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Background: Left ventricular outflow tract (LVOT) obstruction is a major determinant of heart failure symptoms in obstructive hypertrophic cardiomyopathy (oHCM). Aficamten, a next-in-class cardiac myosin inhibitor, may lower gradients and improve symptoms in these patients., Objectives: This study aims to evaluate the safety and efficacy of aficamten in patients with oHCM., Methods: Patients with oHCM and LVOT gradients ≥30 mm Hg at rest or ≥50 mm Hg with Valsalva were randomized 2:1 to receive aficamten (n = 28) or placebo (n = 13) in 2 dose-finding cohorts. Doses were titrated based on gradients and ejection fraction (EF). Safety and changes in gradient, EF, New York Heart Association functional class, and cardiac biomarkers were assessed over a 10-week treatment period and after a 2-week washout., Results: From baseline to 10 weeks, aficamten reduced gradients at rest (mean difference: -40 ± 27 mm Hg, and -43 ± 37 mm Hg in Cohorts 1 and 2, P = 0.0003 and P = 0.0004 vs placebo, respectively) and with Valsalva (-36 ± 27 mm Hg and -53 ± 44 mm Hg, P = 0.001 and <0.0001 vs placebo, respectively). There were modest reductions in EF (-6% ± 7.5% and -12% ± 5.9%, P = 0.007 and P < 0.0001 vs placebo, respectively). Symptomatic improvement in ≥1 New York Heart Association functional class was observed in 31% on placebo, and 43% and 64% on aficamten in Cohorts 1 and 2, respectively (nonsignificant). With aficamten, N-terminal pro-B-type natriuretic peptide was reduced (62% relative to placebo, P = 0.0002). There were no treatment interruptions and adverse events were similar between treatment arms., Conclusions: Aficamten resulted in substantial reductions in LVOT gradients with most patients experiencing improvement in biomarkers and symptoms. These results highlight the potential of sarcomere-targeted therapy for treatment of oHCM., Competing Interests: Funding Support and Author Disclosures The REDWOOD-HCM study was funded by Cytokinetics, Incorporated. Dr Maron has received consultant/advisor fees from Imbria and Takeda; and has received steering committee fees for REDWOOD-HCM from Cytokinetics, Incorporated. Dr Masri has received consultant/advisor fees from Tenaya, Attralus, Cytokinetics, Bristol Myers Squibb, and Ionis; and has received research grants from Ionis, Akcea, Pfizer, Ultromics, and Wheeler Foundation. Dr Olivotto has received Speakers Bureau fees from Boston Scientific, Amicus, and Novartis; has received consultant/advisor fees from Bristol Myers Squibb, Cytokinetics, Sanofi Genzyme, Amicus, Bayer, and Tenaya; and has received research grant funding from Bristol Myers Squibb, Cytokinetics, Sanofi Genzyme, Amicus, Bayer, Menarini International, and Boston Scientific. Dr Saberi has received consultant/advisor fees from Bristol Myers Squibb; and has received research grants from Bristol Myers Squibb, Cytokinetics, Novartis, and Actelion Pharmaceuticals. Dr Wang has received Speakers Bureau fees from Bristol Myers Squibb; has received consultant/advisor fees from Bristol Myers Squibb and Cytokinetics; and has received research grants from Bristol Myers Squibb, Cytokinetics, and Abbott Vascular. Dr Garcia-Pavia has received Speakers Bureau fees from Pfizer and Alnylam; has received consultant/advisor fees from Pfizer, Alnylam, MyoKardia/Bristol Myers Squibb, Cytokinetics, Neuroimmune, BridgeBio, Attralus, and AstraZeneca; and has received research/educational grants to his institution from Pfizer, BridgeBio, and Alnylam. Dr Lakdawala has received consultant/advisor fees from Tenaya, Pfizer, Bristol Myers Squibb, Cytokinetics, and Sarepta; and has received a research grant from Pfizer. Dr Rader has received Speakers Bureau fees from Bristol Myers Squibb and Medtronic; and has received consultant/advisor fees from Bristol Myers Squibb, Cytokinetics, ReCor, and Medtronic. Dr Turer has received consultant/advisor fees from Cytokinetics. Dr Coats has received consultant/advisor fees from Cytokinetics. Dr Fifer has received consultant/advisor fees from Cytokinetics; and has received research grants from Bristol Myers Squibb and Novartis. Dr Owens has received consultant/advisor fees from Cytokinetics, Bristol Myers Squibb/MyoKardia, and Pfizer. Dr Solomon has received consultant/advisor fees from Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GSK, Lilly, Merck, MyoKardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, Dinaqor, Tremeau, CellProThera, Moderna, American Regent, Sarepta, Lexicon, Anacardio, Akros, and Puretech Health; and has received research grants from Actelion, Alnylam, Amgen, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Celladon, Cytokinetics, Eidos, Gilead, GSK, Ionis, Lilly, Mesoblast, MyoKardia, NIH/NHLBI, Neurotronik, Novartis, NovoNordisk, Respicardia, Sanofi Pasteur, Theracos, and US2.AI. Dr Watkins has received consultant/advisor fees from Cytokinetics, BioMarin, and BridgeBio. Dr Barriales-Villa has received consultant/advisor fees from MyoKardia/Bristol Myers Squibb. Dr Kramer has received consultant/advisor fees from Cytokinetics, and Bristol Myers Squibb; and has received research grants from Cytokinetics and Bristol Myers Squibb. Dr Wong has received Speakers Bureau fees from Projects in Knowledge, PCM Scientific; and has served as an unpaid consultant/advisor for Bristol Myers Squibb and Cytokinetics. Drs Heitner, Kupfer, Malik, Meng, and Wohltman are employees of Cytokinetics Incorporated; and holds stock in Cytokinetics Incorporated. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Obesity has been linked to the development of hypertension, but whether total adiposity or site-specific fat accumulation underpins this relationship is unclear., Objectives: This study sought to determine the relationship between adipose tissue distribution and incident hypertension., Methods: Normotensive participants enrolled in the Dallas Heart Study were followed for a median of 7 years for the development of hypertension (systolic blood pressure [SBP] ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or initiation of blood pressure medications). Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) was quantified by magnetic resonance imaging and proton-spectroscopic imaging, and lower body fat (LBF) was imaged by dual-energy x-ray absorptiometry. Multivariable relative risk regression was performed to test the association between individual fat depots and incident hypertension, adjusting for age, sex, race/ethnicity, diabetes, smoking, SBP, and body mass index (BMI)., Results: Among 903 participants (median age, 40 years; 57% women; 60% nonwhite; median BMI 27.5 kg/m(2)), 230 (25%) developed incident hypertension. In multivariable analyses, higher BMI was significantly associated with incident hypertension (relative risk: 1.24; 95% confidence interval: 1.12 to 1.36, per 1-SD increase). However, when VAT, SAT, and LBF were added to the model, only VAT remained independently associated with incident hypertension (relative risk: 1.22; 95% confidence interval: 1.06 to 1.39, per 1-SD increase)., Conclusions: Increased visceral adiposity, but not total or subcutaneous adiposity, was robustly associated with incident hypertension. Additional studies will be needed to elucidate the mechanisms behind this association., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The goal of this study was to investigate the association between natriuretic peptides and body fat distribution in a multiethnic cohort., Background: Natriuretic peptides stimulate lipolysis, reduce weight gain, and promote adipocyte browning in animal models, but data are lacking in humans., Methods: A total of 2,619 participants without heart failure in the Dallas Heart Study underwent measurements of 1) B-type natriuretic peptide (BNP) and N-terminal pro-B-type natriuretic peptide (NT-proBNP); and 2) body fat distribution by dual energy x-ray absorptiometry and magnetic resonance imaging. Cross-sectional associations of natriuretic peptides with adiposity phenotypes were examined after adjustment for age, sex, race, comorbidities, and body mass index., Results: Median BNP and NT-proBNP levels in the study cohort (mean age 44 years; 56% women, 48% African Americans, 32% obese) were 3.0 and 28.1 pg/ml, respectively. Natriuretic peptide levels above the median were associated with a more favorable body fat profile and less insulin resistance, including lower visceral fat, liver fat, and homeostasis model assessment of insulin resistance index, and increased lower body fat and higher adiponectin (p < 0.05 for each). In multivariable analyses, NT-proBNP remained inversely associated with visceral fat (beta coefficient = -0.08; p < 0.0001) and liver fat (beta coefficient = -0.14; p < 0.0001) and positively associated with lower body fat (beta coefficient = 0.07; p < 0.0001) independent of age, sex, race, and obesity status; findings were similar with BNP. Adjustment for body composition, homeostasis model assessment of insulin resistance index, circulating androgens, and adipocytokines did not attenuate the associations., Conclusions: Higher natriuretic peptide levels were independently associated with a favorable adiposity profile, characterized by decreased visceral and liver fat and increased lower body fat, suggesting a link between the heart and adipose tissue distribution mediated through natriuretic peptides., (Copyright © 2013 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The purpose of this study was to assess whether: 1) very small increases in troponin T, measured by a new highly sensitive cardiac troponin T (hs-cTnT), may reflect ischemia without necrosis; and 2) serial changes can discriminate ischemia from other causes of cardiac troponin T (cTnT) release., Background: A new hs-cTnT assay offers greater sensitivity than current assays., Methods: Nineteen patients referred for diagnostic catheterization underwent cannulation of the coronary sinus (CS). Serial CS and peripheral plasma samples were obtained at multiple time points during and after incremental rapid atrial pacing. cTnT was quantified using both a standard and a pre-commercial highly sensitive assay. Ischemia was determined by the presence of significant coronary artery disease (CAD) and myocardial lactate release with pacing., Results: cTnT concentrations in CS blood increased from a median of 6.8 pg/ml prior to pacing to 15.6 pg/ml 60 min after termination of rapid atrial pacing (p < 0.0001), changes that were mirrored at 180 min in peripheral blood (5.1 to 11.8 pg/ml, p < 0.0001). Although peripheral cTnT concentrations tended to be higher at 180 min following pacing for patients with CAD and lactate elution (n = 7) when compared with those without either marker (n = 5) (25.0 pg/ml vs. 10.2 pg/ml, p = 0.10), relative (1.7-fold vs. 5.2-fold) and absolute (6.8 pg/ml vs. 8.8 pg/ml, p = 0.50) changes were not different between groups., Conclusions: Brief periods of ischemia, without frank infarction, cause low-level cTnT release, and small increases are common after periods of increased myocardial work, even among patients without objective evidence of myocardial ischemia or obstructive CAD. Additional research is needed before hs-cTnT assays are widely adopted in the management of subjects with chest pain syndromes., (Copyright © 2011 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

With an aging U.S. population and a declining physician supply, the care of critically ill patients will soon be reaching a level of crisis. At the same time, the evidence continues to mount in support of intensivist staffing to improve both patient outcomes and resource utilization in intensive care units (ICUs). Whereas the vast majority of medical and surgical ICUs are staffed by physicians trained in critical care medicine, that is not commonly the case in coronary care units (CCUs) in this country. Despite that, the breadth and diversity of comorbidities in patients that occupy our CCU beds is continuously growing. No longer is the CCU merely an observation unit for peri-infarction complications, but rather it has truly become an ICU for patients with cardiovascular disease. With this in mind, there becomes a growing need for intensivist-trained cardiologists and a push for the development of critical care training pathways in our cardiovascular fellowship programs.