Serial longitudinal changes of coronary calcified plaques with clear outer borders under intensive lipid management: insights from optical coherence tomography.

Percutaneous coronary intervention (PCI) for calcified lesions is one of the most challenging procedures related to worse clinical outcomes. To stabilize vulnerable plaques, intensive lipid management is recommended; however, the serial changes of calcified plaques under intensive lipid management are unknown. A total of 31 patients (mean age, 63 ± 10 years; men, 29 patients) who underwent PCI with intensive lipid management were retrospectively studied. We evaluated the serial longitudinal changes of calcified plaques with clear outer borders using optical coherence tomography (OCT) at two time points: at the time of PCI (baseline) and the chronic phase. The median interval from PCI to chronic phase was 287 (233-429) days. Twenty-eight patients (90.3%) had increased calcium volume at the chronic phase compared with those at baseline (2.6 [1.3-5.1] vs. 1.8 [0.7-4.3] mm2, p < 0.05), and the median increase rate of calcium volume was 27.4% at the chronic phase. According to the median increase rate of calcium volume (27.4%), patients were divided into the following two groups: rapid progression (≥ 27.4%, RP group) and non-rapid progression (< 27.4%, non-RP group). The RP group had more patients with diabetes, and diabetes was independently associated with rapid progression by multivariate analysis. Furthermore, patients with diabetes had significantly higher changes in calcium index and volume from the baseline to the chronic phase than those without diabetes. Coronary calcification progression during relatively short intervals was observed using OCT even under intensive lipid management. Diabetes was an independent predictor for rapid coronary calcification progression.

Incidence, Predictors, and Outcome Associated With Ventricular Tachycardia or Fibrillation in Patients Undergoing Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction.

BACKGROUND: The characteristics and clinical outcomes associated with sustained ventricular tachycardia and fibrillation (VT/VF) in Japanese acute myocardial infarction (AMI) patients remain unknown.Methods and Results: Consecutive AMI patients (n=1,941) transferred to the Hirosaki University Hospital and treated with primary percutaneous coronary intervention (PCI) within 12 h of onset were retrospectively studied. The incidence of VT/VF during hospitalization was 8.3%, and 75% of cases occurred by the end of PCI. Independent predictors associated with VT/VF occurrence by the end of PCI and after PCI, respectively, were identified. Additionally, the differences between patients with VT and VF were examined, which revealed that the characteristics of patients and predictors for VT and VF were clearly different. Additionally, the QRS duration during VT was measured, which demonstrated the possible involvement of Purkinje fibers for VT in the acute phase of AMI. Of the patients with VT/VF, 12% required ECMO support due to refractory VT/VF despite intravenous antiarrhythmic agents such as ß-blockers, amiodarone, and nifekalant. Among the patients discharged alive, 1,690 were followed up for a mean of 3.7 years. VT/VF occurrence during hospitalization did not affect the mid-term clinical outcomes even in patients with VT. CONCLUSIONS: The results clearly indicated that VT/VF is still a serious complications of AMI. We need to identify patients at high risk of developing VT/VF for careful observation and appropriate intervention.

Rivaroxaban attenuates cardiac hypertrophy by inhibiting protease-activated receptor-2 signaling in renin-overexpressing hypertensive mice.

Rivaroxaban (Riv), a direct factor Xa (FXa) inhibitor, exerts anti-inflammatory effects in addition to anticoagulation. However, its role in cardiovascular remodeling is largely unknown. We tested the hypothesis that Riv attenuates the progression of cardiac hypertrophy and fibrosis induced by continuous activation of the renin-angiotensin system (RAS) in renin-overexpressing hypertensive transgenic (Ren-Tg) mice. We treated 12-week-old male Ren-Tg and wild-type (WT) mice with a diet containing Riv (12 mg/kg/day) or a regular diet for 4 weeks. After this, FXa in plasma significantly increased in Ren-Tg mice compared with WT mice, and Riv inhibited this increase. Left ventricular wall thickness (LVWT) and the area of cardiac fibrosis evaluated by Masson's trichrome staining were greater in Ren-Tg mice than in WT mice, and Riv decreased them. Cardiac expression levels of the protease-activated receptor (PAR)-2, tumor necrosis factor-α, transforming growth factor (TGF)-ß1, and collagen type 3 α1 (COL3A1) genes were all greater in Ren-Tg mice than in WT mice, and Riv attenuated these increases. To investigate the possible involvement of PAR-2, we treated Ren-Tg mice with a continuous subcutaneous infusion of 10 µg/kg/day of the PAR-2 antagonist FSLLRY for 4 weeks. FSLLRY significantly decreased LVWT and cardiac expression of PAR-2, TGF-ß1, and COL3A1. In isolated cardiac fibroblasts (CFs), Riv or FSLLRY pretreatment inhibited the FXa-induced increase in the phosphorylation of extracellular signal-regulated kinases. In addition, Riv or FSLLRY inhibited FXa-stimulated wound closure in CFs. Riv exerts a protective effect against cardiac hypertrophy and fibrosis development induced by continuous activation of the RAS, partly by inhibiting PAR-2.

Novel Electrocardiographic Criteria for the Diagnosis of Left Ventricular Hypertrophy in the Japanese General Population.

Although there are several diagnostic criteria for left ventricular hypertrophy (LVH), their sensitivity remains low. A recent study reported that the sum of the amplitude of the deepest S wave in any lead (SD) and the S wave in lead V4 (SV4) (SD + SV4) improved sensitivity compared with commonly used criteria. To test whether this new formula improves sensitivity in the Japanese general population, we analyzed 12-lead electrocardiograms for Japanese residents participating in the Iwaki Health Promotion Project (n = 866). Left ventricular mass was calculated by echocardiography, indicating that 156 (18%) of the study population had LVH. In receiver operating characteristic analyses, the sum of the R wave in limb lead Ι (RLΙ) and the S wave in V4 (SV4) (RLΙ + SV4) showed a higher area under the curve (AUC = 0.76) than the Sokolow-Lyon voltage criteria (0.61) and the SD + SV4 criteria (0.63), and almost the same AUC as the Cornell voltage criteria (0.74) and the Cornell product criteria (0.76). The validation study also showed similar results. The cutoff values of RLΙ + SV4 criteria were ≥1.6 mV in men and ≥1.4 mV in women with a sensitivity of 39% and a specificity of 89%, whereas the sensitivity and specificity calculated based on SD + SV4 criteria were 21% and 94%, respectively. Thus, the diagnostic criterion of RLΙ + SV4 seems to be more useful than the previous criteria for diagnosing LVH in the Japanese general population.

Relationship Between Serum Eicosapentaenoic Acid Levels and J-Waves in a General Population in Japan.

We previously showed that J-waves were found more frequently in patients with low levels of serum eicosapentaenoic acid (EPA) in the acute phase of myocardial infarction, and were associated with the incidence of ischemia-related ventricular arrhythmias. However, the relationship between J-waves and serum EPA levels in a general population remains to be elucidated.The Iwaki Health Promotion Project is an ongoing community-based health promotion study in Iwaki, Hirosaki, which is in northern Japan. A total of 1,052 residents (mean age, 53.9 ± 15.4 years; 390 men) who participated in this project in 2014 were studied. A standard 12-lead electrocardiogram (ECG) was recorded and serum EPA levels were measured to evaluate the relationship between J-waves and serum EPA levels. J-waves were found in 52 (5%) subjects and were observed more frequently in male than female subjects (44 [11%] versus 8 [1%], P < 0.0001). More than half of the J-waves were the notched type (60%), and J-waves were detected most frequently in inferior leads on ECG (52%). The RR interval was longer and QTc duration shorter in subjects with J-waves than those without. No significant difference was found in serum EPA levels between subjects with and without J-waves (70 [49-116] versus 65 [41-106] µg/mL, P = 0.40). In multivariate analysis, male gender and RR interval were independent factors associated with the presence of J-waves.There was no significant relationship between J-waves and serum EPA levels in this general population in Japan. Various mechanisms for manifestation of the J-waves are suggested.