Zvi Vered

Intracoronary injection of basic fibroblast growth factor enhances angiogenesis in infarcted swine myocardium.

OBJECTIVESnThis study was performed to examine the effect of intracoronary exogenous basic fibroblast growth factor (bFGF) on angiogenesis in infarcted myocardial regions.nnnBACKGROUNDnExogenous bFGF is a potent promoter of angiogenesis. Little information is available on its effect on myocardial angiogenesis.nnnMETHODSnMyocardial infarction was induced in 10 pigs by intracoronary injection of microscopic beads. Four pigs served as a control group; in six pigs slow-release bFGF was delivered by the beads. Cardiac performance was evaluated by repeated echocardiographic measurement and angiogenesis was evaluated by immunohistochemical studies 14 days later.nnnRESULTSnAs compared with control pigs, pigs treated with bFGF had higher microvessel counts (mean +/- SEM) in both viable tissue (141 +/- 27 per field vs. 39 +/- 4, p = 0.01) and nonviable tissue (329 +/- 26 per field vs. 95 +/- 7, p < 0.001) within the infarct area. No significant differences in total regional left ventricular wall motion were noted between the two groups throughout the 14-day study period.nnnCONCLUSIONSnIn the swine, direct intracoronary application of bFGF to infarcted myocardium enhances myocardial neovascularization within 2 weeks.

Exercise-induced left ventricular dysfunction in young men with asymptomatic diabetes mellitus (diabetic cardiomyopathy)

Radionuclide ventriculographic studies were performed at rest and during exercise on 30 consecutive men, aged 21 to 35 years with diabetes mellitus without evidence of coronary artery or any other cardiovascular disease, and in 20 normal age-matched subjects. Sixteen (53%) were treated with insulin and 14 (47%) were treated with either diet (6 patients) or oral antidiabetic therapy (8 patients). All patients from both groups had normal left ventricular (LV) ejection fraction (EF) at rest. In 5 of the 30 diabetic patients (17%), LVEF decreased after exercise, in 8 (27%) it remained unchanged and in 17 it increased normally. Mean LVEF at rest and after exercise in this group was 66 +/- 7% and 72 +/- 7% (+/- standard deviation), respectively. In all normal subjects, LVEF increased after exercise. Mean LVEF at rest and after exercise in the normal group was 66 +/- 7% and 76 +/- 9%, respectively. No patient had evidence of regional dysfunction at rest or after exercise. LV function was not related to serum glucose levels during the test, modality of treatment, insulin dependency or duration of the disease. Three of 4 patients with diabetic microvascular complications showed LV dysfunction. In 4 of 5 patients in whom LVEF decreased after exercise, thallium studies showed normal perfusion. Thus, diabetes mellitus may cause exercise-induced global LV dysfunction in young men with no evidence of cardiovascular disease. This phenomenon apparently does not seem to follow the known course of diabetic microvascular complications.

Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy.

PURPOSEnWe have previously found thiamine (vitamin B1) deficiency in patients with congestive heart failure (CHF) who had received long-term furosemide therapy. In the present study, we assessed the effect of thiamine repletion on thiamine status, functional capacity, and left ventricular ejection fraction (LVEF) in patients with moderate to severe CHF who had received furosemide in doses of 80 mg/d or more for at least 3 months.nnnPATIENTS AND METHODSnThirty patients were randomized to 1 week of double-blind inpatient therapy with either i.v. thiamine 200 mg/d or placebo (n = 15 each). All previous drugs were continued. Following discharge, all 30 patients received oral thiamine 200 mg/d as outpatients for 6 weeks. Thiamine status was determined by the erythrocyte thiamine-pyrophosphate effect (TPPE). LVEF was determined by echocardiography.nnnRESULTSnTPPE, diuresis, and LVEF were unchanged with i.v. placebo. After i.v. thiamine, TPPE decreased (11.7% +/- 6.5% to 5.4% +/- 3.2%; P < 0.01). LVEF increased (0.28 +/- 0.11 to 0.32 +/- 0.09; P < 0.05), as did diuresis (1,731 +/- 800 mL/d to 2,389 +/- 752 mL/d; P < 0.02), and sodium excretion (84 +/- 52 mEq/d to 116 +/- 83 mEq/d, P < 0.05). In the 27 patients completing the full 7-week intervention, LVEF rose by 22% (0.27 +/- 0.10 to 0.33 +/- 0.11, P < 0.01).nnnCONCLUSIONSnThiamine repletion can improve left ventricular function and biochemical evidence of thiamine deficiency in some patients with moderate-to-severe CHF who are receiving longterm furosemide therapy.

Prognostic significance of mild mitral regurgitation by color Doppler echocardiography in acute myocardial infarction

Mitral regurgitation (MR) complicating acute myocardial infarction (AMI) is associated with increased mortality. The prognostic significance of only mild MR detected by echocardiography in patients with AMI is unknown. This study assessed the long-term risk associated with mild MR detected by color Doppler echocardiography within the first 48 hours of admission in 417 consecutive patients with AMI. No MR was detected in 271 patients (65%), mild MR was seen in 121 patients (29%), and moderate or severe MR was noted in 25 patients (6%). One-year mortality rates were 4.8%, 12.4%, and 24%, respectively (p<0.001). Multivariate analysis revealed that mild MR was independently associated with increased 1-year mortality (p<0.05) after adjustment for age, gender, previous myocardial infarction, diabetes mellitus, systemic hypertension, Killip grade > or =2 on admission, and left ventricular ejection fraction < or =40%. The hazard ratio for 1-year mortality was 2.31 (95% confidence interval 1.03 to 5.20) for mild MR and 2.85 (95% confidence interval 0.95 to 8.51) for moderate or severe MR. Thus, mild MR detected by color Doppler echocardiography within the first 2 days of admission in patients with AMI is a significant independent risk predictor for 1-year all-cause mortality.

Does external ultrasound accelerate thrombolysis? Results from a rabbit model.

BACKGROUNDnPrior in vitro and in vivo studies have reported that external ultrasound accelerates thrombolysis at intensities too low to have a direct effect on clot dissolution in the absence of a thrombolytic agent. The present study was undertaken to examine the ultrasound effect on thrombolysis and reocclusion in a rabbit thrombosis model.nnnMETHODS AND RESULTSnBlood clots were produced in a femoral artery segment with endothelial damage and distal stenosis. Recombinant tissue-type plasminogen activator (rTPA) was infused at 30 micrograms.kg-1.min-1 for 60 minutes. Femoral artery flow was measured every 5 minutes for 2 hours. Rabbits were randomized to four groups with continuous wave ultrasound on or off with or without intravenous injection of 17 mg/kg aspirin (+US/-US/+Asp/-Asp). Ultrasound frequency and intensity were 1 MHz and 6.3 W/cm2. In seven of eight and five of five rabbits given rTPA and -US/-Asp or -US/+Asp, respectively, reflow was observed, persisting to the end of the observation period. In five of nine and four of five rabbits given rTPA and +US/-Asp or +US/+Asp, reflow was achieved, but persistent reocclusion was subsequently observed in five of five and two of four of these rabbits, respectively. Overall, femoral artery patency was worse and reocclusion occurred more often when ultrasound was added to rTPA (P = .002 by nonparametric ANOVA). However, initial reflow occurred more rapidly with ultrasound exposure (21 +/- 10 and 33 +/- 6 minutes for the +US/+Asp and +US/-Asp groups, respectively) compared with without ultrasound (46 +/- 13 and 74 +/- 14 minutes for the -US/+Asp and -US/-Asp groups, respectively) (P = .03 by ANOVA).nnnCONCLUSIONSnAlthough time to initial reflow was shortened by ultrasound, it was associated with less reperfusion and more reocclusion in this model. A possible explanation for these results is ultrasound-induced platelet activation counterbalancing its thrombolysis-accelerating effect.

Impact of Atrioventricular Compliance on Pulmonary Artery Pressure in Mitral Stenosis An Exercise Echocardiographic Study

BackgroundThe decay of the pressure gradient across a stenotic mitral valve is determined by the size of the orifice and net AV compliance (Cn). We have observed a group of symptomatic patients, usually in sinus rhythm, characterized by pulmonary hypertension (particularly during exercise) despite a relatively large mitral valve area by pressure half-time. We speculated that this discrepancy was due to low atrial compliance causing both pulmonary hypertension and a steep decay of the transmitral pressure gradient despite significant stenosis. We therefore tested the hypothesis that Cn is an important physiological determinant of pulmonary artery pressure at rest and during exercise in mitral stenosis. Methods and ResultsTwenty patients with mitral stenosis were examined by Doppler echocardiography. Cn, calculated from the ratio of effective mitral valve area (continuity equation) and the E-wave downslope, ranged from 1.7 to 8.1 mL/mm Hg. Systolic pulmonary artery pressure (PAP) increased from 43±12 mm Hg at rest to 71±23 mm Hg (range, 40 to 110 mm Hg) during exercise. There was a particularly close correlation between Cn and exercise PAP (r =−0.85). Patients with a low compliance were more symptomatic (P <0.025). Catheter- and Doppler-derived values for Cn, determined in 10 cases, correlated well (r =0.79). ConclusionsCn, which can be noninvasively assessed, is an important physiological determinant of PAP in mitral stenosis. Patients with low Cn represent an important clinical entity, with symptoms corresponding to severe increases in PAP during stress echocardiography.

Shortened Doppler-derived mitral A wave deceleration time: an important predictor of elevated left ventricular filling pressure.

OBJECTIVESnThe aim of this study was to investigate whether a new variable of mitral inflow, A wave deceleration time, identifies patients with elevated left ventricular filling pressures.nnnBACKGROUNDnIn patients with an elevated left ventricular end-diastolic pressure, the increase in left ventricular pressure after atrial contraction rapidly exceeds left atrial pressure, resulting in abrupt cessation of the A wave. Therefore, we postulated that a shortening of A wave deceleration time might be a marker for elevated end-diastolic pressure.nnnMETHODSnAdequate pulsed Doppler mitral inflow velocities could be recorded in 40 of 44 consecutive patients undergoing cardiac catheterization with capillary wedge pressure in 20 patients, and within 1 h after left ventricular end-diastolic pressure recording in 20. Fifteen healthy volunteers were also studied.nnnRESULTSnLeft ventricular end-diastolic pressure was 8 to 35 mm Hg, and mean pulmonary wedge pressure was 6 to 37 mm Hg. Close correlations were found between A wave deceleration time and mean pulmonary wedge pressure (r = -0.87) and left ventricular end-diastolic pressure (r = -0.74). There were modest correlations between both pressures and peak E/A, E wave deceleration time and A wave duration, respectively; r = 0.59, -0.30 and -0.58 for capillary wedge and r = 0.25, -0.38 and -0.49 for end-diastolic pressures. A wave deceleration time </= 60 ms predicted left ventricular end-diastolic and mean pulmonary wedge pressures > 18 mm Hg, respectively, with a sensitivity of 67% and 89% and specificity of 100% for both.nnnCONCLUSIONSnA shortened Doppler mitral inflow A wave deceleration time is a useful index of elevated left ventricular filling pressure.

Effect of thrombolytic therapy on the evolution of significant mitral regurgitation in patients with a first inferior myocardial infarction.

OBJECTIVESnThis study was designed to test the hypothesis that reperfusion therapy with thrombolysis will prevent the development of significant mitral regurgitation in patients with inferior myocardial infarction.nnnBACKGROUNDnThe value of thrombolytic therapy in patients with inferior or posterior wall myocardial infarction has been controversial. We hypothesized that successful reperfusion therapy with intravenous thrombolysis may reduce the incidence and severity of postinfarction mitral regurgitation in this patient group.nnnMETHODSnWe prospectively studied 104 patients with a first inferior myocardial infarction. Thrombolytic therapy was administered to 55 patients (treatment group) 3.2 +/- 2.1 h after the onset of symptoms. The other 49 patients formed the control group. Doppler echocardiographic color flow imaging was performed in all patients within 24 h, at 7 to 10 days and at 28 to 30 days after myocardial infarction. Significant mitral regurgitation was defined as moderate or severe (grade 2 or 3).nnnRESULTSnNo significant differences in baseline clinical characteristics were observed between the treatment and control groups. The overall incidence rates of significant mitral regurgitation at 24 h, 7 to 10 days and at 28 to 30 days were 10 (10%) of 104 patients, 18 (17%) of 104 patients and 11 (11%) of 100 patients, respectively. Multivariate analysis reveals the following independent predictors of the occurrence of significant mitral regurgitation: female gender (at 7 to 10 days, odds ratio 5.3, 90% confidence interval [CI] 1.8 to 15.5; at 28 to 30 days, odds ratio 3.7, 90% CI 1.1 to 12.7), heart failure (at 7 to 10 days, odds ratio 7.7, 90% CI 2.2 to 26.9) and transient complete atrioventricular block (at 24 h of myocardial infarction, odds ratio 5.8, 90% CI 1.2 to 27). Compared with the control group, the treatment group exhibited marked reduction in the incidence of significant mitral regurgitation at 24 h (16% vs. 4%; odds ratio 0.1, 90% CI 0.0 to 0.7); at 7 to 10 days (24% vs. 11%; odds ratio 0.3, 90% CI 0.1 to 0.9) and at 28 to 30 days (15% vs. 7%; odds ratio 0.4, 90% CI 0.1 to 1.6). Severe (grade 3) mitral regurgitation developed in five patients in the control group but in no patient in the treatment group.nnnCONCLUSIONSnThrombolytic therapy in the patients with a first inferior myocardial infarction was associated with a reduced incidence of significant mitral regurgitation. These results support the use of such therapy in patients with inferior myocardial infarction.

Automatic assessment of cardiac function from short-axis MRI : Procedure and clinical evaluation

Cardiac magnetic resonance imaging (MRI) provides a wealth of morphological and physiological information. Automatic extraction of this information is possible by implementing various image processing techniques. However, existing procedures mostly rely on extensive human interaction and are seldom evaluated on a clinical scale. In this study, a nearly automatic process that extracts physiological parameters from cardiac MR images has been both developed and clinically evaluated. Raw images were obtained in the short-axis view and acquired by a gradient-cho (GE) protocol. In images selected to be analyzed, the only manual step required is the indication of a point in the center of the left ventricle (LV). From a set of such images, the process extracts endocardial and epicardial contours and calculates left ventricular volumes, mass and ejection fraction (EF). The process implements novel approaches to image processing techniques such as thresholding and shape extraction and can be adapted to other acquisition protocols. The process has demonstrated a clear potential for accurate extraction of the endocardial contour but a lower one with respect to the epicardial contour as a result of the low contrast between myocardium and some surrounding tissues, generated by the gradient-echo protocol. The ability of the process to asses physiological parameters has been subjected to a systematic clinical evaluation, which compared parameters, derived manually and automatically, in 10 healthy subjects and 10 patients. The evaluation has indicated that although individual volumes and mass were not accurately assessed, the automatic process has shown high potential for assessing the ejection fraction with relatively high accuracy and reliability.

Two-dimensional echocardiographic analysis of proximal left main coronary artery in humans

The left main coronary artery (LMCA) was evaluated in 100 consecutive patients (88 men and 12 women; mean age 63 years) with anginal syndrome, all in New York Heart Association classes II and III. Each patient underwent two-dimensional echocardiography (2DE) from the parasternal short-axis and apical four-chamber views. Coronary angiography was subsequently performed within 24 hours. The LMCA was directly measured by 2DE and coronary angiography at its widest point. Each echocardiogram was blindly evaluated for LMCA aneurysm or obstruction. Eight patients (8%) were excluded because of inadequate visualization of the LMCA. The mean 2DE measurement was 4.4 +/- 0.9 mm vs 4.2 +/- 0.8 mm on coronary angiography (r = 0.86). Atherosclerotic aneurysms of the LMCA were correctly diagnosed in two patients by 2DE. LMCA stenosis (greater than 50%) was found in 11 patients on coronary angiography; three of them had ostial or proximal lesions, three had middle lesions, and five had distal lesions. 2DE correctly diagnosed all three ostial lesions, two of three middle lesions, but only two of five distal lesions. In four patients, dense echoes in the LMCA caused a false positive diagnosis. It was concluded that: the LMCA can be visualized and correctly measured by 2DE; atherosclerotic aneurysms can be detected; and 2DE is yet unable to screen patients for LMCA lesions; however, 2DE is a promising method for evaluating proximal and especially ostial LMCA stenosis.