Non-diabetic Patients Research Articles

Association of Risk Factors of Acute Myocardial Infarction and Heart Blockage Among non-diabetic Patients in a Tertiary Care Hospital – An Observational Study

Introduction: Cardiovascular diseases (CVDs) are a leading cause of death in the world. In 2015, an estimated 442.7 million prevalent cases of CVD were present worldwide. Cardiovascular diseases account for more than 17 million deaths globally each year. Previous studies identified diabetes mellitus, hypertension, hypercholesterolemia, smoking, alcohol consumption, obesity and sedentary lifestyle as risk factors. Aim of the study: The aim of this study was to determine the risk factors for acute myocardial infarction associated with heart blockage among non-diabetic patients. Methods: This was an observational study conducted in the Department of Cardiology of Jashore Medical College Sadar Hospital, Jashore, Bangladesh during the period from April, 2021 to March, 2022. In this study, we included 120 non-diabetic patients who were diagnosed with myocardial infarction. Result: Mean age was 53.03±11.3 years & most of our patients were male. Among all patients, majority (65%) patients had >60% blockage, followed by 30(25%) patients had 40%-60% artery blockage, and <40% blockage was found in 10% patients. Hypertension, dyslipidemia & dyslipidemia with hypertension, age ≥60 years, family history of CHD, smoking, diabetes & obesity were individual risk factors of CHD among non-diabetic patients. The most common risk factors for heart blockage were age >45 years, high blood pressure, high LDL, unhealthy diet, and stressful life. Conclusion: In our study, we found hypertension, history of CHD, dyslipidemia, dyslipidemia with hypertension, stress, age ≥60 years, and obesity were individual risk factors for CHD. These elements work as crucial risk factors for myocardial infarction in non-diabetic patients. Risk factors like age >45 years, high blood pressure, high LDL, unhealthy diet, and stressful life were responsible for the highest heart blockage in myocardial infarction patients. J Inv Clin Cardiol 2023; 5(2): 38-44

Prognostic value of quantitative anatomical and functional measures of coronary artery disease in diabetic and non-diabetic patients

Abstract Background Diabetes is associated with increased risk of coronary artery disease (CAD). However, the relative prognostic importance of anatomical and functional findings of CAD in the presence vs. absence of diabetes is incompletely understood. Technological advances have made quantitative analysis of coronary artery plaques and stenosis feasible by coronary computed tomography angiography (CTA). In turn, positron emission tomography (PET) enables absolute quantification of myocardial blood flow (MBF). Purpose To study long-term prognostic value of quantified severity of coronary atherosclerosis and myocardial perfusion in non-diabetic vs. diabetic patients with suspected CAD. Methods From two academic medical centres, we identified symptomatic patients with suspected CAD who had undergone coronary CTA and [15O]H2O PET myocardial perfusion imaging during adenosine stress. Based on artificial intelligence -guided quantitative analysis of coronary CTA scans, the anatomical severity of CAD was measured as the presence of obstructive CAD (≥50% diameter stenosis) and percent atheroma volume (PAV; higher vs. lower than median). The functional severity of CAD was measured as the presence of regional myocardial ischemia (≥2 adjacent segments with stress MBF <2.3 ml/g/min) and global stress MBF (<2.2 ml/g/min vs. ≥ 2.2 ml/g/min) by PET. Annual rates of adverse events (AER) including all-cause mortality, myocardial infarction (MI), and unstable angina pectoris (UAP) were evaluated. Results Among 1311 patients, 251 (19%) had diabetes. Patients with diabetes had more frequently obstructive CAD (55% vs. 43%, p<0.001) and regional myocardial ischemia (51% vs. 43%, p=0.015), higher plaque burden by PAV (12% vs. 7%, p<0.001), and lower global stress MBF (2.78 ml/g/min vs. 3.05 ml/g/min, p<0.001). During median follow-up of 7.1 years, 171 (13.0%) patients experienced AE (85 deaths, 56 MIs, and 30 UAPs). Patients with diabetes had higher AER than non-diabetic patients (3.1% vs. 1.6%, p<0.001). The presence of obstructive stenosis was associated with increased AER in non-diabetic (2.6% vs. 1.0%, p<0.001) and diabetic patients (4.2% vs. 1.9%, p<0.001). High plaque burden by PAV was associated with increased AER in non-diabetic (2.8% vs. 0.7%, p<0.001) and diabetic patients (3.9% vs. 1.7%, p<0.001). The presence of regional myocardial ischemia was associated with increased AER in non-diabetic (2.5% vs. 1.1%, p<0.001), but not in diabetic patients (3.4% vs. 2.7%, p=0.238). Low global stress MBF was associated with increased AER in non-diabetic (2.9% vs. 1.3%, p<0.001), but not among diabetic patients (3.2% vs. 3.0%, p=0.286). Conclusions Diabetes was associated with more advanced CAD. Quantified severity of anatomical findings predicted long-term adverse outcome in non-diabetic and diabetic patients. In contrast, functional imaging risk stratified non-diabetic patients, whereas diabetic patients had impaired long-term outcome irrespective of perfusion findings.

Effects of Dapagliflozin on myocardial performance in non-diabetic patients with Heart failure with reduced and mid-range ejection fraction (DAPA ECHO trial)

Abstract Background Sodium-glucose cotransporter type-2 inhibitors (SGLT2i) showed to reduced morbidity andmortality in HF patients. The aim of this study was to assess potential effects of dapagliflozin in non-diabetic patients with heart failure (HF) with reduced and mildly reduced ejection fraction (HFrEF and HFmrEF) on cardiac function assessed by speckle tracking echocardiography (STE). Methods This randomized, prospective, single-center, open-label trial compared consecutive non-diabetic outpatients with HFrEF or HFmrEF receiving dapagliflozin with patients treated with optimal medical therapy (OMT) except SGLT2i (Fig.1). Primary endpoint was the modification of left ventricular (LV) global longitudinal strain (GLS), diastolic function (as peak atrial longitudinal strain, PALS) and right ventricular (RV) function by STE from baseline to 6 months. Cardiovascular events and parameters of congestion were assessed as safety-exploratory endpoints. Results Overall, 88 patients (38% HFmrEF) were enrolled and randomized to start dapagliflozin on top of OMT (n=44) or to continue with OMT (n=44). All STE values improved in dapagliflozin group after 6 months, while there was a non-significant improvement in OMT group (Fig.1). Moreover, when comparing the modification of STE parameters at follow up in HFrEF and HFmrEF patients, only the main treatment effect resulted statistically significant in both groups (p<0.0001), indicating a significant difference between dapagliflozin and OMT. Conclusions This study provided randomized data on the beneficial effect of dapagliflozin in non-diabetic patients with HFrEF and HFmrEF in terms of myocardial performance measured by the most sensitive echocardiographic technique i.e. STE. This suggests its usefulness for LV reverse remodeling and better quality of life in patients with HFrEF and HFmrEF.

Efficacy and safety of dapagliflozin in non-diabetic patients with primary anterior ST-elevation myocardial infarction initiated in early hospital period

Abstract Background The effectiveness of SGLT2 inhibitors has been proven in all types of chronic heart failure (HFpEF, HFmrEF, and HFrEF), regardless of the presence of diabetes mellitus. There are still no clear recommendations regarding the timing of SGLT2 inhibitor administration after myocardial infarction (MI) and its influence on prognosis. It can be assumed that it is appropriate to consider the possibility that, if started quickly after the presentation of acute MI, SGLT inhibition might enhance outcomes in patients. Objective This study aims to investigate the efficacy and safety of the SGLT2 inhibitor Dapagliflozin in primary anterior ST-segment elevation myocardial infarction (STEMI) initiated in early hospital period, irrespective of heart failure manifestation. Methods The study includes 124 non-diabetic patients with primary anterior STEMI who underwent primary PCI and had left ventricular ejection fraction (LV EF) ≤45% and NT-proBNP > 900 pg/ml at symptom onset within 24 hours, regardless of heart failure symptom manifestation. Patients with cardiogenic shock were excluded. 62 patients received standard medical treatment including beta-blockers, ACE inhibitors (Control group), while the other 62 patients were administered the SGLT2 inhibitor Dapagliflozin 10 mg once a day during the first 48 hours of inpatient treatment, in addition to standard therapy (Dapa group). All patients were followed up for one year. Echocardiography was performed during the first 24 hours. Echocardiography and NT-proBNP were repeated at the end of the year. The primary endpoint was the one-year heart failure hospitalizations and secondary endpoints included one year cardiovascular mortality and changes in NT-proBNP, plasma creatinine and glycosylated hemoglobin levels. Results The study shows a significant difference in heart failure hospitalization between the groups. In the Control group, it was 25.8%, and in the Dapa group, it was 8.1% (p = 0.008). Initially, there were no significant changes in NT-proBNP levels; 1152.2 ± 222.4 pg/ml in the Control group and 1197.3 ± 279.8 pg/ml in the Dapa group (p= 0.33). At the end of a year, NT-proBNP increased in the Control group (1827.4 ± 317.8 pg/ml), whereas in the Dapa group, it significantly decreased (613.5 ± 215.6 pg/ml) (p < 0.01). One-year cardiovascular mortality in the Control and Dapa groups was 9.7% and 4.8%, respectively(p=0.491). Other blood markers did not differ, and side effects were comparable during the in-hospital period as well as at the end of the year. Conclusion Early administration of Dapagliflozin among non-diabetic patients with primary anterior STEMI is associated with a significant decreasing of heart failure hospitalization rate and NT-proBNP level. Additionally, early administration of dapagliflozin does not impact on safety indicators.

Early coronary revascularization among stable patients with non-ST-segment elevation acute coronary syndromes: the role of diabetes and age

Abstract Background Diabetes mellitus affects 10-30% patients hospitalized with non-ST-segment elevation acute coronary syndrome (NSTE-ACS) and two-fold higher mortality risk compared to non-diabetics. Despite higher post-PCI complications in diabetic patients, guidelines advise early invasive NSTE-ACS treatment for all, based expert opinion, and limited evidence. Purpose To investigate the impact of an early coronary revascularization (<24 hours) compared with initial conservative strategy on clinical outcomes in diabetic patients with NSTE-ACS who are in stable condition at hospital admission. Methods The ISACS-TC database was queried for a sample of diabetic and nondiabetic patients with diagnosis of NSTE-ACS. Patients with cardiac arrest, hemodynamic instability, and serious ventricular arrhythmias were excluded. The characteristics between groups were adjusted using logistic regression and inverse probability of treatment weighting models. Primary outcome measure was all cause 30-day mortality. Risk ratios (RRs) and odds ratios (ORs) with their 95% CIs were employed. Results Of the 7,589 NSTE-ACS patients identified, 2,343 were diabetics. The data show a notable reduction in mortality for the elderly undergoing early revascularization compared to those receiving an initial conservative strategy both in the diabetic (3.3% versus 6.7%; RR: 0.48; 95% CI: 0.28-0.80) and nondiabetic patients (2.7% versus 4.7%: RR: 0.57; 95% CI: 0.36-0.90). In multivariate analyses, diabetes was a strong independent predictor of mortality in the elderly (OR: 1.43; 95% CI: 1.03-1.99), but not in the younger patients OR: 1.04; 95% CI: 0.53-2.06). Conclusions Early coronary revascularization does not lead to any survival advantage within 30 days from admission in young NSTE-ACS patients who present to hospital in stable conditions with and without diabetes. An early invasive management strategy may be best reserved for the elderly. Factors beyond revascularization are of considerable importance for outcome in elderly diabetic subjects with NSTE-ACS.

Effect of empagliflozin on no-reflow in patients with st elevation myocardial infarction undergoing primary percutaneous coronary intervention

Abstract Background Primary percutaneous coronary intervention (PPCI) restores myocardial tissue perfusion successfully in over 90 % of ST-elevation myocardial infarction (STEMI) patients .However there remains a small proportion of patients who exhibit no-reflow.(1) Empagliflozin is a sodium glucose co-transporter 2 (SGLT2) inhibitor that acts as a powerful anti-oxidant and has beneficial effects on endothelial function and reducing burden of ischemia in-vitro.(2) Aim and Objectives: To Assess the effect of Empagliflozin preloading in non-diabetic STEMI patients before PPCI on procedural, in-hospital outcomes and short-term Major Adverse Cardiovascular events (MACE) in a single tertiary center. Patients and Methods: The study was carried out on 200 non-diabetic STEMI patients presenting to our university hospital within the first 8 hours of symptom onset. Patients were randomised into 2 groups , the intervention group received 10mg Empagliflozin before PPCI with the standard medical therapy while the control group received only the standard medical therapy. Patients were assessed for demographic data, risk factors, procedural outcomes, clinical and in-hospital outcomes, and short-term MACE up to 1 month. Results: Our study found a significant difference between the intervention and control groups regarding contrast volume with a mean of 131 ml in the intervention group and 144 ml in control group with a p value of 0.009, incidence of no-reflow with 34.5% in the control group and only 18.2% in the intervention group and a p value of 0.014 and myocardial blush grade (MBG) were 84.1% of the patients in intervention group had MBG III after PCI while only 65.5% of the patients in the control group showed the same results with a p value of 0.019. Also, there was a significant difference in St-segment resolution post PCI as 59.1% of patients in the intervention group had complete ST segment resolution and only 39.1% of the patients in the control group had complete resolution with a p-value of 0.027, and total MACE in the first month which affected 44.8% of the patients in the control group and only 28.4% of those in the intervention group with a p-value of 0.024. Conclusion Our study showed that pre-loading of STEMI patients with Empagliflozin resulted in improvement in procedural outcomes, decreasing the incidence of coronary no-reflow, improvement in patient’s course during hospital stay and short-term MACE. Improvement in MACE was mainly due to reduced HF hospitalisations and anginal symptoms.

Lipoprotein(a) regulates vascular redox state and inflammatory response in patients with coronary artery disease

Abstract Background Circulating Lipoprotein(a) (Lp(a)) is associated with cardiovascular disease, and over 90% of its variation in plasma is genetically determined. However, neither the causal nature of this association nor the underlying mechanisms are fully documented. Purpose We explored the hypothesis that Lp(a) triggers atherogenesis by dysregulating vascular redox-sensitive inflammatory state. Methods 1027 patients with advanced coronary artery disease (CAD) undergoing cardiac surgery were genotyped and a genetic signature (LPA) determining Lp(a) levels was generated. RNA-sequencing and vascular superoxide (O2.-) measurements were performed in internal mammary arteries (IMA), and the contribution of NADPH-oxidases and uncoupled endothelial nitric oxide synthase (eNOS) were determined. Patients were followed up for a median of 5.07 years. Results A genetic screening identified 7 SNPs (LPA) that were associated with increased Lp(a) plasma levels (A). Patients in the alternative LPA variant group, as well as patients with higher plasma Lp(a) levels, had significantly higher basal arterial O2.-. Patients with diabetes had significantly lower plasma Lp(a) compared to non-diabetics and the association between plasma Lp(a) and arterial O2.- was driven by non-diabetic patients. The effect of Lp(a) on vascular redox state was primarily due to eNOS uncoupling, resulting from reduced vascular tetrahydrobiopterin (BH4) bioavailability. Indeed, patients in the alternative LPA variant group or with higher plasma Lp(a) levels had a greater arterial eNOS-derived (LNAME-inhibitable) O2.- production (B,C). Levels of eNOS essential cofactor BH4 (defined by the ratio of plasma BH4 to its oxidation product BH2) were lower in patients with higher plasma Lp(a) levels (D). There was no significant impact of Lp(a) variability on vascular NADPH oxidase-derived O2.-. RNA sequencing of arterial tissue revealed dysregulation of nitrosative and inflammatory signalling in patients with high Lp(a), although there was no association with systemic biomarkers of inflammation (i.e. hsCRP) or oxidative stress (i.e. malondialdehyde). Finally, both LPA and high plasma Lp(a) were associated with elevated risk for cardiovascular mortality (E,F). When the cox regression models were additionally corrected for arterial O2.- production, both the models for the LPA genetic signature (HR[95% CI]=2.053[0.180-23.428], p=0.563) and plasma Lp(a) (HR[95% CI]=1.700[0.325-8.885], p=0.529) lost significance. This implies that redox-sensitive inflammatory signalling may be a link between Lp(a) and cardiovascular risk. All above associations were independent from plasma ApoB. Conclusions This study demonstrates for the first time that a genetically determined increase in plasma Lp(a) results in dysregulated vascular redox/nitrosative signalling in patients with atherosclerosis, revealing new therapeutic opportunities in cardiovascular prevention.

Cystatin C predicts cardiovascular events in patients with coronary artery disease both among patients with and among those without type 2 diabetes

Abstract Cystatin C is an established biomarker for renal function, and, given the close association of chronic kidney disease and cardiovascular disease might indicate new-onset or deteriorating cardiovascular disease. However, evidence for cystatin C as a predictor of cardiovascular events is limited and controversial. We therefore aimed at investigating the role of cystatin C as a predictor of future cardiovascular events in a high risk-cohort of patients with established coronary artery disease (CAD). We prospectively recorded cardiovascular events in 1053 patients with angiographically verified CAD over a mean follow-up of 9.5±5.3 years. At baseline, 352 patients had type 2 diabetes mellitus (T2DM) and 701 did not have T2DM. During follow-up, 560 (53.2%) of our patients suffered cardiovascular events. Cystatin C proved to be a strong and independent predictor for cardiovascular events in the total study cohort (standardized adjusted HR 1.22 [1.12-1.33], p<0.001). When T2DM status was taken into account, cystatin C significantly predicted cardiovascular events both in patients with T2DM (HR 1.18 [1.04-1.35], p=0.011) and in non-diabetic patients (HR 1.23 [1.09-1.38], p<0.001). We conclude that cystatin C predicts cardiovascular events in CAD patients both among those with and among those without T2DM.

Comparing the ability of GRACE 2.0 and GRACE 3 scores for predicting in-hospital mortality in patients with and without diabetes

Abstract Background Sex-specific refinement of GRACE 2.0 was published as GRACE 3.0 (G3). The relative ability of G3 in predicting in-hospital mortality in diabetic patients has not been explored. Purpose Explore the ability of G3 in determining in-hospital mortality in patients with and without diabetes. Methods Retrospective cohort analysis of data on NSTEMI and UA patients admitted in two hospitals between 2010 and 2019 entered into the Myocardial Infarction National Audit Project database. All baseline characteristics and G2, G3 scores were recorded. In hospital death was recorded from hospital records. The discriminative power of the G2 score was determined by comparing the area under the receiver operating characteristic curve (c-statistics). Accuracy of calibration was evaluated by plotting the mean predicted vs observed mortality in each decile of predicted risk, Hosmer-Lemeshow (HL) goodness-off it test and the Nagelkerke R2 (NR2). Results G3 was calculated in 2768 patients (age 69±14yrs, 62.3% male, 877(31.7%) with diabetes. Median risk for the cohort was 1.3%, (95% CI 1.2 to 1.4). G3 risk was higher in patients with diabetes (median 2.0 IQR 0.6 to 5.5 vs 1.0 IQR 0.3 to 3.7, p<0.0001). In-hospital mortality occurred in 68 (2.5%) patients with no difference between the diabetes groups (3.1% and 2.2% died in the DM and non-DM groups respectively). In the whole cohort, G3 reclassified 139(7.5%) patients in low-intermediate to high risk-category and 159(17.4%) patients in high to low-intermediate category. 10.1% and 6.5% were upgraded and 16.1% and 18.1% were downgraded in DM and non-DM groups. Overall discriminatory power of G3 (AUC 0.87, 95% CI 0.86 to 0.88, p<0.0001) was excellent but no different from G2 (AUC 0.86 95% CI 0.85 to 0.88, p<0.0001) (δAUC 0.009, p=0.461). In patients with diabetes, G3 yielded higher AUC (AUC 0.85, 95% CI 0.83 to 0.87, p<0.0001) than G2 (AUC 0.82, 95% CI 0.79 to 0.84, p<0.00101) but this was not statistically significant (δAUC 0.031, p=0.142). In patients without DM, the difference was smaller (δAUC 0.002, p=0.906). Neither G2 (δAUC 0.061, p=0.185) nor G3 (δAUC 0.028, p=0.473) was better in discrimination in DM compared to non-DM groups (Fig1A,B). In the diabetic group, calibration plot for the G3 score showed suboptimal calibration with consistent overestimation of the risk across all risk deciles (Figure1C), with the HL test showing significant differences between the observed and predicted values (p <0.0001) and the NR2 was low 0.09. The GRACE 2 score showed better calibration (Fig1D) (HL: p=0.09, NR2 0.11). In patients without diabetes, calibration plot for the G3 (HL: p= 0.17; NR2 0.33) (Fig1E) and G2 (HL: p=0.15, NR2 0.25) (Fig1F) shows similar pattern of overestimation of the risk less so for latter. Conclusion G3 and G2 shows excellent discrimination for in-hospital mortality in both diabetic and non-diabetic patients. G2 seems to show better calibration than G3 for diabetic patients.

Angina pectoris after coronary angiography or revascularization in pre- and postmenopausal women with coronary artery disease

Abstract Background Menopause is a known risk factor of coronary artery disease (CAD) in women. Earlier studies indicate that the incidence of angina pectoris (AP) increases with age. Some studies suggest that menopause would be a risk factor for AP in women with history of myocardial infarction (MI). However, the evidence is still incomplete. Purpose The aim of this study was to determine whether pre- or postmenopausal women are more symptomatic after revascularization using Canadian Cardiovascular Society (CCS) grading and New York Heart Association (NYHA) classification. We also wanted to evaluate whether the presence of type two diabetes (T2D) had an impact of the volume of the symptoms of CAD. Methods ARTEMIS Study contains 1,947 subjects with angiographically documented CAD with or without T2D (women 31.8%). Nondiabetic patients were matched with T2D patients for age, sex, prior MI and revascularization. Information of the menopause was from 610 women. Results Total of 584 women were at postmenopausal stage and only 26 were at premenopausal stage. The mean age of the premenopausal women was 57.5±10.8 years (P<0.001) and 69.4±7.5 years in postmenopausal women (P<0.001). Among premenopausal women 46.2% were active or ex-smokers and 26.8% of postmenopausal women still smoked or had smoked in the past (P=0.031). There was not statistically significant difference in other baseline characteristics: BMI, LDL or BNP levels, systolic or diastolic blood pressure, syntax score prior or after the revascularization and prevalence of prior MI. Over half of the postmenopausal women (57.4%, p<0.001) reported to suffer chest pain CCS grade ≥ 2 after the revascularization whereas only one fifth of the premenopausal women (23.1%, P<0.001) reported the same level of AP. T2D seemed to increase the symptoms of CAD as 33.3% of the premenopausal and 61.7% of the postmenopausal women with T2D reported AP with severity of CCS grade ≥ 2 (P=0.050). CCS 2 symptoms were reported by 45.7% of the postmenopausal and 19.2% of the premenopausal women, and CCS 3 symptoms by 11.6% of the postmenopausal women, yet only 3.8% of the premenopausal women (p=0.001 for both, respectively). Three quarter of the premenopausal women reported CCS 1 level of symptoms but only 42.6% of the postmenopausal women (P=0.003). Prevalence of each of CCS grade reported within pre- and postmenopausal women with and without T2D are shown in the Table 1. None of the premenopausal women reported NYHA ≥ 2 dyspnea, and the same level of shortness of breath was reported also only from 4.3 % of the postmenopausal women (p=0.005). Among postmenopausal women with T2D, NYHA ≥ 2 symptoms were more common, though statistical significance was not obtained (9.2%, P=0.196). Conclusion Postmenopausal women seem to experience more CAD-related symptoms after angiography or revascularization compared premenopausal women. Presence of T2D seems to associate with higher CCS grade after revascularization.

Real-world eligibility for GLP1-ra therapy in a cohort of heart failure patients

Abstract Background GLP1-ra have demonstrated substantial cardiovascular (CV) benefits in diabetic and, more recently, non-diabetic patients, however their use in heart failure (HF) patients is still limited. Purpose To evaluate real-word eligibility to GLP1-ra in a cohort of HF patients. Methods Demographic and clinical data from HF patients evaluated at a single center HF unit from August 1st 2021 to November 29th 2023 were automatically retrieved from the electronic health record (EHR). Patients were deemed eligible to GLP1-ra based on (1) absence of ongoing treatment with GLP1-ra and (2) either having type 2 diabetes mellitus (T2DM) or satisfying the inclusion criteria of the SELECT trial or those of the STEP-HFpEF trial, which were adapted according to the available information. A sensitivity analysis lowering the body mass-index cut-off to >= 27 kg/m2 also for the STEP-HFpEF trial was performed. Results 1754 patients with an established diagnosis of HF were included; median age was 78.3 (IQR 70.7-83.8) years and 697 patients were female (39.7%). 6 patients had type 1 diabetes mellitus. Among the remaining 1749 patients, 633 (36.2%) patients had T2DM and 14 were already treated with GLP1-ra. Among 1116 patients without diabetes, 302 (27.1%) were eligible to receive GLP1-ra according to the inclusion criteria of the SELECT or STEP-HFpEF trials. 226 (20.2%) satisfied the SELECT trial inclusion criteria and among them 100 (44.8%) had HF with reduced ejection fraction, whereas 136 patients (12.2%) were eligible to receive GLP1-ra according to the STEP-HFpEF trial. Changing the BMI cut-off to >= 27 kg/mq, as in the SELECT trial, 219 patients (19.6%) according to the STEP-HFpEF inclusion criteria and 344 (30.8%) overall were found to be eligible for GLP1-ra therapy. Conclusion Real-word eligibility to GLP1-ra may reach up to 55% of HF patients according to diabetes status or trial inclusion criteria.

Drug-drug interactions of empagliflozin and dapagliflozin

Abstract Introduction The sodium glucose co-transporter2-inhibitors dapagliflozin (Dapa) and empagliflozin (Empa), initially developed as antihyperglycemic agents, are increasingly also prescribed for non-diabetic patients with heart failure (HF). Glucuronidation by uridine-diphosphate glucuronosyltransferase (UGT)1A9 is the main mechanism of metabolism of Dapa, whereas Empa is eliminated mainly by excretion. Both Dapa and Empa are substrates of P-glycoprotein. The risk for drug-drug interactions (DDI) of Empa and Dapa is assumed to be low. Aim of this study was to summarize reports of DDI of Empa and Dapa from the literature. Methods Search-terms in PubMed were "drug-drug interaction" and AND "sodium glucose co-transporter2-inhibitors" OR "SGLT2" OR "dapagliflozin" OR "empagliflozin". The drugs were classified according the Anatomical Therapeutic Chemical (ATC) system. Included were randomized trials, pharmacovigilance studies, case series, case reports, studies in healthy subjects and in vivo data. The funding of the study and the disclosures of the authors were registered. Results In 45 reports DDI of Empa and Dapa with 29 drugs were described (Table). According to the ATC system, these were drugs for the alimentary tract and metabolism (n=5), blood and blood forming organs (n=2), cardiovascular system (n=11), genitourinary system and sex hormones (n=2), antiinfectives (n=2), antineoplastic and immunomodulating agents (n=3), musculo-skeletal system (n=2) and nervous system (n=2). The reports comprised studies in healthy subjects (n=28), case reports (n=7), case series (n=6), pharmacovigilance studies (n=2), a subgroup analysis of a randomized trial (n=1) and in vivo data (n=1). Most of the reports found no clinically relevant DDI (n=32). Dapa and Empa both had a synergistic diuretic effect with bumetanide, and led to severe infections when combined with the interleukin-17-inhibitors secukinumab or ixekizumab. Empa administered with intravenous iron was reported to increase cell-iron availability, with lithium to reduce lithium exposure and with valproate to increase valproate exposure. Dapa administered with sacubitril-valsartan was reported to lead to severe hypotension, with linezolid to pancytopenia, with donafenib to an increased exposure to donafenib, with rifampicin to a reduction and mefenamic acid to an increase in Dapa exposure. Of the 45 reports, 33 were funded by a pharmaceutical company marketing Dapa or Empa and 33 had authors with conflicts of interest with pharmaceutical companies marketing Dapa or Empa. Conclusions Most data about DDI of Empa and Dapa derive from studies in healthy subjects and from the marketing companies. The clinical relevance DDI of Empa and Dapa in polymorbid patients with polymedication is largely unknown. There is an urgent need for independent studies on DDI of these drugs in diabetic and non-diabetic patients with HF.Table

Type 2 diabetes rather than the presence of significant coronary stenoses is associated with quality of life in angiographied coronary patients

Abstract Chronic medical conditions such as type 2 diabetes (T2DM) or coronary artery disease (CAD) and their treatment have a crucial impact on patients’ daily life. The EQ-5D-5L questionnaire is a validated and widely used tool to measure the health-related quality of life (HRQL). We investigated and compared the HRQL in patients with or without T2DM and CAD. We included 481 consecutive patients undergoing coronary angiography for the evaluation of established or suspected stable CAD in a tertiary care setting in Central Europe. Patients’ HRQL was measured using the EQ-5D-5L, comprising the EQ index calculated from the domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. A response rate of 88.1% was achieved. From our patients, 166 (34.5%) had T2DM according to ADA criteria, and 254 (52.8%) had significant CAD with stenoses ≥50% at angiography. Patients with T2DM showed significantly lower EQ index values than patients without T2DM (0.891 [IQR=0.783-0.970]) vs. 0.943, [IQR=0.861-1.0], p=0.002)). Regarding the different dimensions of the questionnaire, patients with T2DM reported to have significantly more problems with anxiety and depression (p=0.002) and mobility (p<0.001) than non-diabetic patients. EQ index values in contrast did not differ significantly between patients with vs. those without significant CAD. Accordingly, in analysis of covariance T2DM (F=7.38, p=0.007) but not significant CAD (F=1.74, p=0.183) predicted EQ index values after adjustment for age, sex and body-mass-index. We conclude that T2DM rather than the presence of significant CAD is associated with quality of life in angiographied coronary patients.

The relationship between daily blood glucose fluctuation and readmission in patients with acute coronary syndrome

Abstract Background Although the comprehensive diagnos and treatment of patients with acute coronary syndrome(ACS) has been greatly improved,the morbidity and mortality are still high. Previous literature has reported that about 70-75% of patients diagnosed with acute coronary syndrome have abnormal blood glucose metabolism1,and there existed gender differences. At present, most research results showed that elevated blood glucose is related to the prognosis of ACS. However, further intervention studies indicated that simply strengthen the reducement of blood glucose did not improve prognosis of these patients2. Glucose fluctuations, another dimension of blood glucose, reflect acute changes in blood glucose. However, there are few studies on the effect of blood glucose fluctuation on the prognosis of patients with ACS. Purpose This study aimed to explore the relationship between seven daily fluctuations of blood glucose and readmission in ACS patients. Methods In this study, a total of 664 patients admitted to our University from January 1, 2019 to December 31, 2019 were included and their blood glucose was monitored seven times a day during their hospitalization. The coefficient of variation of blood glucose (CV) was calculated from the results of seven daily blood glucose monitoring to represent the daily fluctuation of blood glucose. Univariate and multivariate regression analyses were performed to determine whether CV was an independent risk factor for re-hospitalization. In addition, the area under the curve (AUC) was used to evaluate the predictive efficacy of CV for outcome events. Finally, we performed a subgroup analysis based on gender and diabetes status to assess the association between CV and readmission in each subgroup. Results After a median follow-up of 21 months, the rate of readmission was 38.4%. Unstable angina pectoris (71.4%) and heart failure (16.4%) were the most common reasons for readmission. Patients with greater CV levels typically exhibited lower fasting blood glucose, higher post breakfast blood glucose, and higher admission blood glucose.The readmission rate increased with the increasing blood glucose variability after the cox regression analysis. Moreover, independent of glycated hemoglobin,CV could predict the risk of readmission in patients with ACS.When using 26.66% as the cutoff point of CV, the study population was divided into two groups and showed a significant differentiation for rehospitalization.In subgroup analysis, there was no significant association between seven daily blood glucose fluctuations and readmission in female and non-diabetes mellitus patients with acute coronary syndrome. Conclusions Besides some normal blood glucose index,seven daily fluctuations of blood glucose was associated with readmission in ACS patients. ACS patients who were male and combined with diabetes were more likely to be readmitted if their CV levels were greater.

Sex differences related changes in cardiac structure and function after ST-segment elevation myocardial infarction

Abstract Background Sex disparities in presentation, treatment, and outcomes after ST-segment Elevation Myocardial Infarction (STEMI) are well recognized. However, little is known about sex related changes in cardiac structure and function following a STEMI in this contemporary era of early PCI. Purpose To compare sex differences in change of echocardiographic parameters of structure and function following a first-time STEMI. Methods This echocardiographic study involved 380 non-diabetic first-time STEMI patients. Structural and functional parameters were evaluated during initial hospitalization (median 1 day after presentation) and at 4-months. Adverse remodelling was defined as a 20% increase in left ventricular end-diastolic volume (LVEDV) at 4 months compared to the hospitalisation echo. Functional parameters included left ventricular ejection fraction (LVEF) and wall motion score index (WMSI). According to current guidelines, eccentric hypertrophy was defined as left ventricular mass index (LVMI) >95 g/m2 for women and >115 g/m2 for men with a relative wall thickness (RWT) ≤0.42; concentric hypertrophy was defined as LVMI >95 g/m2 for women and >115 g/m2 for men with RWT >0.42. The different patterns in geometry were assessed at 4-months. Results Among 380 patients, comprising 285 males and 95 females, females had a higher prevalence of hypertension (42% vs. 25.6%, p=0.004), lower hemoglobin levels (8.40 mmol/l vs. 9.10, p<0.001), and higher plasma NT-proBNP concentrations upon admission (132 ng/L vs 67, p<0.001) and after 24 hours (1322 ng/l vs 784, p<0.001). During the initial echocardiogram conducted upon hospitalization, as well as during the echocardiogram at 4 months, women had significantly lower LV diameters, LV volumes, LV mass, LAVI and wall thickness compared to man. However, during both evaluations women showed higher E/e’ ratio’s and LVEF. The change in echocardiographic variables between both timepoints did not differ significantly between sexes. Furthermore, no significant difference in LV geometry patterns (eccentric or concentric) were observed between sexes and adverse LV remodelling was similar between both groups at approximately 22-23% (p=0.991). Conclusions Although differences exist between sexes in patient characteristics and individual echocardiographic parameters, no disparity is observed in geometry patterns, adverse LV remodelling, or the change in echocardiographic parameters after STEMI.

Baseline C-reactive protein as a predictor of non-ischemic LGE in myocarditis

Abstract Background Identifying reliable early indicators of myocardial injury in myocarditis is a pressing concern in cardiology. Despite their established role in detecting myocardial necrosis, traditional markers like high-sensitivity cardiac troponin (hs-cTn) may not fully capture the extent of myocardial damage identified by non-ischemic late gadolinium enhancement (LGE) on cardiovascular magnetic resonance (CMR) Purpose To identify early admission biomarkers associated with non-ischemic LGE in patients with myocarditis, offering the potential for improved risk stratification and therapeutic targeting. Methods In this retrospective study, we analyzed 59 myocarditis patients admitted to a high-volume medical center from 2017 to 2023, who underwent CMR to evaluate LGE. 41 patients (69.5%) exhibited non-ischemic LGE and 18 (30.5%) did not. We assessed baseline laboratory and echocardiographic parameters, employing Pearson correlation, logistic regression, and ROC curve analyses to elucidate the potential association of baseline biomarkers with non-ischemic LGE, while also discerning subepicardial from midwall patterns. Results Baseline C-reactive Protein (CRP) levels were significantly correlated with non-ischemic LGE (Pearson's r=0.301, p<0.05). Logistic regression analysis substantiated CRP as a predictor of non-ischemic LGE (OR=1.41, p<0.05), corroborated by a multivariate approach even after accounting for age and sex (OR=1.33; p<0.05). Among non-ischemic patterns, subepicardial LGE exhibited the strongest correlation with CRP (Pearson's r=0.321, p<0.05). In contrast, hs-cTn levels showed no significant association with non-ischemic LGE. The ROC analysis revealed that while both CRP and hs-cTn provide valid predictive values for non-ischemic LGE, with AUCs of 0.7333 and 0.6898 respectively, CRP demonstrated a higher discriminative performance, indicating that CRP may offer a more reliable assessment in this clinical context. Additionally, diabetic status emerged as the most significant condition associated with increased CRP levels, with diabetic patients presenting a substantial elevation in baseline CRP compared to non-diabetic patients (8.75 mg/dl vs 3.21 mg/dl; p<0.05). Conclusion CRP appears as a key early biomarker for non-ischemic LGE in myocarditis, with its predictive value being particularly evident in the subepicardial pattern and notably more pronounced among diabetic patients who demonstrate an increased inflammatory burden. These findings suggest a critical role for CRP in risk stratification right from the point of hospital admission and underline the potential for tailored therapeutic approaches that warrant further investigations. Figure 1: ROC curves comparison for CRP and hs-cTn in predicting non-ischemic LGE in myocarditis patients. Figure 2: Patients with diabetes (DM) exhibit significantly higher CRP levels (mean 8.75 mg/dl, SE = 5.54 mg/dl) than those without DM (mean 3.21 mg/dl, SE = 0.49 mg/dl).ROC curves comparisonCPR in patients with and without DM

Comparison of clinical outcomes in diabetic and non-diabetic patients undergoing coronary bifurcation stenting

Abstract Background Diabetes mellitus (DM) is a well-known risk factor for cardiovascular diseases, including coronary artery diseases (CAD). Due to poor post-intervention outcomes, bypass surgery is often recommended in preference to percutaneous coronary intervention (PCI) in DM patients with complex scenarios, such as bifurcation lesions. Methods In this retrospective, multicentre, observational, real-world registry of 2,648 patients with coronary bifurcation lesions undergoing PCI with 2nd-generation drug-eluting stents (DES), the effect of DM on cardiovascular outcomes was analysed. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of all-cause death, myocardial infarction, and stroke, at 5 years. The adjusted outcomes were compared using 1:1 propensity score (PS) matching. Results Overall, DM patients were more likely to be older, female, and have hypertension or chronic kidney disease. In the PS-matched cohort, the cumulative incidence of the primary outcome was numerically higher in the DM group, but without statistical significance (7.9% vs. 5.5%, log-rank p=0.276). Secondary outcomes including all-cause mortality (5.5% vs. 3.9%, log-rank p=0.090) and cardiac mortality (3.2% vs. 1.8%, log-rank p=0.060) were also comparable between the two groups. Conclusion For patients with coronary bifurcation lesions undergoing contemporary PCI, the outcomes were comparable for DM and non-DM patients. Bifurcation PCI can thus be successfully performed in diabetic patients with 2nd-generation DES.

Similar incidence of ICD-shocks in diabetic compared to non-diabetic patients receiving implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy defibrillator (CRT-D)

Abstract Background and aims Recent studies have suggested that diabetes patients with implantable cardioverter defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) may experience a reduced incidence of appropriate ICD-shocks and an increased mortality rate. This study aims to assess whether there is parity in ATP-treatment and ICD-shocks between patients with and without type 2 diabetes mellitus (T2DM), and to analyze associated mortality rates. Methods Using the Danish pacemaker and ICD registry we included patients who received a first-time ICD or CRT-D implantation with a primary or secondary prophylactic indication, between January 1st 2000 to December 31st 2018. Outcomes were analyzed individually for each outcome. Cause specific Cox was used for i) appropriate ATP therapy or ICD-shock, ii) inappropriate ATP therapy or ICD-shock, and a standard Cox regression model was used for iii) all-cause mortality, iv) mortality rate following an ATP-therapy or ICD-shock. Cumulative incidence curves, generated using the Aalen Johansen estimator, were utilized to compare the incidence rates for ATP therapy and ICD-shock while accounting for competing risk of death, while Kaplan-Meier methodology was utilized for survival curves. Analyses were conducted in the total population and in subgroups divided on indication and device type. Results Out of 14 747 patients who received an ICD or CRT-D, 4377 (30%) had T2DM, 4593 (31%) patients received first-time appropriate ATP therapy or ICD-shock, and 1244 (8,4%) experienced first-time inappropriate treatments, 5 112 (35%) experienced death during the follow-up time (mean 3.9 years (SD 2.7)). T2DM patients were more likely to be male (85% vs 80%), slightly older (66 vs 65 years) and burdened with more comorbidities. No significant differences were seen between T2DM and non-T2DM patients for appropriate ATP therapy (HR 0.96[0.88:1.04] p=0.31), appropriate ICD-shock (HR 0.95[0.86:1.05] p=0.32), inappropriate ATP therapy (HR 0.92 [0.77;1.09] p=0.32) and inappropriate ICD-shock (HR 0.96 [0.78;1.18] p=0.71). In the subgroup analyses, no difference was seen in the primary prophylactic subgroups (Figure 1.), only significant difference was observed in the secondary prophylactic ICD group who received less ATP-therapy at 5-year follow-up (HR0.83[0.70;0.99] p=0.04), and in the secondary prophylactic CRT-D group, were T2DM patients seemed to experience more appropriate ICD-shock treatments (HR 2.07[1.23;3.48] p=0.006). Further, we found a higher mortality rate in T2DM with primary prophylactic ICD (HR 1.46[1.31;1.62] p<0.001) and secondary prophylactic ICD (HR 1.30[1.13;1.51] p<0.001), (Figure 2.) this mortality rate remained largely unchanged post appropriate ATP or ICD-shock in the ICD subgroups. Conclusions Despite similar incidence of ATP-therapy and ICD-shocks, T2DM patients with ICD-device experienced a significantly higher post-treatment mortality and all-cause mortality rate.

Management of Glucocorticoid-Induced Hyperglycemia in Cancer Patients: A Feasibility Study.

Glucocorticoids are commonly used in the management of patients with hematological and solid malignancies. However, their use may be associated with impaired glycemic metabolism and increased treatment-related morbidity and mortality. This study aimed to examine the feasibility and acceptability of a nurse-led model of care (MOC) for screening and managing glucocorticoid-induced hyperglycemia (GIH) in non-diabetic patients requiring high-dose glucocorticoid (HDG) therapies, as well as patients' and health professionals' experiences with the MOC. This study was a single-site feasibility study. Patients with hematological or oncological malignancies who were >18 years of age, receiving a chemotherapy regimen including HDGs, had no prior diagnosis of diabetes or prediabetes, and were not at the end of life were considered eligible for this study. Participants were recruited from a district hospital's Cancer Centre in Australia. All consenting participants were screened for diabetes and were provided with a blood glucose meter to monitor their blood glucose levels (BGLs) four times a day on the days of glucocorticoid therapy (GT) plus one extra day following GT, for the first four cycles of their treatment, to screen for the presence of GIH. Feasibility and acceptability were assessed using rates of consent, study completion, and staff and patient surveys. Forty-eight percent (35/74) of patients approached consented to participate in the study and had screening tests for preexisting diabetes. None were diagnosed with diabetes. Six out of 35 patients withdrew, and 10/29 patients did not complete the recommended BGL monitoring. Thirteen percent (4/29) of patients developed GIH. The most common reasons for non-participation and study withdrawal were related to the self-monitoring of BGLs. While clinical stakeholders found the MOC feasible and acceptable, the results of this study suggest that alternative methods for encouraging self-monitoring of BGL and monitoring the presence of GIH during high-dose chemotherapy need to be explored to address issues associated with adherence and sustainability.

Comparative clinical outcomes of amphilimus-eluting stents in diabetic versus non-diabetic patients

Abstract Background Patients with diabetes mellitus (DM) are at an increased risk of experiencing adverse events following percutaneous coronary intervention (PCI). The Cre8 EVO stent, which releases a formulation of sirolimus with an amphiphilic carrier from laser-dug wells, has demonstrated clinical benefits specifically in diabetic populations. We aimed to explore the impact of DM on clinical outcomes in a large, real-world registry of all-comer patients treated with Cre8 and Cre8 EVO stents. Methods We did an investigator-initiated, prospective, single-arm observational trial at 28 sites in South Korea. The primary endpoint was a composite of cardiac death, target vessel-related myocardial infarction (MI), and clinically-driven repeat revascularization at 12 months. All-cause mortality was a key secondary endpoint. Results A total of 2,045 patients (66.0 ± 11.5 years of age; 76.2% male) were analyzed. Diabetic patients (n = 774; 37.8%) were more likely to be older, female, and have hypertension, dyslipidemia, or chronic kidney disease. There were 39 cases of primary events, 17 (2.5%) in the DM group and 22 (1.9%) in the non-DM group (hazard ratio, 1.34; 95% confidence interval, 0.74–2.41; log-rank p = 0.33). Overall, the primary endpoint occurred in 2.1% of patients, with a cardiac death rate of 0.4%, a target vessel-related MI rate of 0.3%, and a clinically driven TLR rate of 1.8%. Among the secondary endpoints, the DM group exhibited a significantly higher all-cause mortality rate compared to the non-DM group (2.0% vs. 0.9%; hazard ratio, 2.20; 95% confidence interval, 1.04–4.65). Conclusion In this real-world registry, diabetic patients treated with amphilimus-eluting stents demonstrated excellent safety and effectiveness at 12 months, with a similar occurrence of MACE compared to non-diabetics. These results underscore the potential for amphilimus-eluting stents to become a preferred option for PCI in diabetic patients, prompting further investigation into their long-term benefits and mechanisms of action.