Background. In pulmonary hypertension (PH), both post-capillary and pre-capillary pulmonary vascular alterations may affect right ventricular (RV) afterload, eventually contributing to exercise intolerance, RV failure and prognosis. Objectives. To characterize the impact of pulmonary haemodynamics on the RV, exercise pathophysiology, and outcome in patients with PH. Methods. We firstly conducted a retrospective analysis (2007-2014) at a PH referral Center, comparing patients with PH due to left heart disease (LHD) and treatment-naïve idiopathic/heritable pulmonary arterial hypertension (PAH, n=35). Patients with PH-LHD were further subdivided according to pulmonary haemodynamics in Isolated post-capillary PH (IpcPH: diastolic pressure gradient, DPG<7 mmHg and pulmonary vascular resistance, PVR≤3 WU, n=37), Combined post- and pre-capillary PH (CpcPH: DPG≥7 and PVR>3, n=27), and “indeterminate” PH-LHD (either DPG≥7 or PVR>3, n=29). We then conducted a meta-analysis on studies focusing on the association between pulmonary haemodynamics (PVR, DPG and pulmonary arterial compliance, Ca) and outcome in PH-LHD. Results. Haemodynamic severity (pulmonary artery pressures, PVR, pulmonary vascular gradients), prevalence of echocardiographic signs of RV failure (RV dilation + dysfunction), and exercise hyperventilation linearly increased from IpcPH, to “indeterminate”, CpcPH and PAH (p<0.001), while peak oxygen consumption and prevalence of exercise oscillatory ventilation showed an opposite behavior, being higher in IpcPH. Survival did not differ between PH-LHD and PAH; however, CpcPH had worse prognosis than IpcPH and PAH, but similar to “indeterminate” patients. In our retrospective cohort, NT-proBNP and Ca independently predicted survival in PH-LHD. In the meta-analysis, both Ca, PVR and DPG were associated with outcome in PH-LHD. Conclusions. Haemodynamic characterization of PH-LHD according to DPG and PVR is associated with disease severity, exercise pathophysiology, predisposition to RV failure and prognosis. The CpcPH phenotype appear to have haemodynamic profile closer to PAH but with worse outcome. Ca, PVR and DPG are associated with survival in PH-LHD.
Razionale. Nell’ipertensione polmonare (PH), alterazioni sia post- sia pre-capillari possono influire sul postcarico del ventricolo destro (RV), contribuendo alla limitazione della capacità di esercizio, alla disfunzione del RV e alla prognosi. Obiettivi. Caratterizzare l’impatto dell’emodinamica polmonare sul RV, sulla fisiopatologia dell’esercizio e sulla prognosi in pazienti con PH. Metodi. Abbiamo innanzitutto condotto una analisi retrospettiva (2007-2014) presso un centro di riferimento per PH, confrontando pazienti con PH secondaria a malattia del cuore sinistro (LHD) e pazienti con ipertensione arteriosa polmonare idiopatica/ereditaria (PAH, n=35). I pazienti con PH-LHD sono stati ulteriormente suddivisi in funzione dell’emodinamica polmonare in PH post-capillare isolata (IpcPH: gradiente diastolico polmonare, DPG<7 mmHg e resistenza vascolare polmonare, PVR≤3 UW, n=37), PH combinata post- e pre-capillare (CpcPH: DPG≥7 e PVR>3, n=27) e PH-LHD “indeterminata” (DPG≥7 o PVR>3, n=29). Abbiamo quindi condotto una meta-analisi su studi focalizzati sull’associazione tra l’emodinamica polmonare (PVR, DPG e compliance dell’arteria polmonare, Ca) e la sopravvivenza in PH-LHD. Risultati. La severità emodinamica (pressioni arteriose polmonari, PVR, gradienti vascolari polmonari), la prevalenza di segni ecocardiografici di disfunzione del RV (dilatazione + disfunzione del RV), e l’iperventilazione da sforzo aumentavano linearmente da IpcPH a PH-LHD “indeterminati”, CpcPH e PAH (p<0.001), mentre il consumo di ossigeno di picco e la prevalenza di oscillazioni ventilatorie durante esercizio mostrava un comportamento opposto, risultando più alta nei IpcPH. La sopravvivenza dei pazienti PH-LHD non era diversa da quella dei pazienti PAH; tuttavia, i pazienti CpcPH presentavano una prognosi peggiore dei pazienti IpcPH e dei pazienti PAH, ma simile ai pazienti PH-LHD “indeterminati”. Nella nostra coorte retrospettiva, NT-proBNP e Ca risultavano associati in maniera indipendente alla sopravvivenza in PH-LHD. Conclusioni. La caratterizzazione emodinamica dei pazienti PH-LHD in funzione di DPG e PVR è associata alla gravità di malattia, alla fisiopatologia dell’esercizio, alla predisposizione a disfunzione del RV e alla prognosi. Il fenotipo CpcPH sembra avere un profilo emodinamico simile alla PAH ma con una prognosi peggiore. Ca, PVR e DPG sono associate alla sopravvivenza in PH-LHD.
(2019). Clinical phenotypes, right ventricular function, exercise pathophysiology and outcomes of pulmonary hypertension due to left heart disease: role of the precapillary component. (Tesi di dottorato, Università degli Studi di Milano-Bicocca, 2019).
Clinical phenotypes, right ventricular function, exercise pathophysiology and outcomes of pulmonary hypertension due to left heart disease: role of the precapillary component
CARAVITA, SERGIO
2019
Abstract
Background. In pulmonary hypertension (PH), both post-capillary and pre-capillary pulmonary vascular alterations may affect right ventricular (RV) afterload, eventually contributing to exercise intolerance, RV failure and prognosis. Objectives. To characterize the impact of pulmonary haemodynamics on the RV, exercise pathophysiology, and outcome in patients with PH. Methods. We firstly conducted a retrospective analysis (2007-2014) at a PH referral Center, comparing patients with PH due to left heart disease (LHD) and treatment-naïve idiopathic/heritable pulmonary arterial hypertension (PAH, n=35). Patients with PH-LHD were further subdivided according to pulmonary haemodynamics in Isolated post-capillary PH (IpcPH: diastolic pressure gradient, DPG<7 mmHg and pulmonary vascular resistance, PVR≤3 WU, n=37), Combined post- and pre-capillary PH (CpcPH: DPG≥7 and PVR>3, n=27), and “indeterminate” PH-LHD (either DPG≥7 or PVR>3, n=29). We then conducted a meta-analysis on studies focusing on the association between pulmonary haemodynamics (PVR, DPG and pulmonary arterial compliance, Ca) and outcome in PH-LHD. Results. Haemodynamic severity (pulmonary artery pressures, PVR, pulmonary vascular gradients), prevalence of echocardiographic signs of RV failure (RV dilation + dysfunction), and exercise hyperventilation linearly increased from IpcPH, to “indeterminate”, CpcPH and PAH (p<0.001), while peak oxygen consumption and prevalence of exercise oscillatory ventilation showed an opposite behavior, being higher in IpcPH. Survival did not differ between PH-LHD and PAH; however, CpcPH had worse prognosis than IpcPH and PAH, but similar to “indeterminate” patients. In our retrospective cohort, NT-proBNP and Ca independently predicted survival in PH-LHD. In the meta-analysis, both Ca, PVR and DPG were associated with outcome in PH-LHD. Conclusions. Haemodynamic characterization of PH-LHD according to DPG and PVR is associated with disease severity, exercise pathophysiology, predisposition to RV failure and prognosis. The CpcPH phenotype appear to have haemodynamic profile closer to PAH but with worse outcome. Ca, PVR and DPG are associated with survival in PH-LHD.File | Dimensione | Formato | |
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