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.

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.

Intrinsic mechanisms of right ventricular autoregulation.

To elucidate the adaptation of the right ventricle to acute and intermittently sustained afterload elevation, targeted preload reductions and afterload increases were implemented in a porcine model involving 12 pigs. Preload reduction was achieved via balloon occlusion of the inferior vena cava before, immediately and 5 min after acute afterload elevation induced by pulmonary artery occlusion or thromboxane A2 analog (U46619) infusion. Ventricular response was monitored by registration of pressure-volume (PV) loops using a conductance catheter. The end-systolic pressure-volume relationship (ESPVR) during pure preload reduction was adequately described by linear regression (mean and SEM slope of ESPVR (Ees) 0.414 ± 0.064 mmHg/ml), reflecting the classical Frank-Starling mechanism (FSM). The ESPVR during acute afterload elevation exhibited a biphasic trajectory with significantly distinct slopes (mean and SEM Ees bilin1: 1.256 ± 0.066 mmHg ml; Ees bilin2: 0.733 ± 0.063 mmHg ml, p < 0.001). The higher slope during the first phase in the absence of ventricular dilation could be explained by a reduced amount of shortening deactivation (SDA). The changes in PV-loops during the second phase were similar to those observed with a preload intervention. The persistent increase in afterload resulted in an increase in the slopes of ESPVR and preload recruitable stroke work (PRSW) with a slight decrease in filling state, indicating a relevant Anrep effect. This effect became more pronounced after 5 min or TXA infusion. This study demonstrates, for the first time, the relevance of intrinsic mechanisms of cardiac autoregulation in the right ventricle during the adaptation to load. The SDA, FSM, and Anrep effect could be differentiated and occurred successively, potentially with some overlap. Notably, the Anrep effect serves to prevent ventricular dilation.

Prognostic Value of RV Function Analysis During the Interstage Period in Patients with Hypoplastic Left Heart Syndrome.

Cardiac dysfunction is associated with mortality in children with hypoplastic left heart syndrome (HLHS). We evaluated the ability of qualitative and quantitative RV functional parameters to predict outcomes in HLHS patients. In this retrospective, single-center study, echocardiograms from 3 timepoints (pre-stage 1 palliation, 4-8 weeks post-stage 1 palliation, and pre-Glenn) were analyzed in infants with HLHS. Patients were stratified into two groups based on outcome of transplant-free survival post-Glenn (survivors) versus mortality or transplantation prior to Fontan (non-survivors). Images were retrospectively reviewed to obtain RV global longitudinal strain (RVGLS), RV-free wall strain (RVFWS), fractional area change (FAC), tricuspid annular systolic plane excursion (TAPSE), tissue motion annular displacement of the tricuspid valve (TMAD-TV) and qualitative systolic function assessment during the predetermined timepoints. An equal variance t-test and chi-square were used to determine significant differences and ROC curve analysis was performed to derive optimal cutoff values to predict mortality/transplant. A total of 47 patients met inclusion criteria, of which, 21 patients met composite endpoint. There were no significant differences in any RV functional parameter during the pre- or post-stage 1 palliation timepoints. The absolute values of RVFWS, RVGLS, and TMAD-TV were significantly greater in survivors than non-survivors during the pre-Glenn timepoint. A pre-Glenn RVGLS > -15.6 (AUC 0.79), RVFWS > -18.6 (AUC 0.75), and TMAD-TV < 12.6% (AUC 0.82) were sensitive and specific for predicting death or need for transplantation prior to Fontan completion. RVGLS, RVFWS, and TMAD-TV may help identify higher-risk HLHS patients during the interstage period.

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.

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-pulmonary artery coupling is an independent risk factor for coronary artery lesions in children with Kawasaki disease.

BACKGROUND: The recognition ability of right ventricular-pulmonary artery (RV-PA) coupling for coronary artery lesions (CAL) in children with Kawasaki disease (KD) has not been well characterized. This study aimed to determine whether RV-PA coupling is an independent the risk factors for CAL in children with KD. METHODS: Between October 2021 and August 2023, RV-PA coupling was assessed in 59 KD children using the ratio between echocardiographic tricuspid annular plane systolic excursion and pulmonary artery systolic pressure (PASP). Multivariable logistic regression analysis was used to identify the independent risk factors for CAL among the demographic, clinical, laboratory and echocardiographic data. RESULTS: Twenty-nine of 59 KD children had CAL according to the diagnostic criteria of echocardiography. There were significantly different white blood cell count, C-reactive protein, erythrocyte sedimentation rate, left ventricular ejection fraction, PASP and RV-PA coupling at admission, and significantly different acute/subacute phase ratio of RV-PA coupling between KD children with and without CAL ( P  < 0.05). Multivariate logistic regression analysis identified that acute/subacute phase ratio of RV-PA coupling (OR = 26.800; 95% CI, 1.276-562.668; P  = 0.034) was an independent risk factor for CAL in children with KD. The area under receiver operating characteristic curve for the acute/subacute phase ratio of RV-PA coupling was 0.715 (95%CI: 0.624 - 0.825) to predict CAL in KD children ( P  < 0.05), with a sensitivity of 81.25% and a specificity of 62.57% at the optimal cutoff value of 0.839. CONCLUSION: The acute/subacute phase ratio of RV-PA coupling was an independent risk factor for CAL in KD children.

Toward the Implementation of Optimal Cardiac Magnetic Resonance Risk Stratification in Pulmonary Arterial Hypertension.

BACKGROUND: The 2022 European Society of Cardiology/European Respiratory Society pulmonary hypertension (PH) guidelines incorporate cardiac magnetic resonance (CMR) imaging metrics in the risk stratification of patients with pulmonary arterial hypertension (PAH). Thresholds to identify patients at estimated 1-year mortality risks of < 5%, 5% to 20%, and > 20% are introduced. However, these cutoff values are mostly single center-based and require external validation. RESEARCH QUESTION: What are the discriminative prognostic properties of the current CMR risk thresholds stratifying patients with PAH? STUDY DESIGN AND METHODS: We analyzed data from incident, treatment-naïve patients with PAH from the Amsterdam University Medical Centres, Vrije Universiteit, The Netherlands. The discriminative properties of the proposed CMR three risk strata were tested at baseline and first reassessment, using the following PH guideline variables: right ventricular ejection fraction, indexed right ventricular end-systolic volume, and indexed left ventricular stroke volume. RESULTS: A total of 258 patients with PAH diagnosed between 2001 and 2022 fulfilled the study criteria and were included in this study. Of these, 172 had follow-up CMR imaging after 3 months to 1.5 years. According to the CMR three risk strata, most patients were classified at intermediate risk (n = 115 [45%]) upon diagnosis. Only 29 (11%) of patients with PAH were classified at low risk, and 114 (44%) were classified at high risk. Poor survival discrimination was seen between risk groups. Appropriate survival discrimination was seen at first reassessment. INTERPRETATION: Risk stratifying patients with PAH with the recent proposed CMR cutoffs from the European Society of Cardiology/European Respiratory Society 2022 PH guidelines requires adjustment because post-processing consensus is lacking and general applicability is limited. Risk assessment at follow-up yielded better survival discrimination, emphasizing the importance of the individual treatment response.

Three-dimensional echocardiographic evaluation of longitudinal and non-longitudinal components of right ventricular contraction: results from the World Alliance of Societies of Echocardiography study.

AIMS: Right ventricular (RV) functional assessment is mainly limited to its longitudinal contraction. Dedicated three-dimensional echocardiography (3DE) software enabled the separate assessment of the non-longitudinal components of RV ejection fraction (EF). The aims of this study were (i) to establish normal values for RV 3D-derived longitudinal, radial, and anteroposterior EF (LEF, REF, and AEF, respectively) and their relative contributions to global RVEF, (ii) to calculate 3D RV strain normal values, and (iii) to determine sex-, age-, and race-related differences in these parameters in a large group of normal subjects (WASE study). METHODS AND RESULTS: 3DE RV wide-angle datasets from 1043 prospectively enrolled healthy adult subjects were analysed to generate a 3D mesh model of the RV cavity (TomTec). Dedicated software (ReVISION) was used to analyse RV motion along the three main anatomical planes. The EF values corresponding to each plane were identified as LEF, REF, and AEF. Relative contributions were determined by dividing each EF component by the global RVEF. RV strain analysis included longitudinal, circumferential, and global area strains (GLS, GCS, and GAS, respectively). Results were categorized by sex, age (18-40, 41-65, and >65 years), and race. Absolute REF, AEF, LEF, and global RVEF were higher in women than in men (P < 0.001). With aging, both sexes exhibited a decline in all components of longitudinal shortening (P < 0.001), which was partially compensated in elderly women by an increase in radial contraction. Black subjects showed lower RVEF and GAS values compared with white and Asian subjects of the same sex (P < 0.001), and black men showed significantly higher RV radial but lower longitudinal contributions to global RVEF compared with Asian and white men. CONCLUSION: 3DE evaluation of the non-longitudinal components of RV contraction provides additional information regarding RV physiology, including sex-, age-, and race-related differences in RV contraction patterns that may prove useful in disease states involving the right ventricle.

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.

A Noninvasive Circulating Signature of Combined Right Ventricular Pressure and Volume Overload in Tetralogy of Fallot/Pulmonary Atresia/Major Aortopulmonary Collateral Arteries.

Background: Despite surgical advances, children with tetralogy of Fallot/pulmonary atresia/major aortopulmonary collaterals (TOF/PA/MAPCAs) are subject to chronic right ventricular (RV) pressure and volume overload. Current diagnostic tools do not identify adverse myocardial remodeling and cannot predict progression to RV failure. We sought to identify a noninvasive, circulating signature of the systemic response to right heart stress to follow disease progression. Methods: Longitudinal data were collected from patients with TOF/PA/MAPCAs (N = 5) at the time of (1) early RV pressure overload and (2) late RV pressure and volume overload. Plasma protein and microRNA expression were evaluated using high-throughput data-independent mass spectroscopy and Agilent miR Microarray, respectively. Results: At the time of early RV pressure overload, median patient age was 0.34 years (0.02-9.37), with systemic RV pressures, moderate-severe hypertrophy, and preserved systolic function. Late RV pressure and volume overload occurred at a median age of 4.08 years (1.51-10.83), with moderate RV hypertrophy and dilation, and low normal RV function; 277 proteins were significantly dysregulated (log2FC ≥0.6/≤-0.6, FDR≤0.05), predicting downregulation in lipid transport (apolipoproteins), fibrinolytic system, and extracellular matrix structural proteins (talin 1, profilin 1); and upregulation in the respiratory burst. Increasing RV size and decreasing RV function correlated with decreasing structural protein expression. Similarly, miR expression predicted downregulation of extracellular matrix-receptor interactions and upregulation in collagen synthesis. Conclusion: To our knowledge, we show for the first time a noninvasive protein and miR signature reflecting the systemic response to adverse RV myocardial remodeling in TOF/PA/MAPCAs which could be used to follow disease progression.

Advanced hemodynamic and cluster analysis for identifying novel RV function subphenotypes in patients with pulmonary hypertension.

BACKGROUND: Quantifying right ventricular (RV) function is important to describe the pathophysiology of in pulmonary hypertension (PH). Current phenotyping strategies in PH rely on few invasive hemodynamic parameters to quantify RV dysfunction severity. The aim of this study was to identify novel RV phenotypes using unsupervised clustering methods on advanced hemodynamic features of RV function. METHODS: Participants were identified from the University of Arizona Pulmonary Hypertension Registry (n = 190). RV-pulmonary artery coupling (Ees/Ea), RV systolic (Ees), and diastolic function (Eed) were quantified from stored RV pressure waveforms. Consensus clustering analysis with bootstrapping was used to identify the optimal clustering method. Pearson correlation analysis was used to reduce collinearity between variables. RV cluster subphenotypes were characterized using clinical data and compared to pulmonary vascular resistance (PVR) quintiles. RESULTS: Five distinct RV clusters (C1-C5) with distinct RV subphenotypes were identified using k-medoids with a Pearson distance matrix. Clusters 1 and 2 both have low diastolic stiffness (Eed) and afterload (Ea) but RV-PA coupling (Ees/Ea) is decreased in C2. Intermediate cluster (C3) has a similar Ees/Ea as C2 but with higher PA pressure and afterload. Clusters C4 and C5 have increased Eed and Ea but C5 has a significant decrease in Ees/Ea. Cardiac output was high in C3 distinct from the other clusters. In the PVR quintiles, contractility increased and stroke volume decreased as a function of increased afterload. World Symposium PH classifications were distributed across clusters and PVR quintiles. CONCLUSIONS: RV-centric phenotyping offers an opportunity for a more precise-medicine-based management approach.

Right Ventricle and Epigenetics: A Systematic Review.

There is an increasing recognition of the crucial role of the right ventricle (RV) in determining the functional status and prognosis in multiple conditions. In the past decade, the epigenetic regulation (DNA methylation, histone modification, and non-coding RNAs) of gene expression has been raised as a critical determinant of RV development, RV physiological function, and RV pathological dysfunction. We thus aimed to perform an up-to-date review of the literature, gathering knowledge on the epigenetic modifications associated with RV function/dysfunction. Therefore, we conducted a systematic review of studies assessing the contribution of epigenetic modifications to RV development and/or the progression of RV dysfunction regardless of the causal pathology. English literature published on PubMed, between the inception of the study and 1 January 2023, was evaluated. Two authors independently evaluated whether studies met eligibility criteria before study results were extracted. Amongst the 817 studies screened, 109 studies were included in this review, including 69 that used human samples (e.g., RV myocardium, blood). While 37 proposed an epigenetic-based therapeutic intervention to improve RV function, none involved a clinical trial and 70 are descriptive. Surprisingly, we observed a substantial discrepancy between studies investigating the expression (up or down) and/or the contribution of the same epigenetic modifications on RV function or development. This exhaustive review of the literature summarizes the relevant epigenetic studies focusing on RV in human or preclinical setting.

Exercise Stress Echocardiography of the Right Ventricle and Pulmonary Circulation.

BACKGROUND: Exercise echocardiography is used for assessment of pulmonary circulation and right ventricular function, but limits of normal and disease-specific changes remain insufficiently established. OBJECTIVES: The objective of this study was to explore the physiological vs pathologic response of the right ventricle and pulmonary circulation to exercise. METHODS: A total of 2,228 subjects were enrolled: 375 healthy controls, 40 athletes, 516 patients with cardiovascular risk factors, 17 with pulmonary arterial hypertension, 872 with connective tissue diseases without overt pulmonary hypertension, 113 with left-sided heart disease, 30 with lung disease, and 265 with chronic exposure to high altitude. All subjects underwent resting and exercise echocardiography on a semirecumbent cycle ergometer. All-cause mortality was recorded at follow-up. RESULTS: The 5th and 95th percentile of the mean pulmonary artery pressure-cardiac output relationships were 0.2 to 3.5 mm Hg.min/L in healthy subjects without cardiovascular risk factors, and were increased in all patient categories and in high altitude residents. The 5th and 95th percentile of the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure ratio at rest were 0.7 to 2.0 mm/mm Hg at rest and 0.5 to 1.5 mm/mm Hg at peak exercise, and were decreased at rest and exercise in all disease categories and in high-altitude residents. An increased all-cause mortality was predicted by a resting tricuspid annular plane systolic excursion to systolic pulmonary artery pressure <0.7 mm/mm Hg and mean pulmonary artery pressure-cardiac output >5 mm Hg.min/L. CONCLUSIONS: Exercise echocardiography of the pulmonary circulation and the right ventricle discloses prognostically relevant differences between healthy subjects, athletes, high-altitude residents, and patients with various cardio-respiratory conditions. (Right Heart International NETwork During Exercise in Different Clinical Conditions; NCT03041337).

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 Right Heart in Congenital Heart Disease.

PURPOSE OF REVIEW: To analyze the pathophysiologic importance of the right heart in different types of congenital heart disease (CHD), summarize current diagnostic modalities, and discuss treatment options. RECENT FINDINGS: The right ventricle (RV) plays a key role in disease progression and prognosis, either as the subpulmonary or as the systemic ventricle. Volume and/or pressure overload as well as intrinsic myocardial disease are the main factors for RV remodeling. Echocardiography and cardiac magnetic resonance imaging are important noninvasive modalities for assessing anatomy, size, and function of the right heart. Timely repair of related lesions is essential for preventing RV dysfunction. Few inconclusive data exist on conventional pharmacotherapy in CHD-related RV dysfunction. Cardiac resynchronization therapy and ventricular assist devices are an option in patients with advanced systemic RV failure. Right heart disease is highly related with adverse clinical outcomes in CHD. Research should focus on early identification of patients at risk and development of medical and interventional treatments that improve RV function.

Balancing the ventricular outputs of pulsatile total artificial hearts.

BACKGROUND: Maintaining balanced left and right cardiac outputs in a total artificial heart (TAH) is challenging due to the need for continuous adaptation to changing hemodynamic conditions. Proper balance in ventricular outputs of the left and right ventricles requires a preload-sensitive response and mechanisms to address the higher volumetric efficiency of the right ventricle. METHODS: This review provides a comprehensive overview of various methods used to balance left and right ventricular outputs in pulsatile total artificial hearts, categorized based on their actuation mechanism. RESULTS: Reported strategies include incorporating compliant materials and/or air cushions inside the ventricles, employing active control mechanisms to regulate ventricular filling state, and utilizing various shunts (such as hydraulic or intra-atrial shunts). Furthermore, reducing right ventricular stroke volume compared to the left often serves to balance the ventricular outputs. Individually controlled actuation of both ventricles in a pulsatile TAH seems to be the simplest and most effective way to achieve proper preload sensitivity and left-right output balance. Pneumatically actuated TAHs have the advantage to respond passively to preload changes. CONCLUSION: Therefore, a pneumatic TAH that comprises two individually actuated ventricles appears to be a more desirable option-both in terms of simplicity and efficacy-to respond to changing hemodynamic conditions.

Mechanisms of Acute Right Ventricular Injury in Cardiothoracic Surgical and Critical Care Settings: Part 2.

The right ventricle (RV) is intricately linked in the clinical presentation of critical illness; however, the basis of this is not well-understood and has not been studied as extensively as the left ventricle. There has been an increased awareness of the need to understand how the RV is affected in different critical illness states. In addition, the increased use of point-of-care echocardiography in the critical care setting has allowed for earlier identification and monitoring of the RV in a patient who is critically ill. The first part of this review describes and characterizes the RV in different perioperative states. This second part of the review discusses and analyzes the complex pathophysiologic relationships between the RV and different critical care states. There is a lack of a universal RV injury definition because it represents a range of abnormal RV biomechanics and phenotypes. The term "RV injury" (RVI) has been used to describe a spectrum of presentations, which includes diastolic dysfunction (early injury), when the RV retains the ability to compensate, to RV failure (late or advanced injury). Understanding the mechanisms leading to functional 'uncoupling' between the RV and the pulmonary circulation may enable perioperative physicians, intensivists, and researchers to identify clinical phenotypes of RVI. This, consequently, may provide the opportunity to test RV-centric hypotheses and potentially individualize therapies.

Increased quality of life predictive factors after cardiac resynchronization therapy in heart failure patients.

OBJECTIVE: This study aimed to investigate the effects of cardiac resynchronization therapy (CRT) treatment on clinical and echocardiographic findings, the quality of life (QoL) in heart failure (HF) patients, and to identify possible predictors of improvement in QoL. PATIENTS AND METHODS: A total of 97 patients (73 males and 24 females, mean age 62.8±10.6 years) with HF who underwent CRT implantation were included in this study. Demographic characteristics, laboratory findings, transthoracic echocardiography, and quality of life assessment of the MOS 36- Item Short-Form Health Survey (SF-36 score) data were recorded at baseline, and 6 months after CRT. Baseline and 6th-month data were compared. The data of groups with and without improvement in QoL were analyzed, and predictors of improvement in QoL were determined. RESULTS: According to the criteria for response to CRT, we observed good response at 6 months follow-up in at least two-thirds of heart failure patients. Significant improvement was observed in the SF-36 score of 67 patients who underwent CRT, and the procedure was considered successful in terms of improvement in QoL in these patients. In this group, baseline ejection fraction (EF), tricuspid annular plane systolic excursion (TAPSE), and right ventricular lateral peak systolic velocity (RV-lateral-S) values were significantly higher. TAPSE and RV lateral-S values were found to be significant in predicting the improvement in QoL after CRT [OR: 1.77 (1.00-3.14), 2.61 (1.02-6.69), respectively, p<0.05]. The cut-off values of these predictive factors were found to be 15.5 for TAPSE and 9.65 for RV lateral-S. CONCLUSIONS: In our study, we found that TAPSE and RV Lateral-S were predictors of improved quality of life in patients who underwent CRT. Routine evaluation of right ventricular functions before the procedure can provide significant improvement in quality of life as well as clinical symptoms.