Right Ventricular Dysfunction Research Articles

Right ventricular to pulmonary artery coupling in patients with different types of aortic stenosis undergoing TAVI.

Right ventricular (RV) dysfunction in patients undergoing transcatheter aortic valve implantation (TAVI) for aortic stenosis (AS) has long been disregarded. We aimed to assess the predictive value of RV to pulmonary artery coupling (RV/PAc), defined as tricuspid annular plane systolic excursion to systolic pulmonary artery pressure, on mortality in different flow types of AS after TAVI. All patients undergoing TAVI for AS at our centre between 2018 and 2020 were assessed; 862 patients were analysed. The cohort was dichotomized using a ROC analysis (cut-off 0.512mm/mmHg), into 429 patients with preserved and 433 patients with reduced RV/PAc. Reduced RV/PAc was associated with male sex and a higher rate of comorbidities. Short-term VARC-3 endpoints and NYHA classes at follow-up were comparable. Reduced RV/PAc was associated with higher 2-year all-cause mortality (35.0% [30.3-39.3%] vs. 15.4% [11.9-18.7%], hazard ratio 2.5 [1.9-3.4], p < 0.001). Cardiovascular mortality was almost tripled. Results were consistent after statistical adjustment and in a multivariate model. Sub-analyses of AS flow types revealed lower RV/PAc in classical and paradoxical low-flow low-gradient AS, with the majority having reduced RV/PAc (74% and 59%). RV/PAc retained its predictive value in these subgroups. RV dysfunction defined by low RV/PAc is a strong mortality predictor after TAVI independent of flow group. It should be incorporated in future TAVI risk assessment.

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

BackgroundAcute 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.MethodsThis 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.ResultsPulmonary 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.ConclusionIn 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.

Echocardiographic assessment of right ventricular performance in COVID-19 related acute respiratory distress syndrome: the importance of systo-diastolic interaction.

The cardiac manifestations of COVID-19 have been described in patients with acute respiratory distress syndrome (ARDS) admitted to intensive care unit (ICU). The presence and impact of right ventricular (RV) diastolic function and performance has not been studied in this population yet. We describe the prevalence of RV diastolic dysfunction, assessed by the pulmonary valve pre-ejection A wave (PV A wave), and the RV systo-diastolic interaction, using the RV total isovolumic time (t-IVT), in COVID-19 ARDS. Prospective observational study enrolling patients with moderate to severe COVID-19 ARDS admitted to ICU who underwent a transthoracic echocardiogram within 24h of ICU admission and at least a second one during the ICU stay. Respiratory, hemodynamic and biochemistry parameters were collected. 163 patients (age 61.0 ± 9.3years, 72% males) were enrolled. 36 patients (22.1%) had RV dysfunction, 45 (27.1%) LV systolic dysfunction. 73 patients (44.7%) had PV A wave. The RV t-IVT correlated with TAPSE at ICU admission (p < 0.002; r -0.61), presence of PV A wave (p < 0.001; r 0.78), peak inspiratory pressure (PIP) (p < 0.001; r 0.42), PEEP (p < 0.001; r 0.68), dynamic driving pressure (DDP) (p < 0.001; r 0.58), and PaO2/FiO2 ratio (p < 0.01; r -0.35). The presence of PV A wave was associated with higher PIP (p < 0.001; r 0.45), higher PEEP (p < 0.001; r 0.56), higher DDP (p < 0.01, r 0.51), and lower PaO2/FiO2 ratio (p < 0.001; r -0.49). RV t-IVT and the presence of PV A wave are non-invasive means to describe a significant RV diastolic dysfunction and may be consider descriptive signs of RV performance in COVID-19 ARDS.

Refractory cor pulmonale under extracorporeal membrane oxygenation for acute respiratory distress syndrome: the role of conversion to veno-pulmonary arterial assist-a case series.

Pulmonary vascular dysfunction during severe acute respiratory distress syndrome (ARDS) may lead to right ventricle (RV) dysfunction and acute cor pulmonale (ACP). The occurrence/persistence of ACP despite conventional extracorporeal membrane oxygenation (ECMO) is a challenging situation. We explored the usefulness of a specific dual-lumen cannula that bypasses the RV, and on which a veno-pulmonary arterial assist (V-P ECMO) was mounted, in ARDS patients. We report a case-series of ARDS patients put on conventional veno-arterial or veno-venous ECMO and presented refractory ACP as an indication for a reconfiguration to V-P ECMO using the ProtekDuo cannula. The primary endpoint was the mitigation of RV and pulmonary vascular dysfunction as assessed by the change in end-diastolic RV/left ventricle (LV) surface ratio. Six patients had their conventional ECMO reconfigured to V-P ECMO to treat refractory ACP. There was a decrease in end-diastolic RV/LV surface ratio, as well as end-systolic LV eccentricity index, and lactatemia immediately after V-P ECMO initiation. The resolution of refractory ACP was immediately achieved in four of our six (66%) patients. The V-P ECMO was weaned after a median of 26 [8-93] days after implantation. All but one patient were discharged home. We detected one case of severe hemolysis with V-P ECMO and two suspected cases of right-sided infective endocarditis. V-P ECMO is useful to mitigate RV overload and to improve hemodynamics in case of refractory ACP despite conventional ECMO.

Study on the correlation between retrograde ductus arteriosus flow and right ventricular function evaluated by Z-score of tricuspid annular plane systolic excursion in fetuses with Ebstein anomaly.

To analyze the influence of RV dysfunction evaluated by Free-angle M-mode (FAM) TAPSE Z-score on retrograde ductus arteriosus flow (RDAF) in fetuses with Ebstein anomaly (EA). A retrospective cohort study of 30 EA and 60 normal fetuses were enrolled. The EA group was divided into two groups: with RDAF (EA-RDAF group) and without RDAF (EA-NRDAF group). FAM was used to measure TAPSE of EA and normal fetuses, and Z-scores were calculated. The differences of FAM-TAPSE Z-score, gestational week (GW), maternal age (MA), and mitral valve-tricuspid valve distance (MTD) between three groups were compared. The correlation and binary logistic regression between FAM-TAPSE Z-score, GW, MA, MTD, and RDAF were analyzed. FAM-TAPSE Z-score was significantly lower in EA-RDAF group compared to other groups (p < 0.05). FAM-TAPSE Z-score, GW, and MA were negatively correlated with RDAF (p < 0.05), but no correlation was found between TR, MDT, and RDAF (p > 0.05). Multivariate logistic regression showed that FAM-TAPSE Z-score was an independent influencing factor for RDAF (OR = 0.102, p < 0.05). RV dysfunction is an independent factor leading to RDAF in EA fetus, which provides a feasible theoretical basis for further study on improvement of RV function through intrauterine treatment to delay and prevent the RDAF, to avoid death cycle and improve live-birth rate.

Right ventricular dysfunction in chronic heart failure: clinical laboratory and echocardiographic characteristics. (the RIVED-CHF registry).

Right ventricular dysfunction (RVD) and pulmonary hypertension have been recognized as two important prognostic features in patients with left side heart failure. Current literature does not distinguish between right heart failure (RHF) and RVD, and the two terms are used indiscriminately to describe pulmonary hypertension and RVD as well as clinical sign of RHF. Therefore, the right ventricle (RV) adaptation across the whole spectrum of left ventricular ejection fraction (LVEF) values has been poorly investigated. This is a multicenter observational prospective study endorsed by the Italian Society of Cardiology aiming to analyze the concordance between the signs and symptoms of RHF and echocardiographic features of RVD. The protocol will assess patients affected by chronic heart failure in stable condition regardless of the LVEF threshold by clinical, laboratory, and detailed echocardiographic study. During the follow-up period, patients will be observed by direct check-up visit and/or virtual visits every 6 months for a mean period of 3 years. All clinical laboratory and echocardiographic data will be recorded in a web platform system accessible for all centers included in the study. The main study goals are: to investigate the concordance and discordance between clinical signs of RHF and RVD measured by ultrasonographic examination; to evaluate prognostic impact (in terms of cardiovascular mortality and heart failure hospitalization) of RVD and RHF during a mean follow-up period of 3 years; to investigate the prevalence of different right ventricular maladaptation (isolated right ventricular dilatation, isolated pulmonary hypertension, combined pattern) and the related prognostic impact. With this protocol, we would investigate the three main RVD patterns according to heart failure types and stages; we would clarify different RVD and pulmonary hypertension severity according to the heart failure types. Additionally, by a serial multiparametric analysis of RV, we would provide a better definition of RVD stage and how much is it related with clinical signs of RHF (ClinicalTrials.gov Identifier: NCT06002321).

Outcomes of Transcatheter Tricuspid Edge-to-Edge Repair in Patients With Right Ventricular Dysfunction

BACKGROUND: We assessed the safety profile of tricuspid transcatheter edge-to-edge repair (TEER) in patients with right ventricular (RV) dysfunction. METHODS: We identified patients undergoing TEER to treat tricuspid regurgitation from June 2015 to October 2021 and assessed tricuspid annular plane systolic excursion (TAPSE) and RV fractional area change (RVFAC). RV dysfunction was defined as TAPSE &lt;17 mm and RVFAC &lt;35%. The primary end point was 30-day mortality after TEER. We also investigated the change in the RV function in the early phase and clinical outcomes at 2 years. RESULTS: The study participants (n=262) were at high surgical risk (EuroSCORE II, 6.2% [interquartile range, 4.0%–10.3%]). Among them, 44 patients met the criteria of RV dysfunction. Thirty-day mortality was 3.2% in patients with normal RV function and 2.3% in patients with RV dysfunction ( P =0.99). Tricuspid regurgitation reduction to ≤2+ was consistently achieved irrespective of RV dysfunction (76.5% versus 70.5%; P =0.44). TAPSE and RVFAC declined after TEER in patients with normal RV function (TAPSE, 19.0±4.7 to 17.9±4.5 mm; P =0.001; RVFAC, 46.2%±8.1% to 40.3%±9.7%; P &lt;0.001). In contrast, those parameters were unchanged or tended to increase in patients with RV dysfunction (TAPSE, 13.2±2.3 to 15.3±4.7 mm; P =0.011; RVFAC, 29.6%±4.1% to 31.6%±8.3%; P =0.14). Two years after TEER, compared with patients with normal RV function, patients with RV dysfunction had significantly higher mortality (27.0% versus 56.3%; P &lt;0.001). CONCLUSIONS: TEER was safe and feasible to treat tricuspid regurgitation in patients with RV dysfunction. The decline in the RV function was observed in patients with normal RV function but not in patients with RV dysfunction.

Significant disagreement between conventional parameters and 3D echocardiography-derived ejection fraction in the detection of right ventricular systolic dysfunction and its association with outcomes

AimsConventional echocardiographic parameters such as tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), and free-wall longitudinal strain (FWLS) offer limited insights into the complexity of right ventricular (RV) systolic function, while 3D echocardiography-derived RV ejection fraction (RVEF) enables a comprehensive assessment. We investigated the discordance between TAPSE, FAC, FWLS, and RVEF in RV systolic function grading and associated outcomes. MethodsWe analyzed 2D and 3D echocardiography data from two centers including 750 patients followed up for all-cause mortality. RV dysfunction was defined as RVEF<45%, with guideline-recommended thresholds (TAPSE<17 mm, FAC<35%, FWLS>-20%) considered. ResultsAmong patients with normal RVEF, significant proportions exhibited impaired TAPSE (21%), FAC (33%), or FWLS (8%). Conversely, numerous patients with reduced RVEF had normal TAPSE (46%), FAC (26%), or FWLS (41%). Using ROC analysis FWLS exhibited the highest AUC of discrimination for RV dysfunction (RVEF<45%) with 59% sensitivity and 92% specificity.Over a median 3.7-year follow-up, 15% of patients died. Univariable Cox regression identified TAPSE, FAC, FWLS, and RVEF as significant mortality predictors. Combining impaired conventional parameters showed that outcomes are the worst if at least two parameters are impaired and gradually better if only one or none of them (log-rank p<0.005). ConclusionGuideline-recommended cut-off values of conventional echocardiographic parameters of RV systolic function are only modestly associated with RVEF-based assessment. Impaired values of FWLS showed the closest association with the RVEF cut-off. Our results emphasize a multiparametric approach in the assessment of RV function, especially, if 3D echocardiography is not available.

Right Ventricular Function on Cardiovascular Magnetic Resonance Imaging and Long-Term Outcomes in Stable Heart Transplant Recipients.

In heart transplant recipients, right ventricular (RV) dysfunction may occur for a variety of reasons. Whether RV dysfunction in the stable phase after heart transplantation is associated with long-term adverse outcomes is unknown. We aimed to determine the long-term prognostic significance of RV dysfunction identified on cardiovascular magnetic resonance imaging (CMR) at least 1 year after heart transplantation. In consecutive heart transplant recipients who underwent CMR for surveillance, we assessed 2 CMR measures of RV function: RV ejection fraction and RV global longitudinal strain (RVGLS). We investigated associations between RV dysfunction and a composite end point of death or major adverse cardiac events, including retransplantation, nonfatal myocardial infarction, coronary revascularization, and heart failure hospitalization. A total of 257 heart transplant recipients (median age, 59 years; 75% men) who had CMR at a median of 4.3 years after heart transplantation were included. Over a median follow-up of 4.4 years after the CMR, 108 recipients experienced death or major adverse cardiac events. In a multivariable Cox regression analysis adjusted for age, time since transplantation, indication for transplantation, cardiac allograft vasculopathy, history of rejection, and CMR covariates, RV ejection fraction was not associated with the composite end point, but RVGLS was independently associated with the composite end point with a hazard ratio of 1.08 per 1% worsening in RVGLS ([95% CI, 1.00-1.17]; P=0.046). RVGLS provided incremental prognostic value over other variables in multivariable analyses. The association was replicated in subgroups of recipients with normal RV ejection fraction and recipients with late gadolinium enhancement imaging. A similar association was seen with a composite end point of cardiovascular death or major adverse cardiac events. CMR feature tracking-derived RVGLS assessed at least 1 year after heart transplantation was independently associated with the long-term risk of death or major adverse cardiac events. Future studies should investigate its role in guiding clinical decision-making in heart transplant recipients.

Right Ventricular “Bubble Time” to Identify Patients With Right Ventricular Dysfunction

ObjectiveWe propose a novel method of evaluating right ventricular (RV) dysfunction in the emergency department (ED) using RV “bubble time” – the duration of time bubbles from a saline flush are visualized in the RV on echocardiography. The objective was to identify the optimal cutoff value for RV bubble time that differentiates patients with RV dysfunction and report on its diagnostic test characteristics. MethodsThis prospective diagnostic accuracy study enrolled a convenience sample of hemodynamically stable ED patients. A sonographer administered a 10-milliliter saline flush into patient’s intravenous catheter, performed a bedside echocardiogram, and measured RV bubble time. Subsequently, the patient underwent a comprehensive cardiologist-interpreted echocardiogram with 36 hours, which served as the gold standard. Patients with RV strain or enlargement on the latter echocardiogram were considered to have RV dysfunction. Bubble time was evaluated by a second provider, blinded to the initial results, who reviewed the ultrasound clips. The primary outcome measure was the optimal cutoff value of RV bubble time that identifies patients with and without RV dysfunction. ResultsOf 196 patients, median age was 67 and half were female, with 69 (35.2%) having RV dysfunction. Median RV bubble time among patients with RV dysfunction was 62 seconds (interquartile range (IQR): 52, 93) compared with 21 seconds (IQR: 12, 32) among patients without (p<0.0001). The optimal cutoff value of RV bubble time for identifying patients with RV dysfunction was ≥40 seconds, with a sensitivity of 0.97 (95% CI: 0.93, 1.00) and specificity of 0.87 (95% CI: 0.82, 0.93). ConclusionIn ED patients, an RV bubble time of ≥40 seconds had high sensitivity in identifying patients with RV dysfunction, while an RV bubble time of <40 seconds had good specificity in identifying patients without RV dysfunction. These findings warrant further investigation in undifferentiated patient population and by emergency physicians without advanced ultrasound training.

C-reactive Protein and Risk of Right Ventricular Dysfunction and Mortality in Patients With Acute Symptomatic Pulmonary Embolism

BackgroundRight ventricle (RV) dysfunction increases the risk of death from pulmonary embolism (PE). C-reactive protein (CRP) might identify RV inflammation and dysfunction in patients with PE. MethodsThis cohort study enrolled consecutive stable patients with acute PE between 2017 and 2023. We stratified patients by quartiles of CRP. We evaluated the association between CRP quartiles and the presence of RV dysfunction, and used multivariable models to assess for an association between CRP and the outcomes of all-cause and PE-specific mortality during the 30 days of follow-up after PE diagnosis. ResultsThe study included 633 stable patients with PE. Patients without RV dysfunction had significantly lower median (IQR) CRP levels compared with patients with RV dysfunction (n=509, 31.7 [10.0–76.4]mg/L vs n=124, 45.4 [16.0–111.4]mg/L; P=0.018). CRP showed a statistically significant positive association with the presence of RV dysfunction (P<0.01). On multivariable analysis, CRP level was not significantly associated with 30-day all-cause mortality (adjusted odds ratio [OR] per mg/L increment, 1.00; 95% CI, 1.00–1.01; P=0.095), but higher CRP was associated with significantly higher PE-related mortality (adjusted OR, 1.01; 95% CI, 1.00–1.01; P=0.026). Compared with patients in CRP quartile 1, patients in quartiles 2, 3, and 4 had a stepwise increase in the adjusted odds of 30-day all-cause death of 2.41 (P=0.148), 3.04 (P=0.062), and 3.15 (P=0.052), respectively. ConclusionsAs an indicator of RV dysfunction, CRP may improve risk stratification algorithms for hemodynamically stable patients with acute symptomatic PE.

Association between right ventricular global longitudinal strain and mortality in intermediate-risk pulmonary embolism.

Right ventricular (RV) systolic dysfunction has been identified as a prognostic marker for adverse clinical events in patients presenting with acute pulmonary embolism (PE). However, challenges exist in identifying RV dysfunction using conventional echocardiography techniques. Strain echocardiography is an evolving imaging modality which measures myocardial deformation and can be used as an objective index of RV systolic function. This study evaluated RV Global Longitudinal Strain (RVGLS) in patients with intermediate risk PE as a parameter of RV dysfunction, and compared to traditional echocardiographic and CT parameters evaluating short-term mortality. Retrospective single center cohort study of 251 patients with intermediate-risk PE between 2010 and 2018. The primary outcome was all-cause mortality at 30 days. Statistical analysis evaluated each parameter comparing survivors versus non-survivors at 30 days. Receiver operating characteristic (ROC) curves and Kaplan-Meier curves were used for comparison of the two cohorts. Altogether 251 patients were evaluated. Overall mortality rate was 12.4%. Utilizing an ROC curve, an absolute cutoff value of 17.7 for RVGLS demonstrated a sensitivity of 93% and specificity of 70% for observed 30-day mortality. Individuals with an RVGLS ≤17.7 had a 25 times higher mortality rate than those with RVGLS above 17.7 (HR 25.24, 95% CI=6.0-106.4, p<.001). Area under the curve was (.855), RVGLS outperformed traditional echocardiographic parameters, CT findings, and cardiac biomarkers on univariable and multivariable analysis. Reduced RVGLS values on initial echocardiographic assessment of patients with intermediate-risk PE identified patients at higher risk for mortality at 30 days.

Right ventricular preload and afterload challenge induces contractile dysfunction and arrhythmia in isolated hearts of dystrophin-deficient male mice.

Duchenne muscular dystrophy (DMD) is an X-linked recessive myopathy due to mutations in the dystrophin gene. Diaphragmatic weakness in DMD causes hypoventilation and elevated afterload on the right ventricle (RV). Thus, RV dysfunction in DMD develops early in disease progression. Herein, we deliver a 30-min sustained RV preload/afterload challenge to isolated hearts of wild-type (Wt) and dystrophic (Dmdmdx-4Cv) mice at both young (2-6 month) and middle-age (8-12 month) to test the hypothesis that the dystrophic RV is susceptible to dysfunction with elevated load. Young dystrophic hearts exhibited greater pressure development than wild type under baseline (Langendorff) conditions, but following RV challenge exhibited similar contractile function as wild type. Following the RV challenge, young dystrophic hearts had an increased incidence of premature ventricular contractions (PVCs) compared to wild type. Hearts of middle-aged wild-type and dystrophic mice had similar contractile function during baseline conditions. After RV challenge, hearts of middle-aged dystrophic mice had severe RV dysfunction and arrhythmias, including ventricular tachycardia. Following the RV load challenge, dystrophic hearts had greater lactate dehydrogenase (LDH) release than wild-type mice indicative of damage. Our data indicate age-dependent changes in RV function with load in dystrophin deficiency, highlighting the need to avoid sustained RV load to forestall dysfunction and arrhythmia.

Assessing right ventricular peak strain in myocardial infarction patients with mitral regurgitation by cardiac magnetic resonance feature tracking.

Although it is known that mitral regurgitation (MR) in patients with myocardial infarction (MI) may increase the right ventricular (RV) afterload, leading to RV dysfunction, the exact detrimental effects on RV function and myocardial peak strain remain unresolved. In this study, we assessed the impact of MR on the impairment of RV myocardial deformation in patients with MI and explored the independent influential factors of RV peak strain. A total of 199 MI participants without or with MR were retrospectively assessed in this study. The cardiovascular magnetic resonance examination protocol included a late gadolinium-enhanced (LGE) imaging technique and a cine-balanced steady-state free precession sequence. Statistical tests, including two independent sample t-test or Mann-Whitney U-test, analysis of variance, Kruskal-Wallis test, and multiple linear regression analysis models were performed. The MI (MR+) group exhibited significantly lower RV strain parameters in the radial, circumferential and longitudinal directions when compared to the control and the MI (MR-) groups (both P<0.05). The RV global longitudinal peak strain (GLPS) in the MI group significantly decreased when compared with that in the control group (P<0.05). As moderate-severe MR worsened in patients with MI, RV myocardial global peak strain and the peak systolic strain rate (PSSR) gradually decreased. Multiple linear regression analysis revealed that left ventricular (LV) GLPS, triglycerides, and age were independently correlated with RV GLPS (all P<0.05). RV end-systolic volume (RVESV) acted as an independent association factor for RV global peak strain. MR may exacerbate the impairment of RV peak strain and functions in patients with MI. LV GLPS was positively correlated with RV GLPS. However, RVESV, triglycerides, and age acted as independent risk factors associated with worsening RV GLPS.

In-Hospital versus Out-of-Hospital Pulmonary Embolism: Clinical Characteristics, Biochemical Markers and Echocardiographic Indices.

A significant proportion of pulmonary embolisms (PEs) occurs in patients during hospitalisation for another reason. However, limited data regarding differences between out-of-hospital PE (OHPE) and in-hospital PE (IHPE) is available. We aimed to compare these groups regarding their clinical characteristics, biochemical markers, and echocardiographic indices. This was a prospective, single-arm, single-centre study. Adult consecutive patients with non-COVID-related PE from September 2019 to March 2022 were included and followed up for 12 months. The study included 180 (84 women) patients, with 89 (49.4%) suffering from IHPE. IHPE patients were older, they more often had cancer, were diagnosed earlier after the onset of symptoms, they had less frequent pain and higher values of high sensitivity troponin I and brain natriuretic peptide levels compared to OHPE patients. Echocardiographic right ventricular (RV) dysfunction was detected in similar proportions in the 2 groups. IHPE had increased in-hospital mortality (14.6% vs. 3.3%, p = 0.008) and similar post-discharge to 12-month mortality with OHPE patients. In this prospective cohort study, IHPE differed from OHPE patients regarding age, comorbidities, symptoms, and levels of biomarkers associated with RV dysfunction. IHPE patients had higher in-hospital mortality compared to OHPE patients and a similar risk of death after discharge.

Metabolic changes contribute to maladaptive right ventricular hypertrophy in pulmonary hypertension beyond pressure overload: an integrative imaging and omics investigation.

Right ventricular (RV) failure remains the strongest determinant of survival in pulmonary hypertension (PH). We aimed to identify relevant mechanisms, beyond pressure overload, associated with maladaptive RV hypertrophy in PH. To separate the effect of pressure overload from other potential mechanisms, we developed in pigs two experimental models of PH (M1, by pulmonary vein banding and M2, by aorto-pulmonary shunting) and compared them with a model of pure pressure overload (M3, pulmonary artery banding) and a sham-operated group. Animals were assessed at 1 and 8 months by right heart catheterization, cardiac magnetic resonance and blood sampling, and myocardial tissue was analyzed. Plasma unbiased proteomic and metabolomic data were compared among groups and integrated by an interaction network analysis. A total of 33 pigs completed follow-up (M1, n = 8; M2, n = 6; M3, n = 10; and M0, n = 9). M1 and M2 animals developed PH and reduced RV systolic function, whereas animals in M3 showed increased RV systolic pressure but maintained normal function. Significant plasma arginine and histidine deficiency and complement system activation were observed in both PH models (M1&M2), with additional alterations to taurine and purine pathways in M2. Changes in lipid metabolism were very remarkable, particularly the elevation of free fatty acids in M2. In the integrative analysis, arginine-histidine-purines deficiency, complement activation, and fatty acid accumulation were significantly associated with maladaptive RV hypertrophy. Our study integrating imaging and omics in large-animal experimental models demonstrates that, beyond pressure overload, metabolic alterations play a relevant role in RV dysfunction in PH.

The selective serotonin reuptake inhibitor paroxetine improves right ventricular systolic function in experimental pulmonary hypertension

BackgroundPulmonary hypertension (PH) often leads to right ventricle (RV) failure, a significant cause of morbidity and mortality. Despite advancements in PH management, progression to RV maladaptation and subsequent failure remain a clinical challenge. This study explored the effect of paroxetine, a selective serotonin reuptake inhibitor (SSRI), on RV function in a rat model of PH, hypothesizing that it improves RV function by inhibiting G protein-coupled receptor kinase 2 (GRK2) and altering myofilament protein phosphorylation. MethodsThe Su5416/hypoxia (SuHx) rat model was used to induce PH. Rats were treated with paroxetine and compared to vehicle-treated and control groups. Parameters measured included RV morphology, systolic and diastolic function, myofilament protein phosphorylation, GRK2 activity, and sympathetic nervous system (SNS) markers. ResultsParoxetine treatment significantly improved RV systolic function, evidenced by increased stroke volume, cardiac output, and ejection fraction, without significantly affecting RV hypertrophy, myosin heavy chain/titin isoform switching, or fibrosis. Enhanced phosphorylation of titin and myosin light chain-2 was observed, correlating positively with improved systolic function. Contrary to the hypothesis, improvements occurred independently of GRK2 inhibition or SNS modulation, suggesting an alternate mechanism, potentially involving antioxidant properties of paroxetine. ConclusionParoxetine improves RV systolic function in PH rats, likely through mechanisms beyond GRK2 inhibition, possibly related to its antioxidant effects. This highlights the potential of paroxetine in managing RV dysfunction in PH, warranting further investigation into its detailed mechanisms of action and clinical applicability.

Right Ventricular Dysfunction in Patients With Concomitant Tricuspid Regurgitation Undergoing Transcatheter Aortic Valve Implantation.

This study investigated the impact and predictive factors of concomitant significant tricuspid regurgitation (TR) and evaluated the roles of right ventricle (RV) function and the etiology of TR in the clinical outcomes of patients with severe aortic stenosis undergoing transcatheter aortic valve implantation (TAVI).Methods and Results: We assessed grading of TR severity, TR etiology, and RV function in pre- and post-TAVI transthoracic echocardiograms for 678 patients at Keio University School of Medicine. TR etiology was divided into 3 groups: primary TR, ventricular functional TR (FTR), and atrial FTR. The primary outcomes were all-cause and cardiovascular death. At baseline, moderate or greater TR was found in 55 (8%) patients and, after adjustment for comorbidities, was associated with increased all-cause death (hazard ratio [HR] 2.11; 95% confidence interval [CI] 1.19-3.77; P=0.011) and cardiovascular death (HR 2.29; 95% CI 1.06-4.99; P=0.036). RV dysfunction (RVD) also remained an independent predictor of cardiovascular death (HR 2.06; 95% CI 1.03-4.14; P=0.042). Among the TR etiology groups, patients with ventricular FTR had the lowest survival rate (P<0.001). Patients with persistent RVD after TAVI had a higher risk of cardiovascular death than those with a normal or recovered RV function (P<0.001). The etiology of TR and RV function play an important role in predicting outcomes in concomitant TR patients undergoing TAVI.

Echocardiographic haemodynamic monitoring in the context of HeartMate 3™ therapy: a systematic review.

While echocardiography remains essential within haemodynamic monitoring of durable mechanical circulatory support, previous echocardiographic guidelines are missing scientific evidence for the novel HeartMate 3™ (HM3) system. Accordingly, this review aims to summarize available echocardiographic evidence including HM3. This systematic review adhered to the PRISMA 2020 guidelines. Searches were conducted during August 2023 across PubMed, Embase, and Google Scholar using specific echocardiographic terms combined with system identifiers. Study quality was assessed using the Newcastle-Ottawa Scale (NOS) for cohort studies and Critical Appraisal Instrument (PCAI) for cross-sectional studies. Nine studies met the inclusion criteria, of which eight cohort studies and one cross-sectional study. Aortic regurgitation (AR) prevalence at approximately 12months of support exhibited heterogenicity (33.5% (Δ 33%)) in a limited number of studies (n=3). Several studies (n=5) demonstrated an increasing prevalence and severity of AR during HM3 support, generating moderate to high level of evidence. One AR study showed a higher cumulative incidence of death and heart failure (HF) readmission compared with those without significant AR, hazard ratio 3.42 (95% CI 1.48-8.76). A second study showed that a worsening AR group had significantly lower survival-free from HF readmission (59% vs. 89%, P=0.023) with a hazard ratio of 5.18 (95% CI 1.07-25.0), while a third study did not reveal any differences in cardiac-related hospitalizations in the 12months follow-up or non-cardiac-related hospitalization. Mitral regurgitation (MR) prevalence at approximately 12months of support exhibited good consistency 15.0% (Δ 0.8%) in both included studies, which did not reveal any significant pattern of changing prevalence over time. Tricuspid regurgitation (TR) prevalence at approximately 12months of support exhibited fair consistency 28.5% (Δ 8.3%) in a limited number of studies (n=2); both studies showed a statistically un-confirmed trend of increased TR prevalence over time. The evidence of general prevalence of right ventricular dysfunction (RVD) was insufficient due to lack of studies. There are few methodologically consistent studies with focus on long-term haemodynamic effects. Aortic regurgitation still seems to be a prevalent and potentially significant finding. The available evidence concerning right heart function is limited despite clinical relevance and potential prognostic value. Potential interventricular and haemodynamic interplay are identified as a white field for future research.

The role of echocardiography in pulmonary embolism for the prediction of in-hospital mortality: a retrospective study.

Pulmonary Embolism (PE) is the third leading cause of cardiovascular death, following myocardial infarction and stroke. The latest European Society of Cardiology (ESC) guidelines on PE recommend short-term prognostic stratification based on right ventricular (RV) overload detected by transthoracic echocardiography (TTE) or contrast-enhanced chest CT. The aim of the study is to find out which of the signs of right ventricular dysfunction best predicts in-hospital mortality (IHM). This is a monocentric, retrospective study including adult patients admitted from the emergency department with a c-e cCT confirmed diagnosis of PE between January 2018 and December 2022 who underwent a TTE within 48h. 509 patients (median age 76years [IQR 67-84]) were included, with 7.1% IHM. At univariate analysis, RV/LV ratio > 1 (OR 2.23, 95% CI 1.1-4.5), TAPSE < 17mm (OR 4.73, 95% CI 2.3-9.8), the D-shape (OR 3.73, 95% CI 1.71-8.14), and LVEF < 35% (OR 5.78, 95% CI 1.72-19.47) resulted significantly correlated with IHM. However, at multivariate analysis including also haemodynamic instability, PESI class > II, and abnormal hs-cTnI levels, only LVEF < 35% (OR 5.46, 95% CI 1.32-22.61) resulted an independent predictor of IHM. Despite the recognised role of TTE in the early management of patients with circulatory shock and suspected PE, signs of RV dysfunction have been shown to be poor predictors of IHM, whereas severely reduced LVEF is an independent risk factor for in-hospital death.