Anand, Vijesh

Abstract Background Isolated tricuspid regurgitation (TR) repair or replacement carries significant operative mortality risk mainly due to delayed referral. We have recently developed the Tricuspid Regurgitation Impact on Outcomes (TRIO) score to assess risk in TR based on 8 simple variables (age, sex, severe TR, creatinine>2 mg/dl, history of heart failure, history of chronic lung disease, AST >40 units/L, heart rate >90). Whether this score can be used in assessment of TR surgical risk and long term outcome is unknown. Purpose To examine the impact of TRIO scores on the postoperative outcomes of isolated tricuspid valve surgery. Methods Adult patients with severe functional TR who underwent isolated tricuspid valve replacement or repair between 2000-2022 were identified. Postoperative outcomes were compared across low (0-3), intermediate (4-6), and high (7-12) TRIO risk score groups. Results 177 patients were included. Mean age was 70.7 ± 12.2 years, 69 (39%) were male, 34 (19%) were low TRIO score, 111 (63%) intermediate score and 32 (18%) high score. Tricuspid repair was performed in 43 (24.3%) and valve replacement in 134 (75.7%), reflecting the advanced disease stages of this patient cohort. At short term, higher TRIO scores were associated with more frequent need for urgent surgery, prolonged ventilation (>72h) and postoperative dialysis (p<0.05 for all). Perioperative 30-day mortality increased with the TRIO risk score (low: 0%; intermediate: 4.5%; high: 9.4%) but differences did not reach statistical significance (p=0.187). Low risk patients had a shorter hospital and ICU stay (Figure 1A-B). During a mean follow-up of 5.2 ± 3.2 years, 98 (55.4%) patients died. At long term follow-up, lower TRIO scores were associated with improved survival after tricuspid surgery (Figure 1C). Conclusions Patients with higher TRIO scores have more postoperative complications, require longer hospital stay and have higher all-cause mortality at long-term follow-up. Our findings suggest that TRIO score may also be used for risk stratification in patients considered for surgical management of isolated functional TR.

Abstract Background Increased left ventricular (LV) stiffness (LVStiffn) was shown to be associated with mortality in patients with severe aortic stenosis (AS), despite aortic valve replacement (AVR), and may contribute to future heart failure (HF) symptoms. The aim was to assess whether preoperative LVStiffn is a risk factor of HF in these patients. Methods A retrospective analysis was done in patients with severe AS who underwent AVR (93% surgical). LV end-diastolic pressure-volume relations (P=aVb) were reconstructed from LV end-diastolic volumes and estimated end-diastolic pressures (from E/e'); LVStiffn at 30 mmHg (CS30) and capacitance (V30) were then derived. Primary endpoint was development of symptomatic HF at >1 month post AVR. Results 1,837 patients were studied (age 76±10 years, 62% males, LVEF 61±12%; Table). Mean CS30 was 2.2±1.3 mmHg/mL and V30 64±17 mL/m2. Patients with higher CS30 ≥3 mmHg/mL were older, more frequently female, and had more comorbidities. During a median follow-up of 5.0 [3.0–7.9] years, 607 (33%) patients developed HF. A higher CS30 (≥3 mmHg/mL), but not V30 (P=0.32), was associated with higher risk of HF events (HR 1.86 [95% CI 1.52–2.27], P<0.0001), along with other clinical and echo predictors (Table). In multivariate analysis, adjusting for age, sex, comorbidities, advanced NYHA class III–IV, creatinine >1.5 mg/dL, medication use, severity of AS, reduced LVEF <50%, diastolic dysfunction grade ≥2, right ventricular size and pulmonary hypertension, a higher CS30 ≥3 mmHg/mL remained independently associated with HF events (adjusted HR 1.61 [1.29–2.01], P<0.0001; Figure). Conclusion Increased LVStiffn in patients with severe AS undergoing AVR is associated with HF at follow-up, despite the benefits brought by AVR, and can help identify patients with poorer outcomes who may need closer monitoring/more intensive treatment of comorbidities Funding Acknowledgement Type of funding sources: None.

Abstract Funding Acknowledgements Type of funding sources: None. Background Pulmonary hypertension (PH) is a progressive pulmonary vascular disorder with an elevated mortality risk due to right ventricular failure. Pulmonary arterial pulsatility index (PAPi) based on invasively acquired parameters has emerged as a potentially valuable hemodynamic risk predictor. Whether non-invasively derived PAPi (PA pulse pressure/ RA pressure) is valuable is unclear. Purpose To assess whether PAPi measured non-invasively by transthoracic echocardiography acts as a prognostic hemodynamic biomarker of patient risk. Methods Consecutive patients undergoing transthoracic echocardiography for known or suspected PH over a one year period were included. PA systolic and diastolic pressure were estimated in standard fashion from peak tricuspid and end-pulmonary regurgitant Doppler profiles. Right atrial pressure was estimated based on 2D & Doppler assessment of the inferior vena cava hepatic vein. In those patients with PH (mean PA pressure > 20 mm Hg), PAPi was divided into 3 groups based on prior publications with invasive data as <1.5, 1.5 to 3 and >3. Mortality was assessed over 5 years. Results Of 1,045 patients enrolled 64% had PH. Patients with the lowest PAPi (table) had higher NT-proBNP levels, larger right ventricles, worse right heart systolic function (cardiac output, TAPSE, systolic annular velocity, free wall systolic strain) and greater degrees of tricuspid regurgitation (Table). In patients with PH, PAPi was inversely associated with death (figure, p < 0.0001) with each group of PAPi correlating with incrementally worse survival. Patients with a PAPi of <1.5 had worst right heart size and dysfunction on echo (table) and worst survival (figure). Conclusions In patients with PH, low PAPi derived non-invasively by transthoracic echocardiography is associated with markers of right heart failure, right ventricular dysfunction and worse survival. PAPi could be incorporated into the conventional echo parameters reported in patients with known or suspected PH and maybe a useful predictor of outcome. Abstract Table Abstract Figure

Abstract Funding Acknowledgements Type of funding sources: None. Background Tricuspid regurgitation (TR) is a prevalent valvular lesion with three broad morphologic subtypes: primary due to intrinsic pathology of the valve or subvalvular apparatus; secondary due to pulmonary hypertension; and isolated TR associated with chronic atrial fibrillation. The complex pathophysiological, clinical and echocardiographic features between these subtypes require further investigation. Purpose We aimed to identify the different phenotypes of TR using cluster analysis, and determine differences (if present) in clinical outcomes associated with these phenotypes. Methods We included 13611 patients with ≥ moderate TR, either primary or secondary, in the final analyses. The demographic, clinical and echocardiographic data of these patients were evaluated using Ward’s minimum variance cluster analysis including a total of 38 variables. Survival analysis for all-cause mortality was performed using the Kaplan-Meier method, and groups were compared using the log-rank test. Results The mean age of patients was 72.5 ± 13.4 years, 7590 (56%) were females. The clustering identified 5 distinct phenotypes. Cluster 1 represented "low-risk TR" with lesser severity likely related to chronic atrial fibrillation. This cluster had less severe TR, normal sized right ventricle and fewer comorbidities. Clusters 2-5 represented "higher severity TR", "TR associated with lung disease", "TR associated with coronary artery disease and ischemic cardiomyopathy" and "TR associated with chronic kidney disease" respectively (Figure 1). Cluster 1 had the best overall survival, followed by clusters 2, 3 and 4, and lastly cluster 5, with the worst outcome (Figure 2). Conclusions Cluster analysis identifies 5 phenotypically distinct novel subgroups of TR with differences in all-cause mortality. This phenotype-based classification improves our understanding of interaction of different co-morbidities with this complex valve lesion and can inform clinical decision making. Abstract Figure. Cluster Dendrogram Abstract Figure. Kaplan-Meier survival curves

Abstract Funding Acknowledgements Type of funding sources: None. Background Aortic regurgitation (AR) is a common valvular lesion associated with left ventricular (LV) enlargement and dysfunction and increased risk of death with onset of symptoms, significant LV enlargement, or systolic dysfunction. The current guidelines are based on symptoms, LV size and LV function to evaluate the candidacy for surgery in patients with severe AR. Purpose We propose a machine-learning (ML) based algorithm to identify patients at risk for death from AR independent of aortic valve replacement (AVR) surgery (patients were censored at AVR event unless the operation occurred within 100 days of the first visit, in which case baseline AVR is included as a predictor). Methods The model was trained with 5-fold cross-validation on a dataset of 1035 patients. Model performance is reported on an independent dataset of 207 patients. Optimal predictive performance was observed with a Conditional Random Survival Forest model. A subset of 19 / 41 variables were selected for inclusion in the final model. Variable selection was performed with 10-fold cross validation using Random Survival Forest model; variables that were on an average selected by less than 6/10 splits were excluded. Results The mean age of patients was 60 ± 17 years and 198 (18%) were females. The variables included in the models were age, end-diastolic volume, end systolic dimension, body surface area, ejection fraction, NYHA class, body mass index, diastolic blood pressure, bicuspid valve, regurgitant volume, filling pressure, mid ascending aorta diameter, mitral tissue early relaxation velocity, pulmonary artery systolic pressure, and comorbidities, and the relative variable importances averaged across five splits of cross validation in each repeat were evaluated (Figure). The predictive AUC for predicting survival of the best-performing model was 0.84 at 1 year, 0.86 at 2 years, and 0.87 overall, respectively. Conclusion Using commonly observed echo parameters and patient characteristics we successfully trained a ML model to predict survival in patients with severe AR. This technique could identify high-risk patients who would benefit from early intervention, thereby improving patient outcomes. Abstract Figure.

Abstract Background Cardiac power output-to-mass (CPOM) ratio is a measure of myocardial performance that incorporates both pressure and flow output, normalized to left ventricular (LV) mass generating that cardiac work. Prior small studies have shown that CPOM predicts outcomes in patients with ischemic cardiomyopathy and reduced LV ejection fraction (EF). We sought to evaluate the prognostic significance of peak exercise CPOM and power reserve (increase from rest to peak exercise) in patients with normal EF. Methods and results Retrospective study in 24,783 patients (age 59±13 years, 45% females) with EF≥50% and no significant valve disease or right ventricular (RV) dysfunction, undergoing exercise stress echocardiography between 2004–2018. CPOM was calculated as previously described (0.222 x cardiac output x mean blood pressure / LV mass) and expressed in Watts/100g myocardium. Power reserve was calculated as difference in CPOM between peak stress and rest. All-cause mortality was the primary endpoint. Patients were divided into quartiles of power reserve. Patients with higher power reserve were younger, had higher blood pressure and heart rate, lower LV mass, and lower prevalence of prior myocardial infarction. (Table). During follow-up (median (IQR) 3.9 (0.6–8.3) years), 931 (3.8%) patients died. Progressively lower power reserve was associated with increasing mortality (Figure A). Compared to patients with abnormal stress test, patients with the lowest power reserve but otherwise normal stress test had the same survival as those with infarction/cardiomyopathy or ischemia on stress test (Figure B). Resting CPOM had lower predictive value. After adjusting for age, sex, METs achieved, ischemia/infarction on stress test results, and diastolic function grade, both peak exercise CPOM and power reserve were independent predictors of mortality (p<0.0001), incremental to conventional measures. Conclusion Cardiac power output and reserve measured during exercise stress echo provides independent prognostic information in patients with normal resting EF and no significant valve disease or RV dysfunction. The survival of patients with low power reserve but normal stress test was similar to patients with prior infarction/ cardiomyopathy or ischemia on stress test.