Hypoglycemic Drugs in Patients with Diabetes Mellitus and Heart Failure: A Narrative Review.

Over the last few years, given the increase in the incidence and prevalence of both type 2 diabetes mellitus (T2DM) and heart failure (HF), it became crucial to develop guidelines for the optimal preventive and treatment strategies for individuals facing these coexisting conditions. In patients aged over 65, HF hospitalization stands out as the predominant reason for hospital admissions, with their prognosis being associated with the presence or absence of T2DM. Historically, certain classes of glucose-lowering drugs, such as thiazolidinediones (rosiglitazone), raised concerns due to an observed increased risk of myocardial infarction (MI) and cardiovascular (CV)-related mortality. In response to these concerns, regulatory agencies started requiring CV outcome trials for all novel antidiabetic agents [i.e., dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and sodium-glucose cotransporter-2 inhibitors (SGLT2is)] with the aim to assess the CV safety of these drugs beyond glycemic control. This narrative review aims to address the current knowledge about the impact of glucose-lowering agents used in T2DM on HF prevention, prognosis, and outcome.

The Role of Cardiovascular Magnetic Resonance Imaging in Patients with Cardiac Arrhythmias.

Cardiac arrhythmias are associated with significant morbidity, mortality and poor quality of life. Cardiovascular magnetic resonance (CMR) imaging, with its unsurpassed capability of non-invasive tissue characterisation, high accuracy, and reproducibility of measurements, plays an integral role in determining the underlying aetiology of cardiac arrhytmias. CMR can reliably diagnose previous myocardial infarction, non-ischemic cardiomyopathy, characterise congenital heart disease and valvular pathologies, and also detect the underlying substrate concealed on conventional investigations in a significant proportion of patients with arrhythmias. Determining the underlying substrate of arrhythmia is of paramount importance for treatment planning and prognosis. However, CMR imaging in patients with irregular heart rates can be problematic. Understanding the different ways to overcome the limitations of CMR in arrhythmia is essential for providing high-quality imaging, comprehensive information, and definitive answers in this diverse group of patients.

Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Acute Coronary Syndrome: A Modern Cinderella?

PURPOSE: Atherosclerotic cardiovascular disease remains a prominent global cause of mortality, with coronary artery disease representing its most prevalent manifestation. Recently, a novel class of antidiabetic medication, namely sodium-glucose cotransporter-2 (SGLT2) inhibitors, has been reported to have remarkable cardiorenal advantages for individuals with type 2 diabetes mellitus (DM), and they may reduce cardiorenal risk even in individuals without pre-existing DM. Currently, there is no evidence regarding the safety and efficacy of these drugs in acute coronary syndrome (ACS), regardless of diabetes status. This review aims to comprehensively present the available preclinical and clinical evidence regarding the potential role of SGLT2 inhibitors in the context of ACS, as adjuncts to standard-of-care treatment for this patient population, while also discussing potential short- and long-term cardiovascular benefits. METHODS: A literature search was performed through MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, and Scopus until February 26, 2024. Eligible were preclinical and clinical studies, comprising randomized controlled trials (RCTs), real-world studies, and meta-analyses. FINDINGS: Evidence from preclinical models indicates that the use of SGLT2 inhibitors is associated with a blunted ischemia-reperfusion injury and decreased myocardial infarct size, particularly after prior treatment. Although RCTs and real-world data hint at a potential benefit in acute ischemic settings, showing improvements in left ventricular systolic and diastolic function, decongestion, and various cardiometabolic parameters such as glycemia,body weight, and blood pressure, the recently published DAPA-MI (Dapagliflozin in Myocardial Infarction without Diabetes or Heart Failure) trial did not establish a clear advantage regarding surrogate cardiovascular end points of interest. SGLT2 inhibitors appear to provide a benefit in reducing contrast-induced acute kidney injury events in patients with ACS undergoing percutaneous coronary intervention. However, data on other safety concerns, such as treatment discontinuation because of hypotension, hypovolemia, or ketoacidosis, are currently limited. IMPLICATIONS: Despite the well-established cardiovascular benefits observed in the general population with type 2 DM and, more recently, in other patient groups irrespective of diabetes status, existing evidence does not support the use of SGLT2 inhibitors in the context of ACS. Definitive answers to this intriguing research question, which could potentially expand the therapeutic indications of this novel drug class, require large-scale, well-designed RCTs.

An Armored Heart: A Diagnosis Hidden in Plain Sight.

We report a case of an overtly symptomatic patient with delayed diagnosis of massive (>25-mm thickness), circular, constrictive pericarditis. Our patient underwent a successful surgical pericardiectomy-a high-risk procedure-revealing an armored heart, with an impressive clinical improvement. Diagnosis of constrictive pericarditis is challenging and requires high clinical suspicion.

The Effect of Cardiac Resynchronization Therapy on Right Ventricular Function: A Systematic Review and Meta-Analysis.

Background: Right ventricular (RV) failure is an important predicting factor regarding overall and event-free survival regardless of baseline left ventricular (LV) function in patients with severe heart failure (HF). Previous studies have indicated that cardiac resynchronization therapy (CRT) improves LV and RV reverse remodeling in patients with systolic dyssynchrony within the left ventricle. However, there is conflicting evidence regarding the role of CRT in RV function. The aim of this systematic review and meta-analysis was to examine the implications of CRT on RV function indices. Methods: A systematic literature search was conducted using the MedLine and EMBASE databases and the Cochrane Library from their inception until 18 March 2024. Eligible were studies providing information on RV function indices, both at baseline and after CRT. Evidence was summarized using random-effects meta-analytic models. Results: In total, 30 studies were deemed eligible. CRT resulted in a significant improvement in right ventricular fractional area change (mean difference (MD) 5.11%, 95% confidence interval (CI) 2.83 to 7.39), tricuspid annular plane systolic excursion (TAPSE, MD 1.63 mm, 95% CI 1.10 to 2.16), and myocardial systolic excursion velocity (MD 1.85 cm/s, 95% CI 1.24 to 2.47) as well as a significant decrease in pulmonary artery systolic pressure (MD -6.24 mmHg, 95% CI -8.32 to -4.16). A non-significant effect was observed on TAPSE to PASP ratio and right ventricular global longitudinal strain. Conclusions: Our meta-analysis demonstrates that CRT is associated with a significant improvement in echocardiographic parameters of RV function. Further investigation is necessary to elucidate how these changes, both independently and in conjunction with LV improvement, impact patients' long-term prognosis, and to identify the specific patient populations expected to derive the greatest benefit.

The Role of Cardiovascular Magnetic Resonance Imaging in the Assessment of Mitral Regurgitation.

Mitral regurgitation (MR), a primary cause of valvular disease in adults, affects millions and is growing due to an ageing population. Cardiovascular magnetic resonance (CMR) has emerged as an essential tool, offering insights into valvular and myocardial pathology when compared to the primary imaging modality, echocardiography. This review highlights CMR's superiority in high-resolution volumetric assessment and tissue characterization, including also advanced techniques like late gadolinium enhancement imaging, parametric mapping, feature tracking and 4D flow analysis. These techniques provide a deeper understanding of MR's pathophysiology and its effect on cardiac chambers, enabling CMR to surpass echocardiography in predicting hard clinical outcomes and left ventricular (LV) remodelling post mitral valve surgery. Despite its advantages, CMR's application faces limitations like cost, lack of standardization, and susceptibility to arrhythmia artifacts. Nonetheless, as technological advancements continue and new evidence emerges, CMR's role in MR assessment is set to expand, offering a more nuanced and personalized approach to cardiac care. This review emphasizes the need for further research and standardized protocols to maximize CMR's potential in MR management.

Effects of Glucagon-Like Peptide 1 Receptor Agonists on Atrial Fibrillation Recurrence After Catheter Ablation: A Systematic Review and Meta-analysis.

INTRODUCTION: Despite the technological advancements in catheter ablation strategies, the recurrence of atrial fibrillation (AF) post-ablation remains a concern that requires further investigation. Glucagon-like peptide 1 (GLP-1) receptor agonists have shown a significant effect on weight reduction, which in turn is associated with freedom from AF recurrence in both patients who are obese and not obese undergoing ablation. Therefore, we aimed to summarize the available evidence on the efficacy of GLP-1 receptor agonists in maintaining sinus rhythm post-ablation. METHODS: Medline, Cochrane Library, and Scopus were searched until June 9, 2024. Double-independent study selection, data extraction, and quality assessment were performed. Evidence was pooled using DerSimonian-Laird random effects meta-analysis. RESULTS: Three propensity score-matched studies (n = 6031 participants) were analyzed. Over a 12-months follow-up, the use of GLP-1 receptor agonists was associated with a significant reduction in AF recurrence compared to controls, hazard ratio (HR) = 0.549, 95% confidence interval (CI) = [0.315, 0.956], P = 0.034; I2 = 57%. No significant heterogeneity was observed (Q statistic = 4.6, heterogeneity P = 0.1). CONCLUSION: The use of GLP-1 receptor agonists is associated with a lower risk of AF recurrence in patients receiving AF ablation therapy. Further large-scale randomized trials are necessary to explore the efficacy of GLP-1 receptor agonists in maintaining ablation outcomes over the long term.

Multimodality imaging for the global evaluation of aortic stenosis: The valve, the ventricle, the afterload.

Aortic stenosis (AS) is the most common valvular heart disease growing in parallel to the increment of life expectancy. Besides the valve, the degenerative process affects the aorta, impairing its elastic properties and leading to increased systemic resistance. The composite of valvular and systemic afterload mediates ventricular damage. The first step of a thorough evaluation of AS should include a detailed assessment of valvular anatomy and hemodynamics. Subsequently, the ventricle, and the global afterload should be assessed to define disease stage and prognosis. Multimodality imaging is of paramount importance for the comprehensive evaluation of these three elements. Echocardiography is the cornerstone modality whereas Multi-Detector Computed Tomography and Cardiac Magnetic Resonance provide useful complementary information. This review comprehensively examines the merits of these imaging modalities in AS for the evaluation of the valve, the ventricle, and the afterload and ultimately endeavors to integrate them in a holistic assessment of AS.

Moving from left ventricular ejection fraction to deformation imaging in mitral valve regurgitation.

The increasing prevalence of valvular heart diseases, specifically mitral regurgitation (MR), underscores the need for a careful and timely approach to intervention. Severe MR, whether primary or secondary, when left untreated leads to adverse outcomes, emphasizing the critical role of a timely surgical or transcatheter intervention. While left ventricular ejection fraction (LVEF) remains the guideline-recommended measure for assessing left ventricle damage, emerging evidence raises concerns regarding its reliability in MR due to its volume-dependent nature. This review summarizes the existing literature on the role of LVEF and deformation imaging techniques, emphasizing the latter's potential in providing a more accurate evaluation of intrinsic myocardial function. Moreover, it advocates the need for an integrated approach that combines traditional with emerging measures, aiming to optimize the management of patients with MR. It attempts to highlight the need for future research to validate the clinical application of deformation imaging techniques through large-scale studies.

Multiorgan Congestion Assessment by Venous Excess Ultrasound Score in Acute Heart Failure.

BACKGROUND: This study sought to explore the prevalence and clinical utility of different patterns of multiorgan venous congestion as assessed by the venous excess ultrasound (VExUS) score in hospitalized patients with acute heart failure (HF). METHODS: Consecutive patients admitted for acute HF were prospectively enrolled. Inferior vena cava diameter, hepatic vein, portal vein, and renal vein Doppler waveforms were assessed at admission, and patients were stratified based on VExUS score from 0 to 3, with higher values indicating worse congestion. The clinical score Get with the Guidelines (GWTG)-HF for predicting in-hospital mortality in HF was evaluated. In-hospital mortality was recorded. RESULTS: Two hundred ninety patients admitted with acute HF were included, and 114 (39%) of them were classified as VExUS score 3, which was the most prevalent group. Patients with VExUS score 3 suffered more frequently from chronic atrial fibrillation, chronic kidney disease, and anemia. Parameters independently associated with VExUS score 3 were higher mean E/e' ratio, larger right ventricular size, severe tricuspid regurgitation, and impaired right atrial function. A VExUS score of 3 was associated with in-hospital mortality (odds ratio, 8.03; 95% CI [2.25-28.61], P = .001). The addition of VExUS score on top of the GWTG-HF score improved the predictability of the model (Δx2 = +8.44, P = .03) for in-hospital mortality, whereas other indices of venous congestion (right atrial function, inferior vena cava size) did not. CONCLUSIONS: Patients admitted with acute HF commonly had severe venous congestion based on the VExUS score. The VExUS score improved the prediction of in-hospital mortality compared with other indices of venous congestion.

Differentiating Left Ventricular Remodeling in Aortic Stenosis From Systemic Hypertension.

BACKGROUND: Left ventricular (LV) hypertrophy occurs in both aortic stenosis (AS) and systemic hypertension (HTN) in response to wall stress. However, differentiation of hypertrophy due to these 2 etiologies is lacking. The aim was to study the 3-dimensional geometric remodeling pattern in severe AS pre- and postsurgical aortic valve replacement and to compare with HTN and healthy controls. METHODS: Ninety-one subjects (36 severe AS, 19 HTN, and 36 healthy controls) underwent cine cardiac magnetic resonance. Cardiac magnetic resonance was repeated 8 months post-aortic valve replacement (n=18). Principal component analysis was performed on the 3-dimensional meshes reconstructed from 109 cardiac magnetic resonance scans of 91 subjects at end-diastole. Principal component analysis modes were compared across experimental groups together with conventional metrics of shape, strain, and scar. RESULTS: A unique AS signature was identified by wall thickness linked to a LV left-right axis shift and a decrease in short-axis eccentricity. HTN was uniquely linked to increased septal thickness. Combining these 3 features had good discriminative ability between AS and HTN (area under the curve, 0.792). The LV left-right axis shift was not reversible post-aortic valve replacement, did not associate with strain, age, or sex, and was predictive of postoperative LV mass regression (R2=0.339, P=0.014). CONCLUSIONS: Unique remodeling signatures might differentiate the etiology of LV hypertrophy. Preliminary findings suggest that LV axis shift is characteristic in AS, is not reversible post-aortic valve replacement, predicts mass regression, and may be interpreted to be an adaptive mechanism.

Cardiac magnetic resonance for ventricular arrhythmias: a systematic review and meta-analysis.

BACKGROUND: Cardiac magnetic resonance (CMR) allows comprehensive myocardial tissue characterisation, revealing areas of myocardial inflammation or fibrosis that may predispose to ventricular arrhythmias (VAs). With this study, we aimed to estimate the prevalence of structural heart disease (SHD) and decipher the prognostic implications of CMR in selected patients presenting with significant VAs. METHODS: Electronic databases were searched for studies enrolling adult patients that underwent CMR for diagnostic or prognostic purposes in the setting of significant VAs. A random effects model meta-analysis of proportions was performed to estimate the prevalence of SHD. HRs were pooled together in order to evaluate the prognostic value of CMR. RESULTS: The prevalence of SHD was reported in 18 studies. In all-comers with significant VAs, the pooled rate of SHD post-CMR evaluation was 39% (24% in the subgroup of premature ventricular contractions and/or non-sustained ventricular tachycardia vs 63% in the subgroup of more complex VAs). A change in diagnosis after use of CMR ranged from 21% to 66% with a pooled average of 35% (29%-41%). A non-ischaemic cardiomyopathy was the most frequently identified SHD (56%), followed by ischaemic heart disease (21%) and hypertrophic cardiomyopathy (5%). After pooling together data from six studies, we found that the presence of late gadolinium enhancement was associated with increased risk of major adverse outcomes in patients with significant VAs (pooled HR: 1.79; 95% CI 1.33 to 2.42). CONCLUSION: CMR is a valuable tool in the diagnostic and prognostic evaluation of patients with VAs. CMR should be considered early after initial evaluation in the diagnostic algorithm for VAs of unclear aetiology as this strategy may also define prognosis and improve risk stratification.

Right Ventricular and Right Atrial Strain Are Associated with Kidney Dysfunction in Acute Heart Failure.

BACKGROUND: In acute heart failure (HF), low cardiac output and venous congestion are pathophysiological mechanisms that contribute to renal function impairment. This study investigated the association between advanced echocardiographic measures of right ventricular and atrial function and renal impairment in patients with acute HF. METHODS AND RESULTS: A total of 377 patients hospitalized for acute HF were prospectively evaluated. Estimated glomerular filtration rate (eGFR) on admission was measured using the 2021 Chronic Kidney Disease Epidemiology Collaboration creatinine equation. Advanced echocardiographic assessment was performed on admission. Patients with eGFR < 45 mL/min/1.73 m2 were more likely to have chronic heart failure, chronic atrial fibrillation, and type 2 diabetes mellitus compared to patients with eGFR ≥ 45 mL/min/1.73 m2. Patients with lower eGFR had lower cardiac output, higher mean E/e' ratio, larger right ventricular (RV) size, worse RV free wall longitudinal strain, more impaired right atrial (RA) reservoir strain, and more frequent severe tricuspid regurgitation. RV free wall longitudinal strain and RA reservoir strain were the only independent echocardiographic associates of low eGFR, whereas cardiac output was not. CONCLUSIONS: Impaired RV and RA longitudinal strain were independently associated with eGFR < 45 mL/min/1.73 m2 in acute HF, while reduced cardiac output was not. This suggests that RV and RA dysfunction underlying venous congestion and increased renal afterload are more important pathophysiological determinants of renal impairment in acute HF than reduced cardiac output.

Prognostic implications of genotype findings in non-ischaemic dilated cardiomyopathy: A network meta-analysis.

AIMS: Evidence on the relative impact of diverse genetic backgrounds associated with non-ischaemic dilated cardiomyopathy (DCM) remains contradictory. This study sought to synthesize the available data regarding long-term outcomes of different gene groups in DCM. METHODS AND RESULTS: Electronic databases were systematically screened to identify studies reporting prognostic data on pre-specified gene groups. Those included pathogenic/likely pathogenic (P/LP) variants, truncating titin variants (TTNtv), lamin A/C variants (LMNA), and desmosomal proteins. Outcomes were divided into composite adverse events (CAEs), malignant ventricular arrhythmic events (MVAEs) and heart failure events (HFEs). A total of 26 studies (n = 7255) were included in the meta-analysis and 6791 patients with genotyped DCM were analysed. Patients with P/LP variants had a higher risk for CAEs (odds ratio [OR] 2.10, 95% confidence interval [CI] 1.67-2.65), MVAEs (OR 1.86, 95% CI 1.52-2.26), and HFEs (OR 2.01, 95% CI 1.08-3.73) than genotype-negative patients. The presence of TTNtv was linked to a higher risk for CAEs (OR 1.78, 95% CI 1.20-2.63), but not MVAEs or HFEs. LMNA and desmosomal groups suffered a higher risk for CAEs, MVAEs, and HFEs compared to non-LMNA and non-desmosomal groups, respectively. When genes were indirectly compared, the presence of LMNA resulted in a more detrimental effect that TTNtv, with respect to all composite outcomes but no significant difference was found between LMNA and desmosomal genes. Desmosomal genes harboured a higher risk for MVAEs compared to TTNtv. CONCLUSIONS: Different genetic substrates associated with DCM result in divergent natural histories. Routine utilization of genetic testing should be employed to refine risk stratification and inform therapeutic strategies in DCM.

Effects of mineralocorticoid receptor antagonists on new-onset or recurrent atrial fibrillation: a Bayesian and frequentist network meta-analysis of randomized trials.

Background Clinical and translational research suggests that mineralocorticoid receptor antagonists (MRAs) may prevent atrial fibrosis and electrical remodeling associated with atrial fibrillation (AF). This study aimed to consolidate existing evidence from randomized controlled trials (RCTs) evaluating the effect of MRAs on incident or recurrent AF. Methods Medline, Cochrane Library and Scopus were searched until February 12, 2024. Triple-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using both pairwise and Bayesian and frequentist network meta-analyses. Results Twenty-three RCTs (13,358 participants) were identified. Based on the pairwise random effects meta-analysis, MRAs were associated with a significant reduction in AF events compared to placebo or usual care (risk ratio {RR}= 0.75; 95% confidence interval {CI}= [0.66, 0.87]; P< 0.001; I2= 3%). This protective effect was robust both for new-onset and recurrent AF episodes (subgroup p-value= 0.69), while the baseline HF status was not a significant effect modifier (subgroup p-value= 0.58). MRAs demonstrated a significantly higher reduction in AF events for patients with chronic renal disease compared to placebo (RR= 0.78; 95% CI= [0.62, 0.98]; P= 0.03; I2= 0%). The network meta-analyses revealed that only spironolactone was associated with a significant reduction in AF events (Bayesian RR= 0.76; 95% CI= [0.65, 0.89]; P< 0.001; level of evidence moderate; SUCRA 0.731), while eplerenone and finerenone showed a neutral effect. Conclusion MRAs confer a significant benefit in terms of reducing incident or recurrent AF episodes, irrespective of HF status. In this context, spironolactone may be preferable compared to eplerenone or finerenone.