Pislaru, Sorin V.

Abstract Background AI-enhanced electrocardiogram (AI-ECG) is a cost-effective tool for left ventricular dysfunction screening. However, its cost-effectiveness for other forms of structural heart disease (SHD) is unknown. While AI-ECG is inexpensive, the relatively low positive predictive value (PPV) of many models can lead to high costs from unnecessary follow-up tests like transthoracic echocardiography (TTE). Therefore, strategies to improve the yield of AI-ECG-based screening are needed. Purpose To evaluate the cost savings of a stepwise approach to SHD screening using AI-ECG followed by point-of-care ultrasound (POCUS) compared to AI-ECG alone. Methods 286 adult outpatients undergoing AI-ECG were randomly selected to undergo same-day POCUS. All participants were required to have a recent TTE, our gold standard for SHD diagnosis, for comparison purposes. We evaluated four SHDs: aortic stenosis, cardiac amyloidosis, hypertrophic cardiomyopathy, and left ventricular dysfunction (defined as left ventricular ejection fraction <50%). The costs of AI-ECG ($75/test) and TTE ($1,305/test) were sourced from Healthcare Bluebook, while the cost of POCUS ($100/test) was independently estimated. We compared the costs of screening with AI-ECG alone to stepwise screening with AI-ECG followed by POCUS. Costs were analyzed for two paradigms: screening for all forms of SHD in parallel and screening for each SHD individually. Results AI-ECG alone identified potential SHD in 125 out of 286 patients. When compared to TTE, only 39 out of 125 were true positives (31% PPV). Among the AI-ECG-positive patients, POCUS demonstrated findings of SHD in 52 out of 125 cases. When compared to TTE, this stepwise approach yielded 32 true positives and 20 false positives (62% PPV). In the parallel screening paradigm, the cost per patient diagnosed with SHD was $4,733 with AI-ECG alone, which decreased to $3,182 with stepwise screening (33% cost savings). For the individual SHD screening paradigm, cost reductions were as follows: aortic stenosis ($18,724 to $6,315, 66% savings), cardiac amyloidosis ($21,023 to $12,230, 42% savings), hypertrophic cardiomyopathy ($9,883 to $6,175, 38% savings), and left ventricular dysfunction ($4,019 to $3,582, 11% savings). Conclusions Stepwise SDH screening with AI-ECG followed by POCUS markedly reduces costs compared to AI-ECG alone. The greatest cost savings for individual SHD screening were observed for aortic stenosis and cardiac amyloidosis, conditions where AI-ECG models have lower PPVs. Parallel screening for multiple SHDs is also less costly than screening for any individual SHD alone. Therefore, a parallel screening approach may maximize SHD detection while minimizing screening costs. Stepwise Screening Approach for SHD SDH Screening Costs

Abstract Background Bicuspid aortic valve(BAV) disease carries a cumulative lifetime morbidity >80%. This morbidity includes surgery for aortic valve dysfunction, aortic dilatation, infective endocarditis, and aortic dissection. This study assessed surgical intervention patterns for BAV-related morbidity and long-term survival of these patients in a community-based cohort versus a tertiary referral cohort. Methods The tertiary-referral cohort included all patients with BAV-related surgeries across Mayo Clinic sites (Arizona, Florida, and Minnesota), from January 1990 to May 2024. The community-based cohort included all patients with BAV-related surgeries in Olmsted County, Minnesota, from January 1980 to May 2024. The tertiary-referral cohort comprised 2529 BAV patients of which 991(39%) [mean age 53±15 years, 76% males] underwent aortic valve surgery(AVR), aorta surgery, or a combination thereof, while the community-based cohort included 652 BAV patients of whom 262(40%) [mean age 43±20 year, 70% males] had the mentioned interventions. Cumulative survival was calculated by Kaplan-Meier method compared to the U.S population. Statistical significance was evaluated using one-sample log rank statistics. Results In the tertiary-referral cohort, 530/991(54%) patients underwent isolated AVR, 62/991(6%) had isolated aortic surgery, and 399(40%) underwent combined procedures. In the community-based cohort, 179/262(68%) patients underwent isolated AVR, 30/262(11%) underwent isolated aortic surgery, and 53(21%) had combined surgeries. In the tertiary-referral cohort, 940 patients underwent AVR; 57% for aortic stenosis(AS), 29% for aortic regurgitation(AR), 13% for mixed valvular disease, and 1% for endocarditis. In comparison, in the community-based cohort, 236 patients underwent AVR for AS in 71%, AR 20%, mixed valvular disease 7%, and endocarditis 2%. In the tertiary-referral cohort, 459 patients underwent aortic surgery; 21% for the root, 69% for the ascending aorta, 1% for the arch, <1% for aortic dissection, and 8% for coarctation repair. In comparison, 105 patients from the community-based cohort underwent aortic surgery; 33% for the root, 44% for the ascending aorta, 1% for the arch, 4% for aortic dissection and 18% coarctation repair. Compared to age- and sex-matched U.S. population, the relative risk for all cause death in the tertiary-referral cohort was 0.89 [95% CI: 0.70-1.11, p=0.35], whereas in the community-based cohort was 1.06 [95% CI: 0.85-1.32, p=0.57](Figure1). Conclusion Surgical intervention patterns were similar for community and tertiary BAV cohorts, with most patients undergoing isolated AVR or AVR plus aortic surgery, and isolated aortic surgery being uncommon. AVR indications were driven by AS, followed by AR and mixed valvular disease. Aortic surgery indications were driven by ascending aorta dilatation, followed by root dilatation and coarctation. Survival in both cohorts was similar to the U.S. general population.

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

Abstract Aims Pulmonary regurgitation (PR) after reparative intervention for congenital heart disease has been studied extensively. However, the burden, distribution of causes, and outcome of PR in adults is unknown. The study aimed to evaluate the prevalence, types, and outcomes of moderate/severe PR in adults in the community setting. Methods and results A total of 398 adult residents of Olmsted County who had clinically indicated echocardiography 2004–2023 at Mayo Clinic, Rochester, and had moderate or severe PR were identified retrospectively. The median age was 77 years, 48% were females, and 61 (51%) had severe PR. The age- and sex-adjusted US prevalence was 0.11% (vs. 0.67% for ≥moderate tricuspid regurgitation). Moderate/severe PR was due to pulmonary hypertension in 77%, congenital/iatrogenic in 11%, primary pulmonary valve disease in 2% (88% due to carcinoid), and idiopathic isolated in 10%. In contrast, severe PR was due to congenital/iatrogenic disease in 52%, pulmonary hypertension in 39%, primary PR in 5%, and isolated idiopathic in 3%. The all-cause mortality rate per 100 person-year was 73 in primary (mostly carcinoid) PR, 16 in pulmonary hypertension–related PR (not different vs. propensity-matched patients without PR), and 6 in isolated idiopathic PR (not different vs. matched patients without PR). Conclusion Moderate or severe PR had a lower prevalence vs. TR. The most frequent cause was pulmonary hypertension for ≥moderate PR and congenital/iatrogenic for severe PR. Mortality in patients with acquired ≥moderate PR appeared to be related to the underlying cause, with no excess mortality compared with matched patients without PR. Whether specifically severe PR confers excess mortality requires future investigation.

Description of Case: A 40-year-old woman presented with a 3-month history of dyspnea. A murmur was found on examination. Echocardiography reported moderate mitral stenosis and regurgitation with diffuse thickening and calcification of the anterior mitral leaflet (Fig1.A), thought to be due to rheumatic disease. She had runs of supraventricular tachycardias not controlled with diltiazem. Her dyspnea progressively worsened; transesophageal echocardiography(TEE) showed severe mitral stenosis and mitral regurgitation (mean gradient 18 mmHg; Fig1.B) with a dense CW Doppler (Fig 1.C) and a mass on left atrial free wall. Cardiac MRI revealed diffuse left atrial thickening with delayed enhancement of the left atrium, left atrial appendage, and extending into the right upper and left inferior pulmonary veins. The mass was initially suspected to be a thrombus. She was placed on rivaroxaban and scheduled to undergo mitral valve replacement. When she presented to our emergency department with dizziness she was found to have paroxysmal atrial fibrillation and pulmonary embolism. On admission she had an intermittent opening snap and a 1/6 mid-diastolic rumble with a 2/6 holosystolic murmur at the apex. Work-up for infectious disease and antiphospholipid syndrome was negative. NT-proBNP was mildly elevated. At surgery the mass invaded the mitral valve and the anterior, septal, and superior part of the left atrial lateral wall and could only be partially excised (Fig1.D). Pathology showed high-grade undifferentiated pleomorphic cardiac sarcoma. Discussion: This case highlights the diagnostic challenges associated with primary cardiac tumors masquerading as valvular pathology. The presentation included dyspnea, typical auscultation of mitral stenosis and features of stenosis on echocardiography. Presumptive diagnoses included rheumatic heart disease, calcific degeneration, infective endocarditis, and autoimmune processes; the atrial mass was initially thought to be a thrombus. A thorough, multidisciplinary approach to diagnosis, utilizing multimodality imaging techniques and ultimately tissue biopsy were required to make the correct diagnosis. Maintaining a broad differential when dealing with valvular masses is key, since relying solely on imaging findings may not suffice for definitive tissue diagnosis.

Background: AI-ECG is a cost-effective tool for left ventricular dysfunction (LVD) screening. However, its cost-effectiveness for other forms of structural heart disease (SHD) is unknown. While AI-ECG is inexpensive, a drawback is low positive predictive value (PPV), which leads to high costs from unnecessary follow-up tests. Therefore, strategies to improve the yield of AI-ECG-based screening are needed. Aim: To evaluate the cost savings of a stepwise approach to SHD screening with AI-ECG followed by POCUS compared to AI-ECG alone. Methods: 286 adult outpatients undergoing AI-ECG were selected at random. Participants received same-day POCUS and had a recent TTE (our gold standard for SHD). We evaluated four SHDs: aortic stenosis (AS), cardiac amyloidosis (CA), HCM, and LVD. The costs of AI-ECG ($75) and TTE ($1,305) were obtained from Healthcare Bluebook. The cost of POCUS ($100) was estimated independently. Cost savings were analyzed for simultaneous screening for all forms of SHD and screening for individual SHDs. Results: AI-ECG identified potential SHD in 125 patients, but only 39 were true positives by TTE (31% PPV). In AI-ECG positive patients, POCUS demonstrated findings of SHD in 52/125. Compared to TTE, this stepwise approach yielded 32 true positives and 20 false positives (62% PPV). The cost per patient diagnosed with SHD was $4,733 with AI-ECG alone but decreased to $3,182 with stepwise screening (33% cost savings). Screening for individual SHDs resulted in cost reduction from $18,724 to $6,315 (66% savings) for AS, $21,023 to $12,230 (42% savings) for CA, $9,883 to $6,175 (38% savings) for HCM, and $4,019 to $3,582 (11% savings) for LVD. Conclusions: Stepwise screening for SHD with AI-ECG followed by POCUS significantly reduces costs compared to AI-ECG alone. We also suggest a model for parallel screening for multiple SHDs, which is likely more cost-effective than screening for individual SHDs.

Background: Atrial functional mitral regurgitation (AFMR) constitutes ~25% of ≥moderate MR and has been associated with a high prevalence and incidence of HFpEF. Transcatheter edge-to-edge repair (TEER) has shown effectiveness in improving symptoms in AFMR, but its impact on mortality and HF hospitalizations is unknown. Objective: Evaluate rates of mortality and HF hospitalizations in patients with ≥moderate AFMR treated with TEER and compare them to conservative management. Methods: Consecutive adults with ≥moderate AFMR (functional MR with left atrial enlargement, ejection fraction≥50%, and absent >mild left ventricular enlargement) were identified retrospectively. Ecxlusion criteria were previous cardiac surgery, ≥moderate aortic regurgitation/stenosis, infiltrative/hypertrophic cardiomyopathy, regional wall motion abnormalities or malignancy. Propensity score matching was performed (1:1 ratio) between patients treated with TEER and patients treated conservatively based on age, sex, EuroScore II, effective regurgitant orifice area, and the integrative MR severity. To ensure similar technique in evaluation in the 2 groups, variables were obtained from the closest transthoracic echocardiogram before TEER in the TEER group [median 65 (IQR 29-111) days]. Results: Overall, 46 patients with ≥moderate AFMR treated by TEER and 46 treated conservatively were included, Table 1 . Patients undergoing TEER had more frequent atrial fibrillation and NYHA class ≥III. MR improved to ≤moderate in 93% of patients undergoing TEER on procedural transesophageal echocardiography, Figure 1 . On 1–3-month post-TEER follow-up, 64% had NYHA class I/II (vs 33% pre-TEER), Figure 1 . Over median 2.2 (IQR 1.2-3.1) years, 32 patients died (rate 13%/year in each group, log-rank p=0.85), Figure 2 . When adjusted for baseline NYHA, rates of HF hospitalizations were not different between the groups (Wald-test p-value=0.48). Residual ≥moderate AFMR in the TEER group was not associated with mortality (log-rank p=0.83), but ≥1 class improvement of NYHA in patients with baseline NYHA >1 was associated with decreased mortality, Figure 2 . Conclusion: MR severity and NYHA class improved with TEER for AFMR, and improved NYHA class was associated with decreased mortality. However, the association of TEER with decreased risk of mortality or HF hospitalization remains unproven, and larger randomized studies are needed to evaluate the potential role of TEER on these outcomes in AFMR.

Background: Carcinoid heart disease (CaHD) typically affects tricuspid and pulmonary valves and is associated with poor survival. To date, the role of right ventricular (RV) and atrial (RA) strain has not been evaluated in such cohort. Research Questions: To evaluate RV and RA strain patterns and assess their impact on survival and congestive heart failure (CHF) development. Methods: Retrospective study of CaHD patients (ICD 9/10 diagnosis of neuroendocrine tumor and echocardiographic evidence of CaHD prior to any surgical intervention; 2004-2019). Longitudinal strain was evaluated using speckle-tracking, RV/RA-focused view was used. RV strain was averaged from 3 and 6 segments for free wall (FWS) and global strain (GS), respectively. Auto-tracking with manual adjustment was done to ensure optimal tracking. The tracing of RV/RA endocardium was done with 15 points using the tricuspid valve annulus as a reference. The impact of strain parameters on mortality and CHF was evaluated with the Kaplan Meier and Cox proportional hazard analyses. Results: A total of 138 patients were included (mean age was 63 ± 10 years; 47% females). Median follow-up was 5.0 years (3.7-8.2). Significant RA and RV enlargement (72 and 79%, respectively) was more common than RV dysfunction (10%). The most common valvular disease > moderate was tricuspid regurgitation (TR; 97%) followed by pulmonary regurgitation (PR; 70%). RV GS mean was -21 + 6%, with FWS of -23 + 7%. The mean RA strain analysis revealed (93% sinus rhythm): a reservoir of 26 + 11%, a conduit of 14 + 8%, and an atrial contraction of 12 + 8%. Strain parameters were not associated with overall mortality. As opposed to PR/TR severity and RV/RA enlargement/dysfunction, patients with low RA reservoir strain (<23%) were more likely to develop CHF (adjusted-HR=1.80, p=0.04, 95% CI 1.04 - 3.134). Conclusions: Our findings suggests that CaHD patients have RV/RA dysfunction with overall reduced strain parameters. Patients with low RA reservoir had higher risk of CHF, but none of the RV/RA strain parameters were associated with excess mortality. This shows how strain analysis could complement other echocardiographic parameters in CaHD morbidity assessment.