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Heart failure (HF) remains a condition associated with high morbidity, mortality, and associated costs. Although the number of medical and device-based therapies available to treat HF are expanding at a remarkable rate, disparities in the risk for incident HF and treatments delivered to patients are also of growing concern. These disparities span across racial and ethnic groups, socioeconomic status, and apply across the spectrum of HF from stage A to stage D. The complexity of HF risk and treatment is further impacted by the number of patients who experience the downstream impact of social determinants of health. The purpose of this document is to highlight the known health care disparities that exist in the care of patients with HF and to provide a context for how clinicians and researchers should assess both biological and social determinants of HF risk in vulnerable populations. Furthermore, this document provides a framework for future steps that can be used to help diminish inequalities in access and clinical outcomes over time, and offer solutions to help decrease disparities within HF care.

Cardiogenic shock is a multifaceted syndrome that presents with acute impairment in myocardial function resulting in poor distal end organ perfusion and hypoxia. It is a challenging disease to manage despite innovation in therapeutic options. Revascularization, vasopressor and inotropic support, and mechanical circulatory support are processes commonly used for shock management, however there is limited success in affecting long term outcomes. The impact on long term results may rely on protocols emphasizing early intervention in those presenting with advanced stages of cardiogenic shock. Classifying cardiogenic shock can indeed provide practical, clinically relevant risk stratification to implement appropriate therapies. In this chapter we will review the underlying causes and diagnostic criteria, pathophysiology, hemodynamic markers to assess disease severity, establish the indications for mechanical circulatory support and discuss the shock team approach to improve outcomes.

Author(s): Elkind, Jae; Sobczyk, Juliana; Ostberg-Braun, Oscar; Silva Enciso, Jorge; Adler, Eric; Morris, Gerald P | Abstract: BackgroundBridging heart failure patients with mechanical ventricular assist devices (VAD) enables access to transplantation. However, VAD is associated with increased risk for anti-HLA antibodies associated with rejection of subsequent allografts. Factors determining alloantibody formation in these patients remain undefined.MethodsWe performed a single-center retrospective cohort study of 164 patients undergoing heart transplantation from 2014 to 2017. Medical records including use of VAD, transfused blood products, anti-HLA antibody testing, crossmatch, and time to transplant were evaluated.ResultsPatients received an average of 13.8 red blood cell and 1.9 single-donor platelet units associated with VAD. There was a 28.7% increase in the incidence of anti-HLA antibodies after VAD. Development of anti-HLA antibodies did not correlate with volume or type of blood products, but with pre-VAD HLA sensitization status; relative risk of new alloantibodies in patients with pre-VAD antibodies was 3.5-fold higher than those without prior antibodies (P = .008). Development of new anti-HLA antibodies was associated with an increased time to transplant (169 vs 330 days, P = .013).ConclusionsOur findings indicate that the presence of anti-HLA antibodies pre-VAD was the most significant risk factor for developing additional antibodies post-VAD, suggesting that a subset of patients may be predisposed to alloantibody formation.

Background Rheumatic heart disease (RHD), an autoimmune sequela of Group A streptococcal infection, is a chronic valvular disease affecting 32 million people worldwide, predominantly in developing nations. As the predisposition to autoimmune sequela still remains post transplantation, our primary objective was to assess if there were differences in mortality and rejection rates. Methods and results Using the International Society for Heart and Lung Transplantation (ISHLT) adult heart transplant registry, we identified 42 RHD patients who had undergone heart transplantation between 1988 and 2014. We matched the 42 RHD recipients by transplant year, age, and gender to 420 dilated cardiomyopathy (DCM) recipients. One-year mortality in the RHD group was 17.95% vs. 7.92% in the DCM group (P = 0.07). Survival was significantly reduced in the RHD group vs. the DCM group via Kaplan Meier curves (P = 0.04). In a multivariate model, RHD status (OR 3.19, 95% CI 1.15-8.83, P = 0.025) and serum creatinine (OR 1.41, 95% CI 1.09-1.82, P = 0.009) were associated with an increased odds of one-year mortality (P = 0.0013). Conclusions At one year post transplantation, RHD recipients had a significantly lower survival than DCM recipients. RHD status was also an independent predictor of mortality at 1 year post transplantation.

Patients with Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) levels 1-2 who either have or are at risk for right ventricular failure face significant morbidity and mortality after continuous flow left ventricular assist device (CF-LVAD) implantation. Currently, the options for biventricular support are limited the Total Artificial Heart (TAH; CardioWest, Syncardia, Tuscon, AZ) or biventricular assist device (BiVAD), which uses bulky extracorporeal or implantable displacement pumps. We describe a successful series based on an innovative approach for biventricular support in consecutive INTERMACS levels 1-2 patients utilizing a HeartWare Ventricular Assist Device (HVAD; HeartWare, Framingham, MA) in a left ventricular (LV-HVAD) and a right atrial (RA-HVAD) configuration. From June 2014 through May 2016, 11 consecutive INTERMACS levels 1-2 patients with evidence of biventricular failure underwent implantation of a CF LVAD (10 LV-HVAD and 1 HeartMate II LVAD, Thoratec, Pleasanton, CA) and RA-HVAD pumps. A total of 4,314 BiVAD support days were accumulated in our case series. Seven patients have undergone orthotopic heart transplant, whereas 3 are ambulatory and are either waiting transplant or reconsideration for transplantation. There is one mortality in this case series, which was due to an intracranial bleed from supratherapeutic anticoagulation. Two other patients experienced hemorrhagic strokes, but without neurologic sequelae, whereas no patients have experienced ischemic strokes. There were two episodes of gastrointestinal bleeding. This is the largest series to date involving this approach with outcomes superior to those previously described in patients receiving biventricular support. We conclude this novel therapy is a viable alternative to current practices in the management of biventricular failure.

Objectives: The purpose of this study was to assess whether inotropic contractile reserve (ICR) during dobutamine stress echocardiography (DSE) could risk-stratify patients with human immunodeficie...

Background— Patients with human immunodeficiency virus (HIV) infection are at increased risk of accelerated coronary artery disease (CAD) and cardiovascular events. Stress echocardiography (SE) is routinely used for risk stratification and prognosis of patients with known or suspected CAD. The prognostic value of SE in this high-risk group is unknown. The purpose of this study was to evaluate the prognostic value of SE in HIV-infected patients with known or suspected CAD. Methods and Results— We evaluated 311 patients (age, 52±9 years; 74% men; left ventricular ejection fraction, 54±12%) with history of HIV, undergoing SE (56% dobutamine). Left ventricular wall motion was evaluated on a 16-segment model, 5-point scale. An abnormal SE was defined by a fixed (infarction), biphasic, or new (ischemia) wall motion abnormality on stress. Follow-up for cardiac death and myocardial infarction was obtained. Seventy-nine (26%) patients had an abnormal SE. After 2.9±1.9 years, 17 confirmed myocardial infarction and 14 cardiac deaths occurred. SE risk-stratified patients into normal versus abnormal subgroups (event rate, 0.6% per year versus 11.8% per year; P P P =0.009) were independent predictors of cardiac events. On a forward conditional Cox proportional hazards regression model, SE provided incremental prognostic value over clinical, stress ECG, and resting echocardiographic variables (global χ 2 increased from 17.8 to 24.5 to 65 to 109, P Conclusions— SE can effectively risk-stratify and prognosticate patients with HIV. The presence of ischemia and scar during SE provides independent and incremental prognostic value over traditional variables. A normal SE response portends a benign prognosis even in this high-risk subset.

Heart failure and atrial fibrillation (AFib) are the twin epidemics of modern cardiovascular disease. The incidence of new-onset AFib in acute decompensated heart failure (ADHF) patients is difficult to predict and the short- and long-term outcomes of AFib in a cohort of patients admitted with ADHF are unknown.A total of 904 patients admitted with ADHF were studied. Incidence of AFib on admission was recorded and a multivariate analysis was performed using echocardiographic parameters to specify the predictors of AFib incidence in this cohort. In 904 ADHF patients (57% male, mean age 69 ± 14 years), 81% had history of hypertension, 40% were diabetics, and 51% were smokers. A total of 63% of the patients had known heart failure (HF) with mean ejection fraction of 34% ± 21%, and 33% of the patients had ischemic cardiomyopathy as the etiology of HF. Echocardiographic parameters were: left atrial (LA) diameter 4.5 ± 0.8 cm, left ventricular end-systolic 4.1 ± 1.3 cm, left ventricular end-diastolic 5.3 ± 1.1 cm. Right ventricular dysfunction (RVD) was present in 34% of the patients. A total of 191 (21%) patients subsequently developed AFib with two thirds of the cases occurring in patients with RVD. Using a univariate analysis, older age (OR 1.02; P.0001), history of HF (OR 2.93; P.0001), LA dilation (OR 1.58; P.0001), the presence of left ventricular hypertrophy (OR 3.01, P.0001), and RVD (OR 4.93; P.00001) were the strongest predictors for AFib. Controlling for LA size and left ventricular hypertrophy using a forward stepwise regression, RVD remained the strongest predictor (OR 4.45; P.0001). Patients with RVD had more events (cardiac readmission and mortality) than those with normal RV (56% versus 38%; P.00001), notably; all-cause mortality was 4.7%/year in the abnormal RV group versus 2.9%/year in the normal RV group; P.05. RV function analyses by echocardiography further risk stratified these patients based on their rhythm categorizing those patients with abnormal RV and AFib as the ones with the worse prognosis.RV dysfunction is a strong predictor for developing AFib in acutely decompensated systolic failure patients. Patients with AFib and RVD have the worse outcome specially when is combined with LV dysfunction, therefore; evaluation of RV function may substantiate the difference in HF prognosis.

BACKGROUND: The optimal advanced heart failure (HF) therapy strategy for patients aged 60 or older with end-stage HF refractory to optimal medical therapy remains uncertain. This study compares outcomes of three advanced HF therapy strategies in this patient population. METHODS: A single-center retrospective study was conducted in 95 patients aged 60-73 years who had undergone isolated heart transplantation (HTx) or continuous flow left ventricular assist device (LVAD) implantation from 2010 to 2017. Patients were stratified into three cohorts by strategy; HTx-only (N.=25), LVAD-to-HTx (N.=29), and LVAD-only (N.=41). Primary end point was 2-year overall survival. Secondary end points included incidence of post-operative adverse events, freedom from first readmission at 1 year, and percentage of days spent in hospital following advanced HF therapy. RESULTS: Two-year survival was 91% in HTx-only patients, 88% in LVAD-to-HTx patients, and 49% in LVAD-only patients (P=0.0008). No significant difference in post-transplant survival was found between patients with or without LVAD-related adverse events preceding transplantation (P=0.42). One-year freedom from first readmission was 38.3% in HTx-only patients, 17.2% in LVAD-to-HTx patients and 7.3% in LVAD-only patients (P=0.0028). Patients in LVAD-to-HTx cohort had higher incidences of gastrointestinal bleeding (38% vs. 3%; P

Angiotensin-converting enzyme 2 (ACE2) is a newly identified regulator of the renin-angiotensin system. This type I membrane-anchored protein has a catalytically active ectodomain that undergoes shedding. Tumor necrosis factor alpha-converting enzyme (TACE) has been shown to be involved in ACE2 shedding. Although pathophysiological significance of ACE2 shedding has been suggested, regulation of this process by TACE is not clearly defined. We characterized TACE-mediated constitutive ectodomain shedding of ACE2 using wild-type Chinese Hamster Ovary (WT-CHO), the TACE-mutant M2 (M2-CHO) cells, and EC-4 and EC-2 cells that are fibroblasts from wild-type and TACE-null mice, respectively. ACE2 was constitutively cleaved to release two distinct major soluble forms. The deglycosylated molecular masses of the larger (LSF) and smaller soluble form (SSF) were approximately 80 and 70 kDa, respectively. These forms had equivalent enzyme activities. Reduced shedding for the LSF from M2-CHO and EC-2 cells when compared with WT-CHO and EC-4 cells, respectively, was noted. TACE reconstitution in EC-2 cells expressing ACE2 resulted in increase in LSF but not SSF release, demonstrating a main role of TACE in LSF release and distinct regulations of release of the two soluble forms. Deletions of the juxtamembrane region of ACE2 reduced LSF release in CHO cell lines, whereas it abolished TACE-induced shedding in EC-2 cells. Analysis of TACE structural domains confirmed that the active site in the catalytic domain is essential for ACE2 shedding but that noncatalytic domains also play additional roles. These results demonstrate selective and specific regulation of constitutive shedding of ACE2 by TACE.

Advance heart failure (AHF) is a growing epidemic with high morbidity and mortality. Left ventricular assist device (LVAD) has come to offer an opportunity to improve survival and quality of life. This form of therapy however, is not free of complications and poses a challenge to apply to a broader population. Adjunct therapies in combination with LVAD therapy and advances in device technology are in the near future, which may lessen the number of adverse events. This review summarizes the history, clinical outcomes and current challenges facing LVAD therapy. Finally, future directions of LVADs in the treatment of AHF are discussed.

Peripheral vascular disease (PVD) portends increased morbidity and mortality in patients with heart failure. In those with advanced heart failure, heart transplantation (HT) is the only causative therapy to increase survival. However, little is known about the impact of symptomatic PVD on survival of HT recipients in large multicenter cohorts. The aim of this study was to investigate an association between recipient symptomatic PVD and survival after HT. We analyzed 20,297 patients from the United Network of Organ Sharing data set. Survival analysis using a control cohort established by propensity matching was performed. There was an increased prevalence of traditional cardiovascular risk factors in 711 patients with symptomatic PVD compared with 19,586 patients without PVD. Patients with pre-transplant symptomatic PVD had increased post-transplant mortality compared with those without PVD (1-, 5- and 10-year survival rate 91.5% vs 94.9%, 74.8% vs 82.6%, 48.6% vs 54.7%, respectively, log-rank p

The purpose of this study was to assess whether inotropic contractile reserve (ICR) during dobutamine stress echocardiography (DSE) could risk-stratify patients with human immunodeficiency virus (HIV) cardiomyopathy and predict improvement of left ventricular ejection fraction (LVEF).HIV cardiomyopathy is an important cause of heart failure and death. ICR is associated with better survival and improvement of LVEF in patients with ischemic and nonischemic cardiomyopathies. However, the prognostic value of ICR in patients with HIV cardiomyopathy is unknown.Patients with HIV cardiomyopathy and a LVEF45% who were referred for DSE were enrolled. ICR was evaluated by the delta wall motion score index (ΔWMSI), calculated as the difference between rest and peak WMSI. Patients were followed for cardiac death and change in LVEF on follow-up.Sixty patients (75% men; age, 54 ± 9 years) with HIV cardiomyopathy (mean LVEF, 28 ± 11%) formed the study group. After 2.4 ± 2.1 years, 11 cardiac deaths occurred (event rate of 7.6%/year). A receiver-operating characteristic curve identified a ΔWMSI of 0.38 as an optimal cut point for the presence of ICR, with a specificity of 88% and a sensitivity of 73% for the prediction of cardiac death. On univariable analysis, the absence of ICR (hazard ratio: 6.6; 95% confidence interval: 1.93 to 22.62; p = 0.003) and New York Heart Association functional class IV (hazard ratio: 7.2; 95% confidence interval: 2.20 to 23.65; p = 0.001) were the only predictors of cardiac death. After 2.1 ± 1.8 years, 41 patients had a follow-up echocardiogram. LVEF improvement from baseline occurred in 23 patients (56%), more so in patients with ICR than without ICR. A ΔWMSI of 0.59 predicted improvement in the LVEF with a specificity of 78% and a sensitivity of 74%.The presence of ICR during DSE can risk-stratify and predict subsequent improvement in LVEF in patients with HIV cardiomyopathy.

Ventricular assist devices (VADs) have fundamentally changed the treatment of end-stage heart failure. However, despite great advances, long-term VAD use is still associated with frequent hospitalizations, serious complications, and a 2-year survival of approximately 70% [(1)][1]. Although

Open saline-irrigated tip ablation catheters have largely supplanted standard 4 mm tip ablation catheters for pulmonary vein isolation (PVI) of atrial fibrillation (AF), based on the assumption that the procedure is safer and more efficacious. However, outcomes after procedures that use identical techniques but different radiofrequency ablation catheters have not been compared. We studied 432 consecutive patients (age 57 ± 11 yrs) with AF (duration 7.9 ± 6.1 yrs) who underwent PVI; 320 (74 %) using a conventional 4 mm catheter and 112 (26 %) using an open irrigated tip catheter. Segmental PVI targeting the earliest LA-PV activation for all PVs in each patient was used for all patients regardless of catheter for the entire study cohort. Radiofrequency energy was delivered for ≥60 secs at each target site. The pts in the 2 groups were similar with respect to age, gender and duration of AF. All 432 pts had successful complete PVI. There was no significant difference in the total number of lesions delivered per PV in the conventional 4 mm group and the irrigated tip group (Table ) at the initial procedure. Following a single procedure, 227/ 320 (71%) patients in the conventional 4 mm and 75/112 (67%) in the irrigated group were AF-free on no antiarrhythmic drug at 12 mos (p=0.43). The number of patients who required repeat procedures was similar in the conventional group (57/320, 18%) and the irrigated tip group (22/112, 20%) (p=0.66). Serious complications were also similar (2.2% vs. 1.0 %, p=0.21) Contrary to conventional wisdom, the safety and 12 month efficacy of PVI for management of AF was similar for the two types of ablation catheters. These data suggest that PVI cohorts derived from differing ablation techniques can be combined for purposes of clinical investigation. Longer term outcomes may differ and should be studied as well.

The heart failure epidemic has led to an increase in the number of patients with advanced heart failure, which is associated with high morbidity and mortality. Current therapies for advanced heart failure are limited to heart transplantation and mechanical circulatory support, with palliative care reserved for those ineligible to receive advanced therapies. Clinical trials of ventricular assist devices for patients with advanced heart failure demonstrate an improvement in survival and quality of life akin to heart transplantation. The Achilles heal of this therapy is the adverse event burden. Patient selection and multidisciplinary care are two of the strategies being used to improve long-term outcomes. Adjunct therapies in combination with left ventricular assist device therapy and advances in device technology in the near future may lessen the number of adverse events. This review summarizes the clinical outcomes, current challenges and future directions of left ventricular assist device therapy.