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Introduction: Cardiac amyloidosis is a rarely reported and potentially fatal variant of the systemic disease. Its early diagnosis could potentially lead to significantly improved clinical outcomes. Case presentation: A 56-year-old female presented with dyspnea and palpitations. Her physical exam and non-invasive evaluation with cardiac magnetic resonance imaging (CMRI) revealed restrictive cardiomyopathy, and the bone marrow biopsy results showed systemic amyloidosis. Discussion: The diagnosis of cardiac amyloidosis is not always straightforward, and delay can cause the progression of the disease and an increased risk of morbidity and mortality. Electrocardiograms, echocardiograms, cardiac magnetic resonance imaging, and histopathologic evaluation are the main methods for diagnosing cardiac amyloidosis. The treatment consists of controlling heart failure symptoms and disease-modifying interventions, including medical and surgical therapeutic methods. Clinical learning point (conclusion): Cardiac involvement is the main cause of death in systemic amyloidosis. Early suspicion, diagnosis, and treatment are crucial in improving patients' survival. CMRI can play an essential role in the diagnosis of cardiac Amyloidosis. A graphical abstract is provided for visual summary. [ABSTRACT FROM AUTHOR]

Partial cavopulmonary shunt is an established procedure for patients with abnormal right ventricular (RV) physiology. Late failure of the Glenn shunt is usually due to further progression of the primary disease process. However, there may be surprises, as in our patient. We report an 8-year-old child who was diagnosed with tricuspid valve (TV) dysplasia with borderline RV hypoplasia. He underwent TV repair with a right cavopulmonary shunt. He presented with features of heart failure after 6 years of the surgery. An echocardiographic evaluation suggested a restrictive filling pattern of the RV with preserved size and function. Computed tomography and cardiac magnetic resonance imaging revealed a normal pericardial thickness with no evidence of myocardial involvement. Despite the contradicting clinical and imaging features, endomyocardial biopsy confirmed a diagnosis of desmin cardiomyopathy. Restrictive cardiomyopathy may remain an elusive diagnosis despite extensive imaging. In our case, the altered loading conditions due to a cavopulmonary shunt further masked pathophysiological hemodynamic changes.

Abstract Introduction Cardiac amyloidosis is a rarely reported and potentially fatal variant of the systemic disease. Its early diagnosis could potentially lead to significantly improved clinical outcomes. Case presentation A 56-year-old female presented with dyspnea and palpitations. Her physical exam and non-invasive evaluation with cardiac magnetic resonance imaging (CMRI) revealed restrictive cardiomyopathy, and the bone marrow biopsy results showed systemic amyloidosis. Discussion The diagnosis of cardiac amyloidosis is not always straightforward, and delay can cause the progression of the disease and an increased risk of morbidity and mortality. Electrocardiograms, echocardiograms, cardiac magnetic resonance imaging, and histopathologic evaluation are the main methods for diagnosing cardiac amyloidosis. The treatment consists of controlling heart failure symptoms and disease-modifying interventions, including medical and surgical therapeutic methods. Clinical learning point (conclusion) Cardiac involvement is the main cause of death in systemic amyloidosis. Early suspicion, diagnosis, and treatment are crucial in improving patients’ survival. CMRI can play an essential role in the diagnosis of cardiac Amyloidosis. A graphical abstract is provided for visual summary. Graphical Abstract

The follow-up of pregnant patients with cardiomyopathies is a challenge that every cardiologist will be facing sooner or later. We present the first case of a patient with restrictive cardiomyopathy and Alpha-B-crystallinopathy (distal myopathy type), who was followed up during two pregnancies. Cardiac follow-ups were carried out by short-term clinical status monitoring, echocardiography, ECG monitoring and NT-proBNP. At the same time, foetal ultrasound scans should be performed. Follow-up requires constant communication between the cardiologist and the gynaecologist. Any decision concerning the mother or the foetus should be made by consensus between both teams. Despite good follow-up, pregnancy in such complex patients remains a high risk due to heart. Heart failure and neuromuscular symptoms can worsen during or after pregnancy.

Background: Patients with restrictive cardiomyopathy (RCM) have impaired diastolic filling and hemodynamic congestion. Pulmonary transit time (PTT) and pulmonary blood volume index (PBVi) reflect the hemodynamic status, but the relationship with left ventricle (LV) dysfunction remains unclear. Purpose: To evaluate the PTT and PBVi in RCM patients, the association with diastolic dysfunction and LV deformation, and the effects on the occurrence of major adverse cardiac events (MACE) in RCM patients. Study Type: Retrospective. Population: 137 RCM patients (88 men, age 58.80 ± 10.83 years) and 68 age‐ and sex‐matched controls (46 men, age 57.00 ± 8.59 years). Field Strength/Sequence: 3.0T/Balanced steady‐state free precession sequence, recovery prepared echo‐planar imaging sequence, and phase‐sensitive inversion recovery sequence. Assessment: The LV function and peak strain (PS) parameters were measured. The PTT was calculated and corrected by heart rate (PTTc). The PBVi was calculated as the product of PTTc and RV stroke volume index. Statistical Tests: Chi‐squared test, student's t‐test, Mann–Whitney U test, Pearson's or Spearman's correlation, multivariate linear regression, Kaplan–Meier survival analysis, and Cox regression models analysis. A P‐value <0.05 was considered statistically significant. Results: The PTTc showed a significant correlation with the E/A ratio (r = 0.282), and PBVi showed a significant correlation with the E/e′ ratio, E/A ratio, and diastolic dysfunction stage (r = 0.222, 0.320, and 0.270). PTTc showed an independent association with LVEF, LV circumferential PS, and LV longitudinal PS (β = 0.472, 0.299, and 0.328). In Kaplan–Meier analysis, higher PTTc and PBVi were significantly associated with MACE. In multivariable Cox regression analysis, PTTc was a significantly independent predictor of the MACE in combination with both cardiac MRI functional and tissue parameters (hazard ratio: 1.23/1.32, 95% confidence interval: 1.10–1.42/1.20–1.46). Data Conclusion: PTTc and PBVi are associated with diastolic dysfunction and deteriorated LV deformation, and PTTc independently predicts MACE in patients with RCM. Level of Evidence: 3 Technical Efficacy: Stage 2 [ABSTRACT FROM AUTHOR]

OBJECTIVES Restrictive cardiomyopathy is rare and is generally associated with worse clinical outcomes compared to other cardiomyopathies. Ventricular assist device (VAD) support for these children is seldom applied and often hampered by the surgical difficulties. METHODS All paediatric (<19 years) patients with a restricted cardiomyopathy supported by a VAD from the EUROMACS database were included and compared to patients with a dilated cardiomyopathy (retrospective database analyses). Participating centres were retrospectively contacted to provide additional detailed echo and Swan Ganz measurements to analyse the effect of VAD support on pulmonary artery pressure and right ventricular function. RESULTS Forty-four paediatric VAD-supported patients diagnosed with restricted cardiomyopathy were included, with a median age at implantation of 5.0 years. Twenty-six of the 44 patient with a restricted cardiomyopathy survived to transplantation (59.1%), 16 died (36.4%) and 2 are still on ongoing VAD support (4.5%) after a median duration of support of 95.5 days (interquartile range 33.3–217.8). Transplantation probability after 1 and 2 years of VAD support in patients with a restricted cardiomyopathy were comparable to patients with a dilated cardiomyopathy (52.3% vs 51.4% and 59.5% vs 60.1%, P  = 0.868). However, mortality probability was higher in the restricted cardiomyopathy cohort (35.8% vs 17.0% and 35.8% vs 19.0%, P  = 0.005). Adverse event rates were high (cerebrovascular accident in 31.8%, pump thrombosis in 29.5%, major bleeding 25.0%, eventual biventricular support in 59.1%). In the atrially cannulated group, cerebrovascular accident and pump thrombosis occurred in twice as much patients (21.1% vs 40.0%, P  = 0.595 and 15.8% vs 40.0%, P  = 0.464; probably non-significant due to the small numbers). Pulmonary arterial pressures improved after implantation of a VAD, and 6 patients who were initially labelled as ineligible due to pulmonary hypertension could eventually be transplanted. CONCLUSIONS VAD support in children with a restricted cardiomyopathy is rarely performed. Mortality and adverse event rates are high. On the other hand, survival to cardiac transplantation was 59.1% with all patients surviving the 1st 30 days after cardiac transplantation. Pulmonary arterial pressures improved while on support, potentially making cardiac transplantation a viable option for previously ineligible children. [ABSTRACT FROM AUTHOR]

Purpose of Review: Cardiac amyloidosis (CA) is a condition characterized by misfolding and extracellular deposition of proteins, leading to organ dysfunction. While numerous forms of CA exist, two subtypes dominate clinical prevalence: Transthyretin amyloid (ATTR) and immunoglobulin light chain amyloid. Recent Findings: The current scientific landscape reflects the urgency to advance therapeutic interventions with over 100 ongoing clinical trials. Heart failure treatment is affected by CA phenotype with poor tolerance of otherwise frequently used medications. Treating comorbidities including atrial fibrillation and valvular disease remains a challenge in CA, driven by technical difficulties and uncertain outcomes. Tafamidis is the first ATTR-stabilizer approved with a rapidly growing rate of clinical use. In parallel, various new therapeutic classes are in late-stage clinical trials including silencers, antibodies and genetic therapy. Summary: Managing CA is a critical challenge for future heart failure care. This review delineates the current standard-of-care and scientific landscape of CA therapy. [ABSTRACT FROM AUTHOR]

Introduction: Hypereosinophilic Syndrome (HES) is a rare disorder characterized by persistent elevation of eosinophils, leading to multi-organ infiltration and damage. Eosinophilic Myocarditis (EM) is one of its severe complications contributing significantly to morbidity and mortality. Herein, we describe the diagnostic and therapeutic challenges of EM, emphasizing the significance of early recognition and multidisciplinary management. Case presentation: A 51-year-old female with a history of EM, heart failure, and peripheral eosinophilia presented with NYHA class 3b symptoms. Laboratory findings revealed elevated peripheral eosinophil count, NT-Pro BNP, and characteristic electrocardiogram abnormalities. Imaging studies confirmed biventricular thrombi and myocardial abnormalities consistent with EM. Treatment involved Solu-Medrol for HES and heparin for ventricular thrombi, leading to initial clinical improvement. However, refractory heart failure necessitated urgent heart transplantation. Discussion: EM, an under-recognized complication of HES, poses diagnostic and management challenges. Management includes standard heart failure treatments, steroids, and emerging therapies like Mepolizumab. Early diagnosis and aggressive management are pivotal for improving outcomes in this rare and potentially fatal condition. Conclusion: Advancements in the detection of complications, surgical management, and therapeutic options have improved outcomes in HES. Ongoing research is essential to further understand and address the diagnostic and therapeutic challenges of HES and EM. [ABSTRACT FROM AUTHOR]

Cardiomyopathies (CMs), one of the main causes of sudden death among the young population, are a heterogeneous group of myocardial diseases, usually with a genetic cause. Next-Generation Sequencing (NGS) has expanded the genes studied for CMs; however, the yield is still around 50%. The systematic study of Copy Number Variants (CNVs) could contribute to improving our diagnostic capacity. These alterations have already been described as responsible for cardiomyopathies in some cases; however, their impact has been rarely assessed. We analyzed the clinical significance of CNVs in cardiomyopathies by studying 11,647 affected patients, many more than those considered in previously published studies. We evaluated the yield of the systematic study of CNVs in a production context using NGS and a novel CNV detection software tool v2.0 that has demonstrated great efficacy, maximizing sensitivity and avoiding false positives. We obtained a CNV analysis yield of 0.8% that fluctuated depending on the type of cardiomyopathy studied (0.29% HCM, 1.41% DCM, 1.88% ARVC, 1.8% LVNC, 1.45% RCM), and we present the frequency of occurrence for 18 genes that agglutinate the 95 pathogenic/likely pathogenic CNVs detected. We conclude the importance of including in diagnostic tests a systematic study of these genetic alterations for the different cardiomyopathies. [ABSTRACT FROM AUTHOR]

Restrictive cardiomyopathy (RCM) is defined as increased myocardial stiffness and impaired diastolic relaxation leading to elevated ventricular filling pressures. Human variants in filamin C (FLNC) are linked to a variety of cardiomyopathies, and in this study, we investigate an in-frame deletion (c.7416_7418delGAA, p.Glu2472_Asn2473delinAsp) in a patient with RCM. Induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) with this variant display impaired relaxation and reduced calcium kinetics in 2D culture when compared with a CRISPR-Cas9-corrected isogenic control line. Similarly, mutant engineered cardiac tissues (ECTs) demonstrate increased passive tension and impaired relaxation velocity compared with isogenic controls. High-throughput small-molecule screening identifies phosphodiesterase 3 (PDE3) inhibition by trequinsin as a potential therapy to improve cardiomyocyte relaxation in this genotype. Together, these data demonstrate an engineered cardiac tissue model of RCM and establish the translational potential of this precision medicine approach to identify therapeutics targeting myocardial relaxation.

Abstract To provide accurate predictions, current machine learning-based solutions require large, manually labeled training datasets. We implement persistent homology (PH), a topological tool for studying the pattern of data, to analyze echocardiography-based strain data and differentiate between rare diseases like constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM). Patient population (retrospectively registered) included those presenting with heart failure due to CP (n = 51), RCM (n = 47), and patients without heart failure symptoms (n = 53). Longitudinal, radial, and circumferential strains/strain rates for left ventricular segments were processed into topological feature vectors using Machine learning PH workflow. In differentiating CP and RCM, the PH workflow model had a ROC AUC of 0.94 (Sensitivity = 92%, Specificity = 81%), compared with the GLS model AUC of 0.69 (Sensitivity = 65%, Specificity = 66%). In differentiating between all three conditions, the PH workflow model had an AUC of 0.83 (Sensitivity = 68%, Specificity = 84%), compared with the GLS model AUC of 0.68 (Sensitivity = 52% and Specificity = 76%). By employing persistent homology to differentiate the “pattern” of cardiac deformations, our machine-learning approach provides reasonable accuracy when evaluating small datasets and aids in understanding and visualizing patterns of cardiac imaging data in clinically challenging disease states.

Amyloid is an amorphous, fibrillar material formed from various abnormally folded proteins that deposits locally or systemically. Over 95% of cases have been attributed to light chain deposition (AL) or transthyretin deposition (ATTR) amyloidosis. The basic investigations in the evaluation of cardiac amyloidosis include the electrocardiogram, echocardiography and cardiac biomarkers. Echocardiography in a patient with cardiac amyloidosis shows biatrial enlargement, biventricular hypertrophy, diastolic dysfunction, interatrial septal thickening, valvular thickening, a glistening appearance of the interventricular septum, and pericardial effusion. Magnetic resonance imaging can help distinguish amyloidosis from other causes of infiltrative/restrictive cardiomyopathy, from example, sarcoidosis, hemochromatosis, and Fabry disease based on characteristic enhancement patterns in these diseases. The latest Expert Consensus recommends that serum/urine immunofixation electrophoresis along with a serum free light chain assay must be done in all the cases of suspected cardiac amyloidosis. If the light chain assays are positive, we proceed with tissue diagnosis for confirmation of AL amyloidosis. If the screening assays are negative for monoclonal gammopathy, the next step is to obtain cardiac scintigraphy. If the nuclear scan is negative, but the index of suspicion remains high, an endomyocardial biopsy can be done. Once amyloid is demonstrated in histopathologic specimens, it must be typed to distinguish between AL and ATTR. The ideal method for this is tandem mass spectrometry, although this may not be widely available. It has a sensitivity of 88% and specificity of 96% higher than other techniques 23. In resource-poor settings, immunohistochemistry or immunoelectron microscopy can allow this distinction, although with lesser sensitivity.

Abstract Background Kallmann–Morsier syndrome is a rare disease characterized by the association of congenital gonadotropic deficiency and anosmia or hyposmia. The cardiac manifestations associated with this syndrome are little known. Through this case, we will characterize the cardiac involvement of this disease in the light of what is already described in the literature. Case presentation We report the case of a young patient who presented with a picture of cardiac decompensation revealing restrictive heart disease. In her exploration, she was found to have primary amenorrhea, leading to the diagnosis of Kallmann syndrome. Medical treatment was optimized for the management of her cardiac decompensation as well as hormonal replacement treatment for her delayed puberty and growth. Conclusions Cardiac manifestations in Kallmann–Morsier syndrome are few reported in the literature, and restrictive heart disease is uncommon with no cases report till now. This association suggests a possible common genetic origin that should be explored in the future.

Abstract Background IgG4-related disease is a fibro-inflammatory disorder with an unknown etiology, which can affect multiple organ systems, including the cardiovascular system. While most reported cases of cardiovascular involvement are primarily associated with the aorta, there have been sporadic reports of isolated cardiac involvement. Case presentation This paper presents a documented case of IgG4-related systemic disease with symptoms indicative of restrictive cardiomyopathy. Subsequent Cardiac Magnetic Resonance imaging revealed diffuse myopericardial involvement, characterized by pericardial thickening and enhancement, accompanied by subepicardial and myocardial infiltration. Considering the rarity of cardiac involvement in our case, we conducted a thorough review of the existing literature pertaining to various patterns of cardiac involvement in IgG4-related disease, as well as the diagnostic modalities that can be employed for accurate identification and assessment. Conclusions This case report sheds light on the importance of recognizing and evaluating cardiac manifestations in IgG4-related systemic disease to facilitate timely diagnosis and appropriate management.

Cardiac amyloid cardiomyopathy (CM) is a rapidly progressive disease that is frequently underrecognized and frequently diagnosed late in a significant number of individuals suffering from heart failure. Cardiac amyloid infiltration resulting in myocardial hypertrophy and restrictive CM is primarily caused by the misfolding of precursor proteins such as transthyretin, light chain immunoglobulin, and apolipoprotein AI-IV. The utilization of echocardiography, cardiac magnetic resonance, and bone avid radiotracer scintigraphy are essential in establishing a reliable diagnosis and prognosis of cardiac amyloidosis in the majority of patients. However, in certain clinical scenarios, the use of cardiac or extracardiac biopsy is necessary. There are significant developments in the understanding of the pathobiology of amyloid formation, which has paved the way for the development of new-targeted therapies, specifically for transthyretin cardiac amyloidosis. Imaging techniques are developing to monitor quantitatively the progression and regression of cardiac and systemic amyloid infiltration.

Partial cavopulmonary shunt is an established procedure for patients with abnormal right ventricular (RV) physiology. Late failure of the Glenn shunt is usually due to further progression of the primary disease process. However, there may be surprises, as in our patient. We report an 8-year-old child who was diagnosed with tricuspid valve (TV) dysplasia with borderline RV hypoplasia. He underwent TV repair with a right cavopulmonary shunt. He presented with features of heart failure after 6 years of the surgery. An echocardiographic evaluation suggested a restrictive filling pattern of the RV with preserved size and function. Computed tomography and cardiac magnetic resonance imaging revealed a normal pericardial thickness with no evidence of myocardial involvement. Despite the contradicting clinical and imaging features, endomyocardial biopsy confirmed a diagnosis of desmin cardiomyopathy. Restrictive cardiomyopathy may remain an elusive diagnosis despite extensive imaging. In our case, the altered loading conditions due to a cavopulmonary shunt further masked pathophysiological hemodynamic changes. [ABSTRACT FROM AUTHOR]

Amyloidosis is a disease associated with accumulation and deposition of amyloid in the walls of capillaries and internal organs. Depending on the composition of amyloid substances, it is mainly divided into primary (AL), secondary (AA), familial (TTR) and wild type. The subclinical course, diffuse organ involvement and various symptoms that often overlap with those of other diseases predispose to underestimation of this disease and delay in its diagnosis and treatment. Due to the prominent health and economic aspect of amyloidosis and the possibilities of specific therapy, we present a clinical case of a 66-year-old female patient with proven AL type amyloidosis, currently undergoing treatment with Velcade, with a good therapeutic response. The symptoms of the patient's disease began in 2018, and their atypical nature and evolution posed a challenge to cardiologists, nephrologists and hematologists. Timely diagnosis, however, made it possible to start effective targeted cytostatic treatment. [ABSTRACT FROM AUTHOR]

Restrictive cardiomyopathy is one of the rarest forms of cardiomyopathies in paediatric patients characterised by impaired myocardial relaxation or compliance with restricted ventricular filling, leading to a reduced diastolic volume with a preserved systolic function. We report 2 cases—a 5-year-old boy who presented with abdominal distension and palpitation with family history of similar complaints but no definite genetic diagnosis as yet and a 5-year-old girl who presented with chronic cough and shortness of breath. Both cases were diagnosed in a tertiary care hospital in Muscat, Oman, in 2019 and are managed supportively with regular outpatient follow-up. This is the first series of reported cases of paediatric restrictive cardiomyopathy from Oman. [ABSTRACT FROM AUTHOR]

Background: Kallmann–Morsier syndrome is a rare disease characterized by the association of congenital gonadotropic deficiency and anosmia or hyposmia. The cardiac manifestations associated with this syndrome are little known. Through this case, we will characterize the cardiac involvement of this disease in the light of what is already described in the literature. Case presentation: We report the case of a young patient who presented with a picture of cardiac decompensation revealing restrictive heart disease. In her exploration, she was found to have primary amenorrhea, leading to the diagnosis of Kallmann syndrome. Medical treatment was optimized for the management of her cardiac decompensation as well as hormonal replacement treatment for her delayed puberty and growth. Conclusions: Cardiac manifestations in Kallmann–Morsier syndrome are few reported in the literature, and restrictive heart disease is uncommon with no cases report till now. This association suggests a possible common genetic origin that should be explored in the future. [ABSTRACT FROM AUTHOR]

Constrictive pericarditis (CP) is an uncommon but reversible cause of diastolic heart failure if appropriately identified and treated. However, its diagnosis remains a challenge for clinicians. Artificial intelligence may enhance the identification of CP. The authors proposed a deep learning approach based on transthoracic echocardiography to differentiate CP from restrictive cardiomyopathy. Patients with a confirmed diagnosis of CP and cardiac amyloidosis (CA) (as the representative disease of restrictive cardiomyopathy) at Mayo Clinic Rochester from January 2003 to December 2021 were identified to extract baseline demographics. The apical 4-chamber view from transthoracic echocardiography studies was used as input data. The patients were split into a 60:20:20 ratio for training, validation, and held-out test sets of the ResNet50 deep learning model. The model performance (differentiating CP and CA) was evaluated in the test set with the area under the curve. GradCAM was used for model interpretation. A total of 381 patients were identified, including 184 (48.3%) CP, and 197 (51.7%) CA cases. The mean age was 68.7 ± 11.4 years, and 72.8% were male. ResNet50 had a performance with an area under the curve of 0.97 to differentiate the 2-class classification task (CP vs CA). The GradCAM heatmap showed activation around the ventricular septal area. With a standard apical 4-chamber view, our artificial intelligence model provides a platform to facilitate the detection of CP, allowing for improved workflow efficiency and prompt referral for more advanced evaluation and intervention of CP. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: IgG4-related disease is a fibro-inflammatory disorder with an unknown etiology, which can affect multiple organ systems, including the cardiovascular system. While most reported cases of cardiovascular involvement are primarily associated with the aorta, there have been sporadic reports of isolated cardiac involvement. Case presentation: This paper presents a documented case of IgG4-related systemic disease with symptoms indicative of restrictive cardiomyopathy. Subsequent Cardiac Magnetic Resonance imaging revealed diffuse myopericardial involvement, characterized by pericardial thickening and enhancement, accompanied by subepicardial and myocardial infiltration. Considering the rarity of cardiac involvement in our case, we conducted a thorough review of the existing literature pertaining to various patterns of cardiac involvement in IgG4-related disease, as well as the diagnostic modalities that can be employed for accurate identification and assessment. Conclusions: This case report sheds light on the importance of recognizing and evaluating cardiac manifestations in IgG4-related systemic disease to facilitate timely diagnosis and appropriate management. [ABSTRACT FROM AUTHOR]

Alpha-B-crystallin, a member of the small heat shock family of proteins, has been implicated in a variety of cardiomyopathies and in normal cardiac homeostasis. It is known to function as a molecular chaperone, particularly for desmin, but also interacts with a wide variety of additional proteins. The molecular chaperone function is also enhanced by signal-dependent phosphorylation at specific residues under stress conditions. Naturally occurring mutations in CRYAB, the gene that encodes alpha-B-crystallin, have been suggested to alter ionic intermolecular interactions that affect dimerization and chaperone function. These mutations have been associated with myofibrillar myopathy, restrictive cardiomyopathy, and hypertrophic cardiomyopathy and promote pathological hypertrophy through different mechanisms such as desmin aggregation, increased reductive stress, or activation of calcineurin–NFAT signaling. This review will discuss the known mechanisms by which alpha-B-crystallin functions in cardiac homeostasis and the pathogenesis of cardiomyopathies and provide insight into potential future areas of exploration. [ABSTRACT FROM AUTHOR]

Cardiomyopathy is a heart disease clinically characterized by enlargement of the heart, arrhythmia and heart failure alone or simultaneously. Ischemic cardiomyopathy is usually caused by coronary atherosclerotic lesions, but non-ischemic cardiomyopathy (NICM) is different. It is caused by non-coronary atherosclerotic lesions which can cause heart failure, arrhythmia, and even sudden death. However, the pathogeny, diagnosis and treatment methods of NICM are still unclear, and the efficacy needs to be explored further. The article analyzes the pathogeny, diagnosis, current status of drugs and non-drug treatment of NICM, aiming to provide more reference materials for the early prevention of patients with NICM and provide direction for the diagnosis and treatment of NICM.

IntroductionHypereosinophilic Syndrome (HES) is a rare disorder characterized by persistent elevation of eosinophils, leading to multi-organ infiltration and damage. Eosinophilic Myocarditis (EM) is one of its severe complications contributing significantly to morbidity and mortality. Herein, we describe the diagnostic and therapeutic challenges of EM, emphasizing the significance of early recognition and multidisciplinary management.Case presentationA 51-year-old female with a history of EM, heart failure, and peripheral eosinophilia presented with NYHA class 3b symptoms. Laboratory findings revealed elevated peripheral eosinophil count, NT-Pro BNP, and characteristic electrocardiogram abnormalities. Imaging studies confirmed biventricular thrombi and myocardial abnormalities consistent with EM. Treatment involved Solu-Medrol for HES and heparin for ventricular thrombi, leading to initial clinical improvement. However, refractory heart failure necessitated urgent heart transplantation.DiscussionEM, an under-recognized complication of HES, poses diagnostic and management challenges. Management includes standard heart failure treatments, steroids, and emerging therapies like Mepolizumab. Early diagnosis and aggressive management are pivotal for improving outcomes in this rare and potentially fatal condition.ConclusionAdvancements in the detection of complications, surgical management, and therapeutic options have improved outcomes in HES. Ongoing research is essential to further understand and address the diagnostic and therapeutic challenges of HES and EM.

Eosinophilic myocarditis can result in endomyocardial fibrosis affecting both ventricles, leading to restrictive cardiomyopathy. Multimodality imaging is crucial for diagnosis, as demonstrated in this case of a patient presenting with symptoms of heart failure. [ABSTRACT FROM AUTHOR]

The discovery of hypertrophic cardiomyopathy (HCM) dates back to 1958, when the pathologist Donald Teare of the St. George’s Hospital in London performed autopsies in eight cases with asymmetric hypertrophy of the ventricular septum and bizarre disorganization (disarray) at histology, first interpreted as hamartoma. Seven had died suddenly. The cardiac specimens were cut along the long axis, similar to the 2D echo. In the same year, at the National Institute of Health U.S.A., Eugene Braunwald, a hemodynamist, and Andrew Glenn Morrow, a cardiac surgeon, clinically faced a patient with an apparently similar morbid entity, with a systolic murmur and subaortic valve gradient. “Discrete” subaortic stenosis was postulated. However, at surgery, Dr. Morrow observed only hypertrophy and performed myectomy to relieve the obstruction. This first Braunwald–Morrow patient underwent a successful cardiac transplant later at the disease end stage. The same Dr. Morrow was found to be affected by the familial HCM and died suddenly in 1992. The term “functional subaortic stenosis” was used in 1959 and “idiopathic hypertrophic subaortic stenosis” in 1960. Years before, in 1957, Lord Brock, a cardiac surgeon at the Guy’s Hospital in London, during alleged aortic valve surgery in extracorporeal circulation, did not find any valvular or discrete subaortic stenoses. In 1980, John F. Goodwin of the Westminster Hospital in London, the head of an international WHO committee, put forward the first classification of heart muscle diseases, introducing the term cardiomyopathy (dilated, hypertrophic, and endomyocardial restrictive). In 1995, the WHO classification was revisited, with the addition of two new entities, namely arrhythmogenic and purely myocardial restrictive, the latter a paradox of a small heart accounting for severe congestive heart failure by ventricular diastolic impairment. A familial occurrence was noticed earlier in HCM and published by Teare and Goodwin in 1960. In 1989–1990, the same family underwent molecular genetics investigation by the Seidman team in Boston, and a missense mutation of the β-cardiac myosin heavy chain in chromosome 14 was found. Thus, 21 years elapsed from HCM gross discovery to molecular discoveries. The same original family was the source of both the gross and genetic explanations of HCM, which is now named sarcomere disease. Restrictive cardiomyopathy, characterized grossly without hypertrophy and histologically by myocardial disarray, was found to also have a sarcomeric genetic mutation, labeled “HCM without hypertrophy”. Sarcomere missense mutations have also been reported in dilated cardiomyopathy (DCM) and non-compaction cardiomyopathy. Moreover, sarcomeric gene defects have been detected in some DNA non-coding regions of HCM patients. The same mutation in the family may express different phenotypes (HCM, DCM, and RCM). Large ischemic scars have been reported by pathologists and are nowadays easily detectable in vivo by cardiac magnetic resonance with gadolinium. The ischemic arrhythmic substrate enhances the risk of sudden death.

Research on cardiomyopathy models using engineered heart tissue (EHT) created from disease‐specific induced pluripotent stem cells (iPSCs) is advancing rapidly. However, the study of restrictive cardiomyopathy (RCM), a rare and intractable cardiomyopathy, remains at the experimental stage because there is currently no established method to replicate the hallmark phenotype of RCM, particularly diastolic dysfunction, in vitro. In this study, we generated iPSCs from a patient with early childhood‐onset RCM harboring the TNNI3 R170W mutation (R170W‐iPSCs). The properties of R170W‐iPSC‐derived cardiomyocytes (CMs) and EHTs were evaluated and compared with an isogenic iPSC line in which the mutation was corrected. Our results indicated altered calcium kinetics in R170W‐iPSC‐CMs, including prolonged tau, and an increased ratio of relaxation force to contractile force in R170W‐EHTs. These properties were reversed in the isogenic line, suggesting that our model recapitulates impaired relaxation of RCM, i.e., diastolic dysfunction in clinical practice. Furthermore, overexpression of wild‐type TNNI3 in R170W‐iPSC‐CMs and ‐EHTs effectively rescued impaired relaxation. These results highlight the potential efficacy of EHT, a modality that can accurately recapitulate diastolic dysfunction in vitro, to elucidate the pathophysiology of RCM, as well as the possible benefits of gene therapies for patients with RCM. [ABSTRACT FROM AUTHOR]

Background The echocardiographic determination of cardiac causes of stroke focuses on the presence of left ventricular thrombus, valvular vegetations, and patent foramen ovale. Transoesophageal echocardiogram (TEE) is indicated when the transthoracic echocardiogram (TTE) is inconclusive or when there is clinical suspicion of cardiac causes that may have been missed by TTE. The presence of severe diastolic dysfunction on TTE in the absence of any other cardiac abnormality or cardiac history is not usually considered a clue to the cause of stroke. Case summary This is a case of a 52-year-old woman who presented with a stroke. Transthoracic echocardiogram was inconclusive for source of embolus. Transoesophageal echocardiogram revealed left atrial appendage (LAA) thrombus and severely hypokinetic LAA, despite the patient being in normal sinus rhythm (NSR). Retrospective analysis of diastolic function on the prior TTE revealed severe restrictive diastolic dysfunction with evidence of elevated left ventricular end-diastolic pressure. While technetium pyrophosphate scan was negative, magnetic resonance imaging was consistent with cardiac amyloid and further testing revealed multiple myeloma as the cause of the amyloid light chain amyloidosis. This case highlights the importance of scrutinizing diastolic function in patients with a source of embolus and careful assessment for LAA thrombus on TEE, despite NSR. Discussion We present a patient with stroke with inconclusive TTE findings and eventual diagnosis of restrictive cardiomyopathy secondary to cardiac amyloidosis from an undiagnosed multiple myeloma. Severe restrictive diastolic function on TTE may be a clue to the discovery of LAA thrombus on TEE. [ABSTRACT FROM AUTHOR]

Amyloid is an amorphous, fibrillar material formed from various abnormally folded proteins that deposits locally or systemically. Over 95% of cases have been attributed to light chain deposition (AL) or transthyretin deposition (ATTR) amyloidosis. The basic investigations in the evaluation of cardiac amyloidosis include the electrocardiogram, echocardiography and cardiac biomarkers. Echocardiography in a patient with cardiac amyloidosis shows biatrial enlargement, biventricular hypertrophy, diastolic dysfunction, interatrial septal thickening, valvular thickening, a glistening appearance of the interventricular septum, and pericardial effusion. Magnetic resonance imaging can help distinguish amyloidosis from other causes of infiltrative/restrictive cardiomyopathy, from example, sarcoidosis, hemochromatosis, and Fabry disease based on characteristic enhancement patterns in these diseases. The latest Expert Consensus recommends that serum/urine immunofixation electrophoresis along with a serum free light chain assay must be done in all the cases of suspected cardiac amyloidosis. If the light chain assays are positive, we proceed with tissue diagnosis for confirmation of AL amyloidosis. If the screening assays are negative for monoclonal gammopathy, the next step is to obtain cardiac scintigraphy. If the nuclear scan is negative, but the index of suspicion remains high, an endomyocardial biopsy can be done. Once amyloid is demonstrated in histopathologic specimens, it must be typed to distinguish between AL and ATTR. The ideal method for this is tandem mass spectrometry, although this may not be widely available. It has a sensitivity of 88% and specificity of 96% higher than other techniques 23. In resource-poor settings, immunohistochemistry or immunoelectron microscopy can allow this distinction, although with lesser sensitivity. [ABSTRACT FROM AUTHOR]

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Restrictive cardiomyopathy (RCM) is characterized by restrictive ventricular pathophysiology determined by increased myocardial stiffness. While suspicion of RCM is initially raised by clinical evaluation and supported by electrocardiographic and echocardiographic findings, invasive hemodynamic evaluation is often required for diagnosis and management of patients during follow-up. RCM is commonly associated with a poor prognosis and a high incidence of heart failure, and PH is reported in paediatric patients with RCM. Currently, only a few therapies are available for specific RCM aetiologies. Early referral to centres for advanced heart failure treatment is often necessary. The aim of this review is to address questions frequently asked when facing paediatric patients with RCM, including issues related to aetiologies, clinical presentation, diagnostic process and prognosis. [ABSTRACT FROM AUTHOR]

Cardiomyopathies are a significant contributor to cardiovascular morbidity and mortality, mainly due to the development of heart failure and increased risk of sudden cardiac death (SCD). Despite improvement in survival with contemporary treatment, SCD remains an important cause of mortality in cardiomyopathies. It occurs at a rate ranging between 0.15% and 0.7% per year (depending on the cardiomyopathy), which significantly surpasses SCD incidence in the age‐ and sex‐matched general population. The risk of SCD is affected by multiple factors including the aetiology, genetic basis, age, sex, physical exertion, the extent of myocardial disease severity, conduction system abnormalities, and electrical instability, as measured by various metrics. Over the past decades, the knowledge on the mechanisms and risk factors for SCD has substantially improved, allowing for a better‐informed risk stratification. However, unresolved issues still challenge the guidance of SCD prevention in patients with cardiomyopathies. In this review, we aim to provide an in‐depth discussion of the contemporary concepts pertinent to understanding the burden, risk assessment and prevention of SCD in cardiomyopathies (dilated, non‐dilated left ventricular, hypertrophic, arrhythmogenic right ventricular, and restrictive). The review first focuses on SCD incidence in cardiomyopathies and then summarizes established and emerging risk factors for life‐threatening arrhythmias/SCD. Finally, it discusses validated approaches to the risk assessment and evidence‐based measures for SCD prevention in cardiomyopathies, pointing to the gaps in evidence and areas of uncertainties that merit future clarification. [ABSTRACT FROM AUTHOR]

An earlier healthy 64-year-old man with previous surgery for bilateral carpal tunnel syndrome (CTS) in his 50s, presented with dyspnoea on exertion. Cardiac amyloidosis was suspected due to "red flag" signs and symptoms. Further investigations with scintigraphy and genetic testing confirmed the diagnosis of hereditary ATTR variant (ATTRv) amyloidosis. This is the first case report of ATTRv amyloidosis in a patient of Norwegian origin and is caused by the mutation E54A (p.E74A) in the transthyretin (TTR) gene. This mutation is previously not reported in international databases. Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed disease with a poor prognosis. Early recognition remains essential to afford the best treatment efficacy. [ABSTRACT FROM AUTHOR]

This document provides an overview of the 2023 ESC guidelines for the management of cardiomyopathies. The guidelines aim to assist healthcare professionals in diagnosing and managing patients with cardiomyopathies based on the best available clinical evidence. They propose a classification system with five phenotypes of cardiomyopathies and emphasize the importance of a multidisciplinary approach to patient care. The guidelines recommend the use of contrast-enhanced cardiac magnetic resonance and genetic testing for diagnostic purposes. Treatment options include medication, devices, and cardiac transplantation, and exercise recommendations are tailored to individual patients. [Extracted from the article]

BackgroundRestrictive cardiomyopathy (RCM) represents a rare cardiovascular disorder stemming from filament-associated genes. Nonetheless, treating RCM presents considerable challenges, particularly concerning device implantation and mechanical support. Furthermore, elucidating the molecular function of specific variants holds promise in benefiting patients and enhancing prognosis, given the significant heterogeneity among RCM variants.Case presentationThe proband, an eight-year-old female, was admitted to our hospital post cardiopulmonary resuscitation due to sudden cardiac arrest. Echocardiography revealed bilateral atrial enlargement. Whole-exome sequencing uncovered a novel heterozygous mutation (c.509G>A, p.R170Q) in TNNI3. Evaluation using the MutationTaster application deemed c.509G>A pathogenic (probability = 0.99). Following clinical manifestations, imaging assessments, and genetic screening, the proband received an RCM diagnosis. ECMO was recommended along with continuous renal replacement therapy. However, persistent atrial flutter ensued post-ECMO withdrawal. Attempts to restore cardiac rhythm with cardioversion, metoprolol, and amiodarone proved futile. Subsequent heart failure led to the patient's demise due to cardiac shock. Based on crystal protein structural analysis, we observed that cTnI-R170Q and R170W exerted similar impacts on protein structural stability and formation. However, both differed significantly from cTnI-R170G, primarily influencing amino acid regions 32–79 and 129–149, involved in TnC and actin binding. Therefore, cTnI-R170Q was revealed to induce RCM via the same molecular mechanism as cTnI-R170W.ConclusionManaging RCM remains a critical challenge. This study underscores the discouragement of device implantations for cardiac pump functional support in RCM, particularly for non-short-term scheduled HTx. Additionally, considering catheter ablation for atrial fibrosis-induced AFs is recommended. Mechanistically, cTnI-R170Q primarily diminishes troponin-actin interactions and destabilizes thin filaments.

Objective: To explore the diagnostic value of cardiac magnetic resonance feature tracking (CMR-FT) divided left atrial (LA) strain in differentiating constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM). Methods: Patients with CP (n = 40) and RCM (n = 40), and another 40 normal control group were retrospectively enrolled over a period of 8 years at a tertiary cardiac centre. Left ventricular (LV) and biatrial strain and strain rate (SR) were measured. Atrial strain was used to differentiate between patients with CP and RCM. Then, patients were grouped according to their left ventricular ejection fraction (LVEF), either ≥50% or

Background Restrictive cardiomyopathy (RCM) is characterized by impaired diastolic function with preserved ventricular contraction. Several pathogenic variants in sarcomere genes, including TNNI3, are reported to cause Ca2+ hypersensitivity in cardiomyocytes in overexpression models; however, the pathophysiology of induced pluripotent stem cell (iPSC)‐derived cardiomyocytes specific to a patient with RCM remains unknown. Methods and Results We established an iPSC line from a pediatric patient with RCM and a heterozygous TNNI3 missense variant, c.508C>T (p.Arg170Trp; R170W). We conducted genome editing via CRISPR/Cas9 technology to establish an isogenic correction line harboring wild type TNNI3 as well as a homozygous TNNI3‐R170W. iPSCs were then differentiated to cardiomyocytes to compare their cellular physiological, structural, and transcriptomic features. Cardiomyocytes differentiated from heterozygous and homozygous TNNI3‐R170W iPSC lines demonstrated impaired diastolic function in cell motion analyses as compared with that in cardiomyocytes derived from isogenic‐corrected iPSCs and 3 independent healthy iPSC lines. The intracellular Ca2+ oscillation and immunocytochemistry of troponin I were not significantly affected in RCM‐cardiomyocytes with either heterozygous or homozygous TNNI3‐R170W. Electron microscopy showed that the myofibril and mitochondrial structures appeared to be unaffected. RNA sequencing revealed that pathways associated with cardiac muscle development and contraction, extracellular matrix‐receptor interaction, and transforming growth factor‐β were altered in RCM‐iPSC‐derived cardiomyocytes. Conclusions Patient‐specific iPSC‐derived cardiomyocytes could effectively represent the diastolic dysfunction of RCM. Myofibril structures including troponin I remained unaffected in the monolayer culture system, although gene expression profiles associated with cardiac muscle functions were altered.

Abstract Background Diabetes mellitus (DM) is the most common metabolic disease worldwide and a major risk factor for adverse cardiovascular events, while the additive effects of DM on left ventricular (LV) deformation in the restrictive cardiomyopathy (RCM) cohort remain unclear. Accordingly, we aimed to investigate the additive effects of DM on LV deformation in patients with RCM. Materials and methods One hundred thirty-six RCM patients without DM [RCM(DM−)], 46 with DM [RCM (DM+)], and 66 age- and sex-matched control subjects who underwent cardiac magnetic resonance (CMR) scanning were included. LV function, late gadolinium enhancement (LGE) type, and LV global peak strains (including radial, circumferential, and longitudinal directions) were measured. The determinant of reduced LV global myocardial strain for all RCM patients was assessed using multivariable linear regression analyses. The receiver operating characteristic curve (ROC) was performed to illustrate the relationship between DM and decreased LV deformation. Results Compared with the control group, RCM (DM−) and RCM(DM+) patients presented increased LV end-diastolic index and end-systolic volume index and decreased LV ejection fraction. LV GPS in all three directions and longitudinal PDSR progressively declined from the control group to the RCM(DM−) group to the RCM(DM+) group (all p

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Abstract Background Endomyocardial fibrosis is a grim disease. It is the most common restrictive cardiomyopathy worldwide, but the exact etiology and pathogenesis both remain unknown. Endomyocardial fibrosis is recurrently associated with chronic eosinophilia and probable dietary, environmental, and infectious factors, which contribute not only to the onset of the disease (an inflammatory process) but also to its progression and maintenance (endomyocardial damage and scar formation). The trademark of the disease is the fibrotic obliteration of the affected ventricle. The combination of such processes produces focal or diffuse endocardial thickening and fibrosis, which leads to restrictive physiology. Endomyocardial fibrosis affects the apices of the right and the left ventricle in around 50% of cases and most often extends to the posterior leaflet of the mitral valve. Sometimes it involves the papillary muscle and chordae tendineae, causing atrioventricular valve dysfunction. The fibrosis does not affect extracardiac organs. This cardiomyopathy is most recurrent in tropical areas of the world. Case presentation A 67-year-old Black male with past medical history of schistosomiasis infection in childhood presented with progressive dyspnea, lower extremity edema, and weakness for 2 years. He was diagnosed with endomyocardial fibrosis. The echocardiogram showed an increased thickness in the septum (17 mm) and free left ventricular wall (15 mm), obliteration of the left ventricular apex and inflow tract, and mitral valve regurgitation. Cardiac magnetic resonance imaging revealed apical left ventricle wall thickening with left ventricular apical obliteration associated with enlargement of the respective atrium. Delayed enhancement imaging showed endomyocardium enhancement involving left ventricular apex, mitral valve regurgitation due to annulus dilation, and a thrombus at left ventricular apex. He underwent open heart surgery with mitral valve replacement, endocardial decortication, endomyocardiectomy, and two-vessel coronary artery bypass grafting as preoperative coronary angiogram showed mild right coronary artery and proximal left anterior descending artery severe lesions. Postoperative course was uncomplicated, and he was discharged successfully from the hospital. Six months after surgery, he was New York Heart Association functional class I. Conclusion The purpose of this case report is to illustrate the aspects of endomyocardial fibrosis by reporting a case of this entity. In conclusion, progress in imaging techniques and treatment in a reference institution for cardiac diseases contribute to earlier diagnosis and survival in patients with endomyocardial fibrosis.

Background: Restrictive cardiomyopathy (RCM) comprises diverse etiologies with overall poor prognosis. Emerging therapies have significantly impacted some of these entities. However, these therapies may have limited impact in the end-stages and have only recently become available. We sought to assess outcomes before and after transplant in the RCM population stratified into 3 distinct time periods from the recent era. Methods: Retrospective analysis of the United Network of Organ Sharing registry (n = 62,709) for all patients transplanted between 1987 and March 1, 2022, were stratified by RCM status with 1157 patients with RCM. Populations were grouped temporally into classic (1987-2000), contemporary (2000-2013), and current (2014-2022) eras. Multiorgan and repeat transplants were excluded from the analysis. Baseline demographics, listing status, hemodynamics, donor information, and life support methods were compared using Kruskal-Wallis and Pearson’s tests. Longitudinal survival was assessed via Kaplan-Meier survival analysis. Univariate and multivariate analyses using Cox modeling and competing outcomes analyses were performed. Results: RCM patients were older, female, with older donors and longer ischemic times (p

We report the case of a 50-year-old woman with secondary oxalosis following bowel resection resulting in restrictive cardiomyopathy and a diagnosis of cardiac amyloidosis based on the initial workup. The case documented findings by cardiac magnetic resonance imaging and technetium Tc 99m–labeled pyrophosphate scan in patients with cardiac oxalosis, which can mimic findings in cardiac amyloidosis, expanding the differential diagnosis.