Deciphering mortality risk of diabetes medications in heart failure patients with diabetes mellitus under triple guideline-directed medical therapy.

BACKGROUND: Scientific evidence regarding the impact of different combinations of diabetes medications in heart failure patients with diabetes mellitus (HFwDM) remains limited. AIM: We aimed to investigate the effect of monotherapy and combination therapy for DM on all-cause mortality in HFwDM under triple guideline-directed medical therapy (GDMT). METHOD: This nationwide retrospective cohort study included adult HFwDM under triple GDMT between January 1, 2016 and December 31, 2022.We collected the data from the National Electronic Database of the Turkish Ministry of Health.We created various combination including different diabetes medications based on the current guidelines for DM.The primary endpoint was all-cause mortality. RESULTS: A total of 321,525 HFwDM under triple GDMT (female:49%, median age:68[61-75] years) were included. The highest rate of prescribed combination therapy was metformin and sulfonylureas (n = 55,266). In Cox regression analysis, insülin monotherapy had the highest risk for all-cause mortality (HR:2.25, 95CI%:2.06 - 2.45), whereas combination therapy including metformin, SGLT2i, and sulfonylureas provided the most beneficial effect on survival (HR:0.29, 95CI%:0.22-0.39) when compared to patients not receiving diabetes medication. Among patients taking diabetes medications, the inclusion of SGLT2i demonstrated a survival benefit (p < 0.05), despite concurrent use of volume-retaining medications such as insulin and thiazolidinediones. Conversely, combinations of diabetes medications without SGLT2i did not demonstrate any survival benefit compared to patients not taking diabetes medication (p > 0.05). CONCLUSION: This study underscored the use of SGLT2i as monotherapy or as a part of combination diabetes medications to improve survival among HFwDM, while also highlighting that combinations lacking SGLT2i did not confer any survival benefit.

Navigating Heart Failure: Unveiling Sex Disparities in Guideline-Directed Medical Therapy Combinations.

Major heart failure (HF) trials remain insufficient in terms of assessing the differences in clinical characteristics, biomarkers, treatment efficacy, and safety because of the under-representation of women. The study aimed to present sex-related disparities in HF management, including differences in demographics, co-morbidities, cardiac biomarkers, prescribed medications, and treatment outcomes. The study utilized anonymized data from the Turkish Ministry of Health's National Electronic Database between January 1, 2016, and December 31, 2022. The cohort analysis included 2,501,231 adult patients with HF. Specific therapeutic combinations were analyzed using a Cox regression model to obtain relative risk reduction for all-cause death. The primary end point was all-cause mortality. In the cohort, 48.7% (n = 1,218,911) were male, whereas 51.3% (n = 1,282,320) were female. Female patients exhibited a higher median age (71 vs 68 years) and manifested higher prevalence of diabetes mellitus, anemia, atrial fibrillation, anxiety, and ischemic stroke. Male patients demonstrated higher rates of previous myocardial infarction, dyslipidemia, chronic obstructive pulmonary disease, and chronic kidney disease. Higher concentrations of natriuretic peptides were observed in female patients. Renin-angiotensin aldosterone inhibitor, ß blockers, mineralocorticoid receptor antagonists, sodium/glucose cotransporter 2 inhibitor (SGLT2i), and ivabradine were more commonly prescribed in male patients, whereas loop diuretics, digoxin, and ferric carboxymaltose were more frequent in female patients. Male patients had higher rates of cardiac resynchronization therapy and implantable cardioverter defibrillator implantation rates. All-cause mortality and hospitalization rates were higher in male patients. Compared with monotherapy, all combinations, including SGLT2i, showed a beneficial effect on all-cause mortality in both female and male patients with HF. In hospitalized patients with HF, the addition of digoxin to renin-angiotensin aldosterone inhibitor, mineralocorticoid receptor antagonists, and ß blockers was superior to monotherapy regarding all-cause mortality in female patients with HF compared with male patients with HF. In conclusion, this study highlights that sex-specific responses to HF medication combinations compared with monotherapy and differences in co-morbidities underscore the importance of tailored management strategies. Digoxin showed a contrasting effect on all-cause mortality between both sexes after hospitalization, whereas SGLT2i exhibited a consistent beneficial effect in both sexes when added to all combinations.

Visual or computer-based measurements: Which is important for the interpretation of an athlete's electrocardiography?

OBJECTIVE: Preparticipation screening of athletes by electrocardiography is the most crucial step in determining sudden cardiac death risk factors. Several electrocardiography interpretation software programs have been developed for physicians practicing in this field. Our study aimed to assess cardiopoint sudden death screening module by comparing its findings with two cardiologists using Seattle and International criteria. METHODS: A total of 303 licensed national athletes (37% females) were enrolled. electrocardiographies were examined by the cardiopoint sudden death screening module using Seattle criteria and cardiologists. The consistency between cardiologists and software was compared, and the confidence assessment of the module was tested. RESULTS: With regard to Seattle criteria, moderate consistency was found between the cardiopoint sudden death screening module and the 1st (κ=0.41) and 2nd cardiologist (κ=0.59). Consistency between two cardiologists was moderate (κ=0.55). When we applied International criteria, there was moderate consistency between the module and the 1st cardiologist (κ=0.42), and good consistency between the module and the 2nd cardiologist (κ=0.63). Consistency between the two cardiologists was good (κ=0.62). CONCLUSION: The cardiopoint sudden death screening module had similar agreement with cardiologists based on both criteria. However, the software needs to be updated according to International criteria. Using computer-based measurements for preparticipation screening will help to save time and provide standardization of electrocardiography interpretation.

Trends in heart failure between 2016 and 2022 in Türkiye (TRends-HF): a nationwide retrospective cohort study of 85 million individuals across entire population of all ages.

Background: Data on the burden of heart failure (HF) outside western countries are limited, but available data suggest it may present differently in other countries. The aim of this study was to examine the incidence, prevalence, and survival rates of HF in Türkiye, with a specific focus on how these rates vary according to age, sex, comorbidities, and socioeconomic status (SES). Methods: We harnessed the extensive National Electronic Database of the Turkish Ministry of Health, covering Turkey's entire population from January 1, 2016, to December 31, 2022, to identify 2,722,151 cases of HF and their associated comorbidities using ICD-10 codes. Analyzing the primary endpoint of all-cause mortality, our study utilized anonymized data to examine patient demographics, comorbidities, socioeconomic status, and survival patterns, employing statistical techniques to delve into relationships and trends. The data were segmented by gender, socioeconomic status, and age, involving cross-tabulations and statistical metrics to explore connections, odds ratios, and survival rates. Findings: The estimated prevalence of HF was 2.114% in Türkiye at the end of 2022, with an annual incidence ranging between 3.00 and 6.06 per 1000 person years. Females were older than males (69.8 ± 13.9 years vs. 66.8 ± 13.9 years, respectively). The most common comorbidities were congenital heart diseases and anemia under the age of 20, and hypertension and atherosclerotic cardiovascular disease in the adult population. Only 23.6% (643,159/2,722,151) of patients were treated with any triple guideline-directed medical therapy (GDMT) and 3.6% (96,751/2,722,151) of patients were on quadruple GDMT. The survival rates for patients with HF at 1, 5, and 7 years were 83.3% (95% CI: 83.2-83.3), 61.5% (95% CI: 61.4-61.6), and 57.7% (95% CI: 57.6-57.8) among females, and 82.1% (95% CI: 82.0-82.2), 58.2% (95% CI: 58.1-58.3), and 54.2% (95% CI: 54.0-54.3) among males. Despite a tendency for an increase from the highest to the lowest SES, the prevalence of HF and mortality were paradoxically lowest in the lowest SES region. Interpretation: The prevalence, incidence, and survival rates of HF in Türkiye were comparable to western countries, despite the notable difference of HF onset occurring 8-10 years earlier in the Turkish population. Drug usage statistics indicate there is a need for effective strategies to improve treatment with GDMT. Funding: None.

Exercise Prevents Glucocorticoid-Induced Myocardial 4-Hydroxynonenal Production.

PURPOSE: Long-term administration of glucocorticoids (GCs) increases myocardial oxidative stress. 4-Hydroxynonenal (4-HNE) protein adducts, a marker of oxidative damage, have been associated with several cardiovascular diseases, including atherosclerosis, cardiac hypertrophy, cardiomyopathy, and ischemia-reperfusion injury. Exercise training has been shown to have a protective effect on the heart by lowering the level of oxidative stress in cardiomyocytes. Therefore, we aimed to investigate the effect of long-term dexamethasone treatment and exercise training on myocardial 4-HNE levels. METHODS: Twenty-four female Wistar albino rats were assigned to sedentary control-saline treated (C, n = 8), sedentary-dexamethasone treated (D, n = 8), and exercise training-dexamethasone treated (DE, n = 8) groups. Daily dexamethasone was injected for 28 days at a 1 mg kg-1 dose, while C animals were injected with the same volume of saline subcutaneously. DE animals underwent an exercise training protocol of 60 min/day, 5 days a week, at 25 m/min-1 (0% grade) for 28 days. Left ventricular 4-HNE, Hsp72 levels, and pHsp25/Hsp25 ratio were determined by Western blot. RESULTS: The administration of dexamethasone led to a significant elevation in 4-HNE levels in the myocardium of adult rats (p < 0.05; D vs. C). The concurrent implementation of exercise training impeded this increase (p > 0.05; DE vs. C). Exercise training induced a threefold increase in myocardial Hsp72 expression (p < 0.001; DE vs. C and D) and attenuated the dexamethasone-induced increase in Hsp25 phosphorylation (p < 0.05; C vs. D) (p < 0.001; DE vs. D). CONCLUSION: Our results indicate that long-term administration of dexamethasone is associated with an increase in cardiac 4-HNE levels, which is hindered by the addition of exercise training.

Hypoglycemia detected during cardiac arrest of a non-diabetic patient with heart failure.

Hypoglycemia in non-diabetic patients with heart failure is a rare finding. It is thought to be caused by hepatic dysfunction secondary to chronic passive congestion, and reduced gluconeogenesis. In this report we present a 23-year-old man with a history of Duchenne muscular dystrophy hospitalized for decompensated heart failure and implantable cardioverter defibrillator shock. Laboratory examination on admission showed slightly elevated levels of hepatic enzymes. Despite the therapy for heart failure the patient's clinical status deteriorated, and sinus bradycardia and then cardiac arrest occured. After successful 5-minute cardiopulmonary resuscitation, an arterial blood sample revealed metabolic acidosis with a level of pH 7.04, bicarbonate 9.3, and glucose of 22 mg/dl. Acute treatment of metabolic acidosis with hypoglycemia was successfully performed. Based on this case, possible causes of unexplained hypoglycemia in non-diabetic patients with heart failure were described in a short literature review.