The heart consumes circulating nutrients to fuel lifelong contraction, but a comprehensive mapping of human cardiac fuel use is lacking. We used metabolomics on blood from artery, coronary sinus, and ...femoral vein in 110 patients with or without heart failure to quantify the uptake and release of 277 metabolites, including all major nutrients, by the human heart and leg. The heart primarily consumed fatty acids and, unexpectedly, little glucose; secreted glutamine and other nitrogen-rich amino acids, indicating active protein breakdown, at a rate ~10 times that of the leg; and released intermediates of the tricarboxylic acid cycle, balancing anaplerosis from amino acid breakdown. Both heart and leg consumed ketones, glutamate, and acetate in direct proportionality to circulating levels, indicating that availability is a key driver for consumption of these substrates. The failing heart consumed more ketones and lactate and had higher rates of proteolysis. These data provide a comprehensive and quantitative picture of human cardiac fuel use.
Observational studies have identified height as a strong risk factor for atrial fibrillation, but this finding may be limited by residual confounding. We aimed to examine genetic variation in height ...within the Mendelian randomization (MR) framework to determine whether height has a causal effect on risk of atrial fibrillation.
In summary-level analyses, MR was performed using summary statistics from genome-wide association studies of height (GIANT/UK Biobank; 693,529 individuals) and atrial fibrillation (AFGen; 65,446 cases and 522,744 controls), finding that each 1-SD increase in genetically predicted height increased the odds of atrial fibrillation (odds ratio OR 1.34; 95% CI 1.29 to 1.40; p = 5 × 10-42). This result remained consistent in sensitivity analyses with MR methods that make different assumptions about the presence of pleiotropy, and when accounting for the effects of traditional cardiovascular risk factors on atrial fibrillation. Individual-level phenome-wide association studies of height and a height genetic risk score were performed among 6,567 European-ancestry participants of the Penn Medicine Biobank (median age at enrollment 63 years, interquartile range 55-72; 38% female; recruitment 2008-2015), confirming prior observational associations between height and atrial fibrillation. Individual-level MR confirmed that each 1-SD increase in height increased the odds of atrial fibrillation, including adjustment for clinical and echocardiographic confounders (OR 1.89; 95% CI 1.50 to 2.40; p = 0.007). The main limitations of this study include potential bias from pleiotropic effects of genetic variants, and lack of generalizability of individual-level findings to non-European populations.
In this study, we observed evidence that height is likely a positive causal risk factor for atrial fibrillation. Further study is needed to determine whether risk prediction tools including height or anthropometric risk factors can be used to improve screening and primary prevention of atrial fibrillation, and whether biological pathways involved in height may offer new targets for treatment of atrial fibrillation.
COVID-19 and cardiac arrhythmias Bhatla, Anjali; Mayer, Michael M; Adusumalli, Srinath ...
Heart rhythm,
09/2020, Volume:
17, Issue:
9
Journal Article
Peer reviewed
Open access
Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias. Severe acute respiratory syndrome coronavirus 2 infection may cause injury ...to cardiac myocytes and increase arrhythmia risk.
The purpose of this study was to evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19. We also evaluated correlations between the presence of these arrhythmias and mortality.
We reviewed the characteristics of all patients with COVID-19 admitted to our center over a 9-week period. Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias, and inpatient mortality. We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, chronic kidney disease, and intensive care unit (ICU) status as potential risk factors for each arrhythmia.
Among 700 patients (mean age 50 ± 18 years; 45% men; 71% African American; 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs. All cardiac arrests occurred in patients admitted to the ICU. In addition, admission to the ICU was associated with incident AF (odds ratio OR 4.68; 95% confidence interval CI 1.66-13.18) and NSVT (OR 8.92; 95% CI 1.73-46.06) after multivariable adjustment. Also, age and incident AF (OR 1.05; 95% CI 1.02-1.09) and prevalent heart failure and bradyarrhythmias (OR 9.75; 95% CI 1.95-48.65) were independently associated. Only cardiac arrests were associated with acute in-hospital mortality.
Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.
Health care workers (HCWs) caring for patients with coronavirus disease 2019 (COVID-19) are at risk of exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, to our ...knowledge, there is no effective pharmacologic prophylaxis for individuals at risk.
To evaluate the efficacy of hydroxychloroquine to prevent transmission of SARS-CoV-2 in hospital-based HCWs with exposure to patients with COVID-19 using a pre-exposure prophylaxis strategy.
This randomized, double-blind, placebo-controlled clinical trial (the Prevention and Treatment of COVID-19 With Hydroxychloroquine Study) was conducted at 2 tertiary urban hospitals, with enrollment from April 9, 2020, to July 14, 2020; follow-up ended August 4, 2020. The trial randomized 132 full-time, hospital-based HCWs (physicians, nurses, certified nursing assistants, emergency technicians, and respiratory therapists), of whom 125 were initially asymptomatic and had negative results for SARS-CoV-2 by nasopharyngeal swab. The trial was terminated early for futility before reaching a planned enrollment of 200 participants.
Hydroxychloroquine, 600 mg, daily, or size-matched placebo taken orally for 8 weeks.
The primary outcome was the incidence of SARS-CoV-2 infection as determined by a nasopharyngeal swab during the 8 weeks of treatment. Secondary outcomes included adverse effects, treatment discontinuation, presence of SARS-CoV-2 antibodies, frequency of QTc prolongation, and clinical outcomes for SARS-CoV-2-positive participants.
Of the 132 randomized participants (median age, 33 years range, 20-66 years; 91 women 69%), 125 (94.7%) were evaluable for the primary outcome. There was no significant difference in infection rates in participants randomized to receive hydroxychloroquine compared with placebo (4 of 64 6.3% vs 4 of 61 6.6%; P > .99). Mild adverse events were more common in participants taking hydroxychloroquine compared with placebo (45% vs 26%; P = .04); rates of treatment discontinuation were similar in both arms (19% vs 16%; P = .81). The median change in QTc (baseline to 4-week evaluation) did not differ between arms (hydroxychloroquine: 4 milliseconds; 95% CI, -9 to 17; vs placebo: 3 milliseconds; 95% CI, -5 to 11; P = .98). Of the 8 participants with positive results for SARS-CoV-2 (6.4%), 6 developed viral symptoms; none required hospitalization, and all clinically recovered.
In this randomized clinical trial, although limited by early termination, there was no clinical benefit of hydroxychloroquine administered daily for 8 weeks as pre-exposure prophylaxis in hospital-based HCWs exposed to patients with COVID-19.
ClinicalTrials.gov Identifier: NCT04329923.
Conscious sedation is used during transcatheter aortic valve replacement (TAVR) with limited evidence as to the safety and efficacy of this practice.
The National Cardiovascular Data Registry Society ...of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry was used to characterize the anesthesia choice and clinical outcomes of all US patients undergoing elective percutaneous transfemoral TAVR between April 1, 2014, and June 30, 2015. Raw and inverse probability of treatment-weighted analyses were performed to compare patients undergoing TAVR with general anesthesia with patients undergoing TAVR with conscious sedation on an intention-to-treat basis for the primary outcome of in-hospital mortality, and secondary outcomes including 30-day mortality, in-hospital and 30-day death/stroke, procedural success, intensive care unit and hospital length-of-stay, and rates of discharge to home. Post hoc falsification end point analyses were performed to evaluate for residual confounding.
Conscious sedation was used in 1737/10 997 (15.8%) cases with a significant trend of increasing usage over the time period studied (
for trend<0.001). In raw analyses, intraprocedural success with conscious sedation and general anesthesia was similar (98.2% versus 98.5%,
=0.31). The conscious sedation group was less likely to experience in-hospital (1.6% versus 2.5%,
=0.03) and 30-day death (2.9% versus 4.1%,
=0.03). Conversion from conscious sedation to general anesthesia was noted in 102 of 1737 (5.9%) of conscious sedation cases. After inverse probability of treatment-weighted adjustment for 51 covariates, conscious sedation was associated with lower procedural success (97.9% versus 98.6%,
<0.001) and a reduced rate of mortality at the in-hospital (1.5% versus 2.4%,
<0.001) and 30-day (2.3% versus 4.0%,
<0.001) time points. Conscious sedation was associated with reductions in procedural inotrope requirement, intensive care unit and hospital length of stay (6.0 versus 6.5 days,
<0.001), and combined 30-day death/stroke rates (4.8% versus 6.4%,
<0.001). Falsification end point analyses of vascular complications, bleeding, and new pacemaker/defibrillator implantation demonstrated no significant differences between groups after adjustment.
In US practice, conscious sedation is associated with briefer length of stay and lower in-hospital and 30-day mortality in comparison with TAVR with general anesthesia in both unadjusted and adjusted analyses. These results suggest the safety of conscious sedation in this population, although comparative effectiveness analyses using observational data cannot definitively establish the superiority of one technique over another.
Class IC antiarrhythmic drugs (IC-AADs) can effectively suppress premature ventricular contractions (PVCs). However, IC-AADs increase mortality in patients with PVCs and left ventricular dysfunction ...after myocardial infarction. Whether IC-AADs can be safely used to treat premature ventricular contraction-induced cardiomyopathy (PVC-CM) remains to be established.
The purpose of this study was to determine the safety and efficacy of IC-AADs in patients suspected of having PVC-CM.
The electronic medical records at the Hospital of the University of Pennsylvania were screened to identify all patients suspected of having PVC-CM treated with flecainide or propafenone. Clinical, electrocardiographic, and imaging studies were reviewed.
Twenty patients suspected of having PVC-CM were treated with IC-AADs. Patients had undergone an average of 1.3 ± 0.2 previous unsuccessful ablations. Six had an implantable or wearable defibrillator. With IC-AAD treatment, mean PVC burden decreased from 36.2% ± 3.5% to 10.0% ± 2.4% (P <.001). Mean left ventricular ejection fraction (LVEF) increased from 37.4% ± 2.0% to 49.0% ± 1.9% (P <.001). Seven patients with myocardial delayed enhancement on cardiac magnetic resonance imaging (all <5% of the total myocardium) experienced similar improvement in LVEF (from 36.8% ± 4.3% before IC-AAD to 51.7% ± 3.7% afterward; P <.01). Over an average 3.8 ± 0.9 treatment-years, no sustained ventricular arrhythmias or sudden cardiac deaths occurred.
In patients suspected of having PVC-CM, IC-AADs effectively suppressed PVCs, leading to LVEF recovery in the majority. No adverse events occurred in this small cohort.
Pharmacologic activation of branched-chain amino acid (BCAA) catabolism is protective in models of heart failure (HF). How protection occurs remains unclear, although a causative block in cardiac ...BCAA oxidation is widely assumed. Here, we use in vivo isotope infusions to show that cardiac BCAA oxidation in fact increases, rather than decreases, in HF. Moreover, cardiac-specific activation of BCAA oxidation does not protect from HF even though systemic activation does. Lowering plasma and cardiac BCAAs also fails to confer significant protection, suggesting alternative mechanisms of protection. Surprisingly, activation of BCAA catabolism lowers blood pressure (BP), a known cardioprotective mechanism. BP lowering occurred independently of nitric oxide and reflected vascular resistance to adrenergic constriction. Mendelian randomization studies revealed that elevated plasma BCAAs portend higher BP in humans. Together, these data indicate that BCAA oxidation lowers vascular resistance, perhaps in part explaining cardioprotection in HF that is not mediated directly in cardiomyocytes.
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•Systemic activation of BCAA oxidation lowers blood pressure and vascular resistance•Enhanced whole-body BCAA oxidation is cardioprotective after myocardial infarction•But cardiac-specific or muscle-specific activation of BCAA oxidation is not cardioprotective•Improved vascular reactivity may explain cardioprotection by pro-BCAA oxidation agents
Murashige et al. report that the widely studied cardioprotection afforded by pharmacological activation of BCAA oxidation in mice is not mediated by oxidation in cardiomyocytes or by lowering BCAA levels. Instead, the authors surprisingly find that enhanced BCAA oxidation lowers blood pressure and promotes vasorelaxation, perhaps explaining the observed cardioprotection.
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