The care of patients with transthyretin amyloid cardiomyopathy (ATTR-CM) is often fragmented and routine datasets rarely capture real-world clinical trajectories and reasons for diagnosis. We introduce a novel approach, called forensic data acquisition and pathway analysis, to examine the real-world experiences of patients with ATTR-CM in our district general hospital. We retrospectively evaluated inpatient and outpatient healthcare records for our hospital between 2019 to 2025 as a part of a quality improvement project. We identified 26 cases of confirmed or likely wild-type ATTR-CM and four hereditary cases from two families carrying the S77Y variant and estimate the prevalence of transthyretin cardiac amyloidosis to be 1 per 10,000 patients. Many red flags were present in patients, including carpal tunnel syndrome (63.3%) and lumbar spinal stenosis (26.7%), as well as echocardiographic features of left ventricular hypertrophy (86.7%), left atrial dilatation (76.7%), right ventricular hypertrophy (43.3%), and a dense or speckled myocardial appearance (43.3%). Among patients with wild-type disease, the most frequent trigger for further investigation was the presence of suspicious features on transthoracic echocardiography, accounting for 13 cases. Incidental abnormalities detected on cardiac MRI contributed to another six diagnoses. In two patients, non-invasive imaging did not provide sufficient diagnostic certainty, and myocardial biopsy was required to confirm ATTR-CM. Forensic data acquisition and pathway analysis provides a powerful approach for revealing real-world clinical activity in ATTR-CM, exposing diagnostic patterns and missed opportunities that remain hidden in routine datasets.

Chronic active Epstein-Barr virus (CAEBV) infection is a rare and potentially fatal condition involving EBV-infected T or natural killer cells. We herein report a 46-year-old man with CAEBV complicated by cardiomyopathy. Imaging and a biopsy revealed EBV-positive CD3+ T cell infiltration in the myocardium. The patient was treated with high-dose cytarabine-based chemotherapy followed by cord blood transplantation using reduced-intensity conditioning, resulting in complete donor chimerism. Although transient cardiac dysfunction and post-transplant EBV reactivation occurred, the patient remained in remission for five years. This case underscores the importance of a myocardial biopsy and long-term monitoring of CAEBV with cardiac involvement.

Cardiac amyloidosis and cardiac sarcoidosis can be classified as infiltrative cardiomyopathies. Although the aetiology and underlying pathophysiology of these two conditions differ substantially, imaging techniques are becoming increasingly important for both. Only a decade ago myocardial biopsy used to be essential for establishing the diagnosis, contemporary diagnostic algorithms for both diseases now rely predominantly on non-invasive cardiac imaging, enabling not only accurate diagnosis but also guiding therapeutic decision-making. In this review, we aim to highlight the respective strengths and limitations of the available cardiac imaging modalities as they relate to these disorders. Particular emphasis will be placed on disease detection and the differential diagnosis between amyloidosis and sarcoidosis, and its value for prognostic assessment. Where appropriate, we will also discuss recent advances in multimodality imaging and how they have reshaped clinical pathways and management strategies.

ObjectivesTo characterise the myocardial transcriptomic landscape of patients with systemic sclerosis (SSc) with primary heart involvement (pHI) and identify molecular pathways underlying its pathogenesis.DesignA single-centre study exploring the molecular pathogenesis of SSc-pHI through transcriptomic analysis of endomyocardial biopsy specimens.SettingBasic research.ParticipantThis study enrolled seven patients with SSc-pHI and eight patients with dilated cardiomyopathy (DCM) who had undergone endomyocardial biopsy for clinical practice purposes.InterventionsNo intervention.Main outcome measuresNot applicable.MethodsEndomyocardial biopsy specimens from patients with SSc-pHI and those with DCM underwent whole RNA sequencing. To enable indirect comparison with non-failing (NF) myocardium, public RNA sequencing data of NF and DCM samples were integrated using DCM as a shared reference. Differential gene expression, pathway enrichment (Ingenuity Pathway Analysis and Gene Set Enrichment Analysis) and immune and stromal cell deconvolution were performed. Histopathological evaluation included LC3 immunostaining and transmission electron microscopy (TEM).ResultsA total of 700 genes were differentially expressed between SSc and DCM myocardium. Mitochondrial energy metabolism pathways, including oxidative phosphorylation, fatty acid β-oxidation and the tricarboxylic acid cycle, were markedly suppressed in SSc. Indirect comparison with NF myocardium confirmed reciprocal regulation of mitochondrial metabolism and suggested enhanced autophagy. Cell deconvolution revealed enrichment of M1-like macrophages in SSc myocardium. LC3 immunostaining and TEM revealed increased autophagic vacuoles, lipid droplet accumulation and ischaemia-like ultrastructural alterations.ConclusionsSSc myocardium exhibits metabolic reprogramming characterised by mitochondrial dysfunction and enhanced autophagy, accompanied by macrophage activation.

BackgroundAortic stenosis (AS) leads to left ventricular (LV) remodelling and fibrosis. Myocardial fibrosis can be focal and irreversible, associated with poor prognosis, or diffuse and potentially reversible after surgery. Cardiac magnetic resonance imaging (CMR) shows promise in quantifying diffuse myocardial fibrosis (DMF), but methods vary in precision. The aim of this study was to investigate the presence and distribution of DMF from myocardial biopsies and CMR tissue characteristics in severe AS. Secondarily, explore the association between DMF and LV function.MethodsForty-three patients with severe AS underwent CMR and transthoracic echocardiography within 1 week before surgical aortic valve replacement. CMR included balanced steady-state free-precession cine images, T1 relaxometry with Modified Look-Locker Inversion recovery and extracellular volume calculations. Endomyocardial biopsies were sampled.ResultsHistological analysis of 192 biopsies showed a median LV collagen volume fraction (CVF) of 19%, peaking in segment 1, according to the segment model recommended by the American Heart Association (AHA). There were significant moderate correlations between CVF and extracellular volume in AHA segments 1 (r² = 0.54, p<0.01) and 16 (r² = 0.44, p=0.03), where the DMF had the highest prevalence. Functional assessments demonstrated correlations between CVF and global circumferential and radial strain (r2 0.31, p=0.04 respectively r2−0.33, p=0.03), as well as LV ejection fraction (r2−0.34, p=0.03). T1 relaxation time correlated with GLS (r2 0.42, p<0.01), mitral annular plane systolic excursion (r2−0.39, p=0.01) and mean S’ LV (r2−0.45, p<0.01) from transthoracic echocardiography.ConclusionCVF varied across LV segments and was significantly highest at the base of the heart, suggesting the start location for fibrosis. Systolic functional data correlated with CVF and T1 relaxation time.

BackgroundFabry disease (FD) is a rare X-linked lysosomal storage disorder caused by pathogenic variants in the GLA gene and commonly involves the heart. This study aimed to investigate the pathogenicity of a novel missense variant and its amenability to migalastat.MethodsA retrospective analysis was conducted on 28 patients with FD collected over the past 10 years. Pathogenicity was assessed within a family carrying a de novo GLA missense variant through myocardial histopathology, bioinformatic predictions, protein structural modelling and in vitro cellular assays.ResultsIn a cohort of 28 patients (15 males, 13 females), cardiac involvement was prevalent. We further reported a family with GLA c.227T>A (p.Met76Lys) variant. Myocardial biopsy showed cardiomyocyte hypertrophy with diffuse vacuolisation, interstitial fibrosis and microvascular dysfunction. Immunohistochemistry demonstrated markedly decreased expression of α-galactosidase A (α-Gal A) in vacuolated cardiomyocytes. Biochemical testing revealed low-to-normal α-Gal A enzymatic activity together with elevated plasma globotriaosylsphingosine (lyso-Gb3). Bioinformatic analyses suggested this variant was probably pathogenic by altering the three-dimensional structure of GLA protein. AC16 cardiomyocytes overexpressing wild-type and mutant GLA were constructed via lentiviral vectors. Immunofluorescence staining revealed that the intracellular localisation of the mutant protein remained unaltered, whereas α-Gal A enzyme activity was significantly reduced. Treatment with migalastat, a pharmacological chaperone for α-Gal A, partially restored the mutant α-Gal A enzymatic activity.ConclusionsThis study identified GLA c.227T>A (p.Met76Lys) as a novel pathogenic variant that primarily causes cardiac dysfunction. Migalastat may represent a therapeutic option for this variant.

Heart failure with preserved ejection fraction (HFpEF) is a poorly understood, multisystem disease with high morbidity and mortality. To improve understanding of its pathobiology, we analyzed single-nucleus RNA sequencing in human HFpEF myocardium versus controls. Septal myocardial biopsies from 19 HFpEF and 24 nonfailing controls were analyzed using the 10× Genomics Chromium platform, with nuclei isolated from combined samples (6 patients/pool). Genotype-based demultiplexing was performed with souporcell, and gene expression was quantified with CellRanger and CellBender. After quality control, nuclei were annotated by cell types, and differential expression was performed between HFpEF versus controls using limma-voom. Functional analysis was performed using Gene Set Enrichment Analysis. Data were compared with prior single-nucleus RNA sequencing in dilated cardiomyopathy versus controls. We successfully demultiplexed pooled myocardial biopsies, assigning >70% of nuclei to individuals. After quality control, we recovered 48 886 nuclei and identified 14 cell types. Many differentially expressed genes across cell types were detected in HFpEF versus controls (fibroblasts, 5905; cardiomyocytes, 5159; endothelial cells, 2143; pericytes, 1812; and macrophages, 1405). Enriched pathways common to multiple cell types included immune activation, transcription/translation, metabolism, and protein quality control. They were particularly shared between cardiomyocytes and fibroblasts. Vascular smooth muscle cells had a more synthetic, proliferative phenotype. Immune cell analyses suggested enhanced T-cell activation and reduced macrophage clearance programs. Comparative analysis between HFpEF and dilated cardiomyopathy identified transcriptional differences primarily in cardiomyocytes. Two of 3 cardiomyocyte differential expression genes unique to HFpEF were validated to have concordant protein expression changes in HFpEF (MAP2K6 and PLPP3). Our findings reveal a distinct, cell-type-specific transcriptomic landscape in the human HFpEF myocardium. While HFpEF and dilated cardiomyopathy share significant molecular pathways across most cell types, the profound divergence within cardiomyocytes suggests a unique pathological driver for HFpEF. These signatures may provide a high-resolution roadmap for identifying precision therapeutic targets in HFpEF.

HighlightsWhat are the main findings?Direct comparison of mitochondrial ROS production in human and rat cardiac and skeletal muscle revealed species-specific differences in dominant ROS sources: complex I (RET) predominated in humans, whereas complex III (IIIQo) was the major source in rats.When normalized to respiratory activity, human mitochondria exhibited a greater relative capacity for ROS production at complex I, while ROS generation at complex III remained comparatively lower than in rat tissues.What are the implications of the main findings?These results challenge the assumption that ROS production patterns observed in rodent models directly translate to human physiology.Species-specific differences in mitochondrial ROS generation may influence the effectiveness of cardioprotective strategies targeting oxidative stress, highlighting the need for human-focused approaches.Mitochondrial reactive oxygen species (ROS) play a central role in cardiac ischemia/reperfusion injury, heart failure, and arrhythmogenesis, while also serving essential signaling functions under physiological conditions. Among the eleven identified mitochondrial ROS-producing sites, complexes I and III are considered the major contributors, particularly under conditions of impaired electron flow. However, much of the existing knowledge comes from rodent models or cultured cells and is often assumed to apply to humans. Here, ROS production from complexes I and III was measured directly in human myocardial and skeletal muscle biopsies and compared with corresponding rat tissues under identical experimental conditions. Hydrogen peroxide generation was quantified using Amplex UltraRed, with simultaneous monitoring of mitochondrial respiration using a Clark-type oxygen electrode. Across all examined mechanisms—reverse and forward electron transport at complex I and the ubiquinol oxidation site of complex III, rat tissues produced more ROS than human tissues, consistent with their higher respiratory rates. However, the dominant ROS-producing sites differed: in rats, complex III was the primary source, whereas in human tissues the highest ROS production occurred during reverse electron transport at complex I. When normalized to respiration, human tissues showed relatively greater ROS generation at complex I but markedly lower production at complex III. These direct measurements of mitochondrial ROS production in human myocardium provide new insight into cardiac redox physiology and may explain the limited clinical translation of cardioprotective strategies targeting mitochondrial ROS production, such as interventions aimed at modulating reperfusion injury or preconditioning.

The simultaneous detection of atrial fibrillation (AF) and left ventricular (LV) dysfunction raises questions about their relationship and necessitates a nosological diagnosis. This case study presents a 39-year-old patient who has had recurrent AF and moderate LV systolic dysfunction. Concomitantly, the patient has experienced sinus bradycardia, a transient left bundle branch block (LBBB), and prolonged QTc, which precluded the use of antiarrhythmic medication. In 2018, successful radiofrequency ablation (RFA) for paroxysmal AF was performed. However, in 2023, the patient experienced anginal pain, with a reduced ejection fraction to 26%, and persistent AF. After cardioversion, LV dysfunction persisted, and a myocardial biopsy revealed active, virus-negative, lymphocytic myocarditis (LM). The patient was prescribed immunosuppressive therapy, including corticosteroids and azathioprine. Despite recurrent tachyarrhythmic AF, LV dysfunction regressed. A epeat RFA was performed in 2024 but was clinically unsuccessful. Whole-exome sequencing revealed a variant in the RBM20 gene, suggesting that investigating the etiology of AF in patients with LV dysfunction may improve the efficacy of AF treatment and influence the course and outcomes of the underlying disease, which can be obscured by the diagnosis of «idiopathic» AF.

Immune checkpoint inhibitors (ICIs) are increasingly used as adjuvant therapy in high-risk renal cell carcinoma (RCC), but may cause serious immune-related adverse events, such as myocarditis. We report a rare case of myocarditis followed by steroid-induced myopathy during adjuvant pembrolizumab therapy. A 74-year-old man underwent partial and radical nephrectomy for bilateral clear cell RCC (pT1b and pT3a). Pembrolizumab was initiated postoperatively. On day 22, he developed exertional fatigue and cardiac enzyme levels were elevated. Myocardial biopsy confirmed myocarditis, and corticosteroid pulse therapy was started. Although cardiac markers improved initially, they rose again, requiring a second steroid pulse and higher maintenance doses. After 27 days of steroid therapy, the patient developed severe proximal muscle weakness. Myasthenia gravis and other autoimmune diseases were excluded. Steroid-induced myopathy was diagnosed, and steroid tapering plus rehabilitation led to functional recovery. He was later discharged without recurrence of myocarditis. This case highlights the importance of early detection and treatment of ICI-related myocarditis and awareness of secondary complications such as steroid myopathy. Multidisciplinary care is essential in managing these rare but serious conditions.

A homozygous variant in cardiac troponin I3, TNNI3, causes severe pediatric restrictive cardiomyopathy.

The number of patients with transthyretin amyloid cardiomyopathy (ATTR-CM) has been increasing recently, and the early diagnosis and treatment of it are important. 99mTc pyrophosphate scintigraphy (99mTc-PYP) plays a key role in the early diagnosis of ATTR-CM. In patients who underwent 99mTc-PYP, the early diagnosis of ATTR-CM by echocardiography was evaluated, focusing on left ventricular myocardial form and left ventricular wall thickness. The present study was conducted on 144 patients who underwent 99mTc-PYP between February 2020 and March 2024. A comparison was made between the 99mTc-PYP positive (P) and negative (N) groups, and significant factors were subjected to multivariate analysis. 17 of 144 patients were positive (14.9%), and 15 patients were diagnosed with ATTR-CM by myocardial or skin (fat) biopsy. Other positive patients were also clinically considered to have ATTR-CM based on findings such as poor cardiac function and cerebral hemorrhage. 99mTc-PYP positive had a significantly larger CTR (60.3% in the P group vs. 53.9% in the N group, p = 0.007) and a larger left atrial diameter (42.8 mm in the P group vs. 40.0 mm in the N group, p = 0.047). On the other hand, the mean LV wall thickness was significantly thicker (15.7 mm in the P group vs. 12.8 mm in the N group, p < 0.001); however the LV end-diastolic diameter was smaller (41.9 mm in the P group vs. 48.4 mm in the P group, p < 0.001). The LV mass was similar in both groups, thus the relative left ventricular wall thickness (RWT), which indicates relative wall thickening, was significantly higher in the P group (0.85 in the P group vs. 0.52 mm in the N group, p < 0.001). The receiver operating characteristic curve of RWT for assessing 99mTc-PYP positivity had a cut-off value of 0.717 (area under the curve 0.862, 95%CI 0.763-0.961). The evaluation of wall thickness and RWT on echocardiography is important for diagnosing ATTR-CM.

Myocarditis is an infl ammatory disease, one of the most common non-coronary myocardial diseases. During the COVID-19 pandemic, SARS-CoV-2-associated myocarditis has attracted particular interest from the cardiology community. Acute myocardial damage caused by SARS-CoV-2 is based on diff erent mechanisms. At the same time, the nature of the body’s response to various infections, including viral and, in particular, coronavirus, is individual and is largely determined genetically. We present a description of a clinical observation that shows the signifi cance of myocarditis joining a previously asymptomatic genetically determined myocardial damage. A 62-year-old female patient was admitted to the clinic due to shortness of breath with minimal physical exertion and at rest, dilation of the heart chambers, a drop in the ejection fraction (EF) of the left ventricular (LV) myocardium to 25%, and bilateral hydrothorax. Throughout her life, she tolerated stress well and maintained good physical fi tness until the sudden development of biventricular heart failure. The sudden death of her father at the age of 62 and the diagnosis of dilated cardiomyopathy (DCM) in her twin brother could indicate the presence of a genetically determined form of DCM. Myocardial infarction was excluded as a cause of acute decompensation; the later diagnosed thromboembolism of small branches of the pulmonary artery (PE) did not explain the full severity of the myocardial damage. The acute development of myocardial dysfunction in the absence of atrial fi brillation made the diagnosis of myocarditis no less likely, which was subsequently confi rmed morphologically, as well as its coronavirus nature. A month after the start of complex cardiotropic therapy, its ineff ectiveness was established (refractory critical heart failure), which required immediate heart transplantation, for which the patient was transferred to the Federal Scientifi c Center of Therapy and Orthopedics named after N.N. Acad. V. I. Shumakova. A week later, while waiting for a transplant, ventricular fi brillation and circulatory arrest developed. Resuscitation measures were ineff ective, the patient was declared dead. DNA diagnostics, completed after death, revealed a likely pathogenic variant in the titin gene and a variant with unknown clinical signifi cance in the myopalladin gene. Cases of morphologically verifi ed post-COVID myocarditis in patients with titinopathy have not been previously described in the literature. This observation clearly illustrates the insuffi cient information content of all noninvasive methods for diagnosing myocarditis, including magnetic resonance imaging (MRI) of the heart with contrast. In a situation where the patient initially had indications for a heart transplant, an attempt at active immunosuppressive therapy for the identifi ed myocarditis was justifi ed, but it had no eff ect, as did the maximum tolerated cardiotropic therapy. It is highly probable that it was the initial genetic inferiority of the myocardium that predetermined the severe course of myocarditis and the unfavorable outcome of the disease as a whole. In this clinical case, the combination of primary (familial) DCM and morphologically confi rmed SARS-CoV-2-induced lymphocytic myocarditis is of particular interest. Diagnosis and treatment of non-coronary myocardial diseases still pose signifi cant diffi culties. The insuffi ciently studied combination of myocarditis and primary cardiomyopathies may be the reason for the ineff ectiveness of conservative therapy, and heart transplantation remains the only way to save patients. Despite the unfavorable outcome of the disease, this observation demonstrates the need to use all available methods to identify the causes of DCM syndrome (not only MRI, but also myocardial biopsy and whole exome sequencing).

BackgroundThere is no universal agreement on the diagnostic criteria for cardiac sarcoidosis (CS). In 2024, the American Heart Association (AHA) introduced a new diagnostic scheme featuring a quaternary likelihood stratification for CS instead of dichotomy. Its clinical implications are unknown.MethodsWe analyzed 252 patients with CS and proven histology (mean age, 49 years; 61% women). Following the AHA diagnostic stratification, CS was retrospectively considered definite given sarcoid granulomas on myocardial biopsy (n=109), highly probable with both clinical and cardiac imaging findings being CS consistent (n=93), and probable with either clinical or imaging findings alone being CS consistent (n=50). The groups were compared for clinical characteristics and the composite incidence of death, transplantation, implantation of a left ventricular assist device, and ventricular tachyarrhythmia on follow‐up (median, 5.0 years).ResultsIn AHA definite, highly probable, and probable CS: 94%, 99%, and 22% of patients (P<0.001) had high‐grade atrioventricular block, ventricular tachyarrhythmia, or heart failure at presentation; median left ventricular ejection fraction was 42% (interquartile range, 30%–58%), 56% (interquartile range, 47%–62%), and 55% (interquartile range, 47%–65%) (P<0.001); cardiac troponins were elevated in 61%, 33%, and 20% (P<0.001); and the 5‐year event rate (95% CI) was 44% (34%–54%), 20% (11%–29%), and 10% (2%–19%) (P<0.001), respectively. In multivariable analysis, left ventricular ejection fraction (P<0.001) and presentation with ventricular tachyarrhythmia (P<0.001) were the key prognostic factors, with the AHA classification failing to have independent predictive value (P=0.201).ConclusionsThe 2024 AHA stratification of CS likelihood distinguishes groups with differences in clinical characteristics but did not have independent prognostic value in our statistical analysis.

Despite intense investigation through centuries, there is still no scientific consensus on how to describe myocardial microarchitecture. This is mainly because the myocardium must be visualised in three dimensions, and with sufficiently high resolution to fully appreciate its complex nature. X-ray microtomography allows for exactly such visualisation. Using this technique, we herein provide a description of the ventricular mural architecture in a wide range of mammals. Myocardial biopsies from the left ventricle of a human, pig, rabbit, giraffe, elephant, and sei whale were imaged using X-ray microtomography after iodine staining. Aggregations of cardiomyocytes were segmented and visualised in three dimensions, permitting accurate assessment of their shape and orientation. It was possible to segment individual components of the overall mesh using the three-dimensional images in all the studied species. The myocardium is most accurately described as a complex hierarchical meshwork, with the cardiomyocyte as the smallest working unit. The cardiomyocytes are bound together by endomysium to form aggregates, which are themselves compartmented by perimysium. A high degree of variation in the shape of aggregation was found within each biopsy, but, most remarkably, significant differences were observed between species. Some bundles of aggregated cardiomyocytes stand out from the adjacent myocardium within the mesh due to a clear change in their orientation. We provide evidence that the mammalian ventricular myocardium is a complex meshwork of cardiomyocytes. This mesh, although continuous along its direction of contraction, is separated by perimysial clefts into aggregated entities most appropriately described as aggregates. When comparing between species, there is remarkable heterogeneity in this anatomical appearance. We found no evidence of the myocardium being ordered into a large individual band as previously described elsewhere.

Immune checkpoint inhibitors (ICIs) have become standard therapies for various cancers; however, their use can lead to diverse immune-related adverse events (irAEs). While most irAEs are mild, some, such as myocarditis, although rare, have a high mortality rate. This report highlights a case in which aggressive and invasive therapeutic interventions led to successful patient survival after fulminant ICI-induced myocarditis. A 64-year-old male with a malignant pleural mesothelioma was admitted to the hospital with dyspnea on day 22 after the first cycle of ipilimumab plus nivolumab. Upon admission, he presented with cardiogenic shock and pulseless ventricular tachycardia, accompanied by elevated cardiac biomarkers. Owing to a history of ICI treatment, immune-related myocarditis was suspected, and high-dose methylprednisolone was immediately initiated. As his hemodynamic status rapidly deteriorated, extracorporeal membrane oxygenation (VA-ECMO), percutaneous left ventricular assist device (pLVAD), and temporary transvenous cardiac pacing were promptly initiated to stabilize the circulation. A myocardial biopsy confirmed lymphocytic myocarditis. The patient gradually stabilized and was successfully weaned off aggressive circulatory support, leading to patient’s discharge on day 69. Early methylprednisolone pulse therapy is crucial in treating immune-related myocarditis. To bridge the time until the steroids become fully effective, aggressive interventions such as VA-ECMO, pLVAD, and external pacing can play a life-saving supportive role. This underscores the importance of close collaboration with cardiologists to promptly implement these bridging therapies, which are vital for patient survival.

To analyze the regularities and clinical features of sintilimab-related autoimmune myocarditis, and to summarize the differential diagnosis key points between sintilimab-related autoimmune myocarditis and acute myocardial infarction. The case reports about sintilimab-related autoimmune myocarditis were searched on databases from the establishment of the database to April 1st 2024. The relevant medical records were searched on the hospital information system of Beijing Hospital of Traditional Chinese Medicine in the past 3years. The case reports and medical records were collected for statistical analysis. Twenty three cases were collected including 22 case reports and 1 case record. Most of the sintilimab-related autoimmune myocarditis were in elderly men aged 60-75years old and occurred between the end of the first dose of treatment to the beginning of the second dose. The symptom was nonspecific such as chest tightness and palpitation, sometimes with symptom of myasthenia as muscle weakness or myositisand as muscle soreness. Elevated cardiac biomarkers and changes in electrocardiogram were common, and decreased left ventricular ejection fraction was rarely seen in echocardiography. 9 cases underwent coronary angiography or computed coronary tomography angiography, and 3 cases underwent cardiovascular magnetic resonance. The manifestations of sintilimab-related autoimmune myocarditis are not specific. The medication history and concomitant symptoms are of warning value. Coronary angiography or coronary computed coronary tomography angiography can be helpful when ruling out acute myocardial infarction. Cardiovascular magnetic resonance and myocardial biopsy can confirm the diagnosis. Cardiac biomarkers and the electrocardiogram can assist in diagnosis and prognosis assessment.

The validation of promising clinical biomarkers, molecular mechanisms, and novel drug targets in cardiovascular disease (CVD) is hindered by a vast and fragmented biomedical literature, which now exceeds 38 million publications indexed in PubMed. To address the central challenge of navigating and synthesizing a huge fragmented biomedical literature base, we applied our validated machine learning–based text-mining algorithm containing natural language processing (NLP) and incorporated this into a ValIdated Text-mining using Advanced Language model (VITAL) as a complementary framework. Using this approach, we analyzed more than 38 million PubMed abstracts and identified over 5.5 million relevant to six major CVD groups. These curated data then enabled a deep-dive case study on heart failure with preserved ejection fraction (HFpEF). Our computational framework systematically queried, quantified, mapped, and prioritized protein–disease associations, confirming established CVD biomarkers, such as BNP, troponin-I, galectin-3, and renin, and revealing novel protein signatures with potential diagnostic and therapeutic relevance. Ischemic heart disease (IHD, heart attacks), cardiomyopathy (CM, leading to heart failure), and cerebrovascular accidents (CVA, strokes and brain hemorrhages) exhibited the highest protein attribution densities and overlap, suggesting shared molecular pathways. Using HFpEF as a focused case study, our framework identified 5124 proteins associated with this condition, 4879 of which were shared across its major comorbidities (aging, type 2 diabetes/obesity, hypertension, and hyperlipidemia). Additionally, 4991 proteins were co-shared across key pathological mechanisms, including inflammation, mitochondrial dysfunction, and fibrosis, implicating convergent biological networks spanning these domains. To further characterize and prioritize these molecular associations, we performed a series of data science-driven analyses involving HFpEF-associated proteins. The top computationally ranked HFpEF protein candidates were the same top ranked proteins in the comorbidity-domains and in the pathology-domains suggesting that these proteins are important drivers with convergent molecular networks underlying HFpEF. Cross-referencing and validating top-ranked computational HFpEF protein candidates with clinical myocardial and extracardiac biopsy data from HFpEF patients and corresponding controls revealed that most of these proteins are predominantly expressed in the liver, pancreas, adipose tissue, and lymph nodes, rather than in cardiac tissue. This finding supports the emerging concept that HFpEF is fundamentally a multisystemic disorder mediated by inter-organ signaling rather than a disease confined to the heart. Our computational study demonstrates the capacity of text mining to annotate, integrate, and prioritize protein-disease relationships from large-scale textual data, thereby providing a complementary framework to traditional omics approaches for biomarker discovery and drug target identification in CVDs.

Aim . To study novel biomarkers, as well as clinical and morphological features of myocardial remodeling, in patients with the diabetic phenotype (DP) of heart failure with preserved ejection fraction (HFpEF) hospitalized for elective coronary artery bypass grafting. Material and methods. A total of 120 patients of both sexes with stage I-IIA, class I-III HFpEF (60+60) (with or without type 2 diabetes (T2D)), and underlying coronary artery disease and hypertension were studied. In addition to standard examinations, blood levels of N-terminal pro-brain natriuretic peptide and oxytocin were measured, along with assessment of left ventricular (LV) myocardial remodeling and diastolic dysfunction types. The global LV function index was calculated, and general histological and immunohistochemical (caspase-3, bcl-2, ki- 67, and oxytocin receptors) investigations of right atrial appendage myocardial biopsies were performed. Results . Myocardial remodeling in DP of HFpEF was characterized by the predominance of eccentric hypertrophy (43%), type 2 diastolic dysfunction (p=0,028), lower LV ejection fraction (p=0,002), and lower LV global function index (p=0,042) compared to patients without T2D. The morphological profile of the myocardium in DP of HFpEF demonstrated significant activation of angiogenesis (p=0,006), apoptosis (p&lt;0,001), and proliferative potential of cardiomyocytes (p=0,049). The identified changes were accompanied by a significant decrease in blood oxytocin level (p&lt;0,001) and high expression of oxytocin receptors (p&lt;0,001) in the myocardium of patients with DP of HFpEF compared to the group without T2D. Conclusion . A distinctive feature of the myocardial remodeling marker panel in patients with HFpEF in this study was a low blood oxytocin level and a high cardiomyocyte apoptosis index.

Myocardial biopsy plays a critical role in the diagnosis of myocardial disorders, particularly in cases with undetermined etiology. This study was designed to assess the feasibility and safety of a novel approach-ultrasound-guided trans-thoracic myocardial biopsy. Fourteen patients underwent ultrasound-guided trans-thoracic biopsy for myocardial tissue sampling, with evaluation of potential complications. Among these patients, three were initially suspected of having cardiac amyloidosis (CA) based on the clinical evaluation, one was suspected of hypertrophic cardiomyopathy (HCM), one was referred for post-transplantation rejection monitoring, and one presented with a suspected cardiac tumor. The remaining eight cases were suspected to involve various types of cardiomyopathy or myocarditis. Myocardial tissue samples were obtained from 14 patients, yielding a total of 19 specimens. An average of 1.36 ± 0.6 samples was collected per patient, with a mean specimen length of 13.2 ± 5.2mm, which was adequate for histopathological assessment. Pericardial effusion occurred in two patients (14.2%), one of whom required percutaneous drainage, without progression to pericardial tamponade. No cases of nonsustained or sustained ventricular tachycardia, conduction disturbances, cardiac perforation, stroke, or pneumothorax were observed during the procedure or hospitalization. In all cases, the obtained myocardial specimens were sufficient for pathological evaluation. This study demonstrates that ultrasound-guided trans-thoracic myocardial biopsy is a technically feasible procedure with acceptable preliminary safety in a small, highly selected patient cohort.