Sildenafil Improves Exercise Capacity and Quality of Life in Patients With Systolic Heart Failure and Secondary Pulmonary Hypertension

Lewis, Gregory D.; Shah, Ravi; Shahzad, Khurram; Camuso, Janice; Pappagianopoulos, Paul P.; Hung, Judy; Tawakol, Ahmed; Gerszten, Robert E.; Systrom, David M.; Bloch, Kenneth D.; Semigran, Marc J.

doi:10.1161/circulationaha.107.716373

Cited by 443 publications

(180 citation statements)

References 44 publications

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“…While the effects of longer-term PDE5 inhibition in heart failure are less well known, a recent investigation reported on the effects of 12 weeks of therapy with sildenafil in 34 patients. In addition to hemodynamic changes similar to those described in other studies, sildenafil therapy resulted in improved exercise capacity, improved quality of life and reduction of rehospitalizations [81]. Mechanisms other than pulmonary vasodilatation may be responsible for some of the apparent benefits of PDE5 inhibition in heart failure.…”

Section: Pde5 Inhibitors In Clinical Usesupporting

confidence: 65%

Phosphodiesterase inhibition in heart failure

et al. 2008

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Drugs that inhibit cyclic nucleotide phosphodiesterase activity act to increase intracellular cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) content. In total, 11 families of these enzymes-which differ with respect to affinity for cAMP and cGMP, cellular expression, intracellular localization, and mechanisms of regulation-have been identified. Inhibitors of enzymes in the PDE3 family of cyclic nucleotide phosphodiesterases raise intracellular cAMP content in cardiac and vascular smooth muscle, with inotropic and, to a lesser extent, vasodilatory actions. These drugs have been used for many years in the treatment of patients with heart failure, but their long-term use has generally been shown to increase mortality through mechanisms that remain unclear. More recently, inhibitors of PDE5 cyclic nucleotide phosphodiesterases have been used as cGMP-raising agents in vascular smooth muscle. With respect to cardiovascular disease, there is evidence that these drugs are more efficacious in the pulmonary than in the systemic vasculature, for which reason they are used principally in patients with pulmonary hypertension. Effects attributable to inhibition of myocardial PDE5 activity are less well characterized. New information indicating that enzymes from the PDE1 family of cyclic nucleotide phosphodiesterases constitute the majority of cAMP- and cGMP-hydrolytic activity in human myocardium raises questions as to their role in regulating these signaling pathways in heart failure.

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Section: Pde5 Inhibitors In Clinical Usesupporting

confidence: 65%

Phosphodiesterase inhibition in heart failure

et al. 2008

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“…An elevated mean or diastolic transpulmonary pressure gradient (TPG) provides direct evidence of a precapillary component to group 2 PH 154, 161. The beneficial effect of phosphodiesterase type 5 inhibition (PDE5‐I) in HFrEF provides indirect evidence of a precapillary component to group 2 PH given that PDE5‐I is effective in patients with arterial PH 162, 163, 164…”

Section: Ph Phenotypementioning

confidence: 99%

Clinical Phenotypes in Heart Failure With Preserved Ejection Fraction

Samson

Jaiswal

Ennezat

et al. 2016

JAHA

102

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“…Currently, the use of PAH-specific drugs is not recommended. However, these therapies were not selectively targeted to PVH patients with reactive PH [13,14,15]. Our findings provide indirect evidence that endothelial dysfunction is the mechanism leading to reactive PH.…”

Section: Discussionmentioning

confidence: 84%

Characterization of Pulmonary Venous Hypertension Patients with Reactive Pulmonary Hypertension as Compared to Proportional Pulmonary Hypertension

et al. 2011

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Background: Patients with pulmonary venous hypertension (PVH) secondary to left heart disease can be further classified according to their hemodynamic profile: pulmonary hypertension (PH) in proportion to the pulmonary capillary wedge pressure (PCWP) and PH out of proportion to the PCWP or reactive PH. Currently, there are no measures that enable prediction of the development of reactive PH in patients with left heart disease. Objectives: In this study, we aim to characterize PVH patients with reactive PH as compared to proportional PH in an attempt to create a distinct profile for patients with left heart disease carrying a high risk for the development of reactive PH. Methods: Thirty-three PVH patients with reactive PH and 29 PVH patients with proportional PH were analyzed retrospectively over a 6-year period. Clinical, laboratory, echocardiographic and hemodynamic parameters were noted and compared between subgroups. Results: There was no significant difference between PVH patients with reactive and proportional PH with regard to gender, age (65.91 ± 11.9 vs. 66.69 ± 10.5 years) and body surface area (1.89 ± 0.24 vs. 1.9 ± 0.23 m²). Prevalence of the metabolic syndrome components was similar in both groups. Interestingly, PCWP was similar in both groups, as were the structural and functional parameters of the left heart. Conclusions: PVH patients with reactive PH have a similar profile as patients with proportional PH; consequently, the evolution of reactive PH is unpredictable. Therefore, it is imperative that physicians maintain a high index of suspicion for the development of reactive PH even in the early stage of heart disease.

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Sildenafil Improves Exercise Capacity and Quality of Life in Patients With Systolic Heart Failure and Secondary Pulmonary Hypertension

Cited by 443 publications

References 44 publications

Phosphodiesterase inhibition in heart failure

Phosphodiesterase inhibition in heart failure

Clinical Phenotypes in Heart Failure With Preserved Ejection Fraction

Characterization of Pulmonary Venous Hypertension Patients with Reactive Pulmonary Hypertension as Compared to Proportional Pulmonary Hypertension

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