Ioannis Paraskevaidis

Background/Objectives: Atrial fibrillation (AF) after intracerebral hemorrhage (ICH) creates a therapeutic conflict: withholding oral anticoagulation may increase ischemic stroke risk, whereas resumption of anticoagulation may increase recurrent ICH. Left atrial appendage occlusion (LAAO) offers a nonpharmacologic alternative, but isolated stroke or bleeding rates do not describe the overall benefit–harm balance. This focused review examines net clinical benefit (NCB) as a decision framework for LAAO after ICH and presents a secondary benchmark-adjusted analysis derived from our prior systemaatic review and meta-analysis. Methods: Thirteen endocardial LAAO cohorts with complete data for ischemic stroke, recurrent ICH, major bleeding, and all-cause death contributed to the analysis. The component event data and prespecified severity weights were carried forward from the prior meta-analysis; the external benchmark comparison, study-level benchmark-adjusted NCB synthesis, and benchmark-sensitivity analyses were not part of that report and constitute the distinct secondary analysis presented here. Results: Prespecified external benchmark rates were 8.0, 2.0, 3.0, and 6.0 events per 100 patient-years, respectively. Unweighted and severity-weighted NCB were evaluated using both pooled-rate and study-level Hartung–Knapp random-effects approaches. Study-level pooled NCB was 12.20 events per 100 patient-years (95% CI, 8.61–15.79; I² = 96%), and weighted NCB was 14.39 (95% CI, 8.84–19.94; I² = 94%). Additional two-component analyses using PRESTIGE-AF reference rates yielded unweighted NCB estimates of 5.65 and 2.06 events per 100 patient-years for no-OAC and DOAC comparator scenarios, respectively. Excluding all-cause mortality from the original model yielded an unweighted NCB of 8.41. These exploratory results highlight the sensitivity of NCB estimates to comparator selection and endpoint composition. Conclusions: Contemporary randomized evidence, including PRESTIGE-AF, CLOSURE-AF, and CHAMPION-AF, reinforces that benefit–harm balance is population-, comparator-, endpoint-, and time-horizon-dependent. Accordingly, these NCB estimates should be interpreted as decision-analytic and hypothesis-generating rather than causal treatment effects. ICH-specific randomized comparisons remain essential.

Diuretics remain indispensable for the treatment of congestion in cardiovascular disease, particularly in acute and chronic heart failure. Their principal clinical value is rapid symptom relief, reduction in filling pressures and facilitation of decongestion; however, a mortality benefit has not been consistently demonstrated. This distinction is clinically important because long-term diuretic exposure in patients without objective congestion may promote hypotension, renal dysfunction, electrolyte instability, neurohormonal activation, falls, cognitive impairment and avoidable polypharmacy. The challenge is therefore not whether diuretics should be used, but how intensively, for how long and under which monitoring strategy. In this narrative review, we summarize the pharmacology of major diuretic classes, the mechanisms of diuretic resistance, and the clinical consequences of potassium, sodium and magnesium disorders. We also discuss drug interactions, frailty, chronic kidney disease, pregnancy, heart failure with preserved ejection fraction and the emerging role of sodium–glucose cotransporter 2 inhibitors and adjunctive proximal-tubule strategies. A practical approach is proposed: use loop diuretics promptly when congestion is present, reassess response with symptoms, weight, urine output, renal function, electrolytes and congestion markers, and reduce or discontinue therapy once euvolemia is achieved and maintained. Deprescribing should be individualized, gradual and reversible, with explicit thresholds for restarting treatment. Optimized diuretic care requires the same discipline applied to disease-modifying heart failure therapy: phenotype recognition, dose minimization, close follow-up and avoidance of treatment inertia.

The cardiac extracellular matrix (ECM) is a dynamic, tissue-specific scaffold essential for cardiovascular development, homeostasis, and disease. Once considered a passive structural framework, the ECM is now recognized as an active regulator of mechanical, electrical, and biochemical signaling in the heart. Its composition evolves from embryogenesis through adulthood, coordinating cardiomyocyte maturation, chamber formation, and postnatal remodeling. In pathological states, diverse stimuli—including ischemia, pressure or volume overload, metabolic dysfunction, and aging—disrupt ECM homeostasis, triggering fibroblast activation, myofibroblast transformation, and maladaptive collagen deposition. These processes underpin myocardial fibrosis, a key driver of impaired contractility, diastolic dysfunction, arrhythmogenesis, and heart failure across ischemic and non-ischemic cardiac diseases. ECM alterations also exhibit age- and sex-specific patterns that influence susceptibility to cardiovascular pathology. Advances in imaging and circulating biomarkers have improved fibrosis assessment, though limitations persist. Therapeutic strategies targeting ECM remodeling, including modulation of profibrotic signaling pathways, non-coding RNAs, cellular therapies, and nano-delivery systems, show promise but remain largely experimental. Collectively, expanding knowledge of ECM biology highlights its central role in cardiovascular physiology and pathology and underscores the need for targeted diagnostic and therapeutic innovations.

Background/Objectives: Extra virgin olive oil (EVOO) exhibits potent antioxidant and anti-inflammatory properties. Recent findings from our Institute indicate that its bioactive compounds enhance lipid metabolism, suggesting EVOO as a promising nutritional intervention for hyperlipidemic patients. This clinical study aimed to evaluate the effects of EVOO consumption on vascular endothelial function and hemodynamic parameters in hyperlipidemic individuals, while comparing two EVOO types differing in polyphenol content and dosage. Methods: This post hoc analysis included 70 participants: 50 patients with hyperlipidemia and 20 healthy controls. All participants consumed EVOO daily for four weeks. Hyperlipidemic patients were randomized into two subgroups: one receiving high-phenolic EVOO at a low dose and another receiving low-phenolic EVOO at a high dose, ensuring equivalent total polyphenol intake. Vascular endothelial function, assessed via near-infrared spectroscopy (NIRS), served as the primary endpoint, while arterial blood pressure and heart rate were secondary endpoints. Statistical analyses employed mixed linear models. Results: Hyperlipidemic patients exhibited significant improvements in endothelial function, with increased reperfusion rate (p = 0.010) and oxygen consumption rate (p < 0.001) compared to controls. Reductions in maximum hyperemia time (p = 0.004) and hyperemia recovery time (p < 0.05) further indicated enhanced vascular function. Diastolic blood pressure (p = 0.007) and heart rate (p = 0.004) decreased significantly. Among subgroups, high-phenolic EVOO at lower doses was more effective in reducing systolic blood pressure (p = 0.049) and improving reperfusion rate (p = 0.049). Conclusions: EVOO consumption improved endothelial function and hemodynamic parameters in hyperlipidemic patients, with high-phenolic EVOO demonstrating superior vascular benefits at lower doses.

Heart failure (HF) remains a major clinical syndrome traditionally classified by left ventricular ejection fraction (EF) into three phenotypes: reduced (HFrEF), mildly reduced (HFmrEF), and preserved (HFpEF). Although EF-based phenotyping has served as a practical framework for diagnosis and treatment stratification, growing evidence challenges its pathophysiological specificity. Clinical trials often blur these categories by including patients with EF > 40% under the HFpEF umbrella, despite current guidelines reserving that range for HFmrEF. This inconsistency introduces ambiguity and undermines the concept of discrete disease entities. In this comprehensive review, we explore the hypothesis that HF is not a group of separate syndromes but rather a single entity manifesting along a spectrum determined by the balance between pathological insult and the patient’s homeostatic adaptive capacity. Emerging data reveal that all HF phenotypes, regardless of EF, share common molecular, cellular, and systemic mechanisms, including neurohormonal activation, inflammation, mitochondrial dysfunction, fibrosis, and programmed cell death. We propose a paradigm shift: from viewing HF through the lens of EF stratification to a unified, mechanistically driven model that recognizes HF as a syndrome with variable manifestations. Reframing HF in this way could enhance diagnostic precision, therapeutic targeting, and research design.

Background/Objectives: Hyperlipidemia is a major risk factor for cardiovascular disease and atherosclerosis. Polyphenols found in polyphenol-rich extra virgin olive oil (EVOO) have been shown to possess strong antioxidant, anti-inflammatory, and cardioprotective properties. The present study aimed to assess the effects of two types of EVOO with different polyphenol content and dosages on the lipid profile of hyperlipidemic patients. Methods: In this single-blind, randomized clinical trial, 50 hyperlipidemic patients were randomized to receive either a higher-dose, lower-phenolic EVOO (414 mg/kg phenols, 20 g/day) or a lower-dose, higher-phenolic EVOO (1021 mg/kg phenols, 8 g/day), for a period of 4 weeks. These doses were selected to ensure equivalent daily polyphenol intake in both groups (~8.3 mg of total phenols/day), based on chemical analysis performed using NMR spectroscopy. The volumes used (8–20 g/day) reflect typical daily EVOO intake and were well tolerated by participants. A group of 20 healthy individuals, separated into two groups, also received the two types of EVOO, respectively, for the same duration. Primary endpoints included blood levels of total blood cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides, lipoprotein-a (Lpa), and apolipoproteins A1 and B. Measurements were performed at baseline and at the end of the 4-week intervention. Linear mixed models were performed for the data analysis. Results: The higher-phenolic, lower-dose EVOO group showed a more favorable change in total blood cholesterol (p = 0.045) compared to the lower-phenolic, higher-dose group. EVOO intake was associated with a significant increase in HDL (p < 0.001) and reduction in Lp(a) (p = 0.040) among hyperlipidemic patients in comparison to healthy individuals. Conclusions: EVOO consumption significantly improved the lipid profile of hyperlipidemic patients. Higher-phenolic EVOO at lower dosages appears to be more effective in improving the lipid profile than lower-phenolic EVOO in higher dosages.

In humans, heart failure (HF) and cancer are among the leading causes of morbidity and mortality. A growing body of evidence highlights a bidirectional relationship between these conditions, underpinned by shared risk factors and overlapping pathophysiological pathways. This review aims to explore the emerging role of the intestinal microbiome as a common mechanistic link between HF and cancer. Specifically, we examine how microbial dysbiosis and its metabolic products—such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), bile acids, lipopolysaccharides (LPS), and branched-chain amino acids (BCAAs)—contribute to inflammation, immune dysregulation, oxidative stress, and metabolic dysfunction. These mechanisms promote multiorgan impairment and establish a vicious cycle that fuels both tumorigenesis and cardiac deterioration. HF, cancer, and the gut microbiome are not isolated entities but are deeply interconnected through shared biological mechanisms—including chronic inflammation, microbial dysbiosis, immune and neurohumoral modulation, and metabolic derangement. These findings support the concept of a microbiome-centered axis involving the gut, heart, and tumors, which may underlie many chronic disease processes. Understanding these interactions may provide novel insights into disease pathogenesis and uncover promising therapeutic targets that leverage microbiome modulation to prevent or treat HF, cancer, and other systemic diseases.

Advanced heart failure (AHF) represents the terminal stage of heart failure (HF), characterized by persistent symptoms and functional limitations despite optimal guideline-directed medical therapy (GDMT). This review explores the clinical definition, pathophysiology, and therapeutic approaches for AHF. Characterized by severe symptoms, New York Heart Association (NYHA) class III-IV, significant cardiac dysfunction, and frequent hospitalizations, AHF presents substantial challenges in prognosis and management. Pathophysiological mechanisms include neurohormonal activation, ventricular remodeling, and systemic inflammation, leading to reduced cardiac output and organ dysfunction. Therapeutic strategies for AHF involve a multidisciplinary approach, including pharmacological treatments, device-based interventions like ventricular assisted devices, and advanced options such as heart transplantation. Despite progress, AHF management faces limitations, including disparities in access to care and the need for personalized approaches. Novel therapies, artificial intelligence, and remote monitoring technologies offer future opportunities to improve outcomes. Palliative care, which focuses on symptom relief and quality of life, remains crucial for patients ineligible for invasive interventions. Early identification and timely intervention are pivotal for enhancing survival and functional outcomes in this vulnerable population. This review underscores the necessity of integrating innovative technologies, personalized medicine, and robust palliative strategies into AHF management to address its high morbidity and mortality.

Acute and chronic coronary artery disease (CAD) are interconnected, representing two facets of the same condition. Chronic CAD exhibits a dynamic nature, manifesting as stable or acute ischemia, or both. Myocardial ischemia can be transient and reversible. The genesis of CAD involves diverse anatomical and functional mechanisms, including endothelial dysfunction, arteriolar remodeling, capillary rarefaction, and perivascular fibrosis, though no single factor explains its heterogeneity. Chronic CAD is often stable but may present as symptomatic or asymptomatic (e.g., in diabetes) and affect various coronary compartments (epicardial or microcirculation). This complexity necessitates a reappraisal of our approach, as pathophysiological mechanisms vary and often overlap. A comprehensive exploration of these mechanisms using advanced diagnostic techniques can aid in identifying the dynamic processes underlying CAD. The disease may present as obstructive or non-obstructive, stable or unstable, underscoring its diversity. The primary source of CAD lies in the arterial wall, emphasizing the need for research on its components, such as the endothelium and vascular smooth muscle cells, and factors disrupting arterial homeostasis. Shifting focus from arterial luminal status to the arterial wall can provide insights into the genesis of atheromatous plaques, enabling earlier interventions to prevent their development and progression.