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Left atrial appendage occlusion (LAAO) plays an important role in preventing stroke in patients with atrial fibrillation. However, LAAO may interact unfavorably with left atrial (LA) compliance and reservoir function and thus increase the risk of heart failure (HF). The purpose of this study was to identify predictors of subsequent HF after successful LAAO.Methods and Results: A total of 98 patients (mean age 70±9 years, 68% male) who had undergone LAAO were included. The primary endpoint was unexpected HF admission after LAAO. During a mean period of 36±26 months, 16 of the 98 patients (16%) experienced hospital HF admission. In multivariate analysis, higher E/e' (hazard ratio [HR] 1.11, 95% confidence interval [CI] 1.02-1.20, P=0.014), higher left ventricular mass index (HR 1.02, 95% CI 1.00-1.03, P=0.023), history of HF (HR 4.78, 95% CI 1.55-14.7, P=0.006), and lower LA strain (HR 0.80, 95% CI 0.70-0.93, P=0.003) were independently associated with hospital HF admission. Patients with LAAO had a significantly higher incidence of subsequent HF than the control group after propensity score matching (P=0.046).LAAO increases the occurrence of HF, and it is not uncommon after successful LAAO. A previous history of HF, left ventricular mass index, E/e', and abnormal LA strain are independently associated with the development of HF. These parameters should be considered before attempting LAAO.

Noncontrast-enhanced (NCE) cross-sectional images other than contrast-enhanced (CE)-computed tomography (CT) may be necessary for annular sizing before transcatheter aortic valve replacement (TAVR), because of the risk of contrast-induced nephropathy. We aimed to investigate the feasibility of aortic annular measurements using NCE-CT in TAVR candidates by comparing them with CE-CT measurements.We retrospectively enrolled 46 patients who underwent CT for the purpose of pre-TAVR evaluation (17 men; mean age, 82.3 ± 5.0 years). On CE and NCE examination, measurements of the average diameter and perimeter of aortic annulus were performed by 2 observers, and coronary ostial heights were measured. Differences in annular parameters and coronary ostial heights between NCE and CE examinations were assessed using Bland-Altman analysis and intraclass correlation coefficients (ICCs).Aortic annulus measurement values were significantly larger in the NCE examinations compared with those in the CE examinations according to both readers (mean differences of 0.8 mm for the average diameter and 2.1 mm for the perimeter according to observer 1, and 1.1 mm for the average diameter and 3.4 mm for the perimeter according to observer 2; ICC, 0.771-0.923). The mean difference between coronary ostial height measurement on NCE and CE examination was 0.6 mm for left coronary ostium (ICC, 0.795) and 0.7 mm for right coronary ostium (ICC, 0.802). No case showed disagreement between NCE and CE examinations for hypothetical valve sizing.Noncontrast-enhanced cardiac CT examination may be feasible for aortic annular measurements before TAVR and provides comparable measurement values to CE examination.

Background To assess the efficacy and safety of a combination therapy involving fimasartan, amlodipine, and rosuvastatin in patients with essential hypertension and dyslipidemia who fail to respond to fimasartan monotherapy. Methods This phase III, randomized, double-blind, multicenter study was conducted in adults aged 19–70 years. Patients who voluntarily consented were screened for eligibility to enroll in the study. Patients who failed to respond to 4 weeks of fimasartan monotherapy were randomized with a 1:1:1 ratio to the fimasartan 60 mg/amlodipine 10 mg + rosuvastatin 20 mg (FMS/ALD + RSV) as study group, fimasartan 60 mg/amlodipine 10 mg (FMS/ALD) as control 1 group, and fimasartan 60 mg + rosuvastatin 20 mg (FMS + RSV) as control 2 group. The primary efficacy endpoints were the change in the sitting systolic blood pressure and the rate of change in the low-density lipoprotein cholesterol (LDL-C) level from baseline to 8 weeks. The adverse events, adverse drug reactions, physical examination findings, laboratory test results, electrocardiograms, and vital signs were evaluated to assess safety in the study. Results Of 138 randomized patients, 131 were conducted efficacy analysis, and 125 completed the study. For the change in LDL-C and sitting SBP (SiSBP) as primary efficacy assessments, the change in LDL-C at week 8 was significantly reduce in the FMS/ALD + RSV group than in the control 1 group (P P Conclusions The fimasartan/amlodipine + rosuvastatin combination therapy can effectively and safely lower blood pressure and improve lipid levels in patients with essential hypertension and dyslipidemia who fail to respond adequately to fimasartan monotherapy. Trial registration NCT03156842, Registered 17 May 2017

As a percutaneous technique for the reduction of mitral regurgitation, the MitraClip system (Abbott Vascular, Abbott Park, IL, USA) for transcatheter edge-to-edge repair of the mitral valve was developed in 1998 and first used in 2003. Its main advantage is being less invasive than surgery, because it can be performed through a transcatheter approach without any hemodynamic compromise. Recent studies have shown that this procedure reduces symptoms and improves functional capacity with low complication rates. Two randomized clinical trials have investigated the use of this technique for functional mitral regurgitation. The Korean Ministry of Food and Drug Safety approved its use for degenerative mitral regurgitation in 2019, and this procedure started to be performed in Korea in January 2020. Its use for functional mitral regurgitation was also approved in Korea in 2020. In this article, recent evidence on transcatheter edge-to-edge repair of the mitral valve and our initial experiences in Korea will be reviewed.

The fusion of early (E) and late diastolic filling (A) on mitral inflow Doppler, even in the absence of tachycardia, is often found during assessment of left ventricular (LV) diastolic function. We evaluated the echocardiographic characteristics and clinical implications of premature E-A fusion of uncertain cause in the absence of tachycardia.We identified 1014 subjects who showed E-A fusion and normal LV ejection fraction (LVEF) between January 2019 and June 2021 at two tertiary hospitals. Among these, 105 (10.4%) subjects showed premature E-A fusion at heart rates less than 100 beats per minute (bpm). The conventional echocardiographic parameters and LV global longitudinal strain (GLS) were compared with 1:1 age-, sex-, and heart rate-matched controls without E-A fusion.The premature E-A fusion group had a heart rate of 96.4±3.7 bpm. Only 4 (3.8%) subjects were classified as having LV diastolic dysfunction according to current guidelines. The group showed prolonged isovolumic relaxation time (107.2±25.3 msec vs. 61.6±15.6 msec,Premature E-A fusion at heart rates less than 100 bpm is associated with subclinical LV dysfunction. Time-based indices and LV GLS are helpful for evaluating this easily overlooked population.

Behcet disease is a multisystemic inflammatory disorder characterized by vasculitis involving both the arterial and venous systems. Cardiovascular involvement is uncommon but often results in serious outcomes, especially in cases of delayed diagnosis of the disease or its complications ([1][1]).

BackgroundThere are insufficient data regarding the risk factors associated with valve dysfunction of bioprosthetic valves in the mitral position This study aimed to investigate the factors associated with bioprosthetic mitral valve (MV) dysfunction (MVD).MethodsA total of 245 patients (age 67.2±11.2 years, 74.9% women) who were followed up for more than 5 years after surgical bioprosthetic MV replacement were analysed in the setting of retrospective study design. MVD was defined as an increased mean gradient of >5 mm Hg with limited leaflet motion and/or newly developed MV regurgitation of at least moderate severity on follow-up echocardiography. The clinical outcome was defined as a composite of cardiovascular mortality, redo MV surgery or intervention and heart failure-related hospitalisations.ResultsDuring a median of 96.0 months (IQR 67.0–125.0 months), bioprosthetic MVD occurred in 66 (27.6%) patients. Factors associated with bioprosthetic MVD detected by multivariate regression analysis were age at surgery (HR 0.98, 95% CI 0.96 to 0.99, p5.5 mm Hg across the bioprosthetic MV early after operation (HR 2.02, 95% CI 1.08 to 3.78, p=0.028) and average haemoglobin level after surgery (HR 0.80, 95% CI 0.67 to 0.96, p=0.015). Patients with bioprosthetic MVD showed significantly poorer clinical outcomes than those without bioprosthetic MVD (log-rank pConclusionsYoung age at operation, chronic kidney disease, elevated pressure gradient across the bioprosthetic MV early after surgery and postsurgical anaemia are associated with bioprosthetic MVD. Bioprosthetic MVD is associated with poor clinical outcomes.

Backgrounds: There are scarce data on whether immune checkpoint inhibitors (ICIs) increase the risk of cardiac dysfunction when used with cardiotoxic agents. Thus, we evaluated cardiac dysfunction in patients with sarcoma receiving doxorubicin with or without ICI using echocardiography and left ventricular global longitudinal strain (LVGLS). Methods: A total of 95 patients were included in this study. Echocardiography and LVGLS were evaluated at baseline and follow-up (at 3 and 6 months of chemotherapy) and compared with the doxorubicin (Dox; n = 73) and concomitant ICI with doxorubicin (Dox-ICI; n = 22) groups. Cancer therapy-related cardiac dysfunction (CTRCD) was defined as a left ventricular ejection fraction (LVEF) drop of >10% and LVEF of 10%, LVEF of ≥50%, and LVGLS relative reduction of >15% (probable CTRCD) at six months. Results: There were no significant differences in age, cumulative dose of doxorubicin, and cardiovascular risk factors between the two groups. At baseline, the LVEF was similar in the Dox and Dox-ICI groups (p = 0.493). In the Dox group, LVEF decreased to 59 ± 6% (Δ −7 ± 1.3%, p < 0.001) and LVGLS decreased from −17.3 ± 3.2% to −15.4 ± 3.2% (Δ −10.1 ± −1.9%, p < 0.001) at six months. In the Dox-ICI group, LVEF decreased to 55 ± 9% (Δ −9 ± 2.1%, p < 0.001), along with a significant decrease in LVGLS (from −18.6 ± 1.9% to −15.3 ± 3.6%, Δ −12.4 ± −2.4%, p < 0.001). Over a median follow-up of 192 days, there were no cases with clinical manifestations of fulminant myocarditis. In the Dox group, definite and probable CTRCD were observed in seven (10.1%) and five (7.4%) patients, respectively. In the Dox-ICI group, definite and probable CTRCD were observed in four (19%) and four (19%) patients, respectively. The total number of patients who developed CTRCD was significantly higher in the Dox-ICI group than in the Dox group (38.1% vs. 17.4%, p = 0.042). Serum troponin-T level was significantly higher in the Dox-ICI group than in the Dox group (53.3 vs. 27.5 pg/mL, p = 0.023). Conclusions: ICIs may increase the risk of CTRCD when used with cardiotoxic agents. CTRCD should be monitored in patients treated with ICIs by cardiac biomarkers and echocardiography, including LV-GLS.

International audience; No abstract available

We investigate the safety and efficacy of telmisartan plus S-amlodipine single-pill combination in a real-world population. A total of 44,715 patients who had hypertension and received a telmisartan/S-amlodipine single-pill combination at least once were included for safety and efficacy evaluation from 2852 primary to tertiary hospitals in Korea from August 2013 to December 2019. They were followed up for 3–6 months in terms of safety and efficacy of blood pressure (BP) lowering. A total of 44,715 patients were included for safety analysis and 41,579 for efficacy analysis. Mean duration of taking the drug was 175.86 ± 48.45 days. A total of 28,096 (62.8%) patients were on telmisartan 40 mg plus S-amlodipine 2.5 mg combination followed by 80/2.5 mg (8664, 19.4%) and 40/5 mg of the drug (7136, 16.0%). Adverse events, total adverse drug reactions, and serious adverse drug reactions were found in 808 patients (1.81%), 352 (0.79%), and 1 (0.002%), respectively. Dizziness and headache were most common (134 [0.30%] and 81 [0.18%]) among all adverse events. Total edema and leg edema were rarely reported, 38 (0.08%) and 25 (0.06%), respectively. Systolic BP (SBP) and diastolic BP (DBP) was lowered from 143.1 ± 16.1/88.1 ± 11.8 mmHg to 129.6 ± 11.4/80.1 ± 9.0 mmHg (difference − 13.5/− 7.9 mmHg, P

Background The percutaneous access site of transfemoral transcatheter aortic valve implantation (TAVI) procedures is commonly closed using a preclosure technique with suture-type closure devices. We sought to evaluate the predictors and outcomes of percutaneous closure device (PCD) failure during transfemoral TAVI. Methods and Results This single-center retrospective analysis included 184 patients who underwent transfemoral TAVI using 2 ProGlide sutures for severe aortic stenosis between July 2011 and September 2018. PCD failure was observed in 11.4%. The causes of PCD failure included 5 cases of insufficient hemostasis, 13 cases of arterial stenosis or occlusion, and 3 cases of dissection. Closure failures were managed by surgical repair in 10 patients and endovascular treatment in 11 patients. In a multivariate binary logistic model, a minimum lumen diameter of the common femoral artery (CFA) (odds ratio [OR] 0.35, 95% confidence interval [CI] 0.15–0.83, P = 0.017) and left femoral access (OR 2.89, 95% CI 1.01–8.30, P = 0.048) was identified as a predictor of PCD failure. PCD failure was not associated with increased mortality (0% vs. 2.5%, P = 1.000) or a major adverse cardiovascular event (MACE; 4.8% vs. 4.3%, P = 1.000) at 30 days. Conclusions PCD failures were not uncommon in patients undergoing percutaneous transfemoral TAVI. Small CFA diameter and left femoral access are predictors of PCD failure. However, PCD failures were not associated with increased mortality or MACE.

Mitral stenosis is classically caused by rheumatic disease (RMS). However, degenerative mitral stenosis (DMS) is increasingly encountered, particularly in developed countries with aging populations. The aim of this study was to compare clinical and echocardiographic characteristics between the 2 entities. One hundred fifteen patients with DMS were identified from an echocardiographic database in the United States and compared with 510 patients with RMS from Seoul, Korea. All subjects had a mitral valve area (MVA) ≤2.5 cm2 by continuity equation but were otherwise unselected. Patients with DMS were older and had more hypertension, diabetes, chronic kidney disease, and chronic obstructive pulmonary disease than those with RMS. Atrial fibrillation was more common in RMS patients. Mean mitral valve gradient was slightly lower in DMS versus RMS (7.63 ± 3.67 vs 8.50 ± 4.23 mm Hg, p = 0.04) but MVA was strikingly higher in the DMS group (1.35 ± 0.41 vs 0.95 ± 0.38 cm2, p

The timing and indications for surgical intervention in asymptomatic patients with severe aortic stenosis remain controversial.In a multicenter trial, we randomly assigned 145 asymptomatic patients with very severe aortic stenosis (defined as an aortic-valve area of ≤0.75 cmIn the early-surgery group, 69 of 73 patients (95%) underwent surgery within 2 months after randomization, and there was no operative mortality. In an intention-to-treat analysis, a primary end-point event occurred in 1 patient in the early-surgery group (1%) and in 11 of 72 patients in the conservative-care group (15%) (hazard ratio, 0.09; 95% confidence interval [CI], 0.01 to 0.67; P = 0.003). Death from any cause occurred in 5 patients in the early-surgery group (7%) and in 15 patients in the conservative-care group (21%) (hazard ratio, 0.33; 95% CI, 0.12 to 0.90). In the conservative-care group, the cumulative incidence of sudden death was 4% at 4 years and 14% at 8 years.Among asymptomatic patients with very severe aortic stenosis, the incidence of the composite of operative mortality or death from cardiovascular causes during the follow-up period was significantly lower among those who underwent early aortic-valve replacement surgery than among those who received conservative care. (Funded by the Korean Institute of Medicine; RECOVERY ClinicalTrials.gov number, NCT01161732.).

Objective Early warfarin anticoagulation is recommended in patients undergoing surgical bioprosthetic valve implantation or valve repair. It is unclear whether non-vitamin K antagonist oral anticoagulants can be a full alternative to warfarin. This study aimed to compare efficacy and safety of edoxaban with warfarin in patients early after surgical bioprosthetic valve implantation or valve repair. Methods The Explore the Efficacy and Safety of Edoxaban in Patients after Heart Valve Repair or Bioprosthetic Valve Replacement study was a prospective, randomized (1:1), open-label, clinical trial conducted from December 2017 to September 2019. Patients were randomly assigned to receive edoxaban (60 mg or 30 mg once daily) or warfarin for the first 3 months after surgical bioprosthetic valve implantation or valve repair. The primary efficacy outcome was a composite of death, clinical thromboembolic events, or asymptomatic intracardiac thrombosis. The primary safety outcome was the occurrence of major bleeding. Results Of 220 participants, 218 (109 per group) were included in the modified intention-to-treat analysis. The primary efficacy outcome occurred in 4 patients (3.7%) taking warfarin and none taking edoxaban (risk difference, −0.0367; 95% confidence interval, –0.0720 to –0.0014; P Conclusions Edoxaban is noninferior to warfarin for preventing thromboembolism and is potentially comparable for risk of major bleeding during the first 3 months after surgical bioprosthetic valve implantation or valve repair.

We investigated the flow-gradient pattern characteristics and associated factors in severe bicuspid aortic stenosis (AS) compared with severe tricuspid AS.Methods and Results:A total of 252 patients with severe AS (115 bicuspid vs. 137 tricuspid) who underwent aortic valve (AV) replacement were retrospectively analyzed. Patients were classified into 4 groups according to stroke volume index and mean pressure gradient across the AV [normal-flow-high-gradient (NF-HG), low-flow-high-gradient, normal-flow-low-gradient, low-flow-low-gradient (LF-LG)]. In 89 patients who underwent cardiac computed tomography (CT), influential structural parameters of the left ventricular outflow tract (LVOT), AV and ascending aorta were assessed. Bicuspid AS was more likely to present a NF-HG pattern (83.5% vs. 64.2%, P0.001), and significantly fewer presented a LF-LG pattern compared with tricuspid AS. In bicuspid AS, there was a significant mismatch between geometric orifice area (GOA) on CT planimetry and effective orifice area (EOA) calculated using the echocardiographic continuity equation. Bicuspid AS presented with a larger angle between the LVOT-AV and aorta. Multivariate analysis of bicuspid AS revealed that systemic arterial compliance (β=-0.350, P=0.031) and the LVOT-AV-aorta angle (β=-0.538, P=0.001), and stroke volume index (β=0.409, P=0.008) were associated with a discrepancy between GOA and EOA.Flow-gradient patterns in bicuspid AS differ from those of tricuspid AS and are associated with the structural and functional characteristics of the aorta.

Introduction: Functional tricuspid regurgitation (TR) will decrease after atrial septal defect (ASD) closure, but it may persist and require additional tricuspid valve (TV) surgery or intervention. Hypothesis: We aimed to find echocardiographic predictors for persistent TR after successful ASD closure. Methods: Among 348 adults who underwent isolated ASD closure between January 2010 and September 2020, 91 (26.1%) patients with significant TR (at least moderate degree) before ASD closure were included. Persistent TR was defined as a significant TR even after ASD correction on echocardiogram after 6 months to 1 year. To find echocardiographic predictors for persistent TR, conventional and speckle tracking echocardiography performed before ASD closure were analyzed. The right ventricular (RV)-pulmonary arterial coupling was assessed by the ratio of RV global longitudinal strain (RV GLS) and pulmonary arterial systolic pressure (PASP) (RV GLS/PASP). Results: Persistent TR was observed in 22 (24.2%) patients. Patients with persistent TR were significantly older, with larger TR jet area and lower RV GLS/PASP (0.46 ± 0.14 vs. 0.37 ± 0.13, p = 0.013) than those without persistent TR. However, there were no significant differences in RV volumes, RV systolic function, and TV annular diameter between the two groups. On multivariable logistic regression, persistent TR was independently associated with age (HR:2.031, 95% CI, 1.113-2.046; p=0.003) and RV GLS/PASP (HR:0.009, 95% CI, 0.000-0.790; p=0.039). RV GLS/PASP showed a good predictive value for persistent TR after ASD closure (cut off 0.39, the area under the curve 0.702, p=0.003). Conclusions: Persistent TR after successful ASD closure is not uncommon in patients with ASD and significant TR. RV GLS/PASP can predict persistent TR after ASD closure. It can be suggested that concomitant or subsequent TR intervention should be considered in elderly patients and patients with abnormal RV-pulmonary arterial coupling.

Introduction: There is scarce data on whether immune checkpoint inhibitor (ICI) increase the risk of cardiomyopathy, especially when used with cardiotoxic agents. Hypothesis: We evaluated the cardiotoxicity of the ICI in sarcoma patients receiving doxorubicin with or without ICI by echocardiographic parameters and left ventricular global longitudinal strain (LVGLS). Methods: A total of 89 patients were included. Echocardiography and LVGLS were evaluated at baseline and follow-up (after 3 and 6months) and compared between the doxorubicin (n=67) and concomitant ICI with doxorubicin (n=22) groups. Cancer-therapy related cardiac dysfunction (CTRCD) was defined as LVEF drop of >10% and LVEF of 10%, LVEF of > 50% and LVGLS relative reduction of >15% (probable CTRCD) at 6months. Results: There was no significant difference in age, cumulative dose of doxorubicin and cardiovascular risk factors between two groups. At baseline, LVEF was similar between two groups (p=0.493). In doxorubicin group, LVEF decreased to 59±6 % (p Conclusions: ICI increases risk of CTRCD, when concomitantly treated with cardiotoxic agents. Thus, cardiomyopathy should be monitored in patients with ICI by comprehensive echocardiographic assessment including myocardial strain.

Introduction: We aimed to investigate the temporal changes in demographic characteristics, use of multimodal imaging, and treatments in patients with bicuspid aortic valves from a large Korean registry. Methods: A total of 1,514 patients (mean 71.5%, 56 ±14 years old) who were first diagnosed with BAV from Jan 2003 through Dec 2020 in a single tertiary referral center in Korea were investigated. They were divided into 3 groups according to the year of diagnosis: group 1 (2003-2008, n=270), group 2 (2009-2014, n=590), and group 3 (2015-2020, n=654). Significant aortic stenosis (AS) was defined as at least moderate AS and significant aortic regurgitation (AR) was defined as at least moderate AR based on the current guideline. Non-dysfunctional BAV was defined as BAV without significant AR or AR. Presence of aortopathy was defined as any portions of ascending aorta ≥ 45 mm. Use of imaging for diagnosis and the treatment method were comprehensively investigated. Results: Both age at diagnosis [55 (interquartile range [IQR], 44 to 60) in Group 1, 59 (48 to 67) in Group 2, 60 (60 to 68) in Group 3, p for trend Conclusions: In the past 18 years, there were remarkable temporal changes in patients’ demographic characteristics, use of multimodal imaging for diagnosis, complications and treatment in patients with BAV.

BackgroundValve regurgitation can decrease with resolution of hemodynamic loads on the left ventricle (LV) after kidney transplantation (KT). We aimed to investigate the natural course of left-side valve regurgitation after KT and factors associated with progression.MethodsAmong patients who underwent KT in two tertiary centers, 430 (224 men, mean age 50 ± 13 years) were examined by echocardiography within 3 months before KT and between 6 and 36 months after KT. Mitral regurgitation (MR) and aortic regurgitation (AR) were graded according to the current guidelines. Regression was defined as a decrease in regurgitation by one or more steps, and progression was an increase in one or more steps after KT. Clinical and echocardiographic factors associated with progression of MR and AR were analyzed.ResultsMild or greater MR was observed in 216 (50%) patients before KT, and mild or greater AR was observed in 99 (23%). During the follow-up period of 23.4 ± 9.9 months, most patients experienced regression or no change in regurgitation after KT, but 34 patients (7.9%) showed MR progression and 37 (8.6%) revealed AR progression. Patients who showed MR progression were more likely to receive a second KT, have mitral annular calcifications, and show a smaller decrease in LV end-systolic dimension. Patients who showed AR progression were more likely to have persistent hypertension after KT, aortic valve calcifications, and a smaller reduction of LV end-systolic dimension.ConclusionsRisk factors for progression of MR after KT include a second KT, MAC and a smaller decrease in LV end-systolic dimension after KT. Risk factors for progression of AR include valve calcification, persistent hypertension and a smaller decrease in LV end-systolic dimension after KT. Further echocardiographic surveillance and risk factor management after KT are warranted in these patients.

Background: The population is aging and advances in multimodal imaging and transcatheter valve intervention have been prominent in the past two decades. This study investigated temporal trends in demographic characteristics, use of multimodal imaging, treatments, and outcomes in patients with bicuspid aortic valve (BAV).Methods and Results: A total of 1,497 patients (male 71.7%, 57 ± 14 years old) first diagnosed with BAV between January 2003 and December 2020, in a single tertiary center were divided into three groups according to year of diagnosis: group 1 (2003–2008, n = 269), group 2 (2009–2014, n = 594), and group 3 (2015–2020, n = 634). The patients' demographic characteristics, comorbidities, BAV morphology, BAV function, BAV-related disease, use of multimodal diagnostic imaging, treatment modality for BAV, and clinical outcomes were compared among the three groups. The ages at diagnosis and at the time of surgery/intervention increased considerably from group 1 to 3. The patients' comorbidity index also increased progressively. The proportion of non-dysfunctional BAV and significant AS increased, while that of significant AR decreased. The frequency of infective endocarditis as an initial presentation significantly decreased over time. Additionally, the use of multimodal imaging increased markedly in the most recent group. The results also indicated increasing trends in the use of bioprosthetic valves and transcatheter aortic valve replacement. Overall and cardiovascular survival rates improved from group 1 to 3 (log rank p < 0.001).Conclusions: For the past two decades, remarkable temporal changes have occurred in patient characteristics, use of multimodal diagnostic imaging, choice of treatment modality, and clinical outcomes in patients with BAV.

Background There is increasing Interest in bio-prosthetic MVD as recent advances in transcatheter MV interventions, but there is limited data. Objectives The aim of this study was to identify the factors determining mitral valve (MV) dysfunction (MVD) in patients who underwent MV replacement with bio-prosthetic valves. Also, we sought to investigate clinical outcomes in patients with bio-prosthetic MVD. Methods A total of 233 patients underwent surgical bio-prosthetic MV replacement between June 1996 and May 2015. Finally, 226 patients (mean age 66.9±11.5 years, 74.3% of women) were analyzed, excluding patients who followed-up for less than 5 years and patients whose baseline or follow-up echocardiography could not be analyzed. Clinical, echocardiographic, and laboratory data were collected early after the surgery and during follow-up. MVD was defined as an increase in mean gradient ≥5 mmHg with leaflet motion limitation and/or newly developed MV regurgitation during follow-up. Clinical outcome was defined as a composite of cardiovascular death, redo MV surgery or intervention, and hospitalization for heart failure. Results During a median of 102.0 months (interquartile range 72.0 to 132.0 months), 65 patients (28.8%) revealed MVD. 8 (12.3%) patients revealed predominant MV obstruction, and 57 (87.7%) showed predominant MV regurgitation. Factors associated with bio-prosthetic MVD by multivariate regression analysis were young age at operation (hazard ratio 0.97, 95% CI 0.95–0.99, p=0.001), end-stage renal disease (hazard ratio 4.29, 95% CI 1.45–12.71, p=0.007), elevated mean diastolic pressure gradient>5.5 mmHg across the bio-prosthetic MV early after operation (hazard ratio 1.86, 95% CI 0.97–3.74, p=0.063) and anemia after operation (hazard ratio 0.84, 95% CI 0.74–0.95, p=0.007). However, the presence of hypertension, dyslipidemia, or porcine bio-prosthesis was not related to the bio-prosthetic MVD. Kaplan-Meier curves revealed significant differences in event-free survivals for the occurrence of bio-prosthetic MVD according to each factor (Figure 1). Patients with bio-prosthetic MVD showed significantly poor clinical outcomes compared with those without bio-prosthetic MVD (event-free survival 43.1% vs. 91.9%, log-rank p Conclusions Young age at operation, end-stage renal disease, elevated mean pressure gradient early after the operation, and anemia after operation were associated with bio-prosthetic MVD in patients who underwent bio-prosthetic MV replacement. Funding Acknowledgement Type of funding sources: None.

Background: The two-dimensional-based LAAO size prediction system using transesophageal echocardiography is limited by the complex structure of the left atrial appendage (LAA). The LAA anatomy can be evaluated more precisely using three-dimensional images from cardiac CT; however, a CT-based sizing method has not been established. We aimed to assess the accuracy of measurements derived from cardiac computed tomography (CT) images for selecting left atrial appendage occlusion (LAAO) devices.Methods: We retrospectively reviewed 62 patients with Amplatzer Cardiac Plug and Amulet LAAO devices who underwent implantation from 2017 to 2020. The minimal, maximal, average, area-derived, and perimeter-derived diameters of the LAA landing zone were measured using CT-based images. Predicted device sizes using sizing charts were compared with actual successfully implanted device sizes.Results: The mean size of implanted devices was 27.1 ± 3.7 mm. The perimeter-derived diameter predicted device size most accurately (mean error = -0.8 ± 2.4 mm). All other parameters showed significantly larger error (mean error; minimal diameter = -4.9 ± 3.3 mm, maximal diameter = 1.0 ± 2.9 mm, average diameter = -1.6 ± 2.6 mm, area-derived diameter = -2.0 ± 2.6 mm) than the perimeter-derived diameter (all p for difference Conclusions: The perimeter-derived diameter on cardiac CT images provided the most accurate estimation of LAAO device size regardless of landing zone eccentricity. Oversizing was unnecessary when using cardiac CT to predict an accurate LAAO size.

Background: Patients who underwent permanent pacemaker (PM) implantation have a potential risk of left ventricular (LV) systolic dysfunction. However, assessment of LV ejection fraction (LVEF) shows a limited role in identifying subclinical LV systolic dysfunction and predicting cardiovascular (CV) outcomes.Methods: We reviewed 1,103 patients who underwent permanent PM implantation between January 2007 and December 2017. After excluding patients who did not undergo echocardiograms before or after PM implantation and those with LV ejection fraction (LVEF) Results: At 44 ± 28 months after post-PM echocardiogram, 23 patients (7.7%) had experienced CV outcomes. Patients with CV outcomes were older and had more comorbidities and a lower baseline |LV-GLS| than those without CV outcomes. LV mechanical function worsened after PM implantation in patients with CV outcomes. The cut-off value of 11.2% in |LV-GLS| on post-PM echocardiogram had a better predictive value for CV outcomes (AUC; 0.784 vs. 0.647, p = 0.012). CV outcome in patients with |LV-GLS| p < 0.001). Multivariate Cox model revealed that reduced |LV-GLS| was independently associated with CV outcomes.Conclusions: Pacing deteriorates LV mechanical function. Impaired LV-GLS is associated with poor CV outcomes in patients who underwent PM implantation.

ObjectiveThe decision to perform percutaneous mitral commissurotomy (PMC) on asymptomatic patients requires careful weighing of the potential benefits against the risks of PMC, and we conducted a multicentre, randomised trial to compare long-term outcomes of early PMC and conventional treatment in asymptomatic, severe mitral stenosis (MS).MethodsWe randomly assigned asymptomatic patients with severe MS (defined as mitral valve area between 1.0 and 1.5 cm2) to early PMC (84 patients) or to conventional treatment (83 patients). The primary endpoint was a composite of major cardiovascular events, including PMC-related complications, cardiovascular mortality, cerebral infarction and systemic thromboembolic events. The secondary endpoints were death from any cause and mitral valve (MV) replacement during follow-up.ResultsIn the early PMC group, there were no PMC-related complications. During the median follow-up of 6.4 years, the composite primary endpoint occurred in seven patients in the early PMC group (8.3%) and in nine patients in the conventional treatment group (10.8%) (HR 0.77; 95% CI 0.29 to 2.07; p=0.61). Death from any cause occurred in four patients in the early PMC group (4.8%) and three patients in the conventional treatment group (3.6%) (HR 1.30; 95% CI 0.29 to 5.77). Ten patients (11.9%) in the early PMC group and 17 patients (20.5%) in the conventional treatment group underwent MV replacement (HR 0.59; 95% CI 0.27 to 1.29).ConclusionsCompared with conventional treatment, early PMC did not significantly reduce the incidence of cardiovascular events among asymptomatic patients with severe MS during the median follow-up of 6 years.Trial registration numberNCT01406353.

Background and Aims Fabry disease (FD) is an X-linked lysosomal storage disorder caused by pathogenic GLA gene variants. Males with the classic (more severe) phenotype have markedly deficient or no α-galactosidase A activity and early, progressive accumulation of glycosphingolipids (e.g. globotriaosylceramide [GL-3] and deacylated GL-3 [lyso-GL-3]) in cells and body fluids. Particularly compromised are vascular endothelial and smooth muscle cells, most kidney cell types (particularly podocytes), cardiomyocytes and neural cells. Cellular injury triggers inflammatory responses leading to fibrosis with multisystem involvement. Symptoms associated with small fiber neuropathy (e.g. neuropathic pain) appear in childhood, typically followed in adulthood by chronic nephropathy (proteinuria, reduced glomerular filtration rate [GFR]) that may evolve to end-stage renal disease, and progressive cardiomyopathy with left ventricular hypertrophy and early demise. We compared kidney function and cardiomyopathy outcomes after enzyme replacement therapy with agalsidase beta with treatment-naive outcomes in male patients with the classic form of FD. Method The self-controlled comparison (piecewise mixed linear modelling) used Fabry Registry (NCT00196742) data from males with GLA variants associated with the classic FD phenotype (dbfgp.org/dbFgp/fabry/). The patients had received agalsidase beta (average dose of 0.9 − 1.1 mg/kg every 2 weeks) and had ≥2 pre- and ≥2 post-baseline assessments. Baseline was defined as up to 6 months after start of treatment. Follow-up spanned from 5 years pre-treatment (preTx) to 5 years post-treatment (postTx). Patients on dialysis or with a kidney transplant were excluded. Assessed were slopes of estimated GFR (eGFR, CKDEPI equation), ultrasound derived interventricular septum thickness (IVSTd) and left ventricular posterior wall thickness (LVPWTd) during the preTx and postTx periods. Data were stratified by low renal involvement (LRI, ratios [g/g] urine protein-to-creatinine ≤0.5 or albumin-to-creatinine ≤0.3) and high renal involvement (HRI, ratios [g/g] >0.5 or >0.3, respectively). Ages at start of treatment (ageTx) and follow-up durations are expressed as medians. Results Compared with 1.1-year preTx data, eGFR decline was similar during 4.1-year postTx follow-up in 254 males, ageTx 30.8 years. eGFR slopes (preTx vs. postTx) were -2.22 vs. -2.66 ml/min/1.73 m2/year (Ppre-post difference=0.24). The changing patterns among the 165 LRI males, ageTx 25.4 years (slopes preTx vs. postTx: -1.73 vs. -1.92 ml/min/1.73 m2/year; Ppre-post difference=0.66), and the 68 HRI males, ageTx 38.2 years (slopes: -2.93 vs. -4.31 ml/min/1.73 m2/year; Ppre-post difference=0.04), were statistically different (Pinteraction0.05) and 4.1-year postTx follow-up (slopes=-0.02 mm/year, P0>0.05) (Ppre-post difference=0.83), where a P0 0.05) in 87 males, ageTx 35.1 years (Ppre-post difference Conclusion In males with classic FD, treatment with agalsidase beta appeared to stabilize eGFR decline in LRI males. Overall, IVSTd remained stable throughout follow-up and LVPWTd, increasing during pre-treatment follow-up, stabilized post-treatment. Funding: Fabry Registry, abstract: Sanofi Genzyme.

Background Continuous positive airway pressure (CPAP) therapy might decrease left ventricular (LV) and right ventricular (RV) loads and improve cardiac mechanical function in patients with obstructive sleep apnea (OSA). However, the benefits of CPAP therapy for cardiac mechanical function in patients with OSA have not previously been proved in a randomized, sham-controlled clinical trial. This study therefore investigated the effects of CPAP therapy on LV and RV mechanical function in patients with severe OSA and compared them with the effects of a sham intervention. Methods In this randomized sham-controlled trial, we analyzed LV and RV function by conventional and speckle-tracking echocardiography before and after 3 months of treatment in 52 patients with severe OSA. Patients were randomly assigned (1:1) to receive either CPAP or sham treatment for 3 months. The main investigator and patients were masked to the trial randomization. Results After 3 months, CPAP treatment significantly improved LV global longitudinal strain (GLS) compared with the sham treatment (–20.0% ± 2.1% vs –18.0% ± 2.5%; P = .004), although there were no differences in LV dimension or ejection fraction. CPAP treatment reduced RV size and improved the fractional area change (51.3% ± 7.9% vs 46.9% ± 6.7%; P = .038) compared with the sham treatment. CPAP treatment did not ameliorate the RV GLS compared with the sham treatment. Conclusions In patients with severe OSA, CPAP treatment for 3 months improved LV and RV function compared with sham treatment. LV mechanical function assessed by speckle-tracking echocardiography and RV fractional area change assessed by two-dimensional echocardiography were significantly improved by CPAP treatment.

The heart and blood vessels are constantly interfering with each other in a closed system. For a few decades, the concept of ventricular-arterial coupling has been considered as a key pathogenesis of heart failure especially in heart failure with preserved ejection fraction.

Background: The morbidity and mortality of patients with functional mitral regurgitation (MR) remain high, but no pharmacological therapy has been proven effective. The hypothesis of this study was that sacubitril/valsartan would be superior to valsartan alone in improving functional MR via dual inhibition of the renin-angiotensin system and neprilysin. Methods: In this double-blind trial, we randomly assigned 118 patients with heart failure with chronic functional MR secondary to left ventricular (LV) dysfunction to receive either sacubitril/valsartan or valsartan, in addition to standard medical therapy for heart failure. The primary end point was the change in effective regurgitant orifice area of functional MR from baseline to the 12-month follow-up. Secondary end points included changes in regurgitant volume, LV end-systolic volume, LV end-diastolic volume, and incomplete mitral leaflet closure area. Results: The decrease in effective regurgitant orifice area was significantly greater in the sacubitril/valsartan group than in the valsartan group (–0.058±0.095 versus –0.018±0.105 cm 2 ; P =0.032) in an intention-to-treat analysis including 117 (99%) patients. Regurgitant volume was also significantly decreased in the sacubitril/valsartan group in comparison with the valsartan group (mean difference, –7.3 mL; 95% CI, –12.6 to –1.9; P =0.009). There were no significant between-group differences regarding the changes in incomplete mitral leaflet closure area and LV volumes, with the exception of LV end-diastolic volume index ( P =0.044). We noted no significant difference in the change of blood pressure between the treatment groups, and 7 patients (12%) in the sacubitril/valsartan group and 9 (16%) in the valsartan group had ≥1 serious adverse events ( P =0.54). Conclusions: Among patients with secondary functional MR, sacubitril/valsartan reduced MR to a greater extent than did valsartan. Our findings suggest that an angiotensin receptor-neprilysin inhibitor might be considered for optimal medical therapy of patients with heart failure and functional MR. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02687932.

BACKGROUND Infective endocarditis (IE) in cancer patients is increasing, but because little is known about it in these patients, we analyzed patient characteristics and outcomes and compared these factors in IE patients with and without cancer. Methods and Results: This retrospective cohort study included 170 patients with IE newly diagnosed between January 2011 and December 2015. Among 170 patients, 30 (17.6%) had active cancer. The median age of IE patients with cancer was higher than that of non-cancer patients. Nosocomial IE was more common in cancer patients. Non-dental procedures, such as intravenous catheter insertion and invasive endoscopic or genitourinary procedures, were more frequently performed before IE developed in cancer patients. Staphylococcus was the most common pathogen in cancer patients, whereas Streptococcus was the most common in non-cancer patients. In-hospital mortality was significantly higher in cancer patients with IE (34.4% vs. 12.4%, P

Background Electrical dyssynchrony (ED) is one of the important contributing mechanisms in the progression of heart failure. We hypothesized that ED would interfere with cardiac reverse remodeling and affect prognosis after aortic valve surgery. Methods A total of 411 consecutive patients (233 males, mean age 65 ± 11 years) who underwent aortic valve surgery were retrospectively analyzed. The patients were divided into two groups according to the presence of ED [Group 1: no ED (n = 382, 93%), Group 2: ED (n = 29, 7%)]. ED was defined as either left ventricular bundle branch block, or electrical pacing rhythm. Cardiac reverse remodeling was assessed at 1 year after surgery by the changes in left ventricular ejection fraction (LVEF), LV end-systolic volume (LVESV), and left atrial volume index (LAVI). The primary endpoint was a composite of hospitalization for heart failure, and all-cause mortality. Results At 1 year after surgery, group 2 showed lower LVEF (58 ± 15% vs. 64 ± 9%, p = 0.044), and higher LAVI (42 ± 18 ml/m2 vs. 33 ± 13 ml/m2, p = 0.018) than group 1. However, LVESV values (55 ± 38 ml vs. 42 ± 24 ml, p = 0.076) were not significantly different. In particular, in patients with reduced preoperative LVEF, the LVEF was markedly increased in group 1 but not in group 2 after 1 year. During a median follow-up of 39 months, group 2 showed a worse clinical outcome than group 1 (20.7% vs. 7.6%, p = 0.031). After adjusting for confounding factors in the multivariate analyses, age [hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.06–1.16, p Conclusions ED after aortic valve surgery negatively affected cardiac remodeling and prognosis.

BACKGROUND AND OBJECTIVES Decreased left atrial appendage (LAA) emptying velocity in transesophageal echocardiography (TEE) is related with higher incidence of thrombus and increased risk of stroke. Patients with valve disease are at higher risk of thrombus formation before and after surgery. The aim of this study was to investigate the role of 4-dimensional cardiac computed tomography (4DCT) to predict the risk of thrombus formation. METHODS Between March 2010 to March 2015, total of 62 patients (mean 60±15 years old, male: 53.2%) who underwent 4DCT and TEE for cardiac valve evaluation before surgery were retrospectively included in the current study. Fractional area change in TEE view and emptying velocity at left atrial appendage in TEE view (VeTEE) were measured. Ejection fraction (EF) of left atrial appendage in computed tomography (EFCT) was calculated by 4DCT with full volume analysis. The best cut-off value of EFCT predicting presence of spontaneous echo contrast (SEC) or thrombus was evaluated, and correlation between the parameters were also estimated. RESULTS SEC or thrombus was observed in 45.2%. EFCT and VeTEE were significantly correlated (r=0.452, p

Purpose Concerns have been consistently raised in regards to the considerable amount of contrast dye used during transcatheter aortic valve replacement (TAVR) in patients with renal insufficiency. In the present study, we introduced minimal contrast TAVR and compared its 30-day clinical outcomes with conventional TAVR. Materials and Methods We retrospectively investigated 369 patients who underwent TAVR between July 2011 and April 2020 in our institute. Among them, 93 patients with severe aortic stenosis and renal insufficiency (estimated glomerular filtration rate ≤50 mL/min/1.73 m2) were included and divided into a conventional TAVR group (n=56) and a minimal contrast TAVR group (n=37). In the minimal contrast TAVR group, the total amount of contrast was

We sought to investigate the prevalence, functional characteristics, and clinical significance of right ventricular (RV) involvement in patients with hypertrophic cardiomyopathy (HCM). A total of 256 patients with HCM who underwent both cardiac magnetic resonance (CMR) imaging and transthoracic echocardiography within 6 months of each other were retrospectively analysed. RV involvement was defined as an increased RV wall thickness ≥ 7 mm on CMR in the segments of the RV free wall. Primary outcomes were defined as the composite of all-cause death, heart transplantation, and unplanned cardiovascular admission. Thirty-seven (14.4%) patients showed RV involvement. Patients with RV involvement showed a significantly higher left ventricular (LV) maximal wall thickness and left atrial volume index. Multivariate Cox model revealed that RV involvement was independently associated with primary outcomes (HR: 2.30, p = 0.024). In a subgroup analysis of patients with speckle tracking echocardiography (n = 190), those with RV involvement had significantly more impaired RV strain, which was independently associated with primary outcomes. RV involvement in patients with HCM correlated with more advanced LV structure and biventricular dysfunction, suggesting an indicator of severe HCM. RV involvement and impaired RV strain have a prognostic value related to clinical adverse events in patients with HCM.

The rapid spread of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has raised questions about Fabry disease (FD) as an independent risk factor for severe COVID-19 symptoms. Available real-world data on 22 patients from an international group of healthcare providers reveals that most patients with FD experience mild-to-moderate COVID-19 symptoms with an additional complication of Fabry pain crises and transient worsening of kidney function in some cases; however, two patients over the age of 55 years with renal or cardiac disease experienced critical COVID-19 complications. These outcomes support the theory that pre-existent tissue injury and inflammation may predispose patients with more advanced FD to a more severe course of COVID-19, while less advanced FD patients do not appear to be more susceptible than the general population. Given these observed risk factors, it is best to reinforce all recommended safety precautions for individuals with advanced FD. Diagnosis of FD should not preclude providing full therapeutic and organ support as needed for patients with FD and severe or critical COVID-19, although a FD-specific safety profile review should always be conducted prior to initiating COVID-19-specific therapies. Continued specific FD therapy with enzyme replacement therapy, chaperone therapy, dialysis, renin–angiotensin blockers or participation to clinical trials during the pandemic is recommended as FD progression will only increase susceptibility to infection. In order to compile outcome data and inform best practices, an international registry for patients affected by Fabry and infected by COVID-19 should be established.

Background This study aimed to investigate the cardiac manifestations of coronavirus disease 2019 (COVID-19). Methods From February to March 2020, we prospectively and retrospectively enrolled consecutive patients diagnosed with COVID-19. Patient's data such as the demographic characteristics, symptoms, vital signs, laboratory and radiologic findings, electrocardiographic, and echocardiographic data, including the global longitudinal strain (GLS) of both ventricles, were obtained. Results Forty patients (median age, 58 years; 50% men) were enrolled in the initial analysis. Patients were classified into severe and nonsevere groups based on the current guidelines. The 13 patients in the severe group were significantly older, had a greater prevalence of bilateral pneumonia and leukocytosis, and higher aspartate transaminase levels than patients in the nonsevere group. Patients in the severe group had a slightly lower left ventricular ejection fraction (LVEF) than those in the nonsevere group (median [interquartile range], 61.0% [58.5%, 62.3%] vs. 66.7% [60.6%, 69.8%], P = 0.015). In a subgroup of 34 patients in whom GLS could be analyzed, patients in the severe group had a significantly impaired left ventricular GLS (LVGLS) than those in the nonsevere group (−18.1% [−18.8%, −17.1%] vs. −21.7% [−22.9%, −19.9%], P = 0.001). There were no significant differences in total wall (RVGLStotal, −19.3% [−23.9%, −18.4%] vs. −24.3% [−26.0%, −22.6%], P = 0.060) and free wall (RVGLSfw, −22.7% [−27.2%, −18.6%] vs. −28.8% [−30.4%, −24.1%], P = 0.066) right ventricle GLS (RVGLS). Conclusion Patients with severe COVID-19 had lower LVEF and LVGLS. RVGLS was not different between patients with severe and nonsevere COVID-19., Graphical Abstract

Background and objectives Transcatheter aortic valve replacement (TAVR) has been reported as a good alternative for surgical aortic valve replacement in patients with small aortic annulus. Head-to-head comparisons of different transcatheter aortic valves in these patients are insufficient. We compared the outcomes after TAVR between two different types of recent transcatheter aortic valves (self-expanding vs. balloon-expandable) in patients with small aortic annulus. Methods A total of 70 patients with severe aortic stenosis and small annulus (mean diameter ≤23 mm or minimal diameter ≤21 mm on computed tomography) underwent TAVR with either a self-expanding valve with supra-annular location (n=45) or a balloon-expandable valve with intra-annular location (n=25). The echocardiographic hemodynamic parameters after TAVR and 1-year follow-up were compared. Results Between the self-expanding and balloon-expandable valve-treated patients, the clinical outcomes including permanent pacemaker implantation (11.1% vs. 8.0%), acute kidney injury stage 2 or 3 (4.4% vs. 4.0%), and major vascular complication (4.4% vs. 0.0%) were similar without all-cause mortality, stroke, and life-threatening bleeding during 30-day follow-up. Compared with the balloon-expandable valve-treated patients, the self-expanding valve-treated patients presented larger effective orifice area (EOA) (1.46±0.28 vs. 1.75±0.42 cm², p=0.002) and indexed EOA (0.95±0.21 vs. 1.18±0.28 cm²/m², p=0.001), whereas mean aortic valve gradient (11.7±2.9 vs. 8.9±5.2 mmHg, P=0.005) and incidence of ≥moderate prosthesis-patient mismatch (36.0% vs. 8.9%, p=0.009) were lower. These hemodynamic differences were maintained at 1-year follow-up. Conclusions TAVR with self-expanding valves was associated with superior hemodynamic outcomes compared with balloon-expandable valves in patients with small aortic annulus.