Subsequent Left Ventricular Dilation Research Articles

Sudden killer

Sudden killer

Syndecan-1

Cardiac fibrosis is characterized by net accumulation of extracellular matrix in the myocardium and is an integral component of most cardiac pathological conditions. Fibrotic remodeling of the ventricle has profound consequences on cardiac function. Increased deposition of interstitial collagen in the perimysial space is initially associated with a stiffer ventricle and diastolic dysfunction. At a later stage, accumulation of extracellular matrix proteins in the cardiac interstitium activates proteolytic pathways leading to the development of ventricular dilation and systolic failure. Disturbance of the matrix network in the fibrotic heart may cause systolic dysfunction through several distinct mechanisms. First, loss of fibrillar collagen may impair transduction of cardiomyocyte contraction into myocardial force development resulting in uncoordinated contraction of cardiomyocyte bundles. Second, disruption of key interactions between endomysial matrix proteins (eg, laminin and collagen) and their receptors in cardiomyocytes may promote cardiomyocyte death.1 Finally, fibrosis may result in sliding displacement (slippage) of cardiomyocytes leading to a decrease in the number of muscular layers in the ventricular wall and subsequent left ventricular dilation. Beyond its effects on cardiac function, fibrotic ventricular remodeling also promotes arrhythmogenesis through impaired anisotropic conduction and subsequent generation of reentry circuits. Extensive evidence suggests that hemodynamic overload activates the renin-angiotensin system triggering potent fibrogenic signals that stimulate cardiac fibroblasts and enhance collagen deposition in the myocardium. Angiotensin II, the central effector molecule of the renin-angiotensin system, stimulates fibroblast proliferation and promotes matrix protein synthesis through interactions involving the angiotensin II type 1 receptor. Angiotensin II–induced fibrosis appears to be mediated, at least in part, through activation of transforming growth factor (TGF)-β signaling pathways.2 Angiotensin II upregulates TGF-β …

Feasibility of Biventricular Pacing in Patients With Recent Myocardial Infarction: Impact on Ventricular Remodeling

To test the hypothesis that biventricular pacing after a myocardial infarction with reduced ejection fraction can attenuate left ventricular (LV) remodeling, the authors studied 18 patients (myocardial infarction within 30-45 days, ejection fraction <or=30%, narrow QRS) randomized to biventricular therapy (biventricular therapy + defibrillator) (biventricular group) or implantable cardioverter-defibrillator alone (control group). At 1, 6, and 12 months, there were no differences in functional or clinical parameters (New York Heart Association, quality of life, 6-minute walk). Twelve-month LV volume remained stable in the biventricular group, but increased in the control group (median LV end-diastolic volume increase, 6.5 mL in biventricular vs 35 mL in control; P=.03; median LV end-diastolic volume decrease, 5.5 mL in biventricular vs 30.5-mL increase in control; P=.11). Biventricular therapy also prevented an increase in sphericity index at 12 months (median, -2% in biventricular vs 37% in control; P=.06). Delivery of biventricular therapy early after myocardial infarction appears safe and feasible and may attenuate subsequent LV dilation.

The Doppler myocardial performance index during low-dose dobutamine echocardiography predicts mortality and left ventricular dilation after a first acute myocardial infarction

Myocardial viability can be detected by wall motion analysis during low-dose dobutamine echocardiography (LDDE) after acute myocardial infarction (AMI). However, wall motion analysis describes only left ventricular (LV) systolic reserve. The Doppler myocardial performance index (MPI) is a quantitative measure of combined LV systolic and diastolic function. We hypothesized that an increase (deterioration) in MPI during LDDE, reflecting reduced systolic and diastolic LV reserve, could provide prognostic information beyond conventional systolic wall motion analysis on mortality, morbidity, and LV remodeling after AMI. Low-dose dobutamine echocardiography (10 microg/kg per minute) was performed within 24 hours and echocardiography was repeated 5 days and 1, 3, and 6 months after a first AMI in 162 consecutive patients. Patients were followed for 25 +/- 11 months. End points were all-cause mortality and cardiac events (cardiac death or readmission for heart failure or reinfarction). In 72 (44%) patients, MPI increased during LDDE. This was independently associated with subsequent LV dilation at 6 months of follow-up (beta = .73, P < .0001). An increase in MPI during LDDE was a powerful prognostic indicator and remained a predictor of mortality (HR 1.92, 95% CI 1.36-2.71, P < .0001) and cardiac events (HR 2.45, 95% CI 1.83-3.27, P < .0001) after adjustment for clinical data, indices of LV function at rest, and wall motion analysis during LDDE. Early after AMI, deterioration in MPI during LDDE predicts subsequent LV dilation and provides prognostic information incremental to clinical data, indices of LV function at rest, and conventional stress echocardiographic data.

Effect of antecedent systemic hypertension on subsequent left ventricular dilation after acute myocardial infarction (from the Survival and Ventricular Enlargement trial)

Whether antecedent systemic hypertension influences the risk of subsequent left ventricular (LV) dilation in patients after an acute myocardial infarction with LV systolic dysfunction is unclear. We assessed echocardiographic evidence of ventricular remodeling from baseline (mean ± SD 11 ± 3 days) to 2 years after an acute myocardial infarction in 122 hypertensive (defined as a history of treated hypertension, baseline systolic blood pressure ≥140 or baseline diastolic blood pressure ≥90 mm Hg) and 334 nonhypertensive patients in the Survival and Ventricular Enlargement echocardiographic substudy. Compared with nonhypertensives, baseline heart size, defined as the sum of the average short- and long-axis LV cavity areas, was similar (70.1 ± 11.9 vs 68.8 ± 11.2 cm 2, p = 0.33 at end-diastole; 50.1 ± 11.3 vs 48.8 ± 10.8 cm 2, p = 0.31 at end-systole), but short-axis LV myocardial area (24.7 ± 4.3 vs 25.7 ± 5.0 cm 2, p = 0.043) and wall thickness (1.15 ± 0.16 vs 1.21 ± 0.17 cm, p = 0.004) at end-diastole were greater among hypertensives. The myocardial infarct segment lengths were similar in the 2 groups (p = 0.22). Although LV cavity areas increased significantly in the 2 groups from baseline to 2 years (p ≤0.001), the increase was significantly greater in hypertensives than in nonhypertensives (+5.6 ± 11.5 vs +2.2 ± 10.7 cm 2, p = 0.005 at end-diastole; +6.23 ± 12.75 vs +2.94 ± 11.4 cm 2, p = 0.012 at end-systole). There was no concomitant difference in the change in LV myocardial area or LV wall thickness between the 2 groups (p >0.30). After adjusting for known confounders, antecedent hypertension was associated with a doubling of the risk of LV dilation (50.8% vs 37.7%, odds ratio 2.09, 95% confidence interval 1.27 to 3.45, p = 0.004). This association was not modified by diabetes mellitus, myocardial infarct segment length, or captopril use (all p values for interaction >0.10). We conclude that antecedent hypertension is associated with subsequent LV dilation in patients after acute myocardial infarction with LV systolic dysfunction.

Role of osteopontin in cardiac fibrosis and remodeling in angiotensin II-induced cardiac hypertrophy.

Osteopontin (OPN) is upregulated in several experimental models of cardiac fibrosis and remodeling. However, its direct effects remain unclear. We examined the hypothesis that OPN is important for the development of cardiac fibrosis and remodeling. Moreover, we examined whether the inhibitory effect of eplerenone (Ep), a novel aldosterone receptor antagonist, was mediated through the inhibition of OPN expression against cardiac fibrosis and remodeling. Wild-type (WT) and OPN-deficient mice were treated with angiotensin II (Ang II) for 4 weeks. WT mice receiving Ang II were divided into 2 groups: a control group and an Ep treatment group. Ang II treatment significantly elevated blood pressure and caused cardiac hypertrophy and fibrosis in WT mice. Ep treatment and OPN deficiency could reduce the Ang II-induced elevation of blood pressure and ameliorate the development of cardiac fibrosis, whereas Ep-only treatment abolished the development of cardiac hypertrophy. Most compelling, the reduction of cardiac fibrosis led to an impairment of cardiac systolic function and subsequent left ventricular dilatation in Ang II-treated OPN-deficient mice. These results suggest that OPN has a pivotal role in the development of Ang II-induced cardiac fibrosis and remodeling. Moreover, the effect of Ep on the prevention of cardiac fibrosis, but not cardiac hypertrophy, might be partially mediated through the inhibition of OPN expression.

269 Perfusion-metabolic mismatch in Tl-201 and BMIPP scintigraphic imaging in patients with successful reperfusion after myocardial infarction related to subsequent left-ventricular dilatation

269 Perfusion-metabolic mismatch in Tl-201 and BMIPP scintigraphic imaging in patients with successful reperfusion after myocardial infarction related to subsequent left-ventricular dilatation

Association of Killip class on admission and left ventricular dilatation after myocardial infarction: A closer look into an old clinical classification

Background Early identification of patients in whom left ventricular dilatation is likely to occur may have important therapeutic implications. Thus the purpose of this study was to evaluate the relation between Killip class on admission and subsequent left ventricular dilatation after acute myocardial infarction. Methods and Results We serially evaluated 129 consecutive patients by two-dimensional and Doppler echocardiography on days 1, 2, 3, and 7, at 3 and 6 weeks, and at 3, 6, and 12 months after infarction. Killip class on admission >1 was found in 29 of 129 (22.5%) patients, and they had significantly higher end-systolic and end-diastolic volume indexes and wall motion score index from day 1 onward compared with patients with Killip class 1, whereas ejection fraction was lower during the follow-up period in these patients. Patients with Killip class >1 showed the progressive increase of end-diastolic (68.2 ± 2.99 to 88.0 ± 7.55 ml/m2, p = 0.001) and end-systolic volume indexes (43.9 ± 2.67 to 56.3 ± 6.18 ml/m2, p = 0.004) during the follow-up period, whereas ejection fraction and wall motion score index remained unchanged. In patients with Killip class 1, end-systolic volume index did not change (30.8 ± 1.06 to 33.8 ± 2.15 ml/m2, p = 0.064), ejection fraction increased (49.3% ± 0.99% to 51.8% ± 1.17%, p = 0.027), and wall motion score index decreased (1.50 ± 0.03 to 1.35 ± 0.04, p < 0.001). End-systolic volume index was the major independent correlate of Killip class, followed by history of diabetes and peak creatine kinase level. No association was found between Doppler indexes of diastolic filling and Killip class on admission. Conclusions Killip class >1 on admission is associated with both acute and long-term left ventricular dilatation. On the other hand, Killip class 1 is associated with favorable left ventricular functional indices, and it appears that left ventricular function in these patients may improve over time. Initial end-systolic volume index but not ejection fraction is the major correlate of Killip class. (Am Heart J 1999;137:361-7.)

Can plasma level of brain natriuretic peptide in early phase predict subsequent left ventricular dilatation in myocardial infarction?

Can plasma level of brain natriuretic peptide in early phase predict subsequent left ventricular dilatation in myocardial infarction?

Can Plasma Level of Brain Natriuretic Peptide in Early Phase Predict Subsequent Left Ventricular Dilatation in Myocardial Infarction?

Can Plasma Level of Brain Natriuretic Peptide in Early Phase Predict Subsequent Left Ventricular Dilatation in Myocardial Infarction?

Left ventricular wall motion score as an early predictor of left ventricular dilation and mortality after first anterior infarction treated with thrombolysis

To recognize patients prone to subsequent left ventricular dilation after the acute phase of a myocardial infarction treated with thrombolysis, we studied 233 patients with a first anterior infarction, treated with thrombolysis, with 2-dimensional echocardiography within 12 hours after admission and 3 months later. A wall motion score index (WMSI) and left ventricular volumes were assessed, and enzymatic infarct size was expressed as cumulative alphahydroxybutyrate dehydrogenase determined in the first 72 hours after infarction. Patients who died (17 of 233, 7%) after a mean follow-up of 517 days had a significantly higher acute WMSI (2.1 ± 0.3, mean ± SD) than those who survived (1.9 ± 0.4) (p = 0.006). With use of this cutoff value of 2 for WMSI, ventricles with an acute WMSI ≤2 (62%) showed no increase in end-diastolic volume index (EDVI) or end-systolic volume index (ESVI), whereas ventricles with an acute WMSI >2 (38%) showed a significant increase in ESVI (6.1 ± 12.2 ml/m 2) and in EDVI (10.3 ± 16.6 ml/m 2) in the first 3 months. Using a cutoff value of 1,000 U/L for cumulative alphahydroxybutyrate dehydrogenase, only infarcts with a value of > 1,000 U/L (52%) caused a significant increase in EDVI (10.8 ± 14.3 ml/m 2) and ESVI (6.5 ± 10.0 ml/m 2) in the first 3 months. Thus, acutely assessed WMSI of >2 can readily predict subsequent dilation in patients with a first anterior infarction treated with streptokinase and is a good predictor of mortality. Enzymatic infarct size also is a good predictor of dilation, although not available until 3 days after infarction.

Collateral channels that develop after an acute myocardial infarction prevent subsequent left ventricular dilation

We sought to evaluate the effect of collateral channels that develop late after a first anterior myocardial infarction on left ventricular dilation and function. Collateral channels in an infarct-related artery may develop long after occlusion of the artery. Well visualized collateral channels that appear immediately after a myocardial infarction reduce infarct size and preserve left ventricular function. However, the functional significance of collateral channels that develop late after myocardial infarction has not been evaluated in terms of left ventricular function. We studied 21 patients with a first anterior myocardial infarction and an infarct-related artery that remained totally occluded after reperfusion therapy and did not reopen within 1 month of infarction. No collateral channels were observed during the acute period. Patients were classified into two groups according to the extend of collateral formation 1 month after infarction: group C, patients with well developed collateral channels (n = 11), and group NC, patients with absent or poorly developed collateral channels (n = 10). Infarct size was determined by peak creatine kinase activity and thallium-201 single-photon emission computed tomography. Global and regional left ventricular function and left ventricular volumes were assessed by left ventriculography. These measurements were identical in both groups 1 month after infarction. Left ventricular function was reevaluated after 2.12 +/- 0.79 years (mean +/- SD). There were no significant changes in global and regional left ventricular function between the two groups during the long-term follow-up period. However, the end-diastolic volume index of group NC increased from 71 +/- 14 to 85 +/- 19 ml/m2, whereas that of group C decreased from 64 +/- 18 to 59 +/- 12 ml/m2. This important change during the long-term follow-up period resulted in a significant difference (p = 0.0006) in the end-diastolic volume index between the groups 2 years after onset (p = 0.002), whereas 1 month after infarction the difference was not significant (p = 0.36). A similar pattern was observed for the end-systolic volume index (group C: 38 +/- 16 to 35 +/- 14 ml/m2; group NC: 45 +/- 12 to 58 +/- 18 ml/m2, p = 0.018). The power of the tests to detect the observed differences showing nonsignificant results ranged from 0.05 to 0.38, whereas the power of the tests indicating a significant difference in end-diastolic and end-systolic volume indexes was >0.88. Collateral channels that develop after a myocardial infarction do not reduce the infarct size or prevent left ventricular dilation within 1 month of infarction. In contrast, such collateral channels prevent subsequent ventricular dilation and the deterioration of left ventricular function over 2 years. However, our results may have been biased because of the small number of patients.