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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

Aims Methods and results Conclusion The aim of this study was to investigate whether the H2FPEF score, which was developed to improve the diagnosis of heart failure (HF) with preserved ejection fraction, is associated with HF outcomes in patients with hypertrophic cardiomyopathy (HCM).Patients with HCM and preserved left ventricular ejection fraction (LVEF ≥50%) were included from a multicentre registry and the H2FPEF score was calculated. Patients were divided into three groups: low (0–1), intermediate (2–5) and high (6–9) H2FPEF score. The primary combined endpoint was a composite of all‐cause death and HF admissions, while the secondary endpoints were all‐cause death and HF admissions separately. A total of 955 patients were included (age 51 ± 17 years, 310 [32.5%] female). Patients with a high H2FPEF score (n = 105) were more often female, and presented with more symptoms and comorbidities. On echocardiography, patients with a high H2FPEF score had lower LVEF, more impaired diastolic function and more frequently left ventricular outflow tract obstruction. During follow‐up (median 90 months [interquartile range 49–176]), 103 (11%) patients died and 57 (6%) patients had a first HF hospitalization. Event‐free survival rate for the primary combined and secondary endpoints was lower for patients with an intermediate and high H2FPEF score. On multivariate Cox regression analysis, female sex (hazard ratio [HR] 1.670, 95% confidence interval [CI] 1.157–2.410; p = 0.006), Asian ethnicity (HR 6.711, 95% CI 4.076–11.048; p < 0.001), ischaemic heart disease (HR 1.732, 95% CI 1.133–2.650; p =  0.011), left atrial diameter (HR 1.028, 95% CI 1.005–1.051; p = 0.016) and intermediate (HR 2.757, 95% CI 1.612–4.713; p < 0.001) or high H2FPEF score (HR 3.689, 95% CI 1.908–7.134; p < 0.001) were independently associated with the primary combined endpoint.The H2FPEF score is independently associated with HF outcome in patients with HCM and may be considered for risk stratification. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is caused by myocardial hypertrophy, often due to mutations in cardiac sarcomere protein genes such as beta-myosin heavy chain (MYH7) and myosin-binding protein C (MYBPC3). However, a significant proportion of HCM cases lack identified genetic mutations, and genotypephenotype correlations remain unclear. Concurrently, potential associations between HCM and human leukocyte antigen (HLA) types, as well as connective tissue diseases, have been proposed. In this single-center study, we aimed to investigate the genetic and HLA profiles of patients with obstructive hypertrophic cardiomyopathy (HOCM) and connective tissue diseases, particularly focusing on the prevalence of genetic variants and HLA types. We conducted a detailed analysis of five patients with HOCM and connective tissue diseases and sarcoidosis, identifying rare variants in causative genes for HCM in two cases and observing specific HLA types that were relatively common. Notably, 15% of all HOCM cases presented with connective tissue diseases, mainly rheumatoid arthritis. These findings underscore the complexity of HCM etiology and suggest potential implications for both diagnostic strategies and therapeutic approaches in patients with concomitant inflammatory conditions. [ABSTRACT FROM AUTHOR]

Mavacamten is a selective, allosteric, reversible cardiac myosin inhibitor that has been developed for the treatment of adults with symptomatic obstructive hypertrophic cardiomyopathy (HCM). A population pharmacokinetic (PopPK) model was developed to characterize mavacamten pharmacokinetics (PK) and the variation in mavacamten exposure associated with intrinsic and extrinsic factors. Data from 12 clinical studies (phases 1, 2, and 3) were used. Evaluable participants were those who had at least one mavacamten concentration measurement with associated sampling time and dosing information. The base model included key covariates: body weight, cytochrome P450 isozyme 2C19 (CYP2C19) phenotype with respect to PK, and formulation. The final model was generated using stepwise covariate testing and refinement processes. Simulations were performed to evaluate PK: apparent clearance (CL/F); apparent central and peripheral volumes of distribution; and steady‐state average, trough, and maximum concentrations. Overall, 9244 measurable PK observations from 497 participants were included. A two‐compartment model structure was selected. After stepwise covariate model building and refinement, additional covariates included were: specified mavacamten dose, omeprazole or esomeprazole administration, health/disease status, estimated glomerular filtration rate, fed status, and sex. The final PopPK model accurately characterized mavacamten concentrations. At any given dose, CYP2C19 phenotype was the most influential covariate on exposure parameters (e.g., median CL/F was reduced by 72% in CYP2C19:poor metabolizers compared with the reference participant [CYP2C19:normal metabolizer]). CL/F was also approximately 16% higher in women than in men but lower in participants receiving concomitant omeprazole or esomeprazole (by 33% and 42%, respectively) than in participants not receiving such concomitant therapy. [ABSTRACT FROM AUTHOR]

Background: The adverse prognostic impact of diabetes on hypertrophic cardiomyopathy (HCM) is poorly understood. We sought to explore the underlying mechanisms in terms of structural and functional remodelling in HCM patients with coexisting diabetes (HCM-DM). Methods: A total of 45 HCM-DM patients were retrospectively included. Isolated HCM controls (HCM patients without diabetes) were matched to HCM-DM patients in terms of maximal wall thickness, age, and gender distribution. Left ventricular (LV) and atrial (LA) performance were evaluated using cardiac magnetic resonance feature tracking strain analyses. The associations between diabetes and LV/LA impairment were investigated by univariable and multivariable linear regression. Results: Compared with the isolated HCM controls, the HCM-DM patients had smaller end-diastolic volume and stroke volume, lower ejection fraction, larger mass/volume ratio and impaired strains in all three directions (all P < 0.05). In terms of the LA parameters, HCM-DM patients presented impaired LA reservoir and conduit strain/strain rate (all P < 0.05). Among all HCM patients, comorbidity with diabetes was independently associated with a low LV ejection fraction (β = − 6.05, P < 0.001) and impaired global longitudinal strain (β = 1.40, P = 0.007). Moreover, compared with the isolated HCM controls, HCM-DM patients presented with more myocardial fibrosis according to late gadolinium enhancement, which was an independent predictor of impaired LV global radial strain (β = − 45.81, P = 0.008), LV global circumferential strain (β = 18.25, P = 0.003), LA reservoir strain (β = − 59.20, P < 0.001) and strain rate (β = − 2.90, P = 0.002). Conclusions: Diabetes has adverse effects on LV and LA function in HCM patients, which may be important contributors to severe manifestations and outcomes in those patients. The present study strengthened the evidence of the prevention and management of diabetes in HCM patients. [ABSTRACT FROM AUTHOR]

Background: Patients with obstructive hypertrophic cardiomyopathy (oHCM) have a substantial humanistic, clinical, and economic burden due to the array of symptoms and complications associated with the disease. The objective of this review was to identify key evidence gaps related to oHCM, specifically in Europe, North America, and Japan. Methods: A targeted literature review was conducted using PubMed to identify English-language studies published between 2012 and 2022 assessing patients with HCM/oHCM in France, Germany, Italy, Spain, the United Kingdom (UK), the United States (US), Canada, and Japan. Outcomes of interest were epidemiology, natural history, pathophysiology, management, and clinical, economic, and humanistic burden. Identified studies were assessed qualitatively to characterize evidence gaps. Results: Among 2,262 abstracts and 531 full-text articles screened, 178 articles were included from PubMed searches. An additional 16 unique studies were identified via a supplemental Google Scholar search initially conducted in January 2023 and updated in July 2024. Disease natural history, pathophysiology, and management were well documented globally. Significant evidence gaps were noted for the epidemiology, treatment, and burden of oHCM. Although multiple US studies were identified on the clinical, economic, and humanistic burden of oHCM, and one clinical burden study was found for Japan, there was a lack of evidence for France, Germany, Italy, Spain, the UK, and Canada. Conclusions: Major evidentiary gaps exist for the epidemiology, treatment, and burden of oHCM. Future research should address these gaps, with a specific focus on generating real-world evidence for Canada and European countries that will support the evaluation of emerging therapies in these regions. [ABSTRACT FROM AUTHOR]

Deficiency of adipose triglyceride lipase (ATGL) due to mutation in PNPLA2 causes neutral lipid storage disease with myopathy (NLSDM), an autosomal recessive disorder (MIM: #610717). NLSDM patients are mainly affected by progressive myopathy, cardiomyopathy, and hepatomegaly. Cardiac involvement was reported in 40%-50% of NLSDM patients. Patients with cardiac involvement have adult-onset progressive heart failure, mimicking dilated or hypertrophic cardiomyopathy. The clinical characteristics, genotype-phenotype correlation, and prognosis of cardiomyopathy secondary to PNPLA2 mutation are not understood. We reported two male patients carrying a homozygous splicing mutation NM_020376.4 (c.757 + 1G>T) in PNPLA2, presenting with severe dilated cardiomyopathy and mild skeletal muscle involvement. Through the literature review, the ECG and imaging features and the prognosis of 49 previously reported cases of cardiomyopathy caused by the PNPLA2 mutation were summarized. This study suggests that NLSDM should be considered a cause of cardiomyopathy, especially in those with elevated creatine kinase (CK) levels, regardless of whether symptoms such as muscle weakness or atrophy are present. [ABSTRACT FROM AUTHOR]

Rest imaging in hypertrophic cardiomyopathy may underestimate or miss left ventricular outflow tract obstruction, leading to suboptimal management decisions that negatively affect symptomatic patients. The 2024 hypertrophic cardiomyopathy guidelines describe exercise stress testing as an important tool to determine overall exercise tolerance and latent, exercise-provoked left ventricular outflow tract obstruction. [ABSTRACT FROM AUTHOR]

Pathogenic variation in genes encoding proteins of the cardiac sarcomere is responsible for 30%–40% of cases of hypertrophic cardiomyopathy. The main clinical utility of genetic testing is to provide diagnostic confirmation and facilitation of family screening. It also assists in the detection of aetiologies, which require distinct monitoring and treatment approaches. Other clinical applications, including the use of genetic information to inform risk prediction models, have been limited by the challenge of establishing robust genotype–phenotype correlations with actionable consequences, but new data on the interaction between rare and common genetic variation, as well as the emergence of therapies targeting disease-specific pathogenic mechanisms, herald a new era for genetic testing in routine practice. [ABSTRACT FROM AUTHOR]

Simple Summary: Hypertrophic cardiomyopathy is the most common acquired heart disease of cats. Arrhythmias are frequently observed in cats with hypertrophic cardiomyopathy, contributing to the complexity of the condition. Understanding rhythm disturbances associated with feline hypertrophic cardiomyopathy is crucial, as they could contribute to diagnosing the condition, risk stratification, and therapeutic management. By analyzing the current level of knowledge regarding arrythmias associated with feline hypertrophic cardiomyopathy, this study aimed to assess the utility of available diagnostic methods. Even though progress has been made in understanding arrythmias linked to hypertrophic cardiomyopathy, further research is needed to better assess their diagnostic and prognostic value, as well as the potential benefits of anti-arrhythmic therapy for affected cats. Hypertrophic cardiomyopathy (HCM) is a common heart disease in cats, characterized by regional or diffuse hypertrophy of the left ventricular walls, with an uncertain etiology and heterogenous natural history. Several types of rhythm disturbances are often associated with the disease. This study conducts a comprehensive review of the current literature, in order to evaluate the diagnostic and prognostic effectiveness of electrocardiography and Holter monitoring in the management of feline hypertrophic cardiomyopathy. The main subjects of discussion will include general information about HCM and its connection to arrhythmias. We will explore the rhythm disturbances documented in the current literature on Holter monitoring, as well as the techniques used for Holter monitoring. Additionally, the review will cover classical electrocardiography (ECG) and its diagnostic utility. Prognostic indicators and anti-arrhythmic therapy will also be discussed in detail. The findings highlight the importance of understanding arrhythmias in feline HCM for accurate diagnosis, risk assessment, and therapeutic intervention. ECG and Holter monitoring may offer valuable insights into managing feline HCM. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is a genetic disease characterized by unexplained left ventricular hypertrophy (LVH), diastolic dysfunction, and increased sudden-death risk. Early detection of the phenotypic expression of the disease in genetic carriers without LVH (Gen+/Phen−) is crucial for emerging therapies. This clinical study aims to identify echocardiographic predictors of phenotypic development in Gen+/Phen−. Sixteen Gen+/Phen− (one subject with troponin T, six with myosin heavy chain-7, and nine with myosin-binding protein C3 mutations), represented the study population. At first and last visit we performed comprehensive 2D speckle-tracking strain echocardiography. During a follow-up of 8 ± 5 years, five carriers developed LVH (LVH+). At baseline, these patients were older than those who did not develop LVH (LVH−) (30 ± 8 vs. 15 ± 8 years, p = 0.005). LVH+ had reduced peak global strain rate during the isovolumic relaxation period (SRIVR) (0.28 ± 0.05 vs. 0.40 ± 0.11 1/s, p = 0.048) and lower global longitudinal strain (GLS) (−19.8 ± 0.4 vs. −22.3 ± 1.1%; p < 0.0001) than LVH- at baseline. SRIVR and GLS were not correlated with age (overall, p > 0.08). This is the first HCM study investigating subjects before they manifest clinically significant or relevant disease burden or symptomatology, comparing at baseline HCM Gen+/Phen− subjects who will develop LVH with those who will not. Furthermore, we identified highly sensitive, easily obtainable, age- and load-independent echocardiographic predictors of phenotype development in HCM gene carriers who may undergo early preventive treatment. [ABSTRACT FROM AUTHOR]

Aims Methods and results Conclusions The heterogeneous phenotype of hypertrophic cardiomyopathy (HCM) is still not fully understood. Clonal haematopoiesis (CH) is emerging as a cardiovascular risk factor potentially associated with adverse clinical events. The prevalence, phenotype and outcomes related to CH in HCM patients were evaluated.Patients with HCM and available biospecimens from the Peter Munk Cardiac Centre Cardiovascular Biobank were subjected to targeted sequencing for 35 myeloid genes associated with CH. CH prevalence, clinical characteristics, morphological phenotypes assessed by echocardiogram and cardiac magnetic resonance and outcomes were assessed. All patients were evaluated for a 71‐plex cytokines/chemokines, troponin I and B‐type natriuretic peptide analysis. Major adverse cardiovascular events (MACE) were defined as appropriate implantable cardioverter‐defibrillator shock, stroke, cardiac arrest, orthotopic heart transplant and death. Among the 799 patients, CH was found in 183 (22.9%) HCM patients with sarcomeric germline mutations. HCM patients with CH were more symptomatic and with a higher burden of fibrosis than those without CH. CH was associated with MACE in those HCM patients with sarcomeric germline mutations (adjusted hazard ratio [HR] 6.89, 95% confidence interval [CI] 1.78–26.6; p = 0.005), with the highest risk among those that had DNMT3A, TET2 and ASXL1 mutations (adjusted HR 5.76, 95% CI 1.51–21.94; p = 0.010). Several cytokines (IL‐1ra, IL‐6, IL‐17F, TGFα, CCL21, CCL1, CCL8, and CCL17), and troponin I were upregulated in gene‐positive HCM patients with CH.These results indicate that CH in patients with HCM is associated with worse clinical outcomes. In the absence of CH, gene‐positive patients with HCM have lower rates of MACE. [ABSTRACT FROM AUTHOR]

• CRT 2024 shared the latest research in interventional cardiology. • We highlight results from the late-breaking clinical trials. • Areas covered include structural heart disease, coronary and intervention. • Other areas are RDN, peripheral vascular disease, and AI and machine learning. [ABSTRACT FROM AUTHOR]

The HSP70 co-chaperone BAG3 targets unfolded proteins to degradation via chaperone assisted selective autophagy (CASA), thereby playing pivotal roles in the proteostasis of adult cardiomyocytes (CMs). However, the complex functions of BAG3 for regulating autophagy in cardiac disease are not completely understood. Here, we demonstrate that conditional inactivation of Bag3 in murine CMs leads to age-dependent dysregulation of autophagy, associated with progressive cardiomyopathy. Surprisingly, Bag3 -deficient CMs show increased canonical and non-canonical autophagic flux in the juvenile period when first signs of cardiac dysfunction appear, but reduced autophagy during later stages of the disease. Juvenile Bag3 -deficient CMs are characterized by decreased levels of soluble proteins involved in synchronous contraction of the heart, including the gap junction protein Connexin 43 (CX43). Reiterative administration of chloroquine (CQ), an inhibitor of canonical and non-canonical autophagy, but not inactivation of Atg5 , restores normal concentrations of soluble cardiac proteins in juvenile Bag3 -deficient CMs without an increase of detergent-insoluble proteins, leading to complete recovery of early-stage cardiac dysfunction in Bag3 -deficient mice. We conclude that loss of Bag3 in CMs leads to age-dependent differences in autophagy and cardiac dysfunction. Increased non-canonical autophagic flux in the juvenile period removes soluble proteins involved in cardiac contraction, leading to early-stage cardiomyopathy, which is prevented by reiterative CQ treatment. [Display omitted] • Inactivation of Bag3 in CMs initiates hypertrophic cardiomyopathy in juvenile mice • Juvenile but not late stage Bag3 -deficient CMs show increased autophagic flux • Inactivation of Atg5 does not improve cardiac function in juvenile Bag3 -cKO mice • Treatment with chloroquine normalizes cardiac function in juvenile Bag3 -cKO mice • Human BAG3P209L heart samples show similar changes as in Bag3 -cKO mice [ABSTRACT FROM AUTHOR]

The cumulative burden of hypertrophic cardiomyopathy (HCM) is significant, with a noteworthy percentage (10%-15%) of patients with HCM per year experiencing major adverse cardiovascular events (MACEs). A current risk stratification scheme for HCM had only limited accuracy in predicting sudden cardiac death (SCD) and failed to account for a broader spectrum of adverse cardiovascular events and cardiac magnetic resonance (CMR) parameters. This study sought to develop and evaluate a machine learning (ML) framework that integrates CMR imaging and clinical characteristics to predict MACEs in patients with HCM. A total of 758 patients with HCM (67% male; age 49 ± 14 years) who were admitted between 2010 and 2017 from 4 medical centers were included. The ML model was built on the internal discovery cohort (533 patients with HCM, admitted to Fuwai Hospital, Beijing, China) by using the light gradient-boosting machine and internally evaluated using cross-validation. The external test cohort consisted of 225 patients with HCM from 3 medical centers. A total of 14 CMR imaging features (strain and late gadolinium enhancement [LGE]) and 23 clinical variables were evaluated and used to inform the ML model. MACEs included a composite of arrhythmic events, SCD, heart failure, and atrial fibrillation–related stroke. MACEs occurred in 191 (25%) patients over a median follow-up period of 109.0 months (Q1-Q3: 73.0-118.8 months). Our ML model achieved areas under the curve (AUCs) of 0.830 and 0.812 (internally and externally, respectively). The model outperformed the classic HCM Risk-SCD model, with significant improvement (P < 0.001) of 22.7% in the AUC. Using the cubic spline analysis, the study showed that the extent of LGE and the impairment of global radial strain (GRS) and global circumferential strain (GCS) were nonlinearly correlated with MACEs: an elevated risk of adverse cardiovascular events was observed when these parameters reached the high enough second tertiles (11.6% for LGE, 25.8% for GRS, −17.3% for GCS). ML-empowered risk stratification using CMR and clinical features enabled accurate MACE prediction beyond the classic HCM Risk-SCD model. In addition, the nonlinear correlation between CMR features (LGE and left ventricular pressure gradient) and MACEs uncovered in this study provides valuable insights for the clinical assessment and management of HCM. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, we describe the incidence, sites of valve injury, and the influence of aortic valve regurgitation (AR) on outcomes of septal myectomy for obstructive hypertrophic cardiomyopathy. We analyzed patients who underwent transaortic septal myectomy for obstructive hypertrophic cardiomyopathy from 2001 to 2022. The primary study end point was incidence of procedure-related AR, defined as the need for an unplanned aortic valve (AV) procedure or new-onset moderate AR on early postoperative echocardiography. There were 2807 patients who underwent transaortic septal myectomy for hypertrophic cardiomyopathy and had pre- and postoperative transthoracic echocardiograms. Procedure-related AR was observed in 55 (2%) patients; 27 (1%) required unplanned AV procedures at the time of myectomy, and 29 (1%) additional patients developed moderate AR postoperatively. During follow-up, 9 total patients underwent late AV reoperation, 1 patient who developed new moderate AR postoperatively required late AVR due to severe calcific AS, and none of the patients who had unplanned AV procedures required late reoperation. The overall cumulative incidence of AV reoperation at 10 and 15 years was 1% and 5%. The predicted probability of moderate or severe AR at 5 and 10 years was 1.4% and 1.8%, respectively. There was no difference in survival comparing patients with or without early postoperative mild or worse AR (P =.69). Procedure-related AR was observed in 2% of patients undergoing transaortic septal myectomy, and unplanned AV procedures were necessary for half of these patients. Intraoperative identification and valve repair mitigate the impact of cusp injury on late reintervention and survival. [Display omitted] [ABSTRACT FROM AUTHOR]

Patients with hypertrophic cardiomyopathy (HCM) are at risk of sudden death, and individuals with ≥1 major risk markers are considered for primary prevention implantable cardioverter-defibrillators. Guidelines recommend cardiac magnetic resonance (CMR) imaging to identify high-risk imaging features. However, CMR imaging is resource intensive and is not widely accessible worldwide. The purpose of this study was to develop electrocardiogram (ECG) deep-learning (DL) models for the identification of patients with HCM and high-risk imaging features. Patients with HCM evaluated at Tufts Medical Center (N = 1930; Boston, MA) were used to develop ECG-DL models for the prediction of high-risk imaging features: systolic dysfunction, massive hypertrophy (≥30 mm), apical aneurysm, and extensive late gadolinium enhancement. ECG-DL models were externally validated in a cohort of patients with HCM from the Amrita Hospital HCM Center (N = 233; Kochi, India). ECG-DL models reliably identified high-risk features (systolic dysfunction, massive hypertrophy, apical aneurysm, and extensive late gadolinium enhancement) during holdout testing (c-statistic 0.72, 0.83, 0.93, and 0.76) and external validation (c-statistic 0.71, 0.76, 0.91, and 0.68). A hypothetical screening strategy using echocardiography combined with ECG-DL–guided selective CMR use demonstrated a sensitivity of 97% for identifying patients with high-risk features while reducing the number of recommended CMRs by 61%. The negative predictive value with this screening strategy for the absence of high-risk features in patients without ECG-DL recommendation for CMR was 99.5%. In HCM, novel ECG-DL models reliably identified patients with high-risk imaging features while offering the potential to reduce CMR testing requirements in underresourced areas. [Display omitted] [ABSTRACT FROM AUTHOR]

Purpose of Review: Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac condition with potential for severe complications including sudden cardiac death. Early diagnosis allows appropriate risk stratification and prompt intervention to minimise the potential for adverse outcomes. The implications of poorly coordinated screening are significant, either missing relatives at high-risk or burdening low-risk individuals with a diagnosis associated with reduced life expectancy. We aim to guide clinicians through the diagnostic pathway through to novel treatment options. Several conditions mimic the condition, and we discuss the phenocopies and how to differentiate from HCM. Recent Findings: We summarise the latest developments informing clinical decision making in the modern era of myosin inhibitors and future gene editing therapies. Early identification will enable prompt referral to specialist centres. Summary: A diagnostic flowchart is included, to guide the general cardiology and heart failure clinician in important decision making regarding the care of the HCM patient and importantly their relatives at risk. We have highlighted the importance of screening because genotype-positive/phenotype-negative patients are likely to have the most to gain from novel therapies. [ABSTRACT FROM AUTHOR]

A 15‐month‐old female Ragdoll cat was evaluated for progressive lethargy, tachypnoea and increased respiratory effort for 1 week after routine ovariohysterectomy. Thoracic radiographs and an echocardiogram showed evidence of congestive heart failure and a hypertrophic cardiomyopathy phenotype, respectively. The maximum left ventricular wall thickness in end diastole was 6.2 mm. The serum cardiac troponin I concentration was 20.86 ng/mL. The cat was treated with furosemide and clopidogrel and discharged after 3 days. A repeat echocardiogram 2 weeks later showed complete resolution of the hypertrophic cardiomyopathy phenotype (maximum left ventricular wall thickness: 5.0 mm). A repeat cardiac troponin I concentration was 0.041 ng/mL. All cardiac medications were discontinued. A final recheck 4 weeks later revealed stable normal echocardiogram and further reduction in cardiac troponin I concentration to 0.004 ng/mL. This case report demonstrates that resolution of transient myocardial thickening can take 2 weeks after the echocardiographic diagnosis of left ventricular thickening. [ABSTRACT FROM AUTHOR]

The use of various model organisms has made a huge contribution to understanding the causes and mechanisms of disease development and the study of pathological processes occurring during the development of diseases of the human cardiovascular system, and, in particular, hypertrophic cardiomyopathy (HCM). The optimal solution in the study of primary molecular disturbances is the use of cellular models such as induced pluripotent stem cells (iPSCs), primary rodent cardiomyocytes (CMs), and immortalized lines. In this review, we have focused on the most commonly used cell models, including freshly isolated adult and neonatal rodent CMs, and on the commercially available immortalized cell lines (HL-1, AC16, and H9c2). In order to assess the adequacy of these lines as CM models for studying human myocardial pathologies, a comparative analysis of phenotypic characteristics (morphology, metabolism, calcium homeostasis, etc.) and the nuances of practical use (availability, response to hypertrophic inducers, transfection, etc.) was carried out. The latest published data on the use of these models to assess the pathogenicity of HCM-associated mutations, as well as to screen the effectiveness of developed therapeutic drugs, are also summarized. [ABSTRACT FROM AUTHOR]

Background: Inherited cardiomyopathies (HCM, DCM, ACM) and cardiac ion channelopathies (long QT/Brugada syndromes, CPVT) are associated with significant morbidity and mortality; however, diagnosis of a familial pathogenic variant in a proband allows for subsequent cascade screening of their at-risk relatives. Aims: We investigated the diagnostic yield from cardiac gene panel testing and reviewed variants of uncertain significance from patients attending three specialist cardiogenetics services in Ireland in the years 2002 to 2020. Results: Reviewing molecular genetic diagnostic reports of 834 patients from 820 families, the initial diagnostic yield of pathogenic/likely pathogenic variants was 237/834 patients (28.4%), increasing to 276/834 patients (33.1%) following re-evaluation of cases with variant(s) of uncertain significance. Altogether, 42/85 patients with VUS reviewed (49.4%) had a re-classification that could change their clinical management. Females were more likely to carry pathogenic/likely pathogenic variants than males (139/374, 37.2% vs 137/460, 29.8%, respectively, p = 0.03), and the diagnostic yields were highest in the 0 to < 2 years age group (6/12, 50.0%) and amongst those tested for cardiomyopathy gene panels (13/35, 37.1%). Variants in the MYBPC3/MYH7 (87/109, 79.8%) and KCNQ1/KCNH2 (91/100, 91.0%) genes were the predominant genetic causes for hypertrophic cardiomyopathy and long QT syndrome, respectively. Conclusion: Our study highlights the importance of collation and review of pre-ACMG genetic variants to increase diagnostic utility of genetic testing for inherited heart disease. Almost half of patients with pre-ACMG VUS reviewed had their variant re-classified to likely pathogenic/likely benign which resulted in a positive clinical impact for patients and their families. [ABSTRACT FROM AUTHOR]

This article discusses a case report of two sisters with hypertrophic cardiomyopathy (HCM) who exhibit differences in genetic mutations and clinical presentation. HCM is a genetic disorder characterized by thickening of the heart muscle. The sisters both experienced symptoms such as chest pain and palpitations, but one sister also had a cerebral infarction. Genetic testing revealed mutations in the MYH7 and RYR2 genes in both sisters, while the younger sister carried an additional mutation in the AKAP9 gene. The findings suggest that different mutations can lead to variations in the severity and clinical manifestations of HCM. Further research is needed to understand the role of AKAP9 in HCM. [Extracted from the article]

Aims: The study aims to investigate exercise‐limiting factors in hypertrophic cardiomyopathy (HCM) using combined stress echocardiography and cardiopulmonary exercise test. Methods and results: A symptom‐limited ramp bicycle exercise test was performed in the semi‐supine position on a tilting dedicated ergometer. Echocardiographic images were obtained concurrently with gas exchange measurements along predefined stages of exercise. Oxygen extraction was calculated using the Fick equation at each activity level. Thirty‐six HCM patients (mean age 67 ± 6 years, 72% men, 18 obstructive HCM) were compared with age and sex‐matched 29 controls. At rest, compared with controls, E/E′ ratio (6.26 ± 2.3 vs. 14 ± 2.5, P < 0.001) and systolic pulmonary artery pressures (SPAP) (22.6 ± 3.4 vs. 34 ± 6.2 mmHg, P = 0.023) were increased. Along with the stages of exercise (unloaded; anaerobic threshold; peak), diastolic function worsened (E/e′ 8.9 ± 2.6 vs. 13.8 ± 3.6 P = 0.011; 9.4 ± 2.3 vs. 18.6 ± 3.3 P = 0.001; 8.7 ± 1.9 vs. 21.5 ± 4, P < 0.001), SPAP increased (23 ± 2.7 vs. 33 ± 4.4, P = 0.013; 26 ± 3.2 vs. 40 ± 2.9, P < 0.001; 26 ± 3.5 vs. 45 ± 7 mmHg, P < 0.001), and oxygen consumption (6.6 ± 1.7 vs. 6.8 ± 1.6, P = 0.86; 18.1 ± 2.2 vs. 14.6 ± 1.5, P = 0.008; 20.3 ± 3 vs. 15.1 ± 2.1 mL/kg/min, P = 0.01) was reduced. Oxygen pulse was blunted (6.3 ± 1.8 vs. 6.2 ± 1.9, P = 0.79; 10 ± 2.1 vs. 8.8 ± 1.6, P = 0.063; 12.2 ± 2 vs. 8.2 ± 2.3 mL/beat, P = 0.002) due to an insufficient increase in both stroke volume (92.3 ± 17 vs. 77.3 ± 14.5 P = 0.021; 101 ± 19.1 vs. 87.3 ± 15.7 P = 0.06; 96.5 ± 12.2 vs. 83.6 ± 16.1 mL, P = 0.034) and oxygen extraction (0.07 ± 0.03 vs. 0.07 ± 0.02, P = 0.47; 0.13 ± 0.02 vs. 0.10 ± 0.03, P = 0.013; 0.13 ± 0.03 vs. 0.11 ± 0.03, P = 0.03). Diastolic dysfunction, elevated SPAP, and the presence of atrial fibrillation were associated with reduced exercise capacity. Conclusions: Both central and peripheral cardiovascular limitations are involved in exercise intolerance in HCM. Diastolic dysfunction seems to be the main driver for this limitation. [ABSTRACT FROM AUTHOR]