Therapeutic potential of phosphodiesterase type 5 inhibitors in heart failure with preserved ejection fraction and combined post- and pre-capillary pulmonary hypertension

Kramer, Tilmann; Dumitrescu, Daniel; Gerhardt, Felix; Orlova, Kristina V.; Freyhaus, Henrik ten; Hellmich, Martin; Baldus, Stephan; Rosenkranz, Stephan

doi:10.1016/j.ijcard.2018.12.078

Cited by 44 publications

(31 citation statements)

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“…These improvements were presumably caused by the effective elimination of high PVR, since there were correlations between the changes in estimated PVR and RV function. Our findings are in accordance with the results of Guazzi M. and colleagues [22] and Kramer T. and colleagues [27], suggesting a long-term sustained role of sildenafil in improving RV contractility and RA due to a reduction in PAP in patients with PH and HFpEF. The significant improvement in RV contractile function in our patients (TAPSE and tricuspid s′ velocity increase) could occur due to both RV afterload reduction and enhanced contractility.…”

Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

“…These patients had very high TPG (on average 26 mmHg) and PVR (on average 7 Wood units), assuming pulmonary vascular disease and supporting the idea that the Cpc-PH phenotype may benefit from therapies targeting pulmonary circulation. More recently, Kramer T et al showed in a retrospective study the beneficial effect of PDE5 inhibitors on 6-min walk distance, functional class, NT-proBNP levels, right ventricular function, and hospitalization rate in 40 hemodynamically precisely characterized patients with HFpEF and Cpc-PH [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

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Phosphodiesterase 5 inhibitor sildenafil in patients with heart failure with preserved ejection fraction and combined pre- and postcapillary pulmonary hypertension: a randomized open-label pilot study

Belyavskiy

Овчинников

Потехина

et al. 2020

BMC Cardiovasc Disord

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Background Heart failure with preserved ejection fraction (HFpEF) is frequently complicated by pulmonary hypertension (PH). A pulmonary vascular contribution could be considered as a substantial therapeutic target in HFpEF and PH and combined pre- and postcapillary PH (Cpc-PH). Methods We enrolled 50 patients with HFpEF and Cpc-PH who were determined by echocardiography to have pulmonary artery systolic pressure (PASP) > 40 mmHg, pulmonary vascular resistance > 3 Wood units, and/or transpulmonary gradient > 15 mmHg. Results The patients were assigned to the phosphodiesterase 5 (PDE5) inhibitor sildenafil group (25 mg TID for 3 months followed by 50 mg TID for 3 months; n = 30) or the control group (n = 20). In the sildenafil group after 6 months, the 6-min walk distance increased by 50 m (95% CI, 36 to 64 m); substantial improvement in NYHA functional class and exercise capacity during diastolic stress test were revealed; decreases in early mitral inflow to mitral annulus relaxation velocities ratio by 2.4 (95% CI, − 3.3 to − 1.4) and PASP by 17.0 mmHg (95% CI, 20.4 to 13.5) were observed; right ventricular systolic function (M-mode tricuspid annular plane systolic excursion) increased by 0.42 cm (95% CI, 0.32 to 0.52 cm; P < 0.01 for all). No changes occurred in the control group. Conclusions In a subset of patients with HFpEF and Cpc-PH assessed by echocardiography, PDE5 inhibition was associated with an improvement in exercise capacity, pulmonary haemodynamic parameters, and right ventricular function. The role of sildenafil needs to be considered in randomized trials in selected patients with HFpEF with invasively confirmed Cpc-PH. Trial registration Russian National Information System of Research, Development and Technology Data of Civilian Usage (NIS, https://rosrid.ru), registration number 01201257849. Registered 20 April 2012. This manuscript adheres to the CONSORT guidelines.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Phosphodiesterase 5 inhibitor sildenafil in patients with heart failure with preserved ejection fraction and combined pre- and postcapillary pulmonary hypertension: a randomized open-label pilot study

Belyavskiy

Овчинников

Потехина

et al. 2020

BMC Cardiovasc Disord

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“… 31 In another retrospective cohort of 40 patients with CHFpEF who were optimally diuresed and tolerated sildenafil for a year, there was again an improvement in 6MWT, N-terminal prohormone of Brain Natriuretic Peptide (NTproBNP), and World Health Organization Functional Class (WHO-FC). 32 …”

Section: Discussionmentioning

confidence: 99%

Targeted therapy with phosphodiesterase 5 inhibitors in patients with pulmonary hypertension due to heart failure and elevated pulmonary vascular resistance: a systematic review

2020

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Pulmonary Hypertension due to left heart disease is the most common type of Pulmonary Hypertension. Morbidity and mortality significantly increase once Pulmonary Hypertension is present. Treatment is aimed toward optimizing the underlying condition. Targeted therapy has been evaluated in small studies with mixed results. The goal of this systematic review is to identify the possible benefit and safety of Phosphodiesterase 5 inhibitors in Pulmonary Hypertension due to left heart disease with elevated pulmonary vascular resistance, diagnosed by right heart catheterization. Electronic searches using MEDLINE/PREMEDLINE, EMBASE, and The Cochrane Library were searched on 21 October 2018. Randomized clinical trials comparing Phosphodiesterase 5 inhibitors versus placebo in patients with proven Pulmonary Hypertension by right heart catheterization secondary to left heart disease (both heart failure with reduced ejection fraction and with preserved ejection fraction) and reported pulmonary vascular resistance were included. We identified 436 potentially relevant studies. After reviewing the titles and abstracts to exclude irrelevant articles, five randomized clinical trials were considered for the study. Sildenafil was well tolerated among all studies. Sildenafil was found to improve hemodynamics, exercise capacity, and quality of life in patients with elevated pulmonary vascular resistance. Phosphodiesterase 5 inhibitors therapy in patients with proven Pulmonary Hypertension due to left heart disease and elevated pulmonary vascular resistance by right heart catheterization may improve the quality of life, exercise capacity, and pulmonary hemodynamics. Further prospective randomized controlled studies are needed to confirm.

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“…Besteht jedoch trotz optimierter Therapie einer Linksherzerkrankung eine CpcPH, so kann eine zusätzlich bestehende pulmonal vaskuläre Erkrankung und somit ein therapeutisches Target angenommen werden. Obgleich kleinere Studien Hinweise auf einen therapeutischen Nutzen bei HFpEF und CpcPH zeigten [25,26] und ein Behandlungsversuch im Einzelfall sinnvoll sein kann [20], sind PAH-Medikamente in dieser Situation nicht zugelassen. Kontrollierte Studien sind notwendig.…”

Section: Pulmonale Hypertonie Bei Linksherzerkrankungen (Nizza-gruppe 2)unclassified

Pulmonale Hypertonie: Update 2019

Rosenkranz

2019

Klinikarzt

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ZUSAMMENFASSUNGPulmonale Hypertonie (PH) ist ein hämodynamischer Zustand, der als gemeinsame Konsequenz einer Reihe von Erkrankungen entstehen kann, die aufgrund unterschiedlicher Pathomechanismen zu einer Erhöhung des pulmonal arteriellen Drucks und infolge dessen zu chronischer Rechtsherzbelastung führen. Je nach zugrunde liegender Ursache untergliedert die klinische Klassifikation die PH in 5 Gruppen: Pulmonal arterielle Hypertonie (Gruppe 1), PH in Zusammenhang mit Linksherzerkrankungen (Gruppe 2), PH bei chronischen Lungenerkrankungen (Gruppe 3), chronisch-thromboembolische PH (CTEPH; Gruppe 4) und PH aufgrund unklarer und/oder multifaktorieller Mechanismen (Gruppe 5). Dieser Artikel fokussiert auf die klinische Relevanz dieser Untergliederung und das unterschiedliche Management der verschiedenen PH-Formen. Er beleuchtet zudem kritisch neue Entwicklungen wie die modifizierte hämodynamische Definition der PH.

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Therapeutic potential of phosphodiesterase type 5 inhibitors in heart failure with preserved ejection fraction and combined post- and pre-capillary pulmonary hypertension

Cited by 44 publications

References 46 publications

Phosphodiesterase 5 inhibitor sildenafil in patients with heart failure with preserved ejection fraction and combined pre- and postcapillary pulmonary hypertension: a randomized open-label pilot study

Phosphodiesterase 5 inhibitor sildenafil in patients with heart failure with preserved ejection fraction and combined pre- and postcapillary pulmonary hypertension: a randomized open-label pilot study

Targeted therapy with phosphodiesterase 5 inhibitors in patients with pulmonary hypertension due to heart failure and elevated pulmonary vascular resistance: a systematic review

Pulmonale Hypertonie: Update 2019

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