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A special issue of Diagnostics (ISSN 2075-4418). This special issue belongs to the section "Pathology and Molecular Diagnostics".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 11232

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Dr. Sonu M. M. Bhaskar

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1. Department of Neurology, National Cerebral and Cardiovascular Center, Osaka, Japan
2. Global Health Neurology Lab, Sydney, NSW 2000, Australia
3. NSW Brain Clot Bank, Sydney, Australia
Interests: cerebrovascular disorders; stroke; biomarkers; cardiovascular diseases; global health; social inequalities in health
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Special Issue Information

Dear Colleagues,

This Special Issue addresses the critical and evolving challenges in diagnosing and managing cardiovascular and cerebrovascular diseases, which continue to be the leading causes of morbidity and mortality globally. Given the complexity and severity of these conditions, a multidisciplinary approach is essential for improving patient outcomes. This Special Issue encompasses a comprehensive range of topics, including innovative diagnostic techniques, cutting-edge therapeutic strategies, and integrative care models. It highlights advancements in imaging technologies, the development and application of biomarkers, and the integration of AI-driven diagnostic tools. Additionally, this Special Issue explores novel pharmacological treatments, state-of-the-art surgical interventions, and progressive rehabilitation practices. By bringing together pioneering research from leading experts in the field, this Special Issue seeks to foster collaboration and stimulate future breakthroughs. The integration of advanced technologies and innovative therapeutic approaches is expected to significantly enhance the diagnosis, treatment, and management of cardiovascular and cerebrovascular diseases, ultimately leading to improved patient outcomes.

You may choose our Joint Special Issue in JCM.

Dr. Sonu M. M. Bhaskar
Guest Editor

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Keywords

cardiovascular diseases
cerebrovascular diseases
diagnosis
management
imaging
biomarkers
artificial intelligence
therapeutic strategies
pharmacology
surgery
rehabilitation
multidisciplinary care

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Published Papers (9 papers)

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Research

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13 pages, 571 KiB

Open AccessArticle

A Retrospective Analysis of the Effects of Concomitant Use of Intra-Aortic Balloon Pump (IABP) and Veno-Arterial Extracorporeal Membrane Oxygenation (va-ECMO) Therapy on Procedural Brain Infarction

by Farid Ziayee, Hannan Dalyanoglu, Christian Schnitzler, Kai Jannusch, Matthias Boschheidgen, Judith Boeven, Hug Aubin, Bernd Turowski, Marius Georg Kaschner and Christian Mathys

Diagnostics 2025, 15(6), 699; https://doi.org/10.3390/diagnostics15060699 - 12 Mar 2025

Viewed by 574

Abstract

Background/Objectives: Brain ischemia is a frequent complication in patients undergoing veno-arterial extracorporeal membrane oxygenation (va-ECMO) therapy due to hypoperfusion, low oxygenation, and thromboembolism. While concomitant intra-aortic balloon pump (IABP) therapy may improve the perfusion of the supra-aortic branches, it may also favor thromboembolism. This retrospective study aimed to evaluate the effects of combined va-ECMO and IABP therapy on procedural brain infarction compared to va-ECMO therapy alone, with a specific focus on analyzing the types of infarctions. Methods: Cranial computed tomography (CCT) scans of consecutive patients receiving va-ECMO therapy were analyzed retrospectively. Subgroups were formed for patients with combined therapy (ECMO and IABP) and va-ECMO therapy only. The types of infarctions and the potential impacts of va-ECMO vs. combined therapy with IABP on stroke were investigated. Results: Overall, 146 patients (36 female, 110 male, mean age 61 ± 13.3 years) were included, with 69 undergoing combined therapy and 77 patients receiving va-ECMO therapy alone. In total, 14 stroke events occurred in 11 patients in the ECMO-only group and there were 12 events in 12 patients in the ECMO + IABP-group, showing no significant difference (p = 0.61). The majority of infarctions were of thromboembolic (n = 23; 88%) origin, with 14 stroke-events in 12 patients in the ECMO + IABP-group and 9 stroke events in the ECMO-only group. The survival rate within 30 days of treatment was 29% in the ECMO-only group and 32% in the ECMO + IABP group. Conclusions: The results of this retrospective study show that concomitant IABP therapy appears to be neither protective nor more hazardous in relation to ECMO-related stroke. Thus, the indication for additional IABP therapy should be assessed independently from the procedural risk of brain ischemia. Thromboembolic infarctions seem to represent the most common type of infarction in ECMO, especially within the first 48 h of treatment. Full article

(This article belongs to the Special Issue Grand Challenges in the Diagnosis and Management of Cardiovascular and Cerebrovascular Diseases)

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13 pages, 691 KiB

Open AccessArticle

Impact of Neutrophil-to-Lymphocyte Ratio on Stroke Severity and Clinical Outcome in Anterior Circulation Large Vessel Occlusion Stroke

by Zülfikar Memiş, Erdem Gürkaş, Atilla Özcan Özdemir, Bilgehan Atılgan Acar, Muhammed Nur Ögün, Emrah Aytaç, Çetin Kürşad Akpınar, Eşref Akıl, Murat Çabalar, Ayça Özkul, Ümit Görgülü, Hasan Bayındır, Zaur Mehdiyev, Şennur Delibaş Katı, Recep Baydemir, Ahmet Yabalak, Ayşenur Önalan, Türkan Acar, Özlem Aykaç, Zehra Uysal Kocabaş, Serhan Yıldırım, Hasan Doğan, Mehmet Semih Arı, Mustafa Çetiner, Ferhat Balgetir, Fettah Eren, Alper Eren, Nazım Kızıldağ, Utku Cenikli, Aysel Büşra Şişman Bayar, Ebru Temel, Alihan Abdullah Akbaş, Emine Saygın Uysal, Hamza Gültekin, Cebrail Durmaz, Sena Boncuk Ulaş and Talip Asil Show full author list Hide full author list

Diagnostics 2024, 14(24), 2880; https://doi.org/10.3390/diagnostics14242880 - 21 Dec 2024

Viewed by 1189

Abstract

Background: The prognostic value of the neutrophil–lymphocyte ratio (NLR) in ischemic stroke remains debated due to cohort variability and treatment heterogeneity across studies. This study evaluates the relationship between admission NLR, stroke severity and 90-day outcomes in patients with anterior circulation large vessel occlusion (LVO) undergoing early, successful revascularization. Methods: A retrospective multicenter study was conducted with 1082 patients treated with mechanical thrombectomy for acute ischemic stroke. The relationship between admission NLR, baseline National Institutes of Health Stroke Scale (NIHSS), 24 h NIHSS and 90-day modified Rankin Scale (mRS) outcomes was analyzed using logistic regression. Results: Admission NLR correlated weakly but significantly with both baseline (p = 0.018) and 24 h (p = 0.005) NIHSS scores, reflecting stroke severity. However, multivariate analysis showed that higher 24 h NIHSS scores (OR 0.831, p = 0.000) and prolonged puncture-to-recanalization times (OR 0.981, p = 0.000) were independent predictors of poor 90-day outcomes, whereas NLR was not (p = 0.557). Conclusions: Admission NLR is associated with stroke severity but does not independently predict clinical outcomes at 90 days in patients achieving early and successful revascularization. These findings underscore the critical role of inflammation in the acute phase of stroke but suggest that its prognostic value for long-term outcomes is limited in this context. Full article

(This article belongs to the Special Issue Grand Challenges in the Diagnosis and Management of Cardiovascular and Cerebrovascular Diseases)

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23 pages, 2031 KiB

Open AccessArticle

Evaluating Machine Learning Models for Stroke Prognosis and Prediction in Atrial Fibrillation Patients: A Comprehensive Meta-Analysis

by Bill Goh and Sonu M. M. Bhaskar

Diagnostics 2024, 14(21), 2391; https://doi.org/10.3390/diagnostics14212391 - 26 Oct 2024

Cited by 2 | Viewed by 2112

Abstract

Background/Objective: Atrial fibrillation (AF) complicates the management of acute ischemic stroke (AIS), necessitating precise predictive models to enhance clinical outcomes. This meta-analysis evaluates the efficacy of machine learning (ML) models in three key areas: stroke prognosis in AF patients, stroke prediction in AF patients, and AF prediction in stroke patients. The study aims to assess the accuracy and variability of ML models in forecasting AIS outcomes and detecting AF in stroke patients, while exploring the clinical benefits and limitations of integrating these models into practice. Methods: We conducted a systematic search of PubMed, Embase, and Cochrane databases up to June 2024, selecting studies that evaluated ML accuracy in stroke prognosis and prediction in AF patients and AF prediction in stroke patients. Data extraction and quality assessment were performed independently by two reviewers, with random-effects modeling applied to estimate pooled accuracy metrics. Results: The meta-analysis included twenty-four studies comprising 7,391,645 patients, categorized into groups for stroke prognosis in AF patients (eight studies), stroke prediction in AF patients (thirteen studies), and AF prediction in stroke patients (three studies). The pooled AUROC was 0.79 for stroke prognosis and 0.68 for stroke prediction in AF, with higher accuracy noted in short-term predictions. The mean AUROC across studies was 0.75, with models such as Extreme Gradient Boosting (XGB) and Random Forest (RF) showing superior performance. For stroke prognosis in AF, the mean AUROC was 0.78, whereas stroke prediction yielded a mean AUROC of 0.73. AF prediction post-stroke had an average AUROC of 0.75. These findings indicate moderate predictive capability of ML models, underscoring the need for further refinement and standardization. The absence of comprehensive sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) metrics limited the ability to conduct full meta-analytic modeling. Conclusions: While ML models demonstrate potential for enhancing stroke prognosis and AF prediction, they have yet to meet the clinical standards required for widespread adoption. Future efforts should focus on refining these models and validating them across diverse populations to improve their clinical utility. Full article

(This article belongs to the Special Issue Grand Challenges in the Diagnosis and Management of Cardiovascular and Cerebrovascular Diseases)

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17 pages, 1391 KiB

Open AccessArticle

Usefulness of Atherogenic Indices for Predicting High Values of Avoidable Lost Life Years Heart Age in 139,634 Spanish Workers

by Tomás Sastre-Alzamora, Pedro J. Tárraga López, Ángel Arturo López-González, Daniela Vallejos, Hernán Paublini and José Ignacio Ramírez Manent

Diagnostics 2024, 14(21), 2388; https://doi.org/10.3390/diagnostics14212388 - 26 Oct 2024

Viewed by 1217

Abstract

Background: Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide, accounting for one-third of all global deaths. The World Health Organization (WHO) asserts that prevention is the most effective strategy to combat CVD, emphasizing the need for non-invasive, low-cost tools to identify individuals at high risk of CVD. Atherogenic indices and heart age (HA) are valuable tools for assessing cardiovascular risk (CVR). The aim of our study was to evaluate the association between atherogenic indices and HA. Methods: A cross-sectional study was conducted involving 139,634 Spanish workers to determine the association between three atherogenic indices and HA. ROC curves were employed to identify the cut-off values for the various atherogenic indices used to estimate high HA. The cut-off points, along with their sensitivity, specificity, and Youden index, were determined, and the area under the curve (AUC) was calculated. Results: As the values of the atherogenic indices increased, so did the risk of having elevated avoidable lost life years (ALLY) HA. In the ROC curve analysis, the AUC with the best results corresponded to the total cholesterol/HDL-c atherogenic index, with an AUC of 0.803 in females and 0.790 in males. The LDL-c/HDL-c atherogenic index showed an AUC of 0.780 in women and 0.750 in men, with Youden indices around 0.4. When analyzing the AUC of the atherogenic index for triglycerides/HDL-c, the results were 0.760 in women and 0.746 in men. Conclusions: Atherogenic indices and HA show a close relationship, with an increase in these indices leading to a rise in HA values. Raising patient awareness that as their CVR levels increase, so does their HA may be useful in achieving some benefit in reducing CVR. Full article

(This article belongs to the Special Issue Grand Challenges in the Diagnosis and Management of Cardiovascular and Cerebrovascular Diseases)

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20 pages, 2792 KiB

Open AccessArticle

Identification and Functional Investigation of SOX4 as a Novel Gene Underpinning Familial Atrial Fibrillation

by Wei-Feng Jiang, Yu-Min Sun, Xing-Biao Qiu, Shao-Hui Wu, Yuan-Yuan Ding, Ning Li, Chen-Xi Yang, Ying-Jia Xu, Ting-Bo Jiang and Yi-Qing Yang

Diagnostics 2024, 14(21), 2376; https://doi.org/10.3390/diagnostics14212376 - 25 Oct 2024

Cited by 1 | Viewed by 1012

Abstract

Background: Atrial fibrillation (AF) signifies the most prevalent supraventricular arrhythmia in humans and may lead to cerebral stroke, cardiac failure, and even premature demise. Aggregating strong evidence points to genetic components as a cornerstone in the etiopathogenesis of familial AF. However, the genetic determinants for AF in most patients remain elusive. Methods: A 4-generation pedigree with idiopathic AF and another cohort of 196 unrelated patients with idiopathic AF as well as 278 unrelated healthy volunteers were recruited from the Chinese population of Han ethnicity. A family-based whole-exome sequencing examination followed by a Sanger sequencing assay in all research subjects was implemented. The functional impacts of the identified SOX4 mutations were explored via a dual-reporter assay. Results: Two new heterozygous SOX4 mutations, NM_003107.3: c.211C>T; p.(Gln71*) and NM_003107.3: c.290G>A; p.(Trp97*), were observed in the family and 1 of 196 patients with idiopathic AF, respectively. The two mutations were absent in the 278 control individuals. The biochemical measurements revealed that both Gln71*- and Trp97*-mutant SOX4 failed to transactivate GJA1 (Cx43). Moreover, the two mutations nullified the synergistic activation of SCN5A by SOX4 and TBX5. Conclusions: The findings first indicate SOX4 as a gene predisposing to AF, providing a novel target for antenatal genetic screening, individualized prophylaxis, and precision treatment of AF. Full article

(This article belongs to the Special Issue Grand Challenges in the Diagnosis and Management of Cardiovascular and Cerebrovascular Diseases)

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11 pages, 1218 KiB

Open AccessArticle

Left Ventricular Diastolic Dysfunction Predicts Global Longitudinal Strain Recovery after Surgical Aortic Valve Replacement

by Francesca Bonanni, Sabina Caciolli, Martina Berteotti, Andrea Grasso Granchietti, Valentina Tozzetti, Noemi Cenni, Chiara Servoli, Marta Bandini, Enrico Marchi, Stefano Del Pace, Pierluigi Stefano and Niccolò Marchionni

Diagnostics 2024, 14(19), 2176; https://doi.org/10.3390/diagnostics14192176 - 29 Sep 2024

Cited by 1 | Viewed by 1229

Abstract

Background and Objectives: In patients with severe aortic stenosis (AS), left ventricular systolic dysfunction is one of the main predictors of adverse events after surgical aortic valve replacement (SAVR). However, more patients undergo surgery earlier, often with preserved systolic function. In these cases, global longitudinal strain (GLS) has been proposed as a marker of ventricular remodeling post-surgery. This study aims to evaluate GLS variation in patients undergoing SAVR and explore differences across the diastolic dysfunction classes. Methods: From June 2020 to March 2023, patients with AS and preserved ejection fraction (EF) requiring SAVR were enrolled. Echocardiographic evaluations were conducted preoperatively, seven days post-surgery, and twelve months after surgery. Patients were divided into two groups based on the severity of diastolic dysfunction: Group A (grade I) and Group B (grades II–III). Results: The final analysis included 108 patients (mean age 71.3 ± 7.2 years). Twenty-two patients (20.4%) also underwent coronary artery bypass grafting (CABG). The preoperative EF averaged 61.6 ± 6.03%, with no significant differences between groups. Preoperative GLS was 16 ± 4.3%, decreasing to 12.8 ± 3.4% postoperatively (p < 0.0001). GLS was comparable between the groups preoperatively (p = 0.185) and postoperatively (0.854). After twelve months, GLS improved in both groups (Group A: 17.7 ± 3.4%, Group B: 15.7 ± 3.2%, p < 0.0001), but only Group A showed significant improvement from preoperative values (p = 0.018). SAVR improved GLS regardless of CABG intervention. Conclusions: SAVR in patients with preserved LVEF results in an early reduction in GLS, regardless of diastolic dysfunction. After twelve months, GLS improved significantly, with significant recovery only in patients with mild dysfunction. Full article

(This article belongs to the Special Issue Grand Challenges in the Diagnosis and Management of Cardiovascular and Cerebrovascular Diseases)

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Review

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26 pages, 1968 KiB

Open AccessReview

Atrial Cardiomyopathy in Atrial Fibrillation: A Multimodal Diagnostic Framework

by Paschalis Karakasis, Panayotis K. Vlachakis, Panagiotis Theofilis, Nikolaos Ktenopoulos, Dimitrios Patoulias, Barbara Fyntanidou, Antonios P. Antoniadis and Nikolaos Fragakis

Diagnostics 2025, 15(10), 1207; https://doi.org/10.3390/diagnostics15101207 - 10 May 2025

Viewed by 431

Abstract

Atrial fibrillation (AF) is increasingly recognized as the clinical manifestation of an underlying atrial disease process rather than a purely electrical disorder. This evolving paradigm has given rise to the concept of atrial cardiomyopathy (AtCM), encompassing structural, electrical, contractile, and molecular remodeling of the atrial myocardium that contributes to AF initiation, maintenance, and progression. Although consensus definitions of AtCM now exist, its integration into clinical practice remains limited, with AF management still largely guided by arrhythmic patterns rather than substrate characterization. This review synthesizes current diagnostic strategies for AtCM within the context of AF, emphasizing a multimodal approach. We outline advances in cardiac imaging—including echocardiography, cardiac magnetic resonance, and computed tomography—for detailed assessment of atrial morphology, function, and fibrosis. Electroanatomic mapping is discussed as a key invasive tool for substrate localization, while electrocardiographic indices such as P-wave morphology and dispersion serve as accessible surrogates of electrical remodeling. In parallel, we examine the role of circulating biomarkers and emerging genomic, transcriptomic, and epigenomic markers in refining disease phenotyping. Despite promising progress, significant challenges remain. Standardization of imaging protocols, validation of biomarker thresholds, and integration of artificial intelligence tools are needed to enhance clinical utility. A diagnostic framework informed by atrial substrate assessment may support more tailored therapeutic decision-making in AF. Future research should prioritize the harmonization of diagnostic criteria and explore how substrate profiling in AF may refine risk stratification and improve clinical outcomes. Full article

(This article belongs to the Special Issue Grand Challenges in the Diagnosis and Management of Cardiovascular and Cerebrovascular Diseases)

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42 pages, 1639 KiB

Open AccessReview

Acute Heart Failure and Non-Ischemic Cardiomyopathies: A Comprehensive Review and Critical Appraisal

by Lina Manzi, Federica Buongiorno, Viviana Narciso, Domenico Florimonte, Imma Forzano, Domenico Simone Castiello, Luca Sperandeo, Roberta Paolillo, Nicola Verde, Alessandra Spinelli, Stefano Cristiano, Marisa Avvedimento, Mario Enrico Canonico, Luca Bardi, Giuseppe Giugliano and Giuseppe Gargiulo

Diagnostics 2025, 15(5), 540; https://doi.org/10.3390/diagnostics15050540 - 23 Feb 2025

Viewed by 1447

Abstract

Acute heart failure (AHF) is a complex clinical syndrome characterized by the rapid or gradual onset of symptoms and/or signs of heart failure (HF), leading to an unplanned hospital admission or an emergency department visit. AHF is the leading cause of hospitalization in patients over 65 years, thus significantly impacting public health care. However, its prognosis remains poor with high rates of mortality and rehospitalization. Many pre-existing cardiac conditions can lead to AHF, but it can also arise de novo due to acute events. Therefore, understanding AHF etiology could improve patient management and outcomes. Cardiomyopathies (CMPs) are a heterogeneous group of heart muscle diseases, including dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), non-dilated cardiomyopathy (NDLVC), and arrhythmogenic right ventricular cardiomyopathy (ARVC), that frequently present with HF. Patients with CMPs are under-represented in AHF studies compared to other etiologies, and therefore therapeutic responses and prognoses remain unknown. In DCM, AHF represents the most frequent cause of death despite treatment improvements. Additionally, DCM is the first indication for heart transplant (HT) among young and middle-aged adults. In HCM, the progression to AHF is rare and more frequent in patients with concomitant severe left ventricle (LV) obstruction and hypertrophy or severe LV systolic dysfunction. HF is the natural evolution of patients with RCM and HF is associated with poor outcomes irrespective of RCM etiology. Furthermore, while the occurrence of AHF is rare among patients with ARVC, this condition in NDLVC patients is currently unknown. In this manuscript, we assessed the available evidence on AHF in patients with CMPs. Data on clinical presentation, therapeutic management, and clinical outcomes according to specific CMPs are limited. Future HF studies assessing the clinical presentation, treatment, and prognosis of specific CMPs are warranted. Full article

(This article belongs to the Special Issue Grand Challenges in the Diagnosis and Management of Cardiovascular and Cerebrovascular Diseases)

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16 pages, 728 KiB

Open AccessReview

Identification of Pre-Heart Failure in Early Stages: The Role of Six Stages of Heart Failure

by Monika Jankajova, Ram B. Singh, Krasimira Hristova, Galal Elkilany, Ghizal Fatima, Jaipaul Singh and Jan Fedacko

Diagnostics 2024, 14(23), 2618; https://doi.org/10.3390/diagnostics14232618 - 21 Nov 2024

Cited by 1 | Viewed by 1305

Abstract

Despite increased availability of effective drug therapy for treatment of heart failure (HF), the morbidity and mortality in chronic heart failure (CHF) are unacceptably high. Therefore, there is an urgent need to ascertain new imaging techniques to identify early sub-clinical forms of cardiac dysfunctions, to guide early relevant treatment. It seems that all the behavioral risk factors—such as tobacco, alcoholism, Western-type diet, sedentary behavior and obesity, emotional disorders, and sleep disorder are associated with early cardiac dysfunction, which may be identified by speckle-tracking echocardiography (STE). Cardiac remodeling can also occur chronologically in association with biological risk factors of CHF, such as diabetes mellitus (DM), hypertension, cardiomyopathy, valvular heart disease, and coronary artery disease (CAD). In these conditions, twisting and untwisting of the heart, cardiac fibrosis, and hypertrophy can be identified early and accurately with 2-Dimentional (2D) and 3D echocardiography (2D echo and 3D echo) with tissue Doppler imaging (TDI), strain imaging via STE, and cardiac magnetic resonance imaging (CMR). Both 2D and 3D echo with STE are also useful in the identification of myocardial damage during chemotherapy and in the presence of risk factors. It is possible that global longitudinal systolic strain (GLS) obtained by STE may be an accurate marker for early identification of the severity of CAD in patients with non-ST segment elevation MI. Left ventricular ejection fraction (LVEF) is not the constant indicator of HF and it is normal in early cardiac dysfunction. In conclusion, this review suggests that GLS can be a useful early diagnostic marker of early or pre-cardiac dysfunction which may be treated by suitable drug therapy of HF along with the causes of HF and adhere to prevention strategies for recurrence. In addition, STE may be a superior clinical tool in the identification of cardiac dysfunction in its early stages compared to ejection fraction (EF) based on conventional echocardiography. Therefore, it is suggested that the chances of either stalling or reversing HF are far better for patients who are identified at an early stage of the disease. Full article

(This article belongs to the Special Issue Grand Challenges in the Diagnosis and Management of Cardiovascular and Cerebrovascular Diseases)

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