Clinical relevance of right ventricular diastolic stiffness in pulmonary hypertension

Right ventricular (RV) diastolic stiffness is increased in pulmonary arterial hypertension (PAH) patients. We investigated whether RV diastolic stiffness is associated with clinical progression and assessed the contribution of RV wall thickness to RV systolic and diastolic stiffness.Using single-beat pressure–volume analyses, we determined RV end-systolic elastance (Ees), arterial elastance (Ea), RV–arterial coupling (Ees/Ea), and RV end-diastolic elastance (stiffness, Eed) in controls (n=15), baseline PAH patients (n=63) and treated PAH patients (survival >5 years n=22 and survival <5 years n=23).We observed an association between Eed and clinical progression, with baseline Eed >0.53 mmHg·mL-1 associated with worse prognosis (age-corrected hazard ratio 0.27, p=0.02). In treated patients, Eed was higher in patients with survival <5 years than in patients with survival >5 years (0.91±0.50 versus 0.53±0.33 mmHg·mL-1, p<0.01). Wall-thickness-corrected Eed values in PAH patients with survival >5 years were not different from control values (0.76±0.47 versus 0.60±0.41 mmHg·mL-1, respectively, not significant), whereas in patients with survival <5 years, values were significantly higher (1.52±0.91 mmHg·mL-1, p<0.05 versus controls).RV diastolic stiffness is related to clinical progression in both baseline and treated PAH patients. RV diastolic stiffness is explained by the increased wall thickness in patients with >5 years survival, but not in those surviving <5 years. This suggests that intrinsic myocardial changes play a distinctive role in explaining RV diastolic stiffness at different stages of PAH.

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Differences of right ventricular diastolic stiffness in pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension

10.1183/13993003.congress-2019.pa1437 ◽

2019 ◽

Author(s):

Ahmed A. Bayoumy ◽

Natalia J. Braams ◽

Onno A. Spruijt ◽

Frances S. De Man ◽

Joanne A. Groeneveldt ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Right Ventricular ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Diastolic Stiffness ◽

Thromboembolic Pulmonary Hypertension ◽

Pulmonary Arterial

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Neuregulin-1 attenuates right ventricular diastolic stiffness in experimental pulmonary hypertension

Clinical and Experimental Pharmacology and Physiology ◽

10.1111/1440-1681.13043 ◽

2018 ◽

Vol 46 (3) ◽

pp. 255-265 ◽

Cited By ~ 2

Author(s):

Rui Adão ◽

Pedro Mendes-Ferreira ◽

Carolina Maia-Rocha ◽

Diana Santos-Ribeiro ◽

Patrícia Gonçalves Rodrigues ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Neuregulin 1 ◽

Diastolic Stiffness

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Renal Denervation Reduces Pulmonary Vascular Remodeling and Right Ventricular Diastolic Stiffness in Experimental Pulmonary Hypertension

JACC Basic to Translational Science ◽

10.1016/j.jacbts.2016.09.007 ◽

2017 ◽

Vol 2 (1) ◽

pp. 22-35 ◽

Cited By ~ 11

Author(s):

Denielli da Silva Gonçalves Bos ◽

Chris Happé ◽

Ingrid Schalij ◽

Wioletta Pijacka ◽

Julian F.R. Paton ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Right Ventricular ◽

Vascular Remodeling ◽

Renal Denervation ◽

Pulmonary Vascular Remodeling ◽

Diastolic Stiffness

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Right ventricular end-diastolic stiffness heralds right ventricular failure in monocrotaline-induced pulmonary hypertension

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00202.2016 ◽

2016 ◽

Vol 311 (4) ◽

pp. H1004-H1013 ◽

Cited By ~ 10

Author(s):

Mohamed Alaa ◽

Mahmoud Abdellatif ◽

Marta Tavares-Silva ◽

José Oliveira-Pinto ◽

Lucas Lopes ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Stroke Volume ◽

Right Ventricular ◽

Diastolic Pressure ◽

Stroke Volume Index ◽

Volume Index ◽

Positive Pressure ◽

Stroke Work ◽

Operating Characteristics ◽

Diastolic Stiffness

Recent studies suggest right ventricular (RV) stiffness is important in pulmonary hypertension (PH) prognosis. Smaller stroke volume (SV) variation after a certain RV end-diastolic pressure (EDP) respiratory variation as assessed by spectral transfer function (STF) may identify RV stiffness. Our aim was to evaluate RV stiffness in monocrotaline (MCT)-induced PH progression and to validate STF gain between EDP and SV as marker of stiffness. Seven-week-old male Wistar rats randomly injected with 60 mg/kg MCT or vehicle were divided into three groups ( n = 12 each) according to cardiac index (CI): controls (Ctrl), preserved CI (MCT pCI), and reduced CI (MCT rCI). All underwent RV pressure-volume (PV) evaluation 24–34 days after MCT, under halogenate anesthesia and constant positive-pressure ventilation. End-diastolic stiffness (βi), end-systolic elastance (Eesi), arterial elastance for indexed volumes (Eai), and preload recruitable stroke work (PRSW) were obtained and beat-to-beat fluctuations during ventilation assessed by STF. Eai was the strongest determinant of CI, alongside βi but not PRSW. MCT rCI showed impaired ventricular-vascular coupling (VVC) and higher βi, along with low end-diastolic pressure (EDP) and stroke volume index (SVi) STF gain, denoting impaired preload reserve. On multivariate analysis βi and not Eesi correlated with EDP-SVi STF gain ( P < 0.001). Receiver-operating characteristics (ROC) curve analysis of EDP-SVi STF gain showed an area under curve of 0.84 for βi prediction ( P = 0.002). Afterload, impaired VVC and RV stiffness are major players in RV failure. RV stiffness can be assessed by STF gain analysis of respiratory fluctuations between EDP and SVi, which may constitute a prognostic tool in PH.

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Abstract 14221: Right Ventricular Adaptation to Pressure Overload: Differences Between Chronic Thromboembolic Pulmonary Hypertension and Idiopathic Pulmonary Arterial Hypertension

Circulation ◽

10.1161/circ.142.suppl_3.14221 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Natalia J Braams ◽

Joost W van Leeuwen ◽

anton vonk noordegraaf ◽

Harm Jan Bogaard ◽

Lilian J Meijboom ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Pulmonary Arterial Hypertension ◽

Arterial Hypertension ◽

Right Ventricular ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Idiopathic Pulmonary Arterial Hypertension ◽

Diastolic Stiffness ◽

Thromboembolic Pulmonary Hypertension ◽

Pulmonary Arterial ◽

Rv Function

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) and idiopathic pulmonary arterial hypertension (iPAH)) are both associated with right ventricular (RV) failure and death. Although both conditions develop in the pre-capillary pulmonary vasculature, patient characteristics are different. CTEPH patients are older, predominantly male and more often have a history of venous thromboembolism. Therefore, the RV might be affected differently in CTEPH compared to iPAH. We aimed to compare RV adaptation in CTEPH and iPAH. Methods: Between 2000 and 2019 all treatment naive iPAH and CTEPH patients diagnosed in the Amsterdam UMC were included if a right heart catheterization and cardiac magnetic resonance imaging (CMR) were performed at the time of diagnosis. RV volumes, mass and function were assessed with CMR. RV contractility, afterload, RV-pulmonary artery (RV-PA) coupling and diastolic stiffness (Eed) were obtained using single beat pressure-volume loop analysis. Differences in RV phenotypes between iPAH and CTEPH were analyzed using multiple linear regression with interaction testing after correcting for confounders. Results: A total of 235 patients were included, 116 with CTEPH and 119 with iPAH. CTEPH patients were older, predominantly male, had a higher systemic blood pressure and a lower pulmonary vascular resistance at the time of diagnosis. After correcting for these confounders, RV function and RV-PA coupling were similar in both groups. However, CTEPH patients had a higher RV end-diastolic volume index (87±27 ml/m2 vs. 82±25 ml/m2), and a lower RV wall thickness (0,6±0,1 g/ml vs. 0,7±0,2 g/ml; figure 1A). The increase in afterload in CTEPH was associated with a disproportionally larger increase in diastolic stiffness compared to iPAH, independent of RV wall thickness (figure 1B). Conclusions: Despite a similar RV function, the RV in CTEPH is more dilated and stiffer than the RV in iPAH, independent of age, sex and afterload.

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