Right Ventricular Sarcomere Contractile Depression and the Role of Thick Filament Activation in Human Heart Failure With Pulmonary Hypertension.

BACKGROUND: Right ventricular (RV) contractile dysfunction commonly occurs and worsens outcomes in patients with heart failure with reduced ejection fraction and pulmonary hypertension (HFrEF-PH). However, such dysfunction often goes undetected by standard clinical RV indices, raising concerns that they may not reflect aspects of underlying myocyte dysfunction. We thus sought to characterize RV myocyte contractile depression in HFrEF-PH, identify those components reflected by clinical RV indices, and uncover underlying biophysical mechanisms. METHODS: Resting, calcium-, and load-dependent mechanics were prospectively studied in permeabilized RV cardiomyocytes isolated from explanted hearts from 23 patients with HFrEF-PH undergoing cardiac transplantation and 9 organ donor controls. RESULTS: Unsupervised machine learning using myocyte mechanical data with the highest variance yielded 2 HFrEF-PH subgroups that in turn mapped to patients with decompensated or compensated clinical RV function. This correspondence was driven by reduced calcium-activated isometric tension in decompensated clinical RV function, whereas surprisingly, many other major myocyte contractile measures including peak power and myocyte active stiffness were similarly depressed in both groups. Similar results were obtained when subgroups were first defined by clinical indices, and then myocyte mechanical properties in each group compared. To test the role of thick filament defects, myofibrillar structure was assessed by x-ray diffraction of muscle fibers. This revealed more myosin heads associated with the thick filament backbone in decompensated clinical RV function, but not compensated clinical RV function, as compared with controls. This corresponded to reduced myosin ATP turnover in decompensated clinical RV function myocytes, indicating less myosin in a crossbridge-ready disordered-relaxed (DRX) state. Altering DRX proportion (%DRX) affected peak calcium-activated tension in the patient groups differently, depending on their basal %DRX, highlighting potential roles for precision-guided therapeutics. Last, increasing myocyte preload (sarcomere length) increased %DRX 1.5-fold in controls but only 1.2-fold in both HFrEF-PH groups, revealing a novel mechanism for reduced myocyte active stiffness and by extension Frank-Starling reserve in human heart failure. CONCLUSIONS: Although there are many RV myocyte contractile deficits in HFrEF-PH, commonly used clinical indices only detect reduced isometric calcium-stimulated force, which is related to deficits in basal and recruitable %DRX myosin. Our results support use of therapies to increase %DRX and enhance length-dependent recruitment of DRX myosin heads in such patients.

Longitudinal Follow-Up of Children With HLHS and Association Between Norwood Shunt Type and Long-Term Outcomes: The SVR III Study.

OBJECTIVE: In the SVR trial (Single Ventricle Reconstruction), newborns with hypoplastic left heart syndrome were randomly assigned to receive a modified Blalock-Taussig-Thomas shunt (mBTTS) or a right ventricle-to-pulmonary artery shunt (RVPAS) at Norwood operation. Transplant-free survival was superior in the RVPAS group at 1 year, but no longer differed by treatment group at 6 years; both treatment groups had accumulated important morbidities. In the third follow-up of this cohort (SVRIII [Long-Term Outcomes of Children With Hypoplastic Left Heart Syndrome and the Impact of Norwood Shunt Type]), we measured longitudinal outcomes and their risk factors through 12 years of age. METHODS: Annual medical history was collected through record review and telephone interviews. Cardiac magnetic resonance imaging (CMR), echocardiogram, and cycle ergometry cardiopulmonary exercise tests were performed at 10 through 14 years of age among participants with Fontan physiology. Differences in transplant-free survival and complication rates (eg, arrhythmias or protein-losing enteropathy) were identified through 12 years of age. The primary study outcome was right ventricular ejection fraction (RVEF) by CMR, and primary analyses were according to shunt type received. Multivariable linear and Cox regression models were created for RVEF by CMR and post-Fontan transplant-free survival. RESULTS: Among 549 participants enrolled in SVR, 237 of 313 (76%; 60.7% male) transplant-free survivors (mBTTS, 105 of 147; RVPAS, 129 of 161; both, 3 of 5) participated in SVRIII. RVEF by CMR was similar in the shunt groups (RVPAS, 51±9.6 [n=90], and mBTTS, 52±7.4 [n=75]; P=0.43). The RVPAS and mBTTS groups did not differ in transplant-free survival by 12 years of age (163 of 277 [59%] versus 144 of 267 [54%], respectively; P=0.11), percentage predicted peak Vo2 for age and sex (74±18% [n=91] versus 72±18% [n=84]; P=0.71), or percentage predicted work rate for size and sex (65±20% versus 64±19%; P=0.65). The RVPAS versus mBTTS group had a higher cumulative incidence of protein-losing enteropathy (5% versus 2%; P=0.04) and of catheter interventions (14 versus 10 per 100 patient-years; P=0.01), but had similar rates of other complications. CONCLUSIONS: By 12 years after the Norwood operation, shunt type has minimal association with RVEF, peak Vo2, complication rates, and transplant-free survival. RVEF is preserved among the subgroup of survivors who underwent CMR assessment. Low transplant-free survival, poor exercise performance, and accruing morbidities highlight the need for innovative strategies to improve long-term outcomes in patients with hypoplastic left heart syndrome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT0245531.

The effects of pregnancy in subjects with repaired tetralogy of Fallot.

BACKGROUND: Previous reports reveal inconsistent findings of right ventricular (RV) changes following pregnancy in subjects with repaired tetralogy of Fallot (rTOF). METHODS: A two-center, retrospective cohort study which included women with rTOF who completed pregnancy that were matched to nulliparous women with rTOF by age at the time of baseline cardiac magnetic resonance (CMR), RV ejection fraction (RVEF), and indexed RV end-diastolic volume (RVEDVi). Pre-pregnancy and postpartum cardiac magnetic resonance (CMR) were analyzed and compared to sequential CMR of nulliparous subjects with rTOF. RESULTS: Thirty-six women with rTOF who completed pregnancy were matched to 72 nulliparous women with rTOF. Over a mean period of 3.1 years for the pregnancy group and 2.7 years for the comparison group, there was no significant change in the RVEDVi, RVEF, RV mass, pulmonary regurgitation severity, left ventricular (LV) volumes, LV ejection fraction (LVEF), or LV mass when comparing the baseline CMR and the follow-up CMR in either of the groups. There was a slight increase in RV indexed end-systolic volume (RVESVi) when comparing the baseline CMR and the follow-up CMR in the pregnancy group (68.93, SD 23.34 ml/m2 at baseline vs. 72.97, SD 25.24 mL/m2 at follow-up, P = .028). Using a mixed effects model for CMR parameters change over time; when adjusted for time between baseline and follow-up CMR there was no significant difference in rate of change between the pregnancy and comparison groups. CONCLUSIONS: Most ventricular remodeling parameters measured by CMR did not significantly change in subjects with rTOF who completed pregnancy or in nulliparous subjects with rTOF. In the pregnancy group, RVESVi is larger in those individuals who have undergone pregnancy without a significant change in ventricular function. These patients should be followed longitudinally to determine the long-term ventricular and clinical effects of pregnancy.

Native myocardial T1 and right ventricular size by CMR predict outcome in systemic sclerosis-associated pulmonary hypertension.

OBJECTIVES: Measures of right heart size and function are prognostic in systemic sclerosis-associated pulmonary hypertension (SSc-PH), but the importance of myocardial tissue characterisation remains unclear. We aimed to investigate the predictive potential and interaction of cardiovascular magnetic resonance (CMR) myocardial tissue characterisation and right heart size and function in SSc-PH. METHODS: A retrospective, single-centre, observational study of 148 SSc-PH patients confirmed by right heart catheterization who underwent clinically indicated CMR including native myocardial T1 and T2 mapping from 2016 to 2023 was performed. RESULTS: Sixty-six (45%) patients died during follow-up (median 3.5 years, range 0.1-7.3). Patients who died were older (65 vs 60 years, P = 0.035) with more dilated (P < 0.001), hypertrophied (P = 0.013) and impaired (P < 0.001) right ventricles, more dilated right atria (P = 0.043) and higher native myocardial T1 (P < 0.001).After adjustment for age, indexed right ventricular end-systolic volume (RVESVi, P = 0.0023) and native T1 (P = 0.0024) were independent predictors of all-cause mortality. Both RVESVi and native T1 remained independently predictive after adjusting for age and PH subtype (RVESVi P < 0.001, T1 P = 0.0056). Optimal prognostic thresholds for RVESVi and native T1 were ≤38 mL/m2 and ≤1119 ms, respectively (P < 0.001). Patients with RVESVi ≤ 38 mL/m2 and native T1 ≤ 1119 ms had significantly better outcomes than all other combinations (P < 0.001). Furthermore, patients with RVESVi > 38mL/m2 and native T1 ≤ 1119 ms had significantly better survival than patients with RVESVi > 38mL/m2 and native T1 > 1119ms (P = 0.017). CONCLUSION: We identified prognostically relevant CMR metrics and thresholds for patients with SSc-PH. Assessing myocardial tissue characterisation alongside right ventricular function confers added value in SSc-PH and may represent an additional treatment target.

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.

Increasing Levels of Positive End-expiratory Pressure Cause Stepwise Biventricular Stroke Work Reduction in a Porcine Model.

BACKGROUND: Positive end-expiratory pressure (PEEP) is commonly applied to avoid atelectasis and improve oxygenation in patients during general anesthesia but affects cardiac pressures, volumes, and loading conditions through cardiorespiratory interactions. PEEP may therefore alter stroke work, which is the area enclosed by the pressure-volume loop and corresponds to the external work performed by the ventricles to eject blood. The low-pressure right ventricle may be even more susceptible to PEEP than the left ventricle. The authors hypothesized that increasing levels of PEEP would reduce stroke work in both ventricles. METHODS: This was a prospective, observational, experimental study. Six healthy female pigs of approximately 60 kg were used. PEEP was stepwise increased from 0 to 5, 7, 9, 11, 13, 15, 17, and 20 cm H2O to cover the clinical spectrum of PEEP. Simultaneous, biventricular invasive pressure-volume loops, invasive blood pressures, and ventilator data were recorded. RESULTS: Increasing PEEP resulted in stepwise reductions in left (5,740 ± 973 vs. 2,303 ± 1,154 mmHg · ml; P < 0.001) and right (2,064 ± 769 vs. 468 ± 133 mmHg · ml; P < 0.001) ventricular stroke work. The relative stroke work reduction was similar between the two ventricles. Left ventricular ejection fraction, afterload, and coupling were preserved. On the contrary, PEEP increased right ventricular afterload and caused right ventriculo-arterial uncoupling (0.74 ± 0.30 vs. 0.19 ± 0.13; P = 0.01) with right ventricular ejection fraction reduction (64 ± 8% vs. 37 ± 7%, P < 0.001). CONCLUSIONS: A stepwise increase in PEEP caused stepwise reduction in biventricular stroke work. However, there are important interventricular differences in response to increased PEEP levels. PEEP increased right ventricular afterload leading to uncoupling and right ventricular ejection fraction decline. These findings may support clinical decision-making to further optimize PEEP as a means to balance between improving lung ventilation and preserving right ventricular function.

Novel interventions on the tricuspid valve: how to consider the pulmonary circulation?

PURPOSE OF REVIEW: This review addresses treatment options for moderate to severe tricuspid valve regurgitation and the importance of right ventricular function and the pulmonary circulation. RECENT FINDINGS: Several interventional treatment options for severe tricuspid regurgitation have been developed including transcatheter edge-to-edge repair, annuloplasty and valve replacement. So far, transcatheter edge-to-edge repair is most frequently used with procedural success rates of more than 95% and improvements in functional and quality of life parameters for up to 2 years. Right ventricular function as well as pulmonary artery pressure and resistance levels are important outcome predictors. Mean pulmonary artery pressure more than 30 mmHg, transpulmonary gradient more than 17 mmHg and right ventricular to pulmonary artery coupling ratio less than 0.406 indicate poor outcome. SUMMARY: Despite the remarkable safety of interventional treatment of severe tricuspid regurgitation right ventricular dysfunction and abnormal pulmonary hemodynamics are important determinants of procedural success and clinical outcome.Complete hemodynamic work-up should be an integral part of prerepair assessment although validated data predicting outcome are limited.

Assessment of right ventricular diastolic function in pediatric patients with repaired tetralogy of Fallot by cardiovascular magnetic resonance and echocardiography.

OBJECTIVES: Cardiovascular magnetic resonance (CMR) imaging is routinely performed for assessing right ventricular (RV) systolic but not diastolic function. We aimed to investigate CMR-based assessment of RV diastolic function in pediatric patients with repaired tetralogy of Fallot (rTOF), compared to transthoracic echocardiography (TTE) measurements. METHODS: A total of 130 consecutive pediatric patients with rTOF who underwent clinically indicated CMR and same-day TTE were included. Forty-three controls were recruited. Phase-contrast images were used to measure trans-tricuspid valve flow velocities during early (E) and late diastolic (A) phases (measured in cm/s). Feature tracking of the tricuspid annulus was performed to derive early (e') and late diastolic (a') myocardial velocities (measured in cm/s). RV diastolic function was evaluated by E/A ratio, E/e' ratio, and E-wave deceleration time (measured in milliseconds). Regression analyses were utilized to identify potential variables associated with RV diastolic dysfunction (DD). The performance of CMR-derived parameters in diagnosing RV DD was assessed using receiver-operating characteristic analyses. RESULTS: Good agreement was found between CMR and TTE measurements (ICC 0.70-0.89). Patients with RV DD (n = 67) showed significantly different CMR-derived parameters including E and e' velocities, and E/A and E/e' ratio, compared to patients without DD (n = 63) (all p < 0.05). CMR-derived E and e' velocities and E/e' ratio were independent predictors of RV DD. E/e' of 5.8 demonstrated the highest discrimination of RV DD (AUC 0.76, sensitivity 70%, specificity 86%). CONCLUSIONS: CMR-derived parameters showed good agreement with TTE parameters in determining RV DD. CMR-derived E/e' was proved to be the most effective in identifying RV DD. CLINICAL RELEVANCE STATEMENT: This study demonstrated the feasibility and efficacy of CMR in assessing diastolic function in pediatric patients. RV DD was presented in over half of patients according to current TTE guidelines, highlighting the need for assessing RV diastolic function during follow-up. KEY POINTS: • Routinely acquired cine and phase-contrast cardiovascular magnetic resonance (CMR) images yielded right ventricular (RV) diastolic parameters which demonstrated good agreement with transthoracic echocardiography (TTE) measurements. • There was a high prevalence of RV diastolic function impairment in pediatric patients with repaired tetralogy of Fallot (rTOF). • CMR is a reliable complementary modality of TTE for RV diastolic function evaluation.

Flow pattern analysis of right ventricular outflow tract in repaired tetralogy of Fallot through 4D flow MRI.

Cardiac magnetic resonance imaging (CMR) often shows discrepancies between right ventricular outflow tract (RVOT) flow and left ventricular outflow tract flow in patients with late-stage repaired tetralogy of Fallot (rTOF), leading to potential errors in pulmonary regurgitation fraction (PRF) assessment. This study aimed to identify the conditions under which RVOT flow can be acutely evaluated using four-dimensional (4D) flow CMR. Twenty-seven consecutive patients with rTOF underwent both two-dimensional phase-contrast (2D PC) and 4D flow CMR between 2016 and 2018, excluding those with peripheral pulmonary artery stenosis, RVOT conduit replacement, unknown surgical method, and an aortic valve regurgitation greater than 20%. Seven healthy controls also underwent only 4D Flow CMR. All healthy controls and fifteen patients with rTOF showed laminar RVOT flow, while seven patients exhibited helical, and four patients exhibited vortical RVOT flow in 4D flow CMR visualization. Flow-volume concordance between the pulmonary artery and aortic flow was significantly lower in patients with rTOF and PRF > 40% in 2D PC CMR. This concordance rate in the suprapulmonary valve was high in both the TOF and control groups, comparing at five RVOT locations in 4D flow CMR. Regarding RVOT flow regurgitation in 4D flow, the whole bulk evaluation exhibited greater variation depending on the flow type compared to the whole pixel-wise evaluation. The study confirmed the flow volume at the upper section of the pulmonary valve as the most accurate correlate of aortic flow volume. Furthermore, the 4D flow CMR using the pixel-wise method demonstrated superior accuracy compared to the traditional bulk flow method.

Right Ventricular Limitation: A Tale of Two Elastances.

Right ventricular (RV) dysfunction is a commonly considered cause of low cardiac output in critically ill patients. Its management can be difficult and requires an understanding of how the RV limits cardiac output. We explain that RV stroke output is caught between the passive elastance of the RV walls during diastolic filling and the active elastance produced by the RV in systole. These two elastances limit RV filling and stroke volume and consequently limit left ventricular stroke volume. We emphasize the use of the term "RV limitation" and argue that limitation of RV filling is the primary pathophysiological process by which the RV causes hemodynamic instability. Importantly, RV limitation can be present even when RV function is normal. We use the term "RV dysfunction" to indicate that RV end-systolic elastance is depressed or diastolic elastance is increased. When RV dysfunction is present, RV limitation occurs at lowerpulmonary valve opening pressures and lower stroke volume, but stroke volume and cardiac output still can be maintained until RV filling is limited. We use the term "RV failure" to indicate the condition in which RV output is insufficient for tissue needs. We discuss the physiological underpinnings of these terms and implications for clinical management.

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.

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.

Associations Between Echocardiographic Right Heart Measurements With Short-Term Prognosis in Heart Failure: A Prospective Study.

BACKGROUND: Echocardiographic right ventricular (RV) dysfunction is a strong risk determinant for prognosis in patients with heart failure (HF). Although parameters of RV systolic function are widely used to define RV dysfunction, there is scarce data to suggest these parameters are best suited to predict HF-related outcomes. AIMS: We aimed to understand which morphologic or functional parameters are most closely associated with short-term mortality and HF-related hospitalization in patients with HF. METHODS: A total of 191 patients from eight study centers were included to this study. A detailed echocardiographic examination was done at enrollment, and patients were followed up for 6 months via direct interviews or phone calls. RESULTS: All right-sided echocardiographic parameters other than tricuspid annular plane systolic excursion were associated with outcomes. In a proportional hazards model that included right-heart parameters, RV longitudinal diameter (HR: 1.07, 95%CI: 1.04-1.10, p < 0.001), wall thickness (HR: 1.3, 95%CI: 1.13-1.50, p < 0.001), and tricuspid annular systolic velocity (HR: 0.90, 95%CI: 0.82-0.96, p = 0.02) were found as the independent predictors. However, only RV longitudinal dimension (HR: 1.04, 95%CI: 1.01-1.08, p = 0.01) and RV wall thickness (HR: 1.32, 95%CI: 1.10-1.60, p = 0.004) were associated with short-term outcomes after adjusting for other clinical and left-sided echocardiographic variables. On a Bayesian logistic regression model that included right-sided echocardiography variables, there was strong evidence for including either RV longitudinal diameter (BF10: 190.4) or wall thickness (BF10: 30.7) to the final model. CONCLUSION: Parameters of RV morphology were better predictors of short-term outcomes in HF patients.

Evaluation of right ventricular function in patients with Behcet's disease by four-dimensional echocardiography.

AIM: Behcet's disease (BD) is a systemic disorder characterized by vasculitis, resulting in thickened vascular walls that reduce elasticity and impair function. BD can involve the cardiovascular system in three ways: cardiac, arterial, and venous. In this study, our objective was to evaluate the efficacy of pulmonary arterial stiffness (PAS) and pulmonary pulse transit time (PPTT) measures in demonstrating right ventricular functions in asymptomatic BD patients. We aimed to objectively evaluate right ventricular function in patients with BD using four-dimensional echocardiography (4DE). METHOD: This study included 40 patients diagnosed with BD and 40 healthy subjects. Demographic, clinical, laboratory, and echocardiographic parameters were compared. In addition to standard transthoracic echocardiographic evaluation, right ventricle quantification (RVQ) by using the 4DE and 2D-speckle tracking echocardiography were performed. RESULTS: The sPAP, 4D RVQ, and right ventricular strain values exhibited significant differences between the BD and control groups. Right ventricular end-diastolic diameter (RVDD), right ventricular end-systolic diameter (RVSD), right atrium (RA) area, right ventricular myocardial performance index (RVMPI), and PAS were increased in BD patients compared to the control group. Right ventricular ejection fraction (RVEF), right ventricular fractional area change (RVFAC), tricuspid annular plane systolic excursion (TAPSE), Tricuspid S', and PPTT were decreased in BD patients compared to control subjects. PPTT correlated with right ventricular free wall strain (RV-FWS) and PAS. In a multivariate linear regression analysis, PAS and RVFAC were found to be independent predictors of RVFWS. In addition, RVFAC and TAPSE are independent predictors for PPTT. CONCLUSION: Patients with BD may have elevated pulmonary arterial stiffness (PAS) in correlation with decreased PPTT. To ascertain the prognosis for these individuals, right ventricular (RV) functions must be evaluated. Measurements of RVFAC and RVEF via 4DE and deformation imaging techniques may be more useful in identifying subclinical impairment of RV. Individuals with BD, PAS, and PPTT may suggest a link between early pulmonary vascular remodeling and RV subclinical impairment.

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.

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.

Assessment of the Right Ventricle Function in Patients With Significant Tricuspid Regurgitation: A Review.

Tricuspid regurgitation (TR) is an increasingly prevalent condition, especially in older populations, and presents significant challenges due to its association with right heart failure, hospital admissions, and high mortality rates. The management of TR has evolved, with new percutaneous valve repair and replacement techniques emerging alongside traditional surgical approaches. However, accurately assessing right ventricular (RV) function-a key prognostic factor in TR-remains difficult due to the RV's unique anatomy and sensitivity to loading conditions. Current echocardiographic methods, such as Tricuspid Annular Plane Systolic Excursion (TAPSE), S' wave analysis, and RV fractional area change (FAC), offer valuable insights but have limitations, particularly regarding load dependence and incomplete assessment of RV function. Advances in 3D echocardiography and myocardial strain imaging provide more comprehensive evaluations, yet challenges persist in integrating these measures in routine clinical practice. The review highlights the importance of a multimodal approach to RV assessment in TR patients, considering both the right atrium and pulmonary artery interactions, and explores potential future tools such as myocardial work and dynamic testing to improve prognostic accuracy and patient outcomes.

Right Ventricular Pressure Waveform Analysis-Clinical Relevance and Future Directions.

Continuous measurement of pressure in the right atrium and pulmonary artery has commonly been used to monitor right ventricular function in critically ill and surgical patients. This approach is largely based upon the assumption that right atrial and pulmonary arterial pressures provide accurate surrogates for diastolic filling and peak right ventricular pressures, respectively. However, due to both technical and physiologic factors, this assumption is not always true. Accordingly, recent studies have begun to emphasize the potential clinical value of also measuring right ventricular pressure at the bedside. This has highlighted both past and emerging research demonstrating the utility of analyzing not only the amplitude of right ventricular pressure but also the shape of the pressure waveform. This brief review summarizes data demonstrating that combining conventional measurements of right ventricular pressure with variables derived from waveform shape allows for more comprehensive and ideally continuous bedside assessment of right ventricular function, particularly when combined with stroke volume measurement or 3D echocardiography, and discusses the potential use of right ventricular pressure analysis in computational models for evaluating cardiac function.

Continuous Right Ventricular Pressure Monitoring in Cardiac Surgery.

OBJECTIVE: Right ventricular (RV) dysfunction in cardiac surgery can lead to RV failure, which is associated with increased morbidity and mortality. Abnormal RV function can be identified using RV pressure monitoring. The primary objective of the study is to determine the proportion of patients with abnormal RV early to end-diastole diastolic pressure gradient (RVDPG) and abnormal RV end-diastolic pressure (RVEDP) before initiation and after cardiopulmonary bypass (CPB) separation. The secondary objective is to evaluate if RVDPG before CPB initiation is associated with difficult and complex separation from CPB, RV dysfunction, and failure at the end of cardiac surgery. DESIGN: Prospective study. SETTING: Tertiary care cardiac institute. PARTICIPANTS: Cardiac surgical patients. INTERVENTION: Cardiac surgery. MEASUREMENTS AND MAIN RESULTS: Automated electronic quantification of RVDPG and RVEDP were obtained. Hemodynamic measurements were correlated with cardiac and extracardiac parameters from transesophageal echocardiography and postoperative complications. Abnormal RVDPG was present in 80% of the patients (n = 105) at baseline, with a mean RVEDP of 14.2 ± 3.9 mmHg. Patients experienced an RVDPG > 4 mmHg for a median duration of 50.2% of the intraoperative period before CPB initiation and 60.6% after CPB separation. A total of 46 (43.8%) patients had difficult/complex separation from CPB, 18 (38.3%) patients had RV dysfunction, and 8 (17%) had RV failure. Abnormal RVDPG before CPB was not associated with postoperative outcome. CONCLUSION: Elevated RVDPG and RVEDP are common in cardiac surgery. RVDPG and RVEDP before CPB initiation are not associated with RV dysfunction and failure but can be used to diagnose them.

Association Between Right Ventricular Systolic Parameters Measured by Echocardiography and Stroke Volume Derived From Pulmonary Artery Catheter in Ischemic Cardiogenic Shock.

OBJECTIVE: To determine the right ventricular (RV) systolic function echocardiographic parameter best associated with native stroke volume (SV) by thermodilution via a pulmonary artery catheter (PAC) in patients admitted to intensive care with ST elevation myocardial infarction (STEMI) complicated by cardiogenic shock (CS). DESIGN, SETTING, AND PARTICIPANTS: An observational cohort study of 43 prospectively identified patients admitted to a tertiary cardiac intensive care unit in London, United Kingdom. INTERVENTIONS: Simultaneous collection of comprehensive transthoracic echocardiographic, clinical, and PAC-derived hemodynamic data. Seven RV systolic function parameters were correlated with the PAC-derived SV. MEASUREMENTS AND MAIN RESULTS: The median patient age was 61 years (interquartile range [IQR], 52-67 years), and 36 of the 43 patients (84%) were male. The median PAC-derived SV and left ventricular ejection fraction were 57 mL (IQR, 39-70 mL) and 31% (IQR, 22%-35%), respectively. The RV outflow tract velocity time integral (RVOT VTI) and tricuspid plane systolic excursion (TAPSE) correlated significantly with the PAC-derived SV (r = 0.42 [p = 0.007] and r = 0.37 [p = 0.02], respectively). The RVOT VTI was independently associated with and predicted low PAC-derived SV (odds ratio, 1.3; p = 0.03) with a good area under the curve (AUC = 0.71; p = 0.02). An RVOT VTI <12.7 cm predicted low PAC-derived SV with a sensitivity of 66% and specificity of 72%. CONCLUSIONS: RVOT VTI is the echocardiographic RV systolic function parameter that best correlates with PAC-derived native SV in patients with STEMI complicated by CS. This parameter can help guide the hemodynamic management of this cohort.