Michelena, Héctor I.

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.

Background Echocardiographic evaluation of vegetations is crucial in infective endocarditis ( IE ). Although several studies have noted a link between larger vegetations and an increased risk of embolization, a more comprehensive evaluation of vegetation characteristics in a contemporary cohort has not been conducted. Our study aimed to define the short‐term risk of symptomatic embolization in patients with IE . Methods and Results The Mayo Clinic IE registry was screened to identify patients from 2015 to 2021 who had undergone transesophageal echocardiography. Multivariable subdistribution hazards regression analysis was used to identify factors associated with the cumulative incidence of symptomatic embolism over 30 days accounting for the competing risk of death. Overall, 779 patients with IE were included, of whom 517 (66.4%) were men, median age was 65.0 ( interquartile range, 52.9–74.8) years, and 89.3% were White. In total, 234 patients had a symptomatic embolic event, a 30‐day cumulative incidence of 30.2%. In multivariable analysis, a highly mobile vegetation was the strongest predictor of embolism ( P <0.001). Vegetation length with interaction of IE type was also associated with embolic risk ( P <0.001), with a stronger effect in native valve IE ( P interaction=0.001). Other associated factors included multiple vegetations, younger age, and Staphylococcus aureus . A nomogram that incorporated these factors was constructed to facilitate the prediction of embolic risk. Conclusions Highly mobile, larger vegetations are associated with embolic events. Embolic risk could be assessed by evaluating length as a continuous variable, alongside other echocardiographic findings, using a newly developed scoring tool; external validation is warranted.

Background The prevalence and impact of right ventricular dysfunction (RVD) in degenerative mitral regurgitation (DMR) is unknown. We aimed to determine whether RVD assessed by echocardiography in routine clinical practice is independently associated with mortality in patients with DMR. Methods and Results We used data from the MIDA‐Q (Mitral Regurgitation International DAtabase‐Quantitative) registry, which included patients with isolated DMR due to mitral valve prolapse from January 2003 to January 2020 from 5 tertiary centers across North America, Europe, and the Middle East. A cohort of 2917 (mean age: 66 years, 70.8% male patients, follow‐up: 5.2 [3.3–8.3] years) consecutive patients with severe DMR was included and long‐term mortality was analyzed. RVD, identified in 426 (14.6%) patients, was associated with reduced 8‐year survival (55%±3% versus 77%±1%; P <0.001), overall and in all subgroups of patients, even after comprehensive adjustment including left ventricular dilatation and dysfunction, DMR severity, pulmonary pressures, and surgery (adjusted hazard ratio, 1.44 [95% CI, 1.17–1.77]; P <0.001). This excess mortality was observed under medical management (adjusted hazard ratio, 1.57 [95% CI, 1.20–2.05]; P =0.001) and after surgical correction of mitral regurgitation (adjusted hazard ratio, 1.45 [95% CI, 1.02–2.05]; P =0.039). Patients with RVD undergoing surgery within 3 months of diagnosis experienced a better 8‐year survival (73%±4% versus 43%±4%; P <0.001), even after adjustment (adjusted hazard ratio, 0.44 [95% CI, 0.29–0.67]; P <0.001) despite an increase of 1‐month postoperative mortality (7.1% versus 0.5% for patients without RVD; P <0.001). Conclusions RVD is observed in 14.6% of severe DMR and exhibits a powerful and independent association with excess mortality partially attenuated by mitral surgery. Therefore, assessment of right ventricular systolic function should be included in routine DMR evaluation and in the clinical decision‐making process.

Abstract OBJECTIVES The Ross procedure is currently receiving renewed interest. Its function and durability depend on preservation of pulmonary valve anatomy; limited data exist on normal pulmonary valve geometry. The objective was to compare aortic and pulmonary root and cusp dimensions in adults with normal tricuspid aortic and pulmonary valves. METHODS We reviewed 507 coronary computed tomography studies, selecting those with adequate visibility of both pulmonary and aortic roots for further analysis. Diastolic aortic and pulmonary root and cusp dimensions were measured. Root dimensions at different phases of the cardiac cycle were measured in 3 patients. RESULTS We analysed studies of 50 patients with the mean age of 54 years [standard deviation (SD): 16]. In end-diastole, pulmonary root had a smaller sinutubular to basal ring ratio than the aortic root [0.82 (SD: 0.09) vs 1.14 (SD: 0.12), P &lt; 0.001]. Aortic and pulmonary cusps had similar dimensions; however, pulmonary cusp effective height was lower [5.9 mm (SD: 1.6) vs 8.4 mm (SD: 1.2), P &lt; 0.001]. Pulmonary basal ring perimeter was largest at end-diastole and smallest at end-systole, with the relative difference of 23.5% (SD: 2.7). CONCLUSIONS The pulmonary root has a similar cusp size compared to the aortic root, but a different shape, resulting in a lower pulmonary cusp effective height. The perimeter of the pulmonary basal ring changes during the cardiac cycle. These findings suggest that stabilizing the autograft to normal aortic, rather than pulmonary, root dimensions should result in normal autograft cusp configuration. Computed tomography angiography could become a tool for personalized planning of the Ross procedure.

Background Bicuspid aortic valve (BAV) is the most common congenital heart defect in adults, often leading to complications such as thoracic aortic aneurysms and aortic stenosis. While BAV is frequently associated with 22q11.2 deletion syndrome (22q11.2DS), the contribution of rare copy number variants (CNVs) in this region to non-syndromic BAV is less clear. This study is aimed to assess the role of rare 22q11.2 CNVs in patients with early-onset BAV (EBAV) and to determine whether these variants are linked to an increased risk of complications. Methods Whole genome microarray genotyping was conducted on 272 patients with BAV with early onset valve or aortic disease (EBAV) and 272 biological relatives. CNVs were detected using three independent algorithms, focusing on the 22q11.2 region (18–24 Mb). CNV burden in the EBAV cohort was compared with unselected European ancestry controls. Results Rare duplications and deletions within the 22q11.2 region, particularly involving genes associated with cardiac development, were identified in 7.4% of EBAV probands. These CNVs were significantly enriched compared with the general population and segregated with BAV in families. Individuals carrying rare 22q11.2 CNVs had a higher prevalence of psychiatric diagnoses and learning difficulties, although they did not exhibit the typical features of 22q11.2DS. Importantly, these CNVs were associated with early onset or complex BAV cases, underscoring their potential clinical relevance. Conclusions Rare 22q11.2 CNVs play a role in non-syndromic BAV, particularly in cases with early onset or complex presentations. CNV screening could be considered as part of risk stratification for patients with BAV, helping to predict complications and guide management. Trial registration number NCT01823432 .

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: 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: Optimum timing of surgery for severe primary mitral regurgitation (MR) particularly in the absence of significant symptoms or echo evidence of LV impairment remains unclear. Other modalities of assessment include cardiopulmonary exercise testing (CPET) and novel echo measurements, such as LV global longitudinal strain (LVGLS). We sought to evaluate whether pre-op CPET or LVGLS are associated with survival after surgery. Methods: We identified consecutive patients who had surgery for severe primary MR between 2007 and 2017 and had pre-op CPET. Clinical and mortality data were collected from chart review and our institutional database. LVGLS was retrospectively collected by a single person blinded to patient outcomes. Primary outcome was post surgery all cause death, and we used univariable analysis to identify variables associated with all cause death. Results: We included 176 patients with median age 63 (IQR 51, 71) years, 63 patients (35.8%) were female and 31 patients (14.8%) had a history of atrial fibrillation. 165 patients (93.8%) had mitral repair, 18 (10.2%) had concomitant CABG, 22 (12.5%) had concomitant ablation procedure and 14 (8.0%) had concomitant tricuspid procedure. 114 patients (64.8%) were in NYHA Class I and 56 (31.8%) were in NYHA Class II. There was no operative mortality. Median % predicted peak VO2 (ppVO2) was 89 (74, 101), median ventilatory equivalent of carbon dioxide (VE/VCO2) was 28.0 (25.7, 31.0) l/min/l/min and median respiratory exchange ratio was 1.2 (1.1, 1.2). 73 patients (41.5%) had abnormal CPET (defined as ppVO2<85%). Median LVEF was 65 (60, 68) %, median LVESD was 35 (32, 38) mm and median LVGLS was 18.5 (16.6, 20.3) %. 45 patients (25.9%) had abnormal LVEF (defined as ≤ 60%), 11 patients (6.7%) had abnormal LVESD (defined as ≥45mm) and 35 patients (20.8%) had abnormal LVGLS (defined as <16%). At a median follow up of 10.2 (6.8, 13.2) years, there were 19 (10.8%) deaths. In the univariate analysis, age at surgery (HR 1.12, p<0.001), LVESD (HR 1.11, p=0.009), LVGLS (HR 1.11, p=0.013) and VE/VCO2 (HR 1.08, p=0.044) were associated with all cause mortality. Conclusion: A significant proportion of patients with no or mild symptoms exhibit echocardiographic evidence of LV impairment when having surgery for severe primary MR. CPET parameters such as VE/VCO2 and novel echocardiographic measurements such as LVGLS may predict risk of long term mortality and potentially inform timing of surgery in these patients.

ImportanceSecondary tricuspid regurgitation (STR) is observed in multiple cardiac and pulmonary diseases. Heart failure with preserved ejection fraction (HFpEF) is a common cause of STR that may be overlooked, along with precapillary etiologies of pulmonary hypertension (PH).ObjectivesTo investigate the prevalence of HFpEF and precapillary PH in patients with severe STR of undefined etiology (isolated STR) referred for exercise right heart catheterization (RHC), and to evaluate the performance of noninvasive measures to identify HFpEF.Design, Setting, and ParticipantsThis retrospective cross-sectional study included consecutive adults with severe STR in the absence of EF less than 50%, hemodynamically significant left-sided valve disease, congenital heart disease, infiltrative or hypertrophic cardiomyopathy, pericardial disease, or prior cardiac procedures who underwent rest-and-exercise RHC between February 2006 and June 2023 at Mayo Clinic and transthoracic echocardiography less than 90 days prior. Diastolic dysfunction (DD) was defined by at least 3 of 4 or 2 of 3 abnormal diastolic parameters (medial e’, medial E/e’, tricuspid regurgitation [TR] velocity, left atrial volume index). HFpEF was diagnosed when pulmonary arterial wedge pressure was at least 15 mm Hg at rest, at least 19 mm Hg with feet up, or at least 25 mm Hg during exercise. Data analysis was performed from November 2023 to March 2024.Main Outcomes and MeasuresThe prevalence of HFpEF and precapillary PH in severe isolated STR was determined, and performance of noninvasive measures to identify HFpEF was evaluated.ResultsOverall, 54 patients with severe isolated STR (mean [SD] age, 70.8 [12.5] years; 34 [63%] female) were identified. The primary indication for RHC was evaluation of TR prior to potential intervention in 36 patients (67%), evaluation of PH in 13 (24%), and confirmation of HFpEF in 5 (9%). HFpEF was identified in 40 patients (74%) but was recognized prior to RHC in only 19 patients (35%). Of the 14 remaining patients without HFpEF, precapillary PH was diagnosed in 10 (71%). Guideline-defined DD was absent in 24 patients (60%) who were subsequently diagnosed with HFpEF. Left atrial emptying fraction (area under the receiver operating characteristic curve [AUC] = 0.90; 95% CI, 0.82-0.98) and strain (AUC = 0.91; 95% CI, 0.83-0.99) had robust discrimination for HFpEF.Conclusions and RelevanceThe findings suggest that HFpEF is underdiagnosed and should be rigorously evaluated for in patients with severe isolated STR, along with precapillary PH, as both have distinct requirements for management. Resting DD based on current guidelines is insufficiently sensitive in these patients, indicating a pressing need for other noninvasive diagnostic tools, such as left atrial function assessment.