Survival after Aortic Valve Replacement for Aortic Regurgitation: Prediction from Preoperative Contractility Measurement.

Background: Noninvasive measurement of myocardial contractility (end-systolic wall stress-adjusted change in left ventricular ejection fraction from rest to exercise [ΔLVEF - ΔESS]) predicts heart failure, subnormal LVEFrest, and sudden death in asymptomatic patients with chronic severe aortic regurgitation (AR). Here we assess the relation of preoperative ΔLVEF - ΔESS to survival after aortic valve replacement (AVR).

Methods: Patients who underwent AVR for chronic, isolated, pure severe AR (n = 66) were followed for 13.

Impact of Beta-Blockade on Cardiac Events in Patients with Chronic Severe Nonischemic Mitral Regurgitation.

Objectives: The aim of this study was to examine the impact of beta-blockade on cardiac events among patients with initially asymptomatic chronic severe nonischemic mitral valve regurgitation (MR).

Methods: Data from 52 consecutive patients in our prospective natural history study of isolated chronic severe nonischemic MR were assessed post hoc over 19 years to examine the relation of chronic beta-blockade use to subsequent cardiac events (death or indications for mitral valve surgery, MVS). At entry, all patients were free of surgical indications; 9 received beta-blockers.

Prognostic value of initial elevation in cardiac troponin I level in critically ill patients without acute coronary syndrome.

Background: Cardiac troponin I levels are often obtained to help rule out acute coronary syndrome.

Objective: To determine if elevation of troponin level within 24 hours for patients without acute coronary syndrome admitted to the intensive care unit provides important prognostic information.

Methods: Patients without acute coronary syndrome admitted to the intensive care unit were prospectively divided into 2 groups according to highest serum level of cardiac troponin I within 24 hours of admission (elevated > 0.

Relation of indirect vasodilator use to prognosis in patients with chronic severe mitral regurgitation.

Objectives: The relation of indirect vasodilator use to cardiac events (CE) is undefined for chronic severe nonischemic mitral regurgitation (MR). The aim of this study was to resolve this knowledge deficiency.

Methods: Data from 52 consecutive patients in our prospective natural history study with isolated chronic severe nonischemic MR were assessed post hoc over 19 years to examine the relation of indirect vasodilator use to subsequent CE (death or indications for valve surgery).

Usefulness of preoperative exercise tolerance to predict late survival and symptom persistence after surgery for chronic nonischemic mitral regurgitation.

Exercise duration during exercise treadmill testing (ETT) predicts long-term outcome among asymptomatic patients with mitral regurgitation. However, the prognostic value of preoperative exercise duration in patients who undergo mitral valve surgery is unknown. We examined findings among 45 prospectively followed (average 9.

Nonischemic mitral regurgitation: prognostic value of nonsustained ventricular tachycardia after mitral valve surgery.

Background: Nonsustained ventricular tachycardia (VT), frequent in unoperated severe mitral regurgitation (MR), confers mortality risk [sudden death (SD) and cardiac death (CD)]. The prognostic value of VT after mitral valve surgery (MVS) is unknown; we aimed to define this prognostic value and to assess its modulation by left (LV) and/or right (RV) ventricular ejection fraction (EF) for mortality after MVS.

Methods: In 57 patients (53% females, aged 58 ± 12 years) with severe MR prospectively followed before and after MVS, we performed 24-hour ambulatory electrocardiograms approximately annually.

Fibronectin gene expression in aortic regurgitation: relative roles of mitogen-activated protein kinases.

Objectives: In aortic regurgitation (AR), fibronectin (FN) expression is upregulated. This study sought to determine signal transduction pathways involved in upregulation of FN expression in AR.

Methods: Cardiac fibroblasts (CF) from rabbits with surgically induced AR and matched controls (NL) were cultured and assayed for FN expression and kinase activity with and without inhibitors of kinases JNK, p38 mitogen-activated protein kinase (MAPK) and extracellular response kinase (ERK).

Differential expression of matrix metalloproteinases and tissue inhibitors and extracellular matrix remodeling in aortic regurgitant hearts.

Objectives: Myocardial fibrosis in experimental aortic regurgitation (AR) features abnormal fibronectin with normal collagen content, but the relevant degradative processes have not been assessed.

Methods: To elucidate these degradative processes, mRNA (Northern) and protein levels (Western) of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), as well as MMP activity (zymography), were measured in cardiac fibroblasts (CF) from New Zealand white rabbits with experimental AR paired with normals (NL). Collagen and fibronectin were quantified by immunohistochemical staining.

Prognostic value of exercise tolerance testing in asymptomatic chronic nonischemic mitral regurgitation.

In many heart diseases, exercise tolerance testing (ETT) has useful functional correlates and/or prognostic value. However, its predictive value in mitral regurgitation (MR) is undefined. To determine whether ETT descriptors predict death or indications for mitral valve surgery in patients with MR, we prospectively followed, for 7 +/- 3 end-point-free years, a cohort of 38 patients with chronic severe nonischemic MR who underwent modified Bruce ETT; all lacked surgical indications at study entry.

Cellular response of human cardiac fibroblasts to mechanically simulated aortic regurgitation.

Myocardial fibrosis has been identified in biopsy specimens from catheterization and valve replacement surgery in patients with severe chronic aortic regurgitation (AR). While characterization of these extracellular matrix (ECM) alterations has been incomplete in humans, fibrosis also has been identified in chronic severe experimentally created AR, in which ECM composition features abnormal fibronectin/glycoprotein production, with normal collagen content. Virtually identical ECM variations have been induced when normal rabbit cardiac fibroblasts (CF) are subjected in culture to cyclic mechanical strain mimicking that found in the left ventricle (LV) in severe AR.

Prognostic impact of systolic hypertension on asymptomatic patients with chronic severe aortic regurgitation and initially normal left ventricular performance at rest.

The influence of systolic hypertension (SH) on the natural history of chronic aortic regurgitation (AR) and the clinical effect of antihypertensive medication on patients who have hypertension and AR are incompletely defined. Therefore, we reviewed the clinical course of 80 unoperated patients who were entered prospectively into an assessment of natural history of AR and its predictors and were asymptomatic with normal left ventricular ejection fraction (LVEF) at rest at study entry; 30 of 80 patients had SH (systolic blood pressure >140 mm Hg); 20 of 80 patients (16 had SH) used antihypertensive drugs for the long term (not mandated by protocol). During an average 7.

Left ventricular ejection fraction change with exercise versus ejection fraction at rest in coronary artery disease: implications for using ejection fraction variations in making therapeutic decisions.

Previous studies have differed regarding the prognostic importance of the change (Delta) in left ventricular ejection fraction (LVEF) with exercise among patients with known or suspected coronary artery disease (CAD). Data suggest that these discrepancies may be owing to patient selection, including wide interstudy variations in the range of LVEFrest at study entry; however, the impact of LVEFrest on LVEF exercise response has not been adequately addressed. To test the hypothesis that magnitude and variability in DeltaLVEF are systematically related to LVEFrest, we analyzed data from 2655 patients who underwent rest/exercise radionuclide cineangiography for evaluation of clinically evident CAD, stratified into 5 successive LVEFrest subgroups: <30% (n = 205), 30%-44% (n = 563), 45%-59% (n = 1529), 60%-75% (n = 324), and >75% (n = 34).

Myocardial fibrosis in chronic aortic regurgitation: molecular and cellular responses to volume overload.

Background: Myocardial fibrosis is common in patients with chronic aortic regurgitation (AR). Experimentally, fibrosis with disproportionate noncollagen extracellular matrix (ECM) elements precedes and contributes to heart failure in AR.

Methods And Results: We assessed [3H]-glucosamine and [3H]-proline incorporation in ECM, variations in cardiac fibroblast (CF) gene expression, and synthesis of specific ECM proteins in CF cultured from rabbits with surgically induced chronic AR versus controls.

Localization of (99m)Tc-Labeled ApoB Synthetic Peptide in Arterial Lesions of an Experimental Model of Spontaneous Atherosclerosis.

We have previously shown that after administration of (123)I-SP-4 (a synthetic ApoB peptide fragment) to Watanabe heritable hyperlipidemic (WHHL) rabbits that foci of tracer uptake can be identified by external gamma camera imaging which correspond to regions of the aortas found to contain abundant atherosclerotic lesions at postmortem evaluation. Because (99m)Tc is preferred over (123)I for scintigraphic imaging, we prepared a (99m)Tc-labeled form of the SP-4 peptide, designated (99m)Tc-P199. To assess the feasibility of detecting atherosclerotic lesions using (99m)Tc-P199 and to compare the relative uptake of the (99m)Tc-labeled and radioiodinated peptides by such lesions, an admixture of (99m)Tc-199 and (125)I-SP-4 was administered to 11 WHHL and 2 normal rabbits.