Cardiac Myosin Binding Protein-C Autoantibodies are Potential Early Indicators of Cardiac Dysfunction and Patient Outcome in Acute Coronary Syndrome.
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ABSTRACT:
SUBMITTER: Lynch TL
PROVIDER: S-EPMC5460768 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundDecreased expression of cardiac myosin binding protein C (cMyBPC) as a result of genetic mutations may contribute to the development of hypertrophic cardiomyopathy (HCM); however, the mechanisms that link cMyBPC expression and HCM development, especially contractile dysfunction, remain unclear.Methods and resultsWe evaluated cardiac mechanical function in vitro and in vivo in young mice (8-10 weeks of age) carrying no functional cMyBPC alleles (cMyBPC(-/-)) or 1 functional cMyBPC allele (cMyBPC(±)). Skinned myocardium isolated from cMyBPC(-/-) hearts displayed significant accelerations in stretch activation cross-bridge kinetics. Cardiac MRI studies revealed severely depressed in vivo left ventricular (LV) magnitude and rates of LV wall strain and torsion compared with wild-type (WT) mice. Heterozygous cMyBPC(±) hearts expressed 23±5% less cMyBPC than WT hearts but did not display overt hypertrophy. Skinned myocardium isolated from cMyBPC(±) hearts displayed small accelerations in the rate of stretch induced cross-bridge recruitment. MRI measurements revealed reductions in LV torsion and circumferential strain, as well reduced circumferential strain rates in early systole and diastole.ConclusionsModest decreases in cMyBPC expression in the mouse heart result in early-onset subtle changes in cross-bridge kinetics and in vivo LV mechanical function, which could contribute to the development of HCM later in life.
| S-EPMC3328136 | biostudies-literature
Project description:BackgroundThyroid hormones profoundly influence the cardiovascular system, but the effects of mild thyroid dysfunction on the clinical outcome of acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) are not well defined. This study aimed to determine the effect of mild thyroid dysfunction on 12-month prognosis in ACS patients undergoing PCI.MethodsIn this prospective cohort study with a 12-month follow-up, 1560 individuals were divided into four groups based on thyroid hormone levels upon admission: euthyroidism (used as a reference group), subclinical hypothyroidism, subclinical hyperthyroidism, and low triiodothyronine syndrome (low T3 syndrome). The outcomes measured were all-cause mortality, cardiac mortality, nonfatal rein-farction, and unplanned repeat revascularization.ResultsIn this study, the prevalence of mild thyroid dysfunction was 10.8%. Multivariate analysis showed that low T3 syndrome, but not subclinical hypothyroidism or subclinical hyperthyroidism, was associated with a higher rate of all-cause (HR 2.553, 95% CI 1.093-5.964, p = 0.030) and cardiac mortality (HR 2.594, 95% CI 1.026-6.559, p = 0.034), compared with the euthyroidism group.ConclusionsMild thyroid dysfunction was frequent in patients with ACS undergoing PCI. Low T3 syndrome was the predominant feature and was associated with 12-month adverse outcomes in these patients.
| S-EPMC8015979 | biostudies-literature
Project description:AimsTimely detection of subclinical left ventricular diastolic dysfunction (LVDDF) is of importance for precise risk stratification of asymptomatic subjects. Here, we evaluated the prevalence of LVDDF and its prognostic significance in the general population using two grading approaches: the 2016 ASE/EACVI recommendations and population-derived, age-specific criteria.Methods and resultsWe randomly recruited 1407 community-dwelling participants (mean age, 51.2 years; 51.1% women; 53.5% with cardiovascular risk factors). We measured left heart dimensions, strain, tricuspid regurgitation, transmitral blood flow, and mitral annular tissue velocities using conventional echocardiography and Doppler imaging. We utilized these measurements to grade of LVDDF according to the 2016 recommendations and population-derived, age-specific approach. According to the 2016 recommendations, 26 subjects (1.85%) were classified as having the advanced stage (Grade 2), whereas in 109 participants (7.75%) diastolic function was indeterminate. When applying the population-derived criteria, the prevalence of advanced LVDDF was 17.9% (n = 252). During the follow-up period (8.4 years), 100 participants experienced adverse cardiac events. After full adjustment, we did not observe any significant differences in the risk of events between subjects with indeterminate or any grade of LVDDF and subjects with normal diastolic function when classified according to the 2016 recommendation (P ≥ 0.25). In contrast, the adjusted risks of adverse cardiac events (HR = 1.28; P = 0.0045) were significantly elevated in participants with LVDDF when classified according to the population-derived criteria.ConclusionsOur study underscored the importance of considering age- and population-derived thresholds in LVDDF grading in subjects at high cardiovascular risk which led to a better risk stratification and outcome prediction.
| S-EPMC9065821 | biostudies-literature
Project description:ImportanceProfessional guidelines recommend noninvasive cardiac testing (NIT) within 72 hours of an emergency department (ED) evaluation for suspected acute coronary syndrome. However, there is inexact evidence that this strategy reduces the risk of future death or acute myocardial infarction (MI).ObjectiveTo evaluate the effectiveness of early NIT in reducing the risk of death or acute MI within 30 days.Design, setting, and participantsThis retrospective, multicenter cohort study within the Kaiser Permanente Southern California integrated health care delivery system compared the effectiveness of early noninvasive cardiac testing vs no testing in patients with chest pain and in whom acute MI was ruled out who presented to an ED from January 2015 to December 2017. Patients were followed up for up to 30 days after emergency department discharge.ExposuresNoninvasive cardiac testing performed within 3 days of an ED evaluation for suspected acute coronary syndrome.Main outcomes and measuresThe primary outcome was composite risk of death or acute MI, within 30 days of an ED discharge.ResultsA total of 79 040 patients were evaluated in this study, of whom 57.7% were female. The mean (SD) age of the cohort was 57 (16) years, and 16 164 patients (21%) had completed early NIT. The absolute risk of death or MI within 30 days was low (<1%). Early NIT had the minor benefit of reducing the absolute composite risk of death or MI (0.4% [95% CI, -0.6% to -0.3%]), and, separately, of death (0.2% [95% CI, -0.2% to -0.1%]), MI (-0.3% [95% CI, -0.5% to -0.1%]), and major adverse cardiac event (-0.5% [95% CI, -0.7% to -0.3%]). The number needed to treat was 250 to avoid 1 death or MI, 500 to avoid 1 death, 333 to avoid 1 MI, and 200 to avoid 1 major adverse cardiovascular event within 30 days. Subgroup analysis revealed a number needed to treat of 14 to avoid 1 death or MI in the subset of patients with elevated troponin.Conclusions and relevanceEarly NIT was associated with a small decrease in the risk of death or MI in patients admitted to the ED with suspected acute coronary syndrome, but this clinical strategy may not be optimal for most patients given the large number needed to treat.
| S-EPMC7536619 | biostudies-literature
Project description:Decreased expression of cardiac myosin binding protein C (cMyBPC) in the heart has been implicated as a consequence of mutations in cMyBPC that lead to abnormal contractile function at the myofilament level, thereby contributing to the development of hypertrophic cardiomyopathy in humans. It has not been established whether increasing the levels of cMyBPC in the intact heart can improve myofilament and in vivo contractile function and attenuate maladaptive remodeling processes because of reduced levels of cMyBPC.We performed in vivo gene transfer of cMyBPC by direct injection into the myocardium of cMyBPC-deficient (cMyBPC(-/-)) mice, and mechanical experiments were conducted on skinned myocardium isolated from cMyBPC(-/-) hearts 21 days and 20 weeks after gene transfer. Cross-bridge kinetics in skinned myocardium isolated from cMyBPC(-/-) hearts after cMyBPC gene transfer were significantly slower compared with untreated cMyBPC(-/-) myocardium and were comparable to wild-type myocardium and cMyBPC(-/-) myocardium that was reconstituted with recombinant cMyBPC in vitro. cMyBPC content in cMyBPC(-/-) skinned myocardium after in vivo cMyBPC gene transfer or in vitro cMyBPC reconstitution was similar to wild-type levels. In vivo echocardiography studies of cMyBPC(-/-) hearts after cMyBPC gene transfer revealed improved systolic and diastolic contractile function and reductions in left ventricular wall thickness.This proof-of-concept study demonstrates that gene therapy designed to increase expression of cMyBPC in the cMyBPC-deficient myocardium can improve myofilament and in vivo contractile function, suggesting that cMyBPC gene therapy may be a viable approach for treatment of cardiomyopathies because of mutations in cMyBPC.
| S-EPMC4860813 | biostudies-literature
Project description:Cardiac myosin binding protein-C (cMyBP-C) phosphorylation prevents aging-related cardiac dysfunction. We tested this hypothesis by aging genetic mouse models of hypophosphorylated cMyBP-C, wild-type equivalent, and phosphorylated-mimetic cMyBP-C for 18 to 20 months. Phosphorylated-mimetic cMyBP-C mice exhibited better survival, better preservation of systolic and diastolic functions, and unchanging wall thickness. Wild-type equivalent mice showed decreasing cMyBP-C phosphorylation along with worsening cardiac function and hypertrophy approaching those found in hypophosphorylated cMyBP-C mice. Intact papillary muscle experiments suggested that cMyBP-C phosphorylation increased cross-bridge detachment rates as the underlying mechanism. Thus, phosphorylating cMyBP-C is a novel mechanism with potential to treat aging-related cardiac dysfunction.
| S-EPMC6978553 | biostudies-literature
Project description:Eisenmenger's syndrome is a complex multisystem disease which occurs as a consequence of large left to right shunt affecting the pulmonary vasculature causing suprasystemic pulmonary artery pressures and subsequent right to left shunt. Usually Eisenmenger's syndrome is characterised by coronary artery dilation but coronary artery disease and occurrence of acute coronary syndrome is a rare association seldom described in literature. We present the case of a 33-year-old man who presented with an anterior wall ST elevation mycocardial infarction and was thrombolysed. The occurrence of acute coronary event in a case of Eisenmenger's syndrome is a rare event and needs to be discussed and kept in mind by physicians and cardiologists who deal with such cases so that a high index of suspicion may be developed and emergent management may be possible.
| S-EPMC3863057 | biostudies-other
Project description:BackgroundThrombotic microangiopathy (TMA) syndromes include thrombotic thrombocytopenic purpura (TTP) and haemolytic uremic syndrome, and contribute to myocardial infarction and multiple organ failure. Although coronary microvascular dysfunction (CMD) is the key for understanding the pathophysiology of cardiac involvement in TMA, there is limited knowledge on the recovery from CMD in patients with TMA.Case summaryAn 80-year-old woman was brought to the emergency department due to worsening back pain, dyspnoea on exertion, jaundice, and fever. Although she had typical TTP symptoms and elevated cardiac troponin level, ADAMTS13 activity was preserved (34%), leading to the diagnosis of TMA with myocardial infarction. She underwent plasma exchange and was administered aspirin and prednisolone. Magnetic resonance imaging revealed iliopsoas abscess, which is a possible aetiologic factor of sepsis-related TTP. She had impaired coronary flow reserve (CFR) with angiographically non-obstructive epicardial coronary arteries. Improved CFR was observed on follow-up, suggesting existence of transient CMD caused by TMA. After treatment of the iliopsoas abscess with antibiotics for 3 months, she was discharged without any adverse complications.DiscussionCoronary microvascular dysfunction is an underlying mechanism of myocardial infarction, with or without epicardial obstructive coronary artery stenosis. TMA is characterized by pathological lesions caused by endothelial cell damage in small terminal arteries and capillaries, with complete or partial occlusion caused by platelet and hyaline thrombi. CMD and its recovery are keys for understanding the natural history of cardiac involvement in TMA. In vivo evaluations of CMD can provide mechanistic insights into the cardiac involvement in TMA.
| S-EPMC10020975 | biostudies-literature
Project description:Vasospastic angina results from temporary spasm of one or more coronary segments. Although prognosis of patients presenting with coronary vasospasm appears to be generally good, multivessel coronary vasospasm may increase the risk of life-threatening cardiac events. We present a case of a 51-year-old man admitted to the emergency room due to severe retrosternal pain, who was documented with multifocal coronary vasospasm. <Learning objective: The case described illustrates the importance of recognizing coronary vasospasm as a cause of reversible ischemia. Although vasospastic angina is associated with a favorable prognosis, multivessel involvement may increase the risk of life-threatening cardiac events.>.
| S-EPMC6278680 | biostudies-literature
Project description:Sotos syndrome, characterized by cerebral gigantism with neurologic disorders, is an overgrowth syndrome caused by mutations of the NSD1 gene, with an estimated prevalence of 1:10,000-1:50,000. We herein describe the first case of Sotos syndrome complicated by acute coronary syndrome, for which emergency coronary artery bypass grafting was performed. (Level of Difficulty: Intermediate.).
| S-EPMC8543145 | biostudies-literature