Search Results (145)

Imaging techniques such as positron emission tomography/computed tomography (PET/CT) and positron emission tomography/magnetic resonance imaging (PET/MR) have emerged as powerful and versatile tools for the comprehensive assessment of coronary artery disease (CAD). By combining anatomical and functional information in a single examination, these modalities offer complementary insights that significantly enhance diagnostic accuracy and support clinical decision-making. This is particularly relevant in complex clinical scenarios, such as multivessel disease, balanced ischemia, or suspected microvascular dysfunction, where conventional imaging may be inconclusive. This review aims to provide clinicians with an up-to-date summary of the principles, technical considerations, and clinical applications of hybrid PET/CT and PET/MR in CAD. Here, we describe how these techniques can improve the evaluation of myocardial perfusion, coronary plaque characteristics, and ischemic burden. Advantages such as improved sensitivity, spatial resolution, and quantification capabilities are discussed alongside limitations including cost, radiation exposure, availability, and workflow challenges. A dedicated focus is given to the emerging role of artificial intelligence (AI), which is increasingly being integrated to optimize image acquisition, fusion processes, and interpretation. AI has the potential to streamline hybrid imaging and promote a more personalized and efficient management of CAD. Finally, we outline future directions in the field, including novel radiotracers, automated quantitative tools, and the expanding use of hybrid imaging to guide patient selection and therapeutic decisions, particularly in revascularization strategies. Full article

Coronary microvascular dysfunction (CMD) is increasingly being recognized as a significant contributor of ischemic heart disease, particularly affecting women with angina and non-obstructive coronary arteries. This contemporary review synthesizes recent landmark evidence (2022–2024) revealing a striking paradox in CMD management. While diagnostic capabilities have advanced dramatically—with CMD now identified in 41% of patients with non-obstructive coronary disease—this diagnostic success has not translated into therapeutic benefits. Recent meta-analyses demonstrate that CMD doubles cardiovascular risk (HR 2.08–2.45), yet the first randomized trial of invasive endotyping (CorCTA) found that improved diagnosis failed to improve symptoms despite a 4-fold enhancement in diagnostic accuracy. This diagnosis–treatment gap represents one of the most pressing challenges in contemporary cardiovascular medicine, reflecting fundamental failures that demand urgent reconceptualization. We examine current evidence on its prevalence, diagnostic approaches, and prognostic implications, highlighting the urgent need for CMD-specific therapies to bridge the gap between diagnostic capability and clinical outcomes. Until CMD-specific therapies emerge from dedicated research programs, clinicians must optimize available treatments while advocating for the resources and research focus this condition deserves. Full article

Coronary microvascular dysfunction (CMD) is presently recognized as a condition characterized by a reduction in coronary blood flow. CMD is associated with poor cardiac outcomes, and mounting evidence suggests that coronary microcirculation may be impaired in various cardiology pathologies. Non-invasive assessment of CMD remains challenging, and several imaging modalities—positron emission tomography (PET), computed tomography (CT), cardiac magnetic resonance (CMR), myocardial contrast echocardiography (MCE), and transthoracic Doppler echocardiography (TTE)—are proven to quantify coronary flow reserve (CFR) and myocardial blood flow (MBF), both valuable markers of CMD. However, each modality is limited by availability, standardization, and diagnostic utility. Furthermore, a growing number of studies have attempted to correlate CMD indices with systolic myocardial function markers, such as left ventricular ejection fraction, global longitudinal strain, and myocardial work indices. This review refers to the current evidence on CMD imaging and examines the association between CMD indices and systolic function in cardiovascular diseases. Understanding the impact of CMD on myocardial function is essential, as it highlights the coronary microcirculation impairment pathway as a potential target for therapeutic strategies. Full article

Background: The integration of global longitudinal strain (GLS) with stress echocardiography (SE) represents a significant advancement in non-invasive cardiac diagnostics, particularly in the evaluation of coronary artery disease (CAD). GLS, derived from speckle-tracking echocardiography, quantifies myocardial deformation and offers superior sensitivity for detecting subclinical myocardial dysfunction compared to conventional metrics like wall motion and ejection fraction. Recent studies have validated the prognostic and diagnostic efficacy of GLS both at rest and during stress, notably enhancing the detection of obstructive and non-obstructive CAD, microvascular dysfunction, and other cardiac pathologies. Methods: This manuscript synthesizes extensive clinical data demonstrating the added value of GLS during stress echocardiography across diverse cardiac conditions—including valvular heart disease, heart failure, cardio-oncology, and pediatric cardiology. Novel metrics like longitudinal strain reserve (LSR), myocardial work indices, and post-systolic strain have further enriched risk stratification strategies. Results: The combination of GLS with SE has been shown to approximate the accuracy of invasive coronary angiography in intermediate-risk patients and in cases with equivocal traditional SE findings. Despite its clinical promise, the utility of GLS is challenged by technical limitations, including image quality dependency, inter-vendor variability, and limited applicability during high heart rate states. Conclusions: As technological refinement and standardization progress, GLS integrated with SE is poised to become a mainstay in precision cardiology, improving diagnostic yield, guiding therapeutic decisions, and enhancing patient outcomes. Full article

Heart failure with preserved ejection fraction (HFpEF) represents a growing global public health challenge, now accounting for approximately half of all heart failure cases and often linked to a systemic pathophysiological process in older adults with multiple comorbidities. Despite increasing recognition of the vascular contributions to HFpEF, the precise molecular mechanisms, particularly the role of noncoding Ribonucleic Acids (ncRNAs) in mediating vascular aging and subsequent cardiac dysfunction, remain incompletely understood. This review provides a comprehensive overview of the mechanistic link between vascular aging and HFpEF, with a specific focus on the pivotal roles of ncRNAs in this complex interplay. We delineate the classification of vascular aging, its cellular hallmarks, including endothelial senescence, vascular smooth muscle cell phenotypic switching, and extracellular matrix remodeling, and its systemic implications, such as inflammaging, oxidative stress, and reduced nitric oxide bioavailability. We then detail how these vascular alterations, including increased ventricular afterload and impaired myocardial perfusion due to coronary microvascular dysfunction, contribute to HFpEF pathophysiology. The review extensively discusses recent findings on how diverse classes of ncRNAs, notably microRNAs, long noncoding RNAs, and circular RNAs, along with emerging evidence for PIWI-interacting RNAs, small nuclear RNAs, small nucleolar RNAs, and tRNA-derived small RNAs, regulate these vascular aging processes and serve as molecular bridges connecting vascular dysfunction to heart failure. In conclusion, understanding the regulatory landscape of ncRNAs in vascular aging may reveal novel biomarkers and therapeutic avenues, offering new strategies for precision medicine in HFpEF. Full article

Ischemia with non-obstructive coronary arteries (INOCA) is a chronic coronary condition associated with poor prognosis and reduced quality of life. The increasing use of invasive assessments of microcirculatory function and provocative spasm testing has significantly advanced the understanding of INOCA’s pathophysiology, which ranges from coronary microvascular dysfunction to vasomotor disorders. However, the optimal management and therapeutic approach for INOCA remain to be determined. Significant sex-based differences in the pathophysiology of INOCA have been reported, resulting in variations in prevalence, phenotype, and natural history between male and female patients. The aim of this narrative review is to provide a comprehensive overview of the sex-specific pathophysiological mechanisms underlying INOCA and to summarize the differences in INOCA phenotype and prognosis. Additionally, we will explore the current knowledge on management and therapy, with the goal of advancing towards sex-based personalized treatment strategies for INOCA. Full article

Background/Objectives: Cardiac involvement in systemic sclerosis (SSc) ranges from subclinical to severe. While pulmonary artery hypertension (PAH) is well-documented, the mechanism of left ventricular (LV) ischemia remains unclear. Oxygen-sensitive cardiovascular magnetic resonance (OS-CMR) imaging offers a novel approach to assessing myocardial oxygenation and ischemia. This study evaluated the changes in myocardial deoxygenation in response to stress using LV OS-CMR in SSc patients without known cardiac disease. Methods: We prospectively recruited SSc patients without prior cardiac disease or risk factors, and age- and sex-matched healthy volunteers (HVs). All participants underwent transthoracic echocardiography (TTE) and 3T CMR, including native T1 mapping, rest/stress OS-CMR, stress perfusion, and late gadolinium enhancement (LGE). The primary outcome was a change in the LV OS-CMR signal intensity (SI) after adenosine stress. Results: Thirty-three participants (23 SSc, 10 HV) were enrolled. SSc patients had significantly lower global LV OS-CMR SI compared to HV (13.4 ± 6.5 vs. 19.5 ± 3.6, p = 0.011). OS-CMR SI change ≤ 10% was observed in at least one segment in 20 (87%) SSc patients and globally in 12 (52%). LGE was present in 5 (22%) patients, and 18 (78%) had ≥1 abnormal T1 mapping segment. LV global longitudinal strain (GLS) was reduced in SSc patients compared to the HVs (−19.04 ± 3.86 vs. −21.92 ± 3.72, p = 0.045). All HVs had normal CMR and TTE findings. Conclusions: SSc patients without known cardiovascular disease or PAH demonstrated subclinical LV ischemia with an impaired myocardial oxygenation response to stress. They further demonstrated LV myocardial deformation abnormalities and LV diffuse fibrosis when compared to an age-matched control group. Our findings support the presence of early coronary microvascular dysfunction and LV myocardial fibrosis in this population, which may explain the adverse cardiovascular risk seen in this population, independent of the presence of PAH. Full article

Heart failure (HF) has become an epidemic, with a prevalence of ~7 million cases in the USA. Despite accounting for nearly 50% of all HF cases, heart failure with a preserved ejection fraction (HFpEF) remains challenging to treat. Common pathophysiological mechanisms in HFpEF include oxidative stress, microvascular dysfunction, and chronic unresolved inflammation. Our lab focuses on oxidative stress-mediated cellular dysfunction, particularly the toxic effects of lipid peroxidation products like 4-hydroxy-2-nonenal (4HNE). Aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme, plays a vital role in detoxifying 4HNE and thereby protecting the heart against pathological stress. ALDH2 activity is reduced in various metabolic stress-mediated cardiac pathologies. The dysfunction of coronary vascular endothelial cells (CVECs) is critical in initiating HFpEF development. Thus, we hypothesized that ectopic overexpression of ALDH2 in CVECs could mitigate metabolic stress-induced HFpEF pathogenesis. In this study, we tested the efficacy of intracardiac injections of the ALDH2 gene into CVECs in db/db mice—a model of obesity-induced type 2 diabetes mellitus (T2DM)—and their controls, db/m mice, by injection with ALDH2 constructs (AAV9-VE-cadherin-hALDH2-HA tag-P2A) or control constructs (AAV9-VE-cadherin-HA tag-P2A-eGFP). We found that intracardiac ALDH2 gene transfer increased ALDH2 levels specifically in CVECs compared to other myocardial cells. Additionally, we observed increased ALDH2 levels and activity, along with decreased 4HNE adducts, in the hearts of mice receiving ALDH2 gene transfer compared to control GFP transfer. Furthermore, ALDH2 gene transfer to CVECs improved diastolic function compared to GFP control alone. In conclusion, ectopic ALDH2 expression in CVECs can contribute, at least partially, to the amelioration of HFpEF. Full article

Coronary microvascular obstruction and dysfunction (CMVO) frequently arise following primary percutaneous coronary intervention (PCI), particularly in individuals with myocardial infarction. Despite the restoration of epicardial blood flow, microvascular perfusion might still be compromised, resulting in negative clinical outcomes. CMVO is a complex condition resulting from a combination of ischemia, distal thrombotic embolization, reperfusion injury, and individual susceptibilities such as inflammation and endothelial dysfunction. The pathophysiological features of this condition include microvascular spasm, endothelial swelling, capillary plugging by leukocytes and platelets, and oxidative stress. Traditional angiographic assessments, such as Thrombolysis in Myocardial Infarction (TIMI) flow grade and myocardial blush grade, have limited sensitivity. Cardiac magnetic resonance imaging (CMR) stands as the gold standard for identifying CMVO, while the index of microvascular resistance (IMR) is a promising invasive option. Treatment approaches involve powerful antiplatelet drugs, anticoagulants, and supersaturated oxygen, yet no treatment has been definitively shown to reverse established CMVO. CMVO remains a significant therapeutic challenge in coronary artery disease management. Enhancing the comprehension of its core mechanisms is vital for the development of more effective and personalized treatment strategies. Full article

Diabetes Mellitus (DM) is among the most common non-infectious causes of death globally, with Type 2 DM (T2DM) representing the majority of cases. T2DM is primarily characterized by insulin resistance, leading to hyperglycemia and compensatory hyperinsulinemia. Rapid changes in lifestyle, technological advancement, and societal evolution have fueled a global rise in T2DM, making it a major public health concern. The condition is associated with numerous complications—both macrovascular and microvascular—including coronary artery disease, heart failure, chronic kidney disease, and diabetic retinopathy, all of which contribute to increased morbidity and early mortality. Chronic tissue inflammation is now recognized as a key factor in the development of T2DM, with elevated inflammatory markers serving as predictors of the disease. In particular, the NLRP3 inflammasome complex has emerged as a central player in this inflammatory process. NLRP3 acts as an intracellular sensor for danger signals and tissue injury, triggering inflammatory responses and contributing to endothelial dysfunction and T2DM pathogenesis. Its role in linking metabolic stress to inflammation has positioned it as a promising therapeutic target. This review focuses on the mechanisms underlying NLRP3 inflammasome activation and its role in T2DM and related vascular complications. Additionally, it highlights emerging therapies that target NLRP3, offering new potential strategies for the prevention and treatment of T2DM. Full article

Myocardial infarction (MI) remains a leading cause of morbidity and mortality worldwide. While timely reperfusion therapies such as percutaneous coronary intervention (PCI) and thrombolysis are essential for salvaging ischemic myocardium, they can paradoxically exacerbate tissue injury through a process known as myocardial infarction reperfusion injury (MIRI). MIRI can contribute to up to 50% of the final infarct size, significantly diminishing the benefits of revascularization and leading to worsened cardiac outcomes. The pathophysiology of MIRI involves complex, interrelated mechanisms including oxidative stress, calcium overload, mitochondrial dysfunction, inflammatory responses, apoptosis, and dysregulated autophagy. Post-reperfusion recovery is further complicated by structural and functional abnormalities such as microvascular obstruction, endothelial dysfunction, and myocardial stunning. Clinically, distinguishing reperfusion injury from ischemic damage is challenging and often requires the use of sensitive biomarkers, such as cardiac troponins, alongside advanced imaging modalities. Although a range of pharmacological (e.g., antioxidants, calcium channel blockers, mitochondrial stabilizers, anti-inflammatory agents) and non-pharmacological (e.g., hypothermia, gene therapy, stem cell-based therapies) interventions have shown promise in preclinical studies, their clinical translation remains limited. This is largely due to the multifactorial and dynamic nature of MIRI. In this context, network pharmacology offers a systems-level approach to understanding the complex biological interactions involved in MIRI, facilitating the identification of multi-target therapeutic strategies. Integrating network pharmacology with omics technologies and precision medicine holds potential for advancing cardioprotective therapies. This review provides a comprehensive analysis of the molecular mechanisms underlying MIRI, examines the current clinical challenges, and explores emerging therapeutic strategies. Emphasis is placed on bridging the translational gap through validated, multi-target approaches and large-scale, multicenter clinical trials. Ultimately, this work aims to support the development of innovative and effective interventions for improving outcomes in patients with myocardial infarction. Full article

Background and Objectives: Nonischemic cardiomyopathies comprise a wide spectrum of heart muscle disorders characterized by different morphological, functional, and tissue abnormalities. Cardiovascular magnetic resonance (CMR) represents the gold standard imaging modality for assessing cardiac morphology, systolic function, and tissue characterization, thereby aiding in early diagnosis, precise phenotyping, and tailored treatment. The aim of this review is to provide an up-to-date overview of CMR techniques for studying myocardial perfusion and their applications to nonischemic cardiomyopathy, not only to rule out an underlying ischemic aetiology but also to investigate the pathophysiological characteristics of microcirculatory dysfunction in these patients. Materials and Methods: We performed a structured review of the literature focusing on first-pass gadolinium perfusion sequences, stress protocols, and emerging pixel-wise perfusion mapping approaches. Studies were selected to illustrate the methods for image acquisition, post-processing, and quantification of myocardial blood flow (MBF) and myocardial perfusion reserve (MPR), as well as to highlight associations with clinical endpoints. Results: First-pass CMR perfusion imaging reliably detects diffuse and regional microvascular dysfunction across cardiomyopathies. Semi-quantitative parameters (e.g., upslope, MPRI) and quantitative MBF mapping (mL/g/min) have demonstrated that impaired perfusion correlates with disease severity, extent of fibrosis, and adverse outcomes, including heart failure hospitalization, arrhythmias, and mortality. Novel automated pixel-wise mapping enhances reproducibility and diagnostic accuracy, distinguishing coronary microvascular dysfunction from balanced three-vessel disease. Microvascular dysfunction—present in approximately 50–60% of dilated cardiomyopathy (DCM), 40–80% of hypertrophic cardiomyopathy (HCM), and >95% of cardiac amyloidosis (CA) patients—has emerged as a key driver of adverse outcomes. Perfusion defects appear early, often preceding overt hypertrophy or fibrosis, and provide incremental prognostic value beyond conventional CMR metrics. Conclusions: CMR represents a powerful tool for detecting myocardial perfusion abnormalities in nonischemic cardiomyopathies, improving phenotyping, risk stratification, and personalized management. Further standardization of quantitative perfusion techniques will facilitate broader clinical adoption. Full article

Background and Objectives: Screening, primary prevention, and the early identification of high-risk individuals are crucial for minimising the burden of cardiovascular diseases (CVDs). In this study, we aimed to evaluate the association of retinal microvascular features with myocardial dysfunction and CVD risk factors in a group of patients with significant coronary artery disease (CAD) compared to patients with newly diagnosed isolated arterial hypertension and healthy controls. Materials and Methods: We performed a single-centre cross-sectional study on 214 individuals divided into three groups: a group of 99 cases diagnosed with significant CAD, a group of 61 cases with newly diagnosed isolated arterial hypertension, and a control group of 54 cases with no confirmed cardiovascular pathology. Colour optic disc-centred retinal photographs were taken in all cases, and the following parameters were quantified using MONA REVA 3.0.0 software (VITO Health, Mol, Belgium): central retinal arteriolar equivalent, central retinal venular equivalent, arteriovenous ratio, fractal dimension, tortuosity index, and lacunarity. Univariable and multivariable statistical analyses were performed to assess changes in retinal microvascular features in CVD. Results: Dyslipidaemia (p = 0.009), systolic blood pressure (p = 0.008), and LDL cholesterol (p = 0.003) were negatively associated while left ventricular (LV) strain (0.043) was positively associated with the CRAE. In the case of the CRVE, the coronary Agatston score (p = 0.016) proved a positive and HDL cholesterol (p = 0.018) a negative association. A lower fractal dimension was associated with the presence of diabetes mellitus (p = 0.006), dyslipidaemia (p = 0.011), and a history of acute myocardial infarction (p = 0.018), while a higher fractal dimension was associated with increased left ventricular ejection fraction (LVEF) (p = 0.006) and medical treatment (p = 0.005). Lacunarity was higher in patients of female gender (p = 0.005), with decreased HDL (p = 0.014) and LVEF (0.005), and with increased age (p < 0.001) and Agatston score (p = 0.001). The vessel tortuosity index increased with LV strain (p = 0.05), medical treatment (p = 0.043), and male gender (p = 0.006). Conclusions: Retinal microvascular features may serve as additional risk stratification tools in patients with CVD, particularly CAD, pending prospective validation. Full article

The understanding of coronary artery disease is evolving, with more attention given currently to the microcirculation compartment. Coronary microvascular dysfunction (CMD) is defined by any structural or functional alteration of the coronary microcirculation, and is prevalent in current clinical practice, being associated with pejorative cardiovascular prognosis. CMD can exist by itself as primary microvascular angina, or in association with a variety of cardiovascular diseases. On the other hand, fractional flow reserve (FFR) represents the gold standard for estimating the hemodynamic impact of moderate coronary artery stenosis, and as such guiding coronary revascularization in clinical practice. The fundamental clinical trials that introduced and validated the use of FFR in current clinical practice were published before acquiring more in-depth knowledge on CMD and the impact it can have on FFR measurements. However, in the setting of CMD, studies have shown that FFR can underestimate the severity of coronary stenosis. In addition, recent findings underline the limitations of FFR to guide revascularization in terms of clinical outcome in specific conditions associated with CMD, such as acute coronary syndrome or multivessel coronary artery disease. As such, new research efforts must be made to investigate the reliability of FFR or to reposition its use in guiding coronary revascularization in the context of CMD, in order to define the clinical value of FFR in this particular setting. Full article

Background/Objectives: Vascular function measurements, including central parameters [pulse wave velocity (PWV) and augmentation index (AI)], as well as peripheral measures [finger photoplethysmography fitness index (PPGF)], have been introduced to detect early vascular damage associated with coronary artery disease (CAD) risk factors. This study aimed to compare peripheral and central vascular function marker levels among subjects with hypertension (HPT), dyslipidemia, and obesity. We also aimed to determine the relationship between these markers and CAD risk factors among these groups. Methods: A total of 320 subjects including healthy individuals and those with CAD risk factors were recruited. Peripheral vascular function was assessed using the PPGF, whereas central vascular markers included measurements of PWV and AI. The Framingham risk score (FRS) was calculated using an online calculator. Results: The mean age of the subjects was 33.73 ± 7.29 years. PWV and AI were significantly higher in HPT subjects (8.03 ± 1.40 m/s and 21.90% ± 10.57%) than the control. PPGF levels showed no significant differences between the groups. PWV was associated with FRS in the HPT and dyslipidemia groups, whereas AI was associated with FRS in the obese group. PPGF showed associations with PWV and AI in the dyslipidemia group. Conclusions: PWV and AI serve as robust macrovascular markers indicating arterial stiffness and systemic vascular resistance linked to CAD risk, while PPGF, as a microvascular marker, offers valuable insights into early endothelial dysfunction and microcirculatory anomalies, especially in dyslipidemia subjects. Full article