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Background: In patients with hypertrophic cardiomyopathy (HCM), impaired augmentation of stroke volume and diastolic dysfunction contribute to exercise intolerance. Systolic–diastolic (S‐D) coupling characterizes how systolic contraction of the left ventricle (LV) primes efficient elastic recoil during early diastole. Impaired S‐D coupling may contribute to the impaired cardiac response to exercise in patients with HCM. Methods: Patients with HCM (n = 25, age = 47 ± 9 years) and healthy adults (n = 115, age = 49 ± 10 years) underwent a cardiopulmonary exercise testing (CPET) and echocardiogram. S‐D coupling was defined as the ratio of LV longitudinal excursion of the mitral annulus during early diastole (EDexc) and systole (Sexc) and compared between groups. Peak oxygen uptake (peak V̇O2) (Douglas bags), cardiac index (C2H2 rebreathe), and stroke volume index (SVi) were assessed during CPET. Linear regression was performed between S‐D coupling and peak V̇O2, peak cardiac index, and peak SVi. Results: S‐D coupling was lower in HCM (Controls: 0.63 ± 0.08, HCM: 0.56 ± 0.10, p < 0.001). Peak V̇O2 and stroke volume reserve were lower in patients with HCM (Peak VO2 Controls: 28.5 ± 5.5, HCM: 23.7 ± 7.2 mL/kg/min, p < 0.001, SV reserve: Controls 39 ± 16, HCM 30 ± 18 mL, p = 0.008). In patients with HCM, S‐D coupling was associated with peak V̇O2 (r = 0.47, p = 0.018), peak cardiac index (r = 0.60, p = 0.002), and peak SVi (r = 0.63, p < 0.001). Conclusion: Systolic–diastolic coupling was impaired in patients with HCM and was associated with fitness and the cardiac response to exercise. Inefficient S‐D coupling may link insufficient stroke volume generation, diastolic dysfunction, and exercise intolerance in HCM. [ABSTRACT FROM AUTHOR]

ObjectiveTo determine whether increases in cardiac work lead to alterations in the plasma metabolome and whether such changes arise from the heart or peripheral organs.BackgroundThere is growing evidence that the heart influences systemic metabolism through endocrine effects and affecting pathways involved in energy homeostasis.MethodsNineteen patients referred for cardiac catheterization were enrolled. Peripheral and selective coronary sinus (CS) blood sampling was performed at serial timepoints following the initiation of pacing, and metabolite profiling was performed by liquid chromatography-mass spectrometry (LC-MS).ResultsPacing-stress resulted in a 225% increase in the median rate·pressure product from baseline. Increased myocardial work induced significant changes in the peripheral concentration of 43 of 125 metabolites assayed, including large changes in purine [adenosine (+99%, p = 0.006), ADP (+42%, p = 0.01), AMP (+79%, p = 0.004), GDP (+69%, p = 0.003), GMP (+58%, p = 0.01), IMP (+50%, p = 0.03), xanthine (+61%, p = 0.0006)], and several bile acid metabolites. The CS changes in metabolites qualitatively mirrored those in the peripheral blood in both timing and magnitude, suggesting the heart was not the major source of the metabolite release.ConclusionsIsolated increases in myocardial work can induce changes in the plasma metabolome, but these changes do not appear to be directly cardiac in origin. A number of these dynamic metabolites have known signaling functions. Our study provides additional evidence to a growing body of literature on metabolic 'cross-talk' between the heart and other organs.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ahj.2007.01.005 Byline: Aslan T. Turer (a), Kenneth W. Mahaffey (a), Kate L. Compton (c)(d), Robert M. Califf (a)(d), Kevin A. Schulman (b)(c) Abstract: Nonpublication of research results threatens the integrity of clinical research, but the extent of nonpublication and factors associated with publication remain poorly documented. We sought to examine rates of publication or presentation of research findings from multicenter clinical trials and determine what factors are associated with dissemination of results. Author Affiliation: (a) Division of Cardiology, Department of Medicine, Duke University Medical Center, Durham, NC (b) Division of General Internal Medicine, Duke University Medical Center, Durham, NC (c) Center for Clinical and Genetic Economics, Duke University Medical Center, Durham, NC (d) Duke Clinical Research Institute, Duke University Medical Center, Durham, NC Article History: Received 3 October 2006; Accepted 9 January 2007

Mavacamten is the first cardiac myosin inhibitor approved for the treatment of obstructive hypertrophic cardiomyopathy (oHCM). The Food and Drug Administration (FDA) instituted a Risk Evaluation and Mitigation Strategy (REMS), requiring frequent echocardiograms and patient assessments reported via an online patient status form (PSF). Additionally, there are extensive drug interactions with other commonly taken medications. We designed and implemented a multi-disciplinary team that included a Clinical Pharmacy Specialist (CPS) in partnership with physicians to maintain a mavacamten program. In this study, we report the REMS compliance, approval outcomes, and pharmacy interventions from this model. The multi-disciplinary team was instituted at the University of Texas Southwestern Hypertrophic Cardiomyopathy Center of Excellence in Spring of 2022 and included a CPS, pharmacy technician, advance practice providers, and two cardiologists. Once the clinician identified the need for mavacamten, the patient was referred to the CPS for initiation, which included counseling, drug-interaction check and pharmacy intervention, if needed. Pharmacy technician completed registration and prior-authorization for the patient. CPS and pharmacy technician facilitated patients' echocardiograms and clinic visits within the PSF windows. For this study, we determined the percentage of patient status forms (PSF) submitted within the window and any interruptions in therapy due to logistical issues. The number of pharmacy interventions and insurance appeals were reviewed. From June 2022 to April 2024, 37 patients with oHCM were initiated on mavacamten. A total of 243 PSFs were submitted and 191 (78.6%) were submitted in the specified time frame resulting in only 1 (0.4%) delay in medication dispensation (4 days). This was caused by a change in insurance coverage. Seventeen pharmacy interventions occurred during this period, and the most common change was to proton pump inhibitors. All patients underwent counselling prior to initiation regarding interactions including OTC products. Nine (24%) of the initial insurance authorizations required appeals for approval. One (3%) was denied and was covered under the manufacturer bridge program. The multidisciplinary team of clinical pharmacy specialist and clinicians kept patients on the appropriate dose timing and ECHO timing to meet the REMS requirements. The multi-disciplinary team reduced physician burden and had only a single short delay in therapy due to an insurance issue. Furthermore, CPS was able to provide pharmacy interventions and insurance appeals. Further study is needed comparing the success of different clinical strategies for mavacamten programs. [ABSTRACT FROM AUTHOR]

Abstract Background Cardiac biomarkers are routinely obtained in the setting of suspected myocardial ischemia and infarction. Evidence suggests these markers may correlate with functional and clinical outcomes, but the strength of this correlation is unclear. The relationship between enzyme measures of myocardial necrosis and left ventricular performance and adverse clinical outcomes were explored. Methods Creatine kinase (CK) and CK-MB data were analyzed, as were left ventricular ejection fraction (LVEF) by angiogram, and infarct size by single-photon emission computed tomography (SPECT) imaging in patients in 2 trials: Prompt Reperfusion In Myocardial-infarction Evolution (PRIME), and Efegatran and Streptokinase to Canalize Arteries Like Accelerated Tissue plasminogen activator (ESCALAT). Both trials evaluated efegatran combined with thrombolysis for treating acute ST-segment elevation myocardial infarction (STEMI). Results Peak CK and CK area-under-the-curve (AUC) correlated significantly with SPECT-determined infarct size 5 to 10 days after enrollment. Peak CK had a statistically significant correlation with LVEF, but CK-AUC and LVEF correlation were less robust. Statistically significant correlations exist between SPECT-determined infarct size and peak CK-MB and CK-MB AUC. However, there was no correlation with LVEF for peak CK-MB and CK-MB AUC. The combined outcome of congestive heart failure and death were significantly associated with CK AUC, CK-MB AUC, peak CK, and peak CK-MB measurements. Conclusion Peak CK and CK-MB values and AUC calculations have significant correlation with functional outcomes (LVEF- and SPECT-determined infarct size) and death or CHF outcomes in the setting of STEMI. Cardiac biomarkers provide prognostic information and may serve as valid endpoint measurements for phase II clinical trials.