Search

BACKGROUND AND AIMS: The role of biomarker testing in the management of obstructive hypertrophic cardiomyopathy is not well defined. This pre-specified analysis of SEQUOIA-HCM (NCT05186818) sought to define the associations between clinical characteristics and baseline concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI), and to evaluate the effect of treatment with aficamten on biomarker concentrations. METHODS: Cardiac biomarkers were measured at baseline and serially throughout the study. Regression analyses determined predictors of baseline NT-proBNP and hs-cTnI concentrations, and evaluated whether early changes in these biomarkers relate to later changes in left ventricular outflow tract gradient (LVOT-G), other echocardiographic measures, health status, and functional capacity. RESULTS: Baseline concentration of NT-proBNP was associated with LVOT-G and measures of diastolic function, while hs-cTnI was associated with left ventricular thickness. Within 8 weeks of treatment with aficamten, NT-proBNP was reduced by 79% (95% confidence interval 76%-83%, P < .001) and hs-cTnI by 41% (95% confidence interval 32%-49%, P < .001); both biomarkers reverted to baseline after washout. Reductions in NT-proBNP and hs-cTnI by 24 weeks were strongly associated with a lowering of LVOT-G, improvement in health status, and increased peak oxygen uptake. N-Terminal pro-B-type natriuretic peptide reduction strongly correlated with the majority of improvements in exercise capacity. Furthermore, the change in NT-proBNP by Week 2 was associated with the 24-week change in key endpoints. CONCLUSIONS: N-Terminal pro-B-type natriuretic peptide and hs-cTnI concentrations are associated with key variables in obstructive hypertrophic cardiomyopathy. Serial measurement of NT-proBNP and hs-cTnI appears to reflect clinical response to aficamten therapy.

Determining the pathogenicity of hypertrophic cardiomyopathy-associated mutations in the β-myosin heavy chain (MYH7) can be challenging due to its variable penetrance and clinical severity. This study investigates the early pathogenic effects of the incomplete-penetrant MYH7 G256E mutation on myosin function that may trigger pathogenic adaptations and hypertrophy. We hypothesized that the G256E mutation would alter myosin biomechanical function, leading to changes in cellular functions. We developed a collaborative pipeline to characterize myosin function across protein, myofibril, cell, and tissue levels to determine the multiscale effects on structure-function of the contractile apparatus and its implications for gene regulation and metabolic state. The G256E mutation disrupts the transducer region of the S1 head and reduces the fraction of myosin in the folded-back state by 33%, resulting in more myosin heads available for contraction. Myofibrils from gene-edited MYH7WT/G256E human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) exhibited greater and faster tension development. This hypercontractile phenotype persisted in single-cell hiPSC-CMs and engineered heart tissues. We demonstrated consistent hypercontractile myosin function as a primary consequence of the MYH7 G256E mutation across scales, highlighting the pathogenicity of this gene variant. Single-cell transcriptomic and metabolic profiling demonstrated upregulated mitochondrial genes and increased mitochondrial respiration, indicating early bioenergetic alterations. This work highlights the benefit of our multiscale platform to systematically evaluate the pathogenicity of gene variants at the protein and contractile organelle level and their early consequences on cellular and tissue function. We believe this platform can help elucidate the genotype-phenotype relationships underlying other genetic cardiovascular diseases.

The polymerization of myosin molecules into thick filaments in muscle sarcomeres is essential for cardiac contractility, with the attenuation of interactions between the heads of myosin molecules within the filaments being proposed to result in hypercontractility, as observed in hypertrophic cardiomyopathy (HCM). However, experimental evidence demonstrates that the structure of these giant macromolecular complexes is highly dynamic, with molecules exchanging between the filaments and a pool of soluble molecules on the minute timescale. Therefore, we sought to test the hypothesis that the enhancement of interactions between the heads of myosin molecules within thick filaments limits the mobility of myosin by taking advantage of mavacamten, a small molecule approved for the treatment of HCM. Myosin molecules were labeled in vivo with a green fluorescent protein (GFP) and imaged in intact hearts using multiphoton microscopy. Treatment of the intact hearts with mavacamten resulted in an unexpected > 5-fold enhancement in GFP-myosin mobility within the sarcomere. In vitro biochemical assays suggested that mavacamten enhanced the mobility of GFP-myosin by increasing the solubility of myosin molecules, through the stabilization of a compact/folded conformation of the molecules, once disassociated from the thick filaments. These findings provide alternative insight into the mechanisms by which molecules exchange into and out of thick filaments and have implications for how mavacamten may affect cardiac contractility.

Hypertrophic burn scars can occur due to imbalances in the healing process and affect quality of life. They can be assessed with the Patient and Observer Scar Assessment Scale (POSAS). This is an assessment instrument with both a patient scale and an observer scale. This study aimed to assess the reliability and validity of the POSAS score to measure the quality of scars in evaluating burns that produce scar tissue. It also aimed to determine similarities in the assessment of scar tissue using the POSAS score according to observers and patients. This cross-sectional study had a sample of 30 patients, including 19 women (63%). Assessments were performed before the initial treatment procedure and 1 and 6 months after. The post-incision scar tissue assessment results using the POSAS instrument were expressed as a score: 5-50 (observer), 6-60 (patient), or 11-110 (both total). The highest degree of burns was superficial-mid-dermal (20 patients; 67%). The POSAS assessment by doctors and patients tended to be the same and decreased at both months 1 and 6 after the treatment procedure. The mean total score was 51.3 ± 12.1 before treatment, 44.2 ± 9.5 at month 1, and 30.3 ± 5.9 at month 6. This study shows that in evaluating burns that produce hypertrophic scars, similarities exist in the POSAS score according to observers and patients. Precautions at the beginning of the observation will affect the POSAS score. [ABSTRACT FROM AUTHOR]

Aims: An association between obesity, metabolic abnormalities and clinical hypertrophic cardiomyopathy (HCM) expression has been reported. We investigated whether managing dyslipidaemia with fibrates could affect the clinical expression of HCM. Methods: We screened patients who used fibrates between 2010 and 2017 from a nationwide database. After excluding patients with a history of HCM, we identified fibrate‐user group (n = 412 823). We then constructed a 1:1 matched cohort of fibrate‐naïve participants (n = 412 823). After a 1 year lag period, we identified the incident HCM cases for the following 5 years. Results: During a median follow‐up period of 3.96 years, we identified 454 incident clinical HCM cases. After adjusting for covariates, fibrate use was associated with a lower risk of clinical HCM expression [hazard ratio (HR) 95% confidence interval (CI): 0.763 (0.630–0.924)]. In subgroup analyses, fibrate use was associated with a reduced risk of clinical HCM expression in patients with a body mass index ≥25 kg/m2 and those with abdominal obesity [HR (95% CI): 0.719 (0.553–0.934) and 0.655 (0.492–0.872)], but not in those without obesity. Fibrate use was also associated with lower risks of incident clinical HCM in patients with triglyceride levels ≥150 mg/dL and those with metabolic syndrome [HR (95% CI): 0.741 (0.591–0.929) and 0.750 (0.609–0.923)], but not in their counterparts. Regarding lifestyle behaviours, fibrate use appeared to provide more prognostic benefits in patients who currently smoked, consumed alcohol or did not engage in regular physical activities. Conclusion: The use of fibrates is associated with a lower incidence of clinical HCM expression. This association was also more prominent in those with obesity, unhealthy metabolic profiles and poor lifestyle behaviours. [ABSTRACT FROM AUTHOR]

Abstract Aims An association between obesity, metabolic abnormalities and clinical hypertrophic cardiomyopathy (HCM) expression has been reported. We investigated whether managing dyslipidaemia with fibrates could affect the clinical expression of HCM. Methods We screened patients who used fibrates between 2010 and 2017 from a nationwide database. After excluding patients with a history of HCM, we identified fibrate‐user group (n = 412 823). We then constructed a 1:1 matched cohort of fibrate‐naïve participants (n = 412 823). After a 1 year lag period, we identified the incident HCM cases for the following 5 years. Results During a median follow‐up period of 3.96 years, we identified 454 incident clinical HCM cases. After adjusting for covariates, fibrate use was associated with a lower risk of clinical HCM expression [hazard ratio (HR) 95% confidence interval (CI): 0.763 (0.630–0.924)]. In subgroup analyses, fibrate use was associated with a reduced risk of clinical HCM expression in patients with a body mass index ≥25 kg/m2 and those with abdominal obesity [HR (95% CI): 0.719 (0.553–0.934) and 0.655 (0.492–0.872)], but not in those without obesity. Fibrate use was also associated with lower risks of incident clinical HCM in patients with triglyceride levels ≥150 mg/dL and those with metabolic syndrome [HR (95% CI): 0.741 (0.591–0.929) and 0.750 (0.609–0.923)], but not in their counterparts. Regarding lifestyle behaviours, fibrate use appeared to provide more prognostic benefits in patients who currently smoked, consumed alcohol or did not engage in regular physical activities. Conclusion The use of fibrates is associated with a lower incidence of clinical HCM expression. This association was also more prominent in those with obesity, unhealthy metabolic profiles and poor lifestyle behaviours.

Hypertrophic cardiomyopathy (HCM) remains the most common cardiomyopathy in humans and cats with few preclinical pharmacologic interventional studies. Small-molecule sarcomere inhibitors are promising novel therapeutics for the management of obstructive HCM (oHCM) patients and have shown efficacy in left ventricular outflow tract obstruction (LVOTO) relief. The objective of this study was to explore the 6-, 24-, and 48-hour (h) pharmacodynamic effects of the cardiac myosin inhibitor, CK-586, in six purpose-bred cats with naturally occurring oHCM. A blinded, randomized, five-treatment group, crossover preclinical trial was conducted to assess the pharmacodynamic effects of CK-586 in this oHCM model. Dose assessments and select echocardiographic variables were assessed five times over a 48-h period. Treatment with oral CK-586 safely ameliorated LVOTO in oHCM cats. CK-586 treatment dose-dependently eliminated obstruction (reduced LVOTOmaxPG), increased measures of systolic chamber size (LVIDs Sx), and decreased select measures of heart function (LV FS% and LV EF%) in the absence of impact on heart rate. At all tested doses, a single oral CK-586 dose resulted in improved or resolved LVOTO with well-tolerated, dose-dependent, reductions in LV systolic function. The results from this study pave the way for the potential use of CK-586 in both the veterinary and human clinical setting.

Mavacamten is a first-in-class, targeted, cardiac-specific myosin inhibitor approved by the US Food and Drug Administration for the treatment of adults with symptomatic New York Heart Association Classes II and III obstructive hypertrophic cardiomyopathy (oHCM). Mavacamten was developed to target the hyper-contractile phenotype, which plays a critical role in the pathophysiology of the disease. In Phase 2 and 3 clinical trials, mavacamten was well tolerated, reduced left ventricular outflow tract gradients, improved exercise capacity and symptoms, and was associated with improvements in other clinically relevant parameters, such as patient-reported outcomes and circulating biomarkers. In addition, treatment with mavacamten was associated with evidence of favourable cardiac remodelling in multi-modality imaging studies. Mavacamten substantially reduced guideline eligibility for septal reduction therapy candidates with oHCM and drug-refractory symptoms. In this article, the available efficacy and safety data from completed and ongoing clinical studies of mavacamten in patients with symptomatic oHCM are reviewed. Longer term extension studies may help address questions related to the positioning of mavacamten in current oHCM management algorithms, interactions with background therapy, as well as the potential for disease modification beyond symptomatic relief of left ventricular outflow tract obstruction.

ObjectiveFeline hypertrophic cardiomyopathy (HCM) remains a disease with little therapeutic advancement. Rapamycin modulates the mTOR pathway, preventing and reversing cardiac hypertrophy in rodent disease models. Its use in human renal allograft patients is associated with reduced cardiac wall thickness. We sought to evaluate the effects of once-weekly delayed-release (DR) rapamycin over 6 months on echocardiographic, biochemical, and biomarker responses in cats with subclinical, nonobstructive HCM.Animals43 client-owned cats with subclinical HCM.MethodsCats enrolled in this double-blinded, multicentered, randomized, and placebo-controlled clinical trial were allocated to low- or high-dose DR rapamycin or placebo. Cats underwent physical examination, quality-of-life assessment, blood pressure, hematology, biochemistry, total T4, urinalysis, N-terminal pro-B-type natriuretic peptide, and cardiac troponin I at baseline and days 60, 120, and 180. Fructosamine was analyzed at screening and day 180. Echocardiograms were performed at all time points excluding day 120. Outcome variables were compared using a repeated measures ANCOVA.ResultsNo demographic, echocardiographic, or clinicopathologic values were significantly different between study groups at baseline, confirming successful randomization. At day 180, the primary study outcome variable, maximum LV myocardial wall thickness at any location, was significantly lower in the low-dose DR rapamycin group compared to placebo (P = .01). Oral DR rapamycin was well tolerated with no significant differences in adverse events between groups.Clinical relevanceResults demonstrate that DR rapamycin was well tolerated and may prevent or delay progressive LV hypertrophy in cats with subclinical HCM. Additional studies are warranted to confirm and further characterize these results.

The relationship between cardiac deformation by 2D speckle tracking, hypertrophy, and the extent of late gadolinium enhancement (LGE) in patients with hypertrophic cardiomyopathy remains uncertain. Our study aims to compare left ventricular global longitudinal strain (GLS) with the extent of LGE and to determine a relationship between GLS and hypertrophy.

This article explores the challenges of managing hypertension in patients with hypertrophic obstructive cardiomyopathy (HCM). It presents a case study of a 52-year-old man with a history of hypertension and other medical conditions. The article emphasizes the importance of understanding the underlying causes of HCM and the different types of antihypertensive medications for effective treatment. It also highlights the need to differentiate between obstructive and nonobstructive forms of HCM and to closely monitor symptoms and avoid certain medications in patients with obstructive physiology. The article concludes by discussing the potential impact of hypertension on HCM and the recommended target blood pressure for patients with this condition. It suggests that a combination of beta-blockers or nondihydropyridine calcium channel blockers may be used as first-line therapy for symptomatic obstructive HCM, but the evidence for this approach is limited. Diuretics should generally be avoided unless there is heart failure. The management of hypertension in HCM should be personalized, considering symptoms, the degree of obstruction, and the risk of exacerbating left ventricular outflow tract obstruction. Collaboration among cardiologists, hypertension specialists, and pharmacists is crucial for optimizing therapy. The article also mentions the potential integration of innovative pharmacotherapies, such as mavacamten, with existing treatments in the future. [Extracted from the article]

Background: Hypertrophic scars are contained within the site of injury and may regress over time, while keloids spread beyond the borders of the initial injury and do not regress. On histologic examination, hypertrophic scars tend to have collagen in a wavy, regular pattern, whereas keloids have no distinct pattern of collagen. Objective: To retrospectively analyze improvement in keloid and hypertrophic scars characteristics following treatment with Ablative 10600 nm and a non-Ablative 1570 nm Hybrid Laser Device. Methods: Treatment parameters with the ProScan Hybrid Mode were 40 W/1.3–1.5 ms for the CO2 and 12 W/4 ms for the 1570 nm in a 1:1 ratio. Outcomes were assessed based on physician scar grading as measured by the Vancouver Scar Scale and patient-reported satisfaction. Excel was used for data analysis, and a p value < 0.05 was considered statistically significant. Adverse events and patient pain were also recorded. Results: A total of 31 hypertrophic scars and 30 keloid scars were treated. There was a significant reduction in Vancouver Scar Scale scores for both hypertrophic and keloid scars (62% ± 8% and 58% ± 7%; p = 2.6E-17 and p = 8.29E-26, respectively). In a scar-based comparison, a statistically significant difference was observed for all measures reflecting favorable outcomes for hypertrophic scars (VSS, p = 1.1E-05; satisfaction, p = 0.0112; pain, p = 0.00081). Only one adverse event was reported, a superficial burn treated with topical antibiotics. Conclusions: The device was found to be safe and effective, with promising results for the treatment of hypertrophic and keloid scars. Level of Evidence II: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266. [ABSTRACT FROM AUTHOR]

BACKGROUND: The health-related quality of life (HRQOL) and cardiopulmonary exercise testing (CPET) performance of individuals with subclinical and early stage hypertrophic cardiomyopathy (HCM) have not been systematically studied. Improved understanding will inform the natural history of HCM and factors influencing well-being. METHODS: VANISH trial (Valsartan for Attenuating Disease Evolution in Early Sarcomeric HCM) participants with early stage sarcomeric HCM (primary analysis cohort) and subclinical HCM (sarcomere variant without left ventricular hypertrophy comprising the exploratory cohort) who completed baseline and year 2 HRQOL assessment via the pediatric quality of life inventory and CPET were studied. Metrics correlating with baseline HRQOL and CPET performance were identified. The impact of valsartan treatment on these measures was analyzed in the early stage cohort. RESULTS: Two hundred participants were included: 166 with early stage HCM (mean age, 23±10 years; 40% female; 97% White; and 92% New York Heart Association class I) and 34 subclinical sarcomere variant carriers (mean age, 16±5 years; 50% female; and 100% White). Baseline HRQOL was good in both cohorts, although slightly better in subclinical HCM (composite pediatric quality of life score 84.6±10.6 versus 90.2±9.8; P=0.005). Both cohorts demonstrated mildly reduced functional status (mean percent predicted peak oxygen uptake 73±16 versus 78±12 mL/kg per minute; P=0.18). Percent predicted peak oxygen uptake and peak oxygen pulse correlated with HRQOL. Valsartan improved physical HRQOL in early stage HCM (adjusted mean change in pediatric quality of life score +4.1 versus placebo; P=0.01) but did not significantly impact CPET performance. CONCLUSIONS: Functional capacity can be impaired in young, healthy people with early stage HCM, despite New York Heart Association class I status and good HRQOL. Peak oxygen uptake was similarly decreased in subclinical HCM despite normal left ventricular wall thickness and excellent HRQOL. Valsartan improved physical pediatric quality of life scores but did not significantly impact CPET performance. Further studies are needed for validation and to understand how to improve patient experience. [ABSTRACT FROM AUTHOR]

OBJECTIVES: The present study aimed to determine the inheritance pattern and genetic cause of congenital radial hemimelia (RH) in cats. METHODS: Clinical and genetic analyses were conducted on a Siamese cat family (n = 18), including two siblings with RH. Radiographs were obtained for the affected kittens and echocardiograms of an affected kitten and sire. Whole genome sequencing was completed on the two cases and the parents. Genomic data were compared with the 99 Lives Cat Genome data set of 420 additional domestic cats with whole genome and whole exome sequencing data. Variants were considered as homozygous in the two cases of the siblings with RH and heterozygous in the parents. Candidate variants were genotyped by Sanger sequencing in the extended pedigree. RESULTS: Radiographs of the female kitten revealed bilateral absence of the radii and bowing of the humeri, while the male kitten showed a dysplastic right radius. Echocardiography suggested the female kitten had restrictive cardiomyopathy with a positive left atrial-to-aortic root ratio (LA:Ao = 1.83 cm), whereas hypertrophic cardiomyopathy was more likely in the sire, showing diastolic dysfunction using tissue Doppler imaging (59.06 cm/s). Twenty-two DNA variants were unique and homozygous in the affected kittens and heterozygous in the parents. Seven variants clustered in one chromosomal region, including two frameshift variants in cardiomyopathy associated 5 (CMYA5) and five variants in junction mediating and regulatory protein, P53 cofactor (JMY ), including a missense and an in-frame deletion. CONCLUSIONS AND RELEVANCE: The present study suggested an autosomal recessive mode of inheritance with variable expression for RH in the Siamese cat family. Candidate variants for the phenotype were identified, implicating their roles in bone development. These genes should be considered as potentially causal for other cats with RH. Siamese cat breeders should consider genetically testing their cats for these variants to prevent further dissemination of the suspected variants within the breed.

BackgroundCommon genetic variants are associated with risk for hypertrophic cardiomyopathy and dilated cardiomyopathy and with left ventricular (LV) traits. Whether these variants are associated with myocardial fibrosis, an important pathophysiological mediator of cardiomyopathy, is unknown.MethodsMulti-Ethnic Study of Atherosclerosis participants with T1-mapping cardiac magnetic resonance imaging in-whom extracellular volume was assessed, and genotyping information was available were included (N=1255). Log extracellular volume (%) was regressed on 50 candidate single nucleotide polymorphisms (previously identified to be associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, and LV traits) adjusting for age, sex, diabetes, blood pressure, and principal components of ancestry. Ancestry-specific results were pooled by fixed-effect meta-analyses. Gene knockdown experiments were performed in human cardiac fibroblasts.ResultsThe SMARCB1 rs2186370 intronic variant (minor allele frequency: 0.18 in White and 0.50 in Black participants), previously identified as a risk variant for dilated cardiomyopathy and hypertrophic cardiomyopathy, was significantly associated with increased extracellular volume (P=0.0002) after adjusting for confounding clinical variables. The SMARCB1 rs2070458 locus previously associated with increased LV wall thickness and mass was similarly significantly associated with increased extracellular volume (P=0.0002). The direction of effect was similar in all 4 ancestry groups, but the effect was strongest in Black participants. The variants are strong expression quantitative loci in human LV tissue and associated with genotype-dependent decreased expression of SMARCB1 (P=7.3×10-22). SMARCB1 knockdown in human cardiac fibroblasts resulted in increased TGF (transforming growth factor)-β1-mediated α-smooth muscle actin and collagen expression.ConclusionsCommon genetic variation in SMARCB1 previously associated with risk for cardiomyopathies and increased LV wall thickness is associated with increased cardiac magnetic resonance imaging-based myocardial fibrosis and increased TGF-β1 mediated myocardial fibrosis in vitro. Whether these findings suggest a pathophysiologic link between myocardial fibrosis and cardiomyopathy risk remains to be proven.

The article explores the association between echocardiographic parameters and health status in patients with obstructive hypertrophic cardiomyopathy. The study, EXPLORER-HCM, involved 251 adults from 13 countries and found that changes in certain echocardiographic parameters were linked to changes in health status over time. The research suggests that LVOT obstruction and septal hypertrophy are key factors influencing patients' health status, providing insights for future studies on treatment with cardiac myosin inhibitors. The study acknowledges limitations such as narrow distributions of baseline variables and the challenge of disentangling the relationship between anatomy, physiology, and health status. [Extracted from the article]

BackgroundA large proportion of genetic risk remains unexplained for structural heart disease involving the interventricular septum (IVS) including hypertrophic cardiomyopathy and ventricular septal defects. This study sought to develop a reproducible proxy of IVS structure from standard medical imaging, discover novel genetic determinants of IVS structure, and relate these loci to diseases of the IVS, hypertrophic cardiomyopathy, and ventricular septal defect.MethodsWe estimated the cross-sectional area of the IVS from the 4-chamber view of cardiac magnetic resonance imaging in 32 219 individuals from the UK Biobank which was used as the basis of genome wide association studies and Mendelian randomization.ResultsMeasures of IVS cross-sectional area at diastole were a strong proxy for the 3-dimensional volume of the IVS (Pearson r=0.814, P=0.004), and correlated with anthropometric measures, blood pressure, and diagnostic codes related to cardiovascular physiology. Seven loci with clear genomic consequence and relevance to cardiovascular biology were uncovered by genome wide association studies, most notably a single nucleotide polymorphism in an intron of CDKN1A (rs2376620; β, 7.7 mm2 [95% CI, 5.8-11.0]; P=6.0×10-10), and a common inversion incorporating KANSL1 predicted to disrupt local chromatin structure (β, 8.4 mm2 [95% CI, 6.3-10.9]; P=4.2×10-14). Mendelian randomization suggested that inheritance of larger IVS cross-sectional area at diastole was strongly associated with hypertrophic cardiomyopathy risk (pIVW=4.6×10-10) while inheritance of smaller IVS cross-sectional area at diastole was associated with risk for ventricular septal defect (pIVW=0.007).ConclusionsAutomated estimates of cross-sectional area of the IVS supports discovery of novel loci related to cardiac development and Mendelian disease. Inheritance of genetic liability for either small or large IVS, appears to confer risk for ventricular septal defect or hypertrophic cardiomyopathy, respectively. These data suggest that a proportion of risk for structural and congenital heart disease can be localized to the common genetic determinants of size and shape of cardiovascular anatomy.

BackgroundCats with hypertrophic cardiomyopathy (HCM) are at risk of cardiogenic arterial thromboembolism (CATE). Neutrophil extracellular traps (NETs) may be a potential biomarker and therapeutic target for cardiomyopathy in cats.Hypothesis/objectivesCharacterize NETs in cats with HCM or CATE. We hypothesized that circulating NETs assessed in the form of cell-free DNA (cfDNA) and citrullinated histone H3 (citH3) are increased in cats with HCM and CATE and associated with reported predisposing factors for thrombus formation.AnimalsEighty-five cats including client-owned cats with HCM and CATE and staff- and student-owned clinically healthy cats without HCM.MethodsAfter echocardiographic evaluations, NETs were measured as cfDNA and citH3.ResultsCats with CATE had significant increases in cfDNA (11.2 ng/μL; interquartile range [IQR], 8.1 to 29.6) compared to those without HCM (8.2 ng/μL; IQR, 5.7 to 11.7 μL; P = .01) and were responsible for 75% to 83% of cases with cfDNA fragments sized 100 to 2000 base pairs. Citrullinated histone 3, detected in 52% of cats with HCM (31.1 ng/mL; IQR, 16.9 to 29.8), was significantly lower than in those with CATE (48.2 ng/mL; IQR, 34.2 to 60.2; P = .007). The citH3 concentrations correlated significantly with reported risk factors of CATE, such as left atrial auricular velocity.Conclusions and clinical importanceNeutrophil extracellualr traps, especially citH3, are increased in cats with HCM and CATE. They may serve as a novel therapeutic target and biomarker of thrombosis in cats with HCM.