients had elevated troponin concentrations. After adjusting for disease severity and relevant clinical factors, even small amounts of myocardial injury (e.g., troponin I0.03 to 0.09 ng/ml; n = 455; 16.6%) were significantly associated with death (adjusted hazard ratio: 1.75; 95% CI: 1.37 to 2.24; p 0.001) while greater amounts (e.g., troponin I0.09 ng/dl; n = 530; 19.4%) were significantly associated with higher risk (adjusted HR: 3.03; 95% CI: 2.42 to 3.80; p 0.001).Myocardial injury is prevalent among patients hospitalized with COVID-19; however, troponin concentrations were generally present at low levels. Patients with CVD are more likely to have myocardial injury than patients without CVD. Troponin elevation among patients hospitalized with COVID-19 is associated with higher risk of mortality.

The coronavirus disease 2019 (COVID-19) pandemic exposes unexpected cardiovascular vulnerabilities and the need to improve cardiometabolic health. Four cardiometabolic drivers—abnormal adiposity, dysglycemia, dyslipidemia, and hypertension—are examined in the context of COVID-19. Specific recommendations are provided for lifestyle change, despite social distancing restrictions, and pharmacotherapy, particularly for those with diabetes. Inpatient recommendations emphasize diligent and exclusive use of insulin to avert hyperglycemia in the face of hypercytokinemia and potential islet cell injury. Continuation of statins is advised, but initiating statin therapy to treat COVID-19 is as yet unsubstantiated by the evidence. The central role of the renin-angiotensin system is discussed. Research, knowledge, and practice gaps are analyzed with the intent to motivate prompt action. An emerging model of COVID-related cardiometabolic syndrome encompassing events before, during the acute phase, and subsequently in the chronic phase is presented to guide preventive measures and improve overall cardiometabolic health so future viral pandemics confer less threat., Central Illustration, Highlights • COVID-19 exposes epidemiological and mechanistic relationships with cardiometabolic links (abnormal adiposity, dysglycemia, dyslipidemia, and hypertension). • Lifestyle, glycemic control, and regulation of the RAS have important implications for management of patients with COVID-19. • CIRCS applies to all stages of COVID-19 illness, including prevention, acute management, and long-term outcomes. • Further research should address gaps in current knowledge and clinical implementation of available strategies to mitigate the adverse consequences of CIRCS.

STRUCTURED ABSTRACTBackgroundThe degree of myocardial injury, reflected by troponin elevation, and associated outcomes among hospitalized patients with Coronavirus Disease (COVID-19) in the US are unknown.ObjectivesTo describe the degree of myocardial injury and associated outcomes in a large hospitalized cohort with laboratory-confirmed COVID-19.MethodsPatients with COVID-19 admitted to one of five Mount Sinai Health System hospitals in New York City between February 27th and April 12th, 2020 with troponin-I (normal value ResultsThe median age was 66.4 years, with 59.6% men. Cardiovascular disease (CVD) including coronary artery disease, atrial fibrillation, and heart failure, was more prevalent in patients with higher troponin concentrations, as were hypertension and diabetes. A total of 506 (18.5%) patients died during hospitalization. Even small amounts of myocardial injury (e.g. troponin I 0.03-0.09ng/mL, n=455, 16.6%) were associated with death (adjusted HR: 1.77, 95% CI 1.39-2.26; P0.09 ng/dL, n=530, 19.4%) were associated with more pronounced risk (adjusted HR 3.23, 95% CI 2.59-4.02).ConclusionsMyocardial injury is prevalent among patients hospitalized with COVID-19, and is associated with higher risk of mortality. Patients with CVD are more likely to have myocardial injury than patients without CVD. Troponin elevation likely reflects non-ischemic or secondary myocardial injury.Unstructured AbstractMyocardial injury reflected as elevated troponin in Coronavirus Disease (COVID-19) is not well characterized among patients in the United States. We describe the prevalence and impact of myocardial injury among hospitalized patients with confirmed COVID-19 and troponin-I measurements within 24 hours of admission (N=2,736). Elevated troponin concentrations (normal

IMPORTANCE: Given the shortage of donor hearts and improvement in outcomes with left ventricular assist device (LVAD) therapy, a relevant but, to date, unanswered question is whether select patients with advanced heart failure should receive LVAD destination therapy as an alternative to heart transplant. OBJECTIVE: To determine whether a strategy of LVAD destination therapy is associated with similar survival benefit as wait-listing for heart transplant with or without LVAD therapy among patients with advanced heart failure. DESIGN, SETTING, AND PARTICIPANTS: This retrospective propensity-matched cohort analysis used data on heart transplants from the United Network for Organ Sharing registry and LVAD implants from the Interagency Registry for Mechanically Assisted Circulatory Support from January 1, 2010, to December 31, 2014. The matched LVAD destination therapy cohort included 3411 patients. Data analysis for this study was conducted from December 22, 2017, to May 24, 2019. MAIN OUTCOMES AND MEASURES: Survival at 5 years was analyzed using Cox proportional hazards models. RESULTS: In total, 8281 patients had albumin level, creatinine level, and BMI data recorded and were included in the analysis. Despite propensity score matching, the 3411 patients receiving LVAD destination therapy still tended to be slightly older than the 3411 patients wait-listed for heart transplant (64.0 years [interquartile range, 55.0-70.0 years] vs 60.0 [interquartile range, 54.0-65.0 years]; P

Introduction While LVAD outflow cannula obstructions are commonly described, we present a rare case of fulminant heart failure secondary to dynamic inflow cannula obstruction due to mobile thrombi within the left ventricular cavity. Case Report A 65 year old man with a history of ischemic cardiomyopathy and chronic kidney disease (CKD) underwent implantation of a continuous flow left ventricular assist device (LVAD; HeartWare™ HVAD™, Medtronic plc) as a bridge to transplantation. Three years following implantation, he presented with progressive fulminant right heart failure (RHF) followed by a sudden decrease in LVAD flow from 3.5 to 1.5 liters/min (Figure 1A). INR was 2.6, lactate dehydrogenase (LDH) level was normal and transthoracic echocardiogram showed a midline septum and the aortic valve opening with every beat. On admission, flows did not improve despite inotropic support. Outflow graft obstruction was suspected, however imaging was not pursued due to the risk of further renal injury with intravenous contrast, and that ultimately definitive treatment strategy remained heart transplantation. His UNOS listing status was upgraded from 4 to 2E. Anticoagulation was not escalated beyond aspirin and warfarin due to recurrent gastrointestinal bleeding. He continued to experience recurrent abrupt changes in LVAD flows (Figure 1B) without additional evidence to support pump thrombosis. Five weeks later, at the time of heart-kidney transplant, a partially obstructive thrombus within the inflow cannula as well as a mobile thrombus attached to the endocardium, prolapsing intermittently into the inflow cannula were visualized (Figure 1C-1D). Summary Dynamic inflow cannula obstruction should be suspected in the setting of heart failure and sudden changes in LVAD pump power consumption even when a lack corroborating imaging and laboratory evidence exists.

Objectives This study sought to determine the prevalence of atrial fibrillation (AF) and its association with cardiac outcomes in patients with left ventricular assist devices (LVADs). Background LVADs are pivotal treatments for end-stage heart failure and a critical bridge to heart transplantation. Methods Medical records of 249 consecutive patients who received an LVAD at Columbia University Medical Center were reviewed. Patient demographics, clinical variables, medications, and outcomes were recorded. Descriptive statistics were generated, and multivariable logistic regression was performed to assess the independent association of clinical variables with the presence of AF. Results Overall, AF was documented in 80 patients (32%) following LVAD placement. Before LVAD placement, 182 patients had no history of AF, whereas 67 patients had documented AF. Among these 67 patients, 56 (84%) continued to have AF following LVAD placement; 24 patients without a history of AF (13%) developed AF after LVAD placement. Patients manifesting AF after LVAD placement were more likely to have had AF before LVAD insertion (p Conclusions AF is common in patients with LVADs, with 32% manifesting AF after placement of their LVAD, including 13% without a prior documented history of AF. The presence of AF was not associated with increased risk of death or stroke.

INTRODUCTION Improved understanding of the clinical course of ambulatory advanced chronic systolic heart failure may improve the provision of appropriate care and is central to the design of clinical trials in this population. METHODS Twenty-one implanting ventricular assist device (VAD) centers enrolled 400 subjects in the Registry Evaluation of Vital Information for VADs in Ambulatory Life (REVIVAL), a prospective, observational study in ambulatory, chronic, advanced systolic heart failure, designed to identify a cohort with an approximately 25% 1-year risk of the primary composite outcome of death, urgent transplant, or durable mechanical circulatory support. Inclusion criteria utilized only information collected during routine clinical care. Exclusion criteria identified patients with contraindications to VAD. Study inclusion required at least 1 of 10 high-risk criteria derived from established hospitalization and non-hospitalization markers of increased mortality risk. We evaluated the test performance characteristics of the high-risk criteria. RESULTS Data on 373 subjects evaluable for the primary composite outcome at the 1-year visit are presented. Baseline data were consistent with a less advanced cohort than Medical Arm for Mechanically Assisted Circulatory Support or Risk Assessment (MedaMACS) and Comparative Effectiveness of Left Ventricular Assist Device and Medical Management in Ambulatory Heart Failure Patients (ROADMAP). Freedom from the primary composite outcome was 75.9%. Non-hospitalization inclusion criteria identified 89% of patients with events. CONCLUSIONS Using routinely obtained clinical information for enrollment, REVIVAL successfully recruited an ambulatory chronic systolic heart failure cohort with an approximately 25% annual risk of the primary composite outcome. Information from this registry will be relevant to the planning of future trials of earlier VAD use and of other interventions in this population.

BACKGROUND Continuous-flow mechanical circulatory support (CF-MCS) is associated with impaired vascular function and increased risk of vasoplegia. One contributing factor to early graft failure (EGF) is severe vasoplegia. We tested the hypothesis that CF-MCS is associated with increased risk of EGF. METHODS Adult primary heart transplant recipients in the ISHLT Registry from 2005 to 2013 were stratified into three groups based on pre-transplant MCS: No MCS (n = 11 748), pulsatile (P)-MCS (n = 718), and CF-MCS (n = 3818). EGF was defined as death/retransplantation due to graft failure within 30 days after HT. Comparisons were made using descriptive statistics and associations. EGF was assessed with multivariable Cox proportional hazard regression. RESULTS The incidence of EGF within 30 days was similar between groups (No MCS 2.2%, P-MCS 3.3%, CF-MCS 2.1%, P = .10). Following multivariable adjustment, the risk of EGF was not statistically different for those with CF-MCS compared with P-MCS (HR 0.75, 95% CI 0.46-1.21, P = .24). The risk of EGF was numerically, but not statistically significantly higher for CF-MCS compared with No MCS (HR 1.24, 95% CI 0.92-1.67, P = .16). CONCLUSION CF-MCS use was not associated with a statistically significant increased risk of EGF resulting in death or retransplantation in the first 30 days after transplant.

The SGLT2 inhibitor empagliflozin reduced cardiovascular mortality by 38% and heart failure (HF) hospitalizations by 35% in diabetic patients. We have recently demonstrated the efficacy of empagliflozin in ameliorating HF and improving cardiac function in a non-diabetic porcine model of HF mediated via a switch in myocardial metabolism that enhances cardiac energetics. Therefore, we hypothesized that the cardiac benefits of empagliflozin can also be extended to non-diabetic HF patients. The EMPA-TROPISM clinical trial is a randomized, double-blind, parallel group, placebo-controlled, trial comparing the efficacy of and safety of empagliflozin in non-diabetic HF patients. Eighty patients with stable HF for over 3 months, LVEF

Background The incidence of permanent pacemaker (PPM) implantation is higher following mitral valve surgery (MVS) with ablation for atrial fibrillation (AF) compared with MVS alone. Objectives This study identified risk factors and outcomes associated with PPM implantation in a randomized trial that evaluated ablation for AF in patients who underwent MVS. Methods A total of 243 patients with AF and without previous PPM placement were randomly assigned to MVS alone (n = 117) or MVS + ablation (n = 126). Patients in the ablation group were further randomized to pulmonary vein isolation (PVI) (n = 62) or the biatrial maze procedure (n = 64). Using competing risk models, this study examined the association among PPM and baseline and operative risk factors, and the effect of PPM on time to discharge, readmissions, and 1-year mortality. Results Thirty-five patients received a PPM within the first year (14.4%), 29 (83%) underwent implantation during the index hospitalization. The frequency of PPM implantation was 7.7% in patients randomized to MVS alone, 16.1% in MVS + PVI, and 25% in MVS + biatrial maze. The indications for PPM were similar among patients who underwent MVS with and without ablation. Ablation, multivalve surgery, and New York Heart Association functional (NYHA) functional class III/IV were independent risk factors for PPM implantation. Length of stay post-surgery was longer in patients who received PPMs, but it was not significant when adjusted for randomization assignment (MVS vs. ablation) and age (hazard ratio [HR]: 0.81; 95% confidence interval [CI]: 0.61 to 1.08; p = 0.14). PPM implantation did not increase 30-day readmission rate (HR: 1.43; 95% CI: 0.50 to 4.05; p = 0.50). The need for PPM was associated with a higher risk of 1-year mortality (HR: 3.21; 95% CI: 1.01 to 10.17; p = 0.05) after adjustment for randomization assignment, age, and NYHA functional class. Conclusions AF ablation, multivalve surgery, and NYHA functional class III/IV were associated with an increased risk for permanent pacing. PPM implantation following MVS was associated with a significant increase in 1-year mortality. (Surgical Ablation Versus No Surgical Ablation for Patients With Atrial Fibrillation Undergoing Mitral Valve Surgery; NCT00903370)

Heart failure can be challenging to diagnose given the spectrum of associated symptoms and the overlap of those symptoms with other diseases (e.g. renal, pulmonary, hepatic) as well as with aging and frailty. Despite advances in modern medicine, the history and physical exam remain the cornerstone of the diagnosis of heart failure, whether acute or chronic. The patient’s history is highlighted by symptoms of fluid overload (“backward failure”), decreased cardiac output (“forward failure”), or both.

Introduction We report a case of end-stage Loeffler's endocarditis treated with a total artificial heart as a bridge to transplant. Case Report A 34 year old man presented with abdominal distention and weight gain. Multimodality imaging showed near obliteration of the left ventricular cavity in systole with a dilated atria, severe atrioventricular valve regurgitation, and right ventricular dysfunction (Figure A-C). These findings led to the diagnosis of Loeffler's endocarditis (eosinophilic myocarditis) in the setting of eosinophilic granulomatosis with polyangiitis (EGPA). He was treated with diuretics and remained stable for two years before presenting with recurrent weight gain and acute kidney injury with congestive hepatopathy. There was no serologic evidence of autoimmune flare and recent positron emission tomography (PET) imaging showed minimal evidence of active inflammation in the heart. Right heart catheterization revealed elevated right sided filling pressures and severely reduced cardiac output. Given the restrictive nature of his disease, use of diuretics resulted in worsening cardiac output and there was a marginal response to inotropes such that his liver and renal function could not be normalized. Endomyocardial resection and direct transplantation were not options given ongoing liver and renal dysfunction, which put him at prohibitive risk of post-operative fulminant end-organ failure. The patient underwent successful placement of a total artificial heart (TAH; SynCardia Systems, LLC) as a bridge to transplantation. Gross pathology revealed severe endomyocardial fibrosis (D-E). His liver and renal function have normalized and the patient is awaiting heart transplant. Summary End-stage Loeffler's endocarditis is a disease with high annual mortality for which medical therapy is insufficient and use of a total artificial heart as a bridge to transplant is a viable option as life-saving therapy.

Background Left ventricular assist devices are increasingly being used in patients with advanced heart failure as both destination therapy and bridge to transplant. We aimed to identify histomorphometric, structural and inflammatory changes after pulsatile- and continuous-flow left ventricular assist device placement. Methods Clinical and echocardiographic data were collected from medical records. Aortic wall diameter, cellularity and inflammation were assessed by immunohistochemistry on aortic tissue collected at left ventricular assist device placement and at explantation during heart transplantation. Expression of adhesion molecules was quantified by Western blot. Results Decellularization of the aortic tunica media was observed in patients receiving continuous-flow support. Both device types showed an increased inflammatory response after left ventricular assist device placement with variable T-cell and macrophage accumulations and increased expression of vascular E-selectin, ICAM and VCAM in the aortic wall. Conclusions Left ventricular assist device implantation is associated with distinct vascular derangements with development of vascular inflammation. These changes are pronounced in patients on continuous-flow left ventricular assist and associated with aortic media decellularization. The present findings help to explain the progressive aortic root dilation and vascular dysfunction in patients after continuous-flow device placement.

Background Adults with congenital heart disease (CHD) are at increased risk for adverse outcomes after heart transplantation (HT). However, small cohorts have constrained the identification of factors associated with poor prognosis. We hypothesized that number of sternotomies and bystander organ dysfunction would be associated with an increased risk for early death after HT. Methods and Results We performed a retrospective observational study of all adult CHD patients who underwent HT at our institution from January 1997 to January 2014. Forty-eight adult CHD patients were followed for a mean of 5 years. Diagnoses included tetralogy of Fallot/pulmonary atresia/double-outlet right ventricle in 15 (31%), D-transposition of the great arteries (TGA) in 10 (21%), tricuspid atresia/double-inlet left ventricle in 9 (19%), ventricular or atrial septal defect in 4 (8%), heterotaxy in 3 (6%), congenitally corrected TGA in 2 (4%), and other diagnoses in 5 (10%). Survival at both 1 and 5 years was 77%. According to multivariate analysis, ≥3 sternotomies (hazard ratio [HR] 8.5; P = .02) and Model for End-Stage Liver Disease Excluding International Normalized Ratio (MELD-XI) score >18 (HR 6.2; P = .01) were significant predictors of mortality. Failed Fontan surgery was not a significant predictor of death ( P = .19). Conclusions In our cohort of adult CHD patients undergoing HT, ≥3 sternotomies and MELD-XI score >18 were significantly associated with death. These findings may be important in patient selection and decision regarding tolerable number of CHD surgeries before considering HT.

We sought to explore differences in distribution and morphology of coronary lesions comparing cardiac allograft vasculopathy and native coronary atherosclerosis (NCA) using intravascular imaging with optical coherence tomography (OCT). At the time of routine surveillance angiography, 17 heart transplant (HT) recipients with a history of high-grade cellular rejection (HGR) and 43 HT recipients with none/mild (low)-grade rejection underwent OCT imaging of the left anterior descending and were compared to 60 patients with NCA without HT. Compared with patients with NCA, patients with HGR had similar intima areas but smaller external elastic lamina areas (7.9 mm(2) [6.3, 11.2] versus 6.6 mm(2) [4.8, 7.5], p = 0.02) resulting in smaller lumen areas (4.5 mm(2) [3.4, 6.6] versus 3.3 mm(2) [2.8, 4.7], p = 0.04) in distal segments and smaller lumen diameters in side branches (1.28 mm [1.19, 1.37] versus 1.09 mm [0.94, 1.24], p = 0.04). Compared with patients with NCA, lesions in patients with HT were more homogeneous, involving the entire coronary vascular tree. Patients with HGR had a higher prevalence of macrophages involving ≥1 quadrant in all 3 segments compared with patients with NCA. The number of microvessels was greater in patients with both HGR and LGR HT versus NCA. In conclusion, distinct findings in the distribution and morphology of coronary lesions between HT recipients and patients with NCA are evident by OCT imaging, suggesting that OCT might be useful to help differentiate cardiac allograft vasculopathy from NCA in vivo.

Objectives This study sought to assess the association of multiple listing with waitlist outcomes and post–heart transplant (HT) survival. Background HT candidates in the United States may register at multiple centers. Not all candidates have the resources and mobility needed for multiple listing; thus this policy may advantage wealthier and less sick patients. Methods We identified 33,928 adult candidates for a first single-organ HT between January 1, 2000 and December 31, 2013 in the Organ Procurement and Transplantation Network database. Results We identified 679 multiple-listed (ML) candidates (2.0%) who were younger (median age, 53 years [interquartile range (IQR): 43 to 60 years] vs. 55 years [IQR: 45 to 61 years]; p Conclusions Multiple listing is a rational response to organ shortage but may advantage patients with the means to participate rather than the most medically needy. The multiple-listing policy should be overturned.

Allogeneic mesenchymal precursor cells (MPCs) have direct cardiac and systemic effects. An important question in stem cell research is whether MPCs have a differential effect based on heart failure etiology. A recent NIH-funded phase II trial of allogeneic mesenchymal precursor cells (MPCs) injected

A 60-year-old woman developed cardiac allograft vasculopathy 9 years after heart transplantation and was treated with a drug-eluting stent in the left anterior descending coronary artery. Recurrence of in-stent restenosis was treated with another drug-eluting stent. Recurrent in-stent restenosis was again observed and a robotic mid–coronary artery bypass graft operation was successfully performed. Mid–coronary artery bypass graft is a plausible alternative in patients with cardiac allograft vasculopathy and offers the benefit of a left internal thoracic artery to a left anterior descending coronary artery graft with a sternotomy-sparing approach. This case report documents the adoption of this technique in a redo heart transplant patient, creating the potential for a new tool in the treatment of cardiac allograft vasculopathy.

We report the case of a 63-year-old woman who presented with typical angina (crushing chest pain) and recurrent frank syncope two years after her heart transplant. She was observed to have transient ST-elevations on continuous ST-segment monitoring that correlated with her symptoms, and coronary angiography revealed severe and transient spasm of the right coronary artery concurrent with her symptoms and ST-segment changes. The observed spasm completely resolved following administration of intracoronary nitroglycerin in the cardiac cathetherization laboratory. Although rare (occurring in ~5% of patients following cardiac transplantation), coronary artery spasm can occur in post-transplanted hearts and is occasionally diagnosed by coronary angiography.

Purpose Readmission after hospitalization for heart failure (HF) remains a major public health problem. We hypothesized that point-of-care (POC) testing using remote dielectric sensing (ReDS) to measure percent lung water volume after HF hospitalization may improve guideline-directed medical therapy (GDMT) and reduce 30-day hospital readmission. Methods Data were collected for patients scheduled for rapid follow-up (RFU) visits within 10 days post-discharge for HF at Mount Sinai Hospital between July 1, 2017 and July 21, 2018 and included whether ReDS readings were obtained and medication changes were made. Diuretics were adjusted using the following algorithm: hold diuretics if ReDS loop diuretic or hospitalization if ReDS > 46%. The association between use of ReDS and 30-day readmission was evaluated with multivariable logistic regression modeling adjusting for baseline confounders. Results Of the 290 patients included in the analysis, 238 (82.1%) presented to RFU clinic. Overall, mean age was 62.8±14.4 years and 36.5% were female. 30-day readmission rate was 35.3% in patients who did not present to RFU clinic versus 11.8% for those who did (p Conclusion Use of ReDS to guide GDMT and diuretic titration for HF was feasible and may be associated with lower 30-day readmission post-discharge for HF. Further longitudinal experience with POC ReDS testing can provide insights into the frequency of congestion early after HF discharge, reductions in hospital readmission and the optimization of GDMT.