Cardiac Resynchronization Therapy Outcomes in Type 2 Diabetic Patients: Role of MicroRNA Changes

Heart failure (HF) and type 2 diabetes mellitus (T2DM) are two growing and related diseases in general population and particularly in elderly people. In selected patients affected by HF and severe dysfunction of left ventricle ejection fraction (LVEF), with left bundle brunch block, the cardiac resynchronization therapy with a defibrillator (CRT) is the treatment of choice to improve symptoms, NYHA class, and quality of life. CRT effects are related to alterations in genes and microRNAs (miRs) expression, which regulate cardiac processes involved in cardiac apoptosis, cardiac fibrosis, cardiac hypertrophy and angiogenesis, and membrane channel ionic currents. Different studies have shown a different prognosis in T2DM patients and T2DM elderly patients treated by CRT-D. We reviewed the literature data on CRT-D effect on adult and elderly patients with T2DM as compared with nondiabetic patients

Brief episodes of silent atrial fibrillation predict clinical vascular brain disease in type 2 diabetic patients

ObjectivesThis study evaluated whether subclinical episodes of atrial fibrillation (AF) were associated with an increased risk of silent cerebral infarct (SCI) and stroke in diabetic patients younger than 60 years who did not have other clinical evidence of AF and cerebrovascular disease at baseline.BackgroundIn type 2 diabetic patients, one-fourth of strokes are of unknown cause, and subclinical episodes of AF may be a common etiologic factor.MethodsA total of 464 type 2 diabetic patients younger than 60 years were included in a longitudinal observational study and matched to patients without diabetes. Patients underwent 48-h electrocardiographic Holter monitoring quarterly to detect brief subclinical episodes of AF (duration of AF <48 h) and were followed up for 37 months. The outcomes were SCI, assessed by magnetic resonance imaging of the brain, and stroke events during the follow-up period.ResultsThe prevalence of subclinical episodes of AF was significantly greater among patients with diabetes compared with matched healthy subjects (11% vs. 1.6%, p < 0.0001). During an average duration of 37 months, 43 stroke events occurred in the diabetic population and no events occurred in healthy subjects. Diabetic patients with silent episodes of AF (n = 176) had a higher baseline prevalence of SCI (61% vs. 29%; p < 0.01) and a higher number of stroke events (17.3% vs. 5.9%; p < 0.01) during the follow-up period than the other patients (n = 288). An episode of silent AF was an independent determinant of SCI (odds ratio: 4.441; p < 0.001; confidence interval: 2.42 to 8.16) and an independent predictor of the occurrence of stroke in diabetic patients (hazard ratio: 4.6; p < 0.01; confidence interval: 2.7 to 9.1).ConclusionsSubclinical episodes of AF occurred frequently in type 2 diabetic patients and were associated with a significantly increased risk of SCI and stroke

Cardiac resynchronization therapy and its effects in patients with type 2 DIAbetes mellitus OPTimized in automatic vs. echo guided approach. Data from the DIA-OPTA investigators

Objectives: To evaluate the effects of cardiac resynchronization therapy (CRTd) in patients with type 2 diabetes mellitus (T2DM) optimized via automatic vs. echocardiography-guided approach. Background: The suboptimal atrio-ventricular (AV) and inter-ventricular (VV) delays optimization reduces CRTd response. Therefore, we hypothesized that automatic CRTd optimization might improve clinical outcomes in T2DM patients. Methods: We designed a prospective, multicenter study to recruit, from October 2016 to June 2019, 191 consecutive failing heart patients with T2DM, and candidate to receive a CRTd. Study outcomes were CRTd responders rate, hospitalizations for heart failure (HF) worsening, cardiac deaths and all cause of deaths in T2DM patients treated with CRTd and randomly optimized via automatic (n 93) vs. echocardiography-guided (n 98) approach at 12 months of follow-up. Results: We had a significant difference in the rate of CRTd responders (68 (73.1%) vs. 58 (59.2%), p 0.038), and hospitalizations for HF worsening (12 (16.1%) vs. 22 (22.4%), p 0.030) in automatic vs. echocardiography-guided group of patients. At multivariate Cox regression analysis, the automatic guided approach (3.636 [1.271–10.399], CI 95%, p 0.016) and baseline highest values of atrium pressure (automatic SonR values, 2.863 [1.537–6.231], CI 95%, p 0.006) predicted rate of CRTd responders. In automatic group, we had significant difference in SonR values comparing the rate of CRTd responders vs. non responders (1.24 ± 0.72 g vs. 0.58 ± 0.46 g (follow-up), p 0.001), the rate of hospitalizations for HF worsening events (0.48 ± 0.29 g vs. 1.18 ± 0.43 g, p 0.001), and the rate of cardiac deaths (1.13 ± 0.72 g vs. 0.65 ± 0.69 g, p 0.047). Conclusions: Automatic optimization increased CRTd responders rate, and reduced hospitalizations for HF worsening. Intriguingly, automatic CRTd and highest baseline values of SonR could be predictive of CRTd responders. Notably, there was a significant difference in SonR values for CRTd responders vs. non responders, and about hospitalizations for HF worsening and cardiac deaths. Clinical trial ClinicalTrials.gov Identifier NCT04547244. © 2020, The Author(s)

COVID-19 and atrial fibrillation: Intercepting lines

Almost 20% of COVID-19 patients have a history of atrial fibrillation (AF), but also a new-onset AF represents a frequent complication in COVID-19. Clinical evidence demonstrates that COVID-19, by promoting the evolution of a prothrombotic state, increases the susceptibility to arrhythmic events during the infective stages and presumably during post-recovery. AF itself is the most frequent form of arrhythmia and is associated with substantial morbidity and mortality. One of the molecular factors involved in COVID-19-related AF episodes is the angiotensin-converting enzyme (ACE) 2 availability. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses ACE2 to enter and infect multiple cells. Atrial ACE2 internalization after binding to SARS-CoV-2 results in a raise of angiotensin (Ang) II, and in a suppression of cardioprotective Ang(1–7) formation, and thereby promoting cardiac hypertrophy, fibrosis and oxidative stress. Furthermore, several pharmacological agents used in COVID-19 patients may have a higher risk of inducing electrophysiological changes and cardiac dysfunction. Azithromycin, lopinavir/ritonavir, ibrutinib, and remdesivir, used in the treatment of COVID-19, may predispose to an increased risk of cardiac arrhythmia. In this review, putative mechanisms involved in COVID-19-related AF episodes and the cardiovascular safety profile of drugs used for the treatment of COVID-19 are summarized

Myocardial infarction with nonobstructive coronary arteries: from pathophysiology to therapeutic strategies

: Myocardial infarction with nonobstructive coronary arteries (MINOCA) is a heterogeneous group of clinical entities characterized by clinical evidence of acute myocardial infarction (AMI) with normal or near-normal coronary arteries on coronary angiography (stenosis &lt; 50%) and without an over the alternative diagnosis for the acute presentation. Its prevalence ranges from 6% to 11% among all patients with AMI, with a predominance of young, nonwhite females with fewer traditional risks than those with an obstructive coronary artery disease (MI-CAD). MINOCA can be due to either epicardial causes such as rupture or fissuring of unstable nonobstructive atherosclerotic plaque, coronary artery spasm, spontaneous coronary dissection and cardioembolism in-situ or microvascular causes. Besides, also type-2 AMI due to supply-demand mismatch and Takotsubo syndrome must be considered as a possible MINOCA cause. Because of the complex etiology and a limited amount of evidence, there is still some confusion around the management and treatment of these patients. Therefore, the key focus of this condition is to identify the underlying individual mechanisms to achieve patient-specific treatments. Clinical history, electrocardiogram, echocardiography, and coronary angiography represent the first-level diagnostic investigations, but coronary imaging with intravascular ultrasound and optical coherent tomography, coronary physiology testing, and cardiac magnetic resonance imaging offer additional information to understand the underlying cause of MINOCA. Although the prognosis is slightly better compared with MI-CAD patients, MINOCA is not always benign and depends on the etiopathology. This review analyzes all possible pathophysiological mechanisms that could lead to MINOCA and provides the most specific and appropriate therapeutic approach in each scenario

Glycated ACE2 reduces anti-remodeling effects of renin-angiotensin system inhibition in human diabetic hearts

High glycated-hemoglobin (HbA1c) levels correlated with an elevated risk of adverse cardiovascular outcomes despite renin-angiotensin system (RAS) inhibition in type-2 diabetic (T2DM) patients with reduced ejection fraction. Using the routine biopsies of non-T2DM heart transplanted (HTX) in T2DM recipients, we evaluated whether the diabetic milieu modulates glycosylated ACE2 (GlycACE2) levels in cardiomyocytes, known to be affected by non-enzymatic glycosylation, and the relationship with glycemic control

Deferral of Coronary Revascularization in Patients With Reduced Ejection Fraction Based on Physiological Assessment: Impact on Long-Term Survival

Background Deferring revascularization in patients with nonsignificant stenoses based on fractional flow reserve (FFR) is associated with favorable clinical outcomes up to 15 years. Whether this holds true in patients with reduced left ventricular ejection fraction is unclear. We aimed to investigate whether FFR provides adjunctive clinical benefit compared with coronary angiography in deferring revascularization of patients with intermediate coronary stenoses and reduced left ventricular ejection fraction. Methods and Results Consecutive patients with reduced left ventricular ejection fraction (≤50%) undergoing coronary angiography between 2002 and 2010 were screened. We included patients with at least 1 intermediate coronary stenosis (diameter stenosis ≥40%) in whom revascularization was deferred based either on angiography plus FFR (FFR guided) or angiography alone (angiography guided). The primary end point was the cumulative incidence of all-cause death at 10 years. The secondary end point (incidence of major adverse cardiovascular and cerebrovascular events) was a composite of all-cause death, myocardial infarction, any revascularization, and stroke. A total of 840 patients were included (206 in the FFR-guided group and 634 in the angiography-guided group). Median follow-up was 7 years (interquartile range, 3.22-11.08 years). After 1:1 propensity-score matching, baseline characteristics between the 2 groups were similar. All-cause death was significantly lower in the FFR-guided group compared with the angiography-guided group (94 [45.6%] versus 119 [57.8%]; hazard ratio [HR], 0.65 [95% CI, 0.49-0.85]; P<0.01). The rate of major adverse cardiovascular and cerebrovascular events was lower in the FFR-guided group (123 [59.7%] versus 139 [67.5%]; HR, 0.75 [95% CI, 0.59-0.95]; P=0.02). Conclusions In patients with reduced left ventricular ejection fraction, deferring revascularization of intermediate coronary stenoses based on FFR is associated with a lower incidence of death and major adverse cardiovascular and cerebrovascular events at 10 years

MULTI-MODALITY IMAGING IN AORTIC STENOSIS:AN EACVI CLINICAL CONSENSUS DOCUMENT

International audienceIn this EACVI clinical scientific update, we will explore the current use of multi-modality imaging in the diagnosis, risk stratification, and follow-up of patients with aortic stenosis, with a particular focus on recent developments and future directions. Echocardiography is and will likely remain the key method of diagnosis and surveillance of aortic stenosis providing detailed assessments of valve haemodynamics and the cardiac remodelling response. Computed tomography (CT) is already widely used in the planning of transcutaneous aortic valve implantation. We anticipate its increased use as an anatomical adjudicator to clarify disease severity in patients with discordant echocardiographic measurements. CT calcium scoring is currently used for this purpose; however, contrast CT techniques are emerging that allow identification of both calcific and fibrotic valve thickening. Additionally, improved assessments of myocardial decompensation with echocardiography, cardiac magnetic resonance, and CT will become more commonplace in our routine assessment of aortic stenosis. Underpinning all of this will be widespread application of artificial intelligence. In combination, we believe this new era of multi-modality imaging in aortic stenosis will improve the diagnosis, follow-up, and timing of intervention in aortic stenosis as well as potentially accelerate the development of the novel pharmacological treatments required for this disease

Infarct size, inflammatory burden, and admission hyperglycemia in diabetic patients with acute myocardial infarction treated with SGLT2-inhibitors: a multicenter international registry

Background: 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. Methods: 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. Results: 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&nbsp;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&nbsp;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. Conclusions: 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. Trial registration: Data are part of the ongoing observational registry: SGLT2-I AMI PROTECT. Clinicaltrials: gov Identifier: NCT05261867

Sex-Related Disparities in Cardiac Masses: Clinical Features and Outcomes

Background. Cardiac masses (CM) represent a heterogeneous clinical scenario, and sex-related differences of these patients remain to be established. Purpose: To evaluate sex-related disparities in CMs regarding clinical presentation and outcomes. Material and Methods. The study cohort included 321 consecutive patients with CM enrolled in our Centre between 2004 and 2022. A definitive diagnosis was achieved by histological examination or, in the case of cardiac thrombi, with radiological evidence of thrombus resolution after anticoagulant treatment. All-cause mortality at follow-up was evaluated. Multivariable regression analysis assessed the potential prognostic disparities between men and women. Results. Out of 321 patients with CM, 172 (54%) were female. Women were more frequently younger (p = 0.02) than men. Regarding CM histotypes, females were affected by benign masses more frequently (with cardiac myxoma above all), while metastatic tumours were more common in men (p &lt; 0.001). At presentation, peripheral embolism occurred predominantly in women (p = 0.03). Echocardiographic features such as greater dimension, irregular margin, infiltration, sessile mass and immobility were far more common in men. Despite a better overall survival in women, no sex-related differences were observed in the prognosis of benign or malignant masses. In fact, in multivariate analyses, sex was not independently associated with all-cause death. Conversely, age, smoking habit, malignant tumours and peripheral embolism were independent predictors of mortality. Conclusions. In a large cohort of cardiac masses, a significant sex-related difference in histotype prevalence was found: Benign CMs affected female patients more frequently, while malignant tumours affected predominantly men. Despite better overall survival in women, sex did not influence prognosis in benign and malignant masses