Pilot Study to Assess the Influence of β-Blockade on Mitral Regurgitant Volume and Left Ventricular Work in Degenerative Mitral Valve Disease

Stewart, Ralph; Raffel, Corey; Kerr, Andrew; Gabriel, Ruvin; Zeng, Irene; Young, Alistair A.; Cowan, Brett R.

doi:10.1161/circulationaha.108.770438

Cited by 27 publications

(37 citation statements)

References 35 publications

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“…In this study, carvedilol (a nonselective adrenergic receptor antagonist) was used because it has beneficial effects of reducing heart rate and afterload, as well as improving myocardial contractility and LVEF, in congestive heart failure. 28 Similar to previous findings, 11,12 heart rate and blood pressure decreased in the β-blockade group in the current study. Rats with organic MR tolerated carvedilol well at the early stages of MR.…”

Section: Differences In β-Blockerssupporting

confidence: 91%

“…Increase in forward stroke volume was associated with a reduction in blood pressure. 12 This study, however, showed that nonselective β-blockade had no beneficial effect on LV remodeling in a rat model of chronic organic MR. In contrast, β-blockade seemed to accelerate the progression of LV remodeling and was associated with worsened LV function with long-term treatment.…”

Section: β-Blockade In Chronic Organic Mrmentioning

confidence: 69%

“…13 However, the effect of β-blockade on LV remodeling in chronic organic MR is uncertain and seems to be different from that on LV function. No prior studies have demonstrated beneficial effects of β-blockade on LV remodeling in organic MR. 12,13 Therefore, the dissociation between a reported improvement in LV function (LVEF) and a lack of effect on LV remodeling in chronic organic MR treated with β-blockers requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

“…Animal studies have shown that β-blockade could improve LV systolic function in chronic MR. [9][10][11] Recent clinical studies have also shown that β1-blockade may improve LV systolic function in chronic organic MR, but a beneficial effect on LV remodeling is uncertain. 12,13 There have been no studies yet demonstrating that β-blockade improves LV remodeling in chronic organic MR. Furthermore, a dissociation between adverse LV remodeling and improvement in cardiac myocyte contractility in experimental MR treated with β-blockers has been reported.…”

Section: Editorial See P 624 Clinical Perspective On P 762mentioning

confidence: 99%

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Effects of Early, Late, and Long-term Nonselective β-Blockade on Left Ventricular Remodeling, Function, and Survival in Chronic Organic Mitral Regurgitation

Gao

et al. 2013

Circ: Heart Failure

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Background-Mitral regurgitation (MR) produces sympathetic nervous system activation which is detrimental in other causes of heart failure. However, whether β-blockade is beneficial in MR has not been determined. Methods and Results-Eighty-seven rats with significant organic MR were randomized to the β-blockade group (n=43) or the control group (n=44). Carvedilol was started in week 2 post MR induction and given for 23 to 35 weeks in the β-blockade group. Echocardiography was performed at baseline and at weeks 2, 6, 12, 24, 30, and 36 after MR induction. After 23 weeks of β-blockade, heart rates were significantly reduced by carvedilol (308±25 versus 351±31 beats per minute; P<0.001). Left ventricular end-diastolic (2.2±0.7 versus 1.59±0.6 mL; P<0.001), end-systolic volumes (0.72±0.42 versus 0.40±0.19 mL; P<0.001), and mass index (2.40±0.55 versus 2.06±0.62 g/kg; P<0.001) were significantly higher, and left ventricular fraction shortening (33±7% versus 38±7%; P<0.001) and ejection fraction (69±11% versus 75±7%; P<0.001) were significantly lower in the β-blockade group than in the control group. Systolic blood pressure was lower in the β-blockade group than in the control group (114±10 versus 93±12 mm Hg; P<0.005). Survival probability was significantly lower in the early β-blockade group than in the control group (88% versus 96%; P=0.03). 14 This dissociation creates a possible pathophysiological contradiction because adverse LV remolding is often associated with LV dysfunction and poor long-term outcome in all forms of congestive heart failure. Therefore, it is important to determine whether beneficial effects of β-blockade could be demonstrated if chronic organic MR was treated in the early stages before the development of LV dysfunction and if treatment is long-term. It is also imperative to determine whether LV remodeling associated with β-blocker therapy could ultimately have a negative impact on LV function in chronic organic MR or if the early improvement in LV function and myocardial contractility observed in prior studies could lead to improvement in LV remodeling if treatment was initiated early and long-term. To clarify this important issue, we performed a prospective study to determine the effects of early, late, and long-term β-blockade on LV remodeling, systolic function, and survival in experimental chronic MR. The study design had the following unique characteristics: (1) the study used a unique rat model of chronic MR developed in our laboratory, 15 allowing us to use a large numbers of animals to test the hypothesis; (2) carvedilol (a nonselective β-adrenergic blocking agent with α 1 -blocking activity) was administered early before the development of LV systolic dysfunction; and (3) a long-term treatment strategy was applied. Conclusions-Early Methods Rat Model of MRThe study protocol was approved by the Institution's Animal Care and Use Committee of the Pennsylvania State University College of Medicine (assurance number A3045-01). The study was performed according to the guidelines of the Amer...

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Section: Differences In β-Blockerssupporting

confidence: 91%

Section: β-Blockade In Chronic Organic Mrmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Section: Editorial See P 624 Clinical Perspective On P 762mentioning

confidence: 99%

See 2 more Smart Citations

Effects of Early, Late, and Long-term Nonselective β-Blockade on Left Ventricular Remodeling, Function, and Survival in Chronic Organic Mitral Regurgitation

Gao

et al. 2013

Circ: Heart Failure

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“…Beta-blockade in patients with primary (“organic”) MR has never produced beneficial effects on LV remodeling [11,19]. In contrast, in rats, Pu et al [12] reported that beta-blockers accelerate the progression of LV remodeling with worsening of LV function.…”

Section: Discussionmentioning

confidence: 99%

Impact of Beta-Blockade on Cardiac Events in Patients with Chronic Severe Nonischemic Mitral Regurgitation

et al. 2017

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Objectives: The aim of this study was to examine the impact of beta-blockade on cardiac events among patients with initially asymptomatic chronic severe nonischemic mitral valve regurgitation (MR). Methods: Data from 52 consecutive patients in our prospective natural history study of isolated chronic severe nonischemic MR were assessed post hoc over 19 years to examine the relation of chronic beta-blockade use to subsequent cardiac events (death or indications for mitral valve surgery, MVS). At entry, all patients were free of surgical indications; 9 received beta-blockers. Cardiac event rate differences were analyzed by Kaplan-Meier log rank comparison. Results: During follow-up, cardiac events included sudden death (1), heart failure (8), atrial fibrillation (6), left ventricular dimensions at systole ≥4.5 cm (11), left ventricular ejection fraction <60% (6), right ventricular ejection fraction <35% (2), and a combination of cardiac events (7). The cardiac event risk was 4-fold higher among patients receiving beta-blockers (average annual risk = 60.6%) versus those not receiving beta-blockers (average annual risk = 15.2%; p = 0.001). These effects remained statistically significant (p = 0.005) when analysis was adjusted for other baseline covariates. Conclusions: Beta-blockade appears to confer an increased risk of sudden cardiac death or indications for MVS among patients with chronic severe nonischemic MR. Randomized trials are needed to confirm these findings.

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The Role of Arterial Hypertension in Mitral Valve Regurgitation

et al. 2019

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Purpose of Review To review medical literature for evidence of association between hypertension and mitral regurgitation (MR) and summarize potential favorable effects of antihypertensive drugs on MR natural history and treatment. Recent Findings Hypertension and MR are common diseases affecting a large proportion of the general population. Contemporary evidence suggests that hypertension may worsen the progression and prognosis of MR through augmented mechanical stress and increased regurgitation volume. Renin-angiotensin axis inhibitors, beta-blockers, and vasodilators have been tested in order to prevent or decrease primary or secondary MR. Summary Although antihypertensive agents may improve hemodynamic parameters and left ventricular remodeling in primary MR, there is no strong evidence of benefit on clinical outcomes. On the other hand, a beneficial effect of these drugs on secondary MR is better established. Moreover, there are no studies evaluating a possible benefit of lower blood pressure targets in MR. Randomized controlled trials are warranted to elucidate the precise role of antihypertensive therapy on treatment of MR.

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Pilot Study to Assess the Influence of β-Blockade on Mitral Regurgitant Volume and Left Ventricular Work in Degenerative Mitral Valve Disease

Cited by 27 publications

References 35 publications

Effects of Early, Late, and Long-term Nonselective β-Blockade on Left Ventricular Remodeling, Function, and Survival in Chronic Organic Mitral Regurgitation

Effects of Early, Late, and Long-term Nonselective β-Blockade on Left Ventricular Remodeling, Function, and Survival in Chronic Organic Mitral Regurgitation

Impact of Beta-Blockade on Cardiac Events in Patients with Chronic Severe Nonischemic Mitral Regurgitation

The Role of Arterial Hypertension in Mitral Valve Regurgitation

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