The role of sirtuin 6 (SIRT6) in atherosclerotic progression of diabetic patients is unknown. We evaluated SIRT6 expression and the effect of incretin-based therapies in carotid plaques of ...asymptomatic diabetic and nondiabetic patients. Plaques were obtained from 52 type 2 diabetic and 30 nondiabetic patients undergoing carotid endarterectomy. Twenty-two diabetic patients were treated with drugs that work on the incretin system, GLP-1 receptor agonists, and dipeptidyl peptidase-4 inhibitors for 26 ± 8 months before undergoing the endarterectomy. Compared with nondiabetic plaques, diabetic plaques had more inflammation and oxidative stress, along with a lesser SIRT6 expression and collagen content. Compared with non-GLP-1 therapy-treated plaques, GLP-1 therapy-treated plaques presented greater SIRT6 expression and collagen content, and less inflammation and oxidative stress, indicating a more stable plaque phenotype. These results were supported by in vitro observations on endothelial progenitor cells (EPCs) and endothelial cells (ECs). Indeed, both EPCs and ECs treated with high glucose (25 mmol/L) in the presence of GLP-1 (100 nmol/L liraglutide) presented a greater SIRT6 and lower nuclear factor-κB expression compared with cells treated only with high glucose. These findings establish the involvement of SIRT6 in the inflammatory pathways of diabetic atherosclerotic lesions and suggest its possible positive modulation by incretin, the effect of which is associated with morphological and compositional characteristics of a potential stable plaque phenotype.
The inflammatory response occurring in acute myocardial infarction (AMI) has been proposed as a potential pharmacological target. Sodium-glucose co-transporter 2 inhibitors (SGLT2-I) currently ...receive intense clinical interest in patients with and without diabetes mellitus (DM) for their pleiotropic beneficial effects. We tested the hypothesis that SGLT2-I have anti-inflammatory effects along with glucose-lowering properties. Therefore, we investigated the link between stress hyperglycemia, inflammatory burden, and infarct size in a cohort of type 2 diabetic patients presenting with AMI treated with SGLT2-I versus other oral anti-diabetic (OAD) agents.
In this multicenter international observational registry, consecutive diabetic AMI patients undergoing percutaneous coronary intervention (PCI) between 2018 and 2021 were enrolled. Based on the presence of anti-diabetic therapy at the admission, patients were divided into those receiving SGLT2-I (SGLT-I users) versus other OAD agents (non-SGLT2-I users). The following inflammatory markers were evaluated at different time points: white-blood-cell count, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-to-platelet ratio (NPR), and C-reactive protein. Infarct size was assessed by echocardiography and by peak troponin levels.
The study population consisted of 583 AMI patients (with or without ST-segment elevation): 98 SGLT2-I users and 485 non-SGLT-I users. Hyperglycemia at admission was less prevalent in the SGLT2-I group. Smaller infarct size was observed in patients treated with SGLT2-I compared to non-SGLT2-I group. On admission and at 24 h, inflammatory indices were significantly higher in non-SGLT2-I users compared to SGLT2-I patients, with a significant increase in neutrophil levels at 24 h. At multivariable analysis, the use of SGLT2-I was a significant predictor of reduced inflammatory response (OR 0.457, 95% CI 0.275-0.758, p = 0.002), independently of age, admission creatinine values, and admission glycemia. Conversely, peak troponin values and NSTEMI occurrence were independent predictors of a higher inflammatory status.
Type 2 diabetic AMI patients receiving SGLT2-I exhibited significantly reduced inflammatory response and smaller infarct size compared to those receiving other OAD agents, independently of glucose-metabolic control. Our findings are hypothesis generating and provide new insights on the cardioprotective effects of SGLT2-I in the setting of coronary artery disease.
Data are part of the ongoing observational registry: SGLT2-I AMI PROTECT.
gov Identifier: NCT05261867.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hyperglycemia has been associated with increased inflammatory indexes and larger infarct sizes in patients with obstructive acute myocardial infarction (obs-AMI). In contrast, no studies have ...explored these correlations in non-obstructive acute myocardial infarction (MINOCA). We investigated the relationship between hyperglycemia, inflammation and infarct size in a cohort of AMI patients that included MINOCA.
Patients with AMI undergoing coronary angiography between 2016 and 2020 were enrolled. The following inflammatory markers were evaluated: C-reactive protein, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and neutrophil-to-platelet ratio (NPR). Myocardial infarct size was measured by peak high sensitivity troponin I (Hs-TnI) levels, left-ventricular-end-diastolic-volume (LVEDV) and left ventricular ejection fraction (LVEF).
The final study population consisted of 2450 patients with obs-AMI and 239 with MINOCA. Hyperglycemia was more prevalent among obs-AMI cases. In all hyperglycemic patients-obs-AMI and MINOCA-NLR, NPR, and LPR were markedly altered. Hyperglycemic obs-AMI subjects exhibited a higher Hs-TnI (p < 0.001), a larger LVEDV (p = 0.003) and a lower LVEF (p < 0.001) compared to normoglycemic ones. Conversely, MINOCA patients showed a trivial myocardial damage, irrespective of admission glucose levels.
Our data confirm the association of hyperglycemic obs-AMI with elevated inflammatory markers and larger infarct sizes. MINOCA patients exhibited modest myocardial damage, regardless of admission glucose levels.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We evaluate whether the thrombus aspiration (TA) before primary percutaneous coronary intervention (PPCI) may improve STEMI outcomes in hyperglycemic patients.
The management of hyperglycemic ...patients during STEMI is unclear.
We undertook an observational cohort study of 3166 first STEMI. Patients were grouped on the basis of whether they received TA or not. Moreover, among these patients we selected a subgroup of STEMI patients with hyperglycemia during the event (glycaemia > 140 mg/dl). The endpoint at 1 year included all-cause mortality, cardiac mortality and re-hospitalization for coronary disease, heart failure and stroke.
One-thousand STEMI patients undergoing PPCI to plus TA (TA-group) and 1504 STEMI patients treated with PPCI alone (no-TA group) completed the study. In overall study-population, Kaplan-Meier-analysis demonstrated no significant difference in mortality rates between patients with and without TA (P = 0.065). After multivariate Cox-analysis (HR: 0.94, 95% CI 0.641-1.383) and the addition of propensity matching (HR: 0.86 95% CI 0.412-1.798) TA was still not associated with decreased mortality. By contrast, in hyperglycemic subgroup STEMI patients (TA-group, n = 331; no-TA group, n = 566), Kaplan-Meier-analysis demonstrated a significantly lower mortality (P = 0.019) in TA-group than the no-TA group. After multivariate Cox-analysis (HR: 0.64, 95% CI 0.379-0.963) and the addition of propensity matching (HR: 0.54, 95% CI 0.294-0.984) TA was still associated with decreased mortality.
TA was not associated with lower mortality in PPCI for STEMI when used in our large all-comer cohort. Conversely, TA during PPCI for STEMI reduces clinical outcomes in hyperglycemic patients. Trial registration NCT02817542. 25th, June 2016.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
There is growing evidence of cardiac injury in COVID‐19. Our purpose was to assess the prognostic value of serial electrocardiograms in COVID‐19 patients.
Methods
We evaluated 269 ...consecutive patients admitted to our center with confirmed SARS‐CoV‐2 infection. ECGs available at admission and after 1 week from hospitalization were assessed. We evaluated the correlation between ECGs findings and major adverse events (MAE) as the composite of intra‐hospital all‐cause mortality or need for invasive mechanical ventilation. Abnormal ECGs were defined if primary ST‐T segment alterations, left ventricular hypertrophy, tachy or bradyarrhythmias and any new AV, bundle blocks or significant morphology alterations (e.g., new Q pathological waves) were present.
Results
Abnormal ECG at admission (106/216) and elevated baseline troponin values were more common in patients who developed MAE (p = .04 and p = .02, respectively). Concerning ECGs recorded after 7 days (159), abnormal findings were reported in 53.5% of patients and they were more frequent in those with MAE (p = .001). Among abnormal ECGs, ischemic alterations and left ventricular hypertrophy were significantly associated with a higher MAE rate. The multivariable analysis showed that the presence of abnormal ECG at 7 days of hospitalization was an independent predictor of MAE (HR 3.2; 95% CI 1.2–8.7; p = .02). Furthermore, patients with abnormal ECG at 7 days more often required transfer to the intensive care unit (p = .01) or renal replacement therapy (p = .04).
Conclusions
Patients with COVID‐19 should receive ECG at admission but also during their hospital stay. Indeed, electrocardiographic alterations during hospitalization are associated with MAE and infection severity.
Heparin administration in COVID-19 patients is recommended by expert consensus, although evidence about dosage, duration and efficacy are limited. We aim to investigate the association between ...different dosages of low molecular weight heparin (LMWH) and mortality among COVID-19 hospitalized patients.
Retrospective study of 450 laboratory-confirmed COVID-19 patients admitted to Sant'Orsola Bologna Hospital from March 01 to April 10, 2020. Clinical, laboratory and treatment data were collected and analyzed. The in-hospital mortality between COVID-19 patients treated with standard prophylactic LMWH dosage vs. intermediate LMWH dosage was compared. Out of 450 patients, 361 received standard deep vein thrombosis (DVT) prophylaxis enoxaparin treatment (40-60mg daily) and 89 patients received intermediate enoxaparin dosage (40-60 mg twice daily) for 7 days. No significant differences in the main demographic characteristics and laboratory testings at admission were observed in the two heparin regimen subgroups, except for older age and prevalence of hypertension in the group treated with "standard" prophylaxis LMWH dosage. The intermediate LMWH administration was associated with a lower in-hospital all-cause mortality compared to the "standard" prophylactic LMWH dosage (18.8% vs. 5.8%, p = 0.02). This difference remained significant after adjustment with the propensity score for variables that differed significantly between the dosage groups (OR= 0.260, 95% CI 0.089-0.758, p=0.014).
Intermediate LMWH dosage seems to be associated with lower incidence of mortality compared to standard DVT prophylaxys in hospitalized COVID-19 patients. Our study paves the way to further pathophysiological investigations and controlled studies of anticoagulation therapy in Covid-19 disease.
Catheter ablation (CA) is a procedure commonly used to restore sinus rhythm in patients with atrial fibrillation (AF). However, AF recurrence after CA remains a relevant clinical issue. We tested the ...effects of an oral antioxidant treatment (alpha lipoic acid ALA) on AF recurrence post-CA. Patients with paroxysmal AF have been enrolled in a randomized, prospective, double-blind, controlled placebo trial. After CA, patients have been randomly assigned to receive ALA oral supplementation (ALA group) or placebo (control group) and evaluated at baseline and after a 12-month follow-up: 73 patients completed the 12-month follow-up (ALA: 33 and control: 40). No significant difference has been detected between the 2 groups at baseline. Strikingly, 1 year after CA, ALA therapy significantly reduced serum markers of inflammation. However, there was no significant difference in AF recurrence events at follow-up comparing ALA with placebo group. Multivariate analysis revealed that the only independent prognostic risk factor for AF recurrence after CA is age. In conclusion, ALA therapy reduces serum levels of common markers of inflammation in ablated patients. Nevertheless, ALA does not prevent AF recurrence after an ablative treatment.
The prognostic role of hyperglycemia in patients with myocardial infarction and obstructive coronary arteries (MIOCA) is acknowledged, while data on non-obstructive coronary arteries (MINOCA) are ...still lacking. Recently, we demonstrated that admission stress-hyperglycemia (aHGL) was associated with a larger infarct size and inflammatory response in MIOCA, while no differences were observed in MINOCA. We aim to investigate the impact of aHGL on short and long-term outcomes in MIOCA and MINOCA patients.
Multicenter, population-based, cohort study of the prospective registry, designed to evaluate the prognostic information of patients admitted with acute myocardial infarction to S. Orsola-Malpighi and Maggiore Hospitals of Bologna metropolitan area. Among 2704 patients enrolled from 2016 to 2020, 2431 patients were classified according to the presence of aHGL (defined as admission glucose level ≥ 140 mg/dL) and AMI phenotype (MIOCA/MINOCA): no-aHGL (n = 1321), aHGL (n = 877) in MIOCA and no-aHGL (n = 195), aHGL (n = 38) in MINOCA. Short-term outcomes included in-hospital death and arrhythmias. Long-term outcomes were all-cause and cardiovascular mortality.
aHGL was associated with a higher in-hospital arrhythmic burden in MINOCA and MIOCA, with increased in-hospital mortality only in MIOCA. After adjusting for age, gender, hypertension, Killip class and AMI phenotypes, aHGL predicted higher in-hospital mortality in non-diabetic (HR = 4.2; 95% CI 1.9-9.5, p = 0.001) and diabetic patients (HR = 3.5, 95% CI 1.5-8.2, p = 0.003). During long-term follow-up, aHGL was associated with 2-fold increased mortality in MIOCA and a 4-fold increase in MINOCA (p = 0.032 and p = 0.016). Kaplan Meier 3-year survival of non-hyperglycemic patients was greater than in aHGL patients for both groups. No differences in survival were found between hyperglycemic MIOCA and MINOCA patients. After adjusting for age, gender, hypertension, smoking, LVEF, STEMI/NSTEMI and AMI phenotypes (MIOCA/MINOCA), aHGL predicted higher long-term mortality.
aHGL was identified as a strong predictor of adverse short- and long-term outcomes in both MIOCA and MINOCA, regardless of diabetes. aHGL should be considered a high-risk prognostic marker in all AMI patients, independently of the underlying coronary anatomy. Trial registration data were part of the ongoing observational study AMIPE: Acute Myocardial Infarction, Prognostic and Therapeutic Evaluation. ClinicalTrials.gov Identifier: NCT03883711.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mitral valve annuloplasty ring dehiscence Spapen, Jerrold; Paolisso, Pasquale; Van Camp, Guy
The International Journal of Cardiovascular Imaging,
09/2021, Letnik:
37, Številka:
9
Journal Article
To evaluate clinical outcomes in patients with diabetes, treated by cardiac resynchronization therapy with a defibrillator (CRT-d), and glucagon-like peptide 1 receptor agonists (GLP-1 RA) in ...addition to conventional hypoglycemic therapy vs. CRTd patients under conventional hypoglycemic drugs.
Patients with diabetes treated by CRTd experienced an amelioration of functional New York Association Heart class, reduction of hospital admissions, and mortality, in a percentage about 60%. However, about 40% of CRTd patients with diabetes experience a worse prognosis.
We investigated the 12-months prognosis of CRTd patients with diabetes, previously treated with hypoglycemic drugs therapy (n 271) vs. a matched cohort of CRTd patients with diabetes treated with GLP-1 RA in addition to conventional hypoglycemic therapy (n 288).
At follow up CRTd patients with diabetes treated by GLP-1 RA therapy vs. CRTd patients with diabetes that did not receive GLP-1 RA therapy, experienced a significant reduction of NYHA class (p value < 0.05), associated to higher values of 6 min walking test (p value < 0.05), and higher rate of CRTd responders (p value < 0.05). GLP-1 RA patients vs. controls at follow up end experienced lower AF events (p value < 0.05), lower VT events (p value < 0.05), lower rate of hospitalization for heart failure worsening (p value < 0.05), and higher rate of CRTd responders (p value < 0.05). To date, GLP-1 RA therapy may predict a reduction of AF events (HR 0.603, CI 0.411-0.884), VT events (HR 0.964, CI 0.963-0.992), and hospitalization for heart failure worsening (HR 0.119, CI 0.028-0.508), and a higher CRT responders rate (HR 3.707, CI 1.226-14.570).
GLP-1 RA drugs in addition to conventional hypoglycemic therapy may significantly reduce systemic inflammation and circulating BNP levels in CRTd patients with diabetes, leading to a significant improvement of LVEF and of the 6 min walking test, and to a reduction of the arrhythmic burden. Consequently, GLP-1 RA drugs in addition to conventional hypoglycemic therapy may reduce hospital admissions for heart failure worsening, by increasing CRTd responders rate. Trial registration NCT03282136. Registered 9 December 2017 "retrospectively registered".
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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