Effects of angiotensin-converting enzyme inhibitor plus irbesartan on maximal and submaximal exercise capacity and neurohumoral activation in patients with congestive heart failure

Blanchet, Martine; Sheppard, Richard; Racine, Normand; Ducharme, Anique; Curnier, Daniel; Tardif, Jean‐Claude; Sirois, Pierré; Lamoureux, Marie-Catherine; Champlain, Jacques de; White, Michel

doi:10.1016/j.ahj.2004.11.011

Cited by 15 publications

(8 citation statements)

References 21 publications

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“…The clinical significance of this may have become apparent in a recent study, where patients with congestive heart failure were exercise tested before and after 6 months add‐on therapy with an AT 1 receptor blocker or placebo. The submaximal exercise capacity was improved by 26% in the active treatment arm, compared to only 7% in the placebo arm (Blanchet et al 2005). Based on such findings and the current data, it is tempting to speculate that attenuated exercise angiotensinolysis may be a potential novel mechanism by which skeletal muscle blood flow is limited during demanding exercise in heart failure patients.…”

Section: Discussionmentioning

confidence: 99%

Exercise‐induced inhibition of angiotensin II vasoconstriction in human thigh muscle

Haslund¹,

Wray

Raven

et al. 2006

The Journal of Physiology

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It is well established that metabolic inhibition of adrenergic vasoconstriction contributes to the maintenance of adequate perfusion to exercising skeletal muscle. However, little is known regarding nonadrenergic vasoconstriction during exercise. We tested the hypothesis that a non-adrenergic vasoconstrictor, angiotensin II (AngII), would be less sensitive to metabolic inhibition than an α 1 -agonist, phenylephrine (PE), in the exercising human thigh. In 11 healthy men, femoral blood flow (FBF, ultrasound Doppler and thermodilution) and blood pressure were evaluated during wide-ranging doses of intra-arterial (femoral) infusions of PE and AngII at rest and during two workloads of steady-state knee-extensor exercise (7 W and 27 W). At rest, the maximal decrease in femoral artery diameter (FAD) during AngII (9.0 ± 0.2 to 8.4 ± 0.4 mm) was markedly less than during PE (9.0 ± 0.3 to 5.7 ± 0.5 mm), whereas maximal reductions in FBF and femoral vascular conductance (FVC) were similar during AngII (FBF: −65 ± 6 and FVC: −66 ± 6%) and PE (−57 ± 5 and −59 ± 4%). During exercise, FAD was not changed by AngII, but moderately decreased by PE. The maximal reductions in FBF and FVC were blunted during exercise compared to rest for both AngII (7 W: −28 ± 5 and −40 ± 5%; 27 W: −15 ± 4% and −29 ± 5%) and PE (7 W: −30 ± 4 and −37 ± 6%; 27 W: −15 ± 2 and −24 ± 6%), with no significant differences between drugs. The major new findings are (1) an exercise-induced intensity-dependent metabolic attenuation of non-adrenergic vasoconstriction in the human leg; and (2) functional evidence that AngII-vasoconstriction is predominantly distal, whereas α 1 -vasoconstriction is proximal and distal within the muscle vascular bed of the human thigh.

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Section: Discussionmentioning

confidence: 99%

Exercise‐induced inhibition of angiotensin II vasoconstriction in human thigh muscle

Haslund¹,

Wray

Raven

et al. 2006

The Journal of Physiology

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“…The submaximal constant load exercise test was performed on a treadmill using a fixed load protocol at an intensity corresponding to 75% of peak VO 2 measured during the maximal exercise test. 19 After a 2 min warm‐up at 30% of the maximal load, the slope and speed observed at 75% of the VO 2 peak was applied. The test was terminated for exhaustion or after 30 min of exercise.…”

Section: Methodsmentioning

confidence: 99%

Right ventricular function and its coupling to pulmonary circulation predicts exercise tolerance in systolic heart failure

et al. 2021

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Aims Right ventricular (RV) dysfunction, pulmonary hypertension, and exercise intolerance have prognostic values, but their interrelation is not fully understood. We investigated how RV function alone and its coupling with pulmonary circulation (RV‐PA) predict cardio‐respiratory fitness in patients with heart failure and reduced ejection fraction (HFrEF). Methods and results The Evaluation of Resynchronization Therapy for Heart Failure (EARTH) study included 205 HFrEF patients with narrow (n = 85) and prolonged (n = 120) QRS duration undergoing implantable cardioverter defibrillator implantation. All patients underwent a comprehensive evaluation with exercise tolerance tests and echocardiography. We investigated the correlations at baseline between RV parameters {size, function [tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RV‐FAC), and RV myocardial performance index (RV‐MPI)], pulmonary artery systolic pressure (PASP), and tricuspid regurgitation}; left ventricular ejection fraction (LVEF), left ventricular end‐diastolic volume index (LVEDVi), and left atrial volume index (LAVi); and cardiopulmonary exercise test (CPET) [peak VO2, minute ventilation/carbon dioxide production (VE/VCO2), 6 min walk distance (6MWD), and submaximal exercise duration (SED)]. We also studied the relationship between RV‐PA coupling (TAPSE/PASP ratio) and echocardiographic parameters in patients with both data available. Univariate and multivariate linear regression models were used. Patients enrolled in EARTH (overall population) were mostly male (73.2%), mean age 61.0 ± 9.8 years, New York Heart Association class II–III (87.8%), mean LVEF of 26.6 ± 7.7%, and reduced peak VO2 (15.1 ± 4.6 mL/kg/min). Of these, 100 had both TAPSE and PASP available (TAPSE/PASP population): they exhibited higher BNP, wider QRS duration, larger LVEDVi, with more having tricuspid regurgitation compared with the 105 patients for whom these values were not available (all P < 0.05). RV‐FAC (β = 7.5), LAVi (β = −0.1), and sex (female, β = −1.9) predicted peak VO2 in the overall population (all P = 0.01). When available, TAPSE/PASP ratio was the only echocardiographic parameter associated with peak VO2 (β = 6.8; P < 0.01), a threshold ≤0.45 predicting a peak VO2 ≤ 14 mL/kg/min (0.39 for VO2 ≤ 12). RV‐MPI was the only echocardiographic parameter associated with ventilatory inefficiency (VE/VCO2) and 6MWD (β = 21.9 and β = −69.3, respectively, both P ≤ 0.01) in the overall population. In presence of TAPSE/PASP, it became an important predictor for those two CPET (β = −18.0 and β = 72.4, respectively, both P < 0.01), together with RV‐MPI (β = 18.5, P < 0.01) for VE/VCO2. Tricuspid regurgitation predicted SED (β = −3.2, P = 0.03). Conclusions Right ventricular function assessed by echocardiography (RV‐MPI and RV‐FAC) is closely associated with exercise tolerance in patients with HFrEF. When the TAPSE/PASP ratio is available, this marker of RV‐PA coupling becomes the stronger echocardiographic predictor of exercise capacity ...

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“…UAL SUPPRESSION OF THE renin angiotensin aldosterone system with combination therapy that includes angiotensin II type I receptor blockers (ARBs) and angiotensin-converting enzyme (ACE) inhibitors is gaining interest among heart failure (HF) experts. [1][2][3][4][5][6][7][8][9][10][11][12][13] However, current guidelines for recommended pharmacotherapy in patients with HF have not endorsed this approach. 14,15 This strategy could be very important given the continuing high mortality and morbidity among patients with HF.…”

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confidence: 99%

Adverse Effects of Combination Angiotensin II Receptor Blockers Plus Angiotensin-Converting Enzyme Inhibitors for Left Ventricular Dysfunction

Phillips¹,

Kashani²,

Ko³

et al. 2007

Arch Intern Med

173

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Background : We performed a meta-analysis of randomized controlled trials to assess ongoing concerns about the safety profile of combination angiotensin II receptor blockers (ARBs) plus angiotensin-converting enzyme (ACE) inhibitors in symptomatic left ventricular dysfunction.Methods: MEDLINE (January 1966-December 2006 and Web sites for the National Institute of Health Clinical Trials and the Food and Drug Administration were searched for eligible RCTs that included 500 or more subjects, had a follow-up of 3 months or longer, and reported adverse effects. We used a random effects model to calculate the relative risk (RR) and 95% confidence interval (CI) for the following outcome measures: medication discontinuations because of adverse effects, worsening renal function (an increase in serum creatinine level of Ͼ0.5 mg/dL [to convert to micromoles per liter, multiply by 88.4]), hyperkalemia (serum potassium level Ͼ5.5 mEq/L [to convert to millimoles per liter, multiply by 1]), and symptomatic hypotension.Results: Four studies (N=17 337; mean follow-up, 25 months [range, 11-41 months]) were selected. Combination ARB plus ACE inhibitor vs control treatment that included ACE inhibitors was associated with significant increases in medication discontinuations because of adverse effects in patients with chronic heart failure (RR, 1.38 [95% CI, 1.22-1.55]) or in patients with acute myocardial infarction with symptomatic left ventricular dysfunction (RR, 1.17 [95% CI, 1.03-1.34]), and for both conditions there were significant increases in worsening renal function (RR, 2.17 [95% CI,] and RR, 1.61 [95% CI, 1.31-1.98], respectively), hyperkalemia (RR, 4.87 [95% CI,.94] and RR, 1.33 [95% CI, 0.90-1.98], respectively; the latter was not significant), and symptomatic hypotension (RR, 1.50 [95% CI, 1.09-2.07], and RR, 1.48 [95% CI, 1.33-3.18], respectively). Conclusion:Combination ARB plus ACE inhibitor therapy in subjects with symptomatic left ventricular dysfunction was accompanied by marked increases in adverse effects.

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Effects of angiotensin-converting enzyme inhibitor plus irbesartan on maximal and submaximal exercise capacity and neurohumoral activation in patients with congestive heart failure

Cited by 15 publications

References 21 publications

Exercise‐induced inhibition of angiotensin II vasoconstriction in human thigh muscle

Exercise‐induced inhibition of angiotensin II vasoconstriction in human thigh muscle

Right ventricular function and its coupling to pulmonary circulation predicts exercise tolerance in systolic heart failure

Adverse Effects of Combination Angiotensin II Receptor Blockers Plus Angiotensin-Converting Enzyme Inhibitors for Left Ventricular Dysfunction

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