Pathophysiology and Treatment of Diabetic Cardiomyopathy and Heart Failure in Patients with Diabetes Mellitus.

There is a close relationship between diabetes mellitus and heart failure, and diabetes is an independent risk factor for heart failure. Diabetes and heart failure are linked by not only the complication of ischemic heart disease, but also by metabolic disorders such as glucose toxicity and lipotoxicity based on insulin resistance. Cardiac dysfunction in the absence of coronary artery disease, hypertension, and valvular disease is called diabetic cardiomyopathy. Diabetes-induced hyperglycemia and hyperinsulinemia lead to capillary damage, myocardial fibrosis, and myocardial hypertrophy with mitochondrial dysfunction. Lipotoxicity with extensive fat deposits or lipid droplets is observed on cardiomyocytes. Furthermore, increased oxidative stress and inflammation cause cardiac fibrosis and hypertrophy. Treatment with a sodium glucose cotransporter 2 (SGLT2) inhibitor is currently one of the most effective treatments for heart failure associated with diabetes. However, an effective treatment for lipotoxicity of the myocardium has not yet been established, and the establishment of an effective treatment is needed in the future. This review provides an overview of heart failure in diabetic patients for the clinical practice of clinicians.

Circulating adipocyte fatty acid-binding protein is a predictor of cardiovascular events in patients with stable angina undergoing percutaneous coronary intervention.

BACKGROUND: Adipocyte fatty acid-binding protein (A-FABP) is expressed in both adipocytes and macrophages. Recent studies have shown that A-FABP is secreted by adipocytes and that the A-FABP concentration is associated with obesity, insulin resistance, and atherosclerosis. We have reported that the coronary atherosclerotic burden is associated with the serum A-FABP concentration. In the present study, we investigated whether the serum A-FABP concentration is associated with prognosis in patients with stable angina pectoris who have undergone percutaneous coronary intervention (PCI). METHODS: This was a prospective single-center trial. In total, 130 patients with stable angina pectoris undergoing their first PCI were enrolled from August 2008 to July 2010 at Kagawa Prefectural Central Hospital. The primary endpoints were cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, revascularization, and hospitalization for heart failure. RESULTS: During the follow-up (median, 50 months; interquartile range, 23-66 months), 49 cardiovascular events occurred. Kaplan-Meier analysis showed that the cumulative incidence of the primary endpoints in the high A-FABP group (median A-FABP concentration of ≥ 18.6 ng/ml) was greater than that in the low A-FABP group. Cox analysis showed that the A-FABP concentration was an independent predictor of cardiovascular events adjusted for age and the presence of multi-vessel disease (hazard ratio, 1.03; 95% confidence interval, 1.01-1.04; p = 0.01). CONCLUSION: The serum A-FABP concentration is associated with prognosis in patients with stable angina undergoing PCI, suggesting that the serum A-FABP concentration could be useful for risk assessment of secondary prevention. TRIAL REGISTRATION: UMIN Clinical Trials Registry UMIN000029283 (registration date: September 25, 2017), retrospectively registered.

Repeated Syncope During Exercise as a Result of Anomalous Origin of Left Coronary Artery With Intramural Aortic Course in a Teenage Boy.

Anomalous origin of the left coronary artery from the opposite sinus of Valsalva with an intramural aortic course (L-ACAOS-IM) can cause syncope, sometimes as a prodrome of lethal events, including sudden cardiac death, in young athletes. The detailed mechanism of syncope in patients with L-ACAOS-IM is still unclear. This case report describes a 17-year-old boy who presented to the hospital because of syncope following chest pain with increasing frequency during exercise, such as playing soccer and running. In a treadmill exercise test, a decrease in blood pressure was seen (from 99/56 mm Hg to 68/38 mm Hg); chest pain and faintness accompanied by ST-segment elevation in lead aVR and ST-segment depression at other leads on electrocardiography were noted. These findings and symptoms disappeared spontaneously within a few minutes while clinicians prepared for emergency medications. Coronary computed tomography angiography (CCTA) showed that the origin of the left coronary artery (LCA) was the opposite sinus of Valsalva, and the course of the LCA was through the aortic wall toward the left coronary sinus. He was diagnosed with L-ACAOS-IM. After surgical treatment by unroofing the intramural part of the LCA and reconstructing a neo-ostium, he no longer experienced syncope during exercise. This case suggests that low cardiac output caused by myocardial ischemia, not life-threatening arrythmia, is a main mechanism of syncope in patients with L-ACAOS-IM. Consideration should be given to performing CCTA before an exercise stress test for young patients with syncope and chest pain to avoid the risk of severe myocardial ischemia.

Innovative clinical pathway shortened the length of hospital stay and prevented readmission in patients with acute decompensated heart failure.

BACKGROUND: With the rapidly aging population in Japan, the number of patients hospitalized for acute decompensated heart failure (ADHF) is increasing. Mitoyo General Hospital created an innovative clinical pathway (CP) for promoting early discharge in patients with ADHF. Major points of the CP were as follows: using tolvaptan as a standard therapy, completing the acute therapies within three days, and starting cardiac rehabilitation from the second day after admission. METHODS: We collected data for patients with ADHF who were admitted to our hospital before introduction of the CP (non-CP group) (April 2014-July 2015) and after introduction of the CP (CP group) (August 2015-July 2019). We investigated the impact of the CP on the length of hospital stay (LOHS) and readmission after discharge. RESULTS: After screening, 593 patients were enrolled in this study. After performing propensity score matching, 129 patients in the non-CP group and 129 patients in the CP group were analyzed. LOHS of patients in the CP group was significantly shorter than that of patients in the non-CP group [20 (14-28) days vs 12 (8-21) days] (p < 0.001) without an increase in mortality during hospitalization or an increase in the rate of readmission due to ADHF within 30 days. Use of the CP was an independent negative factor contributing to LOHS for patients with ADHF, even after adjustment of other factors including the use of tolvaptan (p < 0.001). The CP significantly decreased the proportion of patients readmitted to hospitals due to ADHF within 6 months [n = 32 (27%) vs n = 18 (15%), p = 0.026] and 1 year [n = 40 (34%) vs n = 23 (19%), p = 0.009] after discharge compared to the proportion in the non-CP group. CONCLUSIONS: The CP significantly reduced the LOHS of patients without increasing the in-hospital mortality and it also reduced the risk of readmission in the mid-term and long-term.

High Plasma Docosahexaenoic Acid Associated to Better Prognoses of Patients with Acute Decompensated Heart Failure with Preserved Ejection Fraction.

The clinical relevance of polyunsaturated fatty acids (PUFAs) in heart failure remains unclear. The aim of this study was to investigate the association between PUFA levels and the prognosis of patients with heart failure with preserved ejection fraction (HFpEF). This retrospective study included 140 hospitalized patients with acute decompensated HFpEF (median age 84.0 years, 42.9% men). The patients' nutritional status was assessed, using the geriatric nutritional risk index (GNRI), and their plasma levels of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA), and dihomo-gamma-linolenic acid (DGLA) were measured before discharge. The primary outcome was all-cause mortality. During a median follow-up of 23.3 months, the primary outcome occurred in 37 patients (26.4%). A Kaplan-Meier analysis showed that lower DHA and DGLA levels, but not EPA or AA levels, were significantly associated with an increase in all-cause death (log-rank; p < 0.001 and p = 0.040, respectively). A multivariate Cox regression analysis also revealed that DHA levels were significantly associated with the incidence of all-cause death (HR: 0.16, 95% CI: 0.06-0.44, p = 0.001), independent of the GNRI. Our results suggest that low plasma DHA levels may be a useful predictor of all-cause mortality and potential therapeutic target in patients with acute decompensated HFpEF.

Differences in endothelial dysfunction induced by paroxysmal and persistent atrial fibrillation: Insights from restoration of sinus rhythm by catheter ablation.

BACKGROUND: Atrial fibrillation (AF) is associated with endothelial dysfunction. Studies have shown the incidence of cardiovascular events to be greater in patients with persistent AF (PeAF) than paroxysmal AF (PAF). OBJECTIVE: The aim of this study was to investigate whether endothelial dysfunction and the impact of catheter ablation on the endothelial function differs between PAF and PeAF. METHODS: We prospectively measured the endothelial function by reactive hyperemia peripheral arterial tonometry (RH-PAT) in 103 PAF, 75 PeAF, and 51 control patients at baseline, with follow-up in the AF patients at 6 and 12months after the catheter ablation. RESULTS: The log-transformed RH-PAT index (ln RHI) was the highest in the control group, followed by the PAF and PeAF (0.67±0.23, 0.57±0.29, and 0.45±0.3, respectively, p<0.001) groups. PeAF was determined to be an independent factor of endothelial dysfunction (ln RHI <0.55) even after adjustment for the conventional cardiovascular risk factors. For 12months after the catheter ablation, 102 (99%) PAF and 72 (96%) PeAF patients maintained sinus rhythm. On average, the ln RHI in the PAF group did not change during the follow-up, but it significantly increased in the PeAF group to a level comparable to that of the PAF patients 6months after the catheter ablation (0.53±0.28, p=0.034), and maintained the same level at 12months after the catheter ablation. CONCLUSIONS: The persistent form of AF may independently contribute to endothelial dysfunction. In addition, by catheter ablation, the maintenance of sinus rhythm may protect against exacerbations of endothelial dysfunction.

Early initiation of eicosapentaenoic acid and statin treatment is associated with better clinical outcomes than statin alone in patients with acute coronary syndromes: 1-year outcomes of a randomized controlled study.

BACKGROUND: Early initiation of EPA treatment in combination with a statin within 24h after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (MI) reduces inflammation and ventricular arrhythmia compared with statin monotherapy; however, the impact of early initiation of EPA treatment on cardiovascular events is unclear. We determined whether early eicosapentaenoic acid (EPA) treatment in patients with acute coronary syndrome (ACS) reduces adverse cardiovascular events. METHODS: This prospective, open-label, blind end point-randomized trial consisted of 241 patients with ACS. Patients were randomly assigned to receive pitavastatin (2mg/day) with or without 1800mg/day of EPA initiated within 24h after PCI. The primary endpoint was defined as cardiovascular events occurring within 1year, including death from a cardiovascular cause, nonfatal stroke, nonfatal MI and revascularization. RESULTS: The mean EPA/arachidonic acid ratio at follow-up was 0.40 in the control group and 1.15 in the EPA group. A primary endpoint event occurred in 11 patients (9.2%) in the EPA group and 24 patients (20.2%) in the control group (absolute risk reduction, 11.0%; hazard ratio, 0.42; 95% confidence interval, 0.21 to 0.87; P=0.02). Notably, death from a cardiovascular cause at 1year was significantly lower in the EPA group than in the control group (0.8% vs. 4.2%, P=0.04). CONCLUSIONS: Early initiation of treatment with EPA combined with statin after successful primary PCI reduced cardiovascular events after ACS. CLINICAL TRIAL REGISTRATION: UMIN Clinical Trials Registry (UMIN-CTR); Registry Number, UMIN000016723; URL, http://www.umin.ac.jp/ctr/index-j.htm.