Echocardiographic Manifestations in Patients with Cardiac Sarcoidosis

BackgroundCardiac sarcoidosis is a life-threatening disease with protean clinical manifestations, including congestive heart failure (CHF), conduction disturbance, ventricular arrhythmia and sudden death. Nonetheless, it is difficult to diagnose cardiac sarcoidosis in the clinical setting. Some echocardiographic findings of cardiac sarcoidosis associated with other diagnostic tools (201thallium scintigraphy, 67gallium citrate scan, serum markers and others) may be helpful upon early suspicion and diagnosis of cardiac sarcoidosis.Materials and MethodsFifty-two patients (36 female) with cardiac sarcoidosis, with a mean age of 48 ± 14 years (range, 21–70 yr), underwent a series of echocardiographic follow-up (mean, 88 ± 48 mo) examinations, and important echocardiographic parameters and findings were recorded.ResultsThere were left ventricular (LV) regional wall motion abnormalities (RWMAs) noted in 40 (localized in 16, multiple in 24), dilatation of the LV with impaired LV contractility in 28, thinning of the basal interventricular septum (IVS) in 27, thinning of LV free wall in 18, apical aneurysm in 12, apical thrombus in two, mimicking hypertrophic cardiomyopathy (HCM) in two, pericardial effusion (PE) in two (with cardiac tamponade in one), and LV wall thinning and aneurysm formation after steroid therapy for cardiac sarcoidosis in two of 43 patients.ConclusionThinning of the basal IVS or LV free wall is a specific echocardiographic finding of cardiac sarcoidosis. Other echocardiographic findings of cardiac sarcoidosis may mimic coronary artery disease (LV RWMA or apical aneurysm), CHF, or HCM. PE and thinning of the LV wall after steroid therapy were also noted in rare situations

Long-term Clinical Outcomes Following Elective Stent Implantation for Unprotected Left Main Coronary Artery Disease

Background/PurposePercutaneous coronary intervention (PCI) has been increasingly adopted for unprotected left main coronary artery (LMCA) disease. The aim of this study was to evaluate the predictors of long-term clinical outcomes in patients after elective stent implantation for unprotected LMCA disease.MethodsA total of 122 patients with medically refractory angina who received coronary stenting for unprotected LMCA disease between August 1997 and December 2008 were included.ResultsDuring the follow-up period of 45 ± 35 months (range: 1–137 months), the incidence of repeated PCI and/or coronary artery bypass grafting (CABG), and cardiovascular and total mortality were 28% (34 patients), 20% (24 patients), and 25% (31 patients), respectively. Multivariate analysis revealed that young age [p = 0.02; hazard ratio (HR): 2.19, 95% confidence interval (CI): 1.11–4.30] and bare-metal stent (BMS) use (p = 0.02; HR: 5.35, 95% CI: 1.27–22.57) were the independent predictors of repeated PCI and/or CABG. Only lower left ventricular ejection fraction (LVEF) could predict both cardiovascular mortality (p = 0.003; HR: 4.25, 95% CI: 1.63–11.08) and total mortality (p = 0.002; HR: 3.95, 95% CI: 1.65–9.45). Lower LVEF (p = 0.001; HR: 0.31, 95% CI: 0.16–0.61) and small stent size (p = 0.01; HR: 5.95, 95% CI: 1.43–24.80) could predict the composite endpoint, including target vessel revascularization and total mortality.ConclusionWe showed that young age and BMS implantation could predict repeated PCI and/or CABG after stent implantation for unprotected LMCA disease. Only lower LVEF could predict both cardiovascular and total mortality. Lower LVEF and small stent size but not BMS implantation could predict composite target vessel revascularization/total mortality

Angiotensin II and the ERK pathway mediate the induction of myocardin by hypoxia in cultured rat neonatal cardiomyocytes

Hypoxic injury to cardiomyocytes is a stress that causes cardiac pathology through cardiac-restricted gene expression. SRF (serum-response factor) and myocardin are important for cardiomyocyte growth and differentiation in response to myocardial injuries. Previous studies have indicated that AngII (angiotensin II) stimulates both myocardin expression and cardiomyocyte hypertrophy. In the present study, we evaluated the expression of myocardin and AngII after hypoxia in regulating gene transcription in neonatal cardiomyocytes. Cultured rat neonatal cardiomyocytes were subjected to hypoxia, and the expression of myocardin and AngII were evaluated. Different signal transduction pathway inhibitors were used to identify the pathway(s) responsible for myocardin expression. An EMSA (electrophoretic mobility-shift assay) was used to identify myocardin/SRF binding, and a luciferase assay was used to identify transcriptional activity of myocardin/SRF in neonatal cardiomyocytes. Both myocardin and AngII expression increased after hypoxia, with AngII appearing at an earlier time point than myocardin. Myocardin expression was stimulated by AngII and ERK (extracellular-signal-regulated kinase) phosphorylation, but was suppressed by an ARB (AngII type 1 receptor blocker), an ERK pathway inhibitor and myocardin siRNA (small interfering RNA). AngII increased both myocardin expression and transcription in neonatal cardiomyocytes. Binding of myocardin/SRF was identified using an EMSA, and a luciferase assay indicated the transcription of myocardin/SRF in neonatal cardiomyocytes. Increased BNP (B-type natriuretic peptide), MHC (myosin heavy chain) and [3H]proline incorporation into cardiomyocytes was identified after hypoxia with the presence of myocardin in hypertrophic cardiomyocytes. In conclusion, hypoxia in cardiomyocytes increased myocardin expression, which is mediated by the induction of AngII and the ERK pathway, to cause cardiomyocyte hypertrophy. Myocardial hypertrophy was identified as an increase in transcriptional activities, elevated hypertrophic and cardiomyocyte phenotype markers, and morphological hypertrophic changes in cardiomyocytes

Congestive Heart Failure in the Elderly

Over the past 30 years, the prevalence and incidence of heart failure (HF) have increased markedly with age, with increases of approximately fivefold from the age of 40 to 70 years. HF is predominantly a disorder of the elderly, and over 70% of HF patients are over 65 years old. The most important factor in the increasing prevalence and incidence of HF is the growing proportion of elderly with new-onset diastolic HF resulting from chronic hypertension and coronary heart disease. Other predictors of HF include diabetes, prior stroke, atrial fibrillation, renal dysfunction, reduced ankle-brachial index, increased C-reactive protein, left ventricular hypertrophy, reduced forced expiratory volume, and obesity. At least half of all elderly HF patients have preserved left ventricular systolic function, and they are classified as diastolic HF. There was a strong female predominance (67%) in diastolic HF when compared with male HF patients. The morbidity and mortality of older HF patients are the highest of any chronic cardiovascular disorder. Mortality increases markedly with age. Mortality from diastolic HF is about half of that reported for systolic HF. There are some comorbidities in older HF patients, including renal dysfunction, chronic lung disease, cognitive dysfunction, depression, postural hypotension, urine incontinence, sensory deprivation, nutritional disorders, polypharmacy and frailty, which may precipitate and exacerbate the underlying HF symptoms. Clinical diagnosis of HF may be more difficult in the elderly because of frequently inadequate history taking, less evident HF symptoms for reduced daily activity, and similar symptoms to other frequent disorders. The treatment goals in older HF patients resemble those for any chronic disorder and include relief of symptoms, improvement in functional status, exercise tolerance, quality of life, prevention of acute exacerbation, and finally, prolongation of long-term survival

Angiotensin II and the ERK pathway mediate the induction of myocardin by hypoxia in cultured rat neonatal cardiomyocytes.

Abstract Mechanical cyclic stretch of cardiomyocytes causes cardiac hypertrophy through cardiac-restricted gene expression. Leptin induces cardiomyocyte hypertrophy in response to myocardial stress. In the present study, we evaluated the expression of leptin under cyclic stretch and its role in regulating genetic transcription in cardiomyocytes. Cultured rat neonatal cardiomyocytes were subjected to cyclic stretch, and the expression levels of leptin, ROS (reactive oxygen species) and AngII (angiotensin II) were evaluated. Signal transduction inhibitors were used to identify the pathway of leptin expression. EMSAs were used to identify the binding of leptin/STAT3 (signal transducer and activator of transcription 3) and luciferase assays were used to identify the transcription of leptin in cardiomyocytes. The study also used an in vivo model of AV (aortocaval) shunt in rats to investigate leptin, ROS and AngII expression. Leptin and leptin receptor levels increased after cyclic stretch with the earlier expression of AngII and ROS. Leptin expression was suppressed by AngII receptor blockers, an ROS scavenger [NAC (N-acetylcysteine)], an ERK (extracellular-signal-regulated kinase) pathway inhibitor (PD98059) and ERK siRNA. Binding of leptin/STAT3 was identified by EMSAs, and luciferase assays confirmed the transcription of leptin in neonatal cardiomyocytes after cyclic stretch. Increased MHC (myosin heavy chain) expression and [ 3 H]-proline incorporation in cardiomyocytes was detected after cyclic stretch, which were inhibited by leptin siRNA and NAC. The in vivo model of AV shunt also demonstrated increased levels of plasma and myocardial leptin, ROS and AngII expression after cyclic stretch. Mechanical cyclic stretch in cardiomyocytes increased leptin expression mediated by the induction of AngII, ROS and the ERK pathway to cause cardiomyocyte hypertrophy. Myocardial hypertrophy can be identified by increased transcriptional activity and an enhanced hypertrophic phenotype of cardiomyocytes

Effects of cyclic stretch on the molecular regulation of myocardin in rat aortic vascular smooth muscle cells

BACKGROUND: The expression of myocardin, a cardiac-restricted gene, increases during environmental stress. How mechanical stretch affects the regulation of myocardin in vascular smooth muscle cells (VSMCs) is not fully understood. We identify the mechanisms and pathways through which mechanical stretch induces myocardin expression in VSMCs. RESULTS: Rat VSMCs grown on a flexible membrane base were stretched to 20% of maximum elongation, at 60 cycles per min. An in vivo model of aorta-caval shunt in adult rats was also used to investigate myocardin expression. Cyclic stretch significantly increased myocardin and angiotensin II (AngII) expression after 18 and 6 h of stretch. Addition of extracellular signal-regulated kinases (ERK) pathway inhibitor (PD98059), ERK small interfering RNA (siRNA), and AngII receptor blocker (ARB; losartan) before stretch inhibited the expression of myocardin protein. Gel shift assay showed that myocardin-DNA binding activity increased after stretch. PD98059, ERK siRNA and ARB abolished the binding activity induced by stretch. Stretch increased while myocardin-mutant plasmid, PD98059, and ARB abolished the promoter activity. Protein synthesis by measuring [(3)H]proline incorporation into the cells increased after cyclic stretch, which represented hypertrophic change of VSMCs. An in vivo model of aorta-caval shunt also demonstrated increased myocardin protein expression in the aorta. Confocal microscopy showed increased VSMC size 24 h after cyclic stretch and VSMC hypertrophy after creation of aorta-caval shunt for 3 days. CONCLUSIONS: Cyclic stretch enhanced myocardin expression mediated by AngII through the ERK pathway in cultured rat VSMCs. These findings suggest that myocardin plays a role in stretch-induced VSMC hypertrophy

Use of CHADS₂ and CHA₂DS₂-VASc scores to predict subsequent myocardial infarction, stroke, and death in patients with acute coronary syndrome: data from Taiwan acute coronary syndrome full spectrum registry.

Acute coronary syndrome (ACS) patients have a wide spectrum of risks for subsequent cardiovascular events and death. However, there is no simple, convenience scoring system to identify risk of adverse outcomes. We investigated whether CHADS₂ and CHA₂DS₂-VASc scores were useful tools to assess the risk for adverse events among ACS patients.This observational prospective study was conducted at 39 hospitals. Totally 3,183 patients with ACS were enrolled, and CHADS₂ and CHA₂DS₂-VASc scores were calculated. The primary endpoint was occurrence of adverse event, including subsequent myocardial infarction, stroke, or death, within 1 year of discharge.CHADS₂ and CHA₂DS₂-VASc scores were significant predictors of adverse events in separate multivariate regression analyses. A Kaplan-Meier analysis of CHADS₂ and CHA₂DS₂-VASc scores of ≥2 showed a higher rate of adverse events as compared with scores of <2 (P<0.001;log-rank test). CHA₂DS₂-VASc score was better than CHADS₂ score in predicting subsequent adverse events; the area under the receiver operating characteristic curve increased from 0.66 to 0.70 (p<0.001). Patients with CHADS₂ scores of 0 or 1 were further classified according to CHA₂DS₂-VASc score, using a cutoff value of 2. The rate of adverse events significantly differed between those with a score of <2 and those with a score of ≥2 (4.1% vs.10.7%, P<0.001).CHADS₂ and CHA₂DS₂-VASc scores were useful predictors of subsequent adverse events in ACS patients

Flowchart of adverse event rates and risk scores in the patients with CHADS₂ score of 0 or 1.

<p>(A) Rate of MI, stroke, or death in patients with a CHADS₂ score of 0 or 1, according to CHA₂DS₂-VASc score. The rate of myocardial infarction (MI), stroke, or death progressively increased, from 3.0% to 33.3%, with increasing CHA₂DS₂-VASc score. (B) The flowchart shows the rate of MI, stroke, or death in patients stratified by CHADS₂ and CHA₂DS₂-VASc scores.</p

Receiver operating characteristic (ROC) curves for CHADS₂, CHA₂DS₂-VASc and GRACE scores predicting myocardial infarction (MI), stroke, or death.

<p>Diagnostic performance in predicting MI, stroke, or death was better for CHA₂DS₂-VASc score than for CHADS₂ score. The area under the ROC curve (AUC) increased from 0.66 to 0.70, and the difference was statistically significant (<i>p</i><0.001). Besides, the diagnostic accuracy in predicting adverse events was better for GRACE score than for CHA₂DS₂-VASc score (AUC 0.74 vs. 0.70, <i>p</i><0.001).</p

Rates of adverse events, including myocardial infarction (MI), stroke, or death, according to CHADS₂ and CHA₂DS₂-VASc scores.

<p>The rate of MI, stroke, or death increased as CHADS₂ (A) and CHA₂DS₂-VASc (B) scores increased.</p