Determinants and effects of microvascular obstruction on serial change in left ventricular diastolic function after reperfused acute myocardial infarction.

Background: Although left ventricular (LV) diastolic dysfunction is more related to functional capacity after acute myocardial infarction (AMI), the determinants of LV diastolic functional change after reperfused AMI remain unknown. This study aimed to investigate the effects of microvascular obstruction (MVO) on mid-term changes in LV diastolic function after reperfused AMI. Methods: In a cohort of 72 AMI patients who underwent successful revascularization, echocardiography and cardiovascular magnetic resonance imaging were repeated at 9-month intervals. The late gadolinium enhancement (LGE) amount, segmental extracellular volume fraction, global LV, and left atrial (LA) phasic functions, along with mitral inflow and tissue Doppler measurements, were repeated. Results: Among the included patients, 31 (43%) patients had MVO. During the 9-month interval, LV ejection fraction (EF) and LV global longitudinal strain (GLS) were significantly improved in accordance with a decrease in LGE amount (from 18.2 to 10.3 g, p < 0.001) and LV mass. The deceleration time (DT) of early mitral inflow (188.6 ms-226.3 ms, p < 0.001) and LV elastance index (Ed; 0.133 1/ml-0.127 1/ml, p = 0.049) were significantly improved, but not in conventional diastolic functional indexes. Their improvements occurred in both groups; however, the degree was less prominent in patients with MVO. The degree of decrease in LGE amount and increase in LVEF was significantly correlated with improvement in LV-Ed or LA phasic function, but not with conventional diastolic functional indexes. Conclusions: In patients with reperfused AMI, DT of early mitral inflow, phasic LA function, and LV-Ed were more sensitive diastolic functional indexes. The degree of their improvement was less prominent in patients with MVO.

Edoxaban treatment in atrial fibrillation in routine clinical care: One-year outcomes of the prospective observational ETNA-AF study in South Korean patients.

Background: The real-world outcomes of edoxaban treatment in patients with atrial fibrillation (AF) were analyzed in the ETNA-AF (Edoxaban Treatment in Routine Clinical Practice) study involving data from multiple regional registries. This report addresses effectiveness and safety of edoxaban in the Korean ETNA-AF population. Methods: One-year data from 1887 Korean ETNA-AF participants were analyzed according to edoxaban dose and patient age and compared with results of other ETNA-AF registries. Results: Approximately 70% of patients received the recommended doses of edoxaban (60 mg/30 mg); non-recommended 60 mg and 30 mg doses were prescribed to 9.6% and 19.8% of the patients, respectively. The proportions of reference age (<65 years), youngest-old (65-74 years) and middle-old/oldest-old (≥75 years) groups were 21.4%, 40.2%, and 38.4%, respectively. Incidence of major or clinically relevant nonmajor bleeding was similar within dose (0.57%-1.71%) and age subgroups (1.26%-1.63%). Incidence of net clinical outcome, a composite of stroke, systemic embolic event, major bleeding, and all-cause mortality, was also comparable among dose subgroups (1.14%-3.10%) and age subgroups (2.28%-2.78%). The percentage of Korean patients receiving non-recommended 30 mg (19.8%) was over twice that of the European population (8.4%). However, the clinical outcomes were generally similar among different populations included in the ETNA-AF study. Conclusions: The outcomes in the Korean ETNA-AF population are like those in the global ETNA-AF population, with overall low event rates of stroke, major bleeding and all-cause mortality across age and dose subgroups. Edoxaban can be used effectively and safely in specific populations of Korean AF patients, including the elderly.

Effects of radiofrequency catheter ablation for premature ventricular complexes originating from the right ventricular outflow tract on right ventricular function.

INTRODUCTION: This study aimed to elucidate the relationship between premature ventricular complexes (PVCs) and right ventricular (RV) dysfunction, and the effects of radiofrequency catheter ablation (RFCA) on RV function. METHODS: A total of 110 patients (age, 50.8 ± 14.4 years; 30 men) without structural heart disease who had undergone RFCA for RV outflow tract (RVOT) PVCs were retrospectively included. RV function was assessed using fractional area change (FAC) and global longitudinal strain (GLS) before and after RFCA. Clinical data were compared between the RV dysfunction (n = 63) and preserved RV function (n = 47) groups. The relationship between PVC burden and RV function was analyzed. Change in RV function before and after RFCA was compared between patients with successful and failed RFCA. RESULTS: PVC burden was significantly higher in the RV dysfunction group than in the preserved RV function group (p < .001). FAC and GLS were significantly worse in proportion to PVC burden (p < .001 and p < .001, respectively). The risk factor associated with RV dysfunction was PVC burden [odds ratio (95% confidence interval), 1.092 (1.052-1.134); p < .001]. Improvement in FAC (13.0 ± 8.7% and -2.5 ± 5.6%, respectively; p < .001) and GLS (-6.8 ± 5.7% and 2.1 ± 4.2%, respectively; p < .001) was significant in the patients with successful RFCA, compared to the patients in whom RFCA failed. CONCLUSIONS: Frequent RVOT PVCs are associated with RV dysfunction. RV dysfunction is reversible by successful RFCA.

Effects of high-intensity statin combined with telmisartan versus amlodipine on glucose metabolism in hypertensive atherosclerotic cardiovascular disease patients with impaired fasting glucose: A randomized multicenter trial.

BACKGROUND: There is lacking evidence that telmisartan can improve insulin resistance in patients on high-intensity statins. This study compared the effects of telmisartan and amlodipine on glucose metabolism in hypertensive atherosclerotic cardiovascular disease (ASCVD) patients with impaired fasting glucose (IFG) requiring high-intensity rosuvastatin therapy. METHODS: Ninety-nine patients were randomly assigned to 2 groups [telmisartan-statin group (n=48) and amlodipine-statin group (n=51)] as add-on therapy to high-intensity rosuvastatin therapy (20 mg). The primary endpoint was to assess insulin resistance using the homeostatic model assessment (HOMA-IR) value at week 24. The secondary endpoint was the change in glucose metabolism indices from baseline to week 24. RESULTS: The HOMA-IR at week 24 (2.4 [interquartile range, 1.8-3.8] versus 2.7 [1.7-3.7]; P = .809) and changes in the HOMA-IR from baseline to week 24 (-7.0 [-29.0 to 21.0] versus -5.5 [-53.3 to 27.3]; P = .539) were not significantly different between 2 groups. However, the fasting glucose level at week 24 was significantly lower in the telmisartan-statin group than in the amlodipine-statin group (107.7 ± 13.4 mg/dL versus 113.3 ± 12.4 mg/dL; P = .039) and significantly decreased in the telmisartan-statin group (-3.2 ± 8.6% versus 3.8 ± 13.2%; P = .003). The proportion of patients with fasting glucose ≥100 mg/dL (71.1% versus 89.6%; P = .047) or new-onset diabetes mellitus (12.5% versus 31.4%, P = .044) at week 24 was also significantly lower in the telmisartan-statin group than in the amlodipine-statin group. CONCLUSION: In comparison to amlodipine, telmisartan did not decrease the HOMA-IR. However, telmisartan preserved insulin secretion, led to a regression from IFG to euglycemia and prevented new-onset diabetes mellitus in ASCVD patients with IFG requiring high-intensity statins.

Nonsustained atrial tachycardia in 24-hour Holter monitoring: a potential cardiac source of embolism in acute ischemic stroke.

Background: Whether nonsustained atrial tachycardia (NSAT) has a causative role similar to paroxysmal atrial fibrillation (AF) in ischemic stroke is unclear. We investigated the clinical and imaging features of ischemic stroke patients with NSAT to demonstrate that these patients would have a higher proportion of embolic strokes. Methods: We retrospectively reviewed ischemic stroke patients who underwent Holter monitoring and selected patients with NSAT. The clinical and imaging characteristics were compared between patients with and without NSAT, and the risk factors for embolic stroke were evaluated. Moreover, the images of the selected patients were analyzed according to the Trials of Org 10172 in Acute Stroke Treatment classification. Results: From a total of 1,051 patients who had 24-hour Holter monitoring, 681 patients were selected for the study. Among the selected patients, NSAT was detected in 243 patients. The patients with NSAT had a significantly higher proportion of imaging findings suggestive of cerebral embolism compared with patients without NSAT (27% vs. 14%, P<0.001). Moreover, the presence of NSAT was a statistically significant factor associated with imaging findings suggestive of cerebral embolism in the univariate (OR, 2.22; 95% CI, 1.51-3.27; P<0.001) and multivariate (OR, 2.26; 95% CI, 1.53-3.34; P<0.001) analyses. The patients with NSAT had a significantly older age at diagnosis, higher proportion of female sex, higher proportion of hypertension, lower proportion of smokers, higher CHA2DS2-VASc score, and higher left atrium index value compared with patients without NSAT. Conclusions: The embolic pattern of acute ischemic stroke in patients with NSAT was frequently observed and shared clinical characteristics of AF rather than those of atherosclerosis. As NSAT may be a potential source of cardiac embolism, we suggest a more intensive search for modifiable risk factors such as AF in ischemic stroke in patients with NSAT.

The association between cardiac involvement and long-term clinical outcomes in patients with Duchenne muscular dystrophy.

AIMS: Despite advances in contemporary cardiopulmonary therapies, cardiomyopathy remains the leading cause of death in patients with Duchenne muscular dystrophy (DMD). Also, the long-term clinical outcomes of patients with DMD and cardiomyopathy is unknown. This study investigated long-term clinical outcomes and their associated factors in patients with late-stage DMD. METHODS AND RESULTS: A total of 116 patients with late-stage DMD (age > 15 years) were enrolled in this retrospective study. All enrolled patients were followed up at a single tertiary referral hospital. LV systolic dysfunction was dichotomously defined as reduced [left ventricular ejection fraction (LVEF) ≤ 40%] vs. preserved [>40%] based on the initial echocardiographic result. The primary endpoint was all-cause death. The secondary endpoint was a composite event defined as death or unexpected hospitalization due to cardiovascular reasons including chest pain, dyspnoea, and generalized oedema. The patients were divided into preserved (n = 84, 72.4%) and reduced LVEF groups (n = 32, 27.6%). The mean age was 20.8 ± 5.9 years, the mean disease duration, 8.8 ± 3.7 years, and the mean follow-up duration, 1708 ± 659 days. For primary endpoint, the reduced LVEF group showed a lower rate of overall survival (Reduced LVEF vs. Preserved LVEF; 81.3% vs. 98.8%, log-rank P = 0.005). In the multivariable Cox regression analysis, brain-natriuretic peptide (BNP) level (adjusted hazard ratio [HR] 1.088, 95% confidence interval [CI] 1.019-1.162, P = 0.011) and diuretic use (adjusted HR 9.279, 95%CI 1.651-52.148, P = 0.011) were significant predictors of all-cause death in patients with DMD. For the secondary endpoint, the reduced LVEF group had a lower rate of freedom from composite events than the preserved LVEF group (65.6% vs. 86.9%, log-rank P = 0.005). In the multivariable Cox regression analysis, BNP level (adjusted HR 1.057, 95%CI 1.005-1.112, P = 0.032) and diuretic use (adjusted HR 4.189, 95% CI 1.704-10.296, P = 0.002) were significant predictors of the composite event in patients with DMD. CONCLUSIONS: Patients with DMD and reduced LVEF had worse clinical outcomes than those with preserved LVEF. BNP level and diuretic use were associated with adverse clinical outcomes in patients with late-stage DMD, irrespective of LVEF.

Machine Learning-Predicted Progression to Permanent Atrial Fibrillation After Catheter Ablation.

INTRODUCTION: We developed a prediction model for atrial fibrillation (AF) progression and tested whether machine learning (ML) could reproduce the prediction power in an independent cohort using pre-procedural non-invasive variables alone. METHODS: Cohort 1 included 1,214 patients and cohort 2, 658, and all underwent AF catheter ablation (AFCA). AF progression to permanent AF was defined as sustained AF despite repeat AFCA or cardioversion under antiarrhythmic drugs. We developed a risk stratification model for AF progression (STAAR score) and stratified cohort 1 into three groups. We also developed an ML-prediction model to classify three STAAR risk groups without invasive parameters and validated the risk score in cohort 2. RESULTS: The STAAR score consisted of a stroke (2 points, p = 0.003), persistent AF (1 point, p = 0.049), left atrial (LA) dimension ≥43 mm (1 point, p = 0.010), LA voltage <1.109 mV (2 points, p = 0.004), and PR interval ≥196 ms (1 point, p = 0.001), based on multivariate Cox analyses, and it had a good discriminative power for progression to permanent AF [area under curve (AUC) 0.796, 95% confidence interval (CI): 0.753-0.838]. The ML prediction model calculated the risk for AF progression without invasive variables and achieved excellent risk stratification: AUC 0.935 for low-risk groups (score = 0), AUC 0.855 for intermediate-risk groups (score 1-3), and AUC 0.965 for high-risk groups (score ≥ 4) in cohort 1. The ML model successfully predicted the high-risk group for AF progression in cohort 2 (log-rank p < 0.001). CONCLUSIONS: The ML-prediction model successfully classified the high-risk patients who will progress to permanent AF after AFCA without invasive variables but has a limited discrimination power for the intermediate-risk group.

Long-term Clinical Outcomes and Prognostic Factors After Endovascular Treatment in Patients With Chronic Limb Threatening Ischemia.

BACKGROUND AND OBJECTIVES: Endovascular therapy (EVT) first strategy has been widely adopted for the treatment of chronic limb threatening ischemia (CLTI) patients in real-world practice. This study aimed to investigate long-term outcomes of CLTI patients who underwent EVT and identify prognostic factors. METHODS: From the retrospective cohorts of a Korean multicenter endovascular therapy registry, 1,036 patients with CLTI (792 men, 68.8 ± 9.5 years) were included. The primary endpoint was amputation-free survival (AFS) defined as the absence of major amputation or death. Secondary endpoints were major adverse limb events (MALE; a composite of major amputation, minor amputation, and reintervention). RESULTS: Five-year AFS and freedom from MALE were 69.8% and 61%, respectively. After multivariate analysis, age (hazard ratio [HR], 1.476; p<0.001), end-stage renal disease (ESRD; HR, 2.340; p<0.001), Rutherford category (RC) 6 (HR, 1.456; p=0.036), and suboptimal EVT (HR, 1.798; p=0.005) were identified as predictors of major amputation or death, whereas smoking (HR, 0.594; p=0.007) was protective. Low body mass index (HR, 1.505; p=0.046), ESRD (HR, 1.648; p=0.001), femoropopliteal lesion (HR, 1.877; p=0.004), RC-6 (HR, 1.471; p=0.008), and suboptimal EVT (HR, 1.847; p=0.001) were predictors of MALE. The highest hazard rates were observed during the first 6 months for both major amputation or death and MALE. After that, the hazard rate decreased and rose again after 3-4 years. CONCLUSIONS: In CLTI patients, long-term outcomes of EVT were acceptable. ESRD, RC-6, and suboptimal EVT were common predictors for poor clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02748226.

Effectiveness and Safety of Anticoagulation Therapy in Frail Patients With Atrial Fibrillation.

BACKGROUND: Frail patients with atrial fibrillation (AF) are less likely to receive anticoagulation than nonfrail patients with AF despite frailty being associated with poorer clinical outcomes including stroke. Using a population-based cohort, we sought to assess the effectiveness and safety of oral anticoagulants (OACs) in frail patients with AF. METHODS: This retrospective cohort study analyzed 83 635 patients aged at least 65 years with AF and frailty (≥5 Hospital Frailty Risk Score) between January 1, 2013 and December 31, 2016 from the Korean National Health Insurance Service database. To account for the differences between patients receiving OAC or not and across different OAC regimens, propensity score-weighting was used. Net adverse clinical event, defined as the first event of ischemic stroke, major bleeding, or cardiovascular death, was compared. In addition, each individual outcome was examined separately. RESULTS: In the study population (57.1% women; mean age, 78.5±7.2 years), a total of 14 968 net adverse clinical event, 3718 ischemic stroke, 5536 major bleeding, and 6188 cardiovascular death occurred. In comparison with no OAC use, OAC use was associated with lower risks of net adverse clinical event (hazard ratio, 0.78 [95% CI, 0.75-0.82]), ischemic stroke (hazard ratio, 0.91 [95% CI, 0.86-0.97]), and cardiovascular death (hazard ratio, 0.52 [95% CI, 0.49-0.55]), but no difference was observed for major bleeding (hazard ratio, 1.02 [95% CI, 0.95-1.10]). Compared with warfarin, all four individual direct OAC were associated with decreased risks of net adverse clinical event, ischemic stroke, major bleeding, and cardiovascular death. The associations for OAC use (compared to no OAC use) or direct OAC use (compared to warfarin) with favorable outcomes were more prominent in individuals with a higher CHA2DS2-VASc score of at least 3. CONCLUSIONS: Among frail patients with AF, OAC treatment was associated with a positive net clinical outcome. Direct OACs provided lower incidences of stroke, bleeding, and mortality, compared with warfarin.

Impact of aortic atheroma and distensibility on diastolic function and prognosis in patients with ischemic stroke.

BACKGROUND: Patients with ischemic stroke are vulnerable to heart failure with preserved ejection fraction (HFpEF) because these conditions share common risk factors. Although evaluation of the ascending aorta, aortic arch, and proximal descending thoracic aorta is an essential step to determine the source of the causative embolism, the relationship between the degree of aortic atheroma and left ventricular (LV) diastolic function has not been extensively investigated. METHODS: We analyzed the transesophageal and transthoracic echocardiography in ischemic stroke patients. Patients with previous coronary artery disease, valvular heart disease of more than moderate degree, and an LV ejection fraction of less than 50% were excluded. The relationships between the grade of the aortic atheroma, aortic stiffness indexes, and diastolic functional indexes were evaluated. RESULTS: In 295 patients, the atheroma grade was significantly correlated with aortic stiffness index, ratio of mitral annular and inflow velocities (E/e'), left atrial volume index, and LV diastolic elastance. With further adjustment for age, hypertension, diabetes, estimated glomerular filtration rate, left atrial volume index, and LV mass index, the significance of the atheroma grade was attenuated. In the subgroup analysis, the atheroma grade was significantly and independently related to E/e' in women (ß = 0.181, p = 0.032), but not in men. However, atheroma grade was not associated with poor clinical outcomes in either sex. CONCLUSIONS: Aortic atheroma grade was significantly and independently related to LV diastolic function, especially in women. This suggests that aortic atheroma is an index of arterial stiffness and a potential risk factor for HFpEF through ventricular-vascular interactions, especially in women.

Sex-based approach for the clinical impact of polycythaemia on cardiovascular outcomes in the general population.

AIMS: Although the adverse cardiovascular effect of anaemia has been well described, the effect of polycythaemia on the cardiovascular outcomes of the general population remain unclear. The primary objective is to identify the association between polycythaemia and major adverse cardiovascular events (MACE), and the secondary objective is to identify the specific haemoglobin concentration more associated with an increased risk for MACE. METHODS AND RESULTS: This was a retrospective cohort study, 451 107 subjects were enrolled who underwent national health examinations from the Korean National Sample Cohort. We estimated the risk of MACE, a composite of cardiovascular mortality, incident myocardial infarction (MI), and stroke according to haemoglobin-based four categories. During 3.8-year of follow-up, polycythaemia group showed higher MACE [hazard ratio (HR) = 1.27 (1.13-1.44) and HR = 1.76 (1.08-2.88); in men and women, respectively], incident MI [HR = 1.37 (1.05-1.79) and HR = 3.46 (1.06-14.00)], and incident ischaemic stroke [HR = 1.27 (1.10-1.46) and HR = 1.72 (1.02-2.91)] than normal haemoglobin group (P < 0.001 in all cases). In the normal haemoglobin and polycythaemia groups, a 1 g/dL increase in haemoglobin level was associated with increased risks of MACE [HR = 1.04 (1.01-1.07) and HR = 1.05 (1.01-1.10) in men and women, each P < 0.05]. To investigate the specific haemoglobin concentration related to greater MACE incidence, we analysed the sensitivity/specificity of different haemoglobin levels: ≥16.5 g/dL in men and ≥15.0 g/dL in women showed the highest Youden's index (sensitivity + specificity - 1), with c-indices of 0.82 (0.81-0.83) and 0.83 (0.82-0.84), respectively. CONCLUSION: Even in the Korean general population, polycythaemia was significantly associated with higher rates of MACE, incident MI, and incident ischaemic stroke. Especially, subjects with haemoglobin levels ≥15.0 g/dL in women and ≥16.5 g/dL among men were associated with increased risks of MACE.

Comparison of risk profiles for new-onset atrial fibrillation between patients aged <60 and ≥60 years.

BACKGROUND: Atrial fibrillation (AF) has a heterogeneous pathophysiology according to individual patient characteristics. This study aimed to identify the effects of widely known risk factors on AF incidence according to age and to elucidate the clinical implications of these effects. METHODS AND RESULTS: We analyzed data from 501,668 subjects (≥18years old) without AF and valvular heart disease from the Korean National Health Insurance Service-National Sample Cohort. The total population was divided into two groups according to age, <60years and ≥60years. AF occurred in 0.7% of the overall population (3,416 of 501,668) during the follow-up period (mean 47.6 months). In Cox regression analysis, age, male sex, previous ischemic stroke, heart failure, and hypertension were related to increased risk of new-onset AF in both age groups. Especially in the <60years age group, risk of new-onset AF was increased by relatively modifiable risk factors: obesity (body mass index ≥25kg/m2; hazard ratio[HR] 1.37 [1.22-1.55], p<0.001, interaction p<0.001), and hypertension (HR 1.93[1.69-2.22], p<0.001, interaction p<0.001). Although interactions were not significant, chronic obstructive pulmonary disease (HR 1.41[1.24-1.60], p<0.001) and chronic kidney disease (HR 1.28[1.15-1.41], p<0.001) showed increased trends of the risk of new-onset AF in the ≥60years age group. CONCLUSION: The risk profile for new-onset AF was somewhat different between the <60years and the ≥60years age groups. Compared to the ≥60years group, relatively modifiable risk factors (such as obesity and hypertension) had a greater impact on AF incidence in the <60years age group. Different management strategies to prevent AF development according to age may be needed.

Usefulness of cardiac magnetic resonance images for prediction of sudden cardiac arrest in patients with mitral valve prolapse: a multicenter retrospective cohort study.

BACKGROUND: An association has been identified between mitral valve prolapse (MVP) and sudden cardiac arrest (SCA), and ventricular arrhythmias (VA). This study aimed to elucidate predictive factors for SCA or VA in MVP patients. METHODS: MVP patients who underwent cardiac magnetic resonance (CMR) were retrospectively included. Patients with other structural heart disease or causes of aborted SCA were excluded. Clinical characteristics (sex, age, body mass index, histories of diabetes, hypertension, and dyslipidemia) and electrocardiographic (PR interval, QRS duration, corrected QT interval, inverted T wave in the inferior leads, bundle branch block, and atrial fibrillation), echocardiographic [mitral regurgitation grade, prolapsing mitral leaflet, and right ventricular systolic pressure (RVSP)], and CMR [left atrial volume index, both ventricular ejection fractions, both ventricular end-diastolic and systolic volume indexes, prolapse distance, mitral annular disjunction, systolic curling motion, presence of late gadolinium enhancement (LGE), LGE volume and proportion] parameters were analyzed. RESULTS: Of the 85 patients [age, 54.0 (41.0-65.0) years; 46 men], seven experienced SCA or VA. Younger age and wide QRS complex were observed more often in the SCA/VA group than in the no-SCA/VA group. The SCA/VA group exhibited lower RVSP, more systolic curling motion and LGE, greater LGE volume, and higher LGE proportion. The presence of LGE [hazard ratio (HR), 19.8; 95% confidence interval (CI) 2.65-148.15; P = 0.004], LGE volume (HR 1.08; 95% CI 1.02-1.14; P = 0.006) and LGE proportion (HR 1.32; 95% CI 1.08-1.60; P = 0.006) were independently associated with higher risk of SCA or VA in MVP patients together with systolic curling motion in each model. CONCLUSIONS: The presence of systolic curling motion, high LGE volume and proportion, and the presence of LGE on CMR were independent predictive factors for SCA or VA in MVP patients.

Increased risk of ischemic stroke and systemic embolism in hyperthyroidism-related atrial fibrillation: A nationwide cohort study.

BACKGROUND: We aimed to evaluate the long-term risk of ischemic stroke/systemic embolism of hyperthyroidism-related AF. METHODS: This retrospective population-based cohort study included records of 1,034,099 atrial fibrillation patients between 2005 and 2016 from the Korean National Health Insurance Service database. After exclusion, we identified 615,724 oral anticoagulation-naïve patients aged ≥18 years with new-onset non-valvular atrial fibrillation, of whom 20,773 had hyperthyroidism-related atrial fibrillation. After 3:1 propensity score matching, ischemic stroke and systemic embolism occurrences were compared between hyperthyroidism-related and non-hyperthyroidism-related ("nonthyroidal") atrial fibrillation patients. RESULTS: After exclusion, we identified 615,724 oral anticoagulation-naïve AF patients of whom 20,773 had hyperthyroidism-related AF. Median follow-up duration was 5.9 years. Hyperthyroidism-related AF patients had significantly higher risks of ischemic stroke and systemic embolism than nonthyroidal AF patients (1.83 vs 1.62 per 100-person year, hazard ratio[HR], 1.13; 95% confidence interval[CI], 1.07 to 1.19; P < 0.001). This risk was 36% higher in hyperthyroidism-related than in nonthyroidal AF patients within 1 year of atrial fibrillation diagnosis (3.65 vs 2.67 per 100-person year, HR, 1.36; 95% CI, 1.24 - 1.50; P < 0.001). This difference was also observed in the CHA2DS2-VASc score subgroup analysis. The risk of ischemic stroke and systemic embolism significantly decreased in patients treated for hyperthyroidism (HR, 0.64; 95% CI, 0.58 to 0.70; P < 0.001). CONCLUSIONS: Hyperthyroidism-related AF patients have high risks of ischemic stroke and systemic embolism like nonthyroidal AF, especially when initially diagnosed. This risk is reduced by treating hyperthyroidism.

Left ventricular outflow obstruction occurs immediately after exercise in patients with non-obstructive hypertrophic cardiomyopathy.

We evaluated the hemodynamic and geometric determinants of latent obstruction (LO, trans-left ventricular outflow tract (LVOT) gradient ≥30 mmHg with provocation) in patients with non-obstructive hypertrophic cardiomyopathy (HCMP). A total of 35 patients with non-obstructive HCMP underwent stepwise supine bicycle exercise echocardiography. Trans-LVOT pressure gradients, mitral geometric parameters, left ventricular ejection fractions (LVEF) and left ventricular end-systolic and diastolic dimensions (LVESD, LVEDD) were measured at each stage. The highest peak LVOT pressure gradient predominantly occurred immediately after exercise (n = 32, 91.3%) rather than during peak exercise (n = 3, 8.7%). Significant LO developed in nine patients (25%). No significant differences were found in resting echocardiographic parameters. Compared to the remaining patients, however, patients with LO had longer residual mitral leaflets (defined as residual portions of leaflets after coaptation; 4 ± 4 vs. 13 ± 4 mm, respectively; p = 0.001) and higher resting LVOT pressure gradients (7.4 ± 3.7 vs. 12.9 ± 5.8 mmHg, respectively; p = 0.001). Substantial decreases in mitral annular diameters from peak exercise to recovery after exercise were observed in the LO group, while mitral annular diameters increased after exercise in the non-LO group. In conclusion, the highest peak LVOT pressure gradient predominantly occurred immediately after exercise rather than during peak exercise, regardless of LO. Abrupt decrease of mitral annular diameter immediately after exercise, a longer residual mitral leaflet and a higher resting LVOT pressure gradient at rest might be related to LO.

Effect of sarcomere and mitochondria-related mutations on myocardial fibrosis in patients with hypertrophic cardiomyopathy.

BACKGROUND: Myocardial fibrosis is an important prognostic factor in hypertrophic cardiomyopathy (HCM). However, the contribution from a wide spectrum of genetic mutations has not been well defined. We sought to investigate effect of sarcomere and mitochondria-related mutations on myocardial fibrosis in HCM. METHODS: In 133 HCM patients, comprehensive genetic analysis was performed in 82 nuclear DNA (33 sarcomere-associated genes, 5 phenocopy genes, and 44 nuclear genes linked to mitochondrial cardiomyopathy) and 37 mitochondrial DNA. In all patients, cardiovascular magnetic resonance (CMR) was performed, including 16-segmental thickness, late gadolinium enhancement (LGE), native and post-T1, extracellular volume fraction (ECV), and T2, along with echo-Doppler evaluations. RESULTS: Patients with sarcomere mutation (SM, n = 41) had higher LGE involved segment, % LGE mass, ECV and lower post-T1 compared to patients without SM (n = 92, all p < 0.05). When classified into, non-mutation (n = 67), only mitochondria-related mutation (MM, n = 24), only-SM (n = 36) and both SM and MM (n = 5) groups, only-SM group had higher ECV and LGE than the non-mutation group (all p < 0.05). In non-LGE-involved segments, ECV was significantly higher in patients with SM. Within non-SM group, patients with any sarcomere variants of uncertain significance had higher echocardiographic Doppler E/e' (p < 0.05) and tendency of higher LGE amount and ECV (p > 0.05). However, MM group did not have significantly higher ECV or LGE amount than non-mutation group. CONCLUSIONS: SMs are significantly related to increase in myocardial fibrosis. Although, some HCM patients had pathogenic MMs, it was not associated with an increase in myocardial fibrosis.

Frailty and the Effect of Catheter Ablation in the Elderly Population With Atrial Fibrillation　- A Real-World Analysis.

BACKGROUND: It is unclear whether catheter ablation is beneficial for frail elderly patients with atrial fibrillation (AF). This study evaluated the effect of ablation on outcomes in frail elderly patients with AF.Methods and Results:From the Korean National Health Insurance Service database, 194,928 newly diagnosed AF patients were treated with ablation or medical therapy (rhythm or rate control) between 2005 and 2015. Among these patients, the study included 1,818 (ablation; n=119) frail and 1,907 (ablation; n=230) non-frail elderly (≥75 years) patients. Propensity score matching was used to correct for differences between groups. During 28 months (median) follow up, the risk of all-cause death, composite outcome (all-cause death, heart failure admission, stroke/systemic embolism, and sudden cardiac arrest), and each outcome did not change after ablation in frail elderly patients. However, in non-frail elderly patients, ablation was associated with a lower risk of all-cause death (3.5 and 6.2 per 100 person-years; hazard ratio [HR] 0.48; 95% confidence interval [CI] 0.30-0.79; P=0.004), and composite outcome (6.9 and 11.2 per 100 person-years; HR 0.54; 95% CI 0.38-0.75; P<0.001). CONCLUSIONS: Ablation may be associated with a lower risk of death and composite outcome in non-frail elderly, but the beneficial effect of ablation was not significant in frail elderly patients with AF. The effect of frailty on the outcome of ablation should be evaluated in further studies.

Coronary calcification is associated with elevated serum lipoprotein (a) levels in asymptomatic men over the age of 45 years: A cross-sectional study of the Korean national health checkup data.

ABSTRACT: Lipoprotein a (Lp (a)) and coronary artery calcification (CAC) are markers of coronary artery and cardiovascular diseases. However, the association between Lp (a) and CAC in asymptomatic individuals remains unclear. In this study, we aimed to determine the influence of Lp (a) on CAC in asymptomatic individuals.We included 2019 asymptomatic Korean adults who underwent testing for a coronary artery calcium score (CACS) and Lp (a) at the Gangnam Severance Hospital Health Checkup Center in Korea from January 2017 to August 2019. Participants were divided into 2 groups: CACS = 0 and CACS > 0. Factors affecting the CACS were analyzed by sex. Because age is a major risk factor for atherosclerosis, ≥45 years in men and ≥55 years in women, we further divided participants into 4 subgroups (≥45 and <45 in men, ≥55 and <55 in women). Factors affecting the CACS in the 4 groups were analyzed.There was a positive correlation between the CACS and traditional cardiovascular risk factors. Lp (a) positively correlated with the CACS in men (P < .01) and remained significant after multivariable logistic regression (P < .01). The same result was observed in men aged ≥45 years (P < .01).Lp (a) is an independently associated factor of CAC and a marker of coronary atherosclerosis in asymptomatic men aged ≥45 years. In asymptomatic men aged ≥45 years, Lp (a) should be measured, and intensive Lp (a)-lowering treatment should be considered.

Reduction of mortality by catheter ablation in real-world atrial fibrillation patients with heart failure.

Whether catheter ablation for atrial fibrillation (AF) improves survival and affects other outcomes in real-world heart failure (HF) patients is unclear. This study aimed to evaluate whether ablation reduces death, and other outcomes in real-world AF patients with HF. Among 834,735 patients with AF from 2006 to 2015 in the Korean National Health Insurance Service database, 3173 HF patients underwent AF ablation. Propensity score weighting was used to correct for differences between the groups. During median 54 months follow-up, the risk of all-cause death in ablated patients was less than half of that in patients with medical therapy (2.8 vs. 6.2 per 100 person-years; hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.27-0.65, p < 0.001). Ablation was related with lower risk of cardiovascular death (HR 0.38, 95% CI 0.32-0.62, p < 0.001), HF admission (HR 0.39, 95% CI 0.33-0.46, p < 0.001) and stroke/systemic embolism (HR 0.44, 95% CI 0.37-0.53, p < 0.001). In subgroup analysis, the risk of all-cause death was reduced in most subgroups except in the elderly (≥ 75 years) and strictly anticoagulated patients. Ablation may be associated with reduced risk of all-cause death and cardiovascular death in real-world AF patients with HF, supporting the role of AF ablation in patients with HF.

Effect of Renal and Left Ventricular Function on Serial Pulmonary Arterial Pressure Changes after Device Closure of Atrial Septal Defect.

BACKGROUND: The age of candidates for device closure of atrial septal defect (ASD) has been increasing. Thus, concerns exist about dyspnea aggravation or atrial fibrillation development after device closure due to augmentation of left ventricular (LV) and left atrial (LA) preload. This study aimed to examine patterns and determinants of serial pulmonary arterial pressure and left ventricular filling pressure changes after device closure of ASD. METHODS: Among the 86 consecutive patients who underwent percutaneous device closure of ASD, those with end-stage renal disease or those without pre- or postprocedural Doppler data were excluded. The clinical, transesophageal, and transthoracic echocardiographic findings of 78 patients were collected at baseline, one-day postprocedure, and one-year follow-up. RESULTS: The mean age of study patients was 49.8 ± 15.0 years, and the average maximal defect diameter and device size were 20.2 ± 6.0 mm and 23.8 ± 6.4 mm. Four patients (5.6%) underwent new-onset atrial fibrillation, and five patients (6.4%) took diuretics within one-year after closure. Some patients (n = 21; 27%) exhibited paradoxically increased tricuspid regurgitant velocity (TRV) one-day postprocedure; they also were older with lower e', glomerular filtration rate, and LV ejection fraction and a higher LA volume index. However, even in these patients, TRV deceased below baseline levels one-year later. Both E/e' and LA volume index significantly increased immediately after device closure, but all decreased one-year later. Larger defect size and higher TRV were significantly correlated with immediate E/e' elevation. CONCLUSION: In older, renal, diastolic, and systolic dysfunctional patients with larger LA and scheduled for larger device implantation, peri-interventional preload reduction therapy would be beneficial.