Clinical Outcomes of Mitral Valve Surgery in Atrial Functional Mitral Regurgitation in the REVEAL-AFMR Registry.

Importance: The characteristics and treatment strategies of atrial functional mitral regurgitation (AFMR) are poorly understood. Objective: To investigate the prevalence, clinical characteristics, and outcomes of mitral valve (MV) surgery in AFMR. Design, Setting, and Participants: This retrospective cohort study, called the Real-World Observational Study for Investigating the Prevalence and Therapeutic Options for Atrial Functional Mitral Regurgitation (REVEAL-AFMR), was conducted across 26 Japanese centers (17 university hospitals, 1 national center, 3 public hospitals, and 5 private hospitals). All transthoracic echocardiography procedures performed from January 1 to December 31, 2019, were reviewed to enroll adult patients (aged ≥20 years) with moderate or severe AFMR, defined by preserved left ventricular function, a dilated left atrium, and an absence of degenerative valvular changes. Data were analyzed from May 8, 2023, to May 16, 2024. Exposures: Mitral valve surgery, with or without tricuspid valve intervention. Main Outcomes and Measures: The primary composite outcome included heart failure hospitalization and all-cause mortality. Results: In 177 235 patients who underwent echocardiography, 8867 had moderate or severe MR. Within this group, 1007 (11.4%) were diagnosed with AFMR (mean [SD] age, 77.8 [9.5] years; 55.7% female), of whom 807 (80.1%) had atrial fibrillation. Of these patients, 113 underwent MV surgery, with 92 (81.4%) receiving concurrent tricuspid valve surgery. Patients who underwent surgery were younger but had more severe MR (57.5% [n = 65] vs 9.4% [n = 84]; P < .001), a larger mean (SD) left atrial volume index (152.5 [97.8] mL/m2 vs 87.7 [53.1] mL/m2; P < .001), and a higher prevalence of heart failure (according to the New York Heart Association class III [marked limitation of physical activity] or class IV [symptoms of heart failure at rest], 26.5% [n = 30] vs 9.3% [n = 83]; P < .001) than those who remained under medical therapy. During a median follow-up of 1050 days (IQR, 741-1188 days), 286 patients (28.4%) experienced the primary outcome. Despite a more severe disease status, only the surgical group showed a decrease in natriuretic peptide levels at follow-up and had a significantly lower rate of the primary outcome (3-year event rates were 18.3% vs 33.3%; log-rank, P = .03). Statistical adjustments did not alter these findings. Conclusions and Relevance: The findings of this cohort study suggest that in patients with AFMR, who were typically older and predominantly had atrial fibrillation, MV surgery was associated with lower rates of adverse clinical outcomes. Future studies are warranted to investigate a possible causal relationship to better regulate cardiovascular medicine.

Applying masked autoencoder-based self-supervised learning for high-capability vision transformers of electrocardiographies.

The generalization of deep neural network algorithms to a broader population is an important challenge in the medical field. We aimed to apply self-supervised learning using masked autoencoders (MAEs) to improve the performance of the 12-lead electrocardiography (ECG) analysis model using limited ECG data. We pretrained Vision Transformer (ViT) models by reconstructing the masked ECG data with MAE. We fine-tuned this MAE-based ECG pretrained model on ECG-echocardiography data from The University of Tokyo Hospital (UTokyo) for the detection of left ventricular systolic dysfunction (LVSD), and then evaluated it using multi-center external validation data from seven institutions, employing the area under the receiver operating characteristic curve (AUROC) for assessment. We included 38,245 ECG-echocardiography pairs from UTokyo and 229,439 pairs from all institutions. The performances of MAE-based ECG models pretrained using ECG data from UTokyo were significantly higher than that of other Deep Neural Network models across all external validation cohorts (AUROC, 0.913-0.962 for LVSD, p < 0.001). Moreover, we also found improvements for the MAE-based ECG analysis model depending on the model capacity and the amount of training data. Additionally, the MAE-based ECG analysis model maintained high performance even on the ECG benchmark dataset (PTB-XL). Our proposed method developed high performance MAE-based ECG analysis models using limited ECG data.

Multicenter validation study for automated left ventricular ejection fraction assessment using a handheld ultrasound with artificial intelligence.

We sought to validate the ability of a novel handheld ultrasound device with an artificial intelligence program (AI-POCUS) that automatically assesses left ventricular ejection fraction (LVEF). AI-POCUS was used to prospectively scan 200 patients in two Japanese hospitals. Automatic LVEF by AI-POCUS was compared to the standard biplane disk method using high-end ultrasound machines. After excluding 18 patients due to infeasible images for AI-POCUS, 182 patients (63 ± 15 years old, 21% female) were analyzed. The intraclass correlation coefficient (ICC) between the LVEF by AI-POCUS and the standard methods was good (0.81, p < 0.001) without clinically meaningful systematic bias (mean bias -1.5%, p = 0.008, limits of agreement ± 15.0%). Reduced LVEF < 50% was detected with a sensitivity of 85% (95% confidence interval 76%-91%) and specificity of 81% (71%-89%). Although the correlations between LV volumes by standard-echo and those by AI-POCUS were good (ICC > 0.80), AI-POCUS tended to underestimate LV volumes for larger LV (overall bias 42.1 mL for end-diastolic volume). These trends were mitigated with a newer version of the software tuned using increased data involving larger LVs, showing similar correlations (ICC > 0.85). In this real-world multicenter study, AI-POCUS showed accurate LVEF assessment, but careful attention might be necessary for volume assessment. The newer version, trained with larger and more heterogeneous data, demonstrated improved performance, underscoring the importance of big data accumulation in the field.

Familial cryptogenic stroke.

Familial cryptogenic stroke associated with atrial septal defect and patent foramen ovale is rare. The presence of a family history of cryptogenic stroke may lead to the requirement for careful follow-up for younger family members.

Midterm outcomes of transcatheter aortic valve replacement in patients with active cancer.

OBJECTIVES: The clinical outcomes of transcatheter aortic valve replacement (TAVR) in patients with aortic stenosis (AS) and concomitant active cancer remain insufficiently explored. This study aimed to assess the midterm outcomes of TAVR in patients diagnosed with AS and active cancer. METHODS: Data from the OCEAN-TAVI, a prospective Japanese registry of TAVR procedures, was analysed to compare prognoses and clinical outcomes in patients with and without active cancer at the time of TAVR. RESULTS: Of the 2336 patients who underwent TAVR from October 2013 to July 2017, 89 patients (3.8%) had active cancer, whereas 2247 did not. Among patients with active cancer, 49 had limited-stage cancer (stage 1 or 2). The prevalent cancers identified before TAVR were colon (21%), prostate (18%), lung (15%), liver (11%) and breast (9%). Although the periprocedural complications and 30-day mortality rates were comparable between the groups, the 3-year survival rate after TAVR was notably lower in patients with active cancer (64.7%) than in those without active cancer (74.7%; p=0.016). Nevertheless, the 3-year survival rate of patients with limited-stage cancer (stage 1 or 2) did not significantly differ from those without cancer (70.6% vs 74.7%, p=0.50). CONCLUSIONS: The patients with active cancer exhibited significantly reduced midterm survival rates. However, no distinct disparity existed in those with limited-stage cancer (stage 1 or 2). Although TAVR is a viable treatment in patients with AS with active cancer, the type and stage of cancer and prognosis should be carefully weighed in the decision-making process.

Deep Learning Models for Predicting Left Heart Abnormalities From Single-Lead Electrocardiogram for the Development of Wearable Devices.

BACKGROUND: Left heart abnormalities are risk factors for heart failure. However, echocardiography is not always available. Electrocardiograms (ECGs), which are now available from wearable devices, have the potential to detect these abnormalities. Nevertheless, whether a model can detect left heart abnormalities from single Lead I ECG data remains unclear.Methods and Results: We developed Lead I ECG models to detect low ejection fraction (EF), wall motion abnormality, left ventricular hypertrophy (LVH), left ventricular dilatation, and left atrial dilatation. We used a dataset comprising 229,439 paired sets of ECG and echocardiography data from 8 facilities, and validated the model using external verification with data from 2 facilities. The area under the receiver operating characteristic curves of our model was 0.913 for low EF, 0.832 for wall motion abnormality, 0.797 for LVH, 0.838 for left ventricular dilatation, and 0.802 for left atrial dilatation. In interpretation tests with 12 cardiologists, the accuracy of the model was 78.3% for low EF and 68.3% for LVH. Compared with cardiologists who read the 12-lead ECGs, the model's performance was superior for LVH and similar for low EF. CONCLUSIONS: From a multicenter study dataset, we developed models to predict left heart abnormalities using Lead I on the ECG. The Lead I ECG models show superior or equivalent performance to cardiologists using 12-lead ECGs.

Congenital abnormalities of heart and kidney.

Patients with congenital anomalies of the kidney and urinary tract (CAKUT) may be at risk for congenital cardiac defects or cardiomyopathies as comorbidities. It is crucial to recognize the coexistence of cardiac abnormalities and CAKUT and recommend screening for cardiac involvement in CAKUT patients using echocardiography.

Unsupervised Machine Learning for Assessment of Left Ventricular Diastolic Function and Risk Stratification.

BACKGROUND: The 2016 American Society of Echocardiography guidelines have been widely used to assess left ventricular diastolic function. However, limitations are present in the current classification system. The aim of this study was to develop a data-driven, unsupervised machine learning approach for diastolic function classification and risk stratification using the left ventricular diastolic function parameters recommended in the 2016 American Society of Echocardiography guidelines; the guideline grading was used as the reference standard. METHODS: Baseline demographics, heart failure hospitalization, and all-cause mortality data were obtained for all adult patients who underwent transthoracic echocardiography at Mayo Clinic Rochester in 2015. Patients with prior mitral valve intervention, congenital heart disease, cardiac transplantation, or cardiac assist device implantation were excluded. Nine left ventricular diastolic function variables (mitral E- and A-wave peak velocities, E/A ratio, deceleration time, medial and lateral annular e' velocities and E/e' ratio, and tricuspid regurgitation peak velocity) were used for an unsupervised machine learning algorithm to identify different phenotype clusters. The cohort average of each variable was used for imputation. Patients were grouped according to the algorithm-determined clusters for Kaplan-Meier survival analysis. RESULTS: Among 24,414 patients (mean age, 63.6 ± 16.2 years), all-cause mortality occurred in 4,612 patients (18.9%) during a median follow-up period of 3.1 years. The algorithm determined three clusters with echocardiographic measurement characteristics corresponding to normal diastolic function (n = 8,312), impaired relaxation (n = 11,779), and increased filling pressure (n = 4,323), with 3-year cumulative mortality of 11.8%, 19.9%, and 33.4%, respectively (P < .0001). All 10,694 patients (43.8%) classified as indeterminate were reclassified into the three clusters (n = 3,324, n = 5,353, and n = 2,017, respectively), with 3-year mortality of 16.6%, 22.9%, and 34.4%, respectively. The clusters also outperformed guideline-based grade for prognostication (C index = 0.607 vs 0.582, P = .013). CONCLUSIONS: Unsupervised machine learning identified physiologically and prognostically distinct clusters on the basis of nine diastolic function Doppler variables. The clusters can be potentially applied in echocardiography laboratory practice and future clinical trials for simple, replicable diastolic function-related risk stratification.

Prevalence and Natural History of Mitral Annulus Calcification and Related Valve Dysfunction.

OBJECTIVE: To evaluate the prevalence and natural history of mitral annulus calcification (MAC) and associated mitral valve dysfunction (MVD) in patients undergoing clinically indicated echocardiography. METHODS: A retrospective review was conducted of all adults who underwent echocardiography in 2015. Mitral valve dysfunction was defined as mitral regurgitation or mitral stenosis (MS) of moderate or greater severity. All-cause mortality during 3.0 (0.4 to 4.2) years of follow-up was compared between groups stratified according to the presence of MAC or MVD. RESULTS: Of 24,414 evaluated patients, 5502 (23%) had MAC. Patients with MAC were older (75±10 years vs 60±16 years; P<.001) and more frequently had MVD (MS: 6.6% vs 0.5% [P<.001]; mitral regurgitation without MS: 9.5% vs 6.1% [P<.001]). Associated with MS in patients with MAC were aortic valve dysfunction, female sex, chest irradiation, renal dysfunction, and coronary artery disease. Kaplan-Meier 1-year survival was 76% in MAC+/MVD+, 87% in MAC+/MVD-, 86% in MAC-/MVD+, and 92% in MAC-/MVD-. Adjusted for age, diabetes, renal dysfunction, cancer, chest irradiation, ejection fraction below 50%, aortic stenosis, tricuspid regurgitation, and pulmonary hypertension, MAC was associated with higher mortality during follow-up (adjusted hazard ratio, 1.40; 95% CI, 1.31 to 1.49; P<.001); MVD was associated with even higher mortality in patients with MAC (adjusted hazard ratio, 1.79; 95% CI, 1.58 to 2.01; P<.001). There was no significant interaction between MAC and MVD for mortality (P=.10). CONCLUSION: In a large cohort of adults undergoing echocardiography, the prevalence of MAC was 23%. Mitral valve dysfunction was more than twice as prevalent in patients with MAC. Adjusted mortality was increased in patients with MAC and worse with both MAC and MVD.

Cryptogenic stroke caused by patent foramen ovale with thrombophilia and accessory tricuspid valve in a teenager.

Accessory tricuspid valve is rare congenital abnormality. We describe a case of cryptogenic stroke in teenager boy caused by patent foramen ovale with thrombophilia and accessory tricuspid valve.

Impact of mitral intervention on outcomes of patients with mitral valve dysfunction and annulus calcification.

OBJECTIVES: To compare all-cause mortality in patients with mitral annulus calcification (MAC) and severe mitral valve dysfunction (MVD) who received standard mitral intervention versus no intervention. BACKGROUND: Patients with MAC often have high surgical risk due to advanced age, comorbidities, and technical challenges related to calcium. The impact of a mitral intervention on outcomes of patients with MAC and severe MVD is not well known. METHODS: Retrospective review of patients with MAC by transthoracic echocardiography (TTE) in 2015 at a single institution. Patients with severe mitral stenosis (MS) or regurgitation (MR) were analyzed and stratified into two groups: surgical or transcatheter intervention performed <1 year after the index TTE, and no or later intervention. The primary endpoint was all-cause mortality. RESULTS: Of 5502 patients with MAC, 357 had severe MVD (MS = 27%, MR = 73%). Of those, 108 underwent mitral intervention (surgery = 87; transcatheter = 21). They were younger (73 ± 11 vs. 76 ± 11 years, p < 0.01) and less frequently had cardiovascular diseases compared with no-intervention. Frequency in women was similar (45% vs. 50%, p = 0.44). During median follow-up of 3.2 years, the intervention group had higher estimated survival than those without intervention (80% vs. 72% at 1 year and 55% vs. 35% at 4 year, p < 0.01). Adjusted for age, eGFR, LVEF < 50%, and pulmonary hypertension, mitral intervention was an independent predictor of lower mortality (hazard ratio = 0.66, 95% confidence interval 0.43-0.99, p = 0.046). CONCLUSION: Patients with MAC and severe MVD who underwent mitral intervention <1 year from index TTE had lower mortality than those without intervention. Mitral intervention was independently associated with lower mortality.

Impact of aortic valve replacement for severe aortic stenosis on organic and functional mitral regurgitation.

AIMS: Concurrent mitral regurgitation (MR) influences treatment considerations in patients with severe aortic stenosis (sAS). Limited information exists regarding haemodynamic effects of sAS on MR severity and outcome of these patients. We assessed the impact of aortic valve replacement (AVR) on MR according to mechanism in patients with sAS and MR. METHODS AND RESULTS: In patients with sAS who received surgical or transcatheter AVR from 2008 to 2017, those with effective mitral regurgitant orifice area (ERO) ≥ 10 mm2 prior to AVR were evaluated. The change in MR after AVR was considered significant when there was at least one grade difference. We compared the all-cause mortality of patients with and without improvement in MR. Of 234 patients with sAS and MR (age 80 ± 9 years, 52% male, ERO 19 ± 7 mm2 ), organic and functional MR were present in 166 (71%) and 68 (29%), respectively. MR improved in 136 (58%); improvement occurred with similar frequency in organic versus functional MR (59% and 57%, P = 0.88). Associated determinants were absence of atrial fibrillation in organic MR [odds ratio (OR) 2.09, 95% confidence interval (CI) 1.00-4.37; P = 0.049] and indexed aortic valve area (iAVA) ≤ 0.40 cm2 in functional MR (OR 3.28, 95% CI 1.13-9.47; P = 0.028). In the overall cohort, mitral annulus diameter < 3 cm (OR 1.74, 95% CI 1.02-2.97; P = 0.041) and QRS duration < 115 ms (OR 1.73, 95% CI 1.00-2.98; P = 0.049) were independently associated with improvement in MR. During median follow-up of 3.5 years, lack of improvement in MR was not associated with higher mortality in the overall cohort of patients with ERO ≥ 20 mm2 [adjusted hazard ratio (HR) 1.71, 95% CI 0.90-3.27; P = 0.10, adjusted for age, New York Heart Association III or IV, diabetes, and creatinine ≥ 2.0 mg/dL]. Lack of improvement in organic MR was associated with higher mortality (adjusted HR 3.36, 95% CI 1.40-8.05; P < 0.01). In patients with functional MR, change in MR was not associated with mortality (HR 1.24, 95% CI 0.44-3.47; P = 0.68). CONCLUSIONS: In nearly 60% of patients with sAS and MR, MR improved after AVR, even in the majority of patients with organic MR. Absence of atrial fibrillation in organic MR, iAVA ≤ 0.40 cm2 in functional MR, and mitral annulus diameter < 3 cm and QRS duration < 115 ms in the overall population were associated with MR improvement. Post-operative improvement in organic MR was associated with better survival.

Clinical Experience of Percutaneous Patent Foramen Ovale Closure Using the Amplatzer PFO Occluder in Japanese Patients to Prevent the Recurrence of Cryptogenic Stroke.

Objective Percutaneous patent foramen ovale (PFO) closure is a procedure widely used to prevent recurrence of cryptogenic stroke. Since December 2019, the Amplatzer PFO occluder device has been available in Japan through medical insurance. However, data on the clinical experience with this device are lacking, as it has been approved for use in only a limited number of institutions. This study assessed the clinical data of Japanese patients who underwent PFO closure using the Amplatzer PFO occluder. Methods Between February and October 2020, 14 patients at our institution underwent percutaneous PFO closure using the Amplatzer PFO occluder. The procedural characteristics, safety, and adverse events were retrospectively analyzed. Results The mean age of the patients was 52.4±13.3 years old, and 57.1% were women. Deep vein thrombosis was revealed in 2 patients, and the risk of paradoxical embolism score was 6.6±1.2 points. The PFO height and tunnel length were 2.3±1.4 mm and 11.5±4.1 mm. All patients had a PFO during the bubble study of grade >3 at the Valsalva maneuver on transthoracic echocardiography or transesophageal echocardiography. The average diameter of the PFO measured using a stiff guidewire and sizing balloon was 5.1±1.3 and 7.9±2.3 mm, respectively. Almost all cases (92.9%) were performed with a 25-mm device and without significant complications within approximately 1 hour. Conclusion Percutaneous closure using Amplatzer PFO occluder is a safe procedure for Japanese patients. However, further investigations with a larger sample and longer follow-up are needed to confirm this result.

A Novel Assessment Using Projected Transmitral Gradient Improves Diagnostic Yield of Doppler Hemodynamics in Rheumatic and Calcific Mitral Stenosis.

OBJECTIVES: The aims of this study were to: 1) develop a formula for projected transmitral gradient (TMG), expected gradient under normal heart rate (HR), and stroke volume (SV); and 2) assess the prognostic value of projected TMG. BACKGROUND: In mitral stenosis (MS), TMG is highly dependent on hemodynamics, often leading to discordance between TMG and mitral valve area. METHODS: All patients with suspected MS based on echocardiography from 2001 to 2017 were analyzed. Data were randomly split (2:1); projected TMG was modeled in the derivation cohort, then tested in the validation cohort. The composite endpoint was death or mitral valve intervention. RESULTS: Of 4,973 patients with suspected MS, severe and moderate MS, defined as mitral valve area ≤1.5 and >1.5 to 2.0 cm2, were present in 437 (9%) and 936 (19%), respectively. In the derivation cohort (n = 3,315; age 73 ± 12 years; 34% male), corresponding gradients were TMG ≥6 and 4 to <6 mm Hg, respectively, under normal hemodynamics. Based on the impact of hemodynamics on TMG, the formula was projected TMG = TMG - 0.07 (HR - 70) - 0.03 (SV - 97) in men and projected TMG = TMG - 0.08 (HR - 72) - 0.04 (SV - 84) in women. In the validation cohort (n = 1,658), projected TMG had better agreement with MS severity than TMG (kappa 0.61 vs. 0.28). Among 281 patients with TMG ≥6 mm Hg, projected TMG ≥6 mm Hg, present in 171 patients (61%), was associated with higher probability of the endpoint versus projected TMG <6 mm Hg (adjusted hazard ratio: 1.8; 95% confidence interval: 1.2 to 2.6; p < 0.01). CONCLUSIONS: The novel concept of projected TMG, constructed using the observed impact of HR and SV on TMG, significantly improved the concordance of gradient and valve area in MS and provided better risk stratification than TMG.