Desensitizing highly sensitized heart transplant candidates with the combination of belatacept and proteasome inhibition.

HLA antibodies pose a significant barrier to transplantation and current strategies to reduce allosensitization are limited. We hypothesized that augmenting proteasome inhibitor (PI) based desensitization with costimulation blockade (belatacept) to mitigate germinal center (GC) responses might increase efficacy and prevent rebound. Four highly sensitized (calculated panel reactive antibody [cPRA] class I and/or II >99%, complement-dependent cytotoxicity panel reactive antibody [CDC PRA+], C1q+) heart transplant candidates were treated with the combination of belatacept and PI therapy, which significantly reduced both class I and II HLA antibodies and increased the likelihood of identifying an acceptable donor. Three negative CDC crossmatches were achieved against 3, 6, and 8 donor-specific antibodies (DSA), including those that were historically C1q+ binding. Posttransplant, sustained suppression of 3 of 3, 4 of 6, and 8 of 8 DSA (cases 1-3) was achieved. Analysis of peripheral blood mononuclear cells before and after desensitization in one case revealed a decrease in naïve and memory B cells and a reduction in T follicular helper cells with a phenotype suggesting recent GC activity (CD38, PD1, and ICOS). Furthermore, a shift in the natural killer cell phenotype was observed with features suggestive of activation. Our findings support synergism between PI based desensitization and belatacept facilitating transplantation with a negative CDC crossmatch against historically strong, C1q binding antibodies.

The national financial burden of guideline directed medical therapy for heart failure patients from 2013 to 2021.

BACKGROUND: Guideline Directed Medical Therapy (GDMT) has been revolutionary in improving outcomes of heart failure patients. However, with the addition of more medication classes, the annual cost of these medications on the US healthcare system needs further evaluation. OBJECTIVES: We aim to evaluate the trend of annual cost of GDMT from 2013 to 2021 using the Medicare-part D Database. METHODS: Using Medicare Part D database (2013-2021), we determined the number of beneficiaries receiving these drugs, the total number of 30-day fills for each medication, and the total annual spending on these medications. Linear regression was used to analyze data using Python Programming Language. P value of less than 0.05 was considered to be statistically significant. RESULTS: The estimated annual Medicare- part D spending on empagliflozin had a 50 % increase in cost between 2020 and 2021, which could be attributed to its FDA approval for heart failure with reduced ejection fraction. Empagliflozin cost Medicare 3.73 billion USD in 2021 alone. In addition, sacubitril-valsartan had a strong trajectory since its introduction to the market in 2015. Since its approval in July 2015, it cost Medicare 4.51 billion USD. The Mineralocorticoid Receptor Antagonist class was the least costly class of GDMT. CONCLUSION: The rise in the cost of GDMT is not proportionate amongst the different classes of GDMT. Newer classes of medications cast a significant cost on Medicare in recent years.

Risk factors for cardiogenic shock in thyroid storm: a retrospective and case-series study.

Aim: Thyroid storm (TS) occurs in 10% of thyrotoxicosis patients and 1% of TS patients experience cardiogenic shock (CS), which is associated with poor prognosis. Methods: This is a single institution, retrospective study in which 56 patients with TS were evaluated. Results: BMI (p = 0.002), history of heart failure (OR 8.33 [1.91, 36.28]; p = 0.004), pro-BNP elevation (p = 0.04), chest x-ray showing interstitial edema (OR 3.33 [1.48, 7.52]; p = 0.01) and Burch-Wartofsky score (62.5 vs 40; p = 0.004) showed association with CS. CS patients had increased length of stay (16.5 vs 4 days; p = 0.01) and higher in-hospital mortality (OR 24.5 [2.90, 207.29]; p < 0.001). Conclusion: These risk factors are useful to risk stratify TS patients on admission, institute therapy in a timely manner and decrease mortality.

Angiotensin receptor neprilysin inhibitor use in patients with left ventricular assist devices: A single-center experience.

Though left ventricular assist devices (LVADs) are an increasingly common therapy for ACC/AHA Stage D heart failure, the optimal medical therapy for patients with LVADs is not known. We sought to evaluate the safety and efficacy of angiotensin receptor neprilysin inhibitor (ARNi) therapy in our single center LVAD patient experience. We evaluated patients implanted with LVADs at Columbia University Irving Medical Center between August 2010 and May 2019, and who were treated with an ARNi for at least 3 months. Thirty patients met this criteria. Eighteen (60%) patients transitioned to an ARNi from an angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), while all were on a beta blocker (BB) at the time of ARNi initiation. The primary outcome, NT-proBNP levels at time of initiation and 3 and 6 month follow up, significantly decreased from a median of 1265 pg/mL at initiation to 750 pg/mL at 3 months and 764 pg/mL at 6 months (p = 0.01). No significant change was seen in serum creatinine, BUN, or potassium levels.

Remote Cardiac Monitoring in Patients With Heart Failure: A Review.

Importance: Heart failure (HF) is often characterized by an insidious disease course leading to frequent rehospitalizations and a high use of ambulatory care. Remote cardiac monitoring is a promising approach to detect worsening HF early and intervene prior to an overt decompensation. Observations: Recently, a multitude of novel technologies for remote cardiac monitoring (RCM) in patients with HF have been developed and are undergoing clinical trials. This development has been accelerated by the COVID-19 pandemic. Conclusions and Relevance: This review summarizes the major clinical trials on RCM in patients with HF and present the most recent developments in noninvasive and invasive RCM technologies.