Impaired Left Ventricular Stroke Volume Reserve During Clinical Dobutamine Stress Predicts Future Episodes of Pulmonary Edema

Charoenpanichkit, Charaslak; Little, William C.; Mandapaka, Sangeeta; Dall’Armellina, Erica; Morgan, Timothy M.; Hamilton, Craig; Hundley, W. Gregory

doi:10.1016/j.jacc.2010.10.019

Cited by 15 publications

(12 citation statements)

References 33 publications

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“…The current study enrolled subjects with an earlier stage of HFpEF, where filling pressures were closer to normal at rest and physical examination evidence of congestion was largely absent. Despite the absence of right-sided structural remodeling, RV systolic and diastolic function were significantly impaired in the HFpEF group, differences that became more evident in the setting of β-stimulation, similar to prior studies evaluating LV-systemic arterial reserve with adrenergic stimulation [9][10][11][12][13] or exercise stress. 36,37 In HFpEF subjects, tricuspid annular s′ increased with dobutamine in relation to afterload reduction from dobutamine rather than an increase in contractility, which would manifest by an upward shift in the s′ versus PA pressure relationship.…”

Section: Rv Dysfunction and Rv-pa Coupling In Hfpefsupporting

confidence: 76%

Enhanced Pulmonary Vasodilator Reserve and Abnormal Right Ventricular

Andersen

Hwang

Kane

et al. 2015

Circ: Heart Failure

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Acute stress responses in the cardiovascular system are mediated predominantly though the autonomic nervous system. 8 Previous studies have shown that LV-systemic arterial responses to β-adrenergic stimulation are depressed in patients with HFpEF. Background-Pulmonary hypertension and right ventricular (RV) dysfunction are common in patients with advanced heart failure with preserved ejection fraction (HFpEF), yet their underlying mechanisms remain poorly understood. We sought to examine RV-pulmonary artery (PA) functional reserve responses and RV-PA coupling at rest and during β-adrenergic stimulation in subjects with earlier stage HFpEF. Methods and Results-In a prospective trial, subjects with HFpEF (n=39) and controls (n=18) underwent comprehensive invasive and noninvasive hemodynamic assessment using high fidelity micromanometer catheters, echocardiography, and expired gas analysis at rest and during dobutamine infusion. HFpEF subjects displayed similar RV structure but significantly impaired RV systolic (lower RV dP/dt max /IP and s′) and diastolic function (higher RV τ) coupled with more severe pulmonary vascular disease, manifest by higher PA pressures, higher PA resistance, and lower PA compliance compared with controls. Dobutamine infusion caused greater pulmonary vasodilation in HFpEF compared with controls, with enhanced reductions in PA resistance, greater increase in PA compliance, and a more negative slope in the PA pressure-flow relationship when compared with controls (all P<0.001). RV-PA coupling analysis revealed that dobutamine improved RV ejection in HFpEF subjects through afterload reduction alone, rather than through enhanced contractility, indicating RV systolic reserve dysfunction. Conclusions-Pulmonary hypertension in early stage HFpEF is related to partially reversible pulmonary vasoconstriction coupled with RV systolic and diastolic dysfunction, even in the absence of RV structural remodeling. Pulmonary vascular tone is more favorably responsive to β-adrenergic stimulation in HFpEF than controls, suggesting a potential role for β-agonists in the treatment of patients with HFpEF and pulmonary hypertension. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01418248.(Circ Heart Fail. 2015;8:542-550.

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Section: Rv Dysfunction and Rv-pa Coupling In Hfpefsupporting

confidence: 76%

Enhanced Pulmonary Vasodilator Reserve and Abnormal Right Ventricular

Andersen

Hwang

Kane

et al. 2015

Circ: Heart Failure

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“…The resting CV stiffness and mobility scores identified in the participants in this study are similar to those reported previously in other populations of elderly individuals (44,45). With regard to cardiac metrics, women exhibited a higher LV ejection fraction (p < .001) and CV stiffness (p = .01).…”

Section: Discussionsupporting

confidence: 86%

“…Several demographic features of the study participants including body mass index, medical history, and CV medication use were similar to those found in other studies evaluating middle-aged and older adults both at risk for or with a diagnosis of compensated CHF (5,(44)(45)(46)(47)(48). There were, however, some differences in our population of 445 individuals relative to these other previously studied populations.…”

Section: Discussionsupporting

confidence: 75%

Increased Cardiovascular Stiffness and Impaired Age-related Functional Status

Andersen¹,

Kritchevsky

Morgan

et al. 2014

GERONA

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Our objective was to determine if increased cardiovascular (CV) stiffness is associated with disability in middle-aged and older adults at risk for congestive heart failure. CV stiffness (brachial pulse pressure/left ventricular stroke volume indexed to body surface area) and total disability (the summed assessment of activities of daily living, mobility, and instrumental activities of daily living) were measured in 445 individuals. A subset of 109 randomly selected individuals also underwent physical function testing. Total disability was associated with CV stiffness (p = .01), driven by an association with mobility (p = .005), but not activities of daily living (p = .13) or instrumental activities of daily living (p = .61). After accounting for age, these correlations remained significant for men (p = .04), but not for women. CV stiffness was also associated with increased 400-m walk time (p = .02). In middle-aged and elderly men at risk for congestive heart failure, CV stiffness is associated with decreased mobility and physical function, and increased overall disability.Key Words: Cardiovascular stiffness-Disability-Congestive heart failure. Decision Editor: Rafael de Cabo, PhDPhysical disability reduces quality of life, increases health care costs (due to increased need for support services), and is an independent predictor of mortality (1,2). Mobility and activities of daily living are necessary for maintaining basic independent functioning in middle-aged and older individuals (3). Therapy targeted to attenuate the factors that promote disability could improve quality of life and prognosis in older individuals. Such therapy could provide a mortality benefit, as it has been shown in the elderly individual that all levels of physical activity are associated with lower risk of incident acute myocardial infarction, stroke, and cardiovascular (CV) mortality (4). Previously, it has been shown that abnormally increased cardiac and aortic stiffness is independently associated with reduced peak exercise capacity in elderly individuals with and without left ventricular (LV) systolic dysfunction and congestive heart failure (CHF) (5-10). We hypothesized that similar to exercise capacity, increased CV stiffness would be associated with increased disability in middleaged and elderly individuals at risk for their first episode of symptomatic CHF. To test this hypothesis, we noninvasively assessed CV stiffness (using CV magnetic resonance or CMR) and disability. Additionally, in a randomly selected subgroup of individuals, we formally measured physical function.

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“…Further, HFpEF is characterized by dramatic deficits in systolic reserve capacity during exercise 7, 14, 16 or β-adrenergic stimulation 17 and impaired systolic reserve is associated with reduction in overall exercise capacity, HF symptom severity and incident pulmonary edema 7, 18 .…”

Section: Hfpef Pathophysiologymentioning

confidence: 99%

PhosphdiesteRasE-5 Inhibition to Improve CLinical Status and EXercise Capacity in Diastolic Heart Failure (RELAX) Trial

Redfield

Borlaug

Lewis

et al. 2012

Circ: Heart Failure

107

110

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Heart failure (HF) with preserved ejection fraction (HFpEF) or “diastolic HF” accounts for approximately half of HF cases. To date, neurohumoral antagonists have failed to show a significant benefit on clinical outcomes in HFpEF. While our understanding of the pathophysiology of HFpEF continues to develop, multiple therapeutic targets have been identified in HFpEF which may be modifiable by augmentation of the intracellular second messenger cyclic guanosine monophosphate (cGMP) via phosphodiesterase-5 inhibition (PDE5I) in HFpEF. The PhosphodiesteRasE-5 Inhibition to Improve CLinical Status And EXercise Capacity in Diastolic Heart Failure (RELAX trial; clinicaltrials.gov NCT00763867) is being conducted within the NHLBI sponsored HF clinical research network and tests the hypothesis that chronic PDE5I (sildenafil® 20 mg tid for 12 weeks followed by 60 mg tid for 12 weeks) improves exercise capacity and clinical status in patients with HFpEF. Here we provide the rationale for RELAX by summarizing the pathophysiologic derangements in HFpEF and the evidence that PDE5I may ameliorate these derangements. The design of the RELAX trial is described and the rationale for the primary endpoint in RELAX (change in peak oxygen consumption) is provided.

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Impaired Left Ventricular Stroke Volume Reserve During Clinical Dobutamine Stress Predicts Future Episodes of Pulmonary Edema

Cited by 15 publications

References 33 publications

Enhanced Pulmonary Vasodilator Reserve and Abnormal Right Ventricular

Enhanced Pulmonary Vasodilator Reserve and Abnormal Right Ventricular

Increased Cardiovascular Stiffness and Impaired Age-related Functional Status

PhosphdiesteRasE-5 Inhibition to Improve CLinical Status and EXercise Capacity in Diastolic Heart Failure (RELAX) Trial

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