Cardiovascular magnetic resonance predictors of heart failure in hypertrophic cardiomyopathy: the role of myocardial replacement fibrosis and the microcirculation

Introduction: Heart failure (HF) in hypertrophic cardiomyopathy (HCM) is associated with high morbidity and mortality. Predictors of HF, in particular the role of myocardial fibrosis and microvascular ischemia remain unclear. We assessed the predictive value of cardiovascular magnetic resonance (CMR) for development of HF in HCM in an observational cohort study. Methods: Serial patients with HCM underwent CMR, including adenosine first-pass perfusion, left atrial (LA) and left ventricular (LV) volumes indexed to body surface area (i) and late gadolinium enhancement (%LGE- as a % of total myocardial mass). We used a composite endpoint of HF death, cardiac transplantation, and progression to NYHA class III/IV. Results: A total of 543 patients with HCM underwent CMR, of whom 94 met the composite endpoint at baseline. The remaining 449 patients were followed for a median of 5.6 years. Thirty nine patients (8.7%) reached the composite endpoint of HF death (n = 7), cardiac transplantation (n = 2) and progression to NYHA class III/IV (n = 20). The annual incidence of HF was 2.0 per 100 person-years, 95% CI (1.6–2.6). Age, previous non-sustained ventricular tachycardia, LV end-systolic volume indexed to body surface area (LVESVI), LA volume index ; LV ejection fraction, %LGE and presence of mitral regurgitation were significant univariable predictors of HF, with LVESVI (Hazard ratio (HR) 1.44, 95% confidence interval (95% CI) 1.16–1.78, p = 0.001), %LGE per 10% (HR 1.44, 95%CI 1.14–1.82, p = 0.002) age (HR 1.37, 95% CI 1.06–1.77, p = 0.02) and mitral regurgitation (HR 2.6, p = 0.02) remaining independently predictive on multivariable analysis. The presence or extent of inducible perfusion defect assessed using a visual score did not predict outcome (p = 0.16, p = 0.27 respectively). Discussion: The annual incidence of HF in a contemporary ambulatory HCM population undergoing CMR is low. Myocardial fibrosis and LVESVI are strongly predictive of future HF, however CMR visual assessment of myocardial perfusion was not

Global longitudinal strain to determine optimal timing for surgery in primary mitral regurgitation: a systematic review

Background Primary mitral regurgitation (PMR) results in adverse remodeling changes and left ventricular (LV) dysfunction. Assessing LV function has prognostic value in predicting morbidity and mortality. Indications for surgery include parameters such as LV ejection fraction (LVEF) and systolic dimensions. Current guidelines are limited in identifying patients at optimal time for surgery. Impaired postoperative LVEF indicates poor prognostic outcomes and subsequent heart failure. Global longitudinal strain (GLS) via speckle tracking echocardiography (STE) presents as a promising parameter to detect subclinical dysfunction in asymptomatic patients. Methods Following PRISMA guidelines, a literature search was conducted with Cochrane Library, PudMed, SCOPUS, and Web of Science. Key MeSH terms included “mitral regurgitation,” “mitral valve insufficiency,” “global longitudinal strain,” “deformation,” “LV‐GLS,” and “GLS.” Inclusion criteria included (1) patients with severe PMR, (2) mixed population of symptomatic and asymptomatic patients, (3) standardized methods in assessing LV systolic function using 2D‐STE, (4) valve repair or replacement surgery, and (5) patient outcomes measured after surgery. Search returned 234 papers, 12 of which met the inclusion criteria and were subsequently reviewed. Results Baseline GLS is an independent predictor of postoperative outcomes, ranging from −17.9 to −21.7% GLS. A significant negative correlation was observed between preoperative GLS and postoperative LVEF. Impaired baseline GLS was associated with higher mortality rates. Better long‐term survival rates were seen in patients who underwent early surgery. Conclusion GLS shows sensitivity in predicting long‐term postoperative outcomes. Further analysis is required to determine preoperative GLS threshold to identify asymptomatic patients at the optimal time for mitral valve surgery

Vascular dysfunction and reduced circulating endothelial progenitor cells in young healthy UK South Asian men

OBJECTIVES: The objective of this study was to examine determinants of excess coronary artery disease risk in UK South Asians, more prevalent in this population than UK Caucasians, by examining differences in risk factors, vascular function, and endothelial progenitor cells (EPCs). METHODS AND RESULTS: 24 South Asian and 25 Caucasian healthy age-matched nonsmoking men were studied. Vascular function was assessed by flow-mediated and GTN brachial artery dilatation and blood flow responses to infusion of ACh, SNP, and L-NMMA. EPC number and function were measured by flow cytometry (CD34, CD133, and KDR positive cells), and CFU/migration assays. Traditional risk factors and anthropometric measurements were similar in the groups. South Asians had higher fasting insulin levels (6.01 versus 3.62 microU/mL; P = 0.02). South Asians had lower FMD (6.9 versus 8.5%; P = 0.003), L-NMMA response (0.8 versus 1.3 mL/min/100 mL; P = 0.03), mean SNP response (9.5+/-0.6 versus 11.6+/-0.6; P = 0.02), EPC number (0.046+/-0.005% versus 0.085+/-0.009%; P = < 0.001), and CFU ability (CFU 4.29+/-1.57 versus 18.86+/-4.00; P = 0.005). EPC number was the strongest predictor of FMD. Ethnicity was the strongest predictor of EPC number. CONCLUSIONS: Healthy South Asian men are more insulin resistant, and demonstrate endothelial dysfunction and reduced EPC number and function compared with Caucasians. These abnormalities may contribute to their increased CAD risk

Paradoxical resistance to myocardial ischemia and age-related cardiomyopathy in NHE1 transgenic mice: A role for ER stress?

Sarcolemmal Na+/H+ exchanger (NHE) activity, which is provided by the NHE isoform I (NHE1), has been implicated in ischemia/reperfusion-induced myocardial injury in animal models and humans, on the basis of studies with pharmacological NHE1 inhibitors. We generated a transgenic (TG) mouse model with cardiac-specific over-expression of NHE1 to determine whether this would be sufficient to increase myocardial susceptibility to ischemia/reperfusion-induced injury. TG mouse hearts exhibited increased sarcolemmal NHE activity and normal morphology and function. Surprisingly, they also showed reduced susceptibility to ischemia/reperfusion-induced injury as reflected by improved functional recovery and smaller infarcts. Such protection was sustained in the presence of NHE1 inhibition with zoniporide, indicating a mechanism that is independent of sarcolemmal NHE activity. Immunoblot analysis revealed accumulation of immature NHE1 protein as well as marked upregulation of both cytoprotective (78/94 kDa glucose-regulated proteins, calreticulin, protein disulfide isomerase) and pro-apoptotic (C/EBP homologous protein) components of the endoplasmic reticulum (ER) stress response in TG myocardium. With increasing age, NHE1 TG mice exhibited increased myocyte apoptosis, developed left ventricular contractile dysfunction, underwent cardiac remodelling and died prematurely. Our findings indicate that: (1) Cardiac-specific NHE1 over-expression induces the ER stress response in mouse myrocardium, which may afford protection against ischemia/reperfusion-induced injury despite increased NHE activity; (2) Ageing NHE1 TG mice exhibit myocyte apoptosis, cardiac remodelling and failure, likely as a result of Sustained ER stress; (3) The pluripotent effects of the ER stress response may confound studies that are based on the chronic over-expression of complex proteins in myrocardium. (C) 2008 Elsevier Inc. All rights reserved