Role of polypill in cardiovascular prevention and treatment.

Cardiovascular diseases (CVD) remain the leading cause of mortality globally and require innovative strategies for effective prevention and treatment. The polypill concept, which integrates multiple cardioprotective agents into a single dosage form, has emerged as a promising approach to improve adherence and simplify the management of cardiovascular risk factors. We review clinical trials and observational studies evaluating the impact of the polypill on reducing the incidence of major cardiovascular events (MACEs), its influence on medication adherence, and its potential to fill treatment gaps in diverse populations. Also of note are the pharmacoeconomic implications of the widespread use of the polypill, particularly in low- and middle-income countries where the burden of cardiovascular disease is increasing. Although the polypill demonstrates a favorable profile in improving therapeutic compliance and reducing cardiovascular risk factors, debates persist regarding its efficacy compared to individualized treatment regimens. This review summarizes the current evidence on the efficacy, safety, and cost-effectiveness of the polypill in CVD primary and secondary prevention. Furthermore, potential challenges in implementing the polypill strategy include tailoring the components to patient-specific risk profiles and the need for robust evidence from large-scale randomized controlled trials to substantiate its long-term benefits.

3D transesophageal echocardiographic assessment of acute reverse remodeling of the tricuspid annulus after transcatheter edge-to-edge repair.

AIMS: Our study aims to evaluate the acute remodeling of the tricuspid valve annulus immediately after the T-TEER by using intraprocedural transesophageal three-dimensional (3D) echocardiography. METHODS AND RESULTS: We prospectively enrolled 62 consecutive symptomatic patients with at least severe TR, who underwent T-TEER with the TriClip System between March 2021 and June 2024. The following parameters were assessed using a multiplanar reconstruction analysis performed off-line using a 3D dataset: septal-lateral (SL) and antero-posterior (AP) annulus diameters; annulus area; annulus perimeter and eccentricity index.The acute procedural success was achieved in 85,5%. We observed an acute reduction in SL (from a median of 43 to 38 mm, p<0,0001), AP (from a median of 46 to 45 mm, p<0,0001), area (from a median of 17,9 to 15,95 cm2, p<0,0001), perimeter (from a median of 145,5 to 137 mm, p<0,0001) and eccentricity index (from 0,92 to 0,87, p<0,0001). The TV annulus was progressively larger in patients with higher residual TR. Analysis of the subgroups according to procedural success showed an acute inverse remodeling of the TV annulus independent of the acute procedural success. CONCLUSIONS: The TV geometry necessitates the use of 3D echocardiography for accurate assessment of annular remodeling post T-TEER. The reduction in TR grade and TV annulus dimensions begins immediately after TriClip implantation. Concurrently, the baseline TV geometry influences the procedural results.

Impact of burden and distribution of aortic valve calcification on the hemodynamic performance and procedural outcomes of a self-expanding, intra-annular transcatheter aortic valve system.

Aortic valve calcification (AVC) has been explored as a powerful predictor of procedural complications in patients undergoing transcatheter aortic valve implantation (TAVI). However, little evidence exists on its impact on intra-annular devices' performance. We aimed to investigate the impact of AVC burden and distribution pattern on the occurrence of paravalvular leak (PVL), conduction disturbances requiring permanent pacemaker implantation (PPI) and 30-day clinical outcomes in patients undergoing TAVI with a self-expanding, intra-annular device. According to AVC, 103 patients enrolled in a single medical centre from November 2019 to December 2022 were divided into tertiles. Valve Academic Research Consortium (VARC)-3 definitions were used to classify procedural complications and outcomes. Patients in the highest AVC tertile showed an increased occurrence of mild or more PVL and conduction disorders (p < 0.001 and p = 0.006). AVC tertiles (highest tertile) emerged as an independent predictor of PVL (OR 7.32, 95%CI 3.10-17.28, p < 0.001) and post-TAVI conduction disturbances (OR 3.73, 95%CI 1.31-10.60, p = 0.013) but not of PPI (OR 1.44, 95%CI 0.39-5.35, p = 0.579). Considering calcium distribution, ROC analyses revealed that annular AVC but not left ventricle outflow tract (LVOT) calcium burden significantly indicated the development of PVL (AUC 0.863, 0.77-0.93, p < 0.001) and conduction disorders/PPI (AUC 0.797, 0.70-0.89, p < 0.001 and 0.723, 0.58-0.86, p = 0.018, respectively). After adjustment for age and sex, the highest tertile remained an independent predictor of the 30-day composite outcome (death, myocardial infarction, stroke, major vascular complications, type 3/4 bleedings, acute kidney injury, PPI and ≥ moderate PVL) (OR 3.26; 95%CI 1.26-8.40, p = 0.014). A higher AVC is associated with an increased risk of PVL and conduction disturbances after TAVI with a self-expanding, intra-annular device. However, our findings suggest a minor role for LVOT calcification compared with annular AVC in the performance of this specific prosthesis.

The Spectrum of Coronary Artery Disease in Elite Endurance Athletes-A Long-Standing Debate: State-of-the-Art Review.

Physical activity is recommended for the prevention of primary and secondary cardiovascular (CV) disease as it is linked to a number of health benefits, especially CV. However, recent research suggests that high-volume, long-term endurance exercise may hasten rather than slow the coronary atherosclerosis progression. This contentious theory has generated a great discussion and is still a major source of doubt when it comes to the clinical treatment of coronary artery disease (CAD) in athletes. CAD is the primary cause of sudden cardiac death in athletes over 35 years. Thus, recent studies evaluated the prevalence of CAD in athletes and its clinical and prognostic implications. Indeed, many studies have shown a relationship between endurance sports and higher volumes of coronary calcified plaque as determined by computed tomography. However, the precise pathogenetic substrate for the existence of an increased coronary calcification burden among endurance athletes remains unclear. Moreover, the idea that coronary plaques in elite athletes present a benign morphology has been cast into doubt by some recent studies showing potential association with adverse cardiovascular events. This review aims to analyze the association between physical activity and CAD, explaining possible underlying mechanisms of atherosclerotic progression and non-ischemic coronary lesions, focusing primarily on clinical and prognostic implications, multimodal evaluation, and management of CAD in endurance athletes.

Integrating platelet reactivity in the age, creatinine and ejection fraction score to predict clinical outcomes following percutaneous coronary intervention in patients with chronic coronary syndrome: the PR-ACEF score.

To evaluate if integrating platelet reactivity (PR) evaluation in the original age, creatinine and ejection fraction (ACEF) score could improve the diagnostic accuracy of the model in patients with stable coronary artery disease (CAD). We enrolled patients treated with percutaneous coronary intervention between 2010 and 2011. High PR was included in the model (PR-ACEF). Co-primary end points were a composite of death/myocardial infarction (MI) and major adverse cardiovascular events (MACE). Overall, 471 patients were enrolled. Compared to the ACEF score, the PR-ACEF showed an improved diagnostic accuracy for death/MI (AUC 0.610 vs 0.670, p < 0.001) and MACE (AUC 0.572 vs 0.634, p < 0.001). These findings were confirmed using internal validation with bootstrap resampling. At 5 years, the PR-ACEF value > 1.75 was independently associated with death/MI [HR 3.51, 95% CI (1.97-6.23)] and MACE [HR 2.77, 95% CI (1.69-4.53)]. The PR-ACEF score was effective in improving the diagnostic performance of the ACEF score at the long-term follow-up.

Rethinking weight loss treatments as cardiovascular medicine in obesity, a comprehensive review.

The global escalation of obesity has made it a worldwide health concern, notably as a leading risk factor for cardiovascular disease (CVD). Extensive evidence corroborates its association with a range of cardiac complications, including coronary artery disease, heart failure, and heightened vulnerability to sudden cardiac events. Additionally, obesity contributes to the emergence of other cardiovascular risk factors including dyslipidaemia, type 2 diabetes, hypertension, and sleep disorders, further amplifying the predisposition to CVD. To adequately address CVD in patients with obesity, it is crucial to first understand the pathophysiology underlying this link. We herein explore these intricate mechanisms, including adipose tissue dysfunction, chronic inflammation, immune system dysregulation, and alterations in the gut microbiome.Recent guidelines from the European Society of Cardiology underscore the pivotal role of diagnosing and treating obesity to prevent CVD. However, the intricate relationship between obesity and CVD poses significant challenges in clinical practice: the presence of obesity can impede accurate CVD diagnosis while optimizing the effectiveness of pharmacological treatments or cardiac procedures requires meticulous adjustment, and it is crucial that cardiologists acknowledge the implications of excessive weight while striving to enhance outcomes for the vulnerable population affected by obesity. We, therefore, sought to overcome controversial aspects in the clinical management of heart disease in patients with overweight/obesity and present evidence on cardiometabolic outcomes associated with currently available weight management interventions, with the objective of equipping clinicians with an evidence-based approach to recognize and address CVD risks associated with obesity.

Controlled mitral valvuloplasty using steerable catheter- waist- formed balloon system: A clinical case series.

As the general population ages, the incidence of degenerative mitral stenosis (MS) among patients has increased. Percutaneous mitral valvuloplasty (PMV) has emerged as a well-established option for mitral rheumatic stenosis with specific characteristics. However, a blank therapeutic space must be filled with the treatment options for degenerative or rheumatic mitral stenosis in patients with many comorbidities and contraindication for valvuloplasty. We here present a comprehensive overview of the current possibilities, despite their scarce success. That is the reason why we propose a case series to facilitate a better understanding of our innovative technique in this challenging clinical context.

Periprocedural myocardial infarction after percutaneous coronary intervention and long-term mortality: a meta-analysis.

BACKGROUND AND AIMS: Conflicting data are available regarding the association between periprocedural myocardial infarction (PMI) and mortality following percutaneous coronary intervention. The purpose of this study was to evaluate the incidence and prognostic implication of PMI according to the Universal Definition of Myocardial Infarction (UDMI), the Academic Research Consortium (ARC)-2 definition, and the Society for Cardiovascular Angiography and Interventions (SCAI) definition. METHODS: Studies reporting adjusted effect estimates were systematically searched. The primary outcome was all-cause death, while cardiac death was included as a secondary outcome. Studies defining PMI according to biomarker elevation without further evidence of myocardial ischaemia ('ancillary criteria') were included and reported as 'definition-like'. Data were pooled in a random-effect model. RESULTS: A total of 19 studies and 109 568 patients were included. The incidence of PMI was progressively lower across the UDMI, ARC-2, and SCAI definitions. All PMI definitions were independently associated with all-cause mortality [UDMI: hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.32-1.97; I2 34%; ARC-2: HR 2.07, 95% CI 1.40-3.08, I2 0%; SCAI: HR 3.24, 95% CI 2.36-4.44, I2 78%]. Including ancillary criteria in the PMI definitions were associated with an increased prognostic performance in the UDMI but not in the SCAI definition. Data were consistent after evaluation of major sources of heterogeneity. CONCLUSIONS: All currently available international definitions of PMI are associated with an increased risk of all-cause death after percutaneous coronary intervention. The magnitude of this latter association varies according to the sensitivity and prognostic relevance of each definition.

Combining conventional and smartphone technologies to evaluate the psychomotor status in chronic malnutrition: A cross-sectional pilot study in sub-Saharan Africa.

Malnutrition remains a pressing health concern in developing nations, contributing to growth delay (stunting) and psychomotor impairments among the youth. Tanzania has the highest prevalence of stunting, yet the psychomotor status of its population has not been previously studied. To address this gap, we gathered anthropometric, nutritional, and psychomotor data from 211 children with the aim of assessing the reliability of digital tools as indicators of psychomotor performance in relation to the nutritional status. Collected anthropometric measures included middle-upper arm circumference (MUAC), triceps skinfold thickness (TST), and handgrip strength, while psychomotor variables were assessed using digital finger tapping test (DFTT), eye-tracking test (ETT), and nine-hole peg test (9HPT). Statistical analysis revealed significant associations between age and both MUAC and handgrip strength (R = 0.5, p < 0.001). Moreover, DFTT and 9HPT demonstrated a correlation with each other (p = 0.026) and with MUAC, handgrip strength, and age (p < 0.001). Notably, lower stature was independently linked to slower horizontal eye movements (p < 0.001). Findings underscores the crucial link between nutrition and psychomotor skills in Tanzanian children. Digital tests like DFTT, ETT, and the 9HPT show promise for assessing psychomotor performance. Addressing malnutrition requires comprehensive interventions. Future research should explore long-term effects of interventions in resource-limited settings.

Coronary Chronic Total Occlusion Revascularization: When, Who and How?

Coronary chronic total occlusions (CTO) are an increasingly frequent entity in clinical practice and represent a challenging percutaneous coronary intervention (PCI) scenario. Despite data from randomized trials that have not yet demonstrated a clear benefit of CTO recanalization, the widespread of CTO-PCI has substantially increased. The improvement in operators' techniques, equipment, and training programs has led to an improvement in the success rate and safety of these procedures, which will represent an important field of future development of PCI. The present review will summarize clinical outcomes and technical and safety issues of CTO revascularization with the aim to guide clinical daily cath-lab practice.

Eosinophilic Myocarditis: From Bench to Bedside.

Myocarditis is a polymorphic and potentially life-threatening disease characterized by a large variability in clinical presentation and prognosis. Within the broad spectrum of etiology, eosinophilic myocarditis represents a rare condition characterized by eosinophilic infiltration of the myocardium, usually associated with peripheral eosinophilia. Albeit uncommon, eosinophilic myocarditis could be potentially life-threatening, ranging from mild asymptomatic disease to multifocal widespread infiltrates associated with myocardial necrosis, thrombotic complications, and endomyocardial fibrosis. Moreover, it could progress to dilated cardiomyopathy, resulting in a poor prognosis. The leading causes of eosinophilic myocarditis are hypersensitivity reactions, eosinophilic granulomatosis with polyangiitis, cancer, hyper-eosinophilic syndrome variants, and infections. A thorough evaluation and accurate diagnosis are crucial to identifying the underlying cause and defining the appropriate therapeutic strategy. On these bases, this comprehensive review aims to summarize the current knowledge on eosinophilic myocarditis, providing a schematic and practical approach to diagnosing, evaluating, and treating eosinophilic myocarditis.

Takotsubo Syndrome and Coronary Artery Disease: Which Came First-The Chicken or the Egg?

Takotsubo syndrome (TTS) is a clinical condition characterized by temporary regional wall motion anomalies and dysfunction that extend beyond a single epicardial vascular distribution. Various pathophysiological mechanisms, including inflammation, microvascular dysfunction, direct catecholamine toxicity, metabolic changes, sympathetic overdrive-mediated multi-vessel epicardial spasms, and transitory ischemia may cause the observed reversible myocardial stunning. Despite the fact that TTS usually has an acute coronary syndrome-like pattern of presentation, the absence of culprit atherosclerotic coronary artery disease is often reported at coronary angiography. However, the idea that coronary artery disease (CAD) and TTS conditions are mutually exclusive has been cast into doubt by numerous recent studies suggesting that CAD may coexist in many TTS patients, with significant clinical and prognostic repercussions. Whether the relationship between CAD and TTS is a mere coincidence or a bidirectional cause-and-effect is still up for debate, and misdiagnosis of the two disorders could lead to improper patient treatment with unfavourable outcomes. Therefore, this review seeks to provide a profound understanding of the relationship between CAD and TTS by analyzing potential common underlying pathways, addressing challenges in differential diagnosis, and discussing medical and procedural techniques to treat these conditions appropriately.

Leptin as predictor of cardiovascular events and high platelet reactivity in patients undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: Leptin is a hormone involved in the regulation of food intake. Previous studies suggested an interplay between leptin, platelet aggregation, and cardiovascular outcome but this issue was not investigated in vivo in patients treated with percutaneous coronary intervention (PCI). We designed a study to evaluate the possible relation between leptin, cardiovascular outcome, and platelet reactivity (PR) in patients undergoing PCI. METHODS: 155 PCI patients had preprocedural measurements of PR and leptin plasma levels. The latter were assessed by ELISA. Hyperleptinemia was defined as leptin levels ≥14 ng/ml. PR was evaluated by the VerifyNowP2Y12 assay and expressed as P2Y12 reaction units (PRU). Patients were divided into three groups based on PR values and defined as low (LPR), normal (NPR), and high (HPR). Patients were followed for up 8 years. The primary endpoint was the incidence of Major Acute Cardiac Events (MACE) at long-term follow-up according to leptin groups. Secondary endpoints were the evaluation of leptin levels according to PR groups and the incidence of periprocedural myocardial infarction (PMI) according to leptin groups. RESULTS: Long-term follow-up was completed in 140 patients. Patients with hyperleptinemia experienced a higher MACE rate than the normoleptinemic group (HR 2.3; CI 95% 1.14-4.6, P = 0.02). These results remained unchanged after adjusting for Body Mass Index, hypertension, and gender. Leptin levels were significantly different among groups of PR (P = 0.047). Leptin levels were higher in the HPR group (12.61 ± 16.58 ng/ml) compared to the LPR group (7.83 ± 8.87 ng/ml, P = 0.044) and NPR group (7.04 ± 7.03 ng/ml, P = 0.01). The rate of PMI was higher in hyperleptinemia patients (15.1% vs. 6.5%, P = 0.22). CONCLUSIONS: This study suggests that high leptin levels are associated with a worse clinical outcome in patients undergoing PCI and with HPR. Further studies are needed to define better the pathophysiological pathways underlying this association.

Incretins-Based Therapies and Their Cardiovascular Effects: New Game-Changers for the Management of Patients with Diabetes and Cardiovascular Disease.

Atherosclerosis is the leading cause of death worldwide, especially in patients with type 2 diabetes mellitus (T2D). GLP-1 receptor agonists and DPP-4 inhibitors were demonstrated to play a markedly protective role for the cardiovascular system beyond their glycemic control. Several cardiovascular outcome trials (CVOT) reported the association between using these agents and a significant reduction in cardiovascular events in patients with T2D and a high cardiovascular risk profile. Moreover, recent evidence highlights a favorable benefit/risk profile in myocardial infarction and percutaneous coronary revascularization settings. These clinical effects result from their actions on multiple molecular mechanisms involving the immune system, platelets, and endothelial and vascular smooth muscle cells. This comprehensive review specifically concentrates on these cellular and molecular processes mediating the cardiovascular effects of incretins-like molecules, aiming to improve clinicians' knowledge and stimulate a more extensive use of these drugs in clinical practice as helpful cardiovascular preventive strategies.

Effects of Finerenone on Cardiovascular and Chronic Kidney Diseases: A New Weapon against Cardiorenal Morbidity and Mortality-A Comprehensive Review.

Patients with cardiovascular disease (CVD) and chronic kidney disease (CKD) show high rates of cardiorenal outcomes. In addition, the progression towards renal failure and cardiovascular events rises as CKD worsens. Several studies suggest that the activation of the mineralocorticoid receptor (MR) induces cardiac and renal injury, including inflammation and fibrosis. Finerenone is a novel, nonsteroidal, selective MR antagonist (MRA) which has demonstrated anti-inflammatory and anti-fibrotic effects in pre-clinical studies. Moreover, two large trials (FIDELIO-DKD and FIGARO-DKD) investigated the renal and cardiovascular outcomes in patients with mild to severe CKD in type 2 diabetes which received finerenone. On these bases, this comprehensive review aims to summarize the current knowledge regarding finerenone and its effects on CKD and the cardiovascular system, emphasizing its role in modifying cardiorenal outcomes.

Novel Antidiabetic Agents and Their Effects on Lipid Profile: A Single Shot for Several Cardiovascular Targets.

Type-2 diabetes mellitus (DM) represents one of the most important risk factors for cardiovascular diseases (CVD). Hyperglycemia and glycemic variability are not the only determinant of the increased cardiovascular (CV) risk in diabetic patients, as a frequent metabolic disorder associated with DM is dyslipidemia, characterized by hypertriglyceridemia, decreased high-density lipoprotein (HDL) cholesterol levels and a shift towards small dense low-density lipoprotein (LDL) cholesterol. This pathological alteration, also called diabetic dyslipidemia, represents a relevant factor which could promotes atherosclerosis and subsequently an increased CV morbidity and mortality. Recently, the introduction of novel antidiabetic agents, such as sodium glucose transporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP4i) and glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1 RAs), has been associated with a significant improvement in CV outcomes. Beyond their known action on glycemia, their positive effects on the CV system also seems to be related to an ameliorated lipidic profile. In this context, this narrative review summarizes the current knowledge regarding these novel anti-diabetic drugs and their effects on diabetic dyslipidemia, which could explain the provided global benefit to the cardiovascular system.

Arrhythmias after COVID-19 Vaccination: Have We Left All Stones Unturned?

SARS-CoV-2 vaccination offered the opportunity to emerge from the pandemic and, thereby, worldwide health, social, and economic disasters. However, in addition to efficacy, safety is an important issue for any vaccine. The mRNA-based vaccine platform is considered to be safe, but side effects are being reported more frequently as more and more people around the world become treated. Myopericarditis is the major, but not the only cardiovascular complication of this vaccine; hence it is important not to underestimate other side effects. We report a case series of patients affected by cardiac arrhythmias post-mRNA vaccine from our clinical practice and the literature. Reviewing the official vigilance database, we found that heart rhythm disorders after COVID vaccination are not uncommon and deserve more clinical and scientific attention. Since the COVID vaccine is the only vaccination related to this side effect, questions arose about whether these vaccines could affect heart conduction. Although the risk-benefit ratio is clearly in favor of vaccination, heart rhythm disorders are not a negligible issue, and there are red flags in the literature about the risk of post-vaccination malignant arrhythmias in some predisposed patients. In light of these findings, we reviewed the potential molecular pathways for the COVID vaccine to impact cardiac electrophysiology and cause heart rhythm disorders.

Functional Mitral and Tricuspid Regurgitation across the Whole Spectrum of Left Ventricular Ejection Fraction: Recognizing the Elephant in the Room of Heart Failure.

Functional mitral regurgitation (FMR) and tricuspid regurgitation (FTR) occur due to cardiac remodeling in the presence of structurally normal valve apparatus. Two main mechanisms are involved, distinguishing an atrial functional form (when annulus dilatation is predominant) and a ventricular form (when ventricular remodeling and dysfunction predominate). Both affect the prognosis of patients with heart failure (HF) across the entire spectrum of left ventricle ejection fraction (LVEF), including preserved (HFpEF), mildly reduced (HFmrEF), or reduced (HFrEF). Currently, data on the management of functional valve regurgitation in the various HF phenotypes are limited. This review summarizes the epidemiology, pathophysiology, and treatment of FMR and FTR within the different patterns of HF, as defined by LVEF.