Elevated pulmonary arterial elastance and right ventricular uncoupling are associated with greater mortality in advanced heart failure.

The objectives of this study were to describe right ventricular-pulmonary arterial elastance coupling hemodynamic phenotypes and their frequency in patients with advanced heart failure and to evaluate the association of elastance-based indices with all-cause mortality, cardiac transplantation, and left ventricular assist device therapy. This study included 175 patients with heart failure undergoing right heart catheterization to evaluate candidacy for advanced therapies and 21 healthy controls. We modified a single-beat approach to elastance to account for the magnitude of pulmonary arterial pressure and estimated right ventricular end-systolic elastance (Ees), pulmonary arterial elastance (Ea), and the Ees:Ea ratio. We defined elevated pulmonary arterial load as an Ea > 0.5 mm Hg/ml, and ventriculo-arterial uncoupling as an Ees:Ea < 0.8. We evaluated associations between Ees, Ea, and Ees:Ea with all-cause mortality and composite event-free survival using multivariable Cox proportional-hazard models, adjusted for age and sex. All 21 controls had Ea ≤ 0.5 mm Hg/ml and Ees:Ea ≥ 0.8. Of 175 patients with heart failure, 63% had Ea > 0.5 mm Hg/ml. Ees:Ea was lower in patients than in controls (p < 0.001), and 47% of the patients demonstrated Ees:Ea < 0.8, including 8% with normal Ea. In median follow-up of 2.2 (0.8-4.6) years, 53 died, 37 received cardiac transplantation, and 33 received a left ventricular assist device. By multivariable analysis, Ea (hazard ratios [HR]: 2.01, 95% CI 1.18-3.41) and Ees:Ea (HR: 0.46, 95% CI: 0.26-0.82) were independently associated with mortality, whereas Ees was not. Right ventricular-pulmonary vascular coupling is frequently impaired in heart failure and associated with greater mortality. Elevated pulmonary arterial elastance is associated with greater mortality even when coupling is preserved.

Wright SP ，Groves L ，Vishram-Nielsen JKK ，Karvasarski E ，Valle FH ，Alba AC ，Mak S ... -  《-》

Sex-Related Differences in Dynamic Right Ventricular-Pulmonary Vascular Coupling in Heart Failure With Preserved Ejection Fraction.

Right ventricular (RV) dysfunction is associated with poorer outcomes in heart failure with preserved ejection fraction (HFpEF). Although female subjects are more likely to have HFpEF, male subjects have worse prognosis and resting RV function. The contribution of dynamic RV-pulmonary arterial (RV-PA) coupling between sex and its impact on peak exercise capacity (VO2) in HFpEF is not known. The goal of this study was to investigate the differential effects of sex on RV-PA coupling during maximum incremental exercise in patients with HFpEF. This study examined rest and exercise invasive pulmonary hemodynamics in 22 male patients with HFpEF and 27 female patients with HFpEF. To further investigate the discrepancy in RV-PA response between sex, 26 age-matched control subjects (11 male subjects and 15 female subjects) were included. Single beat analysis of RV pressure waveforms was used to determine the end-systolic elastance (Ees) and pulmonary arterial elastance. RV-PA coupling was determined as the ratio of end-systolic elastance/PA elastance. Both HFpEF groups experienced decreased peak VO2 (% predicted). However, male patients with HFpEF experienced a greater decrement in peak VO2 compared with female patients (58 ± 16% vs 70 ± 15%; P < .05). Male patients with HFpEF had a more pronounced increase in RV afterload, Ea (1.8 ± 0.6 mm Hg/mL/m2 vs 1.3 ± 0.4 mm Hg/mL/m2; P < .05) and failed to increase RV contractility during exercise, resulting in dynamic RV-PA uncoupling (0.9 ± 0.4 vs 1.2 ± 0.4; P < .05) and subsequent reduced stroke volume index augmentation. In contrast, female patients with HFpEF were able to augment RV contractility in the face of increasing afterload, preserving RV-PA coupling during exercise. Male patients with HFpEF were more compromised regarding dynamic RV-PA uncoupling and reduced peak VO2 compared with female patients. This finding was driven by both RV contractile impairment and afterload mismatch. In contrast, female patients with HFpEF had preserved RV-PA coupling during exercise and better peak exercise VO2 compared with male patients with HFpEF.

Singh I ，Oliveira RKF ，Heerdt PM ，Pari R ，Systrom DM ，Waxman AB ... -  《-》

Ventricular-vascular coupling is predictive of adverse clinical outcome in paediatric pulmonary arterial hypertension.

Ventricular-vascular coupling, the ratio between the right ventricle's contractile state (Ees) and its afterload (Ea), may be a useful metric in the management of paediatric pulmonary arterial hypertension (PAH). In this study we assess the prognostic capacity of the ventricular-vascular coupling ratio (Ees/Ea) derived using right ventricular (RV) pressure alone in children with PAH. One hundred and thirty paediatric patients who were diagnosed with PAH via right heart catheterisation were retrospectively reviewed over a 10-year period. Maximum RV isovolumic pressure and end-systolic pressure were estimated using two single-beat methods from Takeuchi et al (Ees/Ea_(Takeuchi)) and from Kind et al (Ees/Ea_(Kind)) and used with an estimate of end-systolic pressure to compute ventricular-vascular coupling from pressure alone. Patients were identified as either idiopathic/hereditary PAH or associated PAH (IPAH/HPAH and APAH, respectively). Haemodynamic data, clinical functional class and clinical worsening outcomes-separated into soft (mild) and hard (severe) event categories-were assessed. Adverse soft events included functional class worsening, syncopal event, hospitalisation due to a proportional hazard-related event and haemoptysis. Hard events included death, transplantation, initiation of prostanoid therapy and hospitalisation for atrial septostomy and Pott's shunt. Cox proportional hazard modelling was used to assess whether Ees/Ea was predictive of time-to-event. In patients with IPAH/HPAH, Ees/Ea_(Kind) and Ees/Ea_(Takeuchi) were both independently associated with time to hard event (p=0.003 and p=0.001, respectively) and when adjusted for indexed pulmonary vascular resistance (p=0.032 and p=0.013, respectively). Neither Ees/Ea_(Kind) nor Ees/Ea_(Takeuchi) were associated with time to soft event. In patients with APAH, neither Ees/Ea_(Kind) nor Ees/Ea_(Takeuchi) were associated with time to hard event or soft event. Ees/Ea derived from pressure alone is a strong independent predictor of adverse outcome and could be a potential powerful prognostic tool for paediatric PAH.

Dufva MJ ，Ivy D ，Campbell K ，Lam A ，Rauff A ，Breeman KTN ，Douwes JM ，Berger RMF ，Kheyfets VO ，Hunter K ... -  《Open Heart》

Pulmonary Arterial Elastance and INTERMACS-Defined Right Heart Failure Following Left Ventricular Assist Device.

Muslem R ，Ong CS ，Tomashitis B ，Schultz J ，Ramu B ，Craig ML ，Van Bakel AB ，Gilotra NA ，Sharma K ，Hsu S ，Whitman GJ ，Leary PJ ，Cogswell R ，Lozonschi L ，Houston BA ，Zijlstra F ，Caliskan K ，Bogers AJJC ，Tedford RJ ... -  《-》

Predictors and prognosis of right ventricular function in pulmonary hypertension due to heart failure with reduced ejection fraction.

Failure of right ventricular (RV) function worsens outcome in pulmonary hypertension (PH). The adaptation of RV contractility to afterload, the RV-pulmonary artery (PA) coupling, is defined by the ratio of RV end-systolic to PA elastances (Ees/Ea). Using pressure-volume loop (PV-L) technique we aimed to identify an Ees/Ea cut-off predictive for overall survival and to assess hemodynamic and morphologic conditions for adapted RV function in secondary PH due to heart failure with reduced ejection fraction (HFREF). This post hoc analysis is based on 112 patients of the prospective Magdeburger Resynchronization Responder Trial. All patients underwent right and left heart echocardiography and a baseline PV-L and RV catheter measurement. A subgroup of patients (n = 50) without a pre-implanted cardiac device underwent magnetic resonance imaging at baseline. The analysis revealed that 0.68 is an optimal Ees/Ea cut-off (area under the curve: 0.697, P < 0.001) predictive for overall survival (median follow up = 4.7 years, Ees/Ea ≥ 0.68 vs. <0.68, log-rank 8.9, P = 0.003). In patients with PH (n = 76, 68%) multivariate Cox regression demonstrated the independent prognostic value of RV-Ees/Ea in PH patients (hazard ratio 0.2, P < 0.038). Patients without PH (n = 36, 32%) and those with PH but RV-Ees/Ea ≥ 0.68 showed comparable RV-Ees/Ea ratios (0.88 vs. 0.9, P = 0.39), RV size/function, and survival. In contrast, secondary PH with RV-PA coupling ratio Ees/Ea < 0.68 corresponded extremely close to cut-off values that define RV dilatation/remodelling (RV end-diastolic volume >160 mL, RV-mass/volume-ratio ≤0.37 g/mL) and dysfunction (right ventricular ejection fraction <38%, tricuspid annular plane systolic excursion <16 mm, fractional area change <42%, and stroke-volume/end-systolic volume ratio <0.59) and is associated with a dramatically increased short and medium-term all-cause mortality. Independent predictors of prognostically unfavourable RV-PA coupling (Ees/Ea < 0.68) in secondary PH were a pre-existent dilated RV [end-diastolic volume >171 mL, odds ratio (OR) 0.96, P = 0.021], high pulsatile load (PA compliance <2.3 mL/mmHg, OR 8.6, P = 0.003), and advanced systolic left heart failure (left ventricular ejection fraction <30%, OR 1.23, P = 0.028). The RV-PA coupling ratio Ees/Ea predicts overall survival in PH due to HFREF and is mainly affected by pulsatile load, RV remodelling, and left ventricular dysfunction. Prognostically favourable coupling (RV-Ees/Ea ≥ 0.68) in PH was associated with preserved RV size/function and mid-term survival, comparable with HFREF without PH.

Schmeißer A ，Rauwolf T ，Groscheck T ，Fischbach K ，Kropf S ，Luani B ，Tanev I ，Hansen M ，Meißler S ，Schäfer K ，Steendijk P ，Braun-Dullaeus RC ... -  《ESC Heart Failure》