Background Patients with moderate aortic stenosis (AS) and concomitant mitral regurgitation (MR) often present with symptoms despite neither lesion individually reaching intervention thresholds. The clinical impact of this dual valvular disease remains a knowledge gap. Objectives The aims of this study were to evaluate the effect of concomitant MR on cardiac remodeling and clinical outcomes in patients with moderate AS using cardiac magnetic resonance (CMR) and to compare with isolated moderate and severe AS. Methods A total of 742 patients with at least moderate AS on CMR (422 with moderate AS, 320 with severe AS) were studied. Patients were stratified by AS severity and MR burden. Remodeling parameters, symptoms, and outcomes, including cardiovascular death and heart failure hospitalization, were analyzed. Multivariable Cox models identified covariates associated with outcomes. Results Among 422 patients with moderate AS, 76 had moderate or greater MR. Compared with isolated moderate AS, combined AS and MR was associated with higher symptom burden (80.3% in NYHA functional classes II-IV), more pronounced remodeling (larger indexed left ventricular volumes, lower left ventricular ejection fractions), and reduced aortic forward flow. Over a median 1.8 years, coexisting moderate or greater MR was independently associated with cardiovascular death or heart failure hospitalization (adjusted HR: 1.86; 95% CI: 1.31-2.65; P < 0.001). This risk was more apparent in the low-flow subgroup (stroke volume index ≤35 mL/m2), whereas in normal-flow patients, there was a trend toward increased risk that did not reach statistical significance. Outcomes in moderate AS with moderate or greater MR were worse than in isolated severe AS and comparable with severe AS populations meeting criteria for intervention. Conclusions Patients with moderate AS and MR constitute a high-risk subgroup with high symptom burden, adverse cardiac remodeling, and poor clinical outcomes. Risk appears more pronounced in the setting of reduced forward flow (stroke volume index ≤35 mL/m2). CMR enables the quantitative assessment of dual valvular burden and may improve risk stratification. These findings highlight a therapeutic gap and support studies of earlier intervention in this high-risk subgroup.

BACKGROUND:Mitral valve prolapse (MVP) is a common cardiac condition that is generally benign, yet a subset of affected patients develop malignant ventricular arrhythmias and sudden cardiac death. Female sex and myocardial fibrosis detected by late gadolinium enhancement on cardiovascular magnetic resonance imaging have been proposed as risk factors though their independent contributions to arrhythmic risk remain uncertain. METHODS:We conducted a prospective cohort study of 550 consecutive patients with MVP referred for cardiovascular magnetic resonance at a tertiary academic center between May 2008 and December 2021. Patients with potential confounders, including coronary artery disease, cardiomyopathy, infiltrative disease, or prior cardiac surgery, were excluded. The primary end point was a composite arrhythmic outcome comprising sudden cardiac death, aborted sudden cardiac arrest, and symptomatic sustained or inducible ventricular tachycardia or ventricular fibrillation leading to implantable cardioverter defibrillator placement or ventricular ablation at an MVP-related scar site. RESULTS:Among the 550 patients (median age, 62 [interquartile range, 52-71] years; 50% women), LGE was present in 210 (38%). Over a median follow-up of 4.4 years (interquartile range, 2.8-7.1; 2700 patient-years), 48 patients (8.7%) reached the primary end point. On univariable analysis, both female sex (hazard ratio, 3.33 [95% CI, 1.72-6.44]; P<0.001) and LGE presence (hazard ratio, 3.17 [95% CI, 1.74-5.77]; P<0.001) were significantly associated with arrhythmic events, and both remained independently associated on multivariable analysis. Women with LGE represented the highest-risk subgroup, with a 5-year event-free survival of 76.5%, compared with 98.5% in men without LGE (P<0.001). CONCLUSIONS:In a large prospective cardiovascular magnetic resonance cohort of patients with MVP, female sex and myocardial fibrosis were each independently associated with life-threatening arrhythmic events. Their combination identified a subgroup at particularly elevated risk, highlighting the importance of integrating sex-specific factors and myocardial tissue characterization into MVP risk stratification strategies.

Background: A low-flow state is associated with worse outcomes in aortic stenosis (AS). Doppler-derived stroke volume accuracy could be limited by geometric assumptions and measurement variability. Cardiac magnetic resonance (CMR) provides comprehensive AS assessment and reproducible direct flow quantification via phase-contrast imaging. We aimed to evaluate the prognostic value of CMR-derived stroke volume index (SVI) in patients with AS and to identify a predictive cutoff associated with adverse outcomes. Methods: Patients with moderate or severe AS on clinically indicated CMR (2008–2023) were identified from the DeBakey CMR Registry. Exclusions included >mild AR or MS, infiltrative cardiomyopathy, pre-capillary pulmonary hypertension, or advanced malignancy. Aortic SVI was measured by LVOT phase-contrast imaging and indexed to BSA. The primary outcome was CV death or HF hospitalization, censored at valve intervention. Penalized spline regression assessed the association between SVI and outcomes. ROC analysis identified the optimal SVI threshold, and Kaplan-Meier analysis compared event-free survival by SVI strata (log-rank test). Multivariable models were adjusted for SVI and relevant covariates. Analyses were performed in R; P < 0.05 was considered significant. Results: A total of 742 patients with moderate (n=422) or severe (n=320) AS were included (median age 72.9 years [IQR: 65.1–80.4]; 57% male). Median AVA was 1.0 cm2 [0.8–1.2], peak gradient 42.2 mmHg [36.0–58.9], LVEF 56% [49–63], and SVI 38.5 mL/m2 [31.1–45.4]. Median Charlson Index was 8 [5–12]; 50.5% were symptomatic (NYHA ≥ II). Lower SVI was associated with higher risk of CV death or HF hospitalization in penalized spline analysis (P < 0.001). (Figure1) ROC analysis identified an optimal 3-year SVI threshold of 36 mL/m2 (AUC 0.69). (Figure 2) Event-free survival was significantly lower with SVI <36 vs. ≥36 (50.6% vs. 72.8%, P < 0.001). (Figure 3) In multivariable analysis adjusting for age, sex, Charlson Index, LVEF, scar, eGFR, and AS severity, each 5-unit SVI decrease was associated with higher risk (HR 1.13; 95% CI: 1.03–1.25; P = 0.014); SVI <36 also conferred increased risk (HR 1.47; 95% CI: 1.03–2.08; P = 0.032). Conclusion: In moderate to severe AS, reduced SVI by CMR was independently associated with increased risk of CV death or HF hospitalization. A threshold of 36 mL/m2 identified a high-risk subgroup, supporting the prognostic value of CMR-derived flow in AS risk stratification.

Right ventricular dysfunction at cardiac MRI in patients with aortic regurgitation was associated with coexisting mitral regurgitation and left ventricular dysfunction and helped independently predict all-cause mortality, cardiovascular death, and perioperative mortality.

BACKGROUND:A recently proposed staging system for cardiac structural and functional abnormalities demonstrated incremental prognostic value in aortic stenosis. OBJECTIVES:The authors investigate a staging system incorporating cardiac magnetic resonance (CMR) in moderate or severe aortic regurgitation (AR). METHODS:Patients prospectively enrolled in DEBAKEY-CMR (DeBakey Cardiovascular Magnetic Resonance Study; NCT04281823) between 2009 and 2020 who had moderate or severe AR by CMR were studied. We excluded patients with a primary cardiomyopathy (eg, hypertrophic cardiomyopathy, amyloidosis, sarcoidosis) or prior valve intervention. The stages were defined as stage 0: no cardiac remodeling; stage 1: left ventricular (LV) remodeling; stage 2: mitral valve or left atrial abnormalities; and stage 3: right heart remodeling. The outcome was all-cause mortality. RESULTS:The authors studied 395 patients, median age 62 years (Q1-Q3: 51-72 years); 79.2% were male, and 25.8% had bicuspid aortic valve. Thirty-two patients (8.10%) were classified as stage 0, 146 (37.0%) as stage 1, 77 (19.5%) as stage 2, and 140 (35.4%) as stage 3. Over a mean follow-up period of 3.9 ± 2.9 years, the annualized mortality rate was 0.68% per year in stage 0, 2.25% per year in stage 1, 3.76% per year in stage 2, and 7.25% per year in stage 3 (P for trend of mortality <0.001). The extent of cardiac remodeling was independently associated with increased hazard for mortality (adjusted HR: 1.69 per increment of stage [95% CI: 1.28-2.23]; P < 0.001) after adjusting for regurgitation severity, aortic valve replacement (AVR), and EuroSCORE II (European System for Cardiac Operative Risk Evaluation). Patients with right heart remodeling had the highest hazard for events. CONCLUSIONS:A cardiac remodeling staging system incorporating CMR findings provides incremental prognostication in AR after adjusting for surgical risk, AVR, and regurgitation severity. Right heart remodeling in AR was associated with the highest mortality. Further research can determine whether the staging system could aid in guiding patient management and the timing of intervention.

Cardiac magnetic resonance (CMR) quantifies aortic regurgitation (AR) and left ventricular (LV) remodeling. We aimed to evaluate the association of baseline CMR findings with reverse remodeling after aortic valve surgery and likelihood of normalization of LV volume/function is not clear. In a multicenter observational study of AR patients undergoing pre- and post-operative CMR, we evaluated AR severity and LV volumes on baseline CMR with reverse remodeling evaluated by LV volumes and function after surgery. We identified chronic AR patients enrolled in institutional databases at 3 centers between 2011 and 2022 with pre- and post-operative CMR. We also prospectively enrolled patients with AR and preop CMR to undergo a research CMR post-operatively at Houston Methodist Hospital during the year 2021. We studied 55 patients in total (17 enrolled prospectively), median age 57.0 (45.4–64.2) years, 87

BACKGROUND:Management of patients with combined aortic and mitral regurgitation (AR and MR) is largely based on expert opinion. Specifically, the outcomes of patients with combined moderate AR and moderate MR under medical surveillance are uncertain. OBJECTIVES:This study aimed to evaluate cardiac remodeling using cardiac magnetic resonance (CMR) in patients with combined AR/MR compared with isolated AR, to assess degree of MR associated with adverse outcomes, and evaluate the outcomes of asymptomatic patients with combined moderate AR and moderate MR under medical surveillance. METHODS:The authors conducted a multicenter observational outcome study of patients with moderate or severe AR on CMR, and evaluated the etiology and degree of concomitant MR in patients with combined AR and MR. They excluded patients if they had prior valvular surgery, > mild valve stenosis, hypertrophic or infiltrative cardiomyopathy, or congenital heart disease except bicuspid aortic valve. The authors evaluated ventricular volumes and function across the spectrum of regurgitation severity. Receiver-operating characteristic analyses for the association of concomitant MR severity with outcomes were performed. The primary outcome was all-cause death. Secondary outcome was all-cause death or heart failure (HF) hospitalization. Patients were censored at the time of valvular surgery or intervention. Propensity score matching was done between isolated AR and the combined AR/MR groups. RESULTS:The authors studied 915 patients with a median age of 61 years (Q1-Q3: 49-72 years), 79.5% male, 29% with bicuspid aortic valve, and a median AR fraction of 38% (Q1-Q3: 32%-45%). In 251 of 915 patients (27.4%) with concomitant MR, the median MR fraction was 24% (Q1-Q3: 17%-35%). The presence of concomitant ≥moderate MR (14.2% of the total population) was associated with a greater increase in ventricular volumes per unit increase in AR severity, and a decline in ventricular function (P for interaction ≤0.01). During a median follow-up of 3.0 years (Q1-Q3: 1.1-5.6 years), there were 152 deaths. Presence of concomitant ≥moderate MR was associated with an increased hazard for all-cause death (HR: 2.77; 95% CI: 1.91-4.01; P < 0.001), and the secondary outcome of death or HF (HR: 2.62; 95% CI: 1.87-3.67; P < 0.001). In asymptomatic or minimally symptomatic patients undergoing medical surveillance, the presence of combined moderate AR and moderate MR was independently associated with a higher hazard for the primary and secondary outcomes compared with isolated AR, independent of age, sex, comorbidities, ejection fraction, and end-systolic volume. Findings were consistent in the propensity matched cohort. CONCLUSIONS:The presence of combined AR and MR on CMR is associated with a greater extent of ventricular remodeling and increased hazard for adverse outcomes, compared with isolated AR. Asymptomatic patients with combined moderate AR and MR under medical surveillance are at higher risk for death and HF, and warrant further study.

Objective: The clinical trajectory of patients with moderate aortic stenosis (AS) complicated by concomitant mitral regurgitation (MR) remains poorly defined. While management strategies in severe AS are well established, patients with moderate AS and MR often fall below guideline-based thresholds for intervention despite symptoms and remodeling. We used cardiac magnetic resonance (CMR)—a robust modality for accurate valve quantification, particularly in mixed valvular disease— to assess the prognostic impact of MR in moderate AS and to compare the outcomes to patients with severe AS. Methods: We analyzed consecutive patients from the DeBakey CMR Registry (2008–2023) with ≥moderate AS on clinically indicated CMR. Exclusions included >mild aortic regurgitation or mitral stenosis, subaortic obstruction, infiltrative cardiomyopathies, pre-capillary pulmonary hypertension, advanced malignancy, or unavailable follow-up. Patients were stratified by AS severity (moderate vs. severe) and MR grade ( Results: In a multivariate Cox regression analysis of 422 patients with moderate AS, both mitral regurgitant (MR) fraction on CMR (hazard ratio [HR] per 5% increase: 1.10; 95% CI: 1.04–1.16; P < 0.001) and the presence of ≥ moderate MR (HR: 1.86; 95% CI: 1.31–2.65; P < 0.001) were independently associated with the composite outcome (Table 1). In moderate AS, penalized spline regression analysis showed a statistically significant increase in risk with increasing MR fraction (P<0.001 for linearity; P=0.028 for non-linearity; Figure 1). Kaplan-Meier curves demonstrated poorer 3-year event-free survival in patients with moderate AS and concomitant ≥moderate MR (33%) compared with both isolated severe AS (71%) and severe AS with ≥moderate MR (49%) (Figure 2). Conclusion: In moderate AS, concomitant MR is an independent predictor of adverse clinical composite outcomes. Patients with moderate AS and ≥moderate MR had worse composite outcomes than those with isolated severe AS, underscoring the additive risk of dual-valve pathology. These findings support more vigilant monitoring and may justify re-evaluation of treatment thresholds in this mixed valvular disease subgroup.

BACKGROUND:Current treatment paradigms assume aortic regurgitation (AR) patients to be a homogenous population, but varied courses of disease progression and outcomes are observed clinically. OBJECTIVES:The aim of this study was to first use unsupervised machine learning to identify unique patient phenoclusters in AR, and subsequently evaluate their prognostic relevance. METHODS:Clinical and cardiac magnetic resonance (CMR) characterization of moderate or severe AR patients was performed across 4 U.S. CENTERS:Data from 2 centers were used for derivation of phenoclusters and validation was performed in the other 2. The outcome was all-cause death. An unsupervised clustering pipeline, Partition Around Medoids, used 23 clinical and CMR variables to derive patient clusters independent of outcomes. RESULTS:Included were 972 patients with mean age 62 ± 23.2 years, 754 (78%) male, 680 (70%) trileaflet valve, and 330 (34%) underwent valve surgery. Over a median follow-up of 2.58 years (Q1-Q3: 1.03-5.50 years), the overall mortality rate was 12%. Four clusters were derived: 1) a younger predominantly male phenotype with majority of bicuspid aortic valve and high extent of left ventricular (LV) remodeling (1% mortality); 2) older male patients with predominantly tricuspid valves and intermediate outcomes (10% mortality); 3) older predominantly male patients with the highest burden of comorbidities, LV scarring, and dysfunction (22% mortality); and 4) a phenotype of predominantly female patients with high mortality and relatively higher symptoms burden, relatively lower extent of LV remodeling, and rate of aortic valve replacement (20% mortality). The clustering algorithm was independently associated with survival after adjustment for time-dependent aortic valve replacement and traditional risk markers of prognosis in patients with AR (C statistic 0.77 vs 0.75; P = 0.009 in the validation cohort). CONCLUSIONS:Unique patient phenoclusters of AR are described using a machine learning approach leveraging comprehensive CMR and clinical characterization. This approach may be an opportunity for a precision medicine approach to enhance risk stratification of patients with AR. Female patients with AR pose a unique phenotype with high mortality, which deserves greater attention.

AIMS:This study aimed to investigate the relationship between diastolic dysfunction (DD) and extracellular volume (ECV), scar burden, and myocyte volume in patients with at least moderate aortic regurgitation (AR) by cardiac magnetic resonance (CMR). We also sought to determine the association of DD with mortality in AR patients. METHODS AND RESULTS:Patients with at least moderate AR and who underwent echocardiographic and CMR imaging with a median time of 4 days between the two studies (interquartile range 1-43 days) were included. CMR was used to obtain left ventricular (LV) volumes, ejection fraction and mass, AR severity, scar extent, and ECV. DD was assessed by comprehensive echocardiography. The study included 323 patients. The mean age was 61.9 ± 16.0 and the median follow-up was 3.8 years, during which 86 patients died and 69 were hospitalized for heart failure. LV end-systolic volume, LV mass index, ECV, indexed cellular volume, and scar burden increased with advanced DD (P < 0.01). In multivariable Cox proportional hazard models, Grades II and III DD were independently associated with increased mortality (HR = 1.49, 95% CI = 1.1-1.98, P = 0.009). CONCLUSION:ECV, scar, and myocyte volume by CMR progressively increase with higher grades of DD by echocardiography, and DD is independently associated with mortality in patients with at least moderate AR.

Abstract INTRODUCTION Immune checkpoint inhibitors (ICI) are associated with neurological immune-related adverse events (NiArE) such as myasthenia gravis (MG) and myositis. These conditions often present with overlapping symptoms, notably ptosis, dyspnea, and extremity weakness. Early recognition and treatment are warranted to prevent disease progression. OBJECTIVE To test the utility of simple bedside ice pack test (IPT) in early recognition and distinction of ICI-mediated MG and myositis ocular manifestations. METHODS We administered IPT in 14 patients who had received ICI in the past 6 months and presented with ptosis. Improvement in ptosis was considered positive IPT (non-fixed, fatigable ptosis) that is suggestive of Immune-mediated MG-predominant process. Work up included myasthenia antibodies, EMG, serum markers of muscle injury (creatine kinase, aldolase), myositis panel and muscle biopsy. Statistical analyses employed median for continuous and frequencies for categorical variables. RESULTS Positive IPT was found in 2 (14%) patients with positive myasthenia antibodies and neuromuscular junction dysfunction on EMG in one patient with repetitive nerve stimulation. These patients had mild elevation in creatine kinase (CK). Muscle biopsy did not reveal a myositic process. Twelve (86%) patients had negative IPT (fixed and non-fatigable ptosis) with significantly elevated CK (>4000), positive myositis panel and muscle biopsy consistent with myositic process. Six of these patients (42%) also had positive myasthenia antibodies. Concomitant myocarditis was observed in 5 (36%) patients. CONCLUSION Clinical overlap between myasthenia and myositis is observed in immune mediated toxicity that may be due to cross-reactivity of antibodies, however, IPT was able to distinguish MG vs myositis-predominant process, thus helping guide management.

AIMS:The association between secondary mitral regurgitation (MR) and right ventricular (RV) dysfunction in heart failure patients with non-ischaemic cardiomyopathy (NICM) is unclear. Hence, our objective was to study the association between secondary MR and the occurrence of RV dysfunction among patients with NICM using cardiac magnetic resonance (CMR). METHODS AND RESULTS:Patients with NICM were enrolled in a prospective observational registry between 2008 and 2019. CMR was used to quantify MR severity along with RV function. The RV dysfunction was defined as RV ejection fraction <45%. The outcome of the study was a composite event of all-cause death, heart transplantation, or left ventricular assist device implantation at follow-up. In the study cohort of 241 patients, RV dysfunction (RVEF < 45%) was present in 148 (61%). In comparison with patients without RV dysfunction, those with RV dysfunction had higher median MR volume {23 mL [interquartile range (IQR) 16-31 mL] vs. 18 mL (IQR 12-25 mL), P = 0.002} and MR fraction [33% (IQR 25-43%) vs. 22% (IQR 15-29%), P < 0.001]. Furthermore, secondary MR was independently associated with RV dysfunction: MR volume ≥ 24 mL (OR 3.21, 95% CI 1.26-8.15, P = 0.01) and MR fraction ≥ 30% (OR 5.46, 95% CI 2.23-13.35, P = 0.002). Increasing RVEF (every 1% increase) was independently associated with lower risk of adverse events (HR 0.98; 95% CI 0.95, 1.00; P = 0.047). CONCLUSION:In patients with NICM, the severity of secondary MR is associated with an increased prevalence of RV dysfunction. The RV dysfunction is not only associated with the severity of LV dysfunction but also with the severity of secondary MR. CLINICAL TRIAL REGISTRATION:https://clinicaltrials.gov/ct2/show/NCT04281823.