Biventricular responses to exercise and their relation to cardiorespiratory fitness in pediatric pulmonary hypertension.

Despite exercise intolerance being predictive of outcomes in pulmonary arterial hypertension (PAH), its underlying cardiac mechanisms are not well described. The aim of the study was to explore the biventricular response to exercise and its associations with cardiorespiratory fitness in children with PAH. Participants underwent incremental cardiopulmonary exercise testing and simultaneous exercise echocardiography on a recumbent cycle ergometer. Linear mixed models were used to assess cardiac function variance and associations between cardiac and metabolic parameters during exercise. Eleven participants were included with a mean age of 13.4 ± 2.9 yr old. Right ventricle (RV) systolic pressure (RVsp) increased from a mean of 59 ± 25 mmHg at rest to 130 ± 40 mmHg at peak exercise (P < 0.001), whereas RV fractional area change (RV-FAC) and RV-free wall longitudinal strain (RVFW-Sl) worsened (35.2 vs. 27%, P = 0.09 and -16.6 vs. -14.6%, P = 0.1, respectively). At low- and moderate-intensity exercise, RVsp was positively associated with stroke volume and O2 pulse (P < 0.1). At high-intensity exercise, RV-FAC, RVFW-Sl, and left ventricular longitudinal strain were positively associated with oxygen uptake and O2 pulse (P < 0.1), whereas stroke volume decreased toward peak (P = 0.04). In children with PAH, the increase of pulmonary pressure alone does not limit peak exercise, but rather the concomitant reduced RV functional reserve, resulting in RV to pulmonary artery (RV-PA) uncoupling, worsening of interventricular interaction and LV dysfunction. A better mechanistic understanding of PAH exercise physiopathology can inform stress testing and cardiac rehabilitation in this population.NEW & NOTEWORTHY In children with pulmonary arterial hypertension, there is a marked increase in pulmonary artery pressure during physical activity, but this is not the underlying mechanism that limits exercise. Instead, right ventricle-to-pulmonary artery uncoupling occurs at the transition from moderate to high-intensity exercise and correlates with lower peak oxygen uptake. This highlights the more complex underlying pathological responses and the need for multiparametric assessment of cardiac function reserve in these patients when feasible.

Sex-dependent remodeling of right ventricular function in a rat model of pulmonary arterial hypertension.

Right ventricular (RV) function is an important prognostic indicator for pulmonary arterial hypertension (PAH), a vasculopathy that primarily and disproportionally affects women with distinct pre- and postmenopausal clinical outcomes. However, most animal studies have overlooked the impact of sex and ovarian hormones on RV remodeling in PAH. Here, we combined invasive measurements of RV hemodynamics and morphology with computational models of RV biomechanics in sugen-hypoxia (SuHx)-treated male, ovary-intact female, and ovariectomized female rats. Despite similar pressure overload levels, SuHx induced increases in end-diastolic elastance and passive myocardial stiffening, notably in male SuHx animals, corresponding to elevated diastolic intracellular calcium. Increases in end-systolic chamber elastance were largely explained by myocardial hypertrophy in male and ovary-intact female rats, whereas ovariectomized females exhibited contractility recruitment via calcium transient augmentation. Ovary-intact female rats primarily responded with hypertrophy, showing fewer myocardial mechanical alterations and less stiffening. These findings highlight sex-related RV remodeling differences in rats, affecting systolic and diastolic RV function in PAH.NEW & NOTEWORTHY Combining hemodynamic and morphological measurements from male, female, and ovariectomized female pulmonary arterial hypertension (PAH) rats revealed distinct adaptation mechanisms despite similar pressure overload. Males showed the most diastolic stiffening. Ovariectomized females had enhanced myocyte contractility and calcium transient upregulation. Ovary-intact females primarily responded with hypertrophy, experiencing milder passive myocardial stiffening and no changes in myocyte shortening. These findings suggest potential sex-specific pathways in right ventricular (RV) adaptation to PAH, with implications for targeted interventions.

Biventricular catheterization combined with pressure-volume loop monitoring provides insight into the dynamic effects of left ventricular assist devices ramp on right ventricular function.

Ramp studies are utilized for speed optimization of continuous flow left ventricular assist devices (CF-LVADs). We here report the utility of combined left and right heart catheterization during a ramp study to ensure a comprehensive understanding of the hemodynamic implications on both ventricles. Pressure-volume loop (PV loop) monitoring uncovered compromised systolic and mildly compromised right ventricular function with increasing LVAD speeds, despite improvement in left ventricular unloading. These findings informed patient management and highlight the potential utility of PV loop monitoring as an adjunct to left and right heart catheterization during ramp studies of next-generation LVADs.

Role of hemolysis on pulmonary arterial compliance and right ventricular systolic function after cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) is associated with intravascular hemolysis which depletes endogenous nitric oxide (NO). The impact of hemolysis on pulmonary arterial compliance (PAC) and right ventricular systolic function has not been explored yet. We hypothesized that decreased NO availability is associated with worse PAC and right ventricular systolic function after CPB. METHODS: This is a secondary analysis of an observational cohort study in patients undergoing cardiac surgery with CPB at Massachusetts General Hospital, USA (2014-2015). We assessed PAC (stroke volume/pulmonary artery pulse pressure ratio), and right ventricular function index (RVFI) (systolic pulmonary arterial pressure/cardiac output), as well as NO consumption at 15 min, 4 h and 12 h after CPB. Patients were stratified by CPB duration. Further, we assessed the association between changes in NO consumption with PAC and RVFI between 15min and 4 h after CPB. RESULTS: PAC was lowest at 15min after CPB and improved over time (n = 50). RVFI was highest -worse right ventricular function- at CPB end and gradually decreased. Changes in hemolysis, PAC and RVFI differed over time by CPB duration. PAC inversely correlated with total pulmonary resistance (TPR). TPR and PAC positively and negatively correlated with RVFI, respectively. NO consumption between 15min and 4 h after CPB correlated with changes in PAC (-0.28 ml/mmHg, 95%CI -0.49 to -0.01, p = 0.012) and RVFI (0.14 mmHg*L-1*min, 95%CI 0.10 to 0.18, p < 0.001) after multivariable adjustments. CONCLUSION: PAC and RVFI are worse at CPB end and improve over time. Depletion of endogenous NO may contribute to explain changes in PAC and RVFI after CPB.

Intubation and Mechanical Ventilation in Patients with Acute Pulmonary Embolism: A Scoping Review.

OBJECTIVES: High-risk acute pulmonary embolism (PE) is associated with significant mortality and may require emergency endotracheal intubation and mechanical ventilation. Intubation and ventilation are thought to exacerbate cardiorespiratory instability. Our purpose was to conduct a systematic literature review to identify studies investigating peri-intubation events in acute PE. METHODS: A systematic search of Medline, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library was performed. Results were screened by two independent observers. Studies reporting on intubation and positive pressure ventilation in acute PE patients were included. The primary outcome was adverse events during the peri-intubation period. Data was synthesized and an assessment of risk of bias was conducted. The review was registered on PROSPERO (CRD42023444483). RESULTS: 4100 unique articles were screened. Three retrospective studies comprising 104 patients with acute PE met criteria and were included. Peri-intubation, hemodynamic collapse was observed in 19%-28% of cases. Patients with hemodynamic collapse exhibited higher rates of echocardiographic RV dysfunction. CONCLUSIONS: Peri-intubation adverse events are common in patients with acute PE. Current evidence is limited and highlights the need for further research to optimize management of respiratory failure in acute PE and patient selection for intubation to improve patient outcomes.

Depressive symptoms, right ventricular function, and muscular strength are associated with peak oxygen uptake in patients with implantable left ventricular assist devices.

BACKGROUND: Left ventricular assist device (LVAD) implantation is among the most effective treatment options for patients with severe heart failure. Although previous studies have examined the factors related to peak oxygen uptake (peak VO2 ), they were limited by the few patients involved and their focus on medical and physical functions. Therefore, this study comprehensively examined the factors associated with peak VO2 , which is an important prognostic factor in patients with implantable LVADs. METHODS: Eighty-nine patients who underwent initial LVAD implantation and were eligible for cardiopulmonary exercise testing (CPX) between May 2014 and September 2021 were included. The patients' mean age was 48 ± 12 years, and 70% were males. Based on previous studies, the cut-off was set at 12 and 14 mL/kg/min for patients taking ß-blocker and those not taking ß-blockers, respectively. Furthermore, factors associated with peak VO2 were examined using multivariate logistic regression analysis. RESULTS: The mean time from surgery to CPX administration was 73 ± 40 days. The high group had a higher cardiac index, right ventricular stroke work index (RVSWI), and isometric knee extensor muscular strength and lower Patient Health Questionnaire-9 (PHQ-9) and B-type natriuretic peptide values than the low group. Multivariate logistic regression analysis showed that RVSWI and KEMS were positively correlated, whereas PHQ-9 was negatively associated with peak VO2 . CONCLUSION: Right ventricular function, depressive symptoms, and lower limb muscular strength were associated with exercise capacity in patients with implantable LVADs.

Immediate cardiopulmonary responses to consecutive pulmonary embolism: a randomized, controlled, experimental study.

BACKGROUND: Acute pulmonary embolism (PE) induces ventilation-perfusion mismatch and hypoxia and increases pulmonary pressure and right ventricular (RV) afterload, entailing potentially fatal RV failure within a short timeframe. Cardiopulmonary factors may respond differently to increased clot burden. We aimed to elucidate immediate cardiopulmonary responses during successive PE episodes in a porcine model. METHODS: This was a randomized, controlled, blinded study of repeated measurements. Twelve pigs were randomly assigned to receive sham procedures or consecutive PEs every 15 min until doubling of mean pulmonary pressure. Cardiopulmonary assessments were conducted at 1, 2, 5, and 13 min after each PE using pressure-volume loops, invasive pressures, and arterial and mixed venous blood gas analyses. ANOVA and mixed-model statistical analyses were applied. RESULTS: Pulmonary pressures increased after the initial PE administration (p < 0.0001), with a higher pulmonary pressure change compared to pressure change observed after the following PEs. Conversely, RV arterial elastance and pulmonary vascular resistance was not increased after the first PE, but after three PEs an increase was observed (p = 0.0103 and p = 0.0015, respectively). RV dilatation occurred following initial PEs, while RV ejection fraction declined after the third PE (p = 0.004). RV coupling exhibited a decreasing trend from the first PE (p = 0.095), despite increased mechanical work (p = 0.003). Ventilatory variables displayed more incremental changes with successive PEs. CONCLUSION: In an experimental model of consecutive PE, RV afterload elevation and dysfunction manifested after the third PE, in contrast to pulmonary pressure that increased after the first PE. Ventilatory variables exhibited a more direct association with clot burden.

Comparison of prognostic value among echocardiographic surrogates of right ventricular-pulmonary arterial coupling: A three-dimensional echocardiographic study.

OBJECTIVES: Right ventricular (RV)-pulmonary arterial (PA) coupling is important in various cardiac diseases. Recently, several echocardiographic surrogates for RV-PA coupling have been proposed and reported to be useful in predicting outcomes. However, it remains unclear which surrogate is the most clinically relevant. This study aimed to comprehensively compare the prognostic value of different echocardiographic RV-PA coupling surrogates. METHODS: We retrospectively reviewed 242 patients with various cardiac conditions who underwent comprehensive transthoracic echocardiography with three-dimensional RV data. In addition to conventional parameters including tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and PA systolic pressure (PASP), we analyzed RV free wall and global longitudinal strain (FWLS and GLS). We also obtained RV ejection fraction (RVEF), stroke volume (SV), and end-systolic volume (ESV) using three-dimensional RV analysis. RV-PA coupling surrogates were calculated as TAPSE/PASP, FAC/PASP, FWLS/PASP, GLS/PASP, RVEF/PASP, and SV/ESV. The study endpoint was a composite outcome of all-cause death or cardiovascular hospitalization within 1 year. RESULTS: In multivariable analysis, all the RV-PA coupling surrogates were independent predictors of the outcome. Among the surrogates, the model with TAPSE/PASP showed the lowest prognostic value in model fit and discrimination ability, whereas the model with RVEF/PASP exhibited the highest prognostic value. The partial likelihood ratio test indicated that the model with RVEF/PASP was significantly better than the model with TAPSE/PASP (p < .024). CONCLUSION: All the RV-PA coupling surrogates were independent predictors of the outcome. Notably, RVEF/PASP had the highest prognostic value among the surrogates.

Quantitative evaluation of right ventricular myocardial function changes in patients with atrial septal defect before and after occlusion by noninvasive right ventricular pressure-strain loop.

OBJECTIVE: The noninvasive right ventricular pressure-strain loop (PSL) represents a novel method for the quantitative assessment of right ventricular myocardial function. Given that atrial septal defect (ASD) is a prevalent congenital heart anomaly associated with right ventricular volume overload, this study aimed to quantitatively assess the myocardial function of the right ventricle in ASD patients pre- and post-occlusion by noninvasive right ventricular PSL. METHODS: This study included 36 patients diagnosed with secundum ASD group and 30 healthy adults (control group). We compared conventional right ventricular echocardiographic parameters, right ventricular strain, and myocardial work in the ASD group before occlusion, two days post-occlusion, and three months post-occlusion, with those in the control group. RESULTS: Prior to and two days following occlusion, the ASD group exhibited higher right ventricular global work index (RVGWI), right ventricular global wasted work (RVGWW), and right ventricular global constructive work (RVGCW) compared to the control group (P < .05). Within the ASD group, post-occlusion, RVGWI, RVGCW, and RVGWW values were significantly reduced compared to pre-occlusion values (P < .001). Furthermore, RVGWI and RVGCW showed a significant decrease three months after occlusion compared to two days post-occlusion (P < .05). Multivariate regression analysis identified ASD diameter and pulmonary artery systolic pressure (PASP) as independent predictors of RVGWI (ß = .405, P < .001; ß = 2.307, P = .037) and RVGCW(ß = .350, P<.001; ß = 1.967, P = .023). CONCLUSIONS: The noninvasive right ventricular PSL effectively demonstrates the alterations in right ventricular myocardial function in ASD patients, pre- and post-occlusion. The metrics of right ventricular myocardial work (RVMW) offer a novel indicator for evaluating right ventricular myocardial function in these patients. Moreover, ASD diameter and PASP emerge as independent determinants of RVGWI and RVGCW.

Feasibility, reproducibility, and accuracy of echocardiographic right ventricular systolic function assessments in childhood cancer survivors at risk for heart failure.

PURPOSE: We sought to assess the feasibility, reproducibility, and accuracy of conventional and newer echocardiographic measures of right ventricular (RV) systolic function in adolescent and young adult childhood cancer survivors treated with anthracyclines. METHODS: Echocardiography and cardiac magnetic resonance imaging (CMR) were acquired ≤60 days apart in prospectively recruited survivors and RV functional measures were quantitated by blinded observers. Repeat quantitation was performed in a subset to evaluate reproducibility. For each echocardiographic measure, Spearman correlations with CMR measures were calculated, and values in participants with CMR RV ejection fraction (RVEF) ≥48% and RVEF <48% were compared using two sample Wilcoxon rank-sum tests. RESULTS: Among 58 participants, mean age was 18.2 years (range 13.1-25.2) and five participants had CMR RVEF <48%. Intra- and inter-observer coefficients of variation were 8.2%-10.1% and 10.5%-12.0% for adjusted automated strain measures, and 5.2%-8.7% and 2.7% for 3D RVEF, respectively. No echocardiographic measures were significantly correlated with CMR RVEF; only tricuspid annular plane systolic excursion was correlated with CMR RV stroke volume (r = .392, p = .003). Participants with RV dysfunction had worse automated global longitudinal strain (-20.3% vs. -23.9%, p = .007) and free wall longitudinal strain (-23.7% vs. -26.7%, p = .09). CONCLUSIONS: Echocardiographic strain and 3D RV function measurements were feasible and reproducible in at-risk childhood cancer survivors. Although not associated with CMR RVEF in this population with predominantly normal RV function, automated strain measurements were more abnormal in participants with RV dysfunction, suggesting potential clinical utility of these measures.