Advanced Diagnostic Approaches in Cardiovascular Diseases: From Imaging to Biomarkers

A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Clinical Diagnosis and Prognosis".

Deadline for manuscript submissions: closed (31 May 2026) | Viewed by 14672

Editors


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Guest Editor
1st Medical Department, University of Medicine and Pharmacy “Grigore T. Popa”, 700115 Iasi, Romania
Interests: atherosclerosis; cardiovascular diseases; thrombosis; cardiovascular prevention; coronary intervention; antithrombotic drugs; dyslipidemia
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Guest Editor
Department of Cardiology, University of Medicine and Pharmacy “Carol Davila” Bucharest, Bucuresti, Romania
Interests: atherosclerosis; cardiovascular diseases; echocardiography; vascular ultrasound; coronary syndromes; dyslipidemia
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Atherosclerosis remains the principal underlying cause of cardiovascular diseases (CVDs), contributing significantly to global morbidity and mortality. Despite remarkable advancements in diagnostic techniques and therapeutic interventions in recent decades, the prevalence of atherosclerotic CVD persists at alarmingly high levels. This underscores the critical need for innovative diagnostic strategies that enable early detection, accurate risk stratification, and personalized treatment approaches.

The early identification of atherosclerosis—beginning in the subclinical stages—is paramount for effective primordial and primary prevention. While numerous imaging modalities and biomarkers have been investigated for their prognostic potential, only a limited number have demonstrated consistent clinical utility. This Special Issue seeks to highlight cutting-edge diagnostic approaches, including advanced imaging technologies (e.g., vascular ultrasound, CT/MRI plaque characterization, and molecular imaging) and newly-discovered biomarkers (e.g., omics-based signatures, circulating proteins, and genetic markers), that aim to improve early detection and risk prediction.

As atherosclerosis progresses to clinical manifestations, its optimal management relies on precise diagnostic tools to guide therapeutic decision-making. Modern pharmacotherapy—including antiplatelet agents, next-generation lipid-lowering drugs, and anticoagulants—has transformed CVD care, yet challenges remain in tailoring treatments to individual patient profiles. Additionally, interventional cardiology continues to evolve, with diagnostics playing a pivotal role in procedural planning and long-term follow-up.

This Special Issue invites original research and reviews addressing the latest innovations in cardiovascular diagnostics, from imaging advancements to biomarker development. We welcome contributions that explore the following topics:

  • Emerging imaging techniques for atherosclerosis detection and characterization;
  • Novel biomarkers for early risk prediction and therapeutic monitoring;
  • Integrative diagnostic approaches combining imaging, biomarkers, and AI-driven analytics;
  • Translational and clinical studies validating diagnostic tools for CVD management.

By bridging gaps between research and clinical practice, this Special Issue aims to foster interdisciplinary collaboration and accelerate the development of precision diagnostics for cardiovascular diseases. We encourage submissions that contribute to refining diagnostic accuracy, improving patient outcomes, and shaping the future of CVD prevention and care.

Dr. Ovidiu Mitu
Dr. Lucia Stefania Magda
Guest Editors

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Keywords

  • medical diagnosis
  • cardiovascular diseases
  • imaging
  • biomarkers
  • AI-driven analytics

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Published Papers (18 papers)

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11 pages, 558 KB  
Article
Diagnostic Yield of Routine Pericardial Fluid Cultures and Clinical Predictors of Bacterial Pericarditis
by Amir Orlev, Alon Ze’ev Yefet, Tali Bdolah-Abram, Elad Asher and Yonit Wiener-Well
Diagnostics 2026, 16(15), 2328; https://doi.org/10.3390/diagnostics16152328 (registering DOI) - 25 Jul 2026
Abstract
Background: Pericardial effusion has a broad differential diagnosis, whereas bacterial pericarditis is rare. Despite this, routine culturing of pericardial fluid is frequently performed, and its diagnostic yield remains uncertain. Methods: We conducted a retrospective study of all pericardial fluid cultures obtained [...] Read more.
Background: Pericardial effusion has a broad differential diagnosis, whereas bacterial pericarditis is rare. Despite this, routine culturing of pericardial fluid is frequently performed, and its diagnostic yield remains uncertain. Methods: We conducted a retrospective study of all pericardial fluid cultures obtained at a tertiary medical center between January 2016 and May 2024. Cultures were classified as true positive if a recognized bacterial pathogen was isolated or if it was deemed clinically pathogenic by an infectious disease’s specialist at the medical record. Contaminants were defined according to CDC criteria. Clinical, laboratory, and imaging variables were analyzed using univariate testing and multivariable logistic regression. Results: Among 198 eligible pericardial fluid cultures, 8 (4%) yielded true bacterial pathogens, whereas 43 (23%) grew contaminants and 147 (73%) remained sterile. Thus, contaminant growth occurred more than five times as frequently as that of true pathogens. The most frequent pathogens were Staphylococcus aureus and Streptococcus species. No demographic features, presenting symptoms, or imaging findings were associated with culture positivity. In multivariable analysis, concurrent bacteremia (odds ratio [OR] 17.49; p = 0.002) and higher peripheral neutrophil percentage (OR 1.20; p = 0.012) independently predicted bacterial pericarditis. In models incorporating pericardial fluid cell counts, a lower mononuclear cell percentage was also independently associated with infection (OR 0.91; p = 0.03). Conclusions: Bacterial pericarditis is uncommon, and routine pericardial fluid cultures, of all pericardial fluid specimens, have a low diagnostic yield with substantial contamination. Laboratory markers, particularly bacteremia and neutrophilia, may help identify patients most likely to benefit from culture. A selective, laboratory-guided approach may improve diagnostic efficiency and reduce unnecessary testing. Full article
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12 pages, 1215 KB  
Article
Predictive Accuracy of Serum N-Terminal Pro-B-Type Natriuretic Peptide Alone and in Combination with Respiratory Function Tests to Identify Systemic Sclerosis-Associated Pulmonary Arterial Hypertension (SSc-PAH)
by Zoe Brown, Dylan Hansen, Laura Ross, Wendy Stevens, Kathleen Morrisroe, Alannah Quinlivan, Maryam Tabesh, Gene-Siew Ngian, Diane Apostolopoulos, Joanne Sahhar, Jennifer G. Walker, Lauren Host, Susanna Proudman and Mandana Nikpour
Diagnostics 2026, 16(14), 2254; https://doi.org/10.3390/diagnostics16142254 - 19 Jul 2026
Viewed by 144
Abstract
Background/Objectives: Pulmonary arterial hypertension (PAH) occurs in >12% of systemic sclerosis (SSc) patients and has a high mortality. Annual screening for all SSc patients is the standard of care and can include spirometry (RFT), serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and echocardiography [...] Read more.
Background/Objectives: Pulmonary arterial hypertension (PAH) occurs in >12% of systemic sclerosis (SSc) patients and has a high mortality. Annual screening for all SSc patients is the standard of care and can include spirometry (RFT), serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) and echocardiography (TTE). We sought to evaluate the accuracy of NT-proBNP alone to screen for SSc-PAH. Methods: We defined groups as low, intermediate and high risk of PAH according to RFT, TTE and RHC (right heart catheter) parameters. NT-proBNP thresholds predictive of risk group were defined, and ROC curves were used to evaluate the predictive accuracy of the calculated cut-points to diagnose SSc-PAH within the following 12 months. Results: A total of 820 SSc patients had NT-proBNP recorded 12 months prior to RHC, or if no RHC had been performed, within 12 months of the most recently recorded annual visit. The majority (335, 40.85%) were assigned to low risk of PAH, 189 (23.05%) to intermediate risk and 176 (21.46%) to high risk. NT-proBNP level < 122.9 ng/L defined the low-risk group, 122.9–186.6 ng/L defined the intermediate risk and >186.6 ng/L defined the high risk. NT-proBNP ≥210 ng/L with RFT (the ‘ASIG algorithm’) had the highest predictive accuracy, with sensitivity of 86.75% (77.52–93.19%), specificity of 60.71% (58.52–62.87%), PPV of 8.47% (6.69–10.55%), NPV of 99.09% (98.38–99.55%) and AUC of 0.74 (0.70–0.78). NT-proBNP ≥ 210 ng/L alone had sensitivity of 67.05% (56.21–76.70), specificity of 71.91% (70.03–73.72), PPV of 8.25% (6.34–10.52), NPV of 98.30% (97.57–98.86) and AUC of 0.69 (0.64–0.74). NT-proBNP thresholds associated with the three defined risk groups performed similarly overall. Conclusions: NT-proBNP alone, compared to the ASIG algorithm, had a slight reduction in NPV and AUC to predict PAH within 12 months. When NT-proBNP is ≥210 ng/L, the NPV remains high (98.0%). Full article
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17 pages, 1068 KB  
Article
Biatrial Inflammatory and Profibrotic Remodeling in Severe Mitral Regurgitation: A Comparative Tissue and Echocardiographic Study Versus CABG Comparator Group
by Adrian-Grigore Merce, Daniel-Dumitru Nișulescu, Anca Hermenean, Oana-Maria Burciu, Iulia-Raluca Munteanu, Adrian-Petru Merce, Daniel-Miron Brie, Anikó Mornoș, Dragoș Constantin Cozma, Raluca Coifan and Cristian Mornoș
Diagnostics 2026, 16(14), 2183; https://doi.org/10.3390/diagnostics16142183 - 13 Jul 2026
Viewed by 200
Abstract
Background/Objectives: Severe mitral regurgitation (MR) is associated with chronic atrial stretch, chamber enlargement, pulmonary pressure elevation, and atrial fibrosis, yet the relationship between tissue inflammatory/profibrotic signaling, histologically quantified fibrosis, and echocardiographic remodeling remains incompletely characterized. This study aimed to compare biatrial tissue remodeling [...] Read more.
Background/Objectives: Severe mitral regurgitation (MR) is associated with chronic atrial stretch, chamber enlargement, pulmonary pressure elevation, and atrial fibrosis, yet the relationship between tissue inflammatory/profibrotic signaling, histologically quantified fibrosis, and echocardiographic remodeling remains incompletely characterized. This study aimed to compare biatrial tissue remodeling in patients with severe MR undergoing mitral valve surgery with a practical non-valvular surgical comparator group undergoing isolated coronary artery bypass grafting (CABG). Methods: This single-center, observational, cross-sectional comparative study included 36 elective cardiac-surgery patients: 22 with severe MR and 14 undergoing isolated CABG without significant valvular disease. Left- and right-atrial tissue samples were collected intraoperatively. IL-6, TNF-α, and TGF-β expression was assessed by quantitative real-time PCR using pooled atrial samples stratified by atrial side and study group, whereas atrial fibrosis was quantified histologically on individual tissue specimens using Masson’s trichrome staining and digital image analysis. Clinical, laboratory, and echocardiographic parameters were compared between groups, and exploratory associations were assessed with cautious interpretation. Results: Compared with the CABG comparator group, patients with severe MR showed a pooled molecular profile compatible with higher aggregate atrial expression of IL-6, TNF-α, and TGF-β; because qPCR was performed on pooled tissue preparations, these molecular findings were interpreted descriptively and were not used for patient-level inferential statistics. Histologically quantified fibrosis was significantly increased in severe MR in both the left atrium (29.69 ± 12.26% vs. 12.17 ± 4.56%, p < 0.0001) and the right atrium (25.25 ± 11.33% vs. 9.01 ± 4.46%, p < 0.0001). The MR group also showed more pronounced echocardiographic remodeling, including larger estimated left atrial volume, higher pulmonary artery systolic pressure, and greater right ventricular diameter. Exploratory individual-level analyses were restricted to histological fibrosis and echocardiographic variables. Conclusions: Severe MR was associated with marked echocardiographic remodeling and significantly greater histologically quantified biatrial fibrosis compared with a CABG surgical comparator group. Pooled qPCR findings support an aggregate inflammatory/profibrotic signal, but they should be interpreted descriptively because individual-level molecular variability could not be assessed. These findings are hypothesis-generating and do not establish causality. Full article
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23 pages, 832 KB  
Article
Relationship Between Salivary and Serum Cardiac Troponin I in Patients Undergoing Cardiac Surgery: A Prospective Longitudinal Observational Study
by Ružica Mrkonjić, Andrej Šribar, Igor Rudež, Jadranka Ristić, Janko Bubnjar, Marin Pavlov, Anita Miljas, Željka Dujmić and Jasminka Peršec
Diagnostics 2026, 16(13), 2077; https://doi.org/10.3390/diagnostics16132077 - 2 Jul 2026
Viewed by 295
Abstract
Background/Objectives: Cardiac troponin I (TnI) is the reference biomarker for detecting myocardial injury. Saliva has recently emerged as a potential non-invasive diagnostic fluid; however, evidence regarding the clinical utility of salivary TnI remains limited. This study aimed to compare serum and salivary TnI [...] Read more.
Background/Objectives: Cardiac troponin I (TnI) is the reference biomarker for detecting myocardial injury. Saliva has recently emerged as a potential non-invasive diagnostic fluid; however, evidence regarding the clinical utility of salivary TnI remains limited. This study aimed to compare serum and salivary TnI concentrations in patients undergoing cardiac surgery and to evaluate their relationship during the perioperative period. Methods: A prospective longitudinal observational study included 54 adult patients undergoing elective cardiac surgery with cardiopulmonary bypass and cardioplegic arrest. Serum and unstimulated saliva samples were collected 18–20 h before surgery, 18–20 h after surgery, and 42–44 h after surgery. TnI concentrations were measured using a high-sensitivity chemiluminescent immunoassay. Salivary pH, salivary flow rate, renal function, and fluid balance were also recorded. Results: Significant perioperative changes in TnI concentrations were observed in both serum and saliva (p < 0.001). Median salivary TnI increased from 3.0 ng/L preoperatively to 9.2 ng/L at 18–20 h postoperatively and decreased to 6.4 ng/L at 42–44 h. Median serum TnI increased from 10.2 ng/L to 2593.1 ng/L and subsequently decreased to 1204.5 ng/L. Despite similar temporal trends, no significant correlation was found between serum and salivary TnI concentrations at any time point. Ischemic time was positively associated with postoperative serum TnI concentrations (ρ = 0.347, p = 0.01), whereas no such association was observed for salivary TnI. Salivary TnI concentrations were not significantly associated with salivary flow rate or pH. Conclusions: Salivary TnI concentrations increased significantly following cardiac surgery, indicating measurable perioperative changes within the salivary compartment. However, no significant association was observed between salivary and serum TnI concentrations under the conditions investigated in this study. Therefore, the present findings do not support the use of salivary TnI as a surrogate marker of circulating troponin concentrations. Further analytical validation of high-sensitivity troponin assays in saliva and additional clinical studies are required before definitive conclusions regarding the biological significance and potential clinical utility of salivary troponin measurements can be made. Full article
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14 pages, 998 KB  
Article
Early Inflammatory Biomarkers, Ventricular Dysfunction and In-Hospital Mortality in Patients with ST-Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention
by Dan Claudiu Magureanu, Maria Luiza Hiceag, Camelia Bianca Rus, Timea Claudia Ghitea and Corina Cinezan
Diagnostics 2026, 16(13), 1978; https://doi.org/10.3390/diagnostics16131978 - 25 Jun 2026
Viewed by 327
Abstract
Background/Objectives: Inflammation plays a central role in the pathophysiology of ST-elevation myocardial infarction (STEMI) and may influence myocardial injury, ventricular dysfunction and clinical outcomes. Simple inflammatory biomarkers derived from routine laboratory tests have been proposed as potential prognostic indicators in patients undergoing primary [...] Read more.
Background/Objectives: Inflammation plays a central role in the pathophysiology of ST-elevation myocardial infarction (STEMI) and may influence myocardial injury, ventricular dysfunction and clinical outcomes. Simple inflammatory biomarkers derived from routine laboratory tests have been proposed as potential prognostic indicators in patients undergoing primary percutaneous coronary intervention (PCI). Objective: This study aimed to evaluate the association between admission inflammatory biomarkers, echocardiographic markers of ventricular dysfunction and in-hospital mortality in patients with STEMI treated with primary PCI. Methods: We conducted a retrospective observational study including 600 consecutive patients admitted with STEMI and treated with primary PCI between January 2021 and August 2025. Inflammatory biomarkers measured at admission included C-reactive protein (CRP); neutrophil-to-lymphocyte ratio (NLR); platelet-to-lymphocyte ratio (PLR); systemic immune-inflammation index (SII) and C-reactive protein-to-lymphocyte ratio (CLR). Echocardiographic parameters and clinical outcomes were recorded. Multivariable logistic regression analysis was performed to identify independent predictors of in-hospital mortality. Results: In-hospital mortality occurred in 54 patients (9.0%). Patients with reduced left ventricular ejection fraction (LVEF ≤ 40%) had significantly higher CRP and CLR levels (p < 0.01). Inflammatory biomarkers were associated with markers of ventricular dysfunction but were not independent predictors of mortality. Age, LVEF < 40% and the number of residual coronary lesions independently predicted in-hospital death. Conclusions: In STEMI patients undergoing primary PCI, early mortality is mainly determined by age; ventricular dysfunction and residual coronary disease burden, while inflammatory biomarkers primarily reflect the severity of myocardial injury rather than independently predicting short-term mortality. Full article
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11 pages, 1585 KB  
Article
The Impact of Intravenous Versus Intra-Arterial Heparin Administration on Radial Artery Spasm During Transradial Coronary Angiography
by Eyyup Tusun, Mehmet Han Mercan, Müslüm Karakaş, Necmettin Korucuk and Veysel Tosun
Diagnostics 2026, 16(11), 1656; https://doi.org/10.3390/diagnostics16111656 - 28 May 2026
Viewed by 320
Abstract
Background/Objectives: Radial artery spasm (RAS) is an important complication during transradial coronary angiography that may negatively affect procedural success and reduce patient comfort. The aim of this study was to comparatively evaluate the effects of intravenous (IV) and intra-arterial (IA) heparin administration on [...] Read more.
Background/Objectives: Radial artery spasm (RAS) is an important complication during transradial coronary angiography that may negatively affect procedural success and reduce patient comfort. The aim of this study was to comparatively evaluate the effects of intravenous (IV) and intra-arterial (IA) heparin administration on the development of RAS. Methods: This prospective, observational parallel-group cohort study included a total of 223 patients undergoing transradial coronary angiography. Patients were divided into two groups, receiving either IV heparin (n = 77) or IA heparin (n = 146). All patients received a standard dose of unfractionated heparin (5000 IU) and an IA spasmolytic cocktail consisting of 2.5 mg verapamil and 100 mcg nitroglycerin. RAS was defined as pain during the procedure, resistance during catheter manipulation, or the need for crossover. Logistic regression analysis and receiver operating characteristic (ROC) curve analyses were performed. Results: RAS developed in 40 of 223 patients (17.9%). The incidence of RAS was significantly higher in the IA heparin group than in the IV heparin group (23.3% [34/146] vs. 7.8% [6/77]; p = 0.004). Crossover to femoral access due to severe spasm was observed only in the IA group (6.2% [9/146] vs. 0% [0/77]; p = 0.026). Patients who developed RAS were younger, required a greater number of catheters, had longer angiography duration, and were exposed to a higher total radiation dose (p < 0.05 for all). In ROC analysis, the number of catheters used and angiography duration showed comparable performance in predicting RAS. In multivariable logistic regression analysis, IA heparin administration and the number of catheters used were identified as independent predictors of RAS. Conclusions: During transradial coronary angiography, intravenous heparin administration is associated with a significantly lower frequency of RAS and a reduced need for femoral crossover compared with intra-arterial administration. IV heparin may represent an easily applicable strategy for RAS prevention, although causality cannot be established from this observational study. Full article
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11 pages, 759 KB  
Article
Bridging the Diagnostic Gap in Peripheral Arterial Disease (PAD): Leveraging Fatty Acid Binding Protein 3 (FABP3) for Biomarker-Guided Detection
by Muzammil H. Syed, Abdelrahman Zamzam, Farah Shaikh, Ori D. Rotstein, David J. Klein, Houssam Younes, Rawand Abdin and Mohammad Qadura
Diagnostics 2026, 16(10), 1457; https://doi.org/10.3390/diagnostics16101457 - 11 May 2026
Viewed by 431
Abstract
Background/Objective: Peripheral arterial disease (PAD) is a widespread but underdiagnosed manifestation of systemic atherosclerosis, associated with high morbidity and mortality. Traditional diagnostic methods such as the ankle-brachial index (ABI) have limited sensitivity in certain populations, highlighting the need for reliable blood-based biomarkers. [...] Read more.
Background/Objective: Peripheral arterial disease (PAD) is a widespread but underdiagnosed manifestation of systemic atherosclerosis, associated with high morbidity and mortality. Traditional diagnostic methods such as the ankle-brachial index (ABI) have limited sensitivity in certain populations, highlighting the need for reliable blood-based biomarkers. Fatty Acid Binding Protein 3 (FABP3) has emerged as a robust biomarker with diagnostic utility in PAD. To evaluate the diagnostic performance of FABP3 when used in combination with traditional clinical risk factors for PAD in patients presenting to vascular surgery clinics. Methods: A retrospective analysis was conducted on 657 patients presenting to ambulatory vascular surgery clinics at St. Michael’s Hospital. Two logistic regression models were compared: (1) Model A: Included standard clinical risk factors (calf pain, age, smoking, diabetes, hypertension, hypercholesterolemia, coronary artery disease, and signs of chronic limb-threatening ischemia); and (2) Model B: Included the same factors as Model A, plus FABP3 levels. Diagnostic metrics including area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy were assessed. Results: Among 657 patients, 423 had PAD and 234 did not. Model B (FABP3-integrated model) outperformed Model A, with a higher AUC (0.86 vs. 0.82), sensitivity (96% vs. 81%), specificity (84% vs. 67%), PPV (92% vs. 81%), NPV (94% vs. 65%), and diagnostic accuracy (93% vs. 76%). FABP3 also improved detection in asymptomatic PAD patients (84% detected vs. 0%). Conclusions: Integrating FABP3 with standard clinical risk factors significantly improves PAD diagnosis, especially in asymptomatic and borderline cases. These findings support the potential role of FABP3 in routine PAD screening, warranting further prospective studies for validation. Full article
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15 pages, 6685 KB  
Article
Development and Initial Validation of the Novel Computational Method for Dynamic Intracardiac Blood Flow Evaluation
by Dmytro Volkov, Dmytro Skoryi, Bogdan Batsak, Iurii Karpenko, Alamjeet Kaur Sidhu, Carola Gianni, Vincenzo Mirko La Fazia, Bryan MacDonald, Joseph Gallinghouse, Rodney Horton, Sanghamitra Mohanty and Andrea Natale
Diagnostics 2026, 16(9), 1352; https://doi.org/10.3390/diagnostics16091352 - 30 Apr 2026
Viewed by 595
Abstract
Background/Objectives: To develop and preliminarily evaluate a practical Python-based program for dynamic intracardiac blood flow visualization and the extraction of new quantitative parameters, serving as an initial step toward future flow-based cardiac evaluation. Methods: The method was technically explored across five [...] Read more.
Background/Objectives: To develop and preliminarily evaluate a practical Python-based program for dynamic intracardiac blood flow visualization and the extraction of new quantitative parameters, serving as an initial step toward future flow-based cardiac evaluation. Methods: The method was technically explored across five imaging modalities (angiography, MRI, ICE, TEE, TTE) using standard diagnostic hardware. Preliminary testing used ECG-gated ICE DICOM images from sixteen patients undergoing first-time AF ablation. Results: The program produced dynamic full-chamber flow visualizations and automatically computed two image-derived surrogate markers of flow-pattern behavior, the *turbulence index (TI)* and *blood mobility fraction (BMF)*, across cardiac cycles. Distinct preliminary flow patterns were observed between sinus rhythm and atrial fibrillation. Outputs are exportable for AI analysis. Conclusions: This proof-of-concept approach demonstrates feasibility for routine intracardiac flow assessments, and introduces TI and BMF as potential flow-based biomarkers for future prognostic use after additional validation. Full article
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20 pages, 2288 KB  
Article
Association of Permanent Atrial Fibrillation with Cognitive Impairment in Stroke-Censored Patients from Western Romania: A Cross-Sectional Study
by Sergiu-Florin Arnautu, Dragos Catalin Jianu, Minodora Andor, Madalin-Marius Margan, Brenda-Cristiana Bernad, Daniel Rus and Diana-Aurora Arnautu
Diagnostics 2026, 16(9), 1251; https://doi.org/10.3390/diagnostics16091251 - 22 Apr 2026
Viewed by 425
Abstract
Background/Objectives: Cognitive impairment is highly prevalent in atrial fibrillation (AF) and frequently occurs in the absence of overt stroke, implicating non-embolic mechanisms. We hypothesized that atrial remodeling and impaired cerebral hemodynamics are associated with mild cognitive impairment (MCI) in permanent AF. Methods [...] Read more.
Background/Objectives: Cognitive impairment is highly prevalent in atrial fibrillation (AF) and frequently occurs in the absence of overt stroke, implicating non-embolic mechanisms. We hypothesized that atrial remodeling and impaired cerebral hemodynamics are associated with mild cognitive impairment (MCI) in permanent AF. Methods: In this cross-sectional study, 252 stroke-free patients with permanent AF receiving direct oral anticoagulants (DOACs) underwent transthoracic echocardiography and transcranial Doppler (TCD) assessment of middle cerebral artery flow. Peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive index (RI) were analyzed. Multivariable logistic regression identified factors independently associated with MCI, and receiver operating characteristic (ROC) curves evaluated discriminative performance. Results: MCI was present in 40% of patients (101/252). AF-MCI patients were older and showed greater left atrial remodeling, reflected by increased left atrial diameter and left atrial volume index (LAVI) (both p ≤ 0.001), without differences in left ventricular systolic function. TCD demonstrated reduced EDV and increased RI in the MCI group (all p ≤ 0.01), whereas PSV showed minimal differences. In multivariable analysis, age, LAVI, and average RI were independently associated with MCI. Age showed excellent discrimination (AUC 0.858), whereas maximum RI demonstrated moderate discrimination (AUC 0.645; p < 0.001 for comparison). Conclusions: In stroke-censored permanent atrial fibrillation, cognitive impairment was associated with atrial remodeling and impaired diastolic cerebral perfusion, consistent with a potential contribution of chronic hypoperfusion and increased microvascular resistance. Combined echocardiographic and cerebral hemodynamic assessment may help characterize hemodynamic patterns associated with cognitive impairment in AF. Full article
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14 pages, 2195 KB  
Article
The Association of Atherogenic Indices with Coronary Slow Flow: Evidence from a Large Cohort Study
by Muzaffer Bayhatun and Sadettin Selçuk Baysal
Diagnostics 2026, 16(5), 717; https://doi.org/10.3390/diagnostics16050717 - 28 Feb 2026
Viewed by 619
Abstract
Background: Coronary slow flow (CSF) is a microvascular disorder characterized by delayed perfusion despite the absence of significant epicardial stenosis. Although its exact pathophysiology remains unclear, endothelial dysfunction, oxidative stress, and atherogenic dyslipidemia have been implicated. Traditional lipid parameters may not fully capture [...] Read more.
Background: Coronary slow flow (CSF) is a microvascular disorder characterized by delayed perfusion despite the absence of significant epicardial stenosis. Although its exact pathophysiology remains unclear, endothelial dysfunction, oxidative stress, and atherogenic dyslipidemia have been implicated. Traditional lipid parameters may not fully capture the atherogenic burden, whereas atherogenic indices such as the atherogenic index of plasma (AIP), atherogenic coefficient (AC), and Castelli risk indices (CRI-I and CRI-II) may provide better predictive value. This study aimed to investigate the association between atherogenic indices and CSF in a large real-world angiographic cohort. Methods: This retrospective study included 25,486 patients who underwent coronary angiography between September 2020 and June 2024. A total of 464 patients with CSF (diagnosed by TIMI frame count criteria) and 408 controls with normal coronary flow (NCF) were identified. Atherogenic indices, including AIP, AC, CRI-I, CRI-II, and non-HDL cholesterol (non-HDL-C), were calculated. Multivariate logistic regression analysis identified independent predictors of CSF, while receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of each lipid-related parameter. Results: Patients with CSF had significantly higher AIP, AC, non-HDL-C, and CRI indices and lower HDL-C levels compared to controls (all, p < 0.05). Multivariate analysis identified AIP (OR: 1.73, 95% CI: 1.18–2.44, p = 0.004), age (OR: 1.02, 95% CI: 1.01–1.06, p = 0.014) and smoking (OR: 2.22, 95% CI: 1.36–2.84, p = 0.003) as independent predictors of CSF. ROC analysis showed modest but statistically significant discriminatory capacity for AIP (cut-off: 0.50; AUC: 0.629; 95% CI: 0.591–0.667; p < 0.001). AIP also demonstrated a weak yet significant correlation with mean TIMI frame count (rho = 0.245, p < 0.001), suggesting a potential link to microvascular dysfunction. Conclusions: Among the evaluated atherogenic indices, only AIP demonstrated an independent association with CSF. Despite modest discriminative performance that does not support standalone clinical prediction, AIP may reflect an underlying metabolic phenotype associated with CSF and serve as a complementary marker alongside traditional risk assessment. These findings should be interpreted as hypothesis-generating and warrant prospective validation. Full article
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13 pages, 1611 KB  
Article
Global Myocardial Work-Derived Nomogram for Coronary Stenosis Assessment in Stable Coronary Artery Disease: Development and External Validation
by Miao Li, Wenfang Wu, Lin Li, Qianshan Ding, Jing Dong and Pingyang Zhang
Diagnostics 2026, 16(4), 570; https://doi.org/10.3390/diagnostics16040570 - 13 Feb 2026
Cited by 1 | Viewed by 616
Abstract
Background: Non-invasive identification of coronary stenosis in stable coronary artery disease (CAD) patients lacking regional wall motion abnormalities (RWMA) remains challenging. This study aimed to develop and validate a myocardial work-derived nomogram for predicting significant coronary stenosis in these patients. Methods: In this [...] Read more.
Background: Non-invasive identification of coronary stenosis in stable coronary artery disease (CAD) patients lacking regional wall motion abnormalities (RWMA) remains challenging. This study aimed to develop and validate a myocardial work-derived nomogram for predicting significant coronary stenosis in these patients. Methods: In this retrospective study, 181 consecutive patients with angiographically confirmed CAD, preserved LVEF (≥55%), and no resting wall motion abnormalities were enrolled. Global myocardial work efficiency (GWE) was assessed using echocardiographic pressure–strain loop analysis. A multivariable-derived nomogram incorporating GWE and clinical biomarkers was developed and externally validated for predicting severe coronary stenosis. Results: The nomogram incorporating GWE, lipoprotein-associated phospholipase A2 (LP-PLA2), N-terminal pro brain natriuretic peptide (NT-proBNP), and serum creatinine (Scr) demonstrated favorable discrimination in both the training set (AUC 0.916, 95% CI 0.866–0.952) and validation set (AUC 0.911, 95% CI 0.853–0.951), with good calibration (mean absolute error: 1.9% vs 3.2% in training vs validation, respectively). Decision curve analysis confirmed clinical utility across all probability thresholds. Conclusions: Our nomogram provides a non-invasive tool for preoperative risk stratification and optimizes the use of invasive diagnostics in stable CAD patients without RWMA. Full article
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24 pages, 48184 KB  
Article
Beat-to-Beat QT Variability: A Population Study of the QT Variability Index Composition
by Jan Řehoř, Kateřina Helánová, Martina Šišáková, Tomáš Novotný, Irena Andršová and Marek Malik
Diagnostics 2026, 16(3), 502; https://doi.org/10.3390/diagnostics16030502 - 6 Feb 2026
Viewed by 823
Abstract
Background/Objectives: One of the topics of electrocardiographic risk factor studies is investigations of beat-to-beat QT interval variability. The seminal study that reported QT variability as a prognostic risk factor introduced the so-called QT variability index (QTVi). QTVi quantification relies not only on [...] Read more.
Background/Objectives: One of the topics of electrocardiographic risk factor studies is investigations of beat-to-beat QT interval variability. The seminal study that reported QT variability as a prognostic risk factor introduced the so-called QT variability index (QTVi). QTVi quantification relies not only on the variance of QT intervals but also on correction factors, including RR interval variance, heart rate, and overall QT interval duration. This study investigated the influence of all the measured factors on QTVi values. Methods: Long-term electrocardiograms (ECGs) were obtained from 251 healthy subjects (mean age 33.6 ± 9.1 years, 108 females) during repeated postural tests that involved supine, sitting, and standing positions maintained for 10 or 15 min. During each position, a 5-min ECG segment with a stable heart rate and without any ectopic disturbances was found. In these segments, standard deviations of normal-to-normal RR (NN) interval durations (SDNN) and of beat-to-beat QT interval durations (SDQT) were measured together with the means of NN and QT intervals. QTVi was subsequently calculated. For each subject, results obtained during each postural position were averaged. Results: In multivariable regression models, evaluated separately in female and male sex-subgroups of the population, QTVi values were significantly dependent on SDQT, SDNN, and mean NN intervals (all p < 0.001) but practically independent of mean QT interval durations. Conclusions: QTVi is significantly influenced by factors that are unrelated to the beat-to-beat changes in QT interval durations. This needs to be considered when interpreting QTVi values. In future studies, multivariable statistical models are needed to ensure that QTVi findings are independent of associated heart rate variability indices. Full article
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13 pages, 1052 KB  
Article
Immunoglobulin Free Light Chains as a Biomarker of Inflammation and Heart Failure in Myocarditis and Non-Inflammatory Heart Disease
by Olga Blagova, Yulia Lutokhina, Maria Kozhevnikova, Elena Zheleznykh and Evgeniya Kogan
Diagnostics 2026, 16(1), 50; https://doi.org/10.3390/diagnostics16010050 - 23 Dec 2025
Viewed by 951
Abstract
Aim: to study the level of immunoglobulin FLC in patients with myocarditis in comparison with non-inflammatory heart diseases, and FLC’s correlation with the severity of CHF. Methods: Ninety-nine patients (41 women, 59.6 ± 14.6 y.o.) were included in the study: 50 [...] Read more.
Aim: to study the level of immunoglobulin FLC in patients with myocarditis in comparison with non-inflammatory heart diseases, and FLC’s correlation with the severity of CHF. Methods: Ninety-nine patients (41 women, 59.6 ± 14.6 y.o.) were included in the study: 50 patients with myocarditis [confirmed by myocardial biopsy (n = 20) and/or cardiac MRI]; 49 patients with non-inflammatory heart disease. CHF was diagnosed in 66% and 65% of patients, respectively. The levels of FLC were determined using the ‘Cloneus S-FLC-K TIA Kit’ and ‘Cloneus S-FLC-L TIA Kit’ reagents. Results: Elevated FLC levels were found in 56% of patients with myocarditis and in 67% of comparison group patients (p > 0.05). Mean FLC kappa levels were 13.4 [11.7; 16.7] and 16.0 [11.3; 23.7] mg/L, FLC lambda 22.7 [16.7; 32.4] and 24.7 [18.1; 39.1] mg/L, FLC kappa/lambda ratio 0.62 [0.50; 0.73] and 0.65 [0.56; 0.76] in myocarditis and comparison groups, respectively; there were no significant differences between groups. Both groups showed correlations of FLC levels with levels of CRP and leukocytes, as well as with glomerular filtration rate, CHF NYHA class, and left ventricular ejection fraction. Only in patients with myocarditis did we observe a significant correlation between both kappa and lambda FLC and NT-proBNP (r = 0.528, p = 0.004, and r = 0.756, p < 0.001) and high-sensitivity troponin (r = 0.829, p = 0.042) levels. Conclusions: Increased FLC level may be considered an important pathogenetic link reflecting both specific mechanisms of myocarditis and severity of CHF. The determination of FLC can be used as an additional diagnostic marker, as well as one predictor of the decompensated course of myocarditis. Full article
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14 pages, 807 KB  
Article
Beyond the GRACE Score: A Multi-Biomarker Model for Improved Risk Stratification in Acute Coronary Syndromes
by Gamze Yeter Arslan and Erkan Baysal
Diagnostics 2026, 16(1), 12; https://doi.org/10.3390/diagnostics16010012 - 19 Dec 2025
Viewed by 1085
Abstract
Background: The GRACE score is widely used to estimate early mortality in acute coronary syndromes (ACS), yet its ability to capture the complex interaction between inflammation, hepatic dysfunction, renal impairment, and myocardial injury remains limited. Integrating biomarkers that reflect these complementary physiological pathways [...] Read more.
Background: The GRACE score is widely used to estimate early mortality in acute coronary syndromes (ACS), yet its ability to capture the complex interaction between inflammation, hepatic dysfunction, renal impairment, and myocardial injury remains limited. Integrating biomarkers that reflect these complementary physiological pathways may enhance risk prediction and allow earlier identification of high-risk patients. This study evaluated whether a multi-biomarker model incorporating the C-reactive protein/albumin ratio (CAR), the albumin–bilirubin (ALBI) score, and the blood urea nitrogen/creatinine (BUN/Cr) ratio provides incremental prognostic value beyond the GRACE score and traditional cardiac markers. Methods: This retrospective study included patients hospitalized with ACS. Baseline laboratory results were used to calculate CAR, ALBI, and BUN/Cr ratios. Troponin and hemoglobin values were recorded as standard cardiac and hematologic indicators. The primary outcome was in-hospital mortality. Logistic regression models, receiver operating characteristic (ROC) curve analysis, and comparisons of area under the curve (AUC) were performed to determine whether the multi-biomarker model improved risk stratification beyond the GRACE score alone. Results: Higher CAR, ALBI, and BUN/Cr values were each associated with increased in-hospital mortality. When combined with the GRACE score, the multi-biomarker model significantly improved predictive accuracy. The integrated model demonstrated a higher AUC compared with GRACE alone, indicating incremental prognostic value across inflammatory, hepatic, and renal pathways. Conclusions: A multi-biomarker strategy combining CAR, ALBI, and BUN/Cr ratios enhances early mortality prediction beyond the GRACE score in patients with ACS. Incorporating these readily available laboratory indices may help clinicians identify high-risk patients more precisely at the time of hospital admission. Full article
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17 pages, 1932 KB  
Article
Association Between Left Ventricular Global Longitudinal Strain and Hepatic Inflammation and Fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease
by Alberto Rodolpho Hüning, Vitor Emer Egypto Rosa, Diogo Silva Piardi, Daniara Viegas Rebelo Assis, Tainá Vanes Ferreira, Leonardo Griseli, Fabio Cañellas Moreira, Luiz Alberto De Carli, Carolina Rigatti Hartmann, Gabriela Perdomo Coral, Roney Orismar Sampaio, Marcelo Luiz Campos Vieira, Flávio Tarasoutchi, Paulo Ernesto Leães and Angelo Alves De Mattos
Diagnostics 2025, 15(23), 3007; https://doi.org/10.3390/diagnostics15233007 - 26 Nov 2025
Cited by 3 | Viewed by 1158
Abstract
Background/Objectives: Cardiovascular disease is the leading cause of mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), which includes simple steatosis (metabolic dysfunction-associated steatotic liver, MASL), metabolic dysfunction-associated steatohepatitis (MASH), and fibrosis. This study aimed to evaluate the association between left [...] Read more.
Background/Objectives: Cardiovascular disease is the leading cause of mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD), which includes simple steatosis (metabolic dysfunction-associated steatotic liver, MASL), metabolic dysfunction-associated steatohepatitis (MASH), and fibrosis. This study aimed to evaluate the association between left ventricular (LV) systolic function, measured by global longitudinal strain (GLS), and liver inflammation and fibrosis in obese patients with MASLD undergoing preoperative evaluation for bariatric surgery. Methods: Intraoperative liver biopsies classified patients into four groups: non-MASLD; MASL; MASH; and MASH with fibrosis. Preoperative transthoracic echocardiography (TTE) was performed, and LV GLS was assessed using automated strain analysis. Results: Ninety-two patients were included: 13 non-MASLD, 34 MASL, 21 MASH, and 24 MASH with fibrosis. Although most patients had normal LV GLS, values were significantly lower in the MASH with fibrosis group compared to the MASL and non-MASLD groups (p = 0.011). In multivariate analysis adjusted for HDL cholesterol and LV mass, LV GLS was associated with inflammation and fibrosis (OR 0.784; 95% CI 0.637–0.965; p = 0.022). Conclusions: LV GLS was significantly lower in patients with MASH and MASH with fibrosis and was associated with hepatic inflammation and fibrosis in obese individuals undergoing bariatric surgery. Full article
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17 pages, 833 KB  
Article
Moving Beyond LDL-C and Non-HDL-C: Apolipoprotein B as the Stronger Lipid-Related Predictor of Coronary Artery Disease in Statin-Treated Patients
by Raul-Alexandru Jigoranu, Ovidiu Mitu, Alexandru-Dan Costache, Alexandru Oancea, Radu-Stefan Miftode, Ana Maria Buburuz, Amin Bazyani, Paul Simion, Radu Sebastian Gavril, Petru Cianga, Mihail Sebastian Harnau, Viviana Onofrei, Antoniu Octavian Petris, Irina-Iuliana Costache Enache and Florin Mitu
Diagnostics 2025, 15(23), 3002; https://doi.org/10.3390/diagnostics15233002 - 26 Nov 2025
Cited by 2 | Viewed by 4523
Abstract
Background/Objectives: Coronary artery disease (CAD) remains the leading cause of death primarily in patients over 65 years old, with an increasing incidence, especially in Eastern European countries. Primary and secondary prevention protocols are based on a large number of cardiovascular (CV) risk factors, [...] Read more.
Background/Objectives: Coronary artery disease (CAD) remains the leading cause of death primarily in patients over 65 years old, with an increasing incidence, especially in Eastern European countries. Primary and secondary prevention protocols are based on a large number of cardiovascular (CV) risk factors, but low-density lipoprotein cholesterol (LDL-C) remains the main treatment target and one of the central determinants of CV risk. Apolipoprotein B (apoB) is the main structural protein in all atherogenic lipoproteins, and, unlike LDL-C, which only reflects the cholesterol content of LDL, apoB directly quantifies the total number of all circulating atherogenic particles. Over the past decade, a growing amount of data has supported the utility of apoB for CV risk assessment; however, its superiority over LDL-C remains unclear. Our study aimed to investigate the predictive value of apoB for both the presence and the severity of CAD in a statin-treated cohort from an Eastern European hospital and to compare it with standard lipid biomarkers. Methods: A total of 121 statin-treated patients, who were evaluated using coronary angiography, were consecutively enrolled and subdivided into three groups: 52 patients with significant coronary artery disease (S-CAD), 36 patients with non-significant coronary artery disease (NS-CAD), and 33 patients without coronary atherosclerosis (N-CAD). Apolipoprotein B was measured at the moment of enrollment using the immunoturbidimetric assay. Results: The mean values of LDL-C, TC, non-HDL-C, and apoB increased progressively across the three studied groups. Unlike traditional lipid biomarkers, apoB levels differed significantly not only between N-CAD and S-CAD, but also between N-CAD and NS-CAD. The diagnostic superiority of apoB extended beyond group mean differences, as it also demonstrated the strongest correlation with CAD severity. ApoB showed a moderate correlation with the Gensini score (r = 0.43, p < 0.001), which was markedly higher compared to LDL-C, TC, or non-HDL-C, all of which presented only a weak correlation (r = 0.26, r = 0.23, and r = 0.28, respectively). Additionally, in a logistic regression analysis, apoB demonstrated the highest predictive power for the presence of significant CAD (per SD increase: OR 2.386, 95% CI 1.52–3.75, p = 0.000), and it was the only biomarker able to predict left main disease (per SD increase: OR 2.433, 95% CI 1.38–4.30, p = 0.002) and three vessel disease (per SD increase: OR 1.639, 95% CI 1.012–2.654, p = 0.044). Residual apoB was also calculated and remained significantly associated with the presence of coronary atherosclerosis. Conclusions: ApoB proved to be a reliable predictor for CAD, independent of LDL-C. Compared to standard lipid biomarkers, apoB was superior in detecting NS-CAD and showed a better correlation with the severity of CAD. Additionally, in our study, only apoB was significantly correlated with left main disease and three vessel disease. Full article
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Review

Jump to: Research, Other

31 pages, 3104 KB  
Review
Mitral Stenosis in the Multimodality Imaging Era: Pitfalls, Stress Echocardiography, and Integrated Therapeutic Assessment
by Barbara Pala, Mariagrazia Piscione, Dario Gaudio, Paola Gualtieri, Mario Laudazi, Simone Steffani, Francesco Giuseppe Garaci, Marco Alfonso Perrone and Laura Di Renzo
Diagnostics 2026, 16(14), 2285; https://doi.org/10.3390/diagnostics16142285 - 22 Jul 2026
Viewed by 243
Abstract
Mitral stenosis (MS) remains a clinically relevant condition worldwide, with rheumatic and degenerative aetiologies contributing to a broad spectrum of disease. Accurate assessment of MS severity is essential for clinical decision-making but is often challenged by technical limitations, complex hemodynamic interactions, and the [...] Read more.
Mitral stenosis (MS) remains a clinically relevant condition worldwide, with rheumatic and degenerative aetiologies contributing to a broad spectrum of disease. Accurate assessment of MS severity is essential for clinical decision-making but is often challenged by technical limitations, complex hemodynamic interactions, and the heterogeneous anatomical characteristics of different MS aetiologies. This review aims to provide a comprehensive overview of the contemporary multimodality imaging assessment of MS, with particular emphasis on the pitfalls of conventional transthoracic echocardiography (TTE), the incremental value of advanced imaging modalities, and their integration into diagnostic and therapeutic decision-making. A targeted narrative review of the literature was conducted focusing on multimodality imaging approaches and their integration into clinical practice. Particular emphasis was placed on TTE parameters, three-dimensional (3D) TTE, stress echocardiography, transoesophageal echocardiography (TOE), cardiac computed tomography (cCT), and cardiac magnetic resonance (CMR), highlighting their complementary roles in anatomical characterization, hemodynamic assessment, procedural planning, and clinical decision-making. Conventional 2D TTE remains the cornerstone for MS evaluation; however, widely used parameters such as mean transmitral gradient (TMG) and pressure half-time (PHT) are highly load-dependent and may lead to misclassification of disease severity in the presence of altered hemodynamic conditions (e.g., tachycardia, atrial fibrillation (AF), or reduced cardiac output). Although direct planimetry remains the anatomical reference standard, its accuracy may be limited by operator dependency, calcification, and complex valve geometry. In this context, three-dimensional TTE (3D TTE) provides incremental value by enabling more accurate visualization of the mitral valve (MV) orifice and improving measurement reproducibility. Stress TTE plays a key role in patients with discordant symptoms or borderline resting findings by unmasking clinically significant disease during exercise. In selected patients, TOE, cCT, and CMR provide complementary information for the evaluation of complex valve morphology, mitral annular calcification (MAC), ventricular remodelling, and procedural planning, particularly in degenerative mitral stenosis (DMS) and candidates for transcatheter interventions. The evaluation of MS requires an integrated, multiparametric, multimodality imaging approach. Combining conventional TTE with stress imaging and complementary advanced modalities improves diagnostic accuracy, facilitates patient selection for intervention, and supports individualized clinical decision-making, particularly in patients with complex anatomy or discordant imaging findings. Full article
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Other

Jump to: Research, Review

3 pages, 358 KB  
Interesting Images
An Uncommon Cause of Angina
by David S. Majdalany, Elaina A. Blickenstaff, Francois Marcotte and Jason H. Anderson
Diagnostics 2025, 15(17), 2241; https://doi.org/10.3390/diagnostics15172241 - 4 Sep 2025
Viewed by 970
Abstract
Coronary anomalies, although rare, should be considered when young patients present with angina. Clinical suspicion and multi-modality imaging including coronary angiography and tomographic imaging should be pursued for symptomatic patients such as the one we are presenting with anomalous right coronary artery from [...] Read more.
Coronary anomalies, although rare, should be considered when young patients present with angina. Clinical suspicion and multi-modality imaging including coronary angiography and tomographic imaging should be pursued for symptomatic patients such as the one we are presenting with anomalous right coronary artery from the pulmonary artery. She was promptly referred for surgical intervention with re-implantation of the right coronary artery onto the aorta. Full article
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