Panagiotis Iliakis

Percutaneous coronary intervention (PCI) effectively treats flow-limiting coronary lesions but does not eliminate the systemic processes that drive atherosclerotic progression and recurrent events. Residual inflammatory risk (RIR), most commonly identified by persistent elevation of high-sensitivity C-reactive protein (hsCRP), has emerged as an important component of this remaining risk and frequently persists despite intensive lipid lowering. Its interpretation after PCI, however, requires attention to timing, since inflammation related to acute myocardial injury and procedural vascular damage must be distinguished from persistent inflammatory activity after clinical stabilisation. In this review, we examine the biological basis of RIR and its relationship with plaque vulnerability, vascular healing, and recurrent events after coronary intervention. We discuss the role of hsCRP and other circulating biomarkers in post-PCI phenotyping, together with cardiometabolic conditions—including obesity, diabetes, chronic kidney disease, atherogenic dyslipidaemia, and hyperuricaemia—that may sustain inflammatory activation despite successful revascularisation. We also critically appraise the therapeutic evidence. Although CANTOS established inflammation as a modifiable component of atherothrombotic risk and colchicine has shown benefit in selected coronary populations, neutral findings with hyperacute colchicine initiation and, more recently, IL-6 inhibition emphasise that biomarker reduction does not necessarily translate into fewer cardiovascular events. Current guidelines recognise anti-inflammatory therapy in selected settings but do not recommend hsCRP-guided treatment after PCI. RIR therefore represents a clinically relevant post-PCI risk phenotype, but its transition from prognostic marker to actionable treatment target will require better definition of timing, inflammatory pathways, and the patients most likely to benefit from intervention.

Coronary microvascular dysfunction (CMD) is a major mechanism of myocardial ischemia and adverse cardiovascular outcomes in patients with angina or dyspnea, both in the absence and in the presence of obstructive coronary artery disease. Because the coronary microcirculation cannot be visualized directly with routine angiography, diagnosis depends on physiological assessment. Non-invasive imaging has moved beyond relative perfusion analysis toward quantification of resting and hyperemic myocardial blood flow and flow reserve. Positron emission tomography (PET) remains the most extensively validated non-invasive method and provides robust absolute flow measurements with strong prognostic evidence. Quantitative stress cardiovascular magnetic resonance (CMR) is rapidly maturing, combining high-resolution perfusion mapping with ventricular and tissue characterization without ionizing radiation. Transthoracic Doppler echocardiography offers an accessible, radiation-free estimate of coronary flow velocity reserve, whereas myocardial contrast echocardiography can assess myocardial blood volume and replenishment kinetics. Dynamic cadmium-zinc-telluride single-photon emission computed tomography and stress computed tomography perfusion extend flow quantification to more widely available platforms, although standardization and outcome validation remain less developed. Across modalities, interpretation requires attention to the adequacy of vasodilator stress, resting hemodynamics, diffuse epicardial atherosclerosis, scar, and technical factors. A reduced flow reserve is not synonymous with isolated microvascular disease and cannot identify acetylcholine-provoked vasospasm. This review provides a clinically oriented framework for selecting, performing, interpreting, and reporting non-invasive CMD testing; examines the evidence, strengths, and limitations of each modality; and defines situations in which invasive coronary function testing remains necessary. Future progress will depend on cross-platform standardization, automated quality control, disease- and sex-specific reference ranges, and prospective trials linking imaging-defined endotypes to effective treatment strategies.

Background/Objectives: Diet quality is a potentially modifiable determinant of heart failure (HF), yet evidence regarding its long-term association with HF incidence remains limited. This study examined the association between baseline diet quality and 20-year incident HF in the population-based ATTICA cohort. Methods: Among 3042 adults free of cardiovascular disease at baseline (2001–2002), HF status was available for 2159 participants in 2022, of whom 241 (11.2%) developed HF. Diet quality, including the relative contributions of healthy and unhealthy food groups, was assessed using the Global Diet Quality Score (GDQS), derived from a validated food-frequency questionnaire. Logistic regression models were sequentially adjusted for age, sex, body mass index, education, physical activity, smoking burden, hypertension, diabetes, and hypercholesterolemia. Results: HF incidence was 20.7%, 5.1%, and 6.6% among participants with low, intermediate, and high diet quality, respectively (p < 0.001). In the fully adjusted analysis (n = 1973), better overall diet quality was associated with lower odds of HF (odds ratio [OR] per 1-point increment, 0.97; 95% confidence interval [CI], 0.94–0.99). A greater contribution of healthy foods was also inversely associated with HF (OR, 0.96; 95% CI, 0.93–0.98), whereas the unhealthy-food component was not independently associated with the outcome (OR, 1.04; 95% CI, 0.96–1.13). Conclusions: Better diet quality, particularly greater consumption of health-promoting foods, was independently associated with lower 20-year HF incidence in a Mediterranean population.

Heart failure with preserved ejection fraction (HFpEF) represents a heterogeneous clinical syndrome characterized by complex pathophysiological mechanisms and substantial diagnostic and prognostic challenges. Recently, circulating biomarkers have emerged as potential tools for improving risk stratification and disease characterization in this population. Among these biomarkers, soluble suppression of tumorigenicity-2 (sST2) and galectin-3 (Gal-3) have gained particular attention due to their association with myocardial fibrosis, inflammation, and adverse cardiac remodeling. This scoping review aimed to evaluate the current evidence on the diagnostic and prognostic roles of sST2 and Gal-3 in patients with HFpEF. A literature search was conducted in PubMed and ScienceDirect to identify studies investigating the clinical significance of these biomarkers in HFpEF. Titles and abstracts were screened, and eligible studies were assessed through full-text review according to predefined inclusion criteria. Ultimately, 11 studies were included in the qualitative synthesis. Evidence from the available literature suggests that both sST2 and Gal-3 are associated with markers of myocardial fibrosis, inflammation, and disease severity in HFpEF. Elevated circulating levels of these biomarkers have been linked to poorer clinical outcomes, including an increased risk of hospitalization and mortality. However, variability across studies in study populations, biomarker thresholds, and methodological approaches limits the direct translation of these findings into routine clinical practice. Overall, sST2 and Gal-3 appear to hold promise as complementary biomarkers for risk stratification in HFpEF. Nonetheless, further large-scale prospective studies are needed to clarify the clinical utility of these biomarkers and determine the subsequent integration into multimarker strategies for the management of patients with HFpEF.

Atrial fibrillation (AF) is traditionally classified using categorical clinical patterns and binary recurrence endpoints. However, these measures do not fully reflect arrhythmia frequency, duration, temporal distribution, or progression. AF burden, defined as the proportion of monitored time spent in AF, provides a more granular measure of disease activity and therapeutic response. Recent advances in cardiac implantable electronic devices, insertable cardiac monitors, wearable technologies, and digital platforms have significantly improved burden assessment, although considerable heterogeneity remains in monitoring methods, definitions, and clinically relevant thresholds. This review examines contemporary approaches to AF burden measurement and its associations with thromboembolic risk, heart failure, hospitalization, symptoms, quality of life, disease progression, and mortality. We particularly discuss the reduction of AF burden as a potential therapeutic target following antiarrhythmic drug therapy and catheter ablation, and the limitations of conventional recurrence definitions based on episodes lasting more than 30 s. This review also focuses on the implications for rhythm-control selection, post-ablation monitoring, anticoagulation, and clinical-trial design, while proposing priorities for standardized burden-based assessment.

Acute coronary syndrome (ACS) remains a leading cause of cardiovascular morbidity and mortality worldwide. Although traditional cardiovascular risk factors remain central to ACS development, recreational drug use is increasingly recognized as a clinically relevant trigger, particularly in younger patients with fewer conventional risk factors. This narrative review synthesized evidence identified through searches of PubMed/MEDLINE and Scopus up to June 2026, including clinical guidelines, systematic reviews, observational studies, mechanistic investigations, and clinically informative case-based evidence. Cannabis, cocaine, amphetamines, methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA), opioids, lysergic acid diethylamide (LSD), synthetic cannabinoids, and polysubstance use may promote myocardial ischemia and infarction through overlapping mechanisms, including sympathetic activation, coronary vasospasm, endothelial dysfunction, oxidative stress, inflammation, platelet activation, thrombosis, arrhythmogenesis, and myocardial oxygen supply–demand mismatch. Clinical presentation may be typical or atypical and may overlap with intoxication, withdrawal, anxiety, neurological symptoms, or non-cardiac chest pain, making diagnosis challenging. Underreporting of recreational drug use is common, and targeted toxicology screening may improve diagnostic accuracy and risk stratification, particularly in patients younger than 50 years, those with few traditional cardiovascular risk factors, or those presenting with otherwise unexplained ST-segment elevation myocardial infarction (STEMI), non-ST-segment elevation myocardial infarction (NSTEMI), coronary vasospasm, arrhythmias, or cardiac arrest. Acute management should generally follow standard ACS guidelines, while considering drug-specific issues such as stimulant-induced vasospasm, sympathetic excess, cautious use of beta-blockers during acute intoxication, and preference for primary percutaneous coronary intervention when fibrinolysis carries increased risk. Long-term care should combine evidence-based secondary prevention with substance-use counseling, addiction medicine referral, cardiac rehabilitation, and behavioural interventions. This review summarizes the pathophysiology, clinical manifestations, epidemiology, treatment considerations, preventive strategies, and knowledge gaps related to recreational drug-associated ACS.

Chronic kidney disease-associated cardiomyopathy (CKD-CM) is a term that captures the spectrum of myocardial disease that begins early in chronic kidney disease (CKD) and progresses as kidney function declines. Historically described as uremic cardiomyopathy, the condition was associated with severe left ventricular hypertrophy and fibrosis in patients with kidney failure. However, functional abnormalities and myocardial injury have been shown to begin much earlier, with diffuse interstitial fibrosis preceding overt hypertrophy or reduced ejection fraction. Fibrosis drives heart failure with preserved ejection fraction (HFpEF)-like physiology and atrial fibrillation and increases arrhythmic risk. In this review, we describe the multiple interacting mechanisms, including abnormal loading, neurohormonal activation, metabolic and inflammatory stress, mineral bone disorder, and microvascular dysfunction. We summarize imaging findings across CKD stages and describe established and emerging therapeutic strategies. A better understanding of CKD-CM pathogenesis is likely to enable early intervention and prevention, with successful outcomes measured by reduced progression to severe cardiomyopathy and lower cardiovascular mortality in CKD.

Assessment of left atrial remodeling in atrial fibrillation (AF) has traditionally relied on anteroposterior diameter, left atrial volume (LAV), and indexed left atrial volume (LAVI). Although these measures remain clinically useful, they reduce a complex, asymmetric, and anatomically constrained chamber to scalar descriptors and therefore cannot fully capture the spatial substrate that underlies AF persistence, thromboembolic risk, or arrhythmia recurrence after catheter ablation. Three-dimensional left atrial reconstruction provides a more refined framework by preserving chamber shape, regional deformation, pulmonary vein (PV) orientation, left atrial appendage (LAA) geometry, posterior wall and roof configuration, left lateral ridge anatomy, wall-thickness heterogeneity, and computational surface features. In this review, we examine how three-dimensional left atrial geometry can extend conventional remodeling assessment from measurement of atrial size toward imaging-based substrate characterization. We discuss the relative strengths and limitations of computed tomography (CT), cardiovascular magnetic resonance (CMR), three-dimensional echocardiography, and electroanatomic mapping (EAM), and summarize key geometry-derived metrics, including LAV, LAVI, left atrial sphericity, asymmetry index, atrial eccentricity index, PV anatomy, LAA morphology, posterior wall geometry, wall thickness, radiomics, and artificial intelligence (AI)-derived shape descriptors. We further synthesize evidence linking geometric remodeling with atrial cardiomyopathy, mechanical dysfunction, fibrosis, low-voltage substrate, and catheter ablation outcomes. The clinical relevance of three-dimensional left atrial geometry may be further redefined by pulsed field ablation (PFA), whose non-thermal lesion biology and tissue selectivity may modify predictors of recurrence established in radiofrequency and cryoballoon cohorts. Finally, we outline the need for standardized segmentation, harmonized metric definitions, prospective multicenter validation, and integration with AI, digital twin modeling, biomarkers, EAM data, and wearable-derived AF burden. Three-dimensional left atrial geometry is not yet a standalone determinant of ablation strategy, but it may become a central component of individualized atrial phenotyping and rhythm-control decision-making.

Pulmonary arterial hypertension (PAH) is a progressive and life-threatening condition characterized by elevated pulmonary vascular resistance eventually causing right ventricular failure and premature death. Despite advances in targeted therapies, morbidity and mortality levels remain high, highlighting the need for additional treatment strategies that address the disease’s multifactorial pathophysiology. Attention has recently centred on two pharmacological groups with proven roles in other cardiovascular settings: sodium–glucose cotransporter 2 inhibitors (SGLT2i) and mineralocorticoid receptor antagonists (MRAs). SGLT2 inhibitors have demonstrated robust clinical benefits in heart failure (HF), type 2 diabetes mellitus (T2DM), and chronic kidney disease (CKD), extending survival and reducing hospitalizations. Although their primary actions involve renal glucose and sodium handling, accumulating evidence suggests they may also exert favourable effects on the pulmonary vasculature, endothelial function, and right ventricular performance. In parallel, elevated aldosterone levels have been implicated in vascular remodelling, inflammation, and fibrosis in PAH, suggesting a potential therapeutic role for MRAs. However, the strength and clinical significance of these associations remain under investigation. The aim of this review is to synthesize and critically appraise the current evidence regarding the potential role of SGLT2 inhibitors and MRAs in the treatment of pulmonary arterial hypertension, exploring their mechanistic rationale, preclinical findings, and available clinical data to determine whether these agents may offer additional therapeutic benefit in PAH management.