Myocardial DNA Damage Predicts Heart Failure Outcome in Various Underlying Diseases.

BACKGROUND: Reliable predictors of treatment efficacy in heart failure have been long awaited. DNA damage has been implicated as a cause of heart failure. OBJECTIVES: The purpose of this study was to investigate the association of DNA damage in myocardial tissue with treatment response and prognosis of heart failure. METHODS: The authors performed immunostaining of DNA damage markers poly(ADP-ribose) (PAR) and γ-H2A.X in endomyocardial biopsy specimens from 175 patients with heart failure with reduced ejection fraction (HFrEF) of various underlying etiologies. They calculated the percentage of nuclei positive for each DNA damage marker (%PAR and %γ-H2A.X). The primary outcome was left ventricular reverse remodeling (LVRR) at 1 year, and the secondary outcome was a composite of cardiovascular death, heart transplantation, and ventricular assist device implantation. RESULTS: Patients who did not achieve LVRR after the optimization of medical therapies presented with significantly higher %PAR and %γ-H2A.X. The ROC analysis demonstrated good performance of both %PAR and %γ-H2A.X for predicting LVRR (AUCs: 0.867 and 0.855, respectively). There was a negative correlation between the mean proportion of DNA damage marker-positive nuclei and the probability of LVRR across different underlying diseases. In addition, patients with higher %PAR or %γ-H2A.X had more long-term clinical events (PAR HR: 1.63 [95% CI: 1.31-2.01]; P < 0.001; γ-H2A.X HR: 1.48 [95% CI: 1.27-1.72]; P < 0.001). CONCLUSIONS: DNA damage determines the consequences of human heart failure. Assessment of DNA damage is useful to predict treatment efficacy and prognosis of heart failure patients with various underlying etiologies.

Recent understandings about hypertension management in type 2 diabetes: What are the roles of SGLT2 inhibitor, GLP-1 receptor agonist, and finerenone?

Diabetes and hypertension often coexist, with about half of patients with diabetes also having hypertension. The risk of cardiovascular disease increases by three to six-fold with the coexistence of diabetes and hypertension; therefore, the management of blood pressure to prevent cardiovascular disease is a particularly important issue in patients with diabetes. Clinical trial findings have resulted in recommendations to control blood pressure to <130/80 mmHg in Japanese patients with diabetes. However, the target blood pressure and selection of anti-hypertensive medications should vary depending on the duration of diabetes and comorbidities, and guidelines and clinical trial results should be interpreted flexibly to provide anti-hypertensive treatment tailored to individual patients. In recent years, a number of drugs have emerged that have significant cardio-renal protective effects in patients with diabetes, and a typical example is sodium-glucose cotransporter 2 inhibitor (SGLT2i), glucagon-like peptide-1 receptor agonist (GLP-1RA), and nonsteroidal mineralocorticoid receptor antagonist, finerenone. They have also shown modest but significant blood pressure-lowering effects. In the future, beyond considering the thresholds for how far to lower blood pressure, blood pressure management in patients with diabetes will require understanding the additive cardioprotective value of drugs aimed at lowering blood pressure and the quality of blood pressure lowering. Clinical questions of blood pressure lowering in patients with diabetes GLP-1RA, glucagon-like peptide-1 receptor agonist; SGLT2i, sodium-glucose cotransporter 2 inhibitor.

Anti-obesity therapy for cardiovascular disease prevention: potential expected roles of glucagon-like peptide-1 receptor agonists.

Obesity is characterized by visceral fat accumulation and various metabolic disturbances that cause metabolic syndrome and obesity-related cardiovascular diseases (ORCVDs). Hence, treatments targeting obesity should also prevent ORCVDs. Nonetheless, lifestyle modification therapy alone is still insufficient to reduce the risk of ORCVDs, although most cardiovascular guidelines still list it as the only treatment for obesity. Additionally, conventional anti-obesity drugs, such as orlistat, phentermine-topiramate, and naltrexone-bupropion, can reduce body weight but have not demonstrated a clear reduction in the risk of ORCVDs. To overcome this unmet clinical need, newer anti-obesity drugs must exhibit not only sufficient and long-lasting weight loss but also obvious cardiovascular benefits. Given recent clinical findings and evidences, in this context glucagon-like peptide-1 receptor agonist is currently available as a candidate that is clinically positioned as a first-line anti-obesity agent for the effective prevention of ORCVDs in people with obesity.

Clinical roles of vascular function assessment in cancer care.

Atherosclerotic cardiovascular disease and cancer often share risk factors and influence each other's pathological features. In addition to the unfavorable effects of cancer on the cardiovascular system, the adverse effects of cancer therapies, such as chemotherapy and radiation, have also been determined. In particular, vascular toxic effects associated with cancer therapy (vasospasm, thrombosis formation, and promotion of arteriosclerosis), which are the second most common complications after myocardial adverse effects, are usually managed after the onset of vascular diseases, because screening and predictive methods are yet to be fully established. However, the onset of these vascular complications has a major influence on the implementation of cancer therapy, resulting in worsening of the quality of cancer care and prognosis of patients with cancer. It is therefore necessary to establish clinical strategies for detecting the vascular adverse effects of cancer therapy and evaluating vascular function during cancer care. In this article, we discuss the expected role of vascular function assessment using physiological testing tools for early detection of vascular adverse effects caused by cancer therapy and also preemptive assessment of vascular function prior to this treatment being initiated.

Spontaneous Internal Mammary Artery Graft Dissection Triggered by Emotional Stress.

Internal mammary artery graft dissection is a rare condition and is usually caused by iatrogenic complications or mechanical stress. We experienced a case of acute myocardial infarction due to spontaneous internal mammary artery graft dissection that was triggered by emotional stress and was successfully treated by percutaneous intervention using drug-eluting stents. (Level of Difficulty: Beginner.).

Multiple potency of ezetimibe in a patient with macroproteinuric chronic kidney disease and statin-intolerant dyslipidemia.

Dyslipidemia is often complicated by chronic kidney disease (CKD). Lipid-lowering medications may be effective, in part, for inhibiting development and progression of CKD. Ezetimibe, a cholesterol absorption inhibitor, has pleiotropic actions, including anti-inflammatory and anti-oxidant effects, contributing to a decreased risk of cardiovascular diseases. A 40-year-old woman was admitted with dyslipidemia and macroproteinuria, whose samples of renal biopsy showed exudative lesions, but without glomerular basement membrane thickening or nodular lesions, in some glomeruli. Blood glycemic parameters were normal. After initiation of atorvastatin, she developed muscle pain and an increase in serum creatine kinase. Twelve months after switching to ezetimibe, serum levels of low-density lipoprotein cholesterol and triglyceride reduced from 170 mg/dL to 116 mg/dL and from 320 mg/dL to 160 mg/dL, respectively. Although serum creatinine levels remained unchanged after 12 months, urinary protein excretion and urinary liver-type fatty acid binding protein were reduced. Flow-mediated dilatation also increased from 4.9% to 5.5% after 12 months, associated with a slight decrease in mean intima-media thickness in the common carotid artery from 0.722 mm to 0.718 mm. These results suggest that ezetimibe protects against renal and vascular damage in patients with CKD and statin-intolerant dyslipidemia. .