Padang, Ratnasari

Abstract Aims Aortic stenosis (AS) is a common and progressive disease, which, if left untreated, results in increased morbidity and mortality. Monitoring and follow-up care can be challenging due to significant variability in disease progression. This study aimed to develop machine learning models to predict the risks of disease progression and mortality in patients with mild AS. Methods and results A comprehensive database including 9611 patients with serial transthoracic echocardiograms was collected from a single institution across three clinical sites. The data set included parameters from echocardiograms, electrocardiograms, laboratory values, and diagnosis codes. Data from a single clinical site were preserved as an independent test group. Machine learning models were trained to identify progression to severe stenosis and all-cause mortality and tested in their performance for endpoints at 2 and 5 years. In the independent test group, the AS progression model differentiated those with progression to severe AS within 2 and 5 years with an area under the curve (AUC) of 0.86 for both. The feature of greatest importance was aortic valve mean gradient, followed by other valve haemodynamic measurements including valve area and dimensionless index. The mortality model identified those with mortality within 2 and 5 years with an AUC of 0.84 and 0.87, respectively. Smaller reduced-input validation models had similarly robust findings. Conclusion Machine learning models can be used in patients with mild AS to identify those at high risk of disease progression and mortality. Implementation of such models may facilitate real-time, patient-specific follow-up recommendations.

Abstract Background Atrial fibrillation (AF) is the most prevalent atrial tachyarrhythmia, affecting an estimated 2-4% of adults worldwide. AF is a well-recognized and treatable risk factor for stroke, but it often remains asymptomatic or subclinical, leading to underdiagnosis. This study aimed to identify distinguishing signs during exercise stress echocardiography (ESE) among patients in sinus rhythm (SR), with and without history of paroxysmal/persistent AF (PAF). Methods An international prospective cohort comprising 1035 consecutive patients was initially considered from 12 cardiology institutions. These patients were referred for clinically-driven ESE as part of the Stress Echo 2020-2030 study network. All patients underwent comprehensive ESE with the ABCDE protocol, which included assessment of B-lines, left ventricle contractile reserve (LVCR), ECG-based heart rate reserve (HRR), LV ejection fraction (EF), LV end-diastolic volume, E/e’, pulmonary artery systolic pressure estimation, tricuspid annular plane sytolic excursion (TAPSE), left atrium volume index (LAVi) and left atrium reservoir phase strain (LASr) at rest and with exercise. Results After excluding 89 patients who were in AF during the ESE, 946 patients in SR were included as the main study cohort (101 with and 845 without a history of PAF). A scoring system was then constructed using all independent variables that differentiate the two groups (those with and without history of PAF). Presence of systemic hypertension, rest LAVI>31ml/m2, rest |LASr|< 21%, stress LAVI >29 ml/m2, stress |LASr| <24%, stress E/e’ >7, ∆TAPSE <4.5 mm, HRR<1.87, and LVCR<1.6 were identified as the discriminators between patients with and without PAF. The composite score, summing all 9 items (with a total score range from 0 to 9), yielded a score of >4 as the best balance between sensitivity (87%) and specificity (60%) in predicting those with PAF. The receiver operating characteristic curve analysis of the scoring model showed an AUC of 0.79 (p-value <0.0001), Figure. Conclusion ESE evaluation can be a valuable adjunct for identifying patients in SR with history of PAF. This multifaceted approach enhances the potential for more accurate detection and clinical management of individuals in SR at risk for AF, who could be considered for aggressive monitoring programs to prevent the development of new onset AF and subsequent increase in cardiovascular risk.

Abstract Background Guidelines recognize the role of exercise stress testing in evaluating functional capacity in patients with asymptomatic severe aortic stenosis (AS). The study aimed to identify the prognostic role of exercise stress echocardiography (ESE) in asymptomatic severe AS. Methods We enrolled 153 asymptomatic patients (70±13 years; 88 male, 57%) with severe AS, aortic valve area (AVA) <1.0 cm2, mean aortic gradient ≥ 40 mmHg, ejection fraction (EF) ≥55%. All were referred for ESE in 7 quality-controlled centers from 5 countries. Rest and ESE assessment also included global longitudinal strain (GLS) and left atrial volume index (LAVI). B-lines were assessed by LUS with the 4-site simplified scan of the third intercostal space. A 4-point ESE score was based on 4 parameters (0 for normal, 1 for abnormal), with the following pre-determined cutoffs of abnormality: ∆-maximal aortic gradient (MAG) ≥20 mmHg; GLS at peak ≤ 19%, according to receiver operating characteristics curve analysis, stress B-lines ≥2; stress LAVI ≥ 34 mL/m2. Follow-up was completed in 142/153 patients (92%). Results At rest, AVA was 0.85±0.14 cm2, maximal aortic gradient: 79±14 mmHg, and peak aortic velocity: 4.42 ± 0.41 m/s. Mean EF at rest: 63.4±5.3% During a median follow-up of 1802 days (IQ range 651-2302), 41 events occurred in 39 patients: 15 all-cause deaths, 17 acute HF, 1 stroke, 1 myocardial infarction, and 7 coronary revascularization. Patients experiencing events displayed a greater increase in MAG during peak ESE, more B-lines with exercise, greater degree of LAVI dilation with exercise and slightly lower GLS compared to those without events (Table). Increase in ESE score was associated with a significant rise (p=0.001) in event incidence from score 0 (n=0/13, 0%) to score 1 (n=2/21, 9.5%), score 2 (n=10/42, 23.8%), and ≥3 (n=27/66, 40.9%), see figure. Conclusions In asymptomatic severe AS cases with preserved LV EF, comprehensive ESE provides early marker of potential cardiac decompensation at follow-up. The composite ESE index, including MAG, GLS, LAVI, and B-lines, holds promise as a prognostic predictor.TableFigure

Abstract Background/Introduction Cardiac stress tests are carried out in populations with a low probability of ischemic heart disease (IHD) much more frequently than in the past. Stress ECG remains a frequently used modality for the diagnosis of IHD in vast areas of the world with limited facilities. Purpose To assess the diagnostic value of stress ECG for diagnosing IHD using inducible regional wall motion abnormalities (RWMA) on stress echocardiography (SE) as the gold standard method of diagnosis. Methods The 12-lead ECG response was retrospectively analyzed in 4317 patients (age 64±13 years, 59.6% males) undergoing SE for chronic coronary syndromes who were prospectively recruited from 39 cardiac centers between March 2021 and February 2024. Exclusion criteria were left bundle branch block or pacemaker rhythm. ECG response was considered ischemic according to standard criteria (if ST-segment deviated >1.0 mm from baseline in ≥2 contiguous leads at 80 ms from J point) during an exercise (n=2980, 69.8%), dobutamine (n = 766, 18.0%), or vasodilator (n=519, 12.2%) SE. All patients underwent a comprehensive SE protocol with an assessment of wall motion score index (WMSI), B-lines (4-site simplified score), left ventricular contractile reserve (LVCR) based on force, coronary flow velocity reserve (CFVR) in the mid-distal left anterior descending artery (LAD), and heart rate reserve (HRR). Results ECG changes occurred in 641 patients (14.8%, Group 1) for the overall studied population. Compared to patients without ECG changes (Group 2, n=3676, 85.2%), patients with ECG changes showed higher values of peak WMSI and lower values of CFVR and LVCR (see table).Amongst patients without inducible RWMA (n=3553), there were 392 (11%) patients with an ischemic ECG at stress (89% specificity). Of 764 patients with inducible RWMA during SE, 249 had an ischemic ECG trace (sensitivity 33%). In patients without inducible RWMA, those with ischemic ECG changes showed similar abnormal stress B-lines (23% vs. 21%, p=0.719), LVCR (61% vs. 63%, p=0.602), CFVR (31% vs 33%, p=0.607) and HRR (37% vs 41%, p=0.097) compared to those without ECG changes. Amongst patients with inducible RWMA and ECG changes, CFVR was significantly lower in patients with ECG changes (39.2% and 60.8%, respectively, p<0.001). Conclusions Simple standard stress ECG diagnostic value in the current era in populations with a low probability of IHD seems to be low. However, during SE, stress-induced ischemic ECG changes are associated with more extensive RWMA and blunted global LVCR, with reduced CFVR in the LAD. Therefore, analysis of ST segment changes during stress imaging studies can offer additional, significant information.

Importance Historically, women with aortic stenosis have experienced worse outcomes and inadequate recognition compared to men, being both underdiagnosed and undertreated, while also facing underrepresentation in clinical trials. Objective To determine whether women with small aortic annuli undergoing transcatheter aortic valve replacement have better clinical and hemodynamic outcomes with a self-expanding valve (SEV) or balloon-expandable valve (BEV). Design, Setting, Participants The Small Annuli Randomized to Evolut or SAPIEN Trial (SMART) was a large-scale randomized clinical trial focusing on patients with small aortic annuli undergoing transcatheter aortic valve replacement, randomized to receive SEVs or BEVs and included 716 patients treated at 83 centers in Canada, Europe, Israel, and the US from April 2021 to October 2022. This prespecified secondary analysis reports clinical and hemodynamic findings for all 621 women enrolled in SMART. Data for this report were analyzed from February to April 2024. Interventions Transcatheter aortic valve replacement with an SEV or a BEV. Main Outcomes and Measures The composite coprimary clinical end point comprised death, disabling stroke, or heart failure–related rehospitalization. The coprimary valve function end point was the incidence of bioprosthetic valve dysfunction, both assessed through 12 months. Secondary end points included the incidence of moderate or severe prosthesis-patient mismatch. Results A total of 621 women (mean [SD] age, 80.2 [6.2] years; 312 randomized to the SEV group and 309 to the BEV group) were included in the present analysis. At 12 months, there were no significant differences in the coprimary clinical end point between the SEV and BEV groups (9.4% vs 11.8%, absolute risk difference −2.3%; 95% CI −7.2 to 2.5, P = .35). However, SEV implantation was associated with less bioprosthetic valve dysfunction (8.4% vs 41.8%; absolute risk difference, −33.4%; 95% CI, −40.4 to −26.4; P < .001). SEV implantation resulted in lower aortic valve gradients and larger effective orifice areas at 30 days and 12 months and less mild or greater aortic regurgitation at 12 months compared to BEV implantation. Prosthesis-patient mismatch was significantly lower with SEVs, regardless of the definition used and adjustment for body mass index. Use of SEVs was associated with better quality of life outcomes as assessed by the Valve Academic Research Consortium-3 ordinal quality of life measure. Conclusions and Relevance Among women with severe symptomatic aortic stenosis and small aortic annuli undergoing transcatheter aortic valve replacement, the use of SEVs, compared to BEVs, resulted in similar clinical outcomes and a markedly reduced incidence of bioprosthetic valve dysfunction through 12 months, including a lower risk of prosthesis-patient mismatch and better 12-month quality of life. Trial Registration ClinicalTrials.gov Identifier: NCT04722250

Abstract Aims Aortic valve calcification (AVC) is prognostic in patients with aortic stenosis (AS). We assessed the AVC prognostic value in non-severe AS patients. Methods and results We conducted a retrospective study of 395 patients with non-severe AS, LVEF ≥ 50%. The Agatston method was used for CT AVC assessment. The log-rank test determined the best AVC cut-offs for survival under medical surveillance: 1185 arbitrary unit (AU) in men and 850 AU in women, lower than the established cut-offs for severe AS (2064 AU in men and 1274 AU in women). Patients were divided into 3 AVC groups based on these cut-offs: low (<1185 AU in men and <850 AU in women), sub-severe (1185–2064 AU in men and 850–1274 AU in women), and severe (>2064 AU in men and >1274 AU in women). Of 395 patients (mean age 73 ± 12 years, 60.5% men, aortic valve area 1.23 ± 0.30 cm2, mean pressure gradient 28 ± 8 mmHg), 218 underwent aortic valve intervention (AVI) and 158 deaths occurred during follow-up, 82 before AVI. Median survival time under medical surveillance was 2.1 (0.7–4.9) years. Compared with the low AVC group, both sub-severe and severe AVC groups had higher risk for all-cause death under medical surveillance after comprehensive adjustment including echocardiographic AS severity and coronary artery calcium score (all P ≤ 0.006); while mortality risk was similar between sub-severe and severe AVC groups (all P ≥ 0.2). This mortality risk pattern persisted in the overall survival analysis after adjustment for AVI. AVI was protective of all-cause death in the sub-severe and severe AVC (all P ≤ 0.01), but not in the low AVC groups. Conclusion Sub-severe AVC is a robust risk stratification parameter in patients with non-severe AS and may inform AVI timing.

Abstract Aims Cardiac amyloidosis (CA) is common in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Cardiac amyloidosis has poor outcomes, and its assessment in all TAVR patients is costly and challenging. Electrocardiogram (ECG) artificial intelligence (AI) algorithms that screen for CA may be useful to identify at-risk patients. Methods and results In this retrospective analysis of our institutional National Cardiovascular Disease Registry (NCDR)-TAVR database, patients undergoing TAVR between January 2012 and December 2018 were included. Pre-TAVR CA probability was analysed by an ECG AI predictive model, with >50% risk defined as high probability for CA. Univariable and propensity score covariate adjustment analyses using Cox regression were performed to compare clinical outcomes between patients with high CA probability vs. those with low probability at 1-year follow-up after TAVR. Of 1426 patients who underwent TAVR (mean age 81.0 ± 8.5 years, 57.6% male), 349 (24.4%) had high CA probability on pre-procedure ECG. Only 17 (1.2%) had a clinical diagnosis of CA. After multivariable adjustment, high probability of CA by ECG AI algorithm was significantly associated with increased all-cause mortality [hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.01–1.96, P = 0.046] and higher rates of major adverse cardiovascular events (transient ischaemic attack (TIA)/stroke, myocardial infarction, and heart failure hospitalizations] (HR 1.36, 95% CI 1.01–1.82, P = 0.041), driven primarily by heart failure hospitalizations (HR 1.58, 95% CI 1.13–2.20, P = 0.008) at 1-year follow-up. There were no significant differences in TIA/stroke or myocardial infarction. Conclusion Artificial intelligence applied to pre-TAVR ECGs identifies a subgroup at higher risk of clinical events. These targeted patients may benefit from further diagnostic evaluation for CA.

Abstract Background Histoplasmosis is an endemic mycosis associated with a wide range of clinical presentations. Cardiovascular histoplasmosis (CVH) was rarely seen at our center before 2007 but has increased in frequency over the last 15 years. Herein, we describe the clinical characteristics of our recent CVH cases. Methods We identified all adults diagnosed with CVH at Mayo Clinic in Rochester, MN, between May 2007 and February 2023. Results Ten cases of CVH were identified, all of whom resided in the Midwest (Table). The majority were male, with a median age of 72 years. Five patients had prosthetic valves, two endovascular grafts, one a prosthetic valve and aortic graft, and one was a heart-kidney transplant recipient. Patients most frequently presented with prolonged night sweats, fever, and dyspnea. Cytopenias, pulmonary nodules, and splenomegaly were common laboratory and imaging findings. The diagnosis was suspected based on a positive Histoplasma antibody (100%) and/or antigen (80%) testing and confirmed by positive culture (blood 60%, explanted valve/graft 20%) and/or histopathology (60%). Identified clinical syndromes included: prosthetic valve endocarditis (PVE; 50%), native valve endocarditis (10%), mycotic aortic aneurysm (10%), aortic graft infection (10%), PVE and aortic graft infection (10%), and myocarditis (10%). Most patients received combined medical and surgical treatment (50%). Three patients (30%) received medical treatment only, including one patient with myocarditis. Two patients (20%) presented progressive clinical decline and were not considered antifungal treatment or surgical candidates. The overall mortality within one year of diagnosis was 50%. Patients with endocarditis and/or graft infection who received only medical treatment had higher mortality than those who received combined medical and surgical treatment (100% vs 20%, respectively).Table.Clinical characteristics of patients presenting with cardiovascular histoplasmosis (N=10) *Patient frequently had more than one comorbidity, symptom, laboratory or imaging finding, positive histoplasmosis testing, or affected valve. **Two patients did not receive treatment given their critical status, and were transitioned to comfort care. Conclusion CVH is being seen more frequently at our institution. One-year mortality of CVH was high, but combined medical and surgical management conferred better outcomes than medical treatment alone. We suggest a high index of suspicion of CVH in patients residing in Histoplasma endemic regions with a history of prior cardiac or vascular surgery presenting with prolonged fevers and/or new cardiomyopathy. Disclosures All Authors: No reported disclosures

Aortic valve stenosis (AS) is increasing in prevalence due to the aging population, and severe AS is associated with significant morbidity and mortality. Echocardiography remains the mainstay for the initial detection and diagnosis of AS, as well as for grading of severity. However, there are important subgroups of patients, for example, patients with low-flow low-gradient or paradoxical low-gradient AS, where quantification of severity of AS is challenging by echocardiography and underestimation of severity may delay appropriate management and impart a worse prognosis. Aortic valve calcium score by computed tomography has emerged as a useful clinical diagnostic test that is complimentary to echocardiography, particularly in cases where there may be conflicting data or clinical uncertainty about the degree of AS. In these situations, aortic valve calcium scoring may help re-stratify grading of severity and, therefore, further direct clinical management. This review presents the evolution of aortic valve calcium score by computed tomography, its diagnostic and prognostic value, as well as its utility in clinical care.