Sakiko Miyazaki

Influencing factors on cardiac structure and function beyond glycemic control in patients with type 2 diabetes mellitus

BackgroundWe hypothesized that clinical factors other than glycemic control may influence abnormal cardiac function in patients with type 2 diabetes mellitus (T2DM). We aimed to investigate the independent factors for abnormal cardiac function among clinical factors in T2DM.MethodsWe studied 148 asymptomatic patients with T2DM without overt heart disease. Echocardiographic findings were compared between diabetic patients and 68 age-matched healthy subjects. Early (E) and late (A) diastolic mitral flow velocity and early diastolic mitral annular velocity (e’) were measured for assessing left ventricular (LV) diastolic function. We evaluated insulin resistance, non-esterified fatty acid, high-sensitive CRP, estimated glomerular filtration rate, waist/hip ratio, abdominal visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) and other clinical characteristics in addition to glycemic control. VAT and SAT were quantified by computed tomography.ResultsIn T2DM, E/A and e’ were significantly lower, and E/e’, left atrial volume and LV mass were significantly greater than in control subjects. In multivariate liner regression analysis, VAT was an independent determinant of left atrial volume (β =0.203, p=0.011), E/A (β =−0.208, p=0.002), e’ (β =−0.354, p<0.001) and E/e’ (β=0.220, p=0.003). Age was also an independent determinant, whereas fasting plasma glucose and hemoglobin A1c levels were not. In addition to systolic blood pressure, waist-hip ratio (β=0.173, p=0.024) and VAT/SAT ratio (β=0.162, p=0.049) were independent determinants of LV mass.ConclusionExcessive visceral fat accompanied by adipocyte dysfunction may play a greater role than glycemic control in the development of diastolic dysfunction and LV hypertrophy in T2DM.

Influence of baseline ejection fraction on the prognostic value of paravalvular leak after transcatheter aortic valve implantation

BACKGROUND Moderate or severe paravalvular leak (PVL ≥ moderate) after transcatheter aortic valve implantation (TAVI) is associated with poor outcomes. The aim of this study was to assess whether the baseline ejection fraction (EF) affects the impact of PVL on mortality after TAVI. METHODS We analyzed 514 consecutive patients with native severe aortic stenosis who underwent TAVI. Patients were divided into two groups: EF < 40% group (n = 84) and EF ≥ 40% group (n = 430) according to baseline EF. RESULTS The mean age was 79.5 years and 49% were male. Patients in the EF < 40% group were younger and with higher logistic EuroSCORE compared to patients in the EF ≥ 40% group. Diabetes, coronary artery disease, atrial fibrillation and renal insufficiency were more prevalent in the EF < 40% group. Patients in the EF <40% group had more mitral regurgitation. In-hospital mortality was significantly higher in the EF < 40% group (8.3% vs. 0.9%, p < 0.0001). PVL ≥ moderate was significantly associated with increased 2-year estimated mortality only in the EF <40% group (65% vs. 20%, log-rank p < 0.0001) whereas no difference was seen in the EF ≥40% group (24% vs. 19%, log-rank p = 0.509). Interaction between PVL ≥ moderate and EF < 40% was statistically significant. CONCLUSIONS The impact of PVL ≥ moderate on mortality after TAVI was significant in the EF <40% group but not in the EF ≥ 40% group in our study. Even though operators should aim to minimize PVL in all TAVI patients, special attention is required for patients with reduced baseline EF.

Comparison of 2-year outcomes between zotarolimus-eluting and everolimus-eluting new-generation cobalt-chromium alloy stents in real-world diabetic patients.

Background: To date, it remains unknown whether different types of new‐generation drug‐eluting stents have a differential impact on long‐term outcomes in diabetic patients. Methods and Results: In this historical cohort study (two Italian centers), we analyzed 400 diabetic patients with 553 coronary lesions treated with new‐generation CoCr zotarolimus‐eluting stents (R‐ZES: 136 patients, 196 lesions) or everolimus‐eluting stents (EES: 264 patients, 357 lesions) between October 2006 and August 2012. Primary endpoint was the occurrence of major adverse cardiac events (MACE) over a 2‐year follow‐up period. MACE was defined as all‐cause mortality, any myocardial infarction (MI) and/or target lesion revascularization (TLR). Multivessel revascularization, intervention for restenotic lesion and use of intravascular ultrasound were significantly higher in the R‐ZES group, whereas small stent (≤2.5 mm) deployment was significantly higher in the EES group. At 2‐year follow‐up, there was no significant difference in occurrence of MACE (R‐ZES vs EES: 22.8% vs 18.9%, P = 0.39). Similarly, no significant differences were observed in the composite endpoint of all‐cause mortality/MI (10.0% vs 10.3%, P = 0.86) or TLR (12.4% vs 7.4%, P = 0.11). Adjustment for confounders and baseline propensity‐score matching did not alter the aforementioned associations. Conclusion: After 2 years of follow up similar outcomes (MACE, all‐cause mortality/MI, TLR) were observed in real‐world diabetic patients, including those with complex lesions and patient characteristics, treated with R‐ZES and EES.

Significance of Coronary Artery Disease and Left Ventricular Afterload in Unoperated Asymptomatic Aortic Stenosis.

BACKGROUND Because the covariates of cardiovascular events in unoperated patients with asymptomatic aortic stenosis (AS) have not been adequately evaluated, we aimed to identify them. METHODSANDRESULTS A total of 230 patients with asymptomatic severe AS were retrospectively enrolled. The patients were divided into 2 groups based on aortic valve replacement (AVR) after enrollment: a non-AVR group (n=112), and an AVR group (n=118). The primary clinical endpoint was cardiovascular events, which were defined as cardiovascular death or hospitalization. Coronary artery disease [hazard ratio (HR): 3.62, 95% confidence interval (CI): 1.585-8.245, P<0.01] and high valvulo-arterial impedance (HR: 3.08, 95% CI: 1.261-7.532, P<0.05) were identified as independent covariates of cardiovascular events in the non-AVR group. The relative risk of cardiovascular events rose with an increase in the number of risk factors (P<0.0001). CONCLUSIONS In unoperated patients with asymptomatic AS, the presence of coronary artery disease and increased global left ventricular afterload may be associated with a poor prognosis.

Registry of Japanese patients with atrial fibrillation focused on anticoagulant therapy in the new era: The RAFFINE registry study design and baseline characteristics

BACKGROUND The management of atrial fibrillation (AF) has evolved with the development of direct oral anticoagulants (DOACs), but data on their clinical effectiveness and safety outside clinical trial settings are limited. METHOD The RAFFINE registry is an observational, multicenter, prospective registry of Japanese patients with AF, designed to follow clinical events over 3 years. Patient enrollment was conducted from 2013 to 2015 at university hospitals, general hospitals, and private clinics to ensure inclusion of a broad spectrum of representative AF patients. The primary outcome events in this study will be ischemic stroke, systemic embolism, and major bleeding. RESULT We enrolled 3901 ambulatory patients with AF from 4 university hospitals and 50 general hospitals/clinics in Japan. The mean patient age was 72.6 years and 68.5% were male. The type of AF was paroxysmal in 37.8%, persistent in 9.3%, and permanent in 51.7%. Major coexisting diseases were hypertension (72.7%), diabetes mellitus (30.3%), congestive heart failure (23.8%), history of ischemic stroke or transient ischemic attack (15.1%), and coronary artery disease (13.7%). Of the entire cohort, 44.6% were treated with warfarin and 43.0% were treated with DOACs. The prescription of DOACs exceeded that of warfarin in the general hospitals and clinics. Risk scores such as CHADS2 score, CHA2DS2-VASc score, and HAS-BLED score were higher in patients at university hospitals than in patients at general hospitals or clinics. CONCLUSION The RAFFINE registry at baseline described the current status of anticoagulation therapy in Japan and long-term follow-up data will identify how outcomes vary between stratified groups in patients with AF in the DOAC era (UMIN Clinical Trials Registry UMIN000009617).

Acute Effects of Positive Airway Pressure on Functional Mitral Regurgitation in Patients with Systolic Heart Failure

Background: Acute effects of positive airway pressure (PAP) [including continuous PAP (CPAP) and adaptive servo-ventilation, an advanced form of bi-level PAP] on functional mitral regurgitation (fMR) in patients with heart failure (HF) with left ventricular (LV) systolic dysfunction remain unclear. Thus, whether PAP therapy reduces fMR in such patients with HF was investigated. Methods and Results: Twenty patients with HF and LV systolic dysfunction defined as LV ejection fraction (LVEF) <50% (14 men; mean LVEF, 35.0 ± 11.5%) with fMR underwent echocardiography during 10-min CPAP (4 and 8 cm H2O) and adaptive servo-ventilation. For fMR assessment, MR jet area fraction, defined as the ratio of MR jet on color Doppler to the left atrial area, was measured. The forward stroke volume (SV) index (fSVI) was calculated from the time-velocity integral, cross-sectional area of the aortic annulus, and body surface area. fMR significantly reduced on CPAP at 8 cm H2O (0.30 ± 0.12) and adaptive servo-ventilation (0.29 ± 0.12), compared with the baseline phase (0.37 ± 0.12) and CPAP at 4 cm H2O (0.34 ± 0.12) (P < 0.001). The fSVI did not change in any of the PAP sessions (P = 0.888). However, significant differences in fSVI responses to PAP were found between sexes (P for interaction, 0.006), with a significant reduction in fSVI in women (P = 0.041) and between patients with baseline fSVI ≥ and < the median value (27.8 ml/m2, P for interaction, 0.018), with a significant fSVI reduction in patients with high baseline fSVI (P = 0.028). In addition, significant differences were found in fSVI responses to PAP between patients with LV end-systolic volume (LVESV) index ≥ and < the median value (62.0 ml/m2, P for interaction, 0.034), with a significant fSVI increase in patients with a high LVESV index (P = 0.023). Conclusion: In patients with HF, LV systolic dysfunction, and fMR, PAP can alleviate fMR without any overall changes in forward SV. However, MR alleviation due to PAP might be associated with a decrease in forward SV in women with high baseline SV, whereas MR alleviation due to PAP might be accompanied by increased forward SV in patients with a dilated LV.

When and how aortic stenosis is first diagnosed: A single-center observational study

BACKGROUND The development of clinical symptoms is associated with cardiovascular events in patients with aortic stenosis (AS). Thus, early diagnosis of AS is clinically important. However, there are few data on symptom status or the severity of AS when patients are first diagnosed, or on how AS is detected in routine practice. We aimed to investigate when and how AS patients are first diagnosed in our hospital. METHODS We retrospectively enrolled 198 AS patients diagnosed from 1989 to 2009, and identified their symptoms and AS severity at the time of the first diagnosis. We also assessed the reasons why they came to the hospital based on their medical records. RESULTS Of the 198 patients, 82 (41.6%) had voluntarily visited or been referred to our hospital after developing clinical symptoms (Symptomatic group). The remaining 116 patients (58.4%) had been asymptomatic, and cardiovascular disease was suspected during an annual or occasional health checkup (Asymptomatic group). The initial findings in the Asymptomatic group that led to the diagnosis of AS were: a systolic murmur on auscultation (62%), abnormal electrocardiography (27%), or abnormal echocardiography (11%). The Symptomatic group had significantly greater AS severity and an increased left ventricular mass index, and experienced more cardiac events (valve replacement or cardiac death) during the follow-up period. CONCLUSIONS About 40% of the AS patients in this study were not diagnosed until they developed clinical symptoms, suggesting that many other patients in the community might have a latent risk of cardiovascular events. Auscultation plays an important role in the early diagnosis of AS.