Restrictive Cardiomyopathy Research Articles (Page 1)

Cardiomyopathies are rare diseases in children but are the primary indication for heart transplantation in this age group. Various causes of paediatric cardiomyopathies, ranging from gene-mediated to underlying infection or systemic disease, result in a wide spectrum of clinical presentations and imaging manifestations. Over the years, the classification and terminology of cardiomyopathy have evolved in children and are currently primarily based on the imaging phenotype (dilated, hypertrophic, and restrictive) and then subdivided based on pathogenesis, organ involvement, genetic or familial inheritance pattern, and aetiology. Dilated and hypertrophic cardiomyopathies are more common than non-compaction, restrictive, and arrhythmogenic cardiomyopathies. Echocardiography remains the first-line modality for functional and structural cardiac assessment. However, cardiac magnetic resonance imaging enhances diagnostic accuracy, provides serial cardiac functional evaluation and tissue characterization, and facilitates individual risk stratification and management in patients with heterogeneous phenotypes. This review provides an overview of paediatric cardiomyopathies with a focus on magnetic resonance imaging indications, technique, and key imaging findings that influence management decision-making.

Restrictive cardiomyopathy (RCM) is an uncommon condition with heterogeneous causes. Amyloidosis, a major subtype, presents with diagnostic complexity, economic burden, and prognostic implications. This study aimed to apply machine learning (ML) techniques to improve the diagnosis of amyloidosis among RCM patients and assess the cost-effectiveness of laboratory tests. This study included patients with RCM who underwent transthoracic echocardiography (TTE) and cardiac magnetic resonance imaging (MRI). Feature selection was performed using least absolute shrinkage and selection operator (LASSO) regression based on variables that showed statistically differences between groups. These selected features were then used to construct eight ML models, which were trained and validated using leave-one-out cross-validation. The best-performing model was evaluated for sample size and interpreted using Shapley additive explanations (SHAP) to enhance model transparency. Laboratory testing costs related to autoimmune, infectious, tumor-related, and amyloidosis evaluations were compared across subgroups. The Random Forest (RF) model achieved the best performance, with an area under the curve (AUC) of 0.977, an accuracy of 0.908, a sensitivity of 0.869, and a specificity of 0.927. The model also showed a favorable Brier score and a satisfying effect size, indicating good performance in distinguishing amyloidosis from other RCM subtypes. Cost analysis revealed that patients without underlying autoimmune, infectious, or tumor-related etiologies incurred unnecessary expenditures. Multivariate regression identified key imaging features associated with amyloidosis, including left ventricular posterior wall (LVPW) and left ventricular ejection fraction (LVEF) from TTE, and left ventricular short axis (LVSA), LVEF, and interventricular septum (IVS) thickness from cardiac MRI. This study established an interpretable ML model based on the RF algorithm and accurately distinguished amyloidosis among RCM patients. By guiding more targeted use of amyloidosis-specific testing, the model offers a potential cost-saving strategy while improving diagnostic efficiency. These findings support the clinical integration of ML-based tools to streamline decision-making and optimize the allocation of healthcare resources.

Background: Restrictive cardiomyopathy (RCM) is a rare cardiac condition characterized by stiff and noncompliant ventricular walls, leading to impaired diastolic filling and normal or near-normal systolic function. This condition often presents with subtle symptoms of heart failure. We present a compelling case of longstanding atrial fibrillation (Afib) and atrial flutter (AFL) culminating in refractory cardiogenic shock, ultimately revealing an undiagnosed restrictive cardiomyopathy. Case: A 40-year-old male with a history of persistent Afib and AFL, unremarkable cardiac MRI on first occurrence for atrial arrhythmias, presented with dyspnea, dizziness, fatigue, and palpitations while on dofetilide. He was found to have atypical AFL with a rapid ventricular response, refractory to pharmacological and electrical cardioversion. His arrhythmia history included multiple catheter ablations for recurrent atrial fibrillation: pulmonary vein and posterior box isolation, anterior wall homogenization, mitral annulus flutter ablation as well as focal atrial tachycardia ablation in the coronary sinus. His family history revealed a sister with refractory Afib at age 30, later diagnosed with restrictive cardiomyopathy, who underwent orthotopic heart transplantation (OHT) at age 44. On admission, echocardiography revealed severe right atrial enlargement and grade III diastolic dysfunction. Attempts at rate and rhythm control with multiple agents were unsuccessful. On day 2 of admission, he developed cardiogenic shock (CI 1.5, RA 20, PCWP 40, PA 50/30 [mPA 40], PVR 3, CPO 0.53, PAPI 1.0), necessitating V-A extracorporeal membrane oxygenation and Impella CP for circulatory support. Discussion: RCM often eludes early detection due to its presentation with preserved ejection fraction and relatively subtle heart failure symptoms. However, Afib or AFL refractory to ablation or cardioversion may serve as an early indication, especially in the context of a strong family history. We suspect progression of cardiomyopathy in this patient who, years ago, had a normal cardiac MRI. Identifying RCM through advanced imaging or genetic screening is crucial, as it enables early consideration of interventions, such as evaluation for OHT, which may prevent catastrophic outcomes. Proactive screening and repeat imaging, such as cardiac MRI, in patients with incessant atrial arrhythmias who also have a significant familial burden, can mitigate delays in treatment and improve prognosis.

Introduction: An 85-year-old man presented to the hospital with acute on chronic diastolic heart failure secondary to transthyretin cardiac amyloidosis. He has a known history of grade III diastolic dysfunction with NYHA Class IIIb symptoms. His past medical history includes paroxysmal atrial fibrillation on Sotalol, hypertension, Type 2 diabetes mellitus, chronic kidney disease stage 3B, hypothyroidism, restrictive cardiomyopathy with heart failure with reduced ejection fraction, and prior triple vessel coronary artery bypass graft. On Presentation: Initial clinical findings including vitals, labs, and imaging are summarized in Figure 1 He was initially treated with intravenous furosemide but had limited response. It was noted that during atrial fibrillation his symptoms worsened, likely due to loss of atrial kick. His home sotalol was changed to amiodarone to improve rhythm control, but this resulted in bradycardia, further contributing to symptoms. Hypothesis: Given his restrictive cardiomyopathy, we suspected a fixed stroke volume and heart rate dependency for cardiac output (CO). Thus, we proceeded with right heart catheterization to better assess his volume status and hemodynamics. Methods: A pulmonary artery catheter was placed for pressure and CO measurements, along with a temporary right atrial pacemaker wire. Pulmonary artery and pulmonary capillary wedge pressures, along with thermodilution CO, were recorded at baseline and during atrial pacing at multiple rates to assess hemodynamic changes. Results: Hemodynamic parameters at baseline and during atrial pacing are shown in Figure 2 . Gradual increases in atrial pacing led to reductions in pulmonary artery and wedge pressures, while cardiac output remained stable. These findings suggest that in restrictive physiology with chronotropic incompetence, modest atrial pacing may lower filling pressures as a result of shortened diastolic filling time, without compromising cardiac output. Conclusion: Current treatment of advanced diastolic heart failure ( Figure 3 ) focuses primarily on preload reduction. We propose atrial pacing to shorten diastolic filling time as an alternate approach to lower left ventricular filling pressures. Further studies are warranted to explore device-based therapy for these patients.

A 63-year-old female with mixed connective tissue disease on long-term immunosuppression (prednisone, azathioprine, hydroxychloroquine (HCQ)) was referred to a tertiary care center for evaluation of progressive dyspnea and exertional chest discomfort. Cardiac history included transient complete heart block and ventricular tachycardia with dual-chamber AICD, and severe aortic stenosis with bicuspid aortic valve. Laboratory evaluation was notable for NT pro-BNP > 5000 pg/mL and elevated but adynamic troponin (300-500 ng/L). Electrocardiogram revealed atrial pacing with first degree atrioventricular block. Echocardiogram confirmed severe aortic stenosis, elevated filling pressures, abnormal left ventricular longitudinal strain and LV hypertrophy. Cardiac MRI, sarcoid PET, and PYP SPECT/CT were without any evidence of edema, scar, inflammation or amyloid deposition. Catheterization revealed severe pulmonary hypertension and elevated filling pressures, without significant coronary disease. Medical treatment included empagliflozin (discontinued due to urosepsis), bumetanide, spironolactone, and metoprolol succinate. Neither TAVR nor transition to biventricular pacing improved LV function. Ultimately, endomyocardial biopsy was performed, revealing histologic features of HCQ-induced cardiotoxicity, including myocyte hypertrophy and interstitial fibrosis. HCQ was discontinued. She was referred to Rheumatology for alternative treatments. HCQ induced cardiomyopathy represents <2% of adverse events of patients treated with HCQ, presenting as hypertrophic or restrictive cardiomyopathy with conduction abnormalities. Mean treatment duration in HCQ cardiomyopathies is approximately 12.7 years. Confirmation of diagnosis requires endomyocardial biopsy, as imaging findings are often non-specific. Management involves discontinuing the offending agent and optimizing heart failure therapy. Around 45% of patients with HCQ cardiomyopathy exhibit resolution of cardiac function following medication discontinuation. This case emphasizes the importance of a systematic approach to unexplained heart failure, particularly in patients with long-term HCQ use. Infiltrative or toxic cardiomyopathies should be considered when imaging suggests myocardial dysfunction. Multimodal imaging and biopsy are crucial for diagnosis. Early recognition is essential to prevent irreversible myocardial damage and improve long-term outcomes.

Cardiomyopathies (CM) are rare, inherited heart diseases. Major types include dilated, hypertrophic, restrictive, and arrhythmogenic right ventricular cardiomyopathy. Hypertrophic cardiomyopathy is the most common. Genetic diagnostic testing can identify disease genes associated with inherited cardiomyopathies, which are crucial for diagnosis, risk stratification, and family screening. This study evaluated the outcomes of clinical genetic testing in patients with suspected HCM and CM/DCM over a five-year period. A retrospective analysis was performed on 949 patient samples with unexplained moderate to severe cardiomyopathy/dilated cardiomyopathy and/or hypertrophic cardiomyopathy referred to clinical genetics laboratory for genetic testing between 2016 and 2024 were included in the study. Among these, 475 were for suspected HCM and 474 for suspected CM/DCM. Genetic screening was performed by next generation sequencing technique. The variants were annotated using disease databases (HGMD, OMIM, ClinVar), Population databases (1000G, ExAC, GnomAD and Indian population specific database). ExomeDepth (v1.1.10), a read-depth comparison method, detected copy number variants (CNVs) from targeted sequence data by comparing test data to a matched aggregate reference dataset. The data was sequentially filtered and variants were prioritized based on clinical symptoms and classified according to ACMG 2015 guidelines. All previously reported variants were re-evaluated using current international databases and classification standards. Diagnostic yield, gene-wise distribution, and reclassification rates were analyzed. Mean age of the subjects (n = 949) was 32 ± 20 years, 66.3% male [Figure 1]. The overall diagnostic yield was 31.7% (301/949), [Figure 2]. HCM had a higher yield of 38.3% (182/475), with the majority of pathogenic variants found in MYBPC3 (37.9%) and MYH7 (35.2%), [Figure 3]. CM/DCM showed a 25.1% yield (119/474), with key genes being TTN (22.7%) and DSP and MYH7 (6.7%) . We detected copy number variants in 5 of them (2LP; 3VUS). Variant reclassification affected 183 samples (22.05%), with 85 upgraded and 98 downgraded and thus the clinical interpretation. Genetic testing yields actionable findings in both HCM and DCM, with greater impact in HCM. Reclassification of variants using updated guidelines improves diagnostic clarity and management strategies. These findings support routine re-evaluation of genetic results in inherited cardiomyopathy care.

Backround: Cardiac amyloidosis (CA) leads to restrictive cardiomyopathy, heart failure, and increased thromboembolic risk. This hypercoagulability condition is determined by the mechanical atrial dysfunction associated with blood stasis and by amyloid deposition linked to endothelial dysfunction. The identification of intracardiac thrombosis and coronary artery disease (CAD) in CA patients remains challenging due to the limitations of conventional imaging methods. Hypothesis: We hypothesize that cardiac computed tomography (CCT) can reliably assess myocardial features, intracardiac thrombosis, and CAD in patients with CA. Methods: We enrolled patients with a recently confirmed or suspected CA diagnosis and a clinical indication for CCT. Photon-counting detector-computed tomography (PCCT) NAEOTOM Alpha protocol included unenhanced imaging for coronary artery calcium (CAC) score, contrast-enhanced angiography for CAD evaluation, and delayed-phase imaging for thrombosis, late iodine enhancement (LIE), and extracellular volume (ECV) assessment. The ECV quantification was based on late-PCCT scan and iodine images of the myocardium. Results: A total of 16 adults (14 transthyretin and 2 light chain CA, 87% male, mean age 78 years) were recruited. CCT showed an Agatson score of 329 (mean), with a score 3 in 40%; obstructive CAD was detected in 1 patient (6%, anterior descending artery disease); myocardial bridge in 19%. LIE displayed an ischemic pattern in 1 patient, while in the others there was a diffuse non-ischemic pattern involving both ventricles (66%) and both atria (15%)(figure 1). No intracardiac thrombi were detected. In the recruited population, ECV was 38% at 5 minutes (figure). Conclusions: CCT may be an effective non-invasive tool for guiding the management of CA, assessing myocardial features like ECV, and LIE, and identifying CAD and structural anomalies in CA patients. It may aid in ruling out cardiac thrombi and support comprehensive patient evaluation, highlighting its potential to guide diagnosis and management in CA patients. Further research is needed to explore the potential role of CCT and the ECV assessment in the diagnostic and therapeutic algorithm of CA.

Background: Transthyretin cardiac amyloidosis (ATTR-CM) is becoming a more prominent and recognized etiology for diastolic heart failure. The debut of disease-modifying therapies have emphasized the importance of early diagnosis in disease course. Screening criteria have highlighted increased left ventricular wall thickness (LVWT) over 1.2 cm as a threshold to suspect cardiac amyloidosis. However, we previously demonstrated that left ventricular wall thickness may be an unreliable screening marker in these patients and highly variable. We aimed to 1) characterize the diagnostic journey of patients with ATTR-CM with LVWT ≤ 1.2 cm and 2) determine alternative screening pathways to better capture more patients with ATTR-CM. Methods: Our study extracted a cohort from a database of all patients diagnosed with ATTR-CM at single large academic center from January 2006 to March 2024. For each of these 1845 patients, dimensions were abstracted from the echocardiogram closest to the diagnosis date. A cohort of 319 (17.2%) patients diagnosed with ATTR-CM with normal posterior wall thickness (≤ 1.2 cm) were sub-selected and evaluated by manual chart abstraction to categorize pre-specified diagnostic pathways. Data were then evaluated to compare the prevalence of various diagnostic pathways. Results: Among 319 patients with diagnosed ATTR-CM, 198 (62.1%) patients were diagnosed with routine evaluation for restrictive cardiomyopathy and 37 (11.6%) were diagnosed as a part of our mandated ATTR-CM screening for TAVR (Table 1). Seventy-two patients were diagnosed with tissue pathology (8.8% with carpal tunnel pathology, 4.4% with intraoperative cardiac pathology, and 3.4% with other noncardiac pathology). Conclusion: Wall thickness may be an unreliable marker in screening patients with ATTR-CM. Clinicians should maintain a high degree of suspicion of and vigilance among select patients with undifferentiated heart failure and lower thresholds for upfront evaluation with imaging or biopsy.

Background: Cardiac troponin I (cTnI, encoded by TNNI3 ) inhibits contraction by preventing actin-myosin interaction. Pathogenic TNNI3 variants can cause cardiomyopathy, but no targeted therapies exist. We identified a family with restrictive cardiomyopathy carrying the cTnI A157V variant. Previously, we generated a homozygous mouse model (cTnI A158V, murine equivalent) that showed impaired cardiac relaxation on invasive hemodynamics but had normal lifespan and no cardiac hypertrophy or fibrosis. Aims: It is known that murine models of cardiomyopathies often exhibit milder phenotypes than humans, limiting their translational utility. Hence, to better model human disease, we generated a homozygous cTnI A158V pig model using CRISPR-Cas9. We aimed to characterize phenotypic and molecular differences between the mouse and pig models to gain insight into disease mechanisms. Methods: Heart tissue was collected from wild-type (WT) and homozygous A158V mice (9-10 months) and from WT and homozygous A158V pigs (2 months). Bulk RNA sequencing (RNA-seq) was performed on RNA extracted from A158V pig hearts (n=5) and compared to publicly available data from age-matched WT pigs (n=10) supplemented by one in-house WT control. Protein lysates were analyzed by Western blot. Isolated myofibrils were measured using the fast solution switching method. Results: A158V pigs had 100% mortality by 2 months (n=7), with gross hypertrophy and fibrosis. Myofibril studies showed significant prolongation of the linear relaxation phase in both A158V pigs (p<0.01) and mice (p<0.01) compared to respective WTs, with no significant differences in active tension in both models. Both models showed reduced phosphorylation of cTnI at serine 23/24, reaching significance in pigs (p=0.046) but not in mice (p=0.064). Unsupervised clustering of bulk-RNAseq data separated A158V from WT, with genotype explaining 44% and 53% of transcriptional variation in mice and pigs, respectively. Gene set enrichment analysis revealed significant upregulation of inflammatory pathways in A158V pigs only. Conclusions: Both A158V mouse and pig models recapitulate impaired cardiac relaxation seen in affected patients as shown by myofibril studies. However, the pig model more closely mirrors the human phenotype, including early mortality, hypertrophy, and fibrosis. Inflammatory pathway upregulation was observed only in A158V pigs, suggesting that inflammation may play a role in the severity or progression of disease.

Background: A subset of patients with non-dilated left ventricular cardiomyopathy (ND-LVCM) presents with restrictive-like physiology despite preserved left ventricular size. However, the pathological and imaging correlates of this diastolic dysfunction remain insufficiently characterized. Hypothesis: We hypothesized that diastolic dysfunction in ND-LVCM is associated with myocardial fibrosis or infiltration and corresponds with specific echocardiographic and MRI findings. Methods: We retrospectively analyzed 169 patients with ND-LVCM (LV end-diastolic diameter <55 mm) who underwent endomyocardial biopsy, cardiac MRI, and echocardiography including global longitudinal strain (GLS). Fibrosis was quantified using Masson's trichrome staining and categorized into interstitial, subendocardial, or perivascular patterns. In cardiac amyloidosis, Congo red–positive deposition was semi-quantified as diffuse, scattered, or perivascular. Restrictive-like physiology was defined by LA diameter >40 mm, E/e′ >15, elevated BNP, and LVEF ≥50%. Results: Diagnoses included cardiac amyloidosis (n=56), sarcoidosis (n=14), Fabry disease (n=12), hypertensive cardiomyopathy (n=49), and hypertrophic cardiomyopathy (n=38). Approximately 40% of patients exhibited restrictive-like physiology. These patients demonstrated significantly greater fibrosis burden (median 10.1% vs. 5.6%, p<0.001), higher prevalence of interstitial and perivascular fibrosis, and more frequent mid-wall or subepicardial late gadolinium enhancement (LGE) on MRI. Echocardiography showed reduced GLS and shortened deceleration time in these cases. In amyloidosis, diffuse deposition was particularly associated with more pronounced impairment in diastolic markers. Fabry disease was characterized by impaired relaxation without overt restrictive features, while sarcoidosis presented with heterogeneous diastolic profiles. Conclusions: Restrictive diastolic physiology in ND-LVCM spans multiple etiologies and correlates with distinct histologic and imaging features. An integrated approach combining echocardiography, MRI, and myocardial biopsy offers valuable insights into disease mechanisms and may aid in the differentiation of restrictive cardiomyopathy phenotypes.

Background: Hypereosinophilic syndrome (HES) is a rare systemic condition characterized by persistent eosinophilia with potential cardiac involvement, manifesting as Loeffler endocarditis. Cardiac involvement in HES can closely resemble infective endocarditis both clinically and echocardiographically, complicating diagnosis and appropriate management. Case Presentation: A 33-year-old woman with sickle cell disease (HbSS) presented with vaso-occlusive crisis, persistent fever, and a new cardiac murmur suggestive of mitral regurgitation. Initial transthoracic echocardiography revealed a mobile, vegetation-like mass (0.9×1.5 cm) on the posterior mitral leaflet (Figure 1). Blood cultures transiently yielded Escherichia coli, prompting treatment with antibiotics for suspected infective endocarditis. Despite antibiotic treatment, the patient continued to have febrile episodes and labs were notable for significant eosinophilia (>1500/µL), raising suspicion for a non-infectious etiology such as Loeffler endocarditis. Methodology: Transesophageal echocardiography demonstrated an extensive lesion (1.4×1.3 cm) contiguous with the subvalvular myocardium, consistent with mural involvement and fibrotic changes atypical for bacterial endocarditis but highly suggestive of eosinophilic endocarditis (Figures 2-3). Comprehensive hematologic evaluation identified elevated serum IgE, tryptase levels, and confirmed the presence of the FIP1L1-PDGFRA fusion gene, supporting a diagnosis of myeloproliferative HES. Results: The patient's management subsequently shifted to targeted HES therapy with high-dose corticosteroids, alongside supportive treatments with hydroxyurea and exchange transfusions for sickle cell disease. Following this adjustment, the patient showed rapid clinical improvement, and follow-up imaging confirmed regression of the cardiac lesion. Discussion: This case highlights the essential role of multimodal echocardiography for differentiating Loeffler endocarditis—with significant myocardial infiltration and fibrosis—from infective endocarditis, especially in atypical cases involving rare pathogens like Gram-negative bacteria. Clinicians should maintain a high index of suspicion for underlying inflammatory causes when faced with persistent symptoms refractory to antibiotics. Early recognition of Loeffler endocarditis enables prompt targeted anti-inflammatory therapy with steroids--thereby improving patient outcomes and preventing progression to restrictive cardiomyopathy.

Relevance . Life-threatening conditions in pediatric oncology are caused either by tumor diseases or treatment of a tumor disease (chemotherapy-induced cardiotoxicity after the administration of anthracyclines, high doses of cyclophosphamide, ifosfamide, etc.). Cardiotoxicity occurs over weeks to months and may manifest as restrictive cardiomyopathy with impaired diastolic function or dilated cardiomyopathy with thinning of the left ventricular wall and development of left ventricular systolic dysfunction. Information on the survival of pediatric patients with malignant neoplasms after veno-arterial extracorporeal membrane oxygenation (VA-ECMO) followed by orthotopic heart transplantation is not found in the published literature. Purpose of the study – to present the experience of a multidisciplinary and multicenter approach in the treatment of a child with osteosarcoma in the event of life-threatening cardiomyopathy with acute circulatory failure, the use of VA-ECMO and subsequent heart transplantation. Materials and methods . A description of a clinical case of treatment of a 13-year-old child with relapse of osteosarcoma after primary treatment in 9-year-old. The child underwent 5 courses of polychemotherapy with the inclusion of anthracyclines without exceeding cumulative doses. After completion of treatment, the child was diagnosed with chemotherapy-induced dilated cardiomyopathy, manifested by congestive heart failure and the development of cardiogenic shock. The child was initiated for vital indications VA-ECMO followed by orthotopic heart transplantation within 10 days. Conclusion. During the time the patient was on ECMO, no significant complications were recorded; the child was in remission of the underlying disease, which made it possible to perform a successful donor heart transplantation with standard immunosuppressive therapy. During the observation period of 14 months, the heart transplant functioned satisfactorily.

Biventricular endomyocardial fibrosis mimicking infective endocarditis

Cardiac amyloidosis is a rare condition often recognised as restrictive cardiomyopathy caused by extracellular accumulation of proteins in the myocardium. A more seldom form is amyloidoma, a solitary, localised tumour-like deposition of amyloid. A man in his forties presented with lethargy, chest discomfort and fever over the preceding three weeks. Transoesophageal echocardiography (TEE) revealed an intracardiac tumour causing severe obstruction and secondary increased diastolic pressure gradient between the left atrium and ventricle. Emergency surgery revealed large tumour masses in both atria, predominantly on the left side. The patient died perioperatively within 24 hours of admission to the local hospital. Histopathological examination confirmed the diagnosis of amyloidoma. Cardiac amyloidoma is an extremely rare finding that can lead to severe haemodynamic compromise. This case highlights the importance of considering cardiac tumours in young adults with atypical cardiac symptoms and urgent investigation with TEE.

Background and aims Sodium-glucose transporter 2 inhibitors have recently shown promise as a therapy to reduce mortality and hospitalisation for heart failure (HF) in patients with and without type 2 diabetes mellitus. The aim of this prospective study was to determine the results of a multiparametric evaluation after the addition of dapagliflozin to standard therapy in patients with heart failure with reduced ejection fraction (HFrEF). Methods From February to November 2022, 45 patients with chronic HF who regularly visited our HF outpatient clinic were selected for this study. Exclusion criteria were severe chronic renal insufficiency (GFR < 25 ml/min), type 1 diabetes, hypertrophic or restrictive cardiomyopathy, active myocarditis, constrictive pericarditis. The included patients took dapagliflozin once daily in addition to sacubitril/valsartan and other HF drugs. The following parameters were recorded before the start of therapy and at the 3-month follow-up: NYHA functional class, characteristics of the cardiopulmonary exercise test (CPET), parameters of the six-minute walk test (6MWT), quality of life (QoL) using the Kansas City Cardiomyopathy Questionnaire (KCCQ), echocardiographic evaluation. Results At 3-month follow-up, a significant increase in peak Vo2 (from 17.5 to 18.2, p < 0.001) and a significant decrease in VE/VCO2 (35.2 to 33.1, p = 0.011) were observed. In addition, Vo2/work gradient and pulse O2 increased significantly. Furthermore, a significant improvement in 6MWT, quality of life and left ventricular dimensions and systolic function was observed. Conclusion This prospective, multiparametric study showed that the additional administration of dapaglifozin to sacubitril/valsartan and other HF drugs is effective after three months.

Introduction . Loeffler endocarditis (LE) is a rare restrictive cardiomyopathy characterized by endocardial and myocardial eosinophil infiltration followed by degranulation, intracardiac thrombus formation, and fibrosis. Fibrosis leads to progressive heart failure (HF), requiring heart transplantation in the end stage. Brief description . A case report of a 20-year-old female patient with LE is presented. The patient presented chest pain, dyspnea, weakness, low-grade fever, and severe eosinophilia (eosinophil count up to 50%, white blood cell count up to 48×109/l). Diagnostic search for eosinophilia causes (eosinophilic leukemia, hematological malignancies, parasitic infections, systemic diseases) did not yield any results. Against the background of progressive heart failure and a decrease in the left ventricular ejection fraction to 35%, the patient was transferred to a federal center. Conservative therapy compensated heart failure, and there were no indications for heart transplantation. Over the next year, there were rehospitalizations to federal centers. Weakness, shortness of breath, grade III mitral regurgitation and eosinophilia persisted. The absence of a permanent attending physician and supervising medical facility made follow-up difficult. Discussion. It seems beneficial to create a registry of LE patients, route patients to specialized centers and manage outpatient follow-up by a multidisciplinary team. This case emphasizes the importance of early diagnosis and timely treatment of LE to improve the prognosis, as well as the need to increase physician awareness of this pathology.

Transthyretin (ATTR) cardiac amyloidosis is an infiltrative, restrictive cardiomyopathy that causes heart failure with both preserved and reduced ejection fraction. Historically considered a disease without treatment, the approval of transthyretin stabilizers brought about a major shift in the paradigm. Following closely on the heels of tafamidis, the United States Food and Drug Administration approved acoramidis for patients with ATTR cardiac amyloidosis in 2024. Similar approvals were also seen across Japan, the European Union, and the United Kingdom. Acoramidis is a highly potent transthyretin (TTR) stabilizer. The mechanism of action of acoramidis centers around its interaction with the unique ultrastructure of the TTR tetramer. The TTR tetramer comprises 2 linked homodimers that are stabilized by the binding of a thyroxine molecule. Acoramidis mimics the transthyretin-stabilizing T119M mutation, stabilizing the tetramer by 2 mechanisms. First, by binding to the TTR thyroxine-binding site to serve as a bridging molecule between the 2 dimeric subcomponents of the tetramer, it dramatically improves its kinetic stability. Second, it engages in hydrogen bond-based enthalpic binding. Cumulatively, this helps achieve TTR stabilization to the order of >90%. In clinical trials, acoramidis has demonstrated a robust safety profile. Acoramidis also improved clinical outcomes such as all-cause mortality and cardiovascular hospitalizations; improved biomechanistic parameters such as 6-minute walk distances, n-terminal pro B-type natriuretic peptide levels, stabilization of myocardial thickness; as well as improved patient-reported outcomes through improved Kansas City Cardiomyopathy Questionnaire scores. The results of the ACT-EARLY trial exploring the preventive benefits of acoramidis are eagerly awaited.

Background: Conventional HF treatment in transthyretin cardiac amyloidosis (ATTR-CA) resulting in restrictive cardiomyopathy is debated due to absent trial evidence in this specific sub-population of heart failure (HF) patients. Current European Society of Cardiology guidelines recommend the use of diuretics and mineralocorticoid receptor antagonists (MRAs). However, beta-blockers (BBs) and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEi/ARBs) are often discontinued due to hypotension or bradycardia. This study assesses real-world HF treatment patterns and their impact on survival in a multinational ATTR-CA cohort. Methods: A retrospective analysis of 794 ATTR-CA patients examined baseline BB, ACEi/ARB, and MRA prescriptions. The cohort was divided based on guideline publication dates. Results: Patients were predominantly male (73.2%) with a median age of 78 years. Prescription of diuretics (52.8%) and disease-modifying therapy (44.9%), mostly tafamidis, was common. BBs (43.7%) and ACEi/ARBs (41.2%) were prescribed more often in patients with higher NYHA class, elevated NT-proBNP, and more comorbidities. Blood pressure and heart rate were similar regardless of BB or ACEi/ARB use. BB prescription and combination therapy with BB and ACEi/ARB increased over time. Neither BB nor ACEi/ARB use significantly impacted mortality when analyzed in a multivariate Cox proportional hazard regression. Conclusions: Use of BBs and ACEi/ARBs has increased over time, particularly in advanced-stage ATTR-CA patients, and although these therapies appear to be reasonably tolerated, survival was not significantly altered.

Cardiomyopathy is a disorder of the myocardium, in which structural and functional abnormalities of the heart muscle result in mechanical and/or electrical cardiac dysfunction. Aging increases susceptibility to molecular damage and related risks of cardiomyopathy, often in combination with other chronic diseases and geriatric syndromes (e.g., frailty, sarcopenia). With the rapidly growing population of older adults, awareness of the most prevalent cardiomyopathies in this population provides important insight to optimize prevention and treatment. Hypertrophic, restrictive and dilated cardiomyopathies are highly prevalent in older adults. Furthermore, coronary artery disease, hypertension and valve disease increase with aging, and often lead to myocardial abnormalities that have many similar features to cardiomyopathy that are important to clarify. This review provides important age-related perspectives regarding pathophysiology, diagnosis, management and prevention. Aging is associated with inflammation and oxidative stress thatcan lead to molecular damage and vulnerability to many chronic diseases,including various cardiomyopathies. However, development is not inevitable. Prevention via lifestyle modification is paramount, with novelgerotherapeutic options targeting biologic hallmarks of aging underinvestigation. This increases the potential to improve the lifespan andhealthspan of older adults.

Cardiac amyloidosis (CA) is an increasingly recognized cause of restrictive cardiomyopathy characterized by amyloid fibril deposition in the heart, leading to severe functional impairments and poor prognosis. This review aims to provide a comprehensive overview of the pathophysiology of CA, emphasizing the mechanisms underlying functional capacity limitations and highlighting the importance of precise physiological assessment tools. We focus on objective measures such as cardiopulmonary exercise testing, field-based functional tests, and frailty evaluations that are vital for prognosis and tailoring patient care. With recent advances in disease-modifying therapies extending survival, maintaining and improving functional status through multidisciplinary rehabilitation emerges as a crucial therapeutic target. Evidence suggests that structured aerobic and resistance training can enhance exercise tolerance, strength, and quality of life in CA patients, although further research is needed to optimize rehabilitation protocols. By integrating clinical, physiological, and rehabilitative insights, this review underscores the value of a patient-centered approach aimed at preserving functional capacity and improving outcomes in this complex and systemic disease.