The association of right ventricular-pulmonary arterial coupling and pulmonary vascular resistance in adult patients with uncorrected atrial septal defect.

BACKGROUND: Atrial septal defects (ASD) are the most common type of adult congenital heart disease (ACHD) associated with a high risk developing of pulmonary arterial hypertension (PAH). ASD closure is not recommended in patients with PAH and Pulmonary Vascular Resistance (PVR) ≥ 5 Wood Unit (WU). Noninvasive methods have been proposed to measure PVR; however, their accuracy remains low. Right Ventricle (RV) - Pulmonary Artery (PA) coupling is defined as the ability of the RV to adapt to high-resistance conditions. Tricuspid Annular Plane Systolic Excursion (TAPSE)/estimated pulmonary artery systolic pressure (ePASP) calculation using echocardiography is a noninvasive technique that has been proposed as a surrogate equation to evaluate RV-PA coupling. Currently, no research has demonstrated a relationship between RV-PA coupling and PVR in patients with ASD. METHODS: The study participants were consecutive eligible patients with ASD who underwent right heart catheterization (RHC) and echocardiography at Hasan Sadikin General Hospital, Bandung. Both the procedures were performed on the same day. RV-PA Coupling, defined as TAPSE/ePASP > 0.31, was assessed using echocardiography. The PVR was calculated during RHC using the indirect Fick method. RESULTS: There were 58 patients with ASD underwent RHC and echocardiography. Among them, 18 had RV/PA Coupling and 40 had RV/PA Uncoupling. The PVR values were significantly different between the two groups (p = 0.000). Correlation test between TAPSE/ePASP with PVR showed moderate negative correlation (r= -0.502, p = 0.001). TAPSE/ePASP ≤ 0.34 is the cutoff point to predict PVR > 5 WU with sensitivity of 91.7% and specificity 63.6%. CONCLUSION: This study showed a moderate negative correlation between TAPSE/ePASP and PVR. TAPSE/ePASP ≤ 0.34 could predict PVR > 5 WU with good sensitivity.

Right ventricular function indices and platelet parameters for early prediction value of bronchopulmonary dysplasia: a retrospective study.

BACKGROUND: To examine the value of early echocardiographic indices for the right ventricular function combined with platelet(PLT) parameters for predicting bronchopulmonary dysplasia (BPD) in preterm infants. METHODS: This retrospective study included infants with gestational age (GA) below 32 weeks, who were admitted to the neonatal intensive care unit(NICU). The detection rate of tricuspid regurgitation jet velocity (TRVJ), ventricular septal flattening, pulmonary artery widening, right ventricular dilation, and right atrial enlargement on the 7th day of life (DOL 7) were compared between BPD and non-BPD infants. Echocardiographic indices of the right ventricular function including tricuspid annular plane systolic excursion (TAPSE) and right ventricular index of myocardial performance (RIMP) were measured on 1 day of life (DOL 1)、on DOL 7 and on 14 day of life (DOL 14) respectively. The PLT parameters including the PLT count, mean platelet volume (MPV), platelet hematocrit (PCT) level, and platelet distribution width (PDW) were measured on the DOL 1,DOL 7, and DOL 14. Multivariate logistic regression was used to analyze the relationship between these parameters and BPD. Receiver operating characteristic curve analysis was performed to assess the predictive value of the right ventricular function indices and PLT parameters for BPD. RESULTS: A total of 220 preterm infants were included in this study, and of these, 85 infants developed BPD among them. The RIMP of the BPD group on DOL 14 was higher than that of the non-BPD group (P < 0.05). The TAPSE of the BPD group on DOL 14 was lower than that of the non-BPD group (P < 0.05). The PLT count of the BPD group on DOL 1 was lower than that of the non-BPD group (P < 0.05), and the MPV of the BPD group on DOL 1 was higher than that of the non-BPD group (P < 0.05). Using multivariate logistic regression, GA、invasive mechanical ventilation duration ≥ 7 days、 PLT、 MPV、 TAPSE and RIMP were found to be independent risk factors for BPD. The area under the receiver operating characteristic curve was 0.846 (95CI: 0.794∼0.899), which improved when using right ventricular function indices combined with platelet parameters. CONCLUSION: TAPSE and RIMP combined with PLT count and MPV can help identify preterm infants at an increased risk of developing BPD.

Right Ventricular Strain Derived from Cardiac MRI Feature Tracking for the Diagnosis and Prognosis of Arrhythmogenic Right Ventricular Cardiomyopathy.

Purpose To demonstrate the myocardial strain characteristics of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), based on revised Task Force Criteria (rTFC), and to explore the prognostic value of strain analysis in ARVC. Materials and Methods This retrospective study included 247 patients (median age, 38 years [IQR, 28-48 years]; 167 male, 80 female) diagnosed with ARVC, based on rTFC, between 2014 and 2018. Patients were divided into "possible" (n =25), "borderline" (n = 40), and "definite" (n = 182) ARVC groups following rTFC. Biventricular global strain parameters were calculated using cardiac MRI feature tracking (FT). The primary outcome was defined as a composite of cardiovascular events, including cardiovascular death, heart transplantation, and appropriate implantable cardioverter defibrillator discharge. Univariable and multivariable cumulative logistic regression and Cox proportional hazards regression analysis were used to evaluate the diagnostic and prognostic value of right ventricle (RV) strain parameters. Results Patients with definite ARVC had significantly reduced RV global strain in all three directions compared with possible or borderline groups (all P < .001). RV global longitudinal strain (GLS) was an independent predictor for disease (odds ratio, 1.09 [95% CI: 1.02, 1.16]; P = .009). During a median follow-up of 3.4 years (IQR, 2.0-4.9 years), 55 patients developed primary end point events. Multivariable analysis showed that RV GLS was independently associated with the occurrence of cardiovascular events (hazard ratio, 1.15 [95% CI: 1.07, 1.24]; P < .001). Kaplan-Meier analysis showed that patients with RV GLS worse than median had a higher risk of combined cardiovascular events (log-rank P < .001). Conclusion RV GLS derived from cardiac MRI FT demonstrated good diagnostic and prognostic value in ARVC. Keywords: MR Imaging, Image Postprocessing, Cardiac, Right Ventricle, Cardiomyopathies, Arrhythmogenic Right Ventricular Cardiomyopathy, Revised Task Force Criteria, Cardiovascular MR, Feature Tracking, Cardiovascular Events Supplemental material is available for this article. © RSNA, 2024.

Sacubitril/valsartan has an underestimated impact on the right ventricle in patients with sleep-disordered breathing, especially central sleep apnoea syndrome.

BACKGROUND: Sacubitril/valsartan has been demonstrated to significantly improve left ventricular performance and remodelling in patients with heart failure. However, its effects on the right ventricle in patients with chronic heart failure and sleep-disordered breathing (SDB) have not been studied. AIM: To investigate the impact of sacubitril/valsartan treatment on right ventricular function in patients with SDB. METHODS: This was a subanalysis of an observational prospective multicentre study involving 101 patients. At inclusion, patients were evaluated by echocardiography and nocturnal ventilatory polygraphy, which allowed patients to be divided into three groups: "central-SDB"; "obstructive-SDB"; and "no-SDB". RESULTS: After 3 months of sacubitril/valsartan therapy, a positive impact on right ventricular function was observed. In the general population, tricuspid annular plane systolic excursion increased by +1.32±4.74mm (P=0.024) and systolic pulmonary artery pressure decreased by -3.1±10.91mmHg (P=0.048). The central-SDB group experienced the greatest echocardiographic improvement, with a significant increase in tricuspid annular plane systolic excursion of +2.1±4.9mm (P=0.045) and a significant reduction in systolic pulmonary artery pressure of -8.4±9.7mmHg (P=0.001). CONCLUSIONS: Sacubitril/valsartan improved right ventricular function in patients with heart failure and SDB after only 3 months of treatment. The greatest improvement in right ventricular function was observed in the central-SDB group.

3D Imaging Reveals Complex Microvascular Remodeling in the Right Ventricle in Pulmonary Hypertension.

BACKGROUND: Pathogenic concepts of right ventricular (RV) failure in pulmonary arterial hypertension focus on a critical loss of microvasculature. However, the methods underpinning prior studies did not take into account the 3-dimensional (3D) aspects of cardiac tissue, making accurate quantification difficult. We applied deep-tissue imaging to the pressure-overloaded RV to uncover the 3D properties of the microvascular network and determine whether deficient microvascular adaptation contributes to RV failure. METHODS: Heart sections measuring 250-µm-thick were obtained from mice after pulmonary artery banding (PAB) or debanding PAB surgery and properties of the RV microvascular network were assessed using 3D imaging and quantification. Human heart tissues harvested at the time of transplantation from pulmonary arterial hypertension cases were compared with tissues from control cases with normal RV function. RESULTS: Longitudinal 3D assessment of PAB mouse hearts uncovered complex microvascular remodeling characterized by tortuous, shorter, thicker, highly branched vessels, and overall preserved microvascular density. This remodeling process was reversible in debanding PAB mice in which the RV function recovers over time. The remodeled microvasculature tightly wrapped around the hypertrophied cardiomyocytes to maintain a stable contact surface to cardiomyocytes as an adaptation to RV pressure overload, even in end-stage RV failure. However, microvasculature-cardiomyocyte contact was impaired in areas with interstitial fibrosis where cardiomyocytes displayed signs of hypoxia. Similar to PAB animals, microvascular density in the RV was preserved in patients with end-stage pulmonary arterial hypertension, and microvascular architectural changes appeared to vary by etiology, with patients with pulmonary veno-occlusive disease displaying a lack of microvascular complexity with uniformly short segments. CONCLUSIONS: 3D deep tissue imaging of the failing RV in PAB mice, pulmonary hypertension rats, and patients with pulmonary arterial hypertension reveals complex microvascular changes to preserve the microvascular density and maintain a stable microvascular-cardiomyocyte contact. Our studies provide a novel framework to understand microvascular adaptation in the pressure-overloaded RV that focuses on cell-cell interaction and goes beyond the concept of capillary rarefaction.

Isoproterenol improves hemodynamics and right ventricle-pulmonary artery coupling after heart transplantation.

Right ventricular failure (RVF) is a major cause of early mortality after heart transplantation (HT). Isoproterenol (Iso) has chronotropic, inotropic, and vasodilatory properties, which might improve right ventricle function in this setting. We aimed to investigate the hemodynamic effects of isoproterenol on patients with post-HT RVF. We conducted a 1-yr retrospective observational study including patients receiving isoproterenol (Iso) and dobutamine for early RVF after HT. A comprehensive multiparametric hemodynamic evaluation was performed successively three times: no isoproterenol, low doses: 0.025 µg/kg/min, and high doses: 0.05 µg/kg/min (henceforth, respectively, called no Iso, low Iso, and high Iso). From June 2022 to June 2023, 25 patients, median [interquartile range (IQR) 25-75] age 54 [38-61] yr, were included. Before isoproterenol was introduced, all patients received dobutamine, and 15 (60%) were on venoarterial extracorporeal membrane oxygenation (VA-ECMO). Isoproterenol significantly increased heart rate from 84 [77-99] (no Iso) to 91 [88-106] (low Iso) and 102 [90-122] beats/min (high Iso, P < 0.001). Similarly, cardiac index rose from 2.3 [1.4-3.1] to 2.7 [1.8-3.4] and 3 [1.9-3.7] L/min/m2 (P < 0.001) with a concomitant increase in indexed stroke volume (28 [17-34] to 31 [20-34] and 33 [23-35] mL/m2, P < 0.05). Effective pulmonary arterial elastance and pressures were not modified by isoproterenol. Pulmonary vascular resistance (PVR) tended to decrease from 2.9 [1.4-3.6] to 2.3 [1.3-3.5] wood units (WU), P = 0.06. Right ventricular ejection fraction/systolic pulmonary artery pressure (sPAP) evaluating right ventricle-pulmonary artery (RV-PA) coupling increased after isoproterenol from 0.8 to 0.9 and 1%·mmHg-1 (P = 0.001). In conclusion, in post-HT RVF, isoproterenol exhibits chronotropic and inotropic effects, thereby improving RV-PA coupling and resulting in a clinically relevant increase in the cardiac index.NEW & NOTEWORTHY This study offers a detailed and comprehensive hemodynamic investigation at the bedside, illustrating the favorable impact of isoproterenol on right ventricular-pulmonary arterial coupling and global hemodynamics. It elucidates the physiological effects of an underused inotropic strategy in a critical clinical scenario. By enhancing cardiac hemodynamics, isoproterenol has the potential to expedite right ventricular recovery and mitigate primary graft dysfunction, thereby reducing the duration of mechanical support and intensive care unit stay posttransplantation.

Prognostic Value and Determinants of High-Sensitivity Cardiac Troponin T in Patients With a Systemic Right Ventricle: Insights From the SERVE Trial.

BACKGROUND: The determinants and prognostic value of high-sensitivity cardiac troponin T (hs-cTnT) among patients with a systemic right ventricle are largely unknown. METHODS AND RESULTS: Ninety-eight patients from the randomized controlled SERVE (Effect of Phosphodiesterase-5 Inhibition With Tadalafil on Systemic Right Ventricular Size and Function) trial were included. The correlation between baseline hs-cTnT concentrations and biventricular volumes and function quantified by cardiac magnetic resonance or cardiac multirow detector computed tomography was assessed by adjusted linear regression models. The prognostic value of hs-cTnT was assessed by adjusted Cox proportional hazards models, survival analysis, and concordance statistics. The primary outcome was time to the composite of clinically relevant arrhythmia, hospitalization for heart failure, or all-cause death. Median age was 39 (interquartile range, 32-48) years, and 32% were women. Median hs-cTnT concentration was 7 (interquartile range, 4-11) ng/L. Coefficients of determination for the relationship between hs-cTnT concentrations and right ventricular end-systolic volume index and right ventricular ejection fraction (RVEF) were +0.368 (P=0.046) and -0.381 (P=0.018), respectively. The sex- and age-adjusted hazard ratio for the primary outcome of hs-cTnT at 2 and 4 times the reference level (5 ng/L) were 2.89 (95% CI, 1.14-7.29) and 4.42 (95% CI, 1.21-16.15), respectively. The prognostic performance quantified by the concordance statistics for age- and sex-adjusted models based on hs-cTnT, right ventricular ejection fraction, and peak oxygen uptake predicted were comparable: 0.71% (95% CI, 0.61-0.82), 0.72% (95% CI, 0.59-0.84), and 0.71% (95% CI, 0.59-0.83), respectively. CONCLUSIONS: Hs-cTnT concentration was significantly correlated with right ventricular ejection fraction and right ventricular end-systolic volume index in patients with a systemic right ventricle. The prognostic accuracy of hs-cTnT was comparable to that of right ventricular ejection fraction and peak oxygen uptake predicted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03049540.

The right ventricle outflow tract systolic function could predict the severity of the cirrhosis.

Background/aim: The distinctive liver framework is converted into structurally abnormal nodules as a consequence of tissue fibrosis in cirrhosis. Cardiac dysfunction in cirrhosis was described, and the term "cirrhotic cardiomyopathy (CCM)" was coined to describe this syndrome. Recent research has shown that the contractile characteristics of the right ventricular outflow tract (RVOT) have a significant impact on right ventricular functions. The right ventricular outflow tract-systolic excursion is an important systolic function marker of RVOT (RVOT-SE). There has yet to be published research on RVOT function in cirrhotic patients. We looked at the relationship between cirrhosis severity and the RVOT-SE. Materials and methods: Sixty-nine consecutive hepatic cirrhotic patients were recruited for the research between June 1, 2018 and January 1, 2022. A medical history, thorough physical examination, laboratory investigations, echocardiographic evaluation, and RVOT-SE were obtained. The patients were separated into two groups: those with compensated cirrhosis (Child-Pugh class 1) and those with decompensated cirrhosis (Child-Pugh class 2 and 3). Results: On the numerous standard echocardiographic parameters that examined the diameter and function of the left ventricle, we observed no significant difference between groups. Nevertheless, a statistically significant difference in Right Ventricle Wall (RVW) (p = 0.014), systolic pulmonary artery pressure (sPAP) (p = 0.034), RVOT-SE (p = 0.003), and Tricuspid Annular Plane Systolic Excursion (TAPSE) (p = 0.042) was detected across cirrhosis groups. The RVOT-SE had a positive correlation with cirrhosis severity (OR: 0.607; 95% CI: 0.425-0.866; p = 0.006), according to multiple logistic regression studies. According to the ROC curve study, RVOT-SE 8.8 cm/s predicted decompensated cirrhosis with 72% sensitivity and 72.7% specificity (AUC = 0.715, p: 0.001). Conclusion: In the current study, we found that RVOT-SE was related to the severity of cirrhosis. Larger patient cohorts and multi-center investigations will provide light on the notion.

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.

Arrhythmogenic right ventricular cardiomyopathy with sustained ventricular tachycardia: a case report.

INTRODUCTION: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an infrequent hereditary disorder distinguished by fibrofatty replacement of the myocardium in the right ventricular, which predisposes individuals to life-threatening arrhythmias. This case delineates an ARVC patient who suffered recurrent bouts of sustained ventricular tachycardia (VT). In this case, we mainly discuss the application of myocardial contrast echocardiography (MCE) in displaying myocardial fibrosis in patients with ARVC. CASE PRESENTATION: A 43-year-old male experienced three episodes of unexplained VT over an eight-year period, accompanied by symptoms of chest discomfort, palpitations and dizziness. Coronary angiography revealed no significant coronary stenosis. The electrocardiogram (ECG) results indicated characteristic epsilon waves in right precordial leads, and subsequent echocardiography identified right ventricular enlargement and right ventricular systolic dysfunction. MCE further disclosed regional myocardial ischemia at the epicardium of the left ventricular apex. Ultimately, cardiovascular magnetic resonance imaging (CMR) corroborated the ARVC diagnosis, highlighting linear intensification in the right ventricle during the delayed enhancement. CONCLUSION: Prompt identification of ARVC is crucial for timely intervention and management. MCE may offer an effective and valuable technique for the detection of myocardial involvement in ARVC patient.

Heterogeneity of right ventricular echocardiographic parameters in systemic lupus erythematosus among four clinical subgroups, as stratified by clinical organ involvement in observational cohort.

BACKGROUND: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease. Cardiac involvement in SLE is rare but plays an important prognostic role. The degree of cardiac involvement according to SLE subsets defined by non-cardiac manifestations is unknown. The objective of this study was to identify differences in transthoracic echocardiography (TTE) parameters associated with different SLE subgroups. METHODS: One hundred eighty-one patients who fulfilled the 2019 American College of Rheumatology/EULAR classification criteria for SLE and underwent baseline TTE were included in this cross-sectional study. We defined four subsets of SLE based on the predominant clinical manifestations. A multivariate multinomial regression analysis was performed to determine whether TTE parameters differed between groups. RESULTS: Four clinical subsets were defined according to non-cardiac clinical manifestations: group A (n=37 patients) showed features of mixed connective tissue disease, group B (n=76 patients) had primarily cutaneous involvement, group C (n=18) exhibited prominent serositis and group D (n=50) had severe, multi-organ involvement, including notable renal disease. Forty TTE parameters were assessed between groups. Per multivariate multinomial regression analysis, there were statistically significant differences in early diastolic tricuspid annular velocity (RV-Ea, p<0.0001), RV S' wave (p=0.0031) and RV end-diastolic diameter (p=0.0419) between the groups. Group B (primarily cutaneous involvement) had the lowest degree of RV dysfunction. CONCLUSION: When defining clinical phenotypes of SLE based on organ involvement, we found four distinct subgroups which showed notable differences in RV function on TTE. Risk-stratifying patients by clinical phenotype could help better tailor cardiac follow-up in this population.

Relationship of TAPSE Normalized by Right Ventricular Area With Pulmonary Compliance, Exercise Capacity, and Clinical Outcomes.

BACKGROUND: While tricuspid annular plane systolic excursion (TAPSE) captures the predominant longitudinal motion of the right ventricle (RV), it does not account for ventricular morphology and radial motion changes in various forms of pulmonary hypertension. This study aims to account for both longitudinal and radial motions by dividing TAPSE by RV area and to assess its clinical significance. METHODS: We performed a retrospective analysis of 71 subjects with New York Heart Association class II to III dyspnea who underwent echocardiogram and invasive cardiopulmonary exercise testing (which defined 4 hemodynamic groups: control, isolated postcapillary pulmonary hypertension, combined postcapillary pulmonary hypertension, and pulmonary arterial hypertension). On the echocardiogram, TAPSE was divided by RV area in diastole (TAPSE/RVA-D) and systole (TAPSE/RVA-S). Analyses included correlations (Pearson and linear regression), receiver operating characteristic, and survival curves. RESULTS: On linear regression analysis, TAPSE/RVA metrics (versus TAPSE) had a stronger correlation with pulmonary artery compliance (r=0.48-0.54 versus 0.38) and peak VO2 percentage predicted (0.23-0.30 versus 0.18). Based on the receiver operating characteristic analysis, pulmonary artery compliance ≥3 mL/mm Hg was identified by TAPSE/RVA-D with an under the curve (AUC) of 0.79 (optimal cutoff ≥1.1) and by TAPSE/RVA-S with an AUC of 0.83 (optimal cutoff ≥1.5), but by TAPSE with only an AUC of 0.67. Similarly, to identify peak VO2 <50% predicted, AUC of 0.66 for TAPSE/RVA-D and AUC of 0.65 for TAPSE/RVA-S. Death or cardiovascular hospitalization at 12 months was associated with TAPSE/RVA-D ≥1.1 (HR, 0.38 [95% CI, 0.11-0.56]) and TAPSE/RVA-S ≥1.5 (HR, 0.44 [95% CI, 0.16-0.78]), while TAPSE was not associated with adverse outcomes (HR, 0.99 [95% CI, 0.53-1.94]). Among 31 subjects with available cardiac magnetic resonance imaging, RV ejection fraction was better correlated with novel metrics (TAPSE/RVA-D r=0.378 and TAPSE/RVA-S r=0.328) than TAPSE (r=0.082). CONCLUSIONS: In a broad cohort with suspected pulmonary hypertension, TAPSE divided by RV area was superior to TAPSE alone in correlations with pulmonary compliance and exercise capacity. As a prognostic marker of right heart function, TAPSE/RVA-D <1.1 and TAPSE/RVA-S <1.5 predicted adverse cardiovascular outcomes.

Physiological mechanisms behind respiratory variations in right atrial pressure in pulmonary hypertension.

Impaired respiratory variation of right atrial pressure (RAP) in severe pulmonary hypertension (PH) suggests difficulty tolerating increased preload during inspiration. Our study explores whether this impairment links to specific factors: right ventricular (RV) diastolic function, elevated RV afterload, systolic RV function, or RV-pulmonary arterial (PA) coupling. We retrospectively evaluated respiratory RAP variation in all participants enrolled in the EXERTION study. Impaired respiratory variation was defined as end-expiratory RAP - end-inspiratory RAP ≤ 2 mm Hg. RV function and afterload were evaluated using conductance catheterization. Impaired diastolic RV function was defined as end-diastolic elastance (Eed) ≥ median (0.19 mm Hg/mL). Seventy-five patients were included; PH was diagnosed in 57 patients and invasively excluded in 18 patients. Of the 75 patients, 31 (41%) had impaired RAP variation, which was linked with impaired RV systolic function and RV-PA coupling and increased tricuspid regurgitation and Eed as compared to patients with preserved RAP variation. In backward regression, RAP variation associated only with Eed. RAP variation but not simple RAP identified impaired diastolic RV function (area under the receiver operating characteristic curve [95% confidence interval]: 0.712 [0.592, 0.832] and 0.496 [0.358, 0.634], respectively). During exercise, patients with impaired RAP variation experienced greater RV dilatation and reduced diastolic reserve and cardiac output/index compared with patients with preserved RAP variation. Preserved RAP variation was associated with a better prognosis than impaired RAP variation based on the 2022 European Society of Cardiology/European Respiratory Society risk score (chi-square P = 0.025) and survival free from clinical worsening (91% vs 71% at 1 year and 79% vs 50% at 2 years [log-rank P = 0.020]; hazard ratio: 0.397 [95% confidence interval: 0.178, 0.884]). Subgroup analyses in patients with group 1 and group 4 PH demonstrated consistent findings with those observed in the overall study cohort. Respiratory RAP variations reflect RV diastolic function, are independent of RV-PA coupling or tricuspid regurgitation, are associated with exercise-induced haemodynamic changes, and are prognostic in PH.Trial registration. NCT04663217.

Normative Values of Echocardiographic Chamber Size and Function in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Echocardiographic (2-dimensional echocardiography) thresholds indicating disease or impaired functional status compared with normal physiological aging in individuals aged ≥65 years are not clearly defined. In the present study, we sought to establish standard values for 2-dimensional echocardiography parameters related to chamber size and function in older adults without cardiopulmonary or cardiometabolic conditions. METHODS: In this cross-sectional study of 3032 individuals who underwent 2-dimensional echocardiography at exam 6 in the MESA (Multi-Ethnic Study of Atherosclerosis), 608 participants fulfilled our inclusion criteria of healthy aging, with normative values defined as the mean ± 1.96 standard deviation and compared across sex and race and ethnicity. Functional status measures included NT-proBNP (N-terminal pro-B-type natriuretic peptide), 6-minute walk distance, and Kansas City Cardiomyopathy Questionnaire. Prognostic performance using MESA cutoffs was compared with established guideline cutoffs using time-to-event analysis. RESULTS: The normative aging cohort (69.5±7.0 years, 46.2% male, 47.5% White) had lower NT-proBNP, higher 6-minute walk distance, and higher (better) Kansas City Cardiomyopathy Questionnaire summary values. Women had significantly smaller chamber sizes and better biventricular systolic function. White participants had the largest chamber dimensions, whereas Chinese participants had the smallest, even after adjustment for body size. Current guidelines identified 81.6% of healthy older adults in MESA as having cardiac abnormalities. CONCLUSIONS: Among a large, diverse group of healthy older adults, we found significant differences in cardiac structure and function by sex and race/ethnicity, which may signal sex-specific cardiac remodeling with advancing age. It is crucial for existing guidelines to consider the observed and clinically significant differences in cardiac structure and function associated with healthy aging. Our study highlights that existing guidelines, which grade abnormalities in echocardiographic cardiac chamber size and function based on younger individuals, may not adequately address the anticipated changes associated with normal aging.

Early Alteration of Right Ventricle-Pulmonary Artery Coupling in Experimental Heart Failure With Preserved Ejection Fraction.

BACKGROUND: Pulmonary hypertension and right ventricular (RV) dysfunction are major prognostic determinants in patients with heart failure with preserved ejection fraction (HFpEF). The underlying pathomechanisms remain unknown. In this context, we sought to study the pathogenesis of pulmonary hypertension and RV dysfunction in a rat model of obesity-associated HFpEF. METHODS AND RESULTS: HFpEF was induced in obesity-prone rats fed a high-fat diet (n=13) and compared with obesity-resistant rats fed with standard chow (n=9). After 12 months, the animals underwent echocardiographic and hemodynamic evaluation followed by tissue sampling for pathobiological assessment. HFpEF rats presented mild RV pressure overload (with increased RV systolic pressure and pulmonary vascular resistance). No changes in pulmonary artery medial thickness and ex vivo vasoreactivity (to acetylcholine and endothelin-1) were observed and RNA sequencing analysis failed to identify gene clustering in HFpEF lungs. However, released nitric oxide levels were decreased in HFpEF pulmonary artery, while lung expression of preproendothelin-1 was increased. In HFpEF rats, RV structure and function were altered, with RV enlargement, decreased RV fractional area change and free wall longitudinal fractional shortening, together with altered right ventricle-pulmonary artery coupling (estimated by tricuspid annular plane systolic excursion/systolic pulmonary artery pressure). Hypertrophy and apoptosis (evaluated by transferase biotin- dUTP nick-end labeling staining) were increased in right and left ventricles of HFpEF rats. There was an inverse correlation between tricuspid annular plane systolic excursion/systolic pulmonary artery pressure and RV apoptotic rate. Plasma levels of soluble suppression of tumorigenicity-2, interleukin-1ß, -6 and -17A were increased in HFpEF rats. CONCLUSIONS: Obesity-associated HFpEF in rats spontaneously evolves to pulmonary hypertension-HFpEF associated with impaired right ventricle-pulmonary artery coupling that appears disproportionate to a slight increase in RV afterload.

Optimal Method for Assessing Right Ventricular to Pulmonary Arterial Coupling in Older Healthy Adults: The Multi-Ethnic Study of Atherosclerosis.

Right ventricular (RV) to pulmonary arterial (PA) coupling describes the ability of the RV to augment contractility in response to increased afterload. Several echocardiographic indexes of RV-PA coupling have been defined; however, the optimal numerator in the coupling ratio is unclear. We sought to establish which of these ratios is best for assessing RV-PA coupling based on their relations with 6-minute walk distance (6MWD), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and the Kansas City Cardiomyopathy Questionnaire (KCCQ) in aging adults. In this study of 1,611 Multi-Ethnic Study of Atherosclerosis participants who underwent echocardiography at Exam 6, we evaluated the association between different numerators, including tricuspid annular planar systolic excursion (TAPSE), fractional area change (FAC), RV free wall strain, and tissue Doppler imaging S' velocity to pulmonary artery systolic pressure (PASP) with 6MWD, NT-proBNP, and KCCQ score, adjusted for socioeconomic and cardiovascular disease risk factors. Our cohort had a mean age of 73 ± 8 years, 54% female, 17% Chinese American, 22% African American, 22% Hispanic, and 39% White participants. The mean ( ± SD) TAPSE/PASP, FAC/PASP, tissue Doppler imaging S' velocity/PASP, and RV free wall strain:PASP ratios were 0.7 ± 0.2, 1.3 ± 0.3, 0.5 ± 0.1, and 0.8 ± 0.2, respectively. All RV-PA coupling indices decreased with age (p <0.0001 for all). TAPSE:PASP ratio was lower in older (³85 years) female (0.59 ± 0.14) versus male (0.65 ± 0.17) participants (p = 0.01), whereas FAC/PASP ratio was higher in the same female versus male participants (p <0.01). TAPSE/PASP and FAC/PASP ratios were significantly and strongly associated with all NT-proBNP, 6MWD, and KCCQ scores in fully adjusted and receiver operating characteristic analysis. In older community-dwelling adults free of heart failure and pulmonary hypertension, both FAC/PASP and TAPSE:PASP ratios are optimal for assessment of RV-PA coupling based on its association with 6MWD, NT-proBNP, and KCCQ score. FAC/PASP ratio has the additional benefit of reflecting age and gender-related geometric and functional changes.

Pilot study to evaluate left-to-right ventricular offset in biventricular pacing-comparison of electrocardiographic imaging and ECG.

INTRODUCTION: Biventricular pacing (BiVp) improves outcomes in systolic heart failure patients with electrical dyssynchrony. BiVp is delivered from epicardial left ventricular (LV) and endocardial right ventricular (RV) electrodes. Acute electrical activation changes with different LV-RV stimulation offsets can help guide individually optimized BiVp programming. We sought to study the BiVp ventricular activation with different LV-RV offsets and compare with 12-lead ECG. METHODS: In five patients with BiVp (63 ± 17-year-old, 80% male, LV ejection fraction 27 ± 6%), we evaluated acute ventricular epicardial activation, varying LV-RV offsets in 20 ms increments from -40 to 80 ms, using electrocardiographic imaging (ECGI) to obtain absolute ventricular electrical uncoupling (VEUabs, absolute difference in average LV and average RV activation time) and total activation time (TAT). For each patient, we calculated the correlation between ECGI and corresponding ECG (3D-QRS-area and QRS duration) with different LV-RV offsets. RESULTS: The LV-RV offset to attain minimum VEUabs in individual patients ranged 20-60 ms. In all patients, a larger LV-RV offset was required to achieve minimum VEUabs (36 ± 17 ms) or 3D-QRS-area (40 ± 14 ms) than that for minimum TAT (-4 ± 9 ms) or QRS duration (-8 ± 11 ms). In individual patients, 3D-QRS-area correlated with VEUabs (r 0.65 ± 0.24) and QRS duration correlated with TAT (r 0.95 ± 0.02). Minimum VEUabs and minimum 3D-QRS-area were obtained by LV-RV offset within 20 ms of each other in all five patients. CONCLUSIONS: LV-RV electrical uncoupling, as assessed by ECGI, can be minimized by optimizing LV-RV stimulation offset. 3D-QRS-area is a surrogate to identify LV-RV offset that minimizes LV-RV uncoupling.