Lewsey, Sabra C

ABSTRACT Purpose To simultaneously measure skeletal muscle energetics and blood flow (BF) before, during, and after dynamic plantar flexion exercise (PFE). Methods Non‐localized pulse‐acquire phosphorus‐31 magnetic resonance spectroscopy ( 31 P MRS) and phase contrast flow magnetic resonance imaging ( 1 H MRI) using golden‐angle rotated spiral readouts were acquired in an interleaved fashion. Data were collected at rest, during PFE to volitional fatigue, and post‐exercise recovery in 10 healthy adults. Interleaved popliteal artery BF was validated against conventional cine phase‐contrast measures at rest and post‐exercise recovery, while calf muscle energetics were validated by comparing to conventional 31 P MRS‐only measures at rest. To minimize motion artifacts during dynamic PFE, flow data were resolved in 3 dimensions (cardiac phase, pedal position, and exercise stage). Results Resting phosphocreatine (PCr) and inorganic phosphate concentrations were similar between both techniques (both p > 0.05). During PFE, PCr declined to 46% ± 10% of rest. PCr recovery time was 43 ± 15 s. Resting BF was 132 ± 43 mL/min and increased up to four‐fold during PFE depending on exercise stage and pedal position. Notably, there was excellent agreement between the interleaved and conventional BF measures ( r 2 = 0.95, slope = 0.977, p < 0.0001) with minimal bias (12.62 mL/min) over a wide range of physiologically relevant BF values (from ∼60 to 600 mL/min). Conclusion The feasibility of simultaneous assessment of skeletal muscle energetics and BF during dynamic exercise by interleaved 31 P MRS/ 1 H flow MRI was demonstrated along with good agreement between interleaved and conventional techniques during rest and recovery. One can now simultaneously quantify critical BF‐metabolism relationships and use this to probe disease‐related adaptations.

ImportanceThe advanced ambulatory heart failure (HF) population comprises patients who have progressed beyond the pillars of recommended stage C HF therapies but can still find meaningful life-years ahead. Although these patients are commonly encountered in practice, national databases selectively capture the small groups accepted for heart transplant listing or left ventricular assist devices. The epidemiology, trajectories, and therapies for other ambulatory patients with advanced HF are poorly understood.ObservationsIn December 2022, the National Heart, Lung and Blood Institute convened a team of experts to identify knowledge gaps and research priorities for the ambulatory population with limiting daily symptoms and transition toward refractory end-stage D HF, designated as stage C2D. This article summarizes the findings from that 3-day workshop. Workshop participants surveyed the initial challenges and knowledge gaps for (1) recognition of ambulatory C2D HF, (2) estimation of the magnitude of the affected population and identifiable subpopulations, and (3) physiologic phenotypes, such as low cardiac output, right HF, cardiorenal syndromes, congestive hepatopathy and frailty, which offer distinct targets for existing and emerging therapies. Social drivers of HF and patient preferences for quality/length of survival were highlighted as essential modifiers for personalization of therapies.Conclusions and RelevanceTen key points summarized workshop findings, with target cohorts for study proposed as a crucial next step. This workshop summary is intended as a call for action to address knowledge gaps and develop new strategies to improve outcomes in the large ambulatory population with C2D HF.

ImportanceBarriers to heart transplant must be overcome prior to listing. It is unclear why Black men and women remain less likely to receive a heart transplant after listing than White men and women.ObjectiveTo evaluate whether race or gender of a heart transplant candidate (ie, patient on the transplant waiting list) is associated with the probability of a donor heart being accepted by the transplant center team with each offer.Design, Setting, and ParticipantsThis cohort study used the United Network for Organ Sharing datasets to identify organ acceptance with each offer for US non-Hispanic Black (hereafter, Black) and non-Hispanic White (hereafter, White) adults listed for heart transplant from October 18, 2018, through March 31, 2023.ExposuresBlack or White race and gender (men, women) of a heart transplant candidate.Main Outcomes and MeasuresThe main outcome was heart offer acceptance by the transplant center team. The number of offers to acceptance was assessed using discrete time-to-event analyses, nonparametrically (stratified by race and gender) and parametrically. The hazard probability of offer acceptance for each offer was modeled using generalized linear mixed models adjusted for candidate-, donor-, and offer-level variables.ResultsAmong 159 177 heart offers with 13 760 donors, there were 14 890 candidates listed for heart transplant; 30.9% were Black, 69.1% were White, 73.6% were men, and 26.4% were women. The cumulative incidence of offer acceptance was highest for White women followed by Black women, White men, and Black men (P &amp;lt; .001). Odds of acceptance were less for Black candidates than for White candidates for the first offer (odds ratio [OR], 0.76; 95% CI, 0.69-0.84) through the 16th offer. Odds of acceptance were higher for women than for men for the first offer (OR, 1.53; 95% CI, 1.39-1.68) through the sixth offer and were lower for the 10th through 31st offers.Conclusions and RelevanceThe cumulative incidence of heart offer acceptance by a transplant center team was consistently lower for Black candidates than for White candidates of the same gender and higher for women than for men. These disparities persisted after adjusting for candidate-, donor-, and offer-level variables, possibly suggesting racial and gender bias in the decision-making process. Further investigation of site-level decision-making may reveal strategies for equitable donor heart acceptance.