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.

Prognostic value of right atrial function in patients with significant tricuspid regurgitation.

AIMS: Although right ventricular (RV) dysfunction is associated with adverse outcomes in tricuspid regurgitation (TR), the potential role of right atrial (RA) function is unknown. We aimed to investigate the relationship between RA function and clinical outcomes in patients with significant TR. METHODS: This retrospective study included 169 outpatients with moderate or severe TR due to left-sided heart diseases who underwent transthoracic echocardiography between June 2020 and April 2023 (average age, 75 ± 10 years; male, 40%). Patients with atrial fibrillation were excluded from this study due to the inaccuracy of the evaluation using 2D speckle-tracking echocardiography. RA function was compared between patients with and without events, which were defined as all-cause mortality or hospitalization due to heart failure. RA function was calculated as RA global longitudinal strain (RAGLS) with the 2D speckle-tracking echocardiography. RESULTS: During a median follow-up of 13 months, 19 patients had events (all-cause mortality: 14 cases, hospitalization due to heart failure: 5 cases). RAGLS was lower in patients with events than in those without events (13% ± 10% vs. 18% ± 9%, P = 0.02). When the patients were categorized into two groups [low RAGLS ≤ 16.2% vs. high RAGLS > 16.2%, high RA volume index (RAVI) ≥ 50 mL/m2 vs. low RAVI < 50 mL/m2], Kaplan-Meier curves showed that patients with low RAGLS had higher event rates than those with high RAGLS (log-rank test, P = 0.003). Patients with high RAVI had higher event rates than those with low RAVI (log-rank test, P < 0.001). In the multivariate Cox regression analysis, low RAGLS (≤16.2%) was significantly associated with events in a model that included RV dysfunction (RV fractional area change ≤ 35%) or high RAVI (≥50 mL/m2) (hazard ratio: 4.55, 95% confidence interval: 1.51-13.71, P < 0.01; hazard ratio: 4.57, 95% confidence interval: 1.52-13.79, P < 0.01, respectively). CONCLUSIONS: RAGLS is associated with all-cause mortality and hospitalization due to heart failure in patients with significant TR. Our results suggest that RA function is a sensitive marker for identifying the risk stratification of significant TR.

Impact of extracardiac sarcoidosis on clinical outcomes in patients with cardiac sarcoidosis: Importance of continued screening for cardiac involvement.

BACKGROUND: The prognostic impact of extracardiac sarcoidosis remains unknown in cardiac sarcoidosis (CS). We aimed to evaluate the influence of extracardiac sarcoidosis on clinical outcomes and the effect of continued outpatient visits for screening of cardiac involvement. METHODS: Ninety-nine patients with CS were divided into two groups: patients with systemic CS who had prior extracardiac sarcoidosis, patients with isolated CS who had no prior extracardiac sarcoidosis. Patients with systemic CS were divided according to the continuation of outpatient visits. The endpoint was cardiac death, fatal ventricular arrhythmia, or hospitalization for heart failure. RESULTS: At the time of diagnosing CS, patients with isolated CS had a higher prevalence of high-grade atrioventricular block or fatal ventricular arrhythmia, and left ventricular contractile dysfunction than those with systemic CS. Over a median follow-up of 42 months, cardiac events occurred in 19 (37%) of 52 patients with systemic CS and in 27 (57%) of 47 patients with isolated CS. The event-free survival rate was worse in patients with isolated CS than in those with systemic CS. Cox proportional hazard analysis showed that the absence of prior extracardiac sarcoidosis was an independent predictor of adverse outcomes. Patients with systemic CS who ceased outpatient visits had a lower left ventricular ejection fraction with severe heart failure symptoms and a worse event-free survival rate than those who continued outpatient visits. CONCLUSIONS: The presence of extracardiac sarcoidosis is associated with clinical outcomes. The cessation of screening for cardiac involvement after diagnosing extracardiac sarcoidosis is associated with adverse outcomes.

Long-term outcome and cardiac function after anatomic repair of congenitally corrected transposition.

OBJECTIVES: There is limited information on long-term outcomes and trajectories of ventricular and valvular functions in patients with congenitally corrected transposition of the great arteries after anatomic repair according to the operative strategy with a median follow-up period of more than 10 years. METHODS: Twenty-nine patients who underwent anatomic repair in Okayama University Hospital between January 1994 and December 2020 were reviewed. Outcomes were compared between patients who underwent a double switch operation (DS group) and patients with an atrial switch with a Rastelli operation (Rastelli-Senning/Mustard group). RESULTS: Fifteen (52%) were in the DS group and 14 (48%) were in the Rastelli-Senning/Mustard group. The median follow-up period after anatomic repair was 12.7 (interquartile range 4.2-18.8) years. There were 3 (10%) early deaths and 3 (10%) late deaths. Survival rates for the entire cohort at 10 and 20 years were 86% and 71%, respectively, and were not different between the 2 groups. Using competing risk analysis, risks of heart failure, cardiac rhythm device implantation and atrial arrhythmia showed no significant differences between the 2 groups, whereas risk of reoperation was higher in the Rastelli-Senning/Mustard group than that in the DS group. Four patients after a DS operation and 1 patient after a Rastelli technique developed more than moderate aortic regurgitation. CONCLUSIONS: During a median follow-up period of more than 10 years, mortality rate and ventricular and valvular functions after anatomic repair were acceptable, though the incidences of late complications were relatively high, especially in the Rastelli-Senning/Mustard group.

Association Between Aortic Valve Calcification and Severity of Concomitant Aortic Regurgitation in Patients With Severe Aortic Stenosis.

BACKGROUND: Patients with severe aortic stenosis (AS) frequently have concomitant aortic regurgitation (AR), but the association between aortic valvular calcification (AVC) and the severity of AR remains unclear.Methods and Results: We retrospectively reviewed patients with severe AS who underwent transthoracic echocardiography and multidetector computed tomography (MDCT) within 1 month. The patients were divided into 3 groups according to the degree of concomitant AR. The association between AVC and the severity of concomitant AR was assessed in patients with severe AS. The study population consisted of 95 patients: 43 men and 52 women with a mean age of 82±7 years. Of the 95 patients with severe AS, 27 had no or trivial AR, 53 had mild AR, and 15 had moderate AR. The AVC score (AVCS) and AVC volume (AVCV) significantly increased as the severity of concomitant AR increased (P=0.014 for both), and similar findings were obtained for the AVCS and AVCV indexes (P=0.004 for both). CONCLUSIONS: The severity of AR correlated with AVCS and AVCV measured by MDCT in patients with severe AS. AVC may cause concomitant AR, leading to worsening of disease condition.

Effects of Agalsidase Alfa Enzyme Replacement Therapy on Left Ventricular Hypertrophy on Electrocardiogram in a Female Patient with Fabry Disease.

Fabry disease is an X-linked lysosomal storage disorder caused by defective enzyme activity of α-galactosidase A and treated with enzyme replacement therapy (ERT) with recombinant α-galactosidase. ERT reduces left ventricular mass assessed by echocardiography or magnetic resonance imaging. However, electrocardiogram changes during ERT have not been fully elucidated. In the present case, ERT with agalsidase alfa for 4 years decreased QRS voltage and negative T depth along with a reduction of left ventricular mass and wall thickness and improvement of symptoms in a female patient with Fabry disease. Long-term observation of electrocardiogram changes might be useful for determining the efficacy of ERT in this case.

Papillary-Ventricular Complex Tugging for Ischemic/Functional Mitral Regurgitation.

Surgical restoration of subvalvular geometry is very important to prevent recurrence of ischemic/functional mitral regurgitation. We evaluated an approach to the radical repair of left ventricular (LV) remodeling for three different cases with responsible coronary lesions. Leaflet tethering was corrected by tugging of the papillary-ventricular complex, which consists of the base of papillary muscles and posterior LV wall. The main lesion of the postinfarction scar was concomitantly excluded. Restoration of LV remodeling diminished mitral regurgitation with minimal leaflet tethering and improved systolic LV function. This technique may be an aggressive and encouraged approach for patients with ischemic/functional mitral regurgitation.

Prognosis and Outcomes of Clinically Diagnosed Cardiac Sarcoidosis Without Positive Endomyocardial Biopsy Findings.

Background: Diagnosis of cardiac sarcoidosis (CS) is sometimes difficult due to a low positive rate of epithelioid granulomas by endomyocardial biopsy (EMB). Accordingly, Japanese guidelines can allow the CS diagnosis using clinical data alone without EMB results (clinical CS) since 2006. However, little is known about prognosis and outcome of clinical CS. Objectives: Purpose of this study was to analyze the prognosis, outcomes, and response to corticosteroid of clinical CS using large-scale cohort survey. Methods: Overall, 422 CS patients (mean age 60 ± 13 years, 68% female, median follow-up period of 5 years), including 345 clinical CS and 77 EMB-positive patients, histologically diagnosed CS (histological CS) by Japanese guidelines, were enrolled and examined. Results: Clinical profile (age, sex, initial cardiac arrhythmias, and abnormal uptake of gallium-67 scintigraphy or 18F-fluorodeoxyglucose positron emission tomography in heart) was similar in both groups. Although clinical CS had better prognosis (P = 0.018) and outcome (all-cause death, appropriate defibrillator therapy, and heart transplantation; P = 0.008), multivariate Cox hazard analysis revealed that left ventricular ejection fraction (LVEF) and sustained ventricular tachycardia history were independently associated with outcome (P < 0.001 and P = 0.002, respectively), but not with the diagnosed CS category. Moreover, similar LVEF recovery after corticosteroid was observed in both groups with low LVEF (≤35%) at the 1-year follow-up period (P < 0.001). Conclusions: In clinical CS according to the Japanese guideline, prophylactic implantable-cardioverter-defibrillator and immunosuppressive therapy are important in patients with low LVEF or ventricular tachycardia history, similar to histological CS.

Percutaneous closure of residual atrial septal defect after surgical closure.

Residual atrial septal defect (ASD) after surgical closure is rare, but some cases are seen during follow-up period. Redo surgery for residual ASD is often declined, while percutaneous closure can be acceptable. However, the indication of percutaneous closure for residual ASD has not been established. We reviewed our experience with percutaneous closure of residual ASD using medical and procedural records. Between 2006 and 2018, residual ASD was seen in seven patients. The median age of patients was 66 years (range 50-81 years), and the median period after surgical closure of ASD was 39 years (range 13-48 years). All patients had symptoms related to ASD. Percutaneous closure of residual ASD was successfully performed in all seven patients. No residual shunts were detected during the median follow-up period of 4.2 years (range 0.5-11 years) after percutaneous closure. Based on transesophageal echocardiographic findings and operative records for surgical closure, we considered two mechanisms causing residual ASD, such as the tear of surgical suture line and the overlooking of defect during surgical closure. Percutaneous closure of residual ASD was safely performed without any complications, suggesting that percutaneous is an effective therapeutic strategy for residual ASD after surgical closure.

Brachial intima-media thickness is associated with coronary artery atherosclerosis in patients with diabetes mellitus.

Coronary artery calcification (CAC) as measured by computed tomography is a strong predictor of coronary artery disease. The brachial intima-media thickness (IMT) was recently reported to be associated with cardiovascular risk factors. This study investigated the association of brachial IMT with CAC, which is a marker of coronary artery atherosclerosis, in patients with diabetes. We enrolled 292 patients with diabetes (mean age, 65 ± 12 years; 59% men) who underwent both endothelial function testing and computed tomography for risk assessment of coronary artery disease. Flow-mediated dilation (FMD) and IMT in the brachial artery were measured with a specialized machine. FMD was lower and brachial IMT was thicker in patients with than without CAC. The CAC score was significantly correlated with both brachial IMT and FMD, while the multivariate logistic analysis demonstrated that brachial IMT (> 0.32 mm) but not FMD (< 5.1%) was significantly associated with the presence of CAC (odds ratio, 2.03; 95% confidence interval, 1.10-3.77; p = 0.02). The receiver operating characteristic curve analysis showed that the area under the curve for discriminating patients with CAC was 0.67 for IMT (p < 0.001) and 0.62 for FMD (p < 0.001). When patients were classified into four groups based on brachial IMT and FMD, the CAC score was higher in patients with thicker brachial IMT and lower FMD than in patients of the other groups (p < 0.001). Measurement of brachial IMT could be useful for the risk assessment of patients with diabetes.

Japanese Antibacterial Drug Management for Cardiac Sarcoidosis (J-ACNES): A multicenter, open-label, randomized, controlled study.

BACKGROUND: Cardiac sarcoidosis (CS) is a noncaseating granulomatous disease of unknown etiology. Lifelong immunosuppressive therapy, most frequently using corticosteroids, is a standard therapy to control hypersensitivity of immune reactions and prevent inflammation. However, it sometimes causes various systemic adverse effects and requires dose escalation. Thus, additional therapy may be required for the treatment of this disease. Recently, Propionibacterium acnes (P. acnes) was reported as one of the etiologic agents of CS, indicating that antibacterial drugs (ABD) may be effective for the treatment of CS. The objective of this study was to investigate the effect of ABD treatment, in addition to standard corticosteroid therapy, in patients with CS. METHODS: The Japanese Antibacterial Drug Management for Cardiac Sarcoidosis (J-ACNES) trial was designed as a prospective, multicenter, randomized, open-label, controlled clinical trial. The patients will be randomized to receive either standard corticosteroid therapy plus ABD therapy (ABD group) or standard corticosteroid therapy (standard group). The primary endpoint is change in the total standardized uptake value at 6 months vs baseline using fluorine-18 fluorodeoxyglucose positron emission tomography and computed tomography. Secondary endpoints include efficacy, prognosis, and safety. RESULTS: The results of this study are currently under investigation. CONCLUSION: The J-ACNES trial will be the first prospective study assessing the clinical benefit and safety of ABD therapy, in addition to corticosteroid treatment, in patients with CS. Our findings may improve treatment of patients with CS, as additional ABD therapy reduces recurrence of inflammation and elucidates the mechanism of sarcoidosis.

Outcomes in patients with high-degree atrioventricular block as the initial manifestation of cardiac sarcoidosis.

Although high-degree atrioventricular block (AVB) is a common initial manifestation of cardiac sarcoidosis, little is known about the outcomes. The aim of this study was to assess outcomes in patients with AVB as an initial manifestation of cardiac sarcoidosis compared with those in patients with ventricular tachyarrhythmia (VT) and/or heart failure (HF). Fifty-three consecutive patients with cardiac sarcoidosis, who had high-degree AVB (n = 22) or VT and/or HF (n = 31), were enrolled. The end point was defined as major adverse cardiac events, including cardiac death, ventricular fibrillation, sustained VT, and hospitalization for HF. Over a median follow-up period of 34 months, the outcomes of major adverse cardiac events were better in patients with high-degree AVB than in those with VT and/or HF (log-rank test, p = 0.046). However, this difference was due mainly to HF hospitalization. The outcomes of fatal cardiac events, including cardiac death, ventricular fibrillation, and sustained VT, were comparable between the 2 groups (log-rank test, p = 0.877). The fatal cardiac events in patients with high-degree AVB were not associated with the initiation of steroid treatment or left ventricular dysfunction. In conclusion, the outcomes of major adverse cardiac events are better in patients with high-degree AVB than in those with VT and/or HF. However, patients with high-degree AVB have a high rate of fatal cardiac events, similar to those with VT and/or HF. An indication for an implantable cardioverter-defibrillator, but not a pacemaker system, can be considered in patients with cardiac sarcoidosis manifested by high-degree AVB.

Three-dimensional echocardiography guided closure of complex multiple atrial septal defects.

Transcatheter closure of complex multiple atrial septal defects (ASDs) remains a challenge. We describe our clinical experience with staged device deployment in a patient with multiple ASDs using four Amplatzer septal occluder devices. Three-dimensional transesophageal echocardiography imaging contributed not only to the therapeutic guidance of successful device deployment but also to the decision making for the staged device delivery approach in a case of morphologically complex multiple ASDs.

Serum N-3 polyunsaturated fatty acid levels correlate with the extent of coronary plaques and calcifications in patients with acute myocardial infarction.

BACKGROUND: The relationship between serum fatty acid levels and the extent of coronary plaques and calcification was examined in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: The serum levels of the n-3 polyunsaturated fatty acids (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) and the n-6 polyunsaturated fatty acids (arachidonic acid (AA) and dihomo-gamma-linolenic acid (DGLA)) were determined using gas chromatography on admission of 95 consecutive patients with their first AMI and 17 controls. Using multidetector-row computed tomography, soft plaques and calcification lesions were scored according to the extent of coronary involvement. Serum logarithmic transformed (log) EPA and logDHA levels were inversely correlated with soft plaque scores (r=-0.546, p<0.0001 and r=-0.377, p<0.0001, respectively). Serum logAA and logDGLA levels were not significantly correlated with soft plaque scores. Serum logEPA and logDHA levels were significantly, but weakly, correlated with calcification scores. Multivariate analysis with clinical characteristics and risk factors selected serum n-3 polyunsaturated fatty acid levels as independent factors associated with the extent of coronary soft plaques. CONCLUSION: The present study demonstrates a significant correlation between serum n-3 polyunsaturated fatty acid levels and the extent of coronary soft plaques and calcification in AMI patients.