A retrospective analysis of anticoagulant safety among heart transplant recipients undergoing endomyocardial biopsy.

BACKGROUND: Transvenous endomyocardial biopsy is an invasive procedure which is used to diagnose rejection following an orthotopic heart transplant. Endomyocardial biopsy is widely regarded as low risk with all-cause complication rates below 5% in most safety studies. Following transplant, some patients require therapeutic anticoagulation. It is unknown whether anticoagulation increases endomyocardial biopsy bleeding risk. METHODS: Records from 2061 endomyocardial biopsies performed for post-transplant rejection surveillance at our institution between November 2016 and August 2022 were reviewed. Bleeding complications were defined as vascular access-related hematoma or bleeding, procedure-related red blood cell transfusion, and new pericardial effusion. Relative risk and small sample-adjusted 95% confidence interval was calculated to investigate the association between bleeding complications and anticoagulation. RESULTS AND CONCLUSIONS: The overall risk of bleeding was 1.2% (25/2061 cases). There was a statistically significant increase in bleeding among patients on intravenous (RR 4.46, CI 1.09-18.32) but not oral anticoagulants (RR .62, CI .15-2.63) compared to patients without anticoagulant exposure. There was a trend toward increased bleeding among patients taking warfarin with INR ≥ 1.8 (RR 3.74, CI .90-15.43). Importantly, no bleeding events occurred in patients taking direct oral anticoagulants such as apixaban. Based on these results, intravenous rather than oral anticoagulation was associated with a significantly higher risk of bleeding complications following endomyocardial biopsy.

Dietary Nitrate Increases VO2peak and Performance but Does Not Alter Ventilation or Efficiency in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Patients with heart failure with reduced ejection fraction (HFrEF) exhibit lower efficiency, dyspnea, and diminished peak oxygen uptake (VO2peak) during exercise. Dietary nitrate (NO3-), a source of nitric oxide (NO), has improved these measures in some studies of other populations. We determined the effects of acute NO3- ingestion on exercise responses in 8 patients with HFrEF using a randomized, double-blind, placebo-controlled, crossover design. METHODS AND RESULTS: Plasma NO3-, nitrite (NO2-), and breath NO were measured at multiple time points and respiratory gas exchange was determined during exercise after ingestion of beetroot juice containing or devoid of 11.2 mmol of NO3-. NO3- intake increased (P < .05-0.001) plasma NO3- and NO2- and breath NO by 1469 ± 245%, 105 ± 34%, and 60 ± 18%, respectively. Efficiency and ventilation during exercise were unchanged. However, NO3- ingestion increased (P < .05) VO2peak by 8 ± 2% (ie, from 21.4 ± 2.1 to 23.0 ± 2.3 mL.min-1.kg-1). Time to fatigue improved (P < .05) by 7 ± 3 % (ie, from 582 ± 84 to 612 ± 81 seconds). CONCLUSIONS: Acute dietary NO3- intake increases VO2peak and performance in patients with HFrEF. These data, in conjunction with our recent data demonstrating that dietary NO3- also improves muscle contractile function, suggest that dietary NO3- supplementation may be a valuable means of enhancing exercise capacity in this population.

Dietary nitrate-induced increases in human muscle power: high versus low responders.

Maximal neuromuscular power is an important determinant of athletic performance and also quality of life, independence, and perhaps even mortality in patient populations. We have shown that dietary nitrate (NO3- ), a source of nitric oxide (NO), improves muscle power in some, but not all, subjects. The present investigation was designed to identify factors contributing to this interindividual variability. Healthy men (n = 13) and women (n = 7) 22-79 year of age and weighing 52.1-114.9 kg were studied using a randomized, double-blind, placebo-controlled, crossover design. Subjects were tested 2 h after ingesting beetroot juice (BRJ) either containing or devoid of 12.3 ± 0.8 mmol of NO3- . Plasma NO3- and nitrite (NO2- ) were measured as indicators of NO bioavailability and maximal knee extensor speed (Vmax ), power (Pmax ), and fatigability were determined via isokinetic dynamometry. On average, dietary NO3- increased (P < 0.05) Pmax by 4.4 ± 8.1%. Individual changes, however, ranged from -9.6 to +26.8%. This interindividual variability was not significantly correlated with age, body mass (inverse of NO3- dose per kg), body mass index (surrogate for body composition) or placebo trial Vmax or fatigue index (in vivo indicators of muscle fiber type distribution). In contrast, the relative increase in Pmax was significantly correlated (r = 0.60; P < 0.01) with the relative increase in plasma NO2- concentration. In multivariable analysis female sex also tended (P = 0.08) to be associated with a greater increase in Pmax. We conclude that the magnitude of the dietary NO3- -induced increase in muscle power is dependent upon the magnitude of the resulting increase in plasma NO2- and possibly female sex.

Clinical Outcomes of Remote Ischemic Preconditioning Prior to Cardiac Surgery: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Multiple randomized controlled trials of remote ischemic preconditioning (RIPC) prior to cardiac surgery have failed to demonstrate clinical benefit. The aim of this updated meta-analysis was to evaluate the effect of RIPC on outcomes following cardiac surgery. METHODS AND RESULTS: Searches of PubMed, Cochrane, EMBASE, and Web of Science databases were performed for 1970 to December 13, 2015. Randomized controlled trials comparing RIPC with a sham procedure prior to cardiac surgery performed with cardiopulmonary bypass were assessed. All-cause mortality, acute kidney injury (AKI), and myocardial infarction were the primary outcomes of interest. We identified 21 trials that randomized 5262 patients to RIPC or a sham procedure prior to undergoing cardiac surgery. The majority of patients were men (72.6%) and the mean or median age ranged from 42.3 to 76.3 years. Of the 9 trials that evaluated mortality, 188 deaths occurred out of a total of 4210 randomized patients, with 96 deaths occurring in 2098 patients (4.6%) randomized to RIPC and 92 deaths occurring in 2112 patients (4.4%) randomized to a sham control procedure, demonstrating no significant reduction in all-cause mortality (risk ratio [RR], 0.987; 95% CI, 0.653-1.492, P=0.95). Twelve studies evaluated AKI in 4209 randomized patients. In these studies, AKI was observed in 516 of 2091 patients (24.7%) undergoing RIPC and in 577 of 2118 patients (27.2%) randomized to a sham procedure. RIPC did not result in a significant reduction in AKI (RR, 0.839; 95% CI, 0.703-1.001 [P=0.052]). In 6 studies consisting of 3799 randomized participants, myocardial infarction occurred in 237 of 1891 patients (12.5%) randomized to RIPC and in 282 of 1908 patients (14.8%) randomized to a sham procedure, resulting in no significant reduction in postoperative myocardial infarction (RR, 0.809; 95% CI, 0.615-1.064 [P=0.13]). A subgroup analysis was performed a priori based on previous studies suggesting that propofol may mitigate the protective benefits of RIPC. Three studies randomized patients undergoing cardiac surgery to RIPC or sham procedure in the absence of propofol anesthesia. Most of these patients were men (60.3%) and the mean or median age ranged from 57.0 to 70.6 years. In this propofol-free subgroup of 434 randomized patients, 71 of 217 patients (32.7%) who underwent RIPC developed AKI compared with 103 of 217 patients (47.5%) treated with a sham procedure. In this cohort, RIPC resulted in a significant reduction in AKI (RR, 0.700; 95% CI, 0.527-0.930 [P=0.014]). In studies of patients who received propofol anesthesia, 445 of 1874 (23.7%) patients randomized to RIPC developed AKI compared with 474 of 1901 (24.9%) who underwent a sham procedure. The RR for AKI was 0.928 (95% CI, 0.781-1.102; P=0.39) for RIPC versus sham. There was no significant interaction between the two subgroups (P=0.098). CONCLUSIONS: RIPC does not reduce morbidity or mortality in patients undergoing cardiac surgery with cardiopulmonary bypass. In the subgroup of studies in which propofol was not used, a reduction in AKI was seen, suggesting that propofol may interact with the protective effects of RIPC. Future studies should evaluate RIPC in the absence of propofol anesthesia.