SGLT-2 inhibitors in heart failure and chronic kidney disease: A review for internists.

Despite current therapies, heart failure and chronic kidney disease continue to be major causes of morbidity and mortality. Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have recently become standard-of-care therapy for these conditions. This review summarizes important randomized controlled trials of SGLT-2 inhibitors and guidelines for using these agents in patients with heart failure and chronic kidney disease in both clinic and hospital settings.

Three-Year Left Ventricular Assist Device Outcomes and Strategy After Heart Transplant Allocation Score Change.

The United Network for Organ Sharing (UNOS) adopted new criteria for the heart allocation score on October 18, 2018 to reflect the changing trends of candidates' mortality while awaiting transplant. We examined the impact of these policy changes on rates of left ventricular assist device (LVAD) implantation and outcomes after transplant from a relatively newer UNOS database. The UNOS registry was used to identify first-time adult heart recipients with LVAD at listing or transplant who underwent transplantation between January 1, 2016 and March 10, 2020. Survival data were collected through March 30, 2023. Those listed before October 18, 2018 but transplanted after were excluded. Patients were divided into before or after change groups. Demographics and clinical parameters were compared. Survival was analyzed with Kaplan-Meier curves and log-rank tests. A p <0.05 was considered significant. We identified 4,387 heart recipients with LVAD in the before (n = 3,606) and after (n = 781) score change eras. The after group had a lower rate of LVAD implantation while listed than the before group (20.4% vs 34.9%, p <0.0001), and were more likely to be female (25.1% vs 20.2%, p = 0.002); in both groups, most recipients (62.8%) were white. There was significantly farther distance from the donor hospital to transplant center in the after group (264.4 NM vs 144.2 NM, p <0.0001) and decreased waitlist days (84.9 ± 105.1 vs 369.2 ± 459.5, p <0.0001). Recipients in the after group were more likely to use extracorporeal membrane oxygenation (3.7% vs 0.5%, p <0.0001) and intravenous inotropes (19.1% vs 7.5%, p <0.0001) and receive a Centers for Disease Control and Prevention increased risk donor organ (37.9% vs 30.5%, p <0.0001). Survival at 3 years was comparable between the 2 groups. The allocation score change in 2018 yielded considerable changes in mechanical circulatory support device implantation strategy and outcomes. The rate of LVAD implantation decreased with increased utilization of temporary mechanical circulatory support devices.

Heart Transplant Human Leukocyte Antigen Matching in the Modern Era.

BACKGROUND: Although numerous reports have studied the consequences of human leukocyte antigen (HLA) mismatching in renal transplantation, there are limited and outdated data analyzing this association in thoracic organ transplantation. Therefore, our study reviewed the impact of HLA mismatching at both the total and the loci levels in the modern-era heart-transplant procedure on survival and chronic rejection outcomes. METHODS: We performed a retrospective analysis of adult patients after heart transplant by using the United Network for Organ Sharing database from January 2005-July 2021. Total HLA and HLA-A, HLA-B and HLA-DR mismatches were analyzed. Survival and cardiac allograft vasculopathy were the outcomes of interest during a 10-year follow-up period using Kaplan-Meier curves, log-rank tests and multivariable regression models. RESULTS: A total of 33,060 patients were included in this study. Recipients with a high degree of HLA mismatching had increased incidences of acute organ rejection. There were no significant differences in mortality rates among any of the total or loci level groups. Similarly, there were no significant differences between total HLA mismatch groups in time to first cardiac allograft vasculopathy, though mismatching at the HLA-DR locus was associated with an increased risk of cardiac allograft vasculopathy. CONCLUSION: Our analysis suggests that HLA mismatch is not a significant predictor of survival in the modern era. Overall, the clinical implications of this study provide reassuring data for the continued use of non-HLA-matched donors in an effort to increase the donor pool. If HLA matching is to be considered for heart transplant donor-recipient selection, matching at the HLA-DR locus should take priority due to its association with cardiac allograft vasculopathy.

Use of a Cardiac Scale to Predict Heart Failure Events: Design of SCALE-HF 1.

BACKGROUND: There is a need for simple, noninvasive solutions to remotely monitor and predict worsening heart failure (HF) events. SCALE-HF 1 (Surveillance and Alert-Based Multiparameter Monitoring to Reduce Worsening Heart Failure Events) is a prospective, multicenter study that will develop and assess the accuracy of the heart function index-a composite algorithm of noninvasive hemodynamic biomarkers from a cardiac scale-in predicting worsening HF events. METHODS: Approximately 300 patients with chronic HF and recent decompensation will be enrolled in this observational study for model development. Patients will be encouraged to take daily cardiac scale measurements. RESULTS: Approximately 50 HF events, defined as an urgent, unscheduled clinic, emergency department, or hospitalization for worsening HF will be used for model development. The composite index will be developed from hemodynamic biomarkers derived from ECG, ballistocardiogram, and impedance plethysmogram signals measured from the cardiac scale. Biomarkers of interest include weight, peripheral impedance, pulse rate and variability, and estimates of stroke volume, cardiac output, and blood pressure captured through the cardiac scale. The sensitivity, unexplained alert rate, and alerting time of the index in predicting worsening HF events will be evaluated and compared with the performance of simple weight-based rule-of-thumb algorithms (eg, weight increase of 3 lbs in 1 day or 5 lbs in 7 days) that are often used in practice. CONCLUSIONS: SCALE-HF 1 is the first study to develop and evaluate the performance of a composite index derived from noninvasive hemodynamic biomarkers measured from a cardiac scale in predicting worsening HF events. Subsequent studies will validate the heart function index and assess its ability to improve patient outcomes. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04882449.

Serum dilutions as a predictive biomarker for peri-operative desensitization: An exploratory approach to transplanting sensitized heart candidates.

Antibody-mediated rejection (AMR) of cardiac allografts mediated by anti-HLA Donor Specific Antibodies (DSA) is one of the major barriers to successful transplantation for the treatment of end-stage heart failure. Therapeutic plasma exchange (TPE) is a first-line treatment for pre-transplant desensitization. However, indications for treatment regimens and treatment end-points have not been well established. In this study, we investigated how sera dilutions could guide TPE regimens for effective peri-operative desensitization and early AMR treatment. Our data show that 1:16 dilutions of EDTA-treated sera and 1.5 volume TPE reduce anti-HLA class I and class II antibody levels in the same manner and, therefore, allows to predict which antibodies would respond to peri-operative TPE. We successfully applied this approach to transplanting three highly sensitized cardiac recipients (CPRA 85-93%) with peri-operative desensitization based on a virtual crossmatch performed on 1:16 diluted serum. Furthermore, we have used sera dilutions to guide DSA treatment post-transplant. Although these findings have to be confirmed in a larger prospective study, our data suggest that serum dilutions can serve as a predictive biomarker to guide peri-operative desensitization and post-transplant immunologic management.

Hemodynamic Response to Exercise in Patients Supported by Continuous Flow Left Ventricular Assist Devices.

OBJECTIVES: This study sought to characterize the hemodynamic response to exercise in LVAD-supported patients and identify parameters most strongly associated with peak oxygen consumption (VO2). BACKGROUND: Despite improved survival for heart failure patients afforded by continuous flow left ventricular assist devices (LVADs), peak exercise capacity remains impaired. Mechanisms underlying this reduced functional capacity remain poorly understood. METHODS: Patients referred for post-VAD hemodynamic optimization from December 2017 through June 2019 were enrolled. Swan Ganz catheters were inserted and upright incremental bicycle ergometry with respiratory gas analysis was performed. Hemodynamic measurements, mixed venous saturation, and arterial blood pressure were recorded every 3 min during exercise. Linear correlations were performed between peak VO2 (ml/min) and peak Fick cardiac output (CO), peak device flow, the assumed intrinsic CO derived as Fick CO-device flow, peak pressure differential across the LVAD (mean arterial pressure-pulmonary capillary wedge pressure), peak pressure differential across right ventricle (mean pulmonary artery pressure - right atrial pressure) and systemic vascular resistance. RESULTS: Forty-five patients supported by axial flow pumps (n = 12) and centrifugal flow pumps (n = 33) were studied. There were 34 men and 11 women. Age averaged 60 ± 10 years. Peak VO2 averaged 10.6 ± 3.1 ml/kg/min. Fick CO had the greatest correlation with peak VO2 with r = 0.73 (p < 0.0001) followed by intrinsic CO (r = 0.67; p < 0.0001). Multivariate model that best predicted peak VO2 included Fick CO and peak arterial venous oxygen (AVO2) difference. CONCLUSIONS: LVAD supported patients have severely impaired peak exercise capacity. The peak Fick cardiac output was the best correlate of peak exercise performance.

Intermediate term hemodynamic effects of single inferior vena cava valve implant for the treatment of severe tricuspid regurgitation.

Severe tricuspid regurgitation (TR) remains a vastly undertreated disease, with sustained elevation of right atrial (RA) pressure directly resulting in chronic end-organ damage. Recently, bi-caval valve implantation has been shown to improve symptoms in patients with symptomatic TR who are at high risk for surgery. We present the first report of intermediate term hemodynamic effects of single inferior vena cava (IVC) valve implantation (CAVI) for treatment of severe TR. We performed CAVI on a 66-year-old female with severe TR, who suffered from repeat hospitalizations for treatment refractory NYHA class III-IV heart failure symptoms and had prohibitive operative risk. Pre-implantation right heart catheterization (RHC) revealed a mean RA pressure of 12 mm Hg, an IVC mean pressure of 13 mm Hg, with V-waves to 16 and 18 mm Hg in the RA and IVC respectively, and a cardiac output (CO) of 3.5 liters per minute (LPM). Postprocedure, mean IVC and RA pressures decreased to 11 and 10 mm Hg, respectively, with CO increasing to 5.1 LPM. At one month, symptoms improved to NYHA class II. At 9 months, mean RA pressure was 5 mm Hg with V-waves to 7 mm Hg and an improvement in CO to 6.3 LPM. CAVI appears to result in similar decreases in RA pressure at intermediate follow-up as compared to bi-caval valve implantation. The favorable hemodynamic effects were likely mediated by redirection of regurgitant blood flow away from the IVC thereby resulting in sustained reduction in right-sided pressures as well as an increase in CO. © 2017 Wiley Periodicals, Inc.

Factors Influencing Physician Counseling on Cardiovascular Risk.

BACKGROUND AND IMPORTANCE: A significant reduction in cardiovascular disease (CVD) mortality is related to aggressive management of modifiable CVD risk factors. Therefore, patients at increased risk for CVD should not only benefit from standard pharmacotherapy but also from counseling regarding lifestyle behavioral changes. OBJECTIVE: To determine the patient factors that influence provision of cardiovascular risk reduction counseling from physicians, as well as the frequencies of counseling. DESIGN, SETTING, AND PARTICIPANTS: Secondary analysis of a prospective, randomized trial among an underserved inner-city and rural population (n = 388) with a 10% or greater CVD risk (Framingham 10-year risk score). Subjects were followed for 1 year and were seen for quarterly assessments, which included evaluation of weight, blood pressure, lipid, and glucose status. At each of the 4 quarterly visits, subjects were asked if their physician had discussed or made recommendations regarding lifestyle behaviors, specifically diet, weight loss, and exercise. RESULTS: The average patient age was 61.3 ± 10.1 years, average A1c was 6.7 ± 1.6%, average total cholesterol was 201 ± 44 mg/dL. The average body mass index (BMI) was 31.8 ± 6.4 kg/m2, and the average blood pressure was 146 ± 18/82 ±11 mm Hg. Using binary logistic regression analysis, BMI (P < .025) was the only clinical factor related to physician lifestyle counseling. All other risk factors showed no statistical relationship. CONCLUSION: The data indicate that BMI is the major factor associated with whether or not physicians provide counseling regarding nutrition and weight loss. Physicians may be missing important opportunities to influence behavior in patients at high risk for CVD by limiting their focus to obese patients.