Ted Plappert

Effect of Cardiac Resynchronization Therapy on Left Ventricular Size and Function in Chronic Heart Failure

Background—Cardiac resynchronization therapy (CRT) has recently emerged as an effective treatment for patients with moderate to severe systolic heart failure and ventricular dyssynchrony. The purpose of the present study was to determine whether improvements in left ventricular (LV) size and function were associated with CRT. Methods and Results—Doppler echocardiograms were obtained at baseline and at 3 and 6 months after therapy in 323 patients enrolled in the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial. Of these, 172 patients were randomized to CRT on and 151 patients to CRT off. Measurements were made of LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, severity of mitral regurgitation (MR), peak transmitral velocities during early (E-wave) and late (A-wave) diastolic filling, and the myocardial performance index. At 6 months, CRT was associated with reduced end-diastolic and end-systolic volumes (both P <0.001), reduced LV mass (P <0.01), increased ejection fraction (P <0.001), reduced MR (P <0.001), and improved myocardial performance index (P <0.001) compared with control. &bgr;-Blocker treatment status did not influence the effect of CRT. Improvements with CRT were greater in patients with a nonischemic versus ischemic cause of heart failure. Conclusions—CRT in patients with moderate-to-severe heart failure who were treated with optimal medical therapy is associated with reverse LV remodeling, improved systolic and diastolic function, and decreased MR. LV remodeling likely contributes to the symptomatic benefits of CRT and may herald improved longer-term survival.

Cardiovascular Death and Left Ventricular Remodeling Two Years After Myocardial Infarction Baseline Predictors and Impact of Long-term Use of Captopril: Information From the Survival and Ventricular Enlargement (SAVE) Trial

BACKGROUND We quantified cardiovascular death and/or left ventricular (LV) dilatation in patients from the SAVE trial to determine whether dilatation continued beyond 1 year, whether ACE inhibitor therapy attenuated late LV dilatation, and whether any baseline descriptors predicted late dilatation. METHODS AND RESULTS Two-dimensional echocardiograms were obtained in 512 patients at 11+/-3 days and 1 and 2 years postinfarction to assess LV size, percentage of the LV that was akinetic/dyskinetic (%AD), and LV shape index. LV function was assessed by radionuclide ejection fraction. Two hundred sixty-three patients (51.4%) sustained cardiovascular death and/or LV diastolic dilatation; 279 (54.5%) had cardiovascular death and/or systolic dilatation. In 373 patients with serial echocardiograms, LV end-diastolic and end-systolic sizes increased progressively from baseline to 2 years (both P<.01). More patients with LV dilatation had a decrease in ejection fraction: 24.8% versus 6.8% (P<.001) (diastole) and 25.7% versus 5.3% (P<.001) (systole). Captopril attenuated diastolic LV dilatation at 2 years (P=.048), but this effect was carried over from the first year of therapy because changes in LV size with captopril beyond 1 year were similar to those with placebo. Predictors of cardiovascular death and/or dilatation were age (P=.023), prior infarction (P<.001), lower ejection fraction (P<.001), angina (P=.007), heart failure (P=.002), LV size (P<.001), and infarct size (%AD) (P<.001). CONCLUSIONS Cardiovascular death and/or LV dilatation occurred in >50% of patients by 2 years. LV dilatation is progressive, associated with chamber distortion and deteriorating function that is unaffected by captopril beyond 1 year.

Right ventricular dysfunction and risk of heart failure and mortality after myocardial infarction.

OBJECTIVES The aim of this study was to determine the prognostic value of right ventricular (RV) function in patients after a myocardial infarction (MI). BACKGROUND Right ventricular function has been shown to predict exercise capacity, autonomic imbalance and survival in patients with advanced heart failure (HF). METHODS Two-dimensional echocardiograms were obtained in 416 patients with left ventricular (LV) dysfunction (ejection fraction [LVEF] < or = 40%) from the Survival And Ventricular Enlargement (SAVE) echocardiographic substudy (mean 11.1 +/- 3.2 days post infarction). Right ventricular function from the apical four-chamber view, assessed as the percent change in the cavity area from end diastole to end systole (fractional area change [FAC]), was related to clinical outcome. RESULTS Right ventricular function correlated only weakly with the LVEF (r = 0.12, p = 0.013). On univariate analyses, the RV FAC was a predictor of mortality, cardiovascular mortality and HF (p < 0.0001 for all) but not recurrent MI. After adjusting for age, gender, diabetes mellitus, hypertension, previous MI, LVEF, infarct size, cigarette smoking and treatment assignment, RV function remained an independent predictor of total mortality, cardiovascular mortality and HF. Each 5% decrease in the RV FAC was associated with a 16% increased odds of cardiovascular mortality (95% confidence interval 4.3% to 29.2%; p = 0.006). CONCLUSIONS Right ventricular function is an independent predictor of death and the development of HF in patients with LV dysfunction after MI.

Sustained Reverse Left Ventricular Structural Remodeling With Cardiac Resynchronization at One Year Is a Function of Etiology Quantitative Doppler Echocardiographic Evidence From the Multicenter InSync Randomized Clinical Evaluation (MIRACLE)

Background— Cardiac resynchronization therapy (CRT) is an effective therapy for patients with moderate to severe heart failure and prolonged QRS duration. The purpose of this study was to determine whether reverse left ventricular (LV) remodeling and symptomatic benefit from CRT were sustained at 12 months, and if so, in what proportion of patients this occurred. Methods and Results— Serial Doppler echocardiograms were obtained at baseline and 6 and 12 months after CRT in 228 patients enrolled in the Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial. Measurements were made of LV end-diastolic (EDV) and end-systolic (ESV) volumes, ejection fraction, LV mass, severity of mitral regurgitation (MR), peak transmitral velocities during early (E wave) and late (A wave) diastolic filling, and myocardial performance index. At both 6 and 12 months, respectively, CRT was associated with reduced LV EDV (P<0.0001 and P=0.007) and LV ESV (P<0.0001 and P<0.0001), improved ejection fraction (P<0.0001 and P<0.0001), regression of LV mass (P=0.012 and P<0.0001), and reduced MR (P<0.0001 and P<0.0001). LV filling time, transmitral E/A ratio, and myocardial performance index all improved at 12 months compared with baseline (P<0.001, P=0.031, and P<0.0001). Reverse LV remodeling with CRT occurred in more patients at 6 than at 12 months (74% versus 60%, respectively; P<0.05) and was greater in patients with a nonischemic than an ischemic etiology. Conclusions— Reverse LV remodeling and symptom benefit with CRT are sustained at 12 months in patients with New York Heart Association class III/IV heart failure but occur to a lesser degree in patients with an ischemic versus a nonischemic etiology, most likely owing to the inexorable progression of ischemic disease.

Left Ventricular Remodeling and Ventricular Arrhythmias After Myocardial Infarction

Background—The relation between left ventricular (LV) remodeling and ventricular arrhythmias after myocardial infarction is poorly documented. We investigated the relations between LV size, hypertrophy, and function and ventricular arrhythmias in 263 patients from the Survival and Ventricular Enlargement (SAVE) study, using quantitative 2D echocardiography and ambulatory ECG monitoring after myocardial infarction. Methods and Results—Transthoracic 2D echocardiograms and arrhythmia monitoring were performed at baseline (mean, 11 days) and 1 and 2 years after infarction. LV size, short-axis muscle (mass) area (LVMA), and function were quantified from 2D echocardiograms. The prevalence of ventricular tachycardia (VT) and frequent ventricular ectopy (premature ventricular contractions [PVCs] >10/h) was assessed from ambulatory ECG. VT and PVCs >10/h occurred in 20% and 29% of patients at baseline, in 22% and 35% at 1 year and 23% and 39% at 2 years, respectively. VT and PVCs >10/h at baseline and 1 and 2 years were significantly related to LV size, LVMA, and function. Furthermore, changes in LV size and function from baseline to 2 years predicted both VT and PVCs >10/h. The study was underpowered to detect treatment effect of ACE inhibitors and &bgr;-adrenergic receptor blockers but did not alter the relations between ventricular arrhythmias, LV size, and function. Conclusions—Quantitative echocardiographic assessment of LV size, LVMA, and function and changes in these measurements over time predict ventricular arrhythmias after infarction. Altered LV architecture and function during postinfarction LV remodeling provide an important substrate for triggering high-grade ventricular arrhythmias.

Cardiac Resynchronization Induces Major Structural and Functional Reverse Remodeling in Patients With New York Heart Association Class I/II Heart Failure

Background— Cardiac resynchronization therapy (CRT) improves LV structure, function, and clinical outcomes in New York Heart Association class III/IV heart failure with prolonged QRS. It is not known whether patients with New York Heart Association class I/II systolic heart failure exhibit left ventricular (LV) reverse remodeling with CRT or whether reverse remodeling is modified by the cause of heart failure. Methods and Results— Six hundred ten patients with New York Heart Association class I/II heart failure, QRS duration ≥120 ms, LV end-diastolic dimension ≥55 mm, and LV ejection fraction ≤40% were randomized to active therapy (CRT on; n=419) or control (CRT off; n=191) for 12 months. Doppler echocardiograms were recorded at baseline, before hospital discharge, and at 6 and 12 months. When CRT was turned on initially, immediate changes occurred in LV volumes and ejection fraction; however, these changes did not correlate with the long-term changes (12 months) in LV end-systolic (r=0.11, P=0.31) or end-diastolic (r=0.10, P=0.38) volume indexes or LV ejection fraction (r=0.07, P=0.72). LV end-diastolic and end-systolic volume indexes decreased in patients with CRT turned on (both P<0.001 compared with CRT off), whereas LV ejection fraction in CRT-on patients increased (P<0.0001 compared with CRT off) from baseline through 12 months. LV mass, mitral regurgitation, and LV diastolic function did not change in either group by 12 months; however, there was a 3-fold greater reduction in LV end-diastolic and end-systolic volume indexes and a 3-fold greater increase in LV ejection fraction in patients with nonischemic causes of heart failure. Conclusions— CRT in patients with New York Heart Association I/II resulted in major structural and functional reverse remodeling at 1 year, with the greatest changes occurring in patients with a nonischemic cause of heart failure. CRT may interrupt the natural disease progression in these patients. Clinical Trial Registration— Clinicaltrials.gov Identifier: NCT00271154.

Ventricular-Arterial Coupling, Remodeling, and Prognosis in Chronic Heart Failure

OBJECTIVES The objective of this study was to compare the physiological determinants of ejection fraction (EF)-ventricular size, contractile function, and ventricular-arterial (VA) interaction-and their associations with clinical outcomes in chronic heart failure (HF). BACKGROUND EF is a potent predictor of HF outcomes, but represents a complex summary measure that integrates several components including left ventricular size, contractile function, and VA coupling. The relative importance of each of these parameters in determining prognosis is unknown. METHODS In 466 participants with chronic systolic HF, we derived quantitative echocardiographic measures of EF: cardiac size (end-diastolic volume [EDV]); contractile function (the end-systolic pressure volume relationship slope [Eessb] and intercept [V0]); and VA coupling (arterial elastance [Ea]/Eessb). We determined the association between these parameters and the following adverse outcomes: 1) the combined endpoint of death, cardiac transplantation, or ventricular assist device (VAD) placement; and 2) cardiac hospitalization. RESULTS Over a median follow-up of 3.4 years, there were 76 deaths, 52 transplantations, 14 VAD placements, and 684 cardiac hospitalizations. EF was independently associated with death, transplantation, and VAD placement (adjusted hazard ratio [HR]: 3.0; 95% confidence interval [CI]: 1.8 to 5.0 comparing third and first tertiles), as were EDV (HR: 2.6; 95% CI: 1.5 to 4.2); V0 (HR: 3.6; 95% CI: 2.1 to 6.1); and Ea/Eessb (HR: 2.1; 95% CI: 1.3 to 3.3). EDV, V0, and Ea/Eessb were also associated with risk of cardiac hospitalization. Eessb was not significantly associated with any adverse outcomes in adjusted analyses. CONCLUSIONS Left ventricular size, V0, and VA coupling are associated with prognosis in systolic HF, but end-systolic elastance (Eessb) is not. Assessment of VA coupling via Ea/Eessb is an additional noninvasively derived metric that can be used to gauge prognosis in human HF.

Changes in Placental Blood Flow in the Normal Human Fetus with Gestational Age

ABSTRACT: We assessed fetoplacental blood volume flow and placental resistance prospectively with Doppler sonog-raphy in 74 normal human fetuses of 19 to 42 wk gestation to determine the changes in placental perfusion with gestational age. Placental blood volume flow was assessed from the umbilical vein as the product of the mean flow velocity integral and the cross-sectional area of the umbil-ical vein. Placental resistance was assessed as the ratio of maximum systolic and minimum diastolic blood flow velocities from an umbilical artery. Umbilical vein blood volume flow increased exponentially (r = 0.86) with gestational age from 19 wk to term, and did not decrease in postdate fetuses. Umbilical vein blood volume flow increased linearly with fetal weight (r = 0.77), although volume flow per unit body weight changed little with gestational age. Umbilical artery velocity ratio decreased progressively, indicating diminishing placental resistance with gestational age, but did not correlate closely with umbilical vein blood volume flow, We submit that fetoplacental blood volume flow can be readily calculated directly from the umbilical vein with Doppler ultrasound and may provide a better index of placental perfusion than the umbilical artery velocity ratio.

Prospective Doppler echocardiographic evaluation of pulmonary artery diastolic pressure in the medical intensive care unit

To test the hypothesis that the noninvasive evaluation of pulmonary regurgitation can provide accurate estimates of pulmonary artery (PA) diastolic pressures and PA wedge pressures, Doppler echocardiographic studies were performed immediately before bedside PA catheterization in 29 medical intensive care unit patients. The characteristic color flow Doppler signal of pulmonary regurgitation was detected in 19 (66%) patients. In 17 of the 29 patients (59%), the gradient between the right ventricle and PA at end-diastole could be calculated from the pulsed-wave Doppler signal of pulmonary regurgitation using the simplified Bernoulli equation. Right atrial pressure was then estimated by examination of the jugular venous pulse or by electronic transduction of the pressure signal from a previously placed central venous catheter. A noninvasive estimate of PA diastolic pressure was made by adding the clinical estimate of right atrial pressure to the end-diastolic pressure gradient across the pulmonary valve. Pulmonary artery catheterization was then performed and stripchart recordings were interpreted by a physician who was unaware of the noninvasively-estimated PA diastolic pressure. The PA diastolic pressure estimated by Doppler echocardiography correlated closely with that found at catheterization (r = 0.94, mean absolute difference 3.3 mm Hg). The noninvasive estimate of PA diastolic pressure also correlated with the PA wedge pressure (r = 0.87, mean absolute difference 3.8 mm Hg). Therefore, in 59% of medical intensive care unit patients, Doppler echocardiographic evaluation of pulmonary regurgitation allowed accurate noninvasive estimation of PA diastolic pressure.

Increased Ascending Aortic Wall Stress in Patients With Bicuspid Aortic Valves

BACKGROUND Patients with bicuspid aortic valves (BAV) are at increased risk of ascending aortic dilatation, dissection, and rupture. We hypothesized that ascending aortic wall stress may be increased in patients with BAV compared with patients with tricuspid aortic valves (TAV). METHODS Twenty patients with BAV and 20 patients with TAV underwent electrocardiogram-gated computed tomographic angiography. Patients were matched for diameter. The thoracic aorta was segmented, reconstructed, and triangulated to create a mesh. Utilizing a uniform pressure load of 120 mm Hg, and isotropic, incompressible, and linear elastic shell elements, finite element analysis was performed to predict 99th percentile wall stress. RESULTS For patients with BAV and TAV, aortic root diameter was 4.0 ± 0.6 cm and 4.0 ± 0.6 cm (p = 0.724), sinotubular junction diameter was 3.6 ± 0.8 cm and 3.6 ± 0.7 cm (p = 0.736), and maximum ascending aortic diameter was 4.0 ± 0.8 cm and 4.1 ± 0.9 cm (p = 0.849), respectively. The mean 99 th percentile wall stress in the BAV group was greater than in the TAV group (0.54 ± 0.06 MPa vs 0.50 ± 0.09 MPa), though this did not reach statistical significance (p = 0.090). When normalized by radius, the 99 th percentile wall stress was greater in the BAV group (0.31 ± 0.06 MPa/cm vs 0.27 ± 0.03 MPa/cm, p = 0.013). CONCLUSIONS Patients with BAV, regardless of aortic diameter, have increased 99 th percentile wall stress in the ascending aorta. Ascending aortic three-dimensional geometry may account in part for the increased propensity to aortic dilatation, rupture, and dissection in patients with BAV.