Aiming at the appropriate target for the treatment of pulmonary hypertension due to left heart disease

Galiè, Nazzareno; Manes, Alessandra; Dardi, Fabio; Palazzini, Massimiliano

doi:10.1093/eurheartj/ehx751

Cited by 10 publications

(4 citation statements)

References 14 publications

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“…The genetic background as well as co‐morbidities may play a role, although this remains speculative. However, the extent and chronicity of backwards transmission of left‐sided filling pressures are thought to represent the key drivers for the transition from IpcPH to CpcPH . This view is supported by our data showing that patients with CpcPH not only have higher PVR but also higher mPAWP than patients with IpcPH.…”

Section: Discussionsupporting

confidence: 75%

“…However, the extent and chronicity of backwards transmission of left-sided filling pressures are thought to represent the key drivers for the transition from IpcPH to CpcPH. 1,9,26 This view is supported by our data showing that patients with CpcPH not only have higher PVR but also higher mPAWP than patients with IpcPH. Interestingly, we found no difference in LVEDP between the CpcPH and IpcPH groups, i.e.…”

Section: Critical Role Of Filling Pressures and Pulmonary Vascular Resupporting

confidence: 63%

“…Importantly, there is no evidence for a beneficial effect of PAH-specific therapies for the management of patients with PH due to left heart disease; the opposite may even be the case. 26 Very recently, a randomized trial evaluating the effect of the phosphodiesterase-5 inhibitor sildenafil in patients with persistent PH several months after valve replacement/repair (median mPAP 39 mmHg, median PVR 3.4 WU) found worse clinical outcomes (death, hospital admission, worsening functional class, global symptom burden) in patients treated with sildenafil compared to placebo. 30 The study included patients with both IpcPH and CpcPH but the effect of sildenafil was similar in both groups.…”

Section: Discussionmentioning

confidence: 99%

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Haemodynamic mechanisms and long‐term prognostic impact of pulmonary hypertension in patients with severe aortic stenosis undergoing valve replacement

Weber

Rickli

Haager

et al. 2018

European J of Heart Fail

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Aims We aimed to investigate the prevalence, detailed invasive haemodynamics, and prognostic impact of pulmonary hypertension (PH) in severe aortic stenosis (AS). Methods and results We studied 503 patients (mean age 74 ± 10 years) with severe AS (indexed aortic valve area 0.4 ± 0.1 cm2/m2, left ventricular ejection fraction 57 ± 12%) undergoing left and right heart catheterization prior to aortic valve replacement. Median follow‐up was 3.7 (interquartile range 2.6–5.4) years. Baseline PH (mean pulmonary artery pressure ≥ 25 mmHg) was found in 239 (48%) patients: 31 patients had pre‐capillary PH [mean pulmonary artery wedge pressure (mPAWP) ≤ 15 mmHg], 144 had isolated post‐capillary PH [IpcPH; mPAWP > 15 mmHg, pulmonary vascular resistance (PVR) ≤ 3 Wood units (WU)], and 64 had combined pre‐ and post‐capillary PH (CpcPH; mPAWP > 15 mmHg, PVR > 3 WU). Patients with CpcPH had higher mortality than those with IpcPH, pre‐capillary PH, and without PH. In the multivariate analysis, CpcPH remained an independent predictor of death (hazard ratio 4.39, 95% confidence interval 2.40–8.03; P < 0.001). Patients with CpcPH had higher mPAWP (26 ± 7 vs. 22 ± 5 mmHg) and lower pulmonary arterial capacitance (1.5 ± 0.6 vs. 2.9 ± 1.2 mL/mmHg) than IpcPH patients but similar left ventricular end‐diastolic pressure (LVEDP; 25 ± 7 vs. 25 ± 7 mmHg). A smaller LVEDP–mPAWP difference was related to larger left atrial size, atrial fibrillation, and more severe mitral regurgitation. Conclusions In patients with severe AS, PH is common but underlying mechanisms differ. Patients with CpcPH have higher mPAWP, lower pulmonary arterial capacitance, and worse survival than all other groups. Left atrial dysfunction and mitral regurgitation seem to be drivers of high mPAWP in CpcPH.

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Section: Discussionsupporting

confidence: 75%

Section: Critical Role Of Filling Pressures and Pulmonary Vascular Resupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

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Haemodynamic mechanisms and long‐term prognostic impact of pulmonary hypertension in patients with severe aortic stenosis undergoing valve replacement

Weber

Rickli

Haager

et al. 2018

European J of Heart Fail

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“…The classical paradigm for PH-LHD assumes that longstanding venous hypertension induces structural alterations of the pulmonary arterial bed that characterize cPC-PH [14]. Medial hypertrophy and intimal proliferation of the distal pulmonary arteries and arterioles dramatically raise PVR [15]. Interstitial lung edema and alveolar hemorrhage is frequently found, and the vasomotor tone of the pulmonary arteries is also increased.…”

Section: The Hemodynamic and Structural Changes Of Ph-lhdmentioning

confidence: 99%

The Biological Bases of Group 2 Pulmonary Hypertension

Fernández

Yotti

González‐Mansilla

et al. 2019

IJMS

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Pulmonary hypertension (PH) is a potentially fatal condition with a prevalence of around 1% in the world population and most commonly caused by left heart disease (PH-LHD). Usually, in PH-LHD, the increase of pulmonary pressure is only conditioned by the retrograde transmission of the left atrial pressure. However, in some cases, the long-term retrograde pressure overload may trigger complex and irreversible biomechanical and biological changes in the pulmonary vasculature. This latter clinical entity, designated as combined pre- and post-capillary PH, is associated with very poor outcomes. The underlying mechanisms of this progression are poorly understood, and most of the current knowledge comes from the field of Group 1-PAH. Treatment is also an unsolved issue in patients with PH-LHD. Targeting the molecular pathways that regulate pulmonary hemodynamics and vascular remodeling has provided excellent results in other forms of PH but has a neutral or detrimental result in patients with PH-LHD. Therefore, a deep and comprehensive biological characterization of PH-LHD is essential to improve the diagnostic and prognostic evaluation of patients and, eventually, identify new therapeutic targets. Ongoing research is aimed at identify candidate genes, variants, non-coding RNAs, and other biomarkers with potential diagnostic and therapeutic implications. In this review, we discuss the state-of-the-art cellular, molecular, genetic, and epigenetic mechanisms potentially involved in PH-LHD. Signaling and effective pathways are particularly emphasized, as well as the current knowledge on -omic biomarkers. Our final aim is to provide readers with the biological foundations on which to ground both clinical and pre-clinical research in the field of PH-LHD.

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Therapeutic augmentation of NO-sGC-cGMP signalling: lessons learned from pulmonary arterial hypertension and heart failure

et al. 2022

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Aiming at the appropriate target for the treatment of pulmonary hypertension due to left heart disease

Cited by 10 publications

References 14 publications

Haemodynamic mechanisms and long‐term prognostic impact of pulmonary hypertension in patients with severe aortic stenosis undergoing valve replacement

Haemodynamic mechanisms and long‐term prognostic impact of pulmonary hypertension in patients with severe aortic stenosis undergoing valve replacement

The Biological Bases of Group 2 Pulmonary Hypertension

Therapeutic augmentation of NO-sGC-cGMP signalling: lessons learned from pulmonary arterial hypertension and heart failure

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