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Abstract Introduction Secondary tricuspid regurgitation (STR) is a highly prevalent valve disease. STR and Heart Failure with preserved Ejection Fraction (HFpEF) share common features including exertional intolerance and high burden of atrial fibrillation (AF) and pulmonary hypertension (PH), making it challenging to disentangle HFpEF from TR. The incidence of clinically-recognized HFpEF in STR and its impact on mortality are not well established. Purposes To define the incidence of newly diagnosed HFpEF and its impact on mortality in a cohort of patients with significant STR and to evaluate the likelihood of a larger hidden burden of HFpEF. Methods Patients with a first diagnosis of ≥moderate-severe STR between 2004-2019 at our institution were retrospectively included. Patients with left ventricle ejection fraction <50%, left-sided valve diseases, and intracardiac device leads were excluded. HFpEF was identified by manual chart review as well as by use of ICD codes. The estimated prevalence of HFpEF was evaluated using an H2FPEF score ≥6, which corresponds to a ≥90% probability of having HFpEF. Results Of 2118 patients (mean age 70 ± 14, 36% females), 1057 (50%) had systemic hypertension (HTN) and 1091 (51%) had AF, with median 2.3 years of follow-up. From this cohort, 536 (25%) patients were diagnosed with HFpEF based upon chart review during the follow up period, while ICD diagnosis was only present in fewer than 50% of these patients (254). High H2FPEF score was present in 880 patients (41.5%), of whom 383 received a chart diagnosis of HFpEF, while 153 patients with H2FPEF score <6 received a chart HFpEF diagnosis. The cumulative incidence of chart-based diagnosis of HFpEF was 20.8% (N=158) at 1-year and 38.6% (N=273) at 5-years in patients with an H2FPEF score ≥6 and 5.5%(N=60) at 1-year and 11.1%(N=111) at 5-years in those with a score <6 (Figure). In Cox regression analyses, the diagnosis of HFpEF during follow-up was associated with increased mortality (HR 2.14, CI 1.86-2.46, p < 0.001) after adjusting for age, sex, body mass index, coronary artery disease, diabetes mellitus, chronic obstructive pulmonary disease, diuretics, HTN, pulmonary hypertension, chronic kidney disease and AF. Conclusions The incidence of clinically documented HFpEF in a cohort of patients with significant STR at index evaluation is high (25%). Use of ICD code underestimates clinical recognition, with the actual burden of HFpEF probably being even greater, as indicated by an H2FPEF score ≥ 6. Among those with significant STR, HFpEF diagnosis is an independent risk factor for mortality.

Abstract Background/Introduction Tricuspid valve regurgitation (TR) is a common valvular disease associated with increased mortality. There is a need for tools to assess the interaction between the pulmonary artery (PA) circulation and the right ventricle (RV) in patients with TR and to investigate their association with outcomes. Various echo parameters have emerged that assess RV-PA coupling, including the ratio of TAPSE to RV systolic pressure (RVSP) and the PA pulsatility index (PAPi). The effective PA elastance (PA Ea) is a composite measure of RV afterload that refers to the measure of the pulmonary vascular load that the RV must overcome to eject blood into the PA. PA Ea is simple to estimate by echo and found to be an independent haemodynamic risk measure in various left heart and pulmonary hypertension (PH) diseases. Whether PA Ea discriminates risk in unselected patients with significant TR and how it compares to other measures of RV-PA coupling is untested. Purpose To ascertain the prognostic value of PA Ea in patients with TR. Methods In consecutive patients with a first diagnosis of ≥ moderate TR (regardless of aetiology), we compared all-cause mortality at five years based on the PA Ea (defined as the RVSP/stroke volume as measured by transthoracic echocardiography). As stroke volume was measured by Doppler at the left ventricular (LV) outflow tract, patients with > moderate aortic valve regurgitation were excluded. The Tricuspid Regurgitation Impact on Outcomes (TRIO) score was calculated as previously described. PA Ea was separated into 4 groups for comparison based on the separation of quartiles of PA Ea rounded to one decimal place. Results In the 13,608 patients studied, PA Ea could be calculated in 12,682 patients (94.4%). The median PA Ea was 0.68 mmHg/mL (IQR 0.50, 0.92). Increasing levels of PA Ea were associated with clinical comorbidities including heart failure, liver and kidney disease and clinical markers of risk such as the TRIO score. Increasing levels of PA Ea were also associated with larger RVs, worse RV systolic function, higher NT-pro BNP levels, and greater degrees of right heart failure (Table). Each quartile of PA Ea was associated with a significant increase in all-cause mortality (Figure). After adjusting for age and sex, PA Ea was associated with higher risk of death (HR 2.41 (2.28-2.56); p<.0001). While worsening degrees of PA Ea correlated with both declining levels of TAPSE/PASP and PAPi (Table), PA Ea was independently predictive of outcome in a combined model: PA Ea HR 1.65 (1.51-1.80, Chi-squ 120, p<.0001); PAPi HR 0.84 (0.80-0.89, Chi-squ 48, p<.0001) and TAPSE/PASP HR 0.32 (017-0.60, Chi-squ 12, p=.0004). Conclusion(s) In patients with significant TR, PA Ea is highly feasible and higher PA Ea is progressively associated with RV dysfunction, right heart failure, and worse survival. Incorporating PA Ea into the routine echo assessment may help stratify disease severity in patients with significant TR. Table Assoc. of PA Ea with mortality in TR

The pathogenesis of chronic aortic regurgitation (AR) is different in male and female. Female patients with AR showed less aortic valve inflammation and collagen accumulation as compared with male. Valvular cells from female patients secreted less inflammatory molecules and collagen and higher levels of proteoglycans. Valvular interstitial cells from females were more sensitive to transforming growth factor (TGF)-β-induced proteoglycans secretion. Our study opens a new perspective oriented toward sex-specific molecular pathways and therapeutic targets in chronic severe AR.

Background: Aortic regurgitation (AR) is a prevalent valve disease with a long latent period to symptoms. Recent data has suggested the role of novel markers of myocardial overload in assessing onset of decompensation. Method: We sought to evaluate the role of unsupervised cluster analyses in identifying different clinical clusters, including clinical status, and a large number of echocardiographic variables including left ventricular (LV) volumes, and their association with mortality. Patients with ≥moderate-severe chronic AR identified using echocardiography at Mayo Clinic, Rochester were retrospectively analyzed. Primary outcome was all-cause mortality censored at aortic valve surgery/last follow-up. Uniform Manifold Approximation and Projection (UMAP) with K -means algorithm was used to cluster patients using clinical and, echocardiographic variables at the time of presentation. Missing data were imputed with the Multiple Imputation by Chained Equations (MICE) method. A supervised approach trained on the training set was used to find cluster membership in a hold-out validation set. Log-rank tests were used to assess differences in mortality rates between the clusters, both in the training and validation sets. Results: Three distinct clusters were identified among 1100 patients (log-rank P for survival <0.001). Cluster 1 (n=337), which included younger males with severe AR but fewer symptoms, showed the best survival, 75.6% (69.5, 82.3). Cluster 2 (n=235), older and more females with elevated filling pressures, showed intermediate survival of 64.2 % (56.8, 72.5). Cluster 3 (n=253), characterized by severe symptomatic AR, demonstrated the lowest survival of 45.3 % (34.4, 59.8) at 5 years. Similar clusters were formed in the internal validation cohort. Conclusion: Distinct clusters with variable echocardiographic features and mortality differences exist within patients with chronic ≥moderate-severe AR. Recognizing these clusters can refine individual risk stratification and clinical decision-making after verification in future prospective studies.

Background Symptomatic limitations in apical hypertrophic cardiomyopathy may occur because of diastolic dysfunction with resultant elevated left ventricular filling pressures, cardiac output limitation to exercise, pulmonary hypertension (PH), valvular abnormalities, and/or arrhythmias. In this study, the authors aimed to describe invasive cardiac hemodynamics in a cohort of patients with apical hypertrophic cardiomyopathy. Methods and Results Patients presenting to a comprehensive hypertrophic cardiomyopathy center with apical hypertrophic cardiomyopathy were identified (n=542) and those who underwent invasive hemodynamic catheterization (n=47) were included in the study. Of these, 10 were excluded due to postmyectomy status or incomplete hemodynamic data. The mean age was 56±18 years, 16 (43%) were women, and ejection fraction was preserved (≥50%) in 32 (91%) patients. The most common indication for catheterization was dyspnea (48%) followed by suspected PH (13%), and preheart transplant evaluation (10%). Elevated left ventricular filling pressures at rest or exercise were present in 32 (86%) patients. PH was present in 30 (81%) patients, with 6 (20%) also having right‐sided heart failure. Cardiac index was available in 25 (86%) patients with elevated resting filling pressures. Of these, 19 (76%) had reduced cardiac index and all 6 with right‐sided heart failure had reduced cardiac index. Resting hemodynamics were normal in 8 of 37 (22%) patients, with 5 during exercise; 3 of 5 (60%) patients had exercise‐induced elevation in left ventricular filling pressures. Conclusions In patients with apical hypertrophic cardiomyopathy undergoing invasive hemodynamic cardiac catheterization, 86% had elevated left ventricular filling pressures at rest or with exercise, 81% had PH, and 20% of those with PH had concomitant right‐sided heart failure.

Background: Clinically significant tricuspid regurgitation (TR) is an important contributor to morbidity and mortality. The Tricuspid Regurgitation Impact on Outcomes (TRIO) score based on 8 parameters (age, gender, chronic heart failure, chronic lung disease, heart rate, creatinine, aspartate transaminase level, and TR severity) is used for risk stratification. The performance of the TRIO score in patients with TR secondary to severe pulmonary hypertension (PH) is unknown. Research Questions: To evaluate whether the TRIO score can be applied in patients with TR and pulmonary hypertension (PH), and to identify other predictors of mortality. Methods: Retrospective study including patients with TR ≥ moderate. Severe PH was defined as right ventricular systolic pressure (RVSP) ≥50 mmHg. The impact of clinical, echocardiographic and laboratory variables on mortality was evaluated with the Cox proportional hazard method. Results: A total of 13,482 patients from the TRIO population were included; severe PH was present in 6,530 (48.4%); mean age 73.4 + 13.3, 55.7% females. TRIO score performance was modest (AUC 0.62) in risk stratification (Figure A). PH patients had significantly higher mortality than those without PH at all levels of TRIO score (Figure B); differences were progressively lower with increasing TRIO scores. At multivariate analysis, only TRIO score [HR = 1.54 (1.35-1.77) per unit change], presence of an elevated NT-proBNP [HR = 1.02 (1.02-1.03) per 1000 pg/ml change], RVSP (HR = 1.08 (1.02-1.16) per 10 mmHg change], presence of RV dysfunction [HR = 1.15, (1.05-1.26)] and pulmonary artery pulsatility index (PAPi) ≤ 4 [HR = 1.34 (1.07-1.67)] were significant predictors of mortality (model AUC 0.65). Conclusions: TRIO score allows risk stratification in PH patients, but performance is modest; incorporating additional factors marginally increased model performance. PH patients have higher mortality at all levels of TRIO score, more so at low scores.

Introduction: Tricuspid regurgitation is a common echocardiographic finding leading to excess morbidity and mortality in adult population. Hypothesis: Racial and ethnic disparities have been observed in various cardiovascular disorders’ prevalence and natural course, including valvular lesions. However, little is known about the epidemiology and clinical correlations of TR among non-Hispanic Black adults. Methods: To examine risk factors and clinical outcomes in non-Hispanic Black adults with moderate or more severe TR, 685 patients (7%) self-identified as non-Hispanic Black and 9127 (93%) self-identified as non-Hispanic White with a first echocardiographic report of moderate or more severe TR between 2005-2016 were studied. Results: Non-Hispanic Black patients had more severe TR when compared to white patients (25% vs. 20%, p<0.001). After adjusting for age and sex, non-Hispanic Black patients had significantly higher 10-year all-cause mortality (HR=1.34 (1.18, 1.52), p<0.001). Black race remained a risk factor for all-cause mortality even after adjustment for comorbidities like CHF, COPD, DM, CKD, hypertension, and ischemic heart disease (HR=1.23 (1.08, 1.40), p=0.002). Conclusions: Significant racial disparities exist in demographic, clinical and echocardiographic characteristics between non-Hispanic Black and White patients with moderate or more severe TR. Black race is a potential disease modifier leading to excess mortality.

Objective Tricuspid regurgitation (TR) is a prevalent valve disease associated with significant morbidity and mortality. We aimed to apply machine learning (ML) to assess risk stratification in patients with ≥moderate TR. Methods Patients with ≥moderate TR on echocardiogram between January 2005 and December 2016 were retrospectively included. We used 70% of data to train ML-based survival models including 27 clinical and echocardiographic features to predict mortality over a 3-year period on an independent test set (30%). To account for differences in baseline comorbidities, prediction was performed in groups stratified by increasing Charlson Comorbidity Index (CCI). Permutation feature importance was calculated using the best-performing model separately in these groups. Results Of 13 312 patients, mean age 72 ± 13 years and 7406 (55%) women, 7409 (56%) had moderate, 2646 (20%) had moderate–severe and 3257 (24%) had severe TR. The overall performance for 1-year mortality by 3 ML models was good, c-statistic 0.74–0.75. Interestingly, performance varied between CCI groups, (c-statistic = 0.774 in lowest CCI group and 0.661 in highest CCI group). The performance decreased over 3-year follow-up (average c-index 0.78). Furthermore, the top 10 features contributing to these predictions varied slightly with the CCI group, the top features included heart rate, right ventricular systolic pressure, blood pressure, diuretic use and age. Conclusions Machine learning of common clinical and echocardiographic features can evaluate mortality risk in patients with TR. Further refinement of models and validation in prospective studies are needed before incorporation into the clinical practice.

Abstract Background Pulmonary veno-occlusive disease (PVOD) is a rare cause of pulmonary hypertension that primarily results in intimal fibrosis of the pulmonary venules and veins, the venous lesions are often associated with changes in interlobular septa, lung parenchyma, and pulmonary arterioles and arteries. Purpose We sought to study the clinical characteristics of patients with confirmed PVOD at a single large referral center. Methods We retrospectively reviewed data from a total of 675 patients with pulmonary hypertension (identified by ICD codes or search of text) from 2017 and 2022 from a database obtained from electronic medical records at our institution. Patients with group 2 pulmonary hypertension were excluded. Only 29 cases were confirmed by histology or genetic testing. Results Out of the 29 patients confirmed with PVOD, 28 (96.5%) had a characteristic histology (lung biopsy (55.1%), explanted lung for transplant (27.5%) and autopsy (13.7%)) and 1 (3.4%) had a positive genetic test for EIF2AK4 biallelic mutation. The age at diagnosis was 53±16 years, 14 (48.2%) were men, 2 (6.8%) had systemic scleroderma, 2 (6.8%) had psoriasis, 2 (6.8%) were exposed to cytotoxic agents, 16 (55.1%) were smokers and 2 (6.8%) had a family history of pulmonary hypertension. All patients had computed tomography of the chest but only 12 (41.3%) had all 3 typical features found in PVOD (ground glass opacities, interlobular septal thickening, and lymphadenopathy). The most common feature was interlobular septal thickening in 26 (89.6%), followed by ground glass opacities present in 25 (86.2%) and lymphadenopathy in 12 (41.3%) of the patients. At diagnosis, mean pulmonary artery pressure was 45±15 mmHg and pulmonary vascular resistance was 9±6 WU. The median DLCO was 41 (34-58) %. On echocardiogram, 14 (48.2%) had severely enlarged right ventricle (RV), RV function was ≥moderately reduced in 17 (58.6%), RV systolic pressure was 63±20 mmHg and 6 (20.6%) had pericardial effusion. Out of 21 (72.4%) patients who received pulmonary vasodilators, 4 (13.7%) received single agent. 10 (34.4%) received 2 agents, 6 (20.6%) 3 agents, and 1 (3.4%) received 4 agents. 35.7% of these treated patients reported an improvement or initial worsening of symptoms with subsequent improvement afterwards. 18 (62%) patients with PVOD died, 12 (41.3%) had a lung transplant and 6 (20.6%) were still alive without the transplant until the day data was collected. Mean duration from diagnosis to death and lung transplantation was 446 ± 405 days and 274±479 days respectively. Conclusion PVOD is a rare and lethal cause of pulmonary hypertension. When suspected, a trial of medical therapy should be initiated carefully. The evaluation for lung transplant should be considered early given its high mortality.