Activation of neurohumoral systems in postinfarction left ventricular dysfunction

Rouleau, Jean L.; Champlain, Jacques de; Klein, M.; Bichet, Daniel G.; Moyé, Lemuel A.; Packer, Milton; Dagenais, Gilles R.; Sussex, Bruce; Arnold, J. Malcolm O.; Sestier, F; Parker, John O.; McEwan, Patricia; Bernstein, Victoria; Cuddy, T. Edward; Lamas, Gervasio A.; Gottlieb, Stephen S.; McCans, John; Nadeau, Christine; Delage, F; Hamm, Peggy; Pfeffer, Marc A.

doi:10.1016/0735-1097(93)90042-y

Cited by 143 publications

(76 citation statements)

References 21 publications

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“…LV remodeling was shown to be regulated by multiple factors, including mechanical, neurohumoral, and therapeutic factors. 16,17 According to stepwise multivariate analysis, administration of MRA as well as infarct size were significant independent predictors of post-infarct remodeling at 1 month. This suggests that therapy with MRA starting just after onset is associated with suppression of ALD extraction and plays a significant role in preventing post-infarct LV remodeling.…”

Section: Mra Effect On Post-infarct LV Remodelingmentioning

confidence: 99%

Immediate Administration of Mineralocorticoid Receptor Antagonist Spironolactone Prevents Post-Infarct Left Ventricular Remodeling Associated With Suppression of a Marker of Myocardial Collagen Synthesis in Patients With First Anterior Acute Myocardial Infarction

et al. 2003

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Background-Aldosterone (ALD) has been shown to stimulate cardiac collagen synthesis and fibroblast proliferation via activation of local mineralocorticoid receptors. In patients with acute myocardial infarction, we demonstrated that ALD was extracted through the infarct heart and extracting ALD-stimulated post-infarct left ventricular (LV) remodeling. Methods and Results-To evaluate the effect of mineralocorticoid receptor antagonist (MRA) spironolactone on post-infarct LV remodeling, 134 patients with first anterior acute myocardial infarction were randomly divided into the MRA (nϭ65) or non-MRA (nϭ69) groups after revascularization. All patients were administered angiotensinconverting enzyme (ACE) inhibitor and study drug just after revascularization. Left ventriculography with contrast medium was performed at the acute stage and after 1 month to evaluate LV remodeling. ALD was measured at aortic root and coronary sinus. There was no difference in the baseline characteristics including infarct size and LV performance between the two groups. However, LV ejection fraction was significantly improved in the MRA group compared with that in the non-MRA group (46.0Ϯ0.6% to 53.2Ϯ0.8% versus 46.5Ϯ0.8% to 51.0Ϯ0.8%, P interaction ϭ0.012). LV end-diastolic volume index was significantly suppressed in the MRA group compared with that in non-MRA group (86.5Ϯ1.0 to 90.6Ϯ2.4 versus 87.5Ϯ1.3 to 106.8Ϯ3.5 mL/m 2 , P interaction ϭ0.002). Transcardiac extraction of ALD through the heart was significantly suppressed in the MRA group (P interaction ϭ0.001), and plasma procollagen type III aminoterminal peptide level, a biochemical marker of fibrosis, was significant lower in the MRA group compared with the non-MRA group (P interaction ϭ0.002). Conclusions-These findings indicate that MRA combined with ACE inhibitor can prevent post-infarct LV remodeling better than ACE inhibitor alone in association with the suppression of a marker of collagen synthesis. (Circulation.

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Section: Mra Effect On Post-infarct LV Remodelingmentioning

confidence: 99%

Immediate Administration of Mineralocorticoid Receptor Antagonist Spironolactone Prevents Post-Infarct Left Ventricular Remodeling Associated With Suppression of a Marker of Myocardial Collagen Synthesis in Patients With First Anterior Acute Myocardial Infarction

et al. 2003

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“…11 Ventricular tachycardia is believed to be due to anisotropic reentry, consequent on slowed impulse propagation velocities through myocardium partially replaced by fibrosis, 10,[12][13][14] which typifies postinfarction remodeling myocardium. In addition, activation of plasma neurohormones after infarction 15 provides a potential electrophysiological substrate for triggering ventricular arrhythmias. 16 ACE inhibitor therapy has been associated with reduced incidence of sudden death after myocardial infarction 17,18 and was used in half of this study population.…”

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confidence: 99%

Left Ventricular Remodeling and Ventricular Arrhythmias After Myocardial Infarction

et al. 2003

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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] Ͼ10/h) was assessed from ambulatory ECG. VT and PVCs Ͼ10/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 Ͼ10/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 Ͼ10/h. The study was underpowered to detect treatment effect of ACE inhibitors and ␤-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.

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“…[1][2][3][4] Plasma levels of neurohumoral factors offer an indication of cardiovascular prognosis 1,4 -6 and may aid risk stratification and choice of therapy. We hypothesized that plasma levels of Ն1 of norepinephrine (NE), the cardiac natriuretic peptides atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), and arginine vasopressin (AVP) would identify patients likely to benefit from treatment with carvedilol.…”

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confidence: 99%

Neurohumoral Prediction of Benefit From Carvedilol in Ischemic Left Ventricular Dysfunction

Richards¹,

Doughty²,

Nicholls³

et al. 1999

Circulation

197

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Background-Plasma neurohormones were analyzed for prediction of adverse outcomes and response to treatment in 415 patients with ischemic left ventricular dysfunction randomly assigned to receive carvedilol or placebo. Methods and Results-Atrial natriuretic peptide, brain natriuretic peptide (BNP), or norepinephrine (NE) levels above the group median were associated with increased mortality rates and heart failure. On multivariate analysis, both BNP and NE interacted with treatment to predict death or heart failure independent of age, New York Heart Association class, and left ventricular ejection fraction. For placebo, supramedian levels of BNP were associated with 3-fold the mortality rate of inframedian levels (20/104; 19% vs 6/99; 6%; PϽ0.01). For carvedilol, mortality rate was comparable in these 2 subgroups (12/109; 11% vs 8/94; 9%; NS). Corresponding rates for heart failure were 29/104 (28%) versus 3/99 (3%; PϽ0.001) for placebo and 16/109 (15%) versus 7/94 (7%; NS) for carvedilol. High NE levels did not predict additional benefit from carvedilol, which significantly reduced heart failure admissions only in those with NE levels below the median (13.1% to 4.0%; PϽ0.01). In the 23% of the study population with supramedian BNP but inframedian levels of NE, carvedilol reduced hospital admission with heart failure by Ͼ90% (PϽ0.001). Conclusions-Carvedilol reduced mortality rates and heart failure in those with higher pretreatment BNP levels but lesser activation of plasma NE. Neurohumoral profiling may guide introduction of ␤-blockade in heart failure. (Circulation. 1999;99:786-792.)

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Activation of neurohumoral systems in postinfarction left ventricular dysfunction

Abstract: Neurohumoral activation occurs in a significant proportion of patients at the time of hospital discharge after infarction. Which neurohormone is activated and which clinical and laboratory variables determine this activation vary from one neurohormone to another.

Cited by 143 publications

References 21 publications

Immediate Administration of Mineralocorticoid Receptor Antagonist Spironolactone Prevents Post-Infarct Left Ventricular Remodeling Associated With Suppression of a Marker of Myocardial Collagen Synthesis in Patients With First Anterior Acute Myocardial Infarction

Immediate Administration of Mineralocorticoid Receptor Antagonist Spironolactone Prevents Post-Infarct Left Ventricular Remodeling Associated With Suppression of a Marker of Myocardial Collagen Synthesis in Patients With First Anterior Acute Myocardial Infarction

Left Ventricular Remodeling and Ventricular Arrhythmias After Myocardial Infarction

Neurohumoral Prediction of Benefit From Carvedilol in Ischemic Left Ventricular Dysfunction

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