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Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease worldwide and may present with or without dynamic left ventricular outflow tract obstruction (LVOTO). Significant advances have been made in the management of obstructive HCM. On the other hand, despite their significant symptomatic burden, patients with non-obstructive HCM (nHCM) (i.e., without LVOTO) still do not have evidence-based therapeutical options. The recent IMPROVE-HCM study, a phase 2 randomized, double-blinded trial, aims to place a first step in filling this gap in knowledge. The study assessed the safety (primary endpoint) and efficacy (secondary endpoint) of ninerafaxstat, a novel cardiac mitotrope drug that increases adenosine triphosphate production. We highlighted the main findings of the trial, contextualizing these results within the larger landscape of completed and ongoing trials in nHCM. [ABSTRACT FROM AUTHOR]

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Aims/Background Research evidence has demonstrated a significant association between hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF), but the causality and pattern of this link remain unexplored. Therefore, this study investigated the causal relationship between HCM and AF using a two-sample and bidirectional Mendelian randomization (MR) approach. Additionally, this assessed the role of cardiovascular proteins (CPs) associated with cardiovascular diseases between HCM and AF by applying a two-step MR analysis. Methods Data for HCM, AF, and 90 CPs were obtained from the Finn Gen and IEU Open GWAS Project databases. MR-Egger, inverse variance weighting (IVW), weighted median estimator (WME), weighted mode, and simple mode were used to estimate causal inferences. Furthermore, Cochran's Q test, MR-Egger's intercept terms, and Leave-one-out methods determined the heterogeneity, horizontal pleiotropy, and sensitivity. Additionally, mediation effects were used to assess the role of CPs in the relationship between HCM and AF. Results Two-sample and bidirectional MR analysis revealed HCM as a risk factor for AF (odds ratio (OR) = 1.008, 95% confidence interval (CI): 1.001–1.016, p = 0.029) and AF was found to increase the risk of developing HCM (OR = 1.145, 95% CI: 0.963–1.361, p = 0.126). Moreover, Two-step MR analyses indicated that 5 CPs were causally associated with HCM; 12 CPs with AF and 1 CP (Melusin) with both HCM and AF. Additionally, Melusin was observed as a protective factor for both HCM and AF and may serve as a mediator variable for these two conditions (mediation effect 0.0004, mediation ratio 5.5178%, 95% CI: 5.4624–5.5731). Conclusion HCM may increase the risk of developing AF, with Melusin serving as a mediator for this risk. [ABSTRACT FROM AUTHOR]

Abstract Background Intracardiac leiomyomatosis (ICL) is an uncommon condition characterized by the proliferation of intravascular tissue within the veins, leading to the development of tumor emboli. This can pose a significant threat to life when the tumor invades cardiac structures. The diagnostic process for this condition is complex and presents considerable challenges. Case presentation We report a case of a 38-year-old female patient whose pulmonary artery computed tomography (CT) revealed low density structure in the branches of the pulmonary artery. Echocardiography revealed a mobile tumor within the right heart chambers and pulmonary trunks as well as characteristic thickening of the ventricular septum consistent with hypertrophic cardiomyopathy (HCM). Magnetic resonance imaging (MRI) revealed a mass in the right anterior uterine wall, extending to the inferior vena cava (IVC) and right iliac vein. Post-surgery histopathological analysis confirmed a diagnosis of intravenous leiomyomatosis (IVL). Conclusions When IVL affects the heart, echocardiography is the best diagnostic tool for detecting the disease. CT and MRI are essential in identifying the location and extent of the tumor, as well as in evaluating prognosis.

Abstract Aims Chronic low‐grade inflammation, often observed in hypertrophic cardiomyopathy (HCM), promotes adverse ventricular remodelling. This study aimed to investigate the relationship between inflammatory markers and myocardial fibrosis (MF) in patients with HCM. Methods and results This study included 102 patients with complete baseline data who underwent septal myectomy. Myocardial samples were stained with Masson's trichrome and analysed to determine myocardial collagen content and MF levels. Plasma levels of inflammatory markers were measured using standard laboratory procedures. Univariate and multivariate logistic regression analyses were performed to explore the relationship between the inflammatory markers and MF. Among the 102 participants included in the analysis, the mean age was 48.9 years, with 69 [67.6%] being men. The overall MF ranged from 2.5% to 40.7% (mean = 15.2 ± 8.1%, median = 13.0%, IQR = 9.9%–18.4%). Participants were divided into two groups based on a median MF of 13%. The high MF group had a larger left atrial diameter and left ventricular ejection fraction. Levels of interleukin (IL)‐2, tumour necrosis factor (TNF)‐α and interferon (IFN)‐α were significantly higher in patients with high MF compared to those with low MF (2.3 vs. 4.0 pg/mL, 3.1 vs. 3.9 pg/mL, 4.2 vs.4.7 pg/mL, respectively; all P

Abstract Aims There are limited data to support direct oral anticoagulant (DOAC) use in patients with hypertrophic cardiomyopathy (HCM) and non‐valvular atrial fibrillation (NVAF). The current study investigated the safety and effectiveness of DOACs versus warfarin in patients in Japan. Methods This retrospective observational study assessed a Japanese cohort of patients diagnosed with HCM and NVAF between July 2011 and June 2021 using a Japanese claims database. Propensity score (PS) matching (2:1 DOAC:warfarin) using the nearest‐neighbour method was applied to balance demographic and clinical characteristics between treatment groups. The primary outcomes were the risk of major bleeding and any bleeding (major or minor). Secondary outcomes included describing baseline demographic and clinical characteristics and the risk of stroke/systemic embolism (SE). Results After PS matching, 2955 DOAC‐ and 1603 warfarin‐treated patients were assessed. The mean [standard deviation (SD)] age in the DOAC and warfarin groups was 74.8 (10.5) and 75.3 (10.2) years, respectively. The majority of patients were male (DOAC, 58.8%; warfarin, 59.6%), had comorbidities (DOAC, 97.5%; warfarin, 96.6%), and were treated with β‐blockers (DOAC, 62.5%; warfarin, 62.3%). The risk of major and any bleeding was similar across cohorts [hazard ratio (HR), 0.80; 95% confidence interval (CI), 0.50–1.27; P = 0.336 and HR, 0.93; 95% CI, 0.78–1.11; P = 0.420] while the risk of stroke/SE was lower among patients treated with DOACs (HR, 0.67; 95% CI, 0.47–0.96; P = 0.027). Factors associated with an increased risk of major bleeding included prior bleeding (HR, 1.97; 95% CI, 1.22–3.17) and chronic kidney disease (HR, 1.87; 95% CI, 1.10–3.18). An increased risk of stroke/SE was associated with prior ischaemic stroke (HR, 2.97; 95% CI, 2.05–4.29), peripheral arterial disease (HR, 1.88; 95% CI, 1.22–2.88) and chronic kidney disease (HR, 1.87; 95% CI, 1.24–2.83). Conclusions DOAC‐treated patients had a lower risk of stroke/SE and a comparable risk of bleeding compared with warfarin‐treated patients. Prior stroke was shown to augment stroke risk by approximately three‐fold. This large real‐world study suggests that patients diagnosed with HCM and NVAF can be safely and effectively treated with DOACs in Japan.

Hypertrophic cardiomyopathy, a genetic hereditary disease, is highly regarded in clinical practice due to its unique pathophysiological changes, course characteristics, and hemodynamic features. With the continuous advance of treatment methods such as medications and surgeries, the prevention, treatment and prognosis of hypertrophic cardiomyopathy has gradually improved. However, inappropriate use of positive inotropic drugs may lead to serious consequences that are difficult to reverse. Therefore, how to smoothly navigate through the perioperative period and ensure clinical safety poses a great challenge for anesthesiologists. This paper discusses the perioperative management of patients with hypertrophic cardiomyopathy, with the hope of enhancing anesthesiologists' management capabilities for this type of disease.

Abstract Hypertrophic cardiomyopathy (HCM) caused by autosomal-dominant mutations in genes coding for structural sarcomeric proteins, is the most common inherited heart disease. HCM is associated with myocardial hypertrophy, fibrosis and ventricular dysfunction. Hypoxia-inducible transcription factor-1α (Hif-1α) is the central master regulators of cellular hypoxia response and associated with HCM. Yet its exact role remains to be elucidated. Therefore, the effect of a cardiomyocyte-specific Hif-1a knockout (cHif1aKO) was studied in an established α-MHC719/+ HCM mouse model that exhibits the classical features of human HCM. The results show that Hif-1α protein and HIF targets were upregulated in left ventricular tissue of α-MHC719/+ mice. Cardiomyocyte-specific abolishment of Hif-1a blunted the disease phenotype, as evidenced by decreased left ventricular wall thickness, reduced myocardial fibrosis, disordered SRX/DRX state and ROS production. cHif1aKO induced normalization of pro-hypertrophic and pro-fibrotic left ventricular remodeling signaling evidenced on whole transcriptome and proteomics analysis in α-MHC719/+ mice. Proteomics of serum samples from patients with early onset HCM revealed significant modulation of HIF. These results demonstrate that HIF signaling is involved in mouse and human HCM pathogenesis. Cardiomyocyte-specific knockout of Hif-1a attenuates disease phenotype in the mouse model. Targeting Hif-1α might serve as a therapeutic option to mitigate HCM disease progression.

Abstract Background Hypertrophic cardiomyopathy (HCM) is a frequently encountered cardiac condition worldwide, often inherited, and characterized by intricate phenotypic and genetic manifestations. The natural progression of HCM is diverse, largely due to mutations in the contractile and relaxation proteins of the heart. These mutations disrupt the normal structure and functioning of the heart muscle, particularly affecting genes that encode proteins involved in the contraction and relaxation of cardiac muscle. Main body This review focused on understanding the role of contractile and relaxation proteins in the pathogenesis of hypertrophic cardiomyopathy. Mutations in contractile proteins such as myosin, actin, tropomyosin, and troponin are associated with hypercontractility and increased sensitivity of the heart muscle, leading to HCM. Additionally, impaired relaxation of the heart muscle, linked to abnormalities in proteins like phospholamban, sarcolipin, titin, myosin binding protein-C, and calsequestrin, contributes significantly to the disease. The review also explored the impact of targeted therapeutic approaches aimed at modulating these proteins to improve patient outcomes. Recent advances in therapeutic strategies, including novel pharmacological agents like mavacamten and aficamten, were examined for their potential to help patients manage the disease and lead more accommodating lifestyles. Conclusions The review underscored the significance of early diagnosis and personalized treatment approaches in managing HCM. Future research should prioritize the development of robust biomarkers for early detection and risk stratification, particularly in diverse populations, to enhance clinical outcomes. Furthermore, it is imperative to delve deeper into the genetic mutations and molecular mechanisms associated with HCM, with a focus on exploring the roles of less-studied myocardial relaxation proteins and their interactions with sarcomere constituents.

INTRODUCTION: Cardiogenic arterial thromboembolism (CATE) is a life-threatening complication of hypertrophic cardiomyopathy (HCM) with a high mortality rate. As the primary responders in hemostasis, platelets play a crucial role in the progression of CATE. Procoagulant platelets are a subpopulation of activated platelets that facilitate thrombin generation to strengthen thrombus structure. Since their discovery, procoagulant platelets have gained a considerable amount of attention due to their potential role in thromboembolic complications. Uncovering the key phenotypic markers and agonists underlying the procoagulant response in feline platelets may provide diagnostic and therapeutic insights in the treatment of CATE. However, species differences in platelet physiology and the sensitive nature of feline platelets pose some significant challenges in studying procoagulant platelets in cats. OBJECTIVES: To first devise a flow cytometric method to sequentially assess procoagulant platelet markers and to identify agonists that could induce procoagulant platelet phenotypes. Furthermore, a novel scoring system was established to evaluate the procoagulant tendency of platelets in cats. METHODS: Platelets were isolated from eight healthy cats and activated by thrombin in the presence or absence of collagen (COL) and convulxin (CVX). The following markers were measured sequentially by flow cytometry: (1) loss of mitochondrial membrane potential (ΔΨm), (2) phosphatidylserine (PS) externalization, and (3) P-selectin upregulation. RESULTS: Thrombin in the presence of CVX significantly reduced ΔΨm and induced P-selectin upregulation (p = 0.0078, p = 0.0128, respectively). In addition, thrombin-treated platelets in the presence of COL and CVX augmented PS externalization significantly (p = 0.043, p = 0.0172, respectively). Of the agonists tested, thrombin and CVX resulted in the highest procoagulant tendency score with 75% cats reaching a score ≥2/3. The number of cats with a procoagulant tendency score of 2 or 3 for thrombin and thrombin + COL was 4/8 (50%) and 5/8 (62.5%), respectively. DISCUSSION: Sequential analysis of procoagulant markers via flow cytometry may be an effective technique for studying procoagulant platelets in cats.

INTRODUCTION: Cats with cardiomyopathy face an increased risk of arterial thromboembolism (ATE). Although clopidogrel is frequently utilized to mitigate this risk, feline responses to this therapy exhibit variability. This study evaluated 2 viscoelastic devices, thromboelastography (TEG) and Viscoelastic Coagulation Monitor (VCM), for monitoring clopidogrel in cats in comparison to light transmission aggregometry (LTA). METHODS: Twenty-eight healthy cats received clopidogrel for 7 days. Blood was collected at baseline and after treatment for analysis by TEG, VCM, and LTA. RESULTS: On LTA, maximum amplitude, slope, and area under the curve (AUC) significantly decreased after treatment (p

Cardiac lymphangiomas represent one of the rarest types of cardiac tumors. We describe the case of a 28-year-old male with cystic lymphangioma and hypertrophic cardiomyopathy. There have been only a few cases reported and to the best of our knowledge this is the first documented case associating a cardiac lymphangioma with cardiomyopathy.

We present a clinical case of a patient with hypertrophic cardiomyopathy (HCM) characterized by an inverted septal curvature phenotype, accompanied by angina and presyncope symptoms. Patients with this type of presentation remain a diagnostic and therapeutic challenge due to their association with midventricular obstruction, apical aneurysm formation, and an increased risk of arrhythmias and sudden cardiac death (SCD). Their treatment and follow-up require a multidisciplinary approach to improve quality of life and prognosis. Various imaging modalities were applied in this case, confirming the presence of severe left ventricular hypertrophy, posterior wall hypertrophy of the right ventricle, and a midventricular gradient. Magnetic resonance imaging (MRI) demonstrated fibrosis involving approximately 25% of the myocardium. The patient was stratified as high-risk patient for SCD. To improve the patient’s quality of life and prognosis, pharmacological therapy was optimized, and an implantable cardioverter-defibrillator (ICD) was placed.

BACKGROUND: The clinical course, pathophysiology, and therapeutic options for valvular and subvalvular (accompanied by hypertrophic cardiomyopathy, HCM) aortic stenosis are well known separately, but the rare combination of severe aortic stenosis (AS) and obstructive HCM presents great diagnostic and treatment challenges. The combination of these diseases during transcatheter aortic valve implantation (TAVI) is associated with significantly worse hospital outcomes, including cardiogenic shock, renal failure, and death. There is evidence that TAVI without prior treatment of left ventricular outflow tract obstruction leads to higher mortality due to exacerbation of subvalvular obstruction. AIM: To evaluate changes in hypertrophy of interventricular septum (IVS) in patients with a combination of AS and HCM following TAVI. MATERIALS AND METHODS: The observational, retrospective, single-center, non-randomized study included 20 patients with diagnosed severe AS, preoperative IVS thickness ≥15 mm, and the preoperative ratio of IVS and left ventricular posterior wall thickness ≥1.3, following TAVI. Mean and maximum follow-up periods were 33 and 92 months, respectively. The primary endpoint was decreased IVS thickness following TAVI as determined by echocardiography. RESULTS: The average age of patients was 72.4±5.5 years, more than half of the subjects were women. 60% of patients were diagnosed with coronary artery disease at the time of TAVI. Pre- and postoperative median IVS thicknesses were 17.7±2.2 and 14.4±3.2 mm, respectively. Long-term outcomes of TAVI included a significant decrease in hypertrophy of IVS (p=0.031) IVS thicknesses mainly decreased over the period up to 24 months after surgery. Cox regression analysis found that each year of patient’s age increased the risk of no postoperative decrease in IVS thickness after surgery by 12% every month. CONCLUSION: There was a statistically significant decrease in hypertrophy of IVS in patients who underwent TAVI. In most cases, IVS thickness decreased within 2 years after surgery. Each year of patient’s age increased the risk of no postoperative decrease in IVS thicknesses by 12% every month.

Veterinary specialists have lately observed comorbidity of heart and kidney diseases known as cardiorenal syndrome. Cardiorenal syndrome is typically defined as dysfunction of a primarily intact kidney under the influence of a complex of pathogenetic damaging factors that arise against the background of an underlying cardiac disease. The purpose of the work is to study the biochemical profile of blood serum in cats with cardiorenal syndrome arising against the background of hypertrophic cardiomyopathy. The studies were carried out on 24 physiologically healthy (control) cats, 24 diseased cats with uncomplicated forms of pathology (first group) and 25 cats with hypertrophic cardiomyopathy complicated by cardiorenal syndrome (second group). It was shown that cardiorenal syndrome may occur as a complication of hypertrophic cardiomyopathy in animals. Biochemical tests in animals with feline cardiorenal syndrome verified cytolysis of cardiomyocytes (increased serum activity of lactate dehydrogenase by 2.69 times, creatine phosphokinase by 2.02 times, increased serum concentration of cardiac troponin by 5.20 times as compared to healthy animals), azotemia (increased concentration in serum creatinine by 2.72 times, urea by 2.94 times, symmetric dimethylarginine by 2.60 times and cystatin C by 1.90 times as compared to healthy animals), enhanced ketogenesis, systemic inflammatory process (increased serum concentration of C-reactive protein by 1.55 times as compared to healthy animals), hypercholesterolemia, oxidative stress (decrease in serum activity of superoxide dismutase by 1.63 times, catalase by 4.67 times and glutathione peroxidase by 1.71 times, increase in the concentration of malondialdehyde by 1.79 times, ceruloplasmin by 2.50 times and diene conjugates by 1.85 times as compared to healthy animals), electrolyte imbalance in the form of hyperkalemia, hyponatremia, hyperphosphatemia and hypomagnesemia. Biochemical indicators such as serum concentrations of creatinine, troponin I, cystatin C, symmetric dimethylarginine and C-reactive protein can be considered reliable diagnostic markers for the presence of cardiorenal syndrome.

Objective: Despite significant advances in understanding hypertrophic cardiomyopathy (HCM) in recent years, there is a need to improve risk stratification for patients at high risk of adverse outcomes. The relationship between inflammation and disease severity in HCM patients is known. Recently, a new inflammation parameter called the pan-immune inflammation value (PIV) has been introduced. However, the relationship between PIV and HCM has not yet been examined. Hence, we aim to investigate the effect of PIV on prognosis in a large series of HCM patients. Methods: The study included 389 consecutive patients with HCM admitted to a tertiary care hospital between 2004 to 2021. The PIV for patients was calculated as: Neutrophil count x platelet count x monocyte count / lymphocyte count. The cohort was categorized into three groups according to PIV, and the association between these groups and long-term mortality was evaluated. Results: Over an average follow-up period of 55.5+-12.7 months, long-term mortality occurred in 47 out of 389 patients. Long-term mortality was recorded in 7 patients in tertile 1, 12 patients in tertile 2, and 28 patients in tertile 3. Multivariate regression analysis revealed that long-term all-cause mortality was 3.5 times higher in tertile 3 compared to tertile 1. The receiver-operating characteristic curve based on the PIV had 62% sensitivity and 65% specificity for long-term mortality. Conclusions: High PIV levels may serve as a predictor of long-term mortality in patients with HCM. PIV could be a useful screening tool for identifying HCM patients at increased risk of adverse outcomes.

ObjectiveTo explore the difference of the left ventricular global longitudinal strain (GLS) and the segment strains between cardiac amyloidosis (CA) and non-obstructive hypertrophic cardiomyopathy (HCM). MethodsTwenty patients with immunoglobulin light chain cardiac amyloidosis (AL-CA) as CA group and 20 patients with non-obstructive HCM selected as controls (HCM group) were enrolled from January 2016 to April 2022 in Zhongshan Hospital, Fudan University. All patients underwent two-dimensional speckle tracking echocardiography (2D-STE). The left ventricle GLS and the segmental strains were calculated. The values of these strains to distinguish AL-CA from HCM were analyzed by receiver operating characteristic (ROC) curves and logistic regression analysis. ResultsIn the CA group, the GLS parameters (3P, 4Ch, 2Ch, 3Ch), as well as the left ventricle segmental strains (MID-ANT/LAT, MID-INF/SEPT, BASAL-ANT/LAT, BASAL-INF/SEPT, MID-ANT, MID-INF, BASAL-ANT, BASAL-INF, MID-INF/LAT, BASAL-ANT/SEPT, and BASAL-INF/LAT) were all lower than those in the HCM group (P＜0.01). ROC results showed that GLS(4Ch), GLS(2Ch), GLS(3Ch), GLS(3P), BASAL-ANT/LAT, BASAL-INF/SEPT, BASAL-ANT, BASAL-INF, BASAL-ANT/SEPT and BASAL-INF/LAT had good efficacy in distinguishing AL-CA from HCM. Logistic regression analysis showed that BASAL-ANT/LAT was an independent factor in distinguishing AL-CA from HCM (P＜0.01). The consistency of test results was good. ConclusionsThe left ventricular segmental myocardial strains show good efficacy in distinguishing AL-CA from HCM, and BASAL-ANT/LAT has highest application value.

Background. Myocardial infarction with non-obstructive coronary arteries is defined by the presence of clinical symptoms and signs of myocardial infarction despite angiographic findings of normal or near-normal coronary arteries. Myocardial infarction with non-obstructive coronary arteries can be classified into myocardial infarction type 1 or type 2. Hypertrophic cardiomyopathy is a possible underlying etiology of myocardial infarction with non-obstructive coronary arteries.The aim. To present the diagnosis of myocardial infarction in a patient with hypertrophic cardiomyopathy.Case descriptions. A clinical case of myocardial infarction with non-obstructive coronary arteries in a man with hypertrophic cardiomyopathy is presented. 57-year-old man presented with retrosternal chest pain that appeared at rest but during an attack of tachyarrhythmia. Electrocardiogram showed right bundle branch block and T inversion in the I, avL, V1-V6. Cardiac troponin T was with a rise and fall in the level. Echocardiography demonstrated asymmetrical septal hypertrophy with thickness of the basal and medium segments of the septum 18 mm, systolic anterior motion of the mitral valve, and left ventricular outflow tract obstruction with a peak systolic pressure gradient of 50 mmHg, diastolic dysfunction of the left ventricle. Coronary angiography revealed stenosis of the left anterior descending artery < 50 %. All these data allow us to diagnose the myocardial infarction with non-obstructive coronary arteries. Type 2 infarction is most likely, however, the absence of an intracoronary imaging does not completely exclude type 1 myocardial infarction.Conclusion. The clinical case demonstrates myocardial infarction in the absence of obstructive coronary artery disease in patient with hypertrophic cardiomyopathy. To exclude plaque disruption intracoronary imaging should be performed.

The aims of this study were to: 1) determine whether 2D and 3D feature tracking cardiac magnetic resonance (FT-CMR) are equivalent in patients with hypertrophic cardiomyopathy (HCM), 2) compare 3D FT-CMR values in HCM and healthy volunteers and 3) compare FT-CMR in most frequent HCM phenotypes.

Abstract Hypertrophic cardiomyopathy (HCM) due to thick filament variants is more common; however, HCM due to thin filament variants (HCM‐Thin) may be associated with a more malignant phenotype with an increased risk of sudden cardiac death. The aim of this study was to review all the published cases of HCM‐Thin to better understand the natural history and clinical outcomes of this disease. A literature review of HCM‐Thin identified 21 studies with a total of 177 patients that were suitable for analysis. There were three outcomes of interest, which included a heart failure composite, a ventricular arrhythmia composite and a heart failure and arrhythmia composite outcome. Kaplan–Meier (KM) survival analyses for freedom from each of the abovementioned composite outcomes were completed for the entire cohort and stratified by age of onset and sarcomeric variant. The heart failure composite occurred in 24 (13.6%) patients, the ventricular arrhythmia composite occurred in 30 patients (16.9%) and the combined heart failure and arrhythmia composite occurred in 50 patients (28.2%). In regard to left ventricular ejection fraction (LVEF), the majority of patients were preserved (LVEF > 50%) compared with mildly reduced (LVEF 41%–50%) and reduced (LVEF ≤ 40%) (respectively 26.6% vs. 0.6% vs. 3.4%). The median maximal left ventricular wall thickness (LVWT) was 19.0 mm [interquartile range (IQR) 5.3]. Only 10.7% of the cohort had evidence of left ventricular outflow tract (LVOT) obstruction. Those with paediatric‐onset HCM had earlier onset and were at higher risk for each endpoint than their adult counterparts. When stratified by genetic variant, patients with TNNI3 and TPM1 were at a higher risk of the heart failure composite endpoint and the combined heart failure and arrhythmia composite endpoint in comparison with those with the other genetic variants. HCM‐Thin is associated with significant morbidity and mortality, with a high arrhythmia burden despite low rates of cardiac obstruction and mild hypertrophy. The paediatric onset of disease and certain sarcomeric variants appear to be associated with a worse prognosis than their adult‐onset and other sarcomeric variant counterparts. HCM‐Thin seems to have a distinct phenotype, which may require a different management approach.

Abstract Aim The diagnosis of hypertrophic cardiomyopathy (HCM) with moderate hypertrophy is challenging. Hypertensive heart disease (HHD) is the most common differential diagnosis that mimics the LVH of HCM. The aim of this study was to compare the QRS duration in HCM and HHD to create a novel diagnostic tool to identify primary HCM. Methods and results We conducted an international retrospective multicentre study enrolling patients with true HCM and HHD. A total of 547 individuals with HCM and 139 with HHD were included. The median QRS duration was significantly shorter in HCM than in HHD (88 ms [80–94] vs. 98 ms [88–108]; P

Abstract Aims The fibrosis‐4 index (FIB‐4) is a non‐invasive tool to assess fibrosis risk in chronic liver disease. We aimed to explore the relationship between the FIB‐4 index and long‐term major adverse cardiovascular events (MACE) in HCM patients. Methods and results Consecutive patients diagnosed with HCM were included. Patients were divided into two groups using a defined cutoff value established through a ROC analysis for predicting MACE (FIB‐4 ≥ 2.37 and FIB‐4

Abstract Aims End‐stage hypertrophic cardiomyopathy (ES‐HCM) is a disease with severe complications and a poor prognosis. This study aimed to explore the influencing and prognostic factors of ES‐HCM. Methods and results A total of 1282 patients with HCM who were hospitalized for the first time at Fujian Medical University Union Hospital between 1 January 2013 and 30 September 2021 were recorded. The patients with HCM and left ventricular ejection fraction (LVEF)

Abstract Background A significant proportion of cardiomyopathy patients remain genetically unsolved. Our aim was to use the large genomes cohort of the 100,000 genomes project (100KGP) to explore the proportion of potentially causal mitochondrial (mtDNA) variants in cardiomyopathy patients, particularly in genotype-elusive participants. The homoplasmic MT-TI 4300A>G is unusual in that it typically presents with a cardiac-only phenotype, but MT-TI is currently not part of the genes analysed for non-syndromic cardiomyopathies. Results We analysed 1363 cardiomyopathy genomes from the 100KGP project (of which only 172 had been previously solved) to detect disease causing mtDNA variants. MitoHPC was used to call variants. For controls, 1329 random subjects not recruited for a cardiomyopathy diagnosis and not related to any participant in the cardiomyopathy cohort were selected. We have additionally compared the frequency of detected variants with published UK Biobank data. Pathogenicity annotations were assigned based on MitoMap. Four patients, all with a diagnosis of hypertrophic cardiomyopathy (HCM) and without a previously identified genetic cause from the 100KGP clinical-standard analysis, were found to harbour the pathogenic MT-TI m.4300A>G variant (0.6% of HCM cases without a diagnosis). Conclusion These data support the inclusion of MT-TI in the initial genetic testing panel for (non-syndromic) HCM.

Abstract Analysis of heart sound signals plays an essential role in preventing and diagnosing cardiac diseases. This study proposes a multi-level feature encoding algorithm based on frequency-balanced power spectral intensity for heart sound signal classification. Firstly, a wavelet threshold function is employed to denoise the heart sound signals. Then, the frequency-balanced power spectral intensity envelope is calculated, and an encoder is utilized to extract multi-level features based on the envelope. Finally, an ensemble bagging tree classifier is selected for classification. The experimental data includes binary classification data from the 2016 PhysioNet/CinC Challenge and ternary classification data from the self-collected hypertrophic cardiomyopathy dataset. Results demonstrate that the proposed algorithm performs well, achieving an average classification accuracy of 98.73% for normal and abnormal heart sounds, and 98.12% for normal and two types of hypertrophic cardiomyopathy heart sounds. The proposed method holds significant reference value for the early diagnosis of heart diseases.

Background and Aim: Cardiac biomarkers, such as serum galectin-3 (Gal-3) and titin levels, may be related to cats with sarcomeric gene mutations. This study evaluated cardiac biomarkers and echocardiographic parameters in cats with or without myosin-binding protein C3 (MYBPC3) gene mutations. Materials and Methods: Forty-two healthy cats without cardiac symptoms, including Bengal, Maine Coon, Scottish fold, and Ragdoll cats, were enrolled in this study. Cats were categorized into three groups: Homozygous wild type (n = 17), homozygous MYBPC3 gene mutation (n = 14), and heterozygous MYBPC3 gene mutation (n = 11). All recruited cats underwent echocardiography, and blood samples were collected for DNA extraction. DNA sequencing for MYBPC3 gene mutations at A31P and A74T loci was first examined by Sanger sequencing. The biomarkers of cardiac fibrosis (Gal-3) and myocardial stiffness (titin) were measured by enzyme-linked immunosorbent assay. Results: Gal-3 levels >250 pg/mL were associated with echocardiographic parameters. However, Gal-3 levels were not significantly different between cats with MYBPC3 gene mutations and those in the wild-type group. Titin was associated with the left ventricular (LV) thickness and systolic function (r = 0.405, p = 0.013). Qualitative measurement of titin antibodies showed that the highest percentage of these antibodies was found in homozygous wild-type cats. No correlation was found between titin levels and MYBPC3 gene mutations. Weight was positively associated with interventricular septum (r = 0.312, p = 0.056) and LV wall thickness (LVPW) (r = 0.219, p = 0.187). However, they were not associated with Gal-3 levels. Conclusion: LVPW was correlated with weight in cats with sarcomeric gene mutations. Serum titin may be an underlying factor for cardiac hypertrophy in cats.

This case report shows unique aneurysm at the left ventricular apex associated with a double-chambered left ventricle (DCLV) in asymptomatic 69-year-old female. The aneurysm was located at the apex of an accessory chamber, which was formed by hypertrophied muscle band and the interventricular septum, along with a pronounced jet flow directed towards the apex aneurysm. These finding suggests that the obstruction at the base of the accessory chamber caused a pressure overload at the apex, ultimately leading to the development of the aneurysm. To best of our knowledge, this is the first case to prove the underlying cause of aneurysm formation in DCLV.

Abstract Aims Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic cardiac disorder characterized by unexplained left ventricular hypertrophy. It can cause a wide spectrum of clinical manifestations, ranging from asymptomatic to heart failure and sudden cardiac death (SCD). Approximately half of HCM cases are caused by variants in sarcomeric proteins, including α‐tropomyosin (TPM1). In this study, we aimed to characterize the clinical and molecular phenotype of HCM in an Iranian pedigree with SCD. Methods and Results The proband and available family members underwent comprehensive clinical evaluations, including echocardiography, cardiac magnetic resonance (CMR) imaging and electrocardiography (ECG). Whole‐exome sequencing (WES) was performed in all available family members to identify the causal variant, which was validated, and segregation analysis was conducted via Sanger sequencing. WES identified a novel missense variant, c.761A>G:p.D254G (NM_001018005.2), in the TPM1 gene, in the proband, his father and one of his sisters. Bioinformatic analysis predicted it to be likely pathogenic. Clinical features in affected individuals were consistent with HCM. Conclusions The identification of a novel TPM1 variant in a family with HCM and SCD underscores the critical role of genetic screening in at‐risk families. Early detection of pathogenic variants can facilitate timely intervention and management, potentially reducing the risk of SCD in individuals with HCM.

Abstract Background Hypertrophic cardiomyopathy (HCM) can cause myocardial fibrosis, which can be a substrate for fatal ventricular arrhythmias and subsequent sudden cardiac death. Although late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) represents myocardial fibrosis and is associated with sudden cardiac death in patients with HCM, CMR is resource-intensive, can carry an economic burden, and is sometimes contraindicated. In this study for patients with HCM, we aimed to distinguish between patients with positive and negative LGE on CMR using deep learning of echocardiographic images. Methods In the cross-sectional study of patients with HCM, we enrolled patients who underwent both echocardiography and CMR. The outcome was positive LGE on CMR. Among the 323 samples, we randomly selected 273 samples (training set) and employed deep convolutional neural network (DCNN) of echocardiographic 5-chamber view to discriminate positive LGE on CMR. We also developed a reference model using clinical parameters with significant differences between patients with positive and negative LGE. In the remaining 50 samples (test set), we compared the area under the receiver-operating-characteristic curve (AUC) between a combined model using the reference model plus the DCNN-derived probability and the reference model. Results Among the 323 CMR studies, positive LGE was detected in 160 (50%). The reference model was constructed using the following 7 clinical parameters: family history of HCM, maximum left ventricular (LV) wall thickness, LV end-diastolic diameter, LV end-systolic volume, LV ejection fraction

Tino Severinsen,1,2 Helga Lillian Gudmundsdottir,1,2 Anna Axelsson Raja,2,3 Emil Loldrup Fosbøl,2,3 Henning Bundgaard,2,3 Jens Jakob Thune1,2 1Department of Cardiology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Copenhagen, Denmark; 2Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; 3Department of Cardiology, The Heart Center, Copenhagen University Hospital - Rigshospitalet, Copenhagen, DenmarkCorrespondence: Jens Jakob Thune, Department of Cardiology, Copenhagen University Hospital - Bispebjerg and Frederiksberg, Nordre Fasanvej 57, Frederiksberg, 2000, Denmark, Tel +45 50470723, Email Jens.Jakob.thune@regionh.dkPurpose: To assess the positive predictive value (PPV) of the diagnostic codes for hypertrophic cardiomyopathy (HCM) in the Danish National Patient Register (DNPR) and identify factors affecting the PPV.Patients and Methods: We randomly sampled 200 patients registered in DNPR with the diagnostic codes DI421 (obstructive) or DI422 (non-obstructive) HCM, from Eastern Denmark, between December 1st, 2017, and September 16th, 2021. We assessed patients’ medical records and classified whether the diagnosis of HCM was correct, incorrect, or uncertain according to the European Society of Cardiology (ESC) guidelines. Overall PPVs were estimated for all hospitals irrespective of specialty and for dedicated centers for inherited cardiac diseases.Results: Of the 200 patients, seven were excluded; six were younger than 18 years when initially diagnosed and one adult patient had requested that their medical records be unavailable for research purposes. Of the 193 patients (median age 61 years, Interquartile range (IQR) 50– 70, 40% female) with medical records available for assessment, 148 (77%) patients were registered correctly, 41 (21%) were incorrectly registered and for four (2%) patients there was insufficient data to determine if the diagnosis was correct. The overall PPV was 0.77 (95% confidence interval (CI) 0.70– 0.82). The PPV for patients diagnosed in dedicated centers for inherited cardiac diseases was 0.91 (95% CI 0.84– 0.95). For patients diagnosed in a dedicated center for inherited cardiac diseases with more than one clinical visit, the PPV increased to 0.99 (95% CI 0.93– 1), however with the risk of a reduced sensitivity as these patients constituted only 52% of the correctly registered patients.Conclusion: The overall PPV of the HCM diagnostic codes in the DNPR was 0.77 (95% CI 0.70– 0.82). The validity of the diagnosis was higher at dedicated centers for inherited cardiac diseases. These findings may prove useful for future register-based research.Keywords: Register, hypertrophic cardiomyopathy, Denmark, sample filters

Abstract Background: Tetralogy of Fallot (TOF) and hypertrophic cardiomyopathy (HCM) are common types of congenital heart disease with unique pathophysiologic features. Mutations in LBX1, a key regulator of muscle precursor cell migration, may disrupt these critical developmental processes, resulting in severe developmental abnormalities. Case presentation: This case reports on a 4-year-old girl diagnosed with both TOF and HCM. Genetic analysis revealed iUPI-F (uniparental disomy) on the entire chromosome 10, with a c.808G > A (p. Glu270Lys) pure mutation in the LBX1. Conclusion: This patient exhibited both TOF and HCM with mutations in the LBX1 gene, suggesting a potentially novel genetic link. This case study emphasizes the need for further studies on the function of the LBX1 gene in cardiac development and its potential impact on TOF and HCM.

Hypertrophic cardiomyopathy (HCM) is characterized by abnormal thickening of the left ventricular myocardium. Apical HCM is a less common variant of HCM where the hypertrophy is limited to the apical segments and can be challenging to diagnose based on traditional echocardiography alone. Patients with HCM can present with exertional angina. We present a series of four different cases, where patients were advised computed tomography (CT) coronary angiography for the evaluation of coronary artery disease. While CT coronary angiography excluded obstructive coronary artery disease, a detailed evaluation of the retrospective electrocardiogram-gated CT coronary angiography data helped in establishing the diagnosis of apical HCM in these patients. We discuss the importance of a systematic analysis of cardiac CT for diagnosing HCM variants and highlight the utility of reconstructed static and cine CT images which are readily available from the data obtained during retrospective gated CT coronary angiography for diagnosing HCM.

Our study examined the relationships and interactions among 30 genes related to the NOD-like receptor protein 3 (NLRP3) inflammasome. We identified 368 interconnections between these 30 genes, with NLRP3 participating in 38 interactions. The potential roles of these genes in atherosclerosis were evaluated based on protein–protein interaction networks and coexpression analysis. We identified differential expression in 20 genes, five of which were significantly upregulated: P2RX7, CASP1, CD36, GBP5, and PYCARD. We also observed a strong positive association between P2RX7 and PYCARD and as a notable negative association between RELA and CD36. Furthermore, our analysis revealed a clear association between the expression of inflammasome-associated genes and immune cell infiltration in disease specimens. To diagnose AS, a logistic regression model based on six inflammasome-related genes, achieved an Area under the curve of 0.996, indicating excellent diagnostic performance. Genomic enrichment analysis indicated that inflammasome-related genes were primarily involved in various pathways, such as hypertrophic cardiomyopathy and ribosomal function. To validate our findings, we confirmed the expression of risk genes in AS cells using qRT-PCR and Western blot techniques. Additionally, we observed a shift toward M2 polarization in THP-1 macrophages upon P2RX7 knockdown, further supporting our findings. [ABSTRACT FROM AUTHOR]

Background: GTPBP3 catalyzes τm5(s2) U biosynthesis at the 34th wobble position of mitochondrial tRNAs, the hypomodification of τm5U leads to mitochondrial disease. While twenty-three variants of GTPBP3 have been reported worldwide, the genetic landscape in China remains uncertain. Methods: By using whole-exome sequencing, the candidate individuals carrying GTPBP3 variants were screened and identified. Pathogenicity analysis of variants was biochemically verified by patients-derived immortalized lymphocytes and cell models. Results: Through whole-exome sequencing, thirteen variants associated with GTPBP3 were identified in nine Chinese pedigrees, with eight of these variants being newly reported. Affected individuals displayed classic neurologic phenotypes and heart complications including developmental delay, seizures, hypotonia, exercise intolerance, and hypertrophic cardiomyopathy. Additionally, they displayed new symptoms such as eye problems like strabismus and heart issues related to valve function. Studies conducted on patient-derived cells provided evidence of reduced levels of GTPBP3 and impairment in mitochondrial energetic biogenesis. Re-expressing GTPBP3 variants in knockout cell lines further defined the pathogenicity of the novel variants. Analysis of the genetic spectrum in the Chinese population highlighted a concentration in exons 4 and 6, with c.689A > C being the prominent hotspot. Conclusion: Our findings emphasize the extensive clinical and genetic implications of GTPBP3-related mitochondrial disorders, particularly within the Chinese population, but further investigations are needed to explore the phenotype-genotype correlation. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is one of the most common cardiovascular diseases with no effective treatment due to its complex pathogenesis. A novel cell death, disulfidptosis, has been extensively studied in the cancer field but rarely in cardiovascular diseases. This study revealed the potential relationship between disulfidptosis and hypertrophic cardiomyopathy and put forward a predictive model containing disulfidptosis-associated genes (DRGs) of GYS1, MYH10, PDMIL1, SLC3A2, CAPZB, showing excellent performance by SVM machine learning model. The results were further validated by western blot, RNA sequencing and immunohistochemistry in a TAC mice model. In addition, resveratrol was selected as a therapeutic drug targeting core genes using the CTD database. In summary, this study provides new perspectives for exploring disulfidptosis-related biomarkers and potential therapeutic targets for hypertrophic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusion Atrial fibrillation (AF) is the most common sustained arrhythmia among patients with hypertrophic cardiomyopathy (HCM), leading to increased symptom burden and risk of thromboembolism. The HCM‐AF score was developed to predict new‐onset AF in patients with HCM, though sensitivity and specificity of this conventional tool are limited. Thus, there is a need for more accurate tools to predict new‐onset AF in HCM. The objective of the present study was to develop a better model to predict new‐onset AF in patients with HCM using machine learning (ML).In this prospective, multicentre cohort study, we enrolled 1069 patients with HCM without a prior history of AF. We built a ML model (logistic regression with Lasso regularization) using clinical variables. We developed the ML model using the cohort from one institution (training set) and applied it to an independent cohort from a separate institution (test set). We used the HCM‐AF score as a reference model. We compared the area under the receiver‐operating characteristic curve (AUC) between the ML model and the reference model using the DeLong's test. Median follow‐up time was 2.1 years, with 128 (12%) patients developing new‐onset AF. Using the ML model developed in the training set to predict new‐onset AF, the AUC in the test set was 0.84 (95% confidence interval [CI] 0.77–0.91). The ML model outperformed the reference model (AUC 0.64; 95% CI 0.54–0.73; DeLong's p < 0.001). The ML model had higher sensitivity (0.82; 95% CI 0.65–0.93) than that of the reference model (0.67; 95% CI 0.52–0.88). The ML model also had higher specificity (0.76; 95% CI 0.71–0.81) than that of the reference model (0.57; 95% CI 0.41–0.70). Among the most important clinical variables included in the ML‐based model were left atrial volume and diameter, left ventricular outflow tract gradient with exercise stress and at rest, late gadolinium enhancement on cardiac magnetic resonance imaging, peak heart rate during exercise stress, age at diagnosis, positive genotype, diabetes mellitus, and end‐stage renal disease.Our ML model showed superior performance compared to the conventional HCM‐AF score for the prediction of new‐onset AF in patients with HCM. [ABSTRACT FROM AUTHOR]

Mavacamten is a potential inducer of cytochrome P450 (CYP) 3A4 and could reduce the effectiveness of concomitant drugs that are metabolized by CYP3A4, such as midazolam. This study aimed to determine if repeat doses of mavacamten achieving clinically relevant exposures affected midazolam exposure. This was a single‐center, open‐label study in healthy participants. Participants received: on day 1, midazolam 5 mg; on days 2–3, mavacamten 25 mg; on days 4–16, mavacamten 15 mg; and on day 17, mavacamten 15 mg and midazolam 5 mg. Plasma concentrations of mavacamten, midazolam, and the midazolam metabolite 1′‐hydroxymidazolam were measured. A physiologically based pharmacokinetic (PBPK) model was used to simulate the effect of mavacamten‐mediated CYP3A4 induction on midazolam exposure by CYP2C19 phenotype. Thirteen adult participants were enrolled (46.2% were female; mean [SD] age: 34.0 [9.0] years). Compared with midazolam alone, midazolam coadministered with mavacamten decreased the maximum observed plasma concentration (Cmax), area under the drug concentration‐time curve (AUC) from time zero to infinity (AUC0‐inf), and AUC from time zero to last measurable concentration (AUC0‐last) for midazolam by 7%, 13%, and 24%, respectively; for 1′‐hydroxymidazolam, AUC0–inf and AUC0–last increased by 20% and 11%, respectively. Ten participants experienced adverse events and the majority were mild in severity. The PBPK model predicted the clinical trial data well. The PBPK simulation assessed that the overall impact of mavacamten on midazolam Cmax and AUC was predicted to be weak regardless of CYP2C19 phenotype. At clinically relevant exposures, mavacamten had a negligible effect on midazolam exposure. [ABSTRACT FROM AUTHOR]

The cardiac myosin binding protein-C (cMyBP-C) regulates cross-bridge formation and controls the duration of systole and diastole at the whole heart level. As known, mutations in cMyBP-C increase the cross-bridge number and rate of their cycling, hypercontractility, and myocardial hypertrophy. We investigated the effects of the mutations D75N and P161S of cMyBP-C related to hypertrophic cardiomyopathy on the mechanism of force generation in isolated slow skeletal muscle fibers. The mutation D75N slowed the kinetics of force development but did not affect the relaxation rate. The mutation P161S slowed both the relaxation and force development. The mutation D75N increased the calcium sensitivity of force, and the mutation P161S decreased it. The mutation D75N decreased the maximal isometric tension and increased the tension and stiffness at low calcium. Both mutations studied disrupt the calcium regulation of contractile force and affect the kinetics of its development and thus may impair cardiac diastolic function and cause myocardial hypertrophy. [ABSTRACT FROM AUTHOR]

Cardiac transthyretin amyloidosis is an underdiagnosed disorder with significant diagnostic difficulties due to its non-specific clinical manifestations. It is caused by the deposition of protein aggregates with an abnormal tertiary structure in the extracellular matrix. Their accumulation leads to the development of hypertrophic and restrictive cardiomyopathy and, at a later stage, heart failure with preserved ejection fraction syndrome. Depending on the pathogenesis, there are different types of the disease—hereditary and age-related wild-type transthyretin amyloidosis. We present the case of an 85-year-old woman who was referred to the department with a two-month history of exertional dyspnea in New York Heart Association functional class II. After reviewing the initial findings, several red flags for cardiac amyloidosis (CA) were identified. Following the diagnostic algorithm, scintigraphy was performed and showed significant radioisotope accumulation in the myocardium, confirming the suspected disease. In this manuscript, we present the current recommendations and diagnostic pathway, discussing in detail both available and emerging treatment options. As early diagnosis is essential to prevent the development of serious complications, we would like to highlight the pitfalls in diagnosing CA and emphasize the need to be aware of its variable clinical presentation and red flags. [ABSTRACT FROM AUTHOR]

Background and Aims Long-term safety and efficacy of mavacamten in patients with obstructive hypertrophic cardiomyopathy (HCM) are unknown. MAVA-LTE (NCT03723655) is an ongoing, 5-year, open-label extension study designed to evaluate the long-term effects of mavacamten. Methods Participants from EXPLORER-HCM (NCT03470545) could enrol in MAVA-LTE upon study completion. Results At the latest data cut-off, 211 (91.3%) of the 231 patients originally enrolled in MAVA-LTE still received mavacamten. Median (range) time on study was 166.1 (6.0–228.1) weeks; 185 (80.1%) and 99 (42.9%) patients had completed the Week 156 and 180 visits, respectively. Sustained reductions from baseline to Week 180 occurred in left ventricular outflow tract gradients [mean (standard deviation): resting, −40.3 (32.7) mmHg; Valsalva, −55.3 (33.7) mmHg], N-terminal pro B-type natriuretic peptide [median (interquartile range): −562 (−1162.5, −209) ng/L], and EQ-5D-5L score [mean (standard deviation): 0.09 (0.17)]. Mean left ventricular ejection fraction (LVEF) decreased from 73.9% (baseline) to 66.6% (Week 24) and 63.9% (Week 180). At Week 180, 74 (77.9%) of the 95 patients improved by at least one New York Heart Association class from baseline. Over 739 patient-years exposure, 20 patients (8.7%; exposure-adjusted incidence: 2.77/100 patient-years) experienced 22 transient reductions in LVEF to <50% resulting in temporary treatment interruption (all recovered LVEF of ≥50%). Five (2.2%) patients died (all considered unrelated to mavacamten). Conclusions Long-term mavacamten treatment resulted in sustained improvements in cardiac function and symptoms in patients with obstructive HCM, with no new safety concerns identified. Transient, reversible reductions in LVEF were observed in a small proportion of patients during long-term follow-up. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to explore the correlation between PET and CMR in integrated [68Ga]Ga-FAPI-04 PET/CMR multimodal imaging and its value in the diagnosis and risk assessment of hypertrophic cardiomyopathy (HCM). Methods: This study included 20 HCM patients and 11 age- and gender-matched controls. PET analysis evaluated left ventricular (LV) [68Ga]Ga-FAPI-04 uptake, including SUVmax, TBR, cardiac fibroblast activity (CFA) and volume (CFV), and total SUV of the 16 segments. CMR tissue characterization parameters included cardiac function, myocardial thickness, late gadolinium enhancement (LGE), relaxation time, extracellular volume (ECV), and peak strain parameters. The 5-year sudden cardiac death (SCD) risk score and the 2-year and 5-year atrial fibrillation (AF) risk scores were calculated for each patient. The study analyzed differences between HCM patients and controls, the correlation between [68Ga]Ga-FAPI-04 PET and concurrent CMR imaging results, and the predictive value of PET/CMR. Result: The FAPI uptake, myocardial mass, myocardial thickness, and T1/T2 mapping values were significantly higher in HCM patients compared to controls. Twenty HCM patients and their 320 myocardial segments were discussed. Increased [68Ga]Ga-FAPI-04 uptake in the left ventricular wall was observed in 95% (19/20) of the patients, covering 48.8% (156/320) of the segments. On concurrent CMR, 80% (16/20) of the patients showed LGE, including 95 (29.7%) segments. The FAPI(+)LGE(+) segments exhibited the highest myocardial PET uptake, greatest thickness, longest T1/T2 native values, largest ECV value and the greatest loss of myocardial strain capacity (P < 0.05). There was a significant correlation between FAPI uptake and CMR parameters (P < 0.05). Higher [68Ga]Ga-FAPI-04 uptake showed a positive correlation with SCD and AF risk scores (P < 0.05). The number of LGE(+) segments, mapping parameters, and ECV values in CMR also had prognostic significance. Combining PET with CMR aided in further risk stratification of HCM. Conclusion: [68Ga]Ga-FAPI-04 PET/CMR multimodal imaging has potential value in the detection of damaged myocardial lesions and risk assessment of HCM patients. [68Ga]Ga-FAPI-04 PET can detect more affected myocardium compared to CMR, and segments with abnormalities in both PET and CMR show more severe myocardial damage. [ABSTRACT FROM AUTHOR]

The impact of hypertension (HT) on phenotypic expression in individuals with hypertrophic cardiomyopathy (HCM) is unclear. Thirty-six HCM individuals without HT, 27 HCM with HT, and 20 age- and sex-matched healthy controls who underwent cardiovascular magnetic resonance imaging (CMR) to evaluate left ventricular (LV) function and strain were enrolled. Three groups' LV function and strain were compared. We also investigated whether HT was associated with reduced LV strain in HCM patients using univariate and multivariate linear regression analyses. HCM (with/without HT) patients had higher LV mass and LV mass index than the normal controls group. Furthermore, global radial strain, global circumferential strain (GCS), global longitudinal strain, global peak systolic strain rate of radial, and global peak diastolic strain rate of radial were significantly lower in HCM patients with HT, intermediate in HCM patients without HT, and greater in the normal controls (all, P<0.05). Worse GCS was observed in HCM patients with HT than those without HT (P<0.05). Multivariable linear regression analysis showed that HT was independently associated with impaired LV ejection fraction and reduced strain (all P<0.05). The presence of HT was associated with an adverse phenotype, including worse ejection fraction and reduced strains in HCM patients. In addition, management of HT and its effect on the clinical outcomes in HCM patients needs to be studied. • HT had an additive deleterious effect on LV strain in patients with HCM. • HT was associated with reduced strains in patients HCM. • CMR may be a valuable tool for detecting LV injury in HCM patients with HT. [ABSTRACT FROM AUTHOR]

Summary: Evidence suggests an association between obesity and the risk for cardiomyopathy development; however, robust evidence is still lacking. In this study we sought to explore the relationship of obesity with hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) and possible interactions with sex using large‐scale epidemiological real‐world data. We analysed data from the Nationwide Inpatient Sample of US hospitalisations for the years 2015–2019. There were a total of 46 934 admissions with diagnosis of HCM and 170 924 with DCM. There was a significant interaction between cardiomyopathies' diagnosis with sex and age subgroups; the rates of both DCM and HCM increased with age (p <.001 for both); DCM diagnosis was significantly higher in males compared with females (0.85% vs. 0.35%, p <.001). After adjustment for age, sex, race and presence of arterial hypertension there was a significant stepwise positive association between obesity and the population rates of both cardiomyopathy subtypes. For hospitalised patients with a body mass index (BMI) ≥30 kg/m2 there was an odds ratio (OR) of 1.68 (95% CI: 1.55–1.81, p <.001) for HCM and OR = 1.82 (95% CI: 1.79–1.84, p <.001) for DCM. More importantly, the positive relationship between a cardiomyopathy diagnosis (HCM or DCM) with increasing BMI was driven by the male sex (p <.001 for both) and it was non‐significant in females. The findings from this nationwide observational analysis support a sexual dimorphism in the relationship between obesity and HCM or DCM, which should be further investigated. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM), a common cardiomyopathy in children, is an important cause of morbidity and mortality. Early recognition and appropriate management are important. An electrocardiogram (ECG) is often used as a screening tool in children to detect heart disease. The ECG patterns in children with HCM are not well described.ECGs collected from an international cohort of children, and adolescents (≤ 21 years) with HCM were reviewed. 482 ECGs met inclusion criteria. Age ranged from 1 day to 21 years, median 13 years. Of the 482 ECGs, 57 (12%) were normal. The most common abnormalities noted were left ventricular hypertrophy (LVH) in 108/482 (22%) and biventricular hypertrophy (BVH) in 116/482 (24%) Of the patients with LVH/BVH (n = 224), 135 (60%) also had a strain pattern (LVH in 83, BVH in 52). Isolated strain pattern (in the absence of criteria for hypertrophy) was seen in 43/482 (9%). Isolated pathologic Q waves were seen in 71/482 (15%). Pediatric HCM, 88% have an abnormal ECG. The most common ECG abnormalities were LVH or BVH with or without strain. Strain pattern without hypertrophy and a pathologic Q wave were present in a significant proportion (24%) of patients. Thus, a significant number of children with HCM have ECG abnormalities that are not typical for "hypertrophy". The presence of the ECG abnormalities described above in a child should prompt further examination with an echocardiogram to rule out HCM. [ABSTRACT FROM AUTHOR]

In children with hypertrophic cardiomyopathy (HCM), the genotype–phenotype association of abnormal electrocardiographic (ECG) features in the backdrop of gene positivity has not been well described. This study aimed to describe the abnormal ECG findings in children with HCM harboring who have genetic variants and determine the association with major adverse cardiac events (MACE). We retrospectively analyzed 81 variants-positive, phenotype-positive (V+P+), 66 variant-positive, phenotype-negative (V+P−), and 85 non-sarcomeric subjects. We analyzed ECG findings and clinical outcomes in the three groups of subjects. Repolarization abnormalities (ST and T wave changes) and pathologic Q waves were the most common abnormalities in variant and non-sarcomeric subjects. The V+P+ group showed higher occurrence of ST segment changes and T wave abnormalities compared to V+P− group. Independent predictors of MACE included ST segment changes (OR 3.54, CI 1.20–10.47, p = 0.022). T wave changes alone did not predict outcome (OR 2.13, CI 0.75–6.07, p = 0.157), but combined repolarization abnormalities (ST+T changes) were strong predictors of MACE (OR 5.84, CI 1.43–23.7, p = 0.014) than ST segment changes alone. Maximal wall z score by echocardiography was a predictor of MACE (OR 1.21, CI 1.07–1.37, p = 0.002). Despite the presence of significant myocardial hypertrophy (z score > 4.7), voltage criteria for LVH were much less predictive. In the non-sarcomeric group, RVH was significantly associated with MACE (OR 3.85, CI 1.08–13.73, p = 0.038). These abnormal ECG findings described on the platform of known genetic status and known myocardial hypertrophy may add incremental value to the diagnosis and surveillance of disease progression in children with HCM. Select ECG findings, particularly repolarization abnormalities, may serve as predictors of MACE in children. [ABSTRACT FROM AUTHOR]

The clinical significance of numerous cardiovascular gene variants remains to be determined. CRISPR/Cas9 allows for the introduction and/or correction of a certain variant in induced pluripotent stem cells (iPSCs). The resulting isogenic iPSC lines can be differentiated into cardiomyocytes and used as a platform to assess the pathogenicity of the variant. In this study, isogenic iPSC lines were generated for a variant of unknown significance found previously in a patient with hypertrophic cardiomyopathy (HCM), p.N515del (c.1543_1545delAAC) in MYBPC3. The deletion was corrected with CRISPR/Cas9 in the patient-specific iPSCs. The iPSC lines with the corrected deletion in MYBPC3 maintained pluripotency and a normal karyotype and showed no off-target CRISPR/Cas9 activity. The isogenic iPSC lines, together with isogenic iPSC lines generated earlier via introducing the p.N515del (c.1543_1545delAAC) variant in MYBPC3 of iPSCs of a healthy donor, were differentiated into cardiomyocytes. The cardiomyocytes derived from both panels of the isogenic iPSCs showed an increased size in the presence of the deletion in MYBPC3, which is one of the HCM traits at the cellular level. This finding indicates the effectiveness of these iPSC lines for studying the impact of the variant on HCM development. [ABSTRACT FROM AUTHOR]

The combination of hypertrophic cardiomyopathy with outflow tract obstruction, severe pre-capillary and post-capillary pulmonary hypertension, and severe primary mitral regurgitation is rare and presents distinct management challenges. Background and Clinical Significance: Pulmonary hypertension is an independent predictor of all-cause mortality in patients with hypertrophic cardiomyopathy managed medically and often precludes patients from undergoing cardiopulmonary bypass due to increased surgical morbidity and mortality. In studies specifically evaluating surgical myectomy, however, survival is favorable in patients with moderate-to-severe pulmonary hypertension. Case Presentation: We present a case of a 74-year-old male with six months of dyspnea with minimal exertion. A diagnostic work-up with transthoracic echocardiogram showed asymmetric left ventricular hypertrophy, left ventricular outflow tract obstruction with a peak gradient of 200 mmHg, right ventricular systolic pressure of 99 mmHg, systolic anterior motion of the mitral valve and flail anterior mitral leaflet. The patient was evaluated by a multi-disciplinary team and underwent extended septal myectomy and mitral valve repair with significant improvement in functional capacity post-operatively. Conclusions: While pulmonary hypertension increases the risk of morbidity and mortality during cardiopulmonary bypass, moderate-to-severe pulmonary hypertension in hypertrophic cardiomyopathy with outflow tract obstruction is a unique indication for septal reduction therapy that may not be associated with higher surgical mortality. [ABSTRACT FROM AUTHOR]