Hildo J. Lamb

Effect of Posterolateral Scar Tissue on Clinical and Echocardiographic Improvement After Cardiac Resynchronization Therapy

Background— Currently, one third of patients treated with cardiac resynchronization therapy (CRT) do not respond. Nonresponse to CRT may be explained by the presence of scar tissue in the posterolateral left ventricular (LV) segments, which may result in ineffective LV pacing and inadequate LV resynchronization. In the present study, the relationship between transmural posterolateral scar tissue and response to CRT was evaluated. Methods and Results— Forty consecutive patients with end-stage heart failure (NYHA class III/IV), LV ejection fraction ≤35%, QRS duration >120 ms, left bundle-branch block, and chronic coronary artery disease were included. The localization and transmurality of scar tissue were evaluated with contrast-enhanced MRI. Next, LV dyssynchrony was assessed at baseline and immediately after implantation with tissue Doppler imaging. Clinical parameters, LV volumes, and LV ejection fraction were assessed at baseline and at a 6-month follow-up. Fourteen patients (35%) had a transmural (>50% of LV wall thickness) posterolateral scar. In contrast to patients without posterolateral scar tissue, these patients showed a low response rate (14% versus 81%; P<0.05) and did not show improvement in clinical or echocardiographic parameters. In addition, LV dyssynchrony remained unchanged after CRT implantation (84±46 versus 78±41 ms; P=NS). Patients without posterolateral scar tissue and severe baseline dyssynchrony (≥65 ms) showed an excellent response rate of 95% compared with patients with a posterolateral scar and/or absent LV dyssynchrony (11%). Conclusions— CRT does not reduce LV dyssynchrony in patients with transmural scar tissue in the posterolateral LV segments, resulting in clinical and echocardiographic nonresponse to CRT.

Myocardial Steatosis Is an Independent Predictor of Diastolic Dysfunction in Type 2 Diabetes Mellitus

OBJECTIVES The purpose of this study was to compare myocardial triglyceride content and function between patients with uncomplicated type 2 diabetes mellitus (T2DM) and healthy subjects within the same range of age and body mass index (BMI), and to study the associations between myocardial triglyceride content and function. BACKGROUND T2DM is a major risk factor for cardiovascular disease. Increasing evidence is emerging that lipid oversupply to cardiomyocytes plays a role in the development of diabetic cardiomyopathy, by causing lipotoxic injury and myocardial steatosis. METHODS Myocardial triglyceride content and myocardial function were measured in 38 T2DM patients and 28 healthy volunteers in the same range of age and BMI by proton magnetic resonance (MR) spectroscopy and MR imaging, respectively. Myocardial triglyceride content was calculated as a percentage relative to the signal of myocardial water. RESULTS Myocardial triglyceride content was significantly higher in T2DM patients compared with healthy volunteers (0.96 +/- 0.07% vs. 0.65 +/- 0.05%, p < 0.05). Systolic function did not significantly differ between both groups. Indexes of diastolic function, including the ratio of maximal left ventricular early peak filling rate and the maximal left ventricular atrial peak filling rate (E/A) and E peak deceleration, were significantly impaired in T2DM compared with those in healthy subjects (1.08 +/- 0.04 ml/s(2) x 10(-3) vs. 1.24 +/- 0.06 ml/s(2) x 10(-3) and 3.6 +/- 0.2 ml/s(2) x 10(-3) vs. 4.4 +/- 0.3 ml/s(2) x 10(-3), respectively, p < 0.05). Multivariable analysis indicated that myocardial triglyceride content was associated with E/A and E peak deceleration, independently of diabetic state, age, BMI, heart rate, visceral fat, and diastolic blood pressure. CONCLUSIONS Myocardial triglyceride content is increased in uncomplicated T2DM and is associated with impaired left ventricular diastolic function, independently of age, BMI, heart rate, visceral fat, and diastolic blood pressure.

Infarct tissue heterogeneity assessed with contrast-enhanced MRI predicts spontaneous ventricular arrhythmia in patients with ischemic cardiomyopathy and implantable cardioverter-defibrillator.

Background—The relation between infarct tissue heterogeneity on contrast-enhanced MRI and the occurrence of spontaneous ventricular arrhythmia (or sudden cardiac death) is unknown. Therefore, the study purpose was to evaluate the predictive value of infarct tissue heterogeneity assessed with contrast-enhanced MRI on the occurrence of spontaneous ventricular arrhythmia with subsequent implantable cardioverter-defibrillator (ICD) therapy (as surrogate of sudden cardiac death) in patients with previous myocardial infarction. Methods and Results—Ninety-one patients (age, 65±11 years) with previous myocardial infarction scheduled for ICD implantation underwent cine MRI to evaluate left ventricular function and volumes and contrast-enhanced MRI for characterization of scar tissue (infarct gray zone as measure of infarct tissue heterogeneity, infarct core, and total infarct size). Appropriate ICD therapy was documented in 18 patients (20%) during a median follow-up of 8.5 months (interquartile range, 2.1 to 20.3). Multivariable Cox proportional hazards analysis revealed that infarct gray zone was the strongest predictor of the occurrence of spontaneous ventricular arrhythmia with subsequent ICD therapy (hazard ratio, 1.49/10 g; CI, 1.01 to 2.20; &khgr;2=4.0; P=0.04). Conclusions—Infarct tissue heterogeneity on contrast-enhanced MRI is the strongest predictor of spontaneous ventricular arrhythmia with subsequent ICD therapy (as surrogate of sudden cardiac death) among other clinical and MRI variables, that is, total infarct size and left ventricular function and volumes, in patients with previous myocardial infarction.

Diastolic dysfunction is associatedwith altered myocardial metabolism inasymptomatic normotensive patientswith well-controlled type 2 diabetes mellitus

AbstractObjectives: This study evaluated myocardial function in relation to high-energy phosphate (HEP) metabolism in asymptomatic patients with uncomplicated type 2 diabetes mellitus using magneti...

Infarct Tissue Heterogeneity Assessed with Contrast-Enhanced Magnetic Resonance Imaging Predicts Spontaneous Ventricular Arrhythmia in Patients with Ischemic Cardiomyopathy and Implantable Cardioverter-Defibrillator

Background—The relation between infarct tissue heterogeneity on contrast-enhanced MRI and the occurrence of spontaneous ventricular arrhythmia (or sudden cardiac death) is unknown. Therefore, the study purpose was to evaluate the predictive value of infarct tissue heterogeneity assessed with contrast-enhanced MRI on the occurrence of spontaneous ventricular arrhythmia with subsequent implantable cardioverter-defibrillator (ICD) therapy (as surrogate of sudden cardiac death) in patients with previous myocardial infarction. Methods and Results—Ninety-one patients (age, 65±11 years) with previous myocardial infarction scheduled for ICD implantation underwent cine MRI to evaluate left ventricular function and volumes and contrast-enhanced MRI for characterization of scar tissue (infarct gray zone as measure of infarct tissue heterogeneity, infarct core, and total infarct size). Appropriate ICD therapy was documented in 18 patients (20%) during a median follow-up of 8.5 months (interquartile range, 2.1 to 20.3). Multivariable Cox proportional hazards analysis revealed that infarct gray zone was the strongest predictor of the occurrence of spontaneous ventricular arrhythmia with subsequent ICD therapy (hazard ratio, 1.49/10 g; CI, 1.01 to 2.20; &khgr;2=4.0; P=0.04). Conclusions—Infarct tissue heterogeneity on contrast-enhanced MRI is the strongest predictor of spontaneous ventricular arrhythmia with subsequent ICD therapy (as surrogate of sudden cardiac death) among other clinical and MRI variables, that is, total infarct size and left ventricular function and volumes, in patients with previous myocardial infarction.

Comparison between manual and semiautomated analysis of left ventricular volume parameters from short-axis MR images

PURPOSE The goal of this study was to evaluate a newly developed semiautomated contour detection algorithm for the quantitative analysis of cardiovascular MRI. METHOD Left ventricular function parameters derived from automatically detected endocardial and epicardial contours were compared with results derived from manually traced contours in short-axis multislice GRE MRI studies of 10 normal volunteers and 10 infarct patients. RESULTS Compared with manual image analysis, the semiautomated method resulted in the following systematic and random differences (auto-manual; mean +/- SD): end-diastolic volume: -5.5 +/- 9.7 ml; end-systolic volume: -3.6 +/- 6.5 ml; ejection fraction: 1.7 +/- 4.1%; left ventricular mass: 7.3 +/- 20.6 g. Total analysis time for a complete study was reduced from 3-4 h for the manual analysis to < 20 min using semiautomated contour detection. CONCLUSION Global left ventricular function parameters can be obtained with a high degree of accuracy and precision using the present semiautomated contour detection algorithm.

Diastolic Dysfunction in Hypertensive Heart Disease Is Associated With Altered Myocardial Metabolism

BACKGROUND Hypertension is an important clinical problem and is often accompanied by left ventricular (LV) hypertrophy and dysfunction. Whether the myocardial high-energy phosphate (HEP) metabolism is altered in human hypertensive heart disease and whether this is associated with LV dysfunction is not known. METHODS AND RESULTS Eleven patients with hypertension and 13 age-matched healthy subjects were studied with magnetic resonance imaging at rest and with phosphorus-31 magnetic resonance spectroscopy at rest and during high-dose atropine-dobutamine stress. Hypertensive patients showed higher LV mass (98+/-28 g/m2) than healthy control subjects (73+/-13 g/m2, P<0.01). LV filling was impaired in patients, reflected by a decreased peak rate of wall thinning (PRWThn), E/A ratio, early peak filling rate, and early deceleration peak (all P<0. 05), whereas systolic function was still normal. The myocardial phosphocreatine (PCr)/ATP ratio determined in patients at rest (1. 20+/-0.18) and during stress (0.95+/-0.25) was lower than corresponding values obtained from healthy control subjects at rest (1.39+/-0.17, P<0.05) and during stress (1.16+/-0.18, P<0.05). The PCr/ATP ratio correlated significantly with PRWThn (r=-0.55, P<0.01), early deceleration peak (r=-0.56, P<0.01), and with the rate-pressure product (r=-0.53, P<0.001). CONCLUSIONS Myocardial HEP metabolism is altered in patients with hypertensive heart disease. In addition, there is an association between impaired LV diastolic function and altered myocardial HEP metabolism in humans. The level of myocardial PCr/ATP is most likely determined by the level of cardiac work load.

Findings from left ventricular strain and strain rate imaging in asymptomatic patients with type 2 diabetes mellitus

Regional left ventricular (LV) myocardial functional changes in early diabetic cardiomyopathy have not been well documented. LV multidirectional strain and strain rate analyses by 2-dimensional speckle tracking were used to detect subtle myocardial dysfunction in 47 asymptomatic, male patients (age 57 +/- 6 years) with type 2 diabetes mellitus. The results were compared to those from 53 male controls matched by age, body mass index, and body surface area. No differences were found in the LV end-diastolic volume index (40.7 +/- 8.9 vs 44.1 +/- 7.8 ml/m(2), p = NS), end-systolic volume index (16.0 +/- 4.8 vs 17.8 +/- 4.3 ml/m(2), p = NS), ejection fraction (61.0 +/- 5.5% vs 59.8 +/- 5.3%, p = NS). The transmitral E/A (0.95 +/- 0.21 vs 1.12 +/- 0.32, p = 0.007) and pulmonary S/D (1.45 +/- 0.28 vs 1.25 +/- 0.27, p = 0.001) ratios were more impaired in the patients with diabetes mellitus. Importantly, the diabetic patients had impaired longitudinal, but preserved circumferential and radial systolic and diastolic, function. Diabetes mellitus was an independent predictor for longitudinal strain, systolic strain rate and early diastolic strain rate on multiple linear regression analysis (all p <0.001). In conclusion, the LV longitudinal systolic and diastolic function were impaired, but the circumferential and radial functions were preserved in patients with uncomplicated type 2 diabetes mellitus.

Reproducibility of MRI-derived measurements of right ventricular volumes and myocardial mass

Magnetic resonance (MR) imaging has been shown to provide accurate measurements of right ventricular (RV) volumes and myocardial mass. The purpose of this study was to evaluate the reproducibility of MR imaging, which in clinical practice may be as important as its absolute accuracy. The reproducibility of MR imaging measurements of the right ventricle was assessed by analyzing 40 serial functional MR imaging examinations of the right ventricle with variance component analysis. Standard deviations and 95% ranges for change were: for RV myocardial mass, 5.9 and 16 g; and for RV ejection fraction, 6.0% and 16%, respectively. Reproducibility was similar for cine and spin-echo MR imaging. The intraobserver and interobserver errors were especially large, indicating that observer subjectivity is the limiting factor in the interpretation of the MR images. This study suggests that the reproducibility of RV measurements is adequate to detect RV hypertrophy and a low ejection fraction in the individual patient. For accurate follow-up examinations, whereby smaller changes are to be detected, the reproducibility of MR imaging measurements may not be sufficient. More effort is needed to improve the reproducibility of MR imaging measurements.

Prolonged caloric restriction in obese patients with type 2 diabetes mellitus decreases myocardial triglyceride content and improves myocardial function.

OBJECTIVES This study sought to assess the effects of prolonged caloric restriction in obese patients with type 2 diabetes mellitus (T2DM) on myocardial triglyceride (TG) content and myocardial function. BACKGROUND Myocardial TG content is increased in patients with T2DM and may reflect altered myocardial function. It is unknown whether myocardial TG content is influenced during a therapeutic intervention. METHODS Myocardial TG content (magnetic resonance [MR] spectroscopy), myocardial function (MR imaging), plasma hemoglobin A1c, and body mass index (BMI) were measured in 12 obese, insulin-treated T2DM patients before and after a 16-week very-low-calorie diet (VLCD) (450 kcal/day) to achieve substantial weight loss. Insulin was stopped during the VLCD. RESULTS The BMI decreased from 35.6 +/- 1.2 kg/m(2) (baseline, mean +/- SEM) to 27.5 +/- 1.3 kg/m(2) (after the VLCD, p < 0.001) and was associated with an improvement in hemoglobin A1c from 7.9 +/- 0.4% (baseline) to 6.3 +/- 0.3% (after the VLCD, p = 0.006). Myocardial TG content decreased from 0.88 +/- 0.12% to 0.64 +/- 0.14%, respectively (p = 0.019), and was associated with improved diastolic function (reflected by the ratio between the early and atrial filling phase) from 1.02 +/- 0.08 to 1.18 +/- 0.06, respectively (p = 0.019). CONCLUSIONS Prolonged caloric restriction in obese T2DM patients decreases BMI and improves glucoregulation associated with decreased myocardial TG content and improved diastolic heart function. Therefore, myocardial TG stores in obese patients with T2DM are flexible and amendable to therapeutic intervention by caloric restriction.