Search Results (234)

Angina or objective myocardial ischaemia in the absence of obstructive coronary artery disease, referred to as ANOCA/INOCA, represents a prevalent and clinically significant condition associated with persistent symptoms, impaired quality of life, and increased healthcare utilisation. Contemporary evidence has reframed these syndromes as manifestations of coronary vascular dysfunction, encompassing structural and functional coronary microvascular dysfunction, epicardial vasospasm, microvascular spasm, and mixed phenotypes. In this context, multimodality imaging should not be conceptualised as sequential test accumulation, but rather as a structured, mechanism-based diagnostic strategy aimed at defining the underlying coronary endotype. The 2024 ESC Guidelines for chronic coronary syndromes endorse dedicated diagnostic pathways beyond a stenosis-centred paradigm and support the use of invasive coronary function testing (ICFT) in selected patients with persistent symptoms or inconclusive non-invasive findings. An integrated approach combining anatomical assessment (coronary computed tomography angiography or invasive angiography ± pressure-based indices), quantitative perfusion imaging (positron emission tomography or stress cardiovascular magnetic resonance), and ICFT (including coronary flow reserve, microvascular resistance indices, and acetylcholine provocation testing) enables comprehensive characterisation of coronary physiology and vasomotor function. This review proposes a pragmatic framework linking diagnostic findings to targeted therapy through a test-to-endotype-to-therapy paradigm. We summarise the strengths and limitations of each modality, discuss implementation challenges, and highlight the clinical relevance of endotype-driven management. By shifting from a stenosis-centred to a physiology- and mechanism-based approach, this strategy has the potential to close the longstanding gap between diagnosis and treatment in patients with ischaemia beyond obstructive coronary disease. Full article

Coronary microvascular dysfunction (CMD) has emerged as a crucial contributor to cardiovascular morbidity and mortality, particularly in patients with ischemia and non-obstructive coronary arteries (INOCA). The condition arises from a complex interplay of structural and functional abnormalities within the small coronary vessels, driven by underlying molecular mechanisms including endothelial nitric oxide synthase (eNOS) uncoupling, oxidative stress, and chronic inflammation. Lipid metabolism plays a central role in this pathology, especially in the setting of elevated low-density lipoprotein cholesterol (LDL-C). Furthermore, the protective capacity of high-density lipoprotein (HDL) is increasingly understood to depend on its functionality rather than absolute levels, as it can become dysfunctional and pro-inflammatory in pathological states. Emerging evidence has identified lipoprotein(a) [Lp(a)] and triglyceride-rich lipoproteins as significant, independent contributors to microvascular injury. Comprehensive clinical assessment of microvascular dysfunction therefore requires integration of advanced lipid profiling, including apolipoprotein B (ApoB), [Lp(a)], and the triglyceride-glucose (TyG) index with invasive and non-invasive measures of coronary flow reserve to more precisely stratify risk. In this narrative review, we synthesize current observational, mechanistic, and early interventional data linking diverse lipid phenotypes to coronary microvascular dysfunction. We propose a concept of lipid-driven CMD endotypes, such as ApoB-/particle overload, dysfunctional HDL, Lp(a)-mediated risk, and metabolic/TyG-high states, and map these to a practical, mechanism-informed management framework. While intensive LDL-C lowering with high-intensity statins and combination therapy remains guideline-directed care for high-risk patients, evidence for dedicated microvascular benefit from newer lipid and cardiometabolic agents is still largely hypothesis-generating. A personalized approach that aligns lipid phenotyping, CMD endotyping, and existing guideline-based therapies may help refine risk assessment and inform future trials. Full article

Fractional flow reserve derived from coronary computed tomography angiography (FFR-CT) has emerged as a non-invasive modality for the functional assessment of coronary artery disease. By using computational fluid dynamics, particularly in its most extensively validated off-site implementation, FFR-CT enables lesion-specific estimation of pressure gradients across coronary stenoses without the need for invasive catheterization. This narrative review summarizes the technical foundations of FFR-CT as well as the evidence demonstrating that FFR-CT enhances the diagnostic accuracy of coronary CT angiography alone by improving specificity for hemodynamically significant stenoses when compared with invasive fractional flow reserve. Beyond diagnosis, FFR-CT provides incremental prognostic information, supporting risk stratification and guiding revascularization decisions. Suggestions for clinical implementation of FFR-CT and guidance on interpreting results within the appropriate clinical context are provided. Despite these advantages, limitations remain, including dependence on image quality, reduced performance in heavily calcified vessels, assumptions regarding hyperemic flow conditions, and limited validation in certain populations. While computational fluid dynamics-based FFR-CT remains the most commonly adopted approach in clinical settings, machine learning-based on-site FFR-CT is rapidly evolving and is expected to become a reliable alternative. As technical refinements continue, FFR-CT is poised to play an expanding role in precision-guided management of coronary artery disease. Full article

Background/Objectives: Fractional flow reserve (FFR) is the reference standard for assessing the functional significance of intermediate coronary stenoses and guiding revascularization. Although a universal ischemic threshold is applied to all epicardial vessels, potential physiological differences between coronary territories remain insufficiently explored. The aim of this study was to evaluate whether the functional significance of intermediate coronary stenoses differs according to coronary artery and to assess the clinical outcomes of FFR-guided deferral across coronary territories. Methods: This single-center retrospective study included patients who underwent single-vessel FFR assessment for angiographically intermediate lesions between 2019 and 2022. Patients with left main disease or multivessel physiological assessment were excluded. Clinical characteristics, FFR values, and long-term outcomes were analyzed according to the investigated coronary artery. Major adverse cardiovascular events (MACE) were defined as a composite of death, myocardial infarction, and urgent revascularization. Results: A total of 310 patients (corresponding to 310 coronary arteries) were included: 211 LAD, 68 RCA, and 31 LCX lesions. Overall, 18.7% of lesions had a positive FFR (≤0.80). The only variable identified in univariable analysis as being associated with FFR positivity was the coronary artery evaluated (p < 0.001). Positive FFR values were observed in 24.6% of LAD lesions, compared with 8.8% in the RCA and none in the LCX. Among patients with negative FFR for whom revascularization was deferred, five-year MACE-free survival was similar across coronary territories (p = 0.12). Conclusions: The functional significance of intermediate coronary stenoses varies according to the coronary territory, with LAD lesions more frequently reaching ischemic thresholds. However, deferral of revascularization based on negative FFR is associated with favorable long-term outcomes across all vessels, supporting a vessel-specific physiological interpretation of coronary stenoses. Full article

Spontaneous coronary artery dissection (SCAD) is an important non-atherosclerotic cause of acute coronary syndrome, predominantly affecting younger women without traditional cardiovascular risk factors. In hemodynamically stable patients, accumulating evidence supports a conservative management strategy owing to the high rate of spontaneous vessel healing, while technically challenging invasive interventions should be reserved for selected high-risk cases. Despite growing evidence regarding acute management, recurrent SCAD and other adverse cardiovascular events have been reported during follow-up, underscoring the need for surveillance. However, optimal strategies for post-acute follow-up and for assessing the appropriateness of treatment decisions remain insufficiently established. This review focuses on clinical decision-making in the management of SCAD, with particular emphasis on follow-up assessment. We summarize the existing evidence regarding indications for conservative versus invasive treatment and discuss the clinical rationale for longitudinal imaging surveillance. Special attention is given to the role of non-invasive follow-up using coronary computed tomography angiography, including confirmation of vessel healing, evaluation of residual intramural hematoma, and assessment of distal coronary flow. Given the heterogeneity of SCAD and the risk of recurrence, individualized treatment decisions and structured follow-up strategies are essential to optimize management, avoid unnecessary invasive procedures, and support care and risk stratification in patients with SCAD. Full article

Nonobstructive coronary artery disease (NOCAD) is increasingly recognized as a heterogeneous condition characterized by diverse pathophysiological mechanisms despite the absence of flow-limiting stenosis. We sought to establish a rule-based dominant imaging phenotype framework integrating functional, structural, and inflammatory dimensions derived from multiparametric coronary computed tomography angiography (CCTA). In this retrospective cohort of 485 patients with NOCAD, CT-derived fractional flow reserve (CT-FFR), quantitative plaque burden and high-risk plaque features, and perivascular fat attenuation index (FAI) were assessed. Using predefined percentile thresholds and hierarchical rules, patients were categorized into function-, structure-, inflammation-dominant, or low-risk phenotypes. During a median follow-up of 36 months, 56 patients (11.5%) experienced major adverse cardiovascular events (MACE). After multivariable adjustment, function dominance was associated with the highest risk (hazard ratio [HR] 4.054, 95% confidence interval [CI] 1.984–8.281; p < 0.001), followed by structure dominance (HR 3.129, 95% CI 1.410–6.944; p = 0.005), whereas isolated inflammation dominance did not show a statistically significant independent association with events, with wide confidence intervals indicating limited precision. These findings suggest a graded pattern of prognostic associations across functional and structural abnormalities in NOCAD and support a phenotype-oriented interpretation of CCTA metrics reflecting distinct biological axes of coronary pathology. Full article

Background: The fat attenuation index (FAI) derived from coronary computed tomography angiography (CTA) is an emerging imaging biomarker of perivascular inflammation. Coronary flow reserve (CFR), assessed by phase-contrast (PC) cine cardiac magnetic resonance (CMR) of the coronary sinus, reflects coronary microvascular function. Although FAI has been linked to adverse outcomes in coronary artery disease (CAD), its relationship with CFR across different CAD stages is not well defined. Methods: We retrospectively evaluated 241 patients (mean age 73.4 ± 10.8 years; 149 men [61.8%]) who underwent both coronary CTA and CMR (122 with known CAD and 119 with suspected CAD). FAI was measured in the proximal left anterior descending (LAD), left circumflex (LCX), and right coronary (RCA) arteries. Impaired CFR was defined as <2.0. Univariable and multivariable logistic regression analyses were performed to identify factors associated with impaired CFR. Results: Impaired CFR was observed in 38 of 122 patients (31.1%) with known CAD and 26 of 119 (21.8%) with suspected CAD. Higher LAD-FAI was associated with impaired CFR in both groups: OR 1.06 (95% CI 1.01–1.11; p = 0.018) in known CAD and OR 1.08 (95% CI 1.02–1.15; p = 0.017) in suspected CAD. Correlation analysis also demonstrated an inverse relationship between LAD-FAI and CFR (p < 0.001), and the strength of association was comparable between the two groups. Conclusions: LAD-FAI was associated with impaired CFR in both suspected and known CAD, with comparable strength of association across the two groups. These findings indicate that perivascular inflammation, reflected by FAI, may relate to coronary microvascular dysfunction in different stages of CAD. Full article

Background: This narrative review introduces the “From Plaque to Perfusion” framework, a clinically pragmatic approach that maps multimodality imaging technologies to critical decision points in the acute coronary syndrome (ACS) patient journey. By integrating non-invasive assessment, invasive procedural guidance, and post-event tissue characterisation, this framework provides a structured pathway for deep phenotyping of ACS. Artificial intelligence (AI) is highlighted as an essential enabling layer that enhances diagnostic precision, automates quantification, and supports scalable, data-driven care. Contemporary ACS management pathways, while effective, often leave residual clinical uncertainty. The diagnostic objective has evolved beyond confirming myocardial injury to comprehensively phenotyping the entire ACS cascade: defining the plaque substrate, identifying the culprit mechanism, and quantifying the myocardial consequence. This requires a systematic integration of advanced imaging modalities. Methods: This narrative review is based on a comprehensive literature search of major medical databases (PubMed/MEDLINE, Scopus, Embase, Google Scholar) for high-level evidence, including randomized controlled trials, meta-analyses, and international expert consensus documents published between January 2010 and February 2026. Results: The “From Plaque to Perfusion” framework consists of three core stages. First, non-invasive assessment with coronary computed tomography angiography (CCTA), fractional flow reserve (FFR-CT), and PET-CT defines plaque substrate and vascular inflammation. Second, invasive precision in the catheterization laboratory, guided by optical coherence tomography (OCT) and intravascular ultrasound (IVUS), resolves the culprit mechanism and optimizes percutaneous coronary intervention (PCI). Third, post-event tissue characterization with cardiac magnetic resonance (CMR) quantifies myocardial injury and refines prognosis. AI-driven platforms are shown to enhance each stage by automating analysis, standardizing interpretation, and providing actionable metrics for clinical decisions, including complex scenarios like Myocardial Infarction with Non-Obstructive Coronary Arteries (MINOCA). Conclusions: The “From Plaque to Perfusion” framework, enabled by AI, reframes ACS imaging as an integrated, mechanism-driven pathway. This approach moves beyond isolated test interpretation toward a scalable model of precision, phenotype-led care that promises to improve diagnostic certainty and personalize patient management. Full article

Background/Objectives: We assessed the prevalence of impaired coronary flow velocity reserve (CFVR) and aimed to identify echocardiographic and clinical predictors of coronary microvascular dysfunction in adolescents after neonatal arterial switch operation (ASO). Methods: This single-center, cross-sectional study included patients that underwent neonatal ASO for simple D-transposition of the great arteries (D-TGA) during 1998–2013. All patients were evaluated by echocardiography with global left ventricular strain measurement (GLS) and cardiac catheterization, including coronary angiography. Coronary flow velocity reserve was assessed by transthoracic Doppler echocardiography in the left anterior descending artery (LAD) using adenosine induced hyperemia. Patients were stratified into two groups according to CFVR: group with impaired CFVR (<2.5) and group with normal CFVR (≥2.5). Spearman correlation was used to assess the relationship between CFVR and echocardiographic variables. Binary logistic regression was used to determine independent predictors of impaired CFVR. Results: Out of 48 patients included (median age 16 years, age range 13 to 23 years, 71% male), impaired CFVR was found in 21 patients (44%). These patients had decreased longitudinal tricuspid annular plane systolic excursion (TAPSE), greater Z scores for left ventricular end-systolic dimensions and higher mean pulmonary artery pressures (mPAP). CFVR showed modest but significant positive correlations with tricuspid annular plane systolic excursion (TAPSE). Left pulmonary artery branch stenosis, reduced TAPSE and mPAP ≥ 20 mmHg, were significantly associated with impaired CFVR, while decreased TAPSE remained independent predictor in multivariable analysis (odds ratio 5.6, 95% confidence interval 1.24–25.26, p = 0.025). Conclusions: Impaired CFVR appears to be frequently observed in adolescents after uncomplicated neonatal ASO for simple D-TGA. Importantly, impaired CFVR is associated with right ventricular dysfunction. Full article

Biological cardiovascular vulnerability is defined as an imaging-derived construct integrating myocardial functional impairment, coronary microvascular dysfunction, and modeled hemodynamic burden, including global longitudinal strain, coronary flow reserve, and derived vascular indices. To evaluate whether advanced echocardiographic and coronary Doppler imaging parameters identify biological cardiovascular vulnerability associated with the severity and complications of infective endocarditis beyond conventional structural findings. In this retrospective single-center cohort study, we analyzed consecutive patients with definite infective endocarditis who underwent advanced echocardiographic and coronary Doppler imaging. Comprehensive transthoracic and transesophageal echocardiography assessed vegetation characteristics, left ventricular function, global longitudinal strain (GLS), diastolic indices, right ventricular function, and pulmonary artery systolic pressure. Coronary microvascular function was evaluated noninvasively using transthoracic Doppler-derived coronary flow reserve (CFR) of the left anterior descending artery. Associations with disease severity and perivalvular complications were evaluated using multivariable regression analysis. Reduced coronary flow reserve was independently associated with the composite severe infective endocarditis phenotype, as defined by perivalvular complications, severe valvular dysfunction, or endocarditis team-guided urgent surgical indication. Coronary flow reserve correlated inversely with vegetation size (r = −0.39; p = 0.002) and regurgitation severity (r = −0.36; p = 0.004). Notably, the inverse association between coronary flow reserve and vegetation size showed substantial interindividual variability, particularly among patients with similar vegetation dimensions, suggesting heterogeneity in microvascular vulnerability beyond structural lesion burden. Despite relatively preserved mean arterial pressure across age groups, advanced imaging revealed progressive increases in systemic vascular resistance, declining wall shear stress, impaired microvascular flow, and reduced myocardial reserve. Imaging-derived cardiovascular vulnerability profiles frequently diverged from chronological age, highlighting heterogeneity in cardiovascular reserve despite apparently stable conventional hemodynamic parameters. Advanced echocardiographic and coronary Doppler imaging characterize a spectrum of biological cardiovascular vulnerability that is associated with clinically adjudicated severity in infective endocarditis, rather than serving as independent prognostic predictors. Full article

Background/Objectives: Physiological assessment of borderline coronary lesions is recommended by current guidelines for revascularization decision-making. The aim of our study was to assess the prognostic utility of physiological indices and determine whether their predictive value differs between patients with and without diabetes (DM). Methods: A physiological assessment was conducted in 381 patients with borderline coronary artery disease. The study cohort was divided according to the presence or absence of DM, and all individuals were followed over a four-year period. Results: Of the 381 patients, 154 (40.4%) had DM. Patients with DM had a higher BMI (30.1 kg/m² vs. 27.8 kg/m², p < 0.0001) and a lower left ventricular ejection fraction at the time of enrollment (50% vs. 55%, p = 0.0414) compared to the non-diabetic group. Patients diagnosed with DM had significantly more positive FFR results for ischemia, regardless of the assessed vessel, positive non-hyperemic evaluation of LAD and more PCI procedures, including PCI of the LAD. The mortality rate in FU among diabetics was 23.4%, while in patients without diabetes, it was 16.8%; (p = 0.1081). The clinical profile of deceased patients was largely comparable between groups. In patients with diabetes, the non-hyperemic physiological assessment by RFR/iFR (OR 0.68, 95%CI: 0.49–0.96; p = 0.0261) as well as iFR alone (OR 0.55, 95%CI: 0.32–0.97; p = 0.0388) was strongly correlated with the risk of death. In contrast to patients with DM, in the non-DM group, the non-hyperemic assessment using RFR (OR 0.37, 95%CI: 0.18–0.78; p = 0.0085) proved to be a significant prognostic factor. Conclusions: Non-hyperemic physiological indices (RFR/iFR) demonstrated a strong prognostic value in both diabetic and non-diabetic populations. Higher RFR/iFR values were consistently associated with a reduced risk of death. In the group of patients with DM, the iFR value may be considered a significant prognostic factor for long-term mortality. In the group without DM, the RFR assessment is such a factor. Full article

Background: The prevalence of chronic total occlusion (CTO) lesions is as high as 30% in patients undergoing coronary angiography (CAG). Some CTO patients do not undergo revascularization due to procedural complexity and high risks. This study aimed to investigate the value of cadmium-zinc-telluride (CZT) SPECT dynamic myocardial perfusion imaging (MPI) for risk stratification and prognosis assessment in patients with coronary CTO. Methods: This study retrospectively included 62 patients who underwent CZT SPECT dynamic MPI examination and were diagnosed with CTO by angiography. The primary endpoint was major adverse cardiovascular events (MACEs), defined as cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, hospitalization for heart failure, late coronary revascularization, or hospitalization for unstable angina. Results: Over a median follow-up of 17 months (IQR 11–23), 15 MACEs occurred. The stress myocardial blood flow (sMBF) and coronary flow reserve (CFR) in the CTO territory were significantly lower in the MACEs group compared to the non-MACEs group (all p < 0.05). Receiver operating characteristic analysis determined the optimal cut-off values for predicting MACEs as sMBF < 0.75 (sensitivity 78.7%, specificity 73.3%, AUC = 0.74, p < 0.05) and CFR < 1.39 (sensitivity 70.2%, specificity 80.0%, AUC = 0.75, p < 0.01). Kaplan–Meier survival analysis showed that patients with impaired sMBF (p < 0.001) or impaired CFR (p < 0.01), defined by these cut-off values, had significantly worse clinical outcomes. Conclusions: The results of this study indicate that sMBF and CFR obtained from CZT SPECT dynamic MPI provide valuable prognostic prediction for patients with coronary CTO lesions, offering critical evidence for identifying high-risk patients requiring active intervention. Full article

A significant proportion of patients undergoing invasive coronary angiography for angina have no obstructive coronary artery disease (CAD). In such patients, coronary microvascular dysfunction (CMD) and vasospastic angina (VSA) represent key pathophysiological mechanisms. We report a case of a 58-year-old male with exertional chest pain and exercise ECG changes typical of left main or multivessel CAD. Coronary computed tomography angiography (CCTA) showed borderline stenosis of the distal left main coronary artery. Coronary angiography revealed no critical stenosis. A comprehensive functional assessment demonstrated reduced coronary flow reserve (CFR = 2.0) and an elevated index of microcirculatory resistance (IMR = 25), consistent with CMD. An intracoronary acetylcholine provocation test induced severe focal vasospasm of the mid-left anterior descending artery (LAD) with ST-segment elevation and anginal pain, promptly relieved by nitroglycerin, confirming VSA. This case highlights the diagnostic and clinical importance of invasive functional testing in patients with angina and non-obstructive coronary arteries (ANOCA/INOCA). The coexistence of CMD and VSA (two distinct but overlapping pathophysiological endotypes) is increasingly recognized as a marker of adverse prognosis. Functional coronary assessment should be considered in all patients with angina and non-obstructive coronary arteries, as identifying mixed endotypes enables precise, mechanism-guided therapy. Full article

Objectives: To assess the diagnostic accuracy of a deep learning (DL)-based algorithm for non-invasive computation of fractional flow reserve (FFR-CT) from coronary computed tomography angiography (CCTA) and to evaluate the model’s ability to automatically assign cardiovascular risk categories according to the Coronary Artery Disease–Reporting and Data System (CAD-RADS). Materials and Methods: Sixty patients with suspected coronary artery disease who underwent both CCTA and invasive coronary angiography (ICA) were retrospectively included in this multicenter study. Curved multiplanar reconstructions derived from CCTA were analyzed by the deep learning-based model to estimate FFR-CT values and to automatically assign CAD-RADS risk categories. The diagnostic performance of the software for the identification of hemodynamically significant coronary stenoses was evaluated using ICA as the reference standard. Receiver operating characteristic (ROC) curve analysis was performed to determine the area under the curve (AUC), sensitivity, and specificity on both a per-patient and per-vessel basis. Finally, agreement between CAD-RADS risk categories assigned by the DL algorithm and those determined by an expert radiologist was assessed. Results: FFR-CT demonstrated high diagnostic accuracy, with AUC of 0.935, sensitivity of 93.2%, specificity of 93.7%, and excellent agreement with reference standard (k = 0.836) on a per-patient level. Per-vessel diagnostic performance was consistently high across all major coronary arteries, with the left anterior descending artery (LAD) showing the highest accuracy (AUC = 0.932). Automated CAD-RADS classifications generated by the software showed good agreement with those assigned by human (k = 0.765). Conclusions: The DL-based model demonstrated high diagnostic accuracy and represents a promising noninvasive approach for ischemia assessment and cardiovascular risk stratification. Full article

Background: Spontaneous recanalized coronary thrombus (SRCT) is an uncommon and often underrecognized coronary pathology that may be angiographically subtle despite having functional significance. Optical coherence tomography (OCT) enables accurate diagnosis and treatment planning. However, optimal treatment strategies remain incompletely defined. Materials and Methods: A 55-year-old man presenting with severe exertional dyspnea, atypical chest pain episodes, and abnormal stress echocardiography underwent invasive coronary assessment with angiography, fractional flow reserve (FFR), and OCT. An SRCT of the left anterior descending artery (LAD) was identified and treated using OCT-guided lesion preparation followed by sirolimus-coated drug-coated-balloon (DCB) angioplasty. Results: Although there was only moderate angiographic disease, a functional assessment confirmed significant ischemia. OCT revealed a characteristic honeycomb morphology. Post-procedural OCT demonstrated satisfactory lumen gain, with preserved vessel integrity. Follow-up imaging showed vessel-healing and late lumen enlargement, and the patient remained asymptomatic. Conclusion: OCT-guided drug-coated-balloon angioplasty may be an effective “leave-nothing-behind” strategy for selected SRCT lesions, highlighting the importance of intracoronary imaging beyond angiography. Full article