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1.
Artigo em Inglês | MEDLINE | ID: mdl-31756118

RESUMO

The functional relevance of right atrial (RA) function in pulmonary hypertension (PH) remains incompletely understood. The purpose of this study was to explore the correlation of cardiac magnetic resonance (CMR) feature tracking-derived RA phasic function with invasively measured pressure-volume (PV) loop-derived right ventricular (RV) end-diastolic elastance (Eed) and RV-arterial coupling [end-systolic/arterial elastance (Ea/Ees)]. In 54 patients with severe PH, CMR was performed within 24 hours of diagnostic right heart catheterization and PV measurements. RA phasic function was assessed by CMR imaging of RA reservoir, passive, and active strain. The association of RA phasic function with indices of RV function was evaluated by Spearman's rank correlation and linear regression analyses. Median [interquartile range] RA reservoir, passive, and active strain were 19.5% [11.0-24.5], 7.0% [4.0-12.0], and 13.0% [7.0-18.5], respectively. Ees/Ea was 0.73 [0.48-1.08] and Eed was 0.14 mm Hg/ml [0.05-0.22]. RV diastolic impairment [RV end-diastolic pressure (EDP) and Eed] was correlated with RA phasic function, but Ea and Ees were not. In addition, RA phasic function was correlated with inferior vena cava diameter. In multivariate linear regression analysis, adjusting for key PV-loop indices, Eed and EDP remained significantly associated with RA phasic function. We conclude that RA phasic function is altered in relation to impaired diastolic function of the chronically overloaded right ventricle, and contributes to backwards venous flow and systemic congestion. These results call for more attention to RA function in the management of patients with PH.

4.
J Am Heart Assoc ; 8(21): e013584, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31630601

RESUMO

Background Persistent congestion with deteriorating renal function is an important cause of adverse outcomes in heart failure. We aimed to characterize new approaches to evaluate renal congestion using Doppler ultrasonography. Methods and Results We enrolled 205 patients with suspected or prediagnosed pulmonary hypertension (PH) undergoing right heart catheterization. Patients underwent renal Doppler ultrasonography and assessment of invasive cardiopulmonary hemodynamics, echocardiography, renal function, intra-abdominal pressure, and neurohormones and hydration status. Four spectral Doppler intrarenal venous flow patterns and a novel renal venous stasis index (RVSI) were defined. We evaluated PH-related morbidity using the Cox proportional hazards model for the composite end point of PH progression (hospitalization for worsening PH, lung transplantation, or PH-specific therapy escalation) and all-cause mortality for 1-year after discharge. The prognostic utility of RVSI and intrarenal venous flow patterns was compared using receiver operating characteristic curves. RVSI increased in a graded fashion across increasing severity of intrarenal venous flow patterns (P<0.0001) and was significantly associated with right heart and renal function, intra-abdominal pressure, and neurohormonal and hydration status. During follow-up, the morbidity/mortality end point occurred in 91 patients and was independently predicted by RVSI (RVSI in the third tertile versus referent: hazard ratio: 4.72 [95% CI, 2.10-10.59; P<0.0001]). Receiver operating characteristic curves suggested superiority of RVSI to individual intrarenal venous flow patterns in predicting outcome (areas under the curve: 0.789 and 0.761, respectively; P=0.038). Conclusions We propose RVSI as a conceptually new and integrative Doppler index of renal congestion. RVSI provides additional prognostic information to stratify PH for the propensity to develop right heart failure. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT03039959.

5.
Circ Cardiovasc Imaging ; 12(9): e009047, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31500448

RESUMO

BACKGROUND: The ratios of tricuspid annular plane systolic excursion (TAPSE)/echocardiographically measured systolic pulmonary artery pressure (PASP), fractional area change/invasively measured mean pulmonary artery pressure, right ventricular (RV) area change/end-systolic area, TAPSE/pulmonary artery acceleration time, and stroke volume/end-systolic area have been proposed as surrogates of RV-arterial coupling. The relationship of these surrogates with the gold standard measure of RV-arterial coupling (invasive pressure-volume loop-derived end-systolic/arterial elastance [Ees/Ea] ratio) and RV diastolic stiffness (end-diastolic elastance) in pulmonary hypertension remains incompletely understood. We evaluated the relationship of these surrogates with invasive pressure-volume loop-derived Ees/Ea and end-diastolic elastance in pulmonary hypertension. METHODS: We performed right heart echocardiography and cardiac magnetic resonance imaging 1 day before invasive measurement of pulmonary hemodynamics and single-beat RV pressure-volume loops in 52 patients with pulmonary arterial hypertension or chronic thromboembolic pulmonary hypertension. The relationships of the proposed surrogates with Ees/Ea and end-diastolic elastance were evaluated by Spearman correlation, multivariate logistic regression, and receiver operating characteristic analyses. Associations with prognosis were evaluated by Kaplan-Meier analysis. RESULTS: TAPSE/PASP, fractional area change/mean pulmonary artery pressure, RV area change/end-systolic area, and stroke volume/end-systolic area but not TAPSE/pulmonary artery acceleration time were correlated with Ees/Ea and end-diastolic elastance. Of the surrogates, only TAPSE/PASP emerged as an independent predictor of Ees/Ea (multivariate odds ratio: 18.6; 95% CI, 0.8-96.1; P=0.08). In receiver operating characteristic analysis, a TAPSE/PASP cutoff of 0.31 mm/mm Hg (sensitivity: 87.5% and specificity: 75.9%) discriminated RV-arterial uncoupling (Ees/Ea <0.805). Patients with TAPSE/PASP <0.31 mm/mm Hg had a significantly worse prognosis than those with higher TAPSE/PASP. CONCLUSIONS: Echocardiographically determined TAPSE/PASP is a straightforward noninvasive measure of RV-arterial coupling and is affected by RV diastolic stiffness in severe pulmonary hypertension. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03403868.

6.
Eur Respir J ; 54(5)2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31515402

RESUMO

Cardiopulmonary exercise testing (CPET) is an important tool for assessing functional capacity and prognosis in pulmonary arterial hypertension (PAH). However, the associations of CPET parameters with the adaptation of right ventricular (RV) function to afterload remain incompletely understood.In this study, 37 patients with PAH (idiopathic in 31 cases) underwent single-beat pressure-volume loop measurements of RV end-systolic elastance (Ees), arterial elastance (Ea) and diastolic elastance (Eed). Pulmonary arterial stiffness was assessed by magnetic resonance imaging. The results were correlated to CPET variables. The predictive relevance of RV function parameters for clinically relevant ventilatory inefficiency, defined as minute ventilation/carbon dioxide production (V' E/V' CO2 ) slope >48, was evaluated using logistic regression analysis.The median (interquartile range) of the V' E/V' CO2 slope was 42 (32-52) and the V' E/V' CO2 nadir was 40 (31-44). The mean±sd of peak end-tidal carbon dioxide tension (P ETCO2 ) was 23±8 mmHg. Ea, Eed and parameters reflecting pulmonary arterial stiffness (capacitance and distensibility) correlated with the V' E/V' CO2 slope, V' E/V' CO2 nadir, P ETCO2 and peak oxygen pulse. RV Ees and RV-arterial coupling as assessed by the Ees/Ea ratio showed no correlations with CPET parameters. Ea (univariate OR 7.28, 95% CI 1.20-44.04) and Eed (univariate OR 2.21, 95% CI 0.93-5.26) were significantly associated with ventilatory inefficiency (p<0.10).Our data suggest that impaired RV lusitropy and increased afterload are associated with ventilatory inefficiency in PAH.

8.
Br J Pharmacol ; 2019 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-31517994

RESUMO

Adaptation of right ventricular (RV) function to increased afterload - known as RV-arterial coupling - is a key determinant of prognosis in pulmonary hypertension. However, measurement of RV-arterial coupling is a complex, invasive process involving analysis of the RV pressure-volume relationship during preload reduction over multiple cardiac cycles. Simplified methods have therefore been proposed, including echocardiographic and cardiac MRI approaches. This review describes the available methods for assessment of RV function and RV-arterial coupling, and the effects of pharmacotherapy on these parameters. Overall, pharmacotherapies for pulmonary hypertension have shown beneficial effects on various measures of RV function, but it is often unclear if these are direct RV effects or indirect results of afterload reduction. Studies of the effects of pharmacotherapies on RV-arterial coupling are limited and mostly restricted to experimental models. Simplified methods to assess RV-arterial coupling should be validated and incorporated into routine clinical follow-up and future clinical trials.

10.
Eur Respir J ; 53(6)2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30956210

RESUMO

Chronic obstructive pulmonary disease (COPD), which comprises the phenotypes of chronic bronchitis and emphysema, is often associated with pulmonary hypertension (PH). However, currently, no approved therapy exists for PH-COPD. Signalling of the nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) axis plays an important role in PH and COPD.We investigated the treatment effect of riociguat, which promotes the NO-cGMP pathway, in the mouse model of smoke-induced PH and emphysema in a curative approach, and retrospectively analysed the effect of riociguat treatment on PH in single patients with PH-COPD.In mice with established PH and emphysema (after 8 months of cigarette smoke exposure), riociguat treatment for another 3 months fully reversed PH. Moreover, histological hallmarks of emphysema were decreased. Microarray analysis revealed involvement of different signalling pathways, e.g. related to matrix metalloproteinases (MMPs). MMP activity was decreased in vivo by riociguat. In PH-COPD patients treated with riociguat (n=7), the pulmonary vascular resistance, airway resistance and circulating MMP levels decreased, while oxygenation at rest was not significantly changed.Riociguat may be beneficial for treatment of PH-COPD. Further long-term prospective studies are necessary to investigate the tolerability, efficacy on functional parameters and effect specifically on pulmonary emphysema in COPD patients.

11.
JACC Cardiovasc Imaging ; 12(11 Pt 1): 2155-2164, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30878422

RESUMO

OBJECTIVES: This study sought to compare cardiac magnetic resonance (CMR) imaging-derived right ventricular (RV) strain and invasively measured pressure-volume loop-derived RV contractility, stiffness, and afterload and RV-arterial coupling in pulmonary hypertension (PH). BACKGROUND: In chronic RV pressure overload, RV-arterial uncoupling is considered the driving cause of RV maladaptation and eventual RV failure. The pathophysiological and clinical value of CMR-derived RV strain relative to that of invasive pressure-volume loop-derived measurements in PH remains incompletely understood. METHODS: In 38 patients with PH, global RV CMR strain was measured within 24 h of diagnostic right heart catheterization and conductance (pressure-volume) catheterization. Associations were evaluated by correlation, multivariate logistic binary regression, and receiver operating characteristic analyses. RESULTS: Long-axis RV longitudinal and radial strain and short-axis RV radial and circumferential strain were -18.0 ± 7.0%, 28.9% [interquartile range (IQR): 17.4% to 46.6%]; 15.6 ± 6.2%; and -9.8 ± 3.5%, respectively. RV-arterial coupling (end-systolic [Eds]/arterial elastance [Ea]) was 0.76 (IQR: 0.47 to 1.07). Peak RV strain correlated with Ees/Ea, afterload (Ea), RV diastolic dysfunction (Tau), and stiffness (end-diastolic elastance [Eed]) but not with contractility (Ees). In multivariate analysis, long-axis RV radial strain was associated with RV-arterial uncoupling (Ees/Ea: <0.805; odds ratio [OR]: 5.50; 95% confidence interval [CI]: 1.50 to 20.18), whereas long-axis RV longitudinal strain was associated with increased RV diastolic stiffness (Eed: ≥0.124 mm Hg/ml; OR: 1.23; 95% CI: 1.10 to 1.51). The long-axis RV longitudinal strain-to-RV end-diastolic volume/body surface area ratio strongly predicted RV diastolic stiffness (area under receiver operating characteristic curve: 0.908). CONCLUSIONS: In chronic RV overload, CMR-determined RV strain is associated with RV-arterial uncoupling and RV end-diastolic stiffness and represents a promising noninvasive alternative to current invasive methods for assessment of RV-arterial coupling and end-diastolic stiffness in patients with PH. (Right Ventricular Haemodynamic Evaluation and Response to Treatment [Rightheart I]; NCT03403868).

14.
Circ Heart Fail ; 12(1): e005512, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30616360

RESUMO

BACKGROUND: Right ventricular (RV) maladaptation and failure determine outcome in pulmonary hypertension. The adaptation of RV function to loading (RV-pulmonary arterial coupling) is defined by a ratio of end-systolic to arterial elastances (Ees/Ea). How RV-pulmonary arterial coupling relates to pulmonary hypertension severity and onset of RV failure (defined by excessive volume increase and ejection fraction [EF] decrease) is not exactly known. METHODS AND RESULTS: We performed cardiac magnetic resonance (CMR) imaging within 24 hours of a diagnostic right heart catheterization and invasive measurement of RV pressure-volume loops in 42 patients with pulmonary hypertension. Median (interquartile range) Ees and Ea were 0.49 (0.35-0.74) and 0.74 (0.45-1.04) mm Hg/mL, respectively; Ees/Ea was 0.73 (0.47-1.07). End-diastolic elastance (Eed) was 0.14 (0.06-0.24) mm Hg/mL. RV EF was 39±13%. End-systolic volume and end-diastolic volume/body surface area (BSA) were 62 (45-101) and 104 (83-143) mL/m2, respectively. Ees/Ea decreased with increasing RV end-diastolic volume/BSA, mass/BSA, and pulmonary arterial stiffness, and with decreasing EF, from 0.89 to 1.09 in the least impaired tertiles to 0.55 to 0.61 in the most impaired tertiles. Eed increased with increasing RV mass/BSA, end-diastolic volume/BSA, and T1 mapping and with decreasing EF. Receiver operating characteristic analysis identified an Ees/Ea cutoff of 0.805 associated with onset of RV failure defined by increased RV volumes with EF <35%. CONCLUSIONS: RV-pulmonary arterial coupling (Ees/Ea) has considerable reserve, from normal values of 1.5-2 to <0.8, and has the ability to detect pending RV failure in patients with pulmonary hypertension. Clinical Trial Registration URL: https://www.clinicaltrials.gov . Unique identifier: NCT03403868.


Assuntos
Pressão Arterial , Insuficiência Cardíaca/etiologia , Hipertensão Pulmonar/complicações , Artéria Pulmonar/fisiopatologia , Volume Sistólico , Disfunção Ventricular Direita/etiologia , Função Ventricular Direita , Adaptação Fisiológica , Idoso , Cateterismo de Swan-Ganz , Doença Crônica , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/fisiopatologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Disfunção Ventricular Direita/diagnóstico , Disfunção Ventricular Direita/fisiopatologia , Remodelação Ventricular
15.
Int J Cardiol ; 266: 229-235, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-29887454

RESUMO

BACKGROUND: The ratio of echocardiography-derived tricuspid annular plane systolic excursion (TAPSE) and pulmonary arterial systolic pressure (PASP) has recently been reported as an independent prognostic parameter in heart failure. The TAPSE/PASP ratio has not been evaluated in detail in patients with pulmonary arterial hypertension (PAH). METHODS: We analyzed TAPSE/PASP in 290 patients with PAH entered into the Giessen Pulmonary Hypertension Registry between November 2003 and July 2014. The prognostic relevance of TAPSE/PASP was assessed with multivariate Cox regression models, adjusting for clinical covariates, echocardiographic parameters, or hemodynamics, and was confirmed by Kaplan-Meier analyses. RESULTS: When stratified by tertile of TAPSE/PASP (low: <0.19 mm/mmHg; middle: 0.19-0.32 mm/mmHg; high: >0.32 mm/mmHg), patients in the low tertile showed significantly compromised hemodynamic, functional, and echocardiographic status compared with patients in the middle and high tertiles. In all multivariate models, TAPSE/PASP remained independently associated with overall mortality: the hazard ratio (95% confidence interval) was 1.87 (1.35-2.59) when adjusting for clinical covariates (p < .001), 5.21 (2.17-12.5) when adjusting for echocardiographic parameters (p < .001), 1.92 (1.30-2.83) when adjusting for hemodynamics (p = .001), and 4.13 (2.02-8.48) when adjusting for a selection of previously identified independent echocardiographic and hemodynamic prognostic indicators (p < .001). Kaplan-Meier analyses showed better overall survival in the middle and high tertiles versus the low tertile (log-rank p < .001). CONCLUSIONS: The TAPSE/PASP ratio is a meaningful prognostic parameter in patients with PAH and is associated with hemodynamics and functional class.

19.
Can Respir J ; 2017: 8381653, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28522921

RESUMO

With rising altitude the partial pressure of oxygen falls. This phenomenon leads to hypobaric hypoxia at high altitude. Since more than 140 million people permanently live at heights above 2500 m and more than 35 million travel to these heights each year, understanding the mechanisms resulting in acute or chronic maladaptation of the human body to these circumstances is crucial. This review summarizes current knowledge of the body's acute response to these circumstances, possible complications and their treatment, and health care issues resulting from long-term exposure to high altitude. It furthermore describes the characteristic mechanisms of adaptation to life in hypobaric hypoxia expressed by the three major ethnic groups permanently dwelling at high altitude. We additionally summarize current knowledge regarding possible treatment options for hypoxia-induced pulmonary hypertension by reviewing in vitro, rodent, and human studies in this area of research.


Assuntos
Adaptação Fisiológica , Doença da Altitude/fisiopatologia , Altitude , Hipertensão Pulmonar/etiologia , Hipóxia/fisiopatologia , Doença da Altitude/complicações , Ventrículos do Coração/fisiopatologia , Humanos , Hipóxia/complicações
20.
BMC Pulm Med ; 16(1): 96, 2016 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-27377832

RESUMO

BACKGROUND: Six-minute walk test (6MWT) is routinely performed in chronic thromboembolic pulmonary hypertension (CTEPH) before pulmonary endarterectomy (PEA). However, the clinical relevance of heart rate response (ΔHR) and exercise-induced oxygen desaturation (EID) during 6MWT is remaining unknown. METHODS: Patients undergoing PEA in our center between 03/2013-04/2014 were assessed prospectively with hemodynamic and exercise parameters prior to and 1 year post-PEA. Patients with symptomatic chronic thromboembolic disease (mean pulmonary artery pressure (mPAP) <25 mmHg) and clinical relevant obstructive pulmonary disease were excluded. The following definitions were used: ΔHR = (peak HR - resting HR), percent heart rate reserve (HRR) = (peak HR -rest HR)/(220 - age - rest HR) x 100 and EID = SpO2 ≤88 %. RESULTS: Thirty-seven patients (of 116 patients screened) with mPAP of 43.2 ± 8.7 mmHg, pulmonary vascular resistance (PVR) of 605.5 ± 228.7 dyn*s/cm(5), cardiac index (CI) of 2.4 ± 0.5 l/min/m(2) and a 6MWT-distance of 404.7 ± 148.4 m and a peak VO2 of 12.3 ± 3.4 ml/min/kg prior to PEA were included. Baseline ΔHR during 6MWT was significantly associated with PVR 1 year post-PEA using linear regression analysis (r = 0.43, p = 0.01). Multivariate analysis indicated an association of HRR during 6MWT and residual PH with a hazard ratio of 1.06 (95 % Confidence interval for hazard ratio 0.99-1.14, p = 0.08). EID was observed commonly during 6MWT but no correlations to outcome parameters were found. CONCLUSIONS: This is the first prospective study to describe an association of ΔHR during 6MWT with pulmonary hemodynamics 1 year post-PEA. Our preliminary results indicate that HRR derived from 6MWT is of clinical significance. EID was commonly observed, albeit failed as a significant prognostic factor.


Assuntos
Frequência Cardíaca , Hipertensão Pulmonar/fisiopatologia , Tromboembolia/complicações , Teste de Caminhada , Idoso , Pressão Arterial , Doença Crônica , Ecocardiografia , Endarterectomia , Feminino , Alemanha , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Consumo de Oxigênio , Estudos Prospectivos , Artéria Pulmonar/fisiopatologia , Tromboembolia/cirurgia , Resistência Vascular
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