Differences in clinical and echocardiographic features and outcomes between atrial functional mitral regurgitation patients with and without posterior mitral leaflet bending.

BACKGROUND: Posterior mitral leaflet (PML) bending is a cause of atrial functional mitral regurgitation (AFMR). We aimed to investigate differences in clinical and echocardiographic features and outcomes between AFMR patients with and without PML bending. METHODS: We retrospectively examined 118 AFMR patients with atrial fibrillation (AF), mild or greater MR without degenerative mitral valve changes, and left ventricular ejection fraction ≥50 %. Patients were classified by the presence of PML bending: PML bending (n=24) and no PML bending (n=94). PML bending was defined as PML-to-anterior mitral leaflet angle ratio ≥3.1 calculated using receiver operating characteristics analysis for eccentric MR jet toward left atrial posterior wall. The study endpoint was a composite of cardiac death, admission for heart failure, and mitral valve surgery. RESULTS: Overall, a total of 88 patients (75 %) had mild MR. There were no between-group differences in clinical and echocardiographic characteristics including AF duration and cardiac cavities size except for the length of inward bending of the left ventricular posterobasal wall and the mitral annular area. The 36-month event-free survival for the composite endpoint was significantly lower in the PML bending group (63 % vs. 78 %; Log-rank p=0.047). In multivariate analysis, PML bending was also associated with the composite outcome. CONCLUSIONS: AFMR patients with PML bending may have worse outcomes than those without PML bending despite similar clinical features.

Forty-year survival after Glenn procedure without Fontan procedure in patients with single ventricle.

OBJECTIVES: There are no data on long-term outcomes beyond 30 years after the Glenn procedure without the subsequent Fontan procedure in patients with single-ventricle physiology. Hence, this study aimed to clarify the very long-term outcomes of these patients. METHODS: This single-centre, retrospective cohort study investigated the clinical outcomes of patients with single-ventricle physiology who underwent the Glenn procedure between 1970 and 1999. Those who underwent the subsequent Fontan procedure were excluded. The primary outcome was all-cause death. The secondary outcome was a composite of all-cause death, arrhythmic events, neurological events or infective endocarditis. The prognostic factors associated with the long-term outcomes were also evaluated. RESULTS: In total, 36 patients were enrolled (median age at Glenn procedure: 6.2 years, 56% male). During a median follow-up of 17.6 years (interquartile range: 6.1-33.4), 21 patients died and 29 experienced the composite outcome. The 20-, 30- and 40-year overall survival after the Glenn procedure was 51.2%, 44.4% and 40.3%, respectively. The 20-, 30- and 40-year event-free survival was 36.0%, 25.5% and 14.5%, respectively. Patients with dominant left ventricular morphology had better overall survival than those with dominant right ventricular morphology (hazard ratio: 0.24, 95% confidence interval: 0.08-0.76, P = 0.014). None of the patients had liver cirrhosis but 1 had protein-losing enteropathy. CONCLUSIONS: The 40-year overall survival after the Glenn procedure without the subsequent Fontan procedure in patients with single-ventricle physiology was 40.3%. Dominant left ventricular morphology may be associated with better long-term overall survival than dominant right ventricular morphology.

Status of adult outpatients with congenital heart disease in Japan: The Japanese Network of Cardiovascular Departments for Adult Congenital Heart Disease Registry.

BACKGROUND: The Japanese Network of Cardiovascular Departments for Adult Congenital Heart Disease (JNCVD-ACHD) was founded in 2011 for the lifelong care of adult patients with congenital heart disease (ACHD patients). This network maintains the first Japanese ACHD registry. METHODS AND RESULTS: From 2011 to 2019, the JNCVD-ACHD registered 54 institutions providing specialized care for ACHD patients in 32 of the 47 prefectures in Japan. The registry collected data on the disease profile for 24,048 patients from 50 institutions and the patient characteristics for 9743 patients from 24 institutions. The most common ACHDs were atrial septal defect (20.5 %), ventricular septal defect (20.5 %), tetralogy of Fallot (12.9 %), and univentricular heart (UVH)/single ventricle (SV; 6.6 %). ACHD patients without biventricular repair accounted for 37.0 % of the population. Also examined were the serious anatomical and/or pathophysiological disorders such as pulmonary arterial hypertension (3.0 %) including Eisenmenger syndrome (1.2 %), systemic right ventricle under biventricular circulation (sRV-2VC; 2.8 %), and Fontan physiology (6.0 %). The sRV-2VC cases comprised congenitally corrected transposition of the great arteries without anatomical repair (61.9 %) and transposition of the great arteries with atrial switching surgery (38.1 %). The primary etiology (86.4 %) for Fontan physiology was UVH/SV. In addition, developmental/chromosomal/genetic disorders were heterotaxy syndromes (asplenia, 0.9 %; polysplenia, 0.7 %), trisomy 21 (4.0 %), 22q11.2 deletion (0.9 %), Turner syndrome (0.2 %), and Marfan syndrome (1.1 %). CONCLUSIONS: Although the specific management of ACHD has systematically progressed in Japan, this approach is still evolving. For ideal ACHD care, the prospective goals for the JNCVD-ACHD are to create local networks and provide a resource for multicenter clinical trials to support evidence-based practice.

Rationale, Design, and Baseline Characteristics of the CURRENT AS Registry-2.

BACKGROUND: There is scarce data evaluating the current practice pattern and clinical outcomes for patients with severe aortic stenosis (AS), including both those who underwent surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) and those who were managed conservatively in the TAVI era.Methods and Results: The Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis (CURRENT AS) Registry-2 is a prospective, physician-initiated, multicenter registry enrolling consecutive patients who were diagnosed with severe AS between April 2018 and December 2020 among 21 centers in Japan. The rationale for the prospective enrollment was to standardize the assessment of symptomatic status, echocardiographic evaluation, and other recommended diagnostic examinations such as computed tomography and measurement of B-type natriuretic peptide. Moreover, the schedule of clinical and echocardiographic follow up was prospectively defined and strongly recommended for patients who were managed conservatively. The entire study population consisted of 3,394 patients (mean age: 81.6 years and women: 60%). Etiology of AS was degenerative in 90% of patients. AS-related symptoms were present in 60% of patients; these were most often heart failure symptoms. The prevalence of high- and low-gradient AS was 58% and 42%, respectively, with classical and paradoxical low-flow low-gradient AS in 4.6% and 6.7%, respectively. CONCLUSIONS: The CURRENT AS Registry-2 might be large and meticulous enough to determine the appropriate timing of intervention for patients with severe AS in contemporary clinical practice.

Lower In-Hospital Mortality With Beta-Blocker Use at Admission in Patients With Acute Decompensated Heart Failure.

Background It remains unclear whether beta-blocker use at hospital admission is associated with better in-hospital outcomes in patients with acute decompensated heart failure. Methods and Results We evaluated the factors independently associated with beta-blocker use at admission, and the effect of beta-blocker use at admission on in-hospital mortality in 3817 patients with acute decompensated heart failure enrolled in the Kyoto Congestive Heart Failure registry. There were 1512 patients (39.7%) receiving, and 2305 patients (60.3%) not receiving beta-blockers at admission for the index acute decompensated heart failure hospitalization. Factors independently associated with beta-blocker use at admission were previous heart failure hospitalization, history of myocardial infarction, atrial fibrillation, cardiomyopathy, and estimated glomerular filtration rate <30 mL/min per 1.73 m2. Factors independently associated with no beta-blocker use were asthma, chronic obstructive pulmonary disease, lower body mass index, dementia, older age, and left ventricular ejection fraction <40%. Patients on beta-blockers had significantly lower in-hospital mortality rates (4.4% versus 7.6%, P<0.001). Even after adjusting for confounders, beta-blocker use at admission remained significantly associated with lower in-hospital mortality risk (odds ratio, 0.41; 95% CI, 0.27-0.60, P<0.001). Furthermore, beta-blocker use at admission was significantly associated with both lower cardiovascular mortality risk and lower noncardiovascular mortality risk. The association of beta-blocker use with lower in-hospital mortality risk was relatively more prominent in patients receiving high dose beta-blockers. The magnitude of the effect of beta-blocker use was greater in patients with previous heart failure hospitalization than in patients without (P for interaction 0.04). Conclusions Beta-blocker use at admission was associated with lower in-hospital mortality in patients with acute decompensated heart failure. Registration URL: https://www.upload.umin.ac.jp/; Unique identifier: UMIN000015238.

Successful Transcatheter Aortic Valve Implantation in a Patient with Radiation-induced Aortic Stenosis for Mediastinal Hodgkin Lymphoma.

Aortic stenosis (AS), a late complication of thoracic radiation therapy for chest lesions, is often coincident with porcelain aorta or hostile thorax. We herein report a 59-year-old man with a history of mediastinal Hodgkin lymphoma treated with radiation therapy but later presenting with heart failure caused by severe AS. Severe calcification in the mediastinum and around the ascending aorta made it difficult to perform surgical aortic valve replacement. The patient therefore underwent transcatheter aortic valve implantation (TAVI). It is important to recognize radiation-induced AS early, now that TAVI is a well-established treatment required by increasing numbers of successfully treated cancer patients.

Longitudinal change in postoperative right ventricular systolic function in patients undergoing surgery for isolated tricuspid regurgitation.

Right ventricular (RV) dysfunction is an indication for tricuspid valve (TV) surgery in patients with severe isolated tricuspid regurgitation (TR). Postoperative RV dysfunction is associated with poor outcome; however, the longitudinal changes in RV function before and after surgery have not been established. We retrospectively analyzed 24 patients who underwent TV surgery for isolated severe TR. For assessing RV systolic function, we measured the RV fractional area change (RVFAC) at baseline, and 1 (immediate) and 4-20 (late) months after surgery. We divided patients into 2 groups according to the RVFAC late after surgery (<35%, post-op. reduced; and ≥35%, post-op. preserved). The mean RVFAC was significantly decreased immediately after surgery compared to baseline (41.5 ± 10.1% vs. 32.2 ± 9.6%; p < 0.001). The RVFAC reduction was still observed late after surgery (35.5 ± 7.4%; p = 0.002). Of 24 patients, 12 patients (50%) had preserved RV systolic function late after surgery. Although there was no significant difference in the preoperative RVFAC between the 2 groups, the preoperative RV end-systolic area (RVESA) /body surface area (BSA) was significantly less in the post-op. preserved RV systolic function group (13.8 ± 4.3 cm2/m2 vs. 8.6 ± 2.6 cm2/m2; p = 0.001). The optimal cut-off value for the preoperative RVESA/BSA in detecting postoperative preserved RV systolic function was 10.8 cm2/m2 (AUC, 0.85; sensitivity, 91.7%; and specificity, 75.0%). In patients undergoing surgery for isolated severe TR, the RVFAC was significantly decreased immediately after surgery and the reduction continued late after surgery. The preoperative RVESA/BSA might be helpful to predict preserved RV function after surgery.

Elective Non-Cardiac Surgery in Patients With Severe Aortic Stenosis　- Observations From the CURRENT AS Registry.

BACKGROUND: Patients with severe aortic stenosis (AS) might be at high risk for adverse cardiovascular events at the time of non-cardiac surgery.Methods and Results:The current study population included 348 patients who underwent elective non-cardiac surgery under general or spinal anesthesia during the follow up of 3,815 patients in the CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry. There were 187 patients with untreated severe AS at time of surgery (untreated severe AS group) and 161 patients who had undergone aortic valve replacement (AVR) before surgery (prior AVR group), including 23 patients with prophylactic AVR. The primary outcome measure was 30-day mortality after non-cardiac surgery. At 30 days after non-cardiac surgery, 8 patients (4.3%) died in the untreated severe AS group, while no patients died in the prior AVR group (P=0.008). The causes of death were cardiovascular in 6 out of 8 patients. Mortality at 30 days was higher in untreated severe AS patients with AS-related symptoms before surgery than in those without AS-related symptoms (7.2% vs. 3.1%). Higher surgical risk estimates of the non-cardiac surgery incrementally increased the risk of 30-day mortality in patients with untreated severe AS, though the difference was not statistically significant (low-risk: 0%, intermediate-risk: 4.3%, and high-risk: 6.6 %, P=0.46). CONCLUSIONS: Symptomatic and asymptomatic severe AS might be associated with higher risk of 30-day mortality if untreated before elective intermediate- and high-risk non-cardiac surgery, while no patient with prior AVR died after elective non-cardiac surgery.

Decline in Left Ventricular Ejection Fraction During Follow-Up in Patients With Severe Aortic Stenosis.

OBJECTIVES: The aim of this study was to investigate the prognostic impact of the decline in left ventricular ejection fraction (LVEF) at 1-year follow-up in patients with severe aortic stenosis (AS) managed conservatively. BACKGROUND: No previous study has explored the association between LVEF decline during follow-up and clinical outcomes in patients with severe AS. METHODS: Among 3,815 patients with severe AS enrolled in the multicenter CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry in Japan, 839 conservatively managed patients who underwent echocardiography at 1-year follow-up were analyzed. The primary outcome measure was a composite of AS-related deaths and hospitalization for heart failure. RESULTS: There were 91 patients (10.8%) with >10% declines in LVEF and 748 patients (89.2%) without declines. Left ventricular dimensions and the prevalence of valve regurgitation and atrial fibrillation or flutter significantly increased in the group with declines in LVEF. The cumulative 3-year incidence of the primary outcome measure was significantly higher in the group with declines in LVEF than in the group with no decline (39.5% vs. 26.5%; p < 0.001). After adjusting for confounders, the excess risk of decline in LVEF over no decline for the primary outcome measure remained significant (hazard ratio: 1.98; 95% confidence interval: 1.29 to 3.06). When stratified by LVEF at index echocardiography (≥70%, 60% to 69%, and <60%), the risk of decline in LVEF on the primary outcome was consistently seen in all the subgroups, without any interaction (p = 0.77). CONCLUSIONS: Patients with severe AS with >10% declines in LVEF at 1 year after diagnosis had worse AS-related clinical outcomes than those without declines in LVEF under conservative management. (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis Registry; UMIN000012140).

Prognostic Impact of Aortic Valve Area in Conservatively Managed Patients With Asymptomatic Severe Aortic Stenosis With Preserved Ejection Fraction.

Background Data are scarce on the role of aortic valve area (AVA) to identify those patients with asymptomatic severe aortic stenosis (AS) who are at high risk of adverse events. We sought to explore the prognostic impact of AVA in asymptomatic patients with severe AS in a large observational database. Methods and Results Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the present study included 1309 conservatively managed asymptomatic patients with left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on AVA (group 1: AVA >0.80 cm2, N=645; group 2: 0.8 cm2 ≥AVA >0.6 cm2, N=465; and group 3: AVA ≤0.6 cm2, N=199). The prevalence of very severe AS patients (peak aortic jet velocity ≥5 m/s or mean aortic pressure gradient ≥60 mm Hg) was 2.0%, 5.8%, and 26.1% in groups 1, 2, and 3, respectively. The cumulative 5-year incidence of AVR was not different across the 3 groups (39.7%, 43.7%, and 39.9%; P=0.43). The cumulative 5-year incidence of the primary outcome measure (a composite of aortic valve-related death or heart failure hospitalization) was incrementally higher with decreasing AVA (24.1%, 29.1%, and 48.1%; P<0.001). After adjusting for confounders, the excess risk of group 3 and group 2 relative to group 1 for the primary outcome measure remained significant (hazard ratio, 2.21, 95% CI, 1.56-3.11, P<0.001; and hazard ratio, 1.34, 95% CI, 1.01-1.78, P=0.04, respectively). Conclusions AVA ≤0.6 cm2 would be a useful marker to identify those high-risk patients with asymptomatic severe AS, who might benefit from early AVR. Clinical Trial Registration URL: www.umin.ac.jp . Unique identifier: UMIN000012140.

B-type natriuretic peptide in patients with asymptomatic severe aortic stenosis.

OBJECTIVES: We sought to evaluate the prognostic impact of the B-type natriuretic peptide (BNP) levels in patients with asymptomatic severe aortic stenosis (AS), who were not referred for aortic valve replacement (AVR). METHODS: We used data from a Japanese multicentre registry, the Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis Registry, which enrolled 3815 consecutive patients with severe AS. Of those, 387 asymptomatic patients who were not referred for AVR without left ventricular dysfunction and very severe AS were subdivided into four groups based on their BNP levels (BNP<100 pg/mL, n=201; 100≤BNP<200 pg/mL, n=94; 200≤BNP<300 pg/mL, n=42 and BNP>300 pg/mL, n=50). RESULTS: The cumulative 5-year incidence of AS-related events (aortic valve-related death or heart failure hospitalisation) was incrementally higher with increasing BNP level (14.2%, 29.6%, 46.3% and 47.0%, p<0.001). After adjusting for confounders, the risk for AS-related events was incrementally greater with increasing BNP levels (HR: 1.97, 95% CI: 0.97 to 3.98, p=0.06; HR: 3.59, 95% CI: 1.55 to 8.32, p=0.03 and HR: 7.38, 95% CI: 3.21 to 16.9, p<0.001, respectively). Notably, asymptomatic patients with BNPlevels of <100 pg/mL had an event rate of only 2.1% at 1 year. CONCLUSIONS: Increased BNP level was associated with a higher risk for AS-related adverse events in patients with asymptomatic severe AS with normal left ventricular ejection fraction who were not referred for AVR. Asymptomatic patients with BNP levels of <100 pg/mL had relatively low event rate, who might be safely followed with watchful waiting strategy. TRAIL REGISTRATION NUMBER: UMIN000012140.

Impact of concomitant tricuspid regurgitation on long-term outcomes in severe aortic stenosis.

AIMS: Tricuspid regurgitation (TR) has been reported to be associated with worse survival in various heart diseases, but there are few data in aortic stenosis (AS). METHODS AND RESULTS: In the Contemporary Outcomes after Surgery and Medical Treatment in Patients with Severe Aortic Stenosis (CURRENT AS) Registry enrolling 3815 consecutive patients with severe AS, there were 628 patients with moderate or severe TR (TR group) and 3187 patients with no or mild TR (no TR group). The study patients were subdivided into the initial aortic valve replacement (AVR) stratum (n = 1197) and the conservative stratum (n = 2618) according to treatment strategy. The primary outcome measure was a composite of aortic valve-related death or hospitalization due to heart failure. The 5-year freedom rate from the primary outcome measure was significantly lower in the TR group than in the no TR group (49.1% vs. 67.3%, P < 0.001). Even after adjusting for confounders, the excess risk of TR relative to no TR for the primary outcome measure remained significant [hazard ratio (HR): 1.25, 95% confidence interval (CI): 1.06-1.48; P = 0.008]. The trend for the excess adjusted risk in the TR group was consistent in the initial AVR and the conservative strata (HR 1.55, 95% CI: 0.97-2.48; P = 0.07; HR 1.22, 95% CI: 1.02-1.46; P = 0.03, respectively). In the initial AVR stratum, the 5-year freedom rate from the primary outcome measure was not different between the two groups with (n = 56) or without (n = 91) concomitant tricuspid annuloplasty (61.5% vs. 72.1%, P = 0.48). CONCLUSION: The presence of clinically significant TR concomitant with severe AS is associated with a poor long-term outcome, regardless of the initial treatment strategy.

Early Surgery vs. Surgery After Watchful Waiting for Asymptomatic Severe Aortic Stenosis.

BACKGROUND: There is no large-scale study comparing postoperative mortality after aortic valve replacement (AVR) for asymptomatic severe aortic stenosis (AS) between initial treatment with AVR vs. eventual AVR after conservative management. Methods and Results: We analyzed data from a multicenter registry enrolling 3,815 consecutive patients with severe AS. Of 1,808 asymptomatic patients, 286 patients initially underwent AVR (initial AVR group), and 377 patients were initially managed conservatively and eventually underwent AVR (AVR after watchful waiting group). Mortality after AVR was compared between the 2 groups. Subgroup analysis according to peak aortic jet velocity (Vmax) at diagnosis was also conducted. There was no significant difference between the 2 groups in 5-year overall survival (OS; 86.0% vs. 84.1%, P=0.34) or cardiovascular death-free survival (DFS; 91.3% vs. 91.1%, P=0.61), but on subgroup analysis of patients with Vmax ≥4.5 m/s at diagnosis, the initial AVR group was superior to the AVR after watchful waiting group in both 5-year OS (88.4% vs. 70.6%, P=0.003) and cardiovascular DFS (91.9% vs. 81.7%, P=0.023). CONCLUSIONS: Asymptomatic severe AS patients who underwent AVR after watchful waiting had a postoperative survival rate similar to those who initially underwent AVR. In a subgroup of patients with Vmax ≥4.5 m/s at diagnosis, however, the AVR after watchful waiting group had worse postoperative survival rate than the initial AVR group.

Malignant disease as a comorbidity in patients with severe aortic stenosis: clinical presentation, outcomes, and management.

Aim: To investigate the effect of malignancy on the outcomes of patients with severe aortic stenosis (AS) and the management strategy for AS with malignancy. Methods and results: Using data of 3815 patients with severe AS in a retrospective multicentre registry [CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry], we compared 3-year clinical outcomes among three groups based on malignancy status: with malignancy currently under treatment including best supportive care (malignancy group), with a history of malignancy without any current treatment (past history group), or without history of malignancy (no malignancy group). Patients in the malignancy group (n = 124) were more often men and had higher prevalence of low body mass index, recurrence of malignancy, anaemia, and asymptomatic status, despite comparable surgical risks and echocardiographic parameters. The malignancy group or the past history group (n = 389) had significantly higher risk for all-cause death [hazard ratio (HR) 2.49, 95% CI (95% confidence interval) 1.98-3.14; HR 1.23, 95% CI 1.04-1.46] and for malignancy-related death (HR 16.2, 95% CI 10.64-24.54; HR 3.66, 95% CI 2.43-5.52) than that of the no malignancy group (n = 3302). The excess risk for aortic valve-related death was not observed in the malignancy group (HR 0.79, 95% CI 0.48-1.29) and was lower in the past history group (HR 0.72, 95% CI 0.53-0.96). In the malignancy group, the treatment strategy (surgery: n = 16, conservative management: n = 108) was determined based on the clinical status of AS or life expectancy. Conclusions: Malignancy had marked effect on all-cause death and malignancy-related death in patients with severe AS. History of malignancy also had a smaller but significant effect on mortality.

Relationship between left ventricular diastolic dysfunction and very late recurrences after multiple procedures for atrial fibrillation ablation.

Although very late recurrences (VLRs) (first recurrence >12 months after the last catheter ablation) of atrial fibrillation (AF) after multiple catheter ablation procedures are rare, it remains a critical issue. The risk factors for VLRs remain largely unclear. From December 2011 to April 2014, 253 patients underwent an initial catheter ablation. Of the 253 patients, 21 had AF recurrences within 1 year after the last catheter ablation. The study was conducted in the remaining 232 patients. Left ventricular diastolic dysfunction (LVDD) was assessed by echocardiography using composite categories with tissue Doppler imaging and left atrial volume measurements, i.e., a septal e' < 8 cm/s, lateral e' < 10 cm/s, and left atrium volume index (LAV/body surface area) (LAVI) ≥34 mL/m2. LVDD was observed in 40 patients. Sinus rhythm was preserved in 220 patients after multiple catheter procedures, and 12 had VLRs. The clinical factors possibly related to VLRs were examined, and a multivariate regression analysis showed that LVDD was the only independent risk factor for VLRs (hazard ratio: 10.31, 95% confidence interval: 2.78-38.18, P < 0.0001). LVDD at baseline is a risk factor for a VLR after multiple catheter ablation procedures for AF.

Causes of Death in Patients with Severe Aortic Stenosis: An Observational study.

Whether patients with severe aortic stenosis (AS) die because of AS-related causes is an important issue for the management of these patients. We used data from CURRENT AS registry, a Japanese multicenter registry, to assess the causes of death in severe AS patients and to identify the factors associated with non-cardiac mortality. We enrolled 3815 consecutive patients with a median follow-up of 1176 days; the 1449 overall deaths comprised 802 (55.3%) from cardiac and 647 (44.7%) from non-cardiac causes. Heart failure (HF) (25.7%) and sudden death (13.0%) caused the most cardiac deaths, whereas infection (13.0%) and malignancy (11.1%) were the main non-cardiac causes. According to treatment strategies, infection was the most common cause of non-cardiac death, followed by malignancy, in both the initial aortic valve replacement (AVR) cohort (N = 1197), and the conservative management cohort (N = 2618). Both non-cardiac factors (age, male, body mass index <22, diabetes, prior history of stroke, dialysis, anemia, and malignancy) and cardiac factors (atrial fibrillation, ejection fraction <68%, and the initial AVR strategy) were associated with non-cardiac death. These findings highlight the importance of close monitoring of non-cardiac comorbidities, as well as HF and sudden death, to improve the mortality rate of severe AS patients.

Predictors of Prognosis in Light-Chain Amyloidosis and Chronological Changes in Cardiac Morphology and Function.

Immune light-chain (AL) amyloidosis with cardiac involvement is associated with a high mortality despite improved therapeutic regimens, but there are few reports on prognostic predictors and chronological changes in cardiac morphology and function. Prognosis and its predictors were evaluated in 36 consecutive patients with cardiac AL amyloidosis. Chronological changes in cardiac morphology and function were also evaluated. The median follow-up period was 0.95 years. The median survival time and the 3-year death-free rate after diagnosis in all-cause and cardiac deaths were 0.85 and 1.06 years and 26% and 36%, respectively. Differences in the median survival time due to left ventricular (LV) wall thickness at diagnosis were not evident. Being female and diastolic wall strain (DWS), as a measure of diastolic stiffness, were independent predictors of all-cause death in the multivariable analysis. The receiver operating characteristic analysis revealed that a DWS cut-off value of 0.189 had a sensitivity of 78% and a specificity of 72% for predicting all-cause death within 1 year after diagnosis (area under the curve = 0.726). The LV size and the stroke volume decreased and DWS worsened during the short-term follow-up period in patients who died within 1 year compared with patients who were alive after 1 year. The prognosis for patients with cardiac AL amyloidosis was poor, and DWS may be a significant predictor of prognosis. Narrowing of the LV cavity and progressive diastolic dysfunction were evident in patients with a poor prognosis.

Prognostic Impact of Peak Aortic Jet Velocity in Conservatively Managed Patients With Severe Aortic Stenosis: An Observation From the CURRENT AS Registry.

BACKGROUND: There are limited data regarding the risk stratification based on peak aortic jet velocity (Vmax) in patients with severe aortic stenosis (AS). METHODS AND RESULTS: Among 3815 consecutive patients with severe AS enrolled in the CURRENT AS (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis) registry, the study population consisted of 1075 conservatively managed patients with Vmax ≥4.0 m/s and left ventricular ejection fraction ≥50%. The study patients were subdivided into 3 groups based on Vmax (group 1, 4.0 ≤ Vmax <4.5 m/s, N=550; group 2, 4.5 ≤ Vmax <5 m/s, N=279; and group 3, Vmax ≥5 m/s, N=246). Cumulative 5-year incidence of AS-related events (aortic valve-related death or heart failure hospitalization) was incrementally higher with increasing Vmax (entire population; 38.0%, 49.4%, and 62.8%, P<0.001; symptomatic patients; 55.7%, 60.9%, and 72.2%, P=0.008; and asymptomatic patients; 29.4%, 38.9%, and 47.7%, P=0.005). After adjusting for confounders, the excess risk of group 2 and group 3 relative to group 1 for AS-related events remained significant (hazard ratio, 1.39; 95% CI, 1.07-1.81; P=0.02, and hazard ratio, 1.53; 95% CI, 1.17-2.00; P=0.002, respectively). The effect size of group 3 relative to group 1 for AS-related events in asymptomatic patients (N=479) was similar to that in symptomatic patients (N=596; hazard ratio, 1.59; 95% CI, 1.01-2.52; P=0.047, and hazard ratio, 1.67; 95% CI, 1.16-2.40, P=0.008, respectively), and there was no significant overall interaction between the symptomatic status and the effect of the Vmax categories on AS-related events (interaction, P=0.88). CONCLUSIONS: In conservatively managed severe AS patients with preserved left ventricular ejection fraction, increasing Vmax was associated with incrementally higher risk for AS-related events. However, the cumulative 5-year incidence of the AS-related events remained very high even in asymptomatic patients with less greater Vmax.

High- Versus Low-Gradient Severe Aortic Stenosis: Demographics, Clinical Outcomes, and Effects of the Initial Aortic Valve Replacement Strategy on Long-Term Prognosis.

BACKGROUND: There is considerable debate on the management of patients with low-gradient severe aortic stenosis (LG-AS), defined as aortic valve area <1 cm2 with peak aortic jet velocity ≤4.0 m/s, and mean aortic pressure gradient ≤40 mm Hg. METHODS AND RESULTS: In the CURRENT AS registry (Contemporary Outcomes After Surgery and Medical Treatment in Patients With Severe Aortic Stenosis), there were 2097 patients (initial aortic valve replacement [AVR] strategy: n=977, and conservative strategy: n=1120) with high-gradient severe aortic stenosis (HG-AS) and 1712 patients (initial AVR strategy: n=219, and conservative strategy: n=1493) with LG-AS. AVR was more frequently performed in HG-AS patients than in LG-AS patients (60% versus 28%) during the entire follow-up. In the comparison between the initial AVR and conservative groups, the propensity score-matched cohorts were developed in both HG-AS (n=887 for each group) and LG-AS (n=218 for each group) strata. The initial AVR strategy when compared with the conservative strategy was associated with markedly lower risk for a composite of aortic valve-related death or heart failure hospitalization in both HG-AS and LG-AS strata (hazard ratio, 0.30; 95% confidence interval, 0.25-0.37; P<0.001 and hazard ratio, 0.46; 95% confidence interval, 0.32-0.67; P<0.001, respectively). Among 1358 patients with LG-AS with preserved left ventricular ejection fraction, the initial AVR strategy was associated with a better outcome than the conservative strategy (adjusted hazard ratio, 0.37; 95% confidence interval, 0.23-0.59; P<0.001). CONCLUSIONS: The initial AVR strategy was associated with better outcomes than the conservative strategy in both HG-AS and LG-AS patients, although AVR was less frequently performed in LG-AS patients than in HG-AS patients. The favorable effect of initial AVR strategy was also seen in patients with LG-AS with preserved left ventricular ejection fraction. CLINICAL TRIAL REGISTRATION: URL: http://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000012140.

Diagnostic accuracy of the Embolic Risk French Calculator for symptomatic embolism with infective endocarditis among Japanese population.

BACKGROUND: Recently, the Embolic Risk French Calculator (ER-Calculator) was designed to predict symptomatic embolism (SE) associated with infective endocarditis (IE), but external validation has not been reported. This study aimed to determine predictors of SE and the diagnostic accuracy of the ER-Calculator in left-sided active IE among a Japanese population. METHODS: This retrospective cohort study included 166 consecutive patients with a definite diagnosis of left-sided IE from 1994 to 2015 in our institution. SE during the period after initiation of antibiotic therapy was defined as new SE and embolism during the period before initiation of antibiotic therapy was defined as previous embolism. The primary endpoint was new SE. RESULTS: The mean age of patients was 63±17 years. New SE occurred in 23 (14%) patients at a median of 6 days (interquartile range: 2.5-12.5 days) after initiation of antibiotic therapy. The cumulative incidence of new SE at 12 weeks was 18.2%. The 2-week probability by the ER-Calculator as well as previously reported predictors, such as previous embolism, vegetation length (>10mm), and their combination, were associated with a high risk of new SE. By receiver operating characteristic analysis, the area under the curve of the 2-week probability by the ER-Calculator for prediction of new SE was 0.75 and the optimal cut-off value was 8%. A 2-week probability >8% by the ER-Calculator was the most useful predictor of new SE (hazard ratio 3.63, 95% confidence interval 1.50-8.37; p=0.006), which was more remarkable for fatal embolic events (hazard ratio 13.9, 95% confidence interval 3.19-95.4; p=0.004). CONCLUSIONS: The ER-Calculator is a useful predictor of new SE. Predictive ability is more remarkable for critical embolic events.