Mihai Gheorghiade, MD-Life and Concepts

How do you capture an idea, shape it, and then bring it into the world? Of his many talents, this ability was a fundamental characteristic of Mihai Gheorghiade. A quick glance through PubMed confirms his prodigious output, likely to overwhelm any novice or even expert scholar. His contribution to heart failure, especially acute heart failure (AHF), is profound, He authored several major concepts in acute heart failure, disseminated further by his students. Most concepts remained indelibly linked to his name: Digoxin trials research(1–3), AHFS (acute heart failure syndromes) definition(4), hemodynamic congestion(5), hospitalized heart failure (HHF) (6), the vulnerable phase(7,8), neutral hemodynamic agents(9), registries(10–12) and pre-trial registries(13), the “6-axis model”(14) and then the “8-axis model”(15). His work shaped the field of AHF

Short-stay units vs routine admission from the emergency department in patients with acute heart failure: The SSU-AHF randomized clinical trial

IMPORTANCE: More than 80% of patients who present to the emergency department (ED) with acute heart failure (AHF) are hospitalized. With more than 1 million annual hospitalizations for AHF in the US, safe and effective alternatives are needed. Care for AHF in short-stay units (SSUs) may be safe and more efficient than hospitalization, especially for lower-risk patients, but randomized clinical trial data are lacking. OBJECTIVE: To compare the effectiveness of SSU care vs hospitalization in lower-risk patients with AHF. DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial randomly assigned low-risk patients with AHF 1:1 to SSU or hospital admission from the ED. Patients received follow-up at 30 and 90 days post discharge. The study began December 6, 2017, and was completed on July 22, 2021. The data were analyzed between March 27, 2020, and November 11, 2023. INTERVENTION: Randomized post-ED disposition to less than 24 hours of SSU care vs hospitalization. MAIN OUTCOMES AND MEASURES: The study was designed to detect at least 1-day superiority for a primary outcome of days alive and out of hospital (DAOOH) at 30-day follow-up for 534 participants, with an allowance of 10% participant attrition. Due to the COVID-19 pandemic, enrollment was truncated at 194 participants. Before unmasking, the primary outcome was changed from DAOOH to an outcome with adequate statistical power: quality of life as measured by the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ-12). The KCCQ-12 scores range from 0 to 100, with higher scores indicating better quality of life. RESULTS: Of the 193 patients enrolled (1 was found ineligible after randomization), the mean (SD) age was 64.8 (14.8) years, 79 (40.9%) were women, and 114 (59.1%) were men. Baseline characteristics were balanced between arms. The mean (SD) KCCQ-12 summary score between the SSU and hospitalization arms at 30 days was 51.3 (25.7) vs 45.8 (23.8) points, respectively (P = .19). Participants in the SSU arm had 1.6 more DAOOH at 30-day follow-up than those in the hospitalization arm (median [IQR], 26.9 [24.4-28.8] vs 25.4 [22.0-27.7] days; P = .02). Adverse events were uncommon and similar in both arms. CONCLUSIONS AND RELEVANCE: The findings show that the SSU strategy was no different than hospitalization with regard to KCCQ-12 score, superior for more DAOOH, and safe for lower-risk patients with AHF. These findings of lower health care utilization with the SSU strategy need to be definitively tested in an adequately powered study. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03302910

Acute Dyspnea and Decompensated Heart Failure

The majority of patients hospitalized with acute heart failure (AHF) initially present to the emergency department (ED). Correct diagnosis followed by prompt treatment ensures optimal outcomes. Paradoxically, identification of high risk is not the unmet need, given nearly all ED AHF patients are hospitalized; rather, it is identification of low-risk. Currently, no risk-stratification instrument can be universally recommended to safely discharge ED patients. With the exception of diagnosis, management recommendations are largely expert opinion, informed by existing evidence and tradition. In the absence of robust evidence, we propose a framework for management to guide the busy clinician

Convergent finite difference schemes for stochastic transport equations

We present difference schemes for stochastic transport equations with low-regularity velocity fields. We establish $L^2$ stability and convergence of the difference approximations under conditions that are less strict than those required for deterministic transport equations. The $L^2$ estimate, crucial for the analysis, is obtained through a discrete duality argument and a comprehensive examination of a class of backward parabolic difference schemes

Approach to Acute Heart Failure in the Emergency Department

Acute heart failure (AHF) patients rarely present complaining of ‘acute heart failure.’ Rather, they initially present to the emergency department (ED) with a myriad of chief complaints, symptoms, and physical exam findings. Such heterogeneity prompts an initially broad differential diagnosis; securing the correct diagnosis can be challenging. Although AHF may be the ultimate diagnosis, the precipitant of decompensation must also be sought and addressed. For those AHF patients who present in respiratory or circulatory failure requiring immediate stabilization, treatment begins even while the diagnosis is uncertain. The initial diagnostic workup consists of a thorough history and exam (with a particular focus on the cause of decompensation), an EKG, chest X-ray, laboratory testing, and point-of-care ultrasonography performed by a qualified clinician or technologist. We recommend initial treatment be guided by presenting phenotype. Hypertensive patients, particularly those in severe distress and markedly elevated blood pressure, should be treated aggressively with vasodilators, most commonly nitroglycerin. Normotensive patients generally require significant diuresis with intravenous loop diuretics. A small minority of patients present with hypotension or circulatory collapse. These patients are the most difficult to manage and require careful assessment of intra- and extra-vascular volume status. After stabilization, diagnosis, and management, most ED patients with AHF in the United States (US) are admitted. While this is understandable, it may be unnecessary. Ongoing research to improve diagnosis, initial treatment, risk stratification, and disposition may help ease the tremendous public health burden of AHF

Improving Postdischarge Outcomes in Acute Heart Failure

The global burden that acute heart failure (AHF) carries has remained unchanged over the past several decades (1). European registries (2–5) showed that 1-year outcome rates remain unacceptably high (Table 1) and confirm that hospitalization for AHF represents a change in the natural history of the disease process(6). As patients hospitalized for HF have a bad prognosis, it is crucial to utilize hospitalization as an opportunity to: 1) assess the individual components of the cardiac substrate; 2) identify and treat comorbidities; 3) identify early, safe endpoints of therapy to facilitate timely hospital discharge and outpatient follow-up; and 4) implement and begin optimization guideline-directed medical therapies (GDMTs). As outcomes are influenced by many factors, many of which are incompletely understood, a systematic approach is proposed that should start with admission and continues through post-discharge (7)

Diverse cell stresses induce unique patterns of tRNA up- and down-regulation: tRNA-seq for quantifying changes in tRNA copy number

Emerging evidence points to roles for tRNA modifications and tRNA abundance in cellular stress responses. While isolated instances of stress-induced tRNA degradation have been reported, we sought to assess the effects of stress on tRNA levels at a systems level. To this end, we developed a next-generation sequencing method that exploits the paucity of ribonucleoside modifications at the 3′-end of tRNAs to quantify changes in all cellular tRNA molecules. Application of this tRNA-seq method to Saccharomyces cerevisiae identified all 76 expressed unique tRNA species out of 295 coded in the yeast genome, including all isoacceptor variants, with highly precise relative (fold-change) quantification of tRNAs. In studies of stress-induced changes in tRNA levels, we found that oxidation (H[subscript 2]O[subscript 2]) and alkylation (methylmethane sulfonate, MMS) stresses induced nearly identical patterns of up- and down-regulation for 58 tRNAs. However, 18 tRNAs showed opposing changes for the stresses, which parallels our observation of signature reprogramming of tRNA modifications caused by H[subscript 2]O[subscript 2] and MMS. Further, stress-induced degradation was limited to only a small proportion of a few tRNA species. With tRNA-seq applicable to any organism, these results suggest that translational control of stress response involves a contribution from tRNA abundance.National Institutes of Health (U.S.) (ES017010)National Institutes of Health (U.S.) (ES002109)National Science Foundation (U.S.) (CHE-1308839)Singapore-MIT Alliance for Research and Technolog