Enzyme estimates of infarct size correlate with functional and clinical outcomes in the setting of ST-segment elevation myocardial infarction

BackgroundCardiac 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.MethodsCreatine 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).ResultsPeak 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.ConclusionPeak 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

Phase 2 study of aficamten in patients with obstructive hypertrophic cardiomyopathy

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

Maximal wall thickness measurement in hypertrophic cardiomyopathy

Objectives The aim of this study was to define the variability of maximal wall thickness (MWT) measurements across modalities and predict its impact on care in patients with hypertrophic cardiomyopathy (HCM). Background Left ventricular MWT measured by echocardiography or cardiovascular magnetic resonance (CMR) contributes to the diagnosis of HCM, stratifies risk, and guides key decisions, including whether to place an implantable cardioverter-defibrillator (ICD). Methods A 20-center global network provided paired echocardiographic and CMR data sets from patients with HCM, from which 17 paired data sets of the highest quality were selected. These were presented as 7 randomly ordered pairs (at 6 cardiac conferences) to experienced readers who report HCM imaging in their daily practice, and their MWT caliper measurements were captured. The impact of measurement variability on ICD insertion decisions was estimated in 769 separately recruited multicenter patients with HCM using the European Society of Cardiology algorithm for 5-year risk for sudden cardiac death. Results MWT analysis was completed by 70 readers (from 6 continents; 91% with >5 years’ experience). Seventy-nine percent and 68% scored echocardiographic and CMR image quality as excellent. For both modalities (echocardiographic and then CMR results), intramodality inter-reader MWT percentage variability was large (range –59% to 117% [SD ±20%] and –61% to 52% [SD ±11%], respectively). Agreement between modalities was low (SE of measurement 4.8 mm; 95% CI 4.3 mm-5.2 mm; r = 0.56 [modest correlation]). In the multicenter HCM cohort, this estimated echocardiographic MWT percentage variability (±20%) applied to the European Society of Cardiology algorithm reclassified risk in 19.5% of patients, which would have led to inappropriate ICD decision making in 1 in 7 patients with HCM (8.7% would have had ICD placement recommended despite potential low risk, and 6.8% would not have had ICD placement recommended despite intermediate or high risk). Conclusions Using the best available images and experienced readers, MWT as a biomarker in HCM has a high degree of inter-reader variability and should be applied with caution as part of decision making for ICD insertion. Better standardization efforts in HCM recommendations by current governing societies are needed to improve clinical decision making in patients with HCM

Waist Circumference as Measure of Abdominal Fat Compartments

This study examines intercorrelations among waist circumference (WC), intraperitoneal fat (IPF), and subcutaneous abdominal fat (SAF) in ethnically diverse Dallas Heart Study consisting of 1538 women and 1212 men (50% Black). Correlations between fat depots and triglyceride or HOMA2-IR, biomarkers of metabolic syndrome, are also reported. Total abdominal fat (TAF), ASF, and IPF masses were measured by magnetic resonance imaging. The highest correlations with WC according to ethnicity and gender were noted for TAF (R2=0.81-0.88) with progressively lower correlations with ASF (0.65–0.82) and IPF (0.29–0.85). The percentage of IPF relative to TAF was not significantly correlated with WC. For all WC categories, higher IPF/ASF ratios were associated with higher triglyceride levels. In contrast, differences in ratios had little or no association with HOMA2-IR. However, when all data were pooled, IPF was positively correlated with both triglyceride (r=0.358 (men) and 0.363 (women)) and HOMA2-IR (r=0.480 (men) and 0.517 (women)); after adjustment for ASF, IPF was still correlated with triglyceride (r=0.353 (men) and 0.348 (women)) and HOMA2-IR (r=0.290 (men) and 0.221 (women)). WC measures TAF reliably, but its association with IPF depends on IPF/ASF ratios that vary by gender and ethnicity

Autophagy as a therapeutic target in cardiovascular disease

The epidemic of heart failure continues apace, and development of novel therapies with clinical efficacy has lagged. Now, important insights into the molecular circuitry of cardiovascular autophagy have raised the prospect that this cellular pathway of protein quality control may be a target of clinical relevance. Whereas basal levels of autophagy are required for cell survival, excessive levels - or perhaps distinct forms of autophagic flux - contribute to disease pathogenesis. Our challenge will be to distinguish mechanisms that drive adaptive versus maladaptive autophagy and to manipulate those pathways for therapeutic gain. Recent evidence suggests this may be possible. Here, we review the fundamental biology of autophagy and its role in a variety of forms of cardiovascular disease. We discuss ways in which this evolutionarily conserved catabolic mechanism can be manipulated, discuss studies presently underway in heart disease, and provide our perspective on where this exciting fi

The Effect of Extractum Cepae, Heparin Sodium, and Allantoin in Experimental Peritoneal Adhesion

WOS:000528311600001The purpose of the study is to investigate the effects of extractum cepae (EC), heparin sodium (HS), and allantoin (AA) on postoperative peritoneal adhesion (PPA) prevention. Forty-eight rats were allocated into six groups (n = 8). PPA was performed by Harris method. In group 1, no additional procedure was done. Abdominal cavity was washed with normal saline in group 2, EC in group 3, HS in group 4, AA in group 5, and EC-HS-AA mixture (EHA-m) in group 6. On the 21st postoperative day, PPA was scored with Nair adhesion score and examined for fibrosis histopathologically and hydroxy-proline levels (OHP) biochemically. Macroscopically, PPA was decreased in groups 2, 4, and 6 compared to groups 1, 3, and 5 (p < 0.05) and decreased in group 2 compared to other groups (p < 0.05). Histopathologically, fibrosis was decreased in groups 2, 4, and 6 compared to other groups and decreased in group 2 compared to other groups (p < 0.05). Tissue OHP level was decreased in groups 2, 3, 4, and 5 compared to groups 1 and 6 (p < 0.05). Tissue OHP level was decreased in group 6 compared to group 1, but the difference was not statistically significant. PPA formation decreases with normal saline, HS and EHA-m, whereas increases with EC and AA both macroscopically and microscopically. Although HS and EHA-m seem to have adhesion prevention effect, washing the intestines with saline seems to be more effective.Kirikkale University Scientific Research CouncilKirikkale University [2014/81]This study was supported by Kirikkale University Scientific Research Council (2014/81) for only purchasing laboratory animal and other materials stated in the methods