Sex differences in the association between epicardial adipose tissue volume and left atrial volume index.

BACKGROUND: Sex disparities in the association between epicardial adipose tissue volume (EATV) and cardiovascular disease have been reported. The sex-dependent effects of EATV on left atrial (LA) size have not been elucidated. METHODS: Consecutive 247 subjects (median 65 [interquartile range 57, 75] years; 67% of men) who underwent multi-detector computed tomography without significant coronary artery disease or moderate to severe valvular disease were divided into two groups: patients with sinus rhythm (SR) or atrial fibrillation (AF). Sex differences in the association between the EATV index (EATVI) (mL/m2) and LA volume index (LAVI) in 63 SR (28 men and 35 women) and 184 AF (137 men and 47 women) patients were evaluated using univariate and multivariate regression analyses. RESULTS: In overall that includes both men and women, the relationship between EATVI and LAVI was not significantly correlated for patients with SR and AF. The relationship between EATVI and LAVI differed between men and women in both SR and AF groups. In SR patients, there was a positive relationship between EATVI and LAVI in men, but not in women. In contrast, in patients with AF, a negative relationship was found between EATVI and LAVI in women, whereas no association was found in men. CONCLUSIONS: We evaluated sex differences in the association between EATVI and LAVI in patients with either SR or AF, and found a positive relationship in men with SR and a negative relationship in women with AF. This is the first report to evaluate sex differences in the relationship between EATVI and LAVI, suggesting that EAT may play a role, at least in part, in sex differences in the etiology of AF.

The association between frailty and chronic kidney disease; cross-sectional analysis of the Nambu Cohort Study.

BACKGROUND: Both frailty and chronic kidney disease (CKD) increase with age and share many similarities. Many studies have demonstrated an association between frailty and chronic kidney disease (CKD), but an association with dipstick proteinuria is limited. METHODS: This is the cross-sectional analysis of the Nambu Cohort Study at the beginning of observation. Frailty was diagnosed using Kihon Checklist. Logistic analysis was used to evaluate the association between frailty and CKD or dipstick proteinuria. RESULTS: Among a total of 630 outpatients [age, 78 (70-84) years, men, 50%], the prevalence of patients with pre-frailty and frailty was 32% and 40%, respectively. The proportion of patients with pre-frailty and frailty increased with decreasing estimated glomerular filtration rate (eGFR) and increasing dipstick proteinuria levels. The odds ratios (95% confidence intervals) for CKD stage of 60 < eGFR ≤ 45 ml/min/1.73 m2, and 45 ml/min/1.73 m2 < eGFR for frailty was 0.87 (0.56-1.35) and 2.54 (1.46-4.53), respectively, compared with non-CKD as a reference. Furthermore, the odds ratios for the frailty of dipstick proteinuria with ± and + or over were 1.36 (0.88-2.09) and 1.78 (1.00-3.17), respectively, when dipstick proteinuria-was used as a reference. Moreover, the combination of eGFR and dipstick proteinuria levels increased the odds ratio for pre-frailty and frailty. CONCLUSION: Elderly patients with CKD had a higher prevalence of pre-frailty and frailty. By adding urinary protein information to eGFR, the link between CKD and frailty becomes even more robust.

Effect of the Epicardial Adipose Tissue Volume on the Prevalence of Paroxysmal and Persistent Atrial Fibrillation.

BACKGROUND: Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with atrial fibrillation (AF), it is controversial whether there is a dose-response relationship of increasing EATV along the continuum of AF. We evaluated the effect of the EATV on the prevalence of paroxysmal AF (PAF) and persistent AF (PeAF) and the relationships with cardiac structure and functional remodeling.Methods and Results:Subjects who underwent multidetector computed tomography (MDCT) coronary angiography because of symptoms suggestive of coronary artery disease were divided into sinus rhythm (SR) (n=112), PAF (n=133), and PeAF (n=71) groups. The EATV index (EATV/body surface area, mL/m2) was strongly associated with the prevalence of PAF and PeAF on the model adjusted for known AF risk factors. The effect of the EATV index on the prevalence of PeAF, but not on that of PAF, was modified by the left atrial (LA) dimension, suggesting that extension of the LA dimension is related to EATV expansion in PeAF. The cutoff value of the EATV index for the prevalence was higher in PeAF than in PAF (64 vs. 55 mL/m2, P<0.01). CONCLUSIONS: The EATV index is associated with the prevalence of PAF and PeAF, and its cutoff values are predictive for PAF and PeAF development independently of other AF risk factors.

Superior Rhythm Discrimination With the SmartShock Technology Algorithm　- Results of the Implantable Defibrillator With Enhanced Features and Settings for Reduction of Inaccurate Detection (DEFENSE) Trial.

BACKGROUND: Shocks delivered by implanted anti-tachyarrhythmia devices, even when appropriate, lower the quality of life and survival. The new SmartShock Technology®(SST) discrimination algorithm was developed to prevent the delivery of inappropriate shock. This prospective, multicenter, observational study compared the rate of inaccurate detection of ventricular tachyarrhythmia using the SST vs. a conventional discrimination algorithm.Methods and Results:Recipients of implantable cardioverter defibrillators (ICD) or cardiac resynchronization therapy defibrillators (CRT-D) equipped with the SST algorithm were enrolled and followed up every 6 months. The tachycardia detection rate was set at ≥150 beats/min with the SST algorithm. The primary endpoint was the time to first inaccurate detection of ventricular tachycardia (VT) with conventional vs. the SST discrimination algorithm, up to 2 years of follow-up. Between March 2012 and September 2013, 185 patients (mean age, 64.0±14.9 years; men, 74%; secondary prevention indication, 49.5%) were enrolled at 14 Japanese medical centers. Inaccurate detection was observed in 32 patients (17.6%) with the conventional, vs. in 19 patients (10.4%) with the SST algorithm. SST significantly lowered the rate of inaccurate detection by dual chamber devices (HR, 0.50; 95% CI: 0.263-0.950; P=0.034). CONCLUSIONS: Compared with previous algorithms, the SST discrimination algorithm significantly lowered the rate of inaccurate detection of VT in recipients of dual-chamber ICD or CRT-D.

Improved paradoxical splitting of the second heart sound after cardiac resynchronization therapy.

The outcome of paradox splitting of the second heart sound (S2) after cardiac resynchronization therapy (CRT) has not been well defined. We present a case of right ventricular pacing induced heart failure with prominent paradox splitting of S2 which markedly improved after upgrading to CRT.

Blood pressure, frailty status, and all-cause mortality in elderly hypertensives; The Nambu Cohort Study.

Antihypertensive therapy is pivotal for reducing cardiovascular events. The 2019 Guidelines for the Management of Hypertension set a target blood pressure (BP) of <140/90 mmHg for persons older than 75 years of age. Optimal BP levels for older persons with frailty, however, are controversial because evidence for the relationship between BP level and prognosis by frailty status is limited. Here, we evaluated the relationship between systolic BP and frailty status with all-cause mortality in ambulatory older hypertensive patients using data from the Nambu Cohort study. A total of 535 patients (age 78 [70-84] years, 51% men, 37% with frailty) were prospectively followed for a mean duration of 41 (34-43) months. During the follow-up period, 49 patients died. Mortality rates stratified by systolic BP and frailty status were lowest in patients with systolic BP < 140 mmHg and non-frailty, followed by those with systolic BP ≥ 140 mmHg and non-frailty. Patients with frailty had the highest mortality regardless of the BP level. The adjusted hazard ratios (95% confidence intervals) of each category for all-cause mortality were as follows: ≥140 mmHg/Non-frailty 3.19 (1.12-11.40), <140 mmHg/Frailty 4.72 (1.67-16.90), and ≥140 mmHg/Frailty 3.56 (1.16-13.40) compared with <140 mmHg/Non-frailty as a reference. These results indicated that frail patients have a poor prognosis regardless of their BP levels. Non-frail patients, however, with systolic BP levels <140 mmHg had a better prognosis. Frailty may be a marker to differentiate patients who are likely to gain benefit from antihypertensive medication among older hypertensives.

RR interval variability in the evaluation of ventricular tachycardia and effects of implantable cardioverter defibrillator therapy.

BACKGROUND: An implantable cardioverter defibrillator (ICD) is the most reliable therapeutic device for preventing sudden cardiac death in patients with sustained ventricular tachycardia (VT). Regarding its effectiveness, targeted VT is defined based on the tachyarrhythmia cycle length. However, variations in RR interval variability of VTs may occur. Few studies have reported on VT characteristics and effects of ICD therapy according to the RR interval variability. We aimed to identify the clinical characteristics of VTs and ICD therapy effects according to the RR interval variability. METHODS: We analyzed 821 VT episodes in 69 patients with ICDs or cardiac resynchronization therapy defibrillators. VTs were classified as irregular when the difference between two successive beats was >20 ms in at least one of 10 RR intervals; otherwise, they were classified as regular. We evaluated successful termination using anti-tachycardia pacing (ATP)/shock therapy, spontaneous termination, and acceleration between regular and irregular VTs. The RR interval variability reproducibility rates were evaluated. RESULTS: Regular VT was significantly more successfully terminated than irregular VT by ATP. No significant difference was found in shock therapy or VT acceleration between the regular and irregular VTs. Spontaneous termination occurred significantly more often in irregular than in regular VT cases. The reproducibility rates of RR interval variability in each episode and in all episodes were 89% and 73%, respectively. CONCLUSIONS: ATP therapy showed greater effectiveness for regular than for irregular VT. Spontaneous termination was more common in irregular than in regular VT. RR interval variability of VTs seems to be reproducible.

Age-Dependent Efficacy of Ezetimibe for Low-Density Lipoprotein Cholesterol Reduction in Japanese Patients with or without Type 2 Diabetes Mellitus.

Ezetimibe reduces cardiovascular risk by lowering the levels of low-density lipoprotein cholesterol (LDL-C). However, there is limited information regarding the factors associated with ezetimibe-mediated LDL-C reduction. We investigated the factors associated with LDL-C reduction after ezetimibe administration in Japanese patients with or without type 2 diabetes mellitus (T2DM). This single-center retrospective observational study enrolled a total of 266 consecutive ezetimibe-naïve patients, of which 154 were excluded because of either switching from statin or fenofibrate to ezetimibe (n = 52) or ezetimibe discontinuation (n = 102). Finally, 112 patients were eligible for analysis. To identify the factors influencing LDL-C levels, univariate and multivariate linear regression analyses were performed after 52 weeks of ezetimibe treatment. Overall, advanced age, T2DM, and high baseline LDL-C were significantly associated with a greater decrease in LDL-C levels. In the non-T2DM group, advanced age and high baseline LDL-C were associated with greater decrease in LDL-C levels. In the T2DM group, baseline LDL-C was the only factor that influenced the change in LDL-C levels. Advanced age was significantly associated with higher LDL-C reduction in non-T2DM patients, but not in T2DM patients. Ezetimibe use might be beneficial in older patients without T2DM. The lack of association between age and the LDL-C lowering effect by ezetimibe in patients with T2DM may be due to yet unknown mechanism except low statistical power.

Cause of Death and Associated Factors in Elderly Patients With Atrial Fibrillation　- Long-Term Retrospective Study.

Background: Oral anticoagulant (OAC) therapy reduces the risk of stroke in patients with atrial fibrillation (AF). This study elucidated the causes of death and related factors in elderly Japanese AF patients. Methods and Results: Over a median (interquartile range [IQR]) follow-up period of 46 (20-76) months, there were 171 all-cause deaths (28% cardiovascular, 46% non-cardiovascular, and 26% unknown causes) among 389 AF patients (median [IQR] age 80 [74-85] years; CHAD2DS2-VASc score 5 [4-6]). Cox regression analysis indicated that diabetes was associated with an increase in all-cause death (hazard ratio [HR] 1.48; 95% confidence interval [CI] 1.02-2.13), whereas hypercholesterolemia (HR 0.53; 95% CI 0.35-0.79), pre-existing heart failure (HR 0.67; 95% CI 0.48-0.95), and OAC use (HR 0.62; 95% CI 0.44-0.88) were associated with reductions in all-cause death. Pre-existing heart failure was associated with both cardiovascular (HR 3.03; 95% CI 1.33-8.20) and non-cardiovascular (HR 0.44; 95% CI 0.30-0.65) deaths, in opposite directions. OAC use was associated with a reduction in cardiovascular death (HR 0.34, 95% CI 0.17-0.69). The predominance of non-cardiovascular death and death-related factors were equivalent regardless of when observations started (before 2009 or in 2009 and later). Conclusions: The predominant cause of death in elderly Japanese AF patients was non-cardiovascular. Distinct clinical factors were associated with cardiovascular and non-cardiovascular death.

Cardiovascular risk profile and frailty in Japanese outpatients: the Nambu Cohort Study.

Epidemiologic findings indicate that unfavorable cardiovascular (CV) risk profiles, such as elevated systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and overweight, decelerate with aging. Few studies, however, have evaluated the association between the CV risk profile and frailty. We performed a cross-sectional analysis using the baseline data of a prospective cohort study. A total of 599 subjects (age, 78 [range: 70-83] years; men, 50%) were analyzed in an outpatient setting. Frailty was diagnosed in 37% of the patients according to the Kihon Checklist score. An unfavorable CV risk profile was associated with a lower risk of frailty. The adjusted odds ratios (ORs; 95% confidence interval [CI]) of each CV risk factor for frailty were as follows: SBP (each 10 mmHg increase) 0.83 (0.72-0.95), LDL-C (each 10 mg/dl increase) 0.96 (0.86-1.05), and body mass index (each 1 kg/m2 increase) 1.03 (0.97-1.10). Moreover, the total number of CV risk factors within the optimal range was significantly associated with the risk of frailty with the following ORs (95% CI): 1, 2.30 (0.75-8.69); 2, 3.22 (1.07-11.97); and 3, 4.79 (1.56-18.05) compared with patients having no risk factors within optimal levels (p for trend 0.008). Abnormal homeostasis might lead to lower levels of CV risk factors, which together result in "reverse metabolic syndrome." Our findings indicate that a favorable CV risk profile is associated with frailty.

Usefulness of Epicardial Adipose Tissue Volume to Predict Recurrent Atrial Fibrillation After Radiofrequency Catheter Ablation.

Although increasing evidence suggests that epicardial adipose tissue volume (EATV) is associated with post-ablation atrial fibrillation (AF), ranges of EATV predictive of post-ablation recurrence of AF remain unclear. In this study, we evaluated: (1) relationships between EATV and characteristics of AF, (2) impact of EATV on recurrent AF after radiofrequency ablation; , and (3) cut-off point for recurrent AF using a receiver operating characteristic curve. In 218 consecutive symptomatic patients undergoing who underwent ablation for AF (143 paroxysmal AF; 78 persistent AF), the EATV index (EATVI: EATV/body surface area, mL/m2) was measured using 320-row multidetector computed tomography. The high EATV group showed specific cardiometabolic derangements as well as left atrial dilatation and left ventricular dysfunction. Multivariate regression analysis showed that the EATVI was an independent predictor of recurrent AF after catheter ablation. High EATV (EATVI ≥ 85 mL/m2) or EATVI cutoff ≥116 mL/m2 can predict recurrent AF after catheter ablation, independent of other risk factors. In conclusion, EATVI was an independent predictor of recurrent AF after catheter ablation; a high EATV tertile or EATVI cutoff may be useful for prediction of recurrent AF after catheter ablation. Future studies should determine the utility of the EATVI in the clinical setting of AF ablation.