Asymptomatic Hypertrophic Cardiomyopathy Research Articles

Left atrial fractional shortening in cats: a comparison between two echocardiographic views

Introduction/objectivesLeft atrial fractional shortening (LAFS%) is a widely used index of left atrial systolic function in cats that has been shown to predict development of hypertrophic cardiomyopathy (HCM) and cardiac mortality. It can be determined by two methods: from an M-mode right parasternal short-axis view (LAFS%RPSA-MM) or two-dimensional right parasternal long-axis four-chamber view (LAFS%RPLA-2D). We aimed to assess the agreement between LAFS%RPSA-MM and LAFS%RPLA-2D in cats and to evaluate the correlation between LAFS%RPSA-MM and LAFS%RPLA-2D and left ventricular systolic performance. Animals, materials, and methodsOne hundred and seventeen cats were enrolled in the study: 40 control, 41 HCM stage B (asymptomatic), and 36 HCM stage C (symptomatic) cats. This was a retrospective case–control study. Bland–Altman analysis was used to assess agreement between LAFS%RPSA-MM and LAFS%RPLA-2D across the whole cohort and in cats with asymptomatic and symptomatic HCM. Correlation analysis was used to assess associations between LAFS% methods and forward aortic flow, left ventricular fractional shortening, and aortic root motion. ResultsThe LAFS% determined by LAFS%RPSA-MM and LAFS%RPLA-2D was similar (P=0.8), but Bland–Altman analysis showed wide limits of agreement between methods. There was a good correlation between LAFS%RPSA-MM and LAFS%RPLA-2D and aortic root motion (r = 0.78 and r = 0.71, respectively) and a fair correlation with left ventricular fractional shortening (r = 0.31 and r = 0.29, respectively). None of the methods showed a correlation with indices of aortic flow. ConclusionsOur study suggests a poor agreement between LAFS%RPSA-MM and LAFS%RPLA-2D, and thus, these methods should not be used interchangeably. Both echocardiographic methods showed good correlation with aortic root motion.

Do ACE inhibitors prolong the life of cats with asymptomatic hypertrophic cardiomyopathy?

Do ACE inhibitors prolong the life of cats with asymptomatic hypertrophic cardiomyopathy?

Abstract 15732: Chronic Mavacamten Treatment Has Opposing Effects on Contractility in Engineered Heart Tissue Models of Severe vs. Mild Hypertrophic Cardiomyopathy

Many hypertrophic cardiomyopathy (HCM) causing mutations result in myocardial hypercontractility by increasing the number of myosin crossbridges in the disordered relaxed (DRX) state, or by sensitizing the sarcomere to the effects of Ca 2+ . Mavacamten (Mava) recently became the first FDA-approved treatment of obstructive HCM that directly targets hypercontractility by reducing the number of DRX cross bridges. Mava improves outcomes in patients with obstructive HCM but has not been approved in children or adults without obstructive HCM. The efficacy of chronic Mava treatment at preventing phenotype development in asymptomatic HCM mutation carriers remains largely unexplored. We recently showed that ablation of cardiac myosin binding protein-C (cMyBP-C -/-) in engineered heart tissue (EHT) causes rapid phenotype development in a dish. Initial hypercontractility progresses to hypocontractility with impaired relaxation, mediated by Ca 2+ mishandling. Here we investigate whether chronic Mava administration prevents phenotype progression. cMyBP-C +/+, +/- and -/- EHT were treated with 100nM Mava starting on day 7 of EHT culture. Serial twitch force (TF) measurements were performed weekly for 5 weeks, using the Mantarray platform. At day 7, prior to Mava treatment, +/- and -/- produced significantly more TF than +/+ EHT (392 ± 9 μN vs. 390 ± 15 μN vs. 199 ± 13 μN). At day 14, Mava treatment reduced TF by 31% (p < 0.001) in +/+ EHT, 30% (p < 0.001) in +/- EHT and 12% (p = 0.115) in -/- EHT. After an additional 4 weeks, chronic Mava treatment reduced TF by 54% (p < 0.001) in +/+ EHT, 65% (p < 0.001) in +/- EHT but increased TF by 23% (p = 0.034) in -/- EHT.These data show that chronic Mava treatment prevents/slows maladaptive remodeling in -/- EHT, but depresses contractility in +/+ and +/- ECT, suggesting that chronic Mava treatment may be detrimental to patients with mild HCM. Our ongoing studies are assessing the effect of chronic Mava treatment on other EHT models of HCM and on Ca 2+ -handling.

MYH7 p.(Arg1712Gln) is pathogenic founder variant causing hypertrophic cardiomyopathy with overall relatively delayed onset.

The MYH7 c.5135G > A p.(Arg1712Gln) variant has been identified in several patients worldwide and is classified as pathogenic in the ClinVar database. We aimed to delineate its associated phenotype and evaluate apotential founder effect. We retrospectively collected clinical and genetic data of 22probands and 74family members from an international cohort. In total, 53individuals carried the MYH7 p.(Arg1712Gln) variant, of whom 38 (72%) were diagnosed with hypertrophic cardiomyopathy (HCM). Mean age at HCM diagnosis was 48.8years (standard deviation:18.1; range: 8-74). The clinical presentation ranged from asymptomatic HCM to arrhythmias (atrial fibrillation and malignant ventricular arrhythmias). Aborted sudden cardiac death (SCD) leading to the diagnosis of HCM occurred in one proband at the age of 68years, and afamily history of SCD was reported by 39% (5/13) probands. Neither heart failure deaths nor heart transplants were reported. Women had agenerally later-onset disease, with 14% of female carriers diagnosed with HCM at age 50years compared with 54% of male carriers. In both sexes, the disease was fully penetrant by age 75years. Haplotypes were reconstructed for 35patients and showed afounder effect in asubset of patients. MYH7 p.(Arg1712Gln) is apathogenic founder variant with aconsistent HCM phenotype that may present with delayed penetrance. This suggested that clinical follow-up should be pursued after the seventh decade in healthy carriers and that longer intervals between screening may be justified in healthy women < 30years.

The Association of Maternal Glycemic Control with Hypertrophic Cardiomyopathy in Infants of Diabetic Mothers

Background: Infants of Diabetic Mothers (IDMs) are at known risk for the development of hypertrophic cardiomyopathy (HCM). Echocardiography is essential for the diagnosis of HCM, to assess the left ventricular function, and the degree of left ventricle obstruction, and to rule out structural cardiac malformations.&#x0D; Objective: To study the association of maternal third-trimester glycemic level with HCM in IDMs.&#x0D; Study Design: Observational cross-sectional study.&#x0D; Participants: 108 diabetic mothers and IDMs.&#x0D; Intervention: Third-trimester Glycosylated hemoglobin (HbA1c) levels were measured and Echocardiography was done for IDMs in their first week of life. Data were analyzed for correlations between various parameters.&#x0D; Outcomes: HCM was diagnosed when the absolute value of Inter Ventricular Septum (IVS) was ≥ 2SD from the mean (5mm) and Asymmetrical Septal Hypertrophy (ASH) was diagnosed when the IVS: LVPW ratio was ≥ 1.3.&#x0D; Results: 85% of the study population had gestational diabetes, and 55.6% of them were on diet control only. The mean HbA1c was 6.69%. The mean birth weight was 3.1 kg. The most common complication observed was hypoglycemia (19.4%). Asymptomatic HCM was seen in 52% and ASH in 25.9% of the study population. HCM was found to be significantly associated with maternal HbA1c levels, birth weight and hypoglycemia.&#x0D; Conclusion: HCM is a frequent finding in IDMs when routinely screened by echocardiography. A significant positive association of HCM with maternal glycemic control was seen in our study and hence strict glycemic control during pregnancy is of paramount significance.

Ventricular arrhythmia and sudden cardiac death in hypertrophic cardiomyopathy: From bench to bedside.

Patients with hypertrophic cardiomyopathy (HCM) mostly experience minimal symptoms throughout their lifetime, and some individuals have an increased risk of ventricular arrhythmias and sudden cardiac death (SCD). How to identify patients with a higher risk of ventricular arrythmias and SCD is the priority in HCM research. The American College of Cardiology/American Heart Association (ACC/AHA) and the European Society of Cardiology (ESC) both recommend the use of risk algorithms to identify patients at high risk of ventricular arrhythmias, to be selected for implantation of implantable cardioverters/defibrillators (ICDs) for primary prevention of SCD, although major discrepancies exist. The present SCD risk scoring systems cannot accurately identify early-stage HCM patients with modest structural remodeling and mild disease manifestations. Unfortunately, SCD events could occur in young asymptomatic HCM patients and even as initial symptoms, prompting the determination of new risk factors for SCD. This review summarizes the studies based on patients' surgical specimens, transgenic animals, and patient-derived induced pluripotent stem cells (hiPSCs) to explore the possible molecular mechanism of ventricular arrhythmia and SCD. Ion channel remodeling, Ca2+ homeostasis abnormalities, and increased myofilament Ca2+ sensitivity may contribute to changes in action potential duration (APD), reentry circuit formation, and trigger activities, such as early aferdepolarization (EAD) or delayed afterdepolarization (DAD), leading to ventricular arrhythmia in HCM. Besides the ICD implantation, novel drugs represented by the late sodium current channel inhibitor and myosin inhibitor also shed light on the prevention of HCM-related arrhythmias. The ideal prevention strategy of SCD in early-stage HCM patients needs to be combined with gene screening, hiPSC-CM testing, machine learning, and advanced ECG studies, thus achieving individualized SCD prevention.

Upright exercise stress echocardiography may unmask dynamic left ventricular obstruction also beyond hypertrophic cardiomyopathy

Abstract Background Dynamic left ventricular outflow obstruction (LVOTO) during exercise stress echocardiography (ESE) is recommended in hypertrophic cardiomyopathy (HCM) to identify the obstructive phenotype. Aim To assess left ventricular outflow gradient (LVOTG) during ESE in different conditions. Methods In a single-group, prospective, observational study, we performed peak and/or post-treadmill ESE with systematic assessment of LVOTG in the orthostatic position by continuous-wave Doppler in 1333 subjects (837 males, mean age 38,2±20 ranging from 6 to 87 years) recruited over a period of twenty years, from 2001 to 2021. Peak LVOTG ≥30 mm Hg was considered abnormal for LVOTO during ESE. We enrolled 7 different populations: asymptomatic healthy controls (n=35); HCM (n=81); genotype-positive, phenotype negative asymptomatic HCM (n=6); patients with chest pain symptoms, suspected myocardial ischemia and either normal coronary arteries (INOCA, n=131,or with very low pre-test probability of coronary artery disease (probable INOCA, n=416) and; fatigue and suspected heart failure with preserved ejection fraction (HFpEF, n=206); amateur athletes with ischemia-like ECG changes during exercise-test or symptoms such as near syncope or chest pain or dizziness (n=457); aborted sudden death and with negative screening (n=1). Results Technical success rate of LVOTG assessment was 1333/1333 at rest and at peak stress (feasibility 100%). Imaging and analysis time were &amp;lt;1 minute. LVOTG at rest was present in 25 pts (2.8%) of the overall population: 23 HCM, 1 INOCA, and 1 HFpEF. Overall prevalence during ESE was 432/1333 (32%). During ESE, LVOTO (see Figure 1 and 2) was 0% (0/35) in normals, 58% (47/81) in HCM (23 with obstruction at rest), 33% (2/6) in genotype-positive, phenotype negative HCM, 37% (33/131) in INOCA, 40% (135/416) in athletes and 1/1 in the patient with aborted sudden death on strenuous exercise. Conclusion LVOTO in orthostatic position is detectable during treadmill ESE in several cardiovascular conditions associated with symptoms such as dyspnea, chest pain or near syncope, and even in asymptomatic patients with genotype-positive, phenotype-negative HCM. The identification of the obstructive phenotype is easy to capture during ESE without any significant additional imaging and analysis burden and can be important also outside HCM. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Associations among echocardiography, cardiac biomarkers, insulin metabolism, morphology, and inflammation in cats with asymptomatic hypertrophic cardiomyopathy.

BackgroundInsulin, insulin‐like growth factor‐1 (IGF‐1), and inflammation possibly are involved in cats with asymptomatic hypertrophic cardiomyopathy (aHCM).ObjectivesTo evaluate echocardiography, morphology, cardiac and inflammatory markers, insulin and IGF‐1 in cats with aHCM.AnimalsFifty‐one client‐owned cats with aHCM.MethodsObservational descriptive study. Variables (body weight [BW], body condition score [BCS], echocardiography, and serum concentrations of N‐terminal pro‐B‐type natriuretic peptide [NT‐proBNP], ultra‐sensitive troponin‐I [c‐TnI], serum amyloid A [SAA], insulin, glucose and IGF‐1) were evaluated for significant increases above echocardiography cutoff values and laboratory reference ranges, associations and effect of left atrial (LA) remodeling and generalized hypertrophy.ResultsCats with aHCM had BCS ≥6/9 (P = .01) and insulin (P < .001), NT‐proBNP (P = .001) and cTn‐I (P < .001) above laboratory reference ranges. Associations were present between NT‐proBNP and maximum end‐diastolic interventricular septum thickness (IVSd; ρ = .32; P = .05), maximum end‐diastolic left ventricular free wall thickness;(ρ = .41; P = .01), LA/Aorta (ρ = .52; P = .001) and LA diameter (LA‐max; ρ = .32; P = .05); c‐TnI and LA/Aorta (ρ = .49; P = .003) and LA‐max (ρ = .28; P = .05); and SAA and number of IVSd regions ≥6 mm thickness (ρ = .28; P = .05). Body weight and BCS were associated with IGF‐1 (r = 0.44; P = .001), and insulin (ρ = .33; P = .02), glucose (ρ = .29; P = .04) and IGF‐1 (ρ = .32; P = .02), respectively. Concentrations of NT‐proBNP (P = .02) and c‐TnI (P = .01), and SAA (P = .02), were higher in cats with LA remodeling, and generalized hypertrophy, respectively.Conclusions and clinical importanceResults suggest potential implications of insulin, IGF‐1, and inflammation in cats with aHCM, but it remains to be confirmed whether these findings represent a physiological process or a part of the pathogenesis and development of disease.

Antioxidant defence and oxidative stress markers in cats with asymptomatic and symptomatic hypertrophic cardiomyopathy: a pilot study

BackgroundHypertrophic cardiomyopathy is the most common cardiovascular cause of death in cats. Although the majority of cats remain asymptomatic, some may develop signs of chronic heart failure due to diastolic failure, arterial thromboembolism (ATE) or sudden cardiac death. Therefore, it is crucial to identify individuals that are in high risk of developing cardiac complications before the onset of life-threatening signs. Oxidative stress is the imbalance between the production and neutralisation of reactive oxygen species. Uncontrolled reactive oxygen species overproduction leads to protein and lipid peroxidation and damages the DNA strands, injuring the cells and leading to their death. The aim of the study was to evaluate the oxidative state in cats with hypertrophic cardiomyopathy and healthy controls.ResultsIn total, 30 cats divided into three groups were assessed: animals with clinically evident hypertrophic cardiomyopathy (HCM; n = 8), subclinical hypertrophic cardiomyopathy (SUB-HCM; n = 11) and healthy controls (n = 11). The activity of superoxide dismutase was statistically significantly lower in animals with symptomatic and asymptomatic hypertrophic cardiomyopathy (HCM 0.99 ± 0.35 U/mL; SUB-HCM 1.39 ± 0.4 U/mL) compared to healthy cats (2.07 ± 0.76 U/mL, p < 0.01). The activity of catalase was significantly lower in the SUB-HCM group (19.4 ± 4.2 nmol/min/mL) compared to the HCM (23.6 ± 5.9 nmol/min/mL) and the control (30 ± 7.5 nmol/min/mL, p < 0.01) group. The activity of glutathione peroxidase was 4196 ± 353 nmol/min/mL in the HCM group, 4331 ± 451 nmol/min/mL in the SUB-HCM group and 4037 ± 341 nmol/min/mL in the control group and did not differ significantly between groups. The total antioxidant capacity of plasma was 602 ± 65.5 copper reducing equivalents (CRE) in the HCM group, 605.9 ± 39.9 CRE in the SUB-HCM group and 629 ± 77.5 CRE in the healthy cats and did not differ significantly between the groups.ConclusionsActivities of superoxide dismutase and catalase differed in cats with hypertrophic cardiomyopathy, however the activity of the latter was only significantly lower in asymptomatic stage of the disease. The potentially beneficial effect of antioxidative substances on the disease progression in the asymptomatic and symptomatic stage of this disease should also be examined.

P873 A rare and potentially treatable cause of left ventricular hypertrophy

Abstract Introduction A 67-year-old man was referred for care of "asymptomatic hypertrophic cardiomyopathy". He did not have hypertension. No significant positive family history could be elicited. Electrocardiogram showed sinus rhythm with voltage criteria of left ventricular hypertrophy (LVH). Outside Transthoracic Echocardiogram (TTE) reported normal ejection fraction with asymmetric septal hypertrophy without outflow obstruction. He was put on observation for few years and was not any treatment. On first encounter in our clinic, physical examination including skin and eye assessment, and laboratory tests including renal function were unremarkable. Procedure TTE was repeated in our clinic showing normal left ventricular size with ejection fraction 55%, and impaired diastolic relaxation. There was asymmetric septal hypertrophy with septal thickness 2.1 cm (Figure A). There was mild systolic anterior motion of mitral apparatus and mild mitral regurgitation, without resting or Valsalva provoked outflow obstruction. Global longitudinal strain was -7.7% with most prominent abnormalities seen at apex, mid to basal anteroseptal and anterior wall (Figure B). Further assessment by Cardiac MRI showed similar asymmetric septal wall thickening. Late gandolinium enhancement study demonstrated patchy fluffy hyperenhancement of the mid wall of the basal to mid anteroseptal segment, and mid to apical anterior segment, suggestive of myocardial fibrosis (Figure C1 and C2). Dried spot blood was sent to Taiwan for enzyme study which revealed partial acid alpha-galactosidase A deficiency. Further genetic study detected a mutation of Hemizygous NM_000169.2(GLA):c.640-801[G &amp;gt; A] at intron 4. Finally endomyocardial biopsy was done which confirmed the cardiac involvement of Fabry disease (Figure D, myelin body shown under electron microscopy). This gentleman was referred for consideration of Enzyme Replacement Therapy (ERT). Discussion Fabry disease is an X-linked glycolipid storage disease with accumulation of globotriaosylceramide in lysosomes in multiple cell types throughout the body leading to various organ involvement. Cardiac manifestations include unexplained LVH, valvular regurgitation, conduction abnormalities etc. It occurs in up to 0.3-5% of patients with hypertrophic cardiomyopathy. Fabry disease should be considered as a differential diagnosis in all men with sporadic or non-autosomal dominant transmission of unexplained LVH, since treatment with ERT is available which may reduce LVH and improve myocardial function, although any impact on long term outcome has not yet been established. Conclusion This case illustrated a rare but potentially treatable cause of hypertrophic cardiomyopathy. Myocardial strain imaging should be integrated in routine TTE study for assessment of unexplained left ventricular hypertrophy. Multi-modality imaging and multi-specialty approach help in identifying patients of cardiac variant of Fabry disease who may benefit from ERT. Abstract P873 Figure.

Left ventricular geometric characteristics predict response to carvedilol in cats with asymptomatic hypertrophic obstructive cardiomyopathy caused by systolic anterior motion of the mitral valve.

Beta-blockers are used to treat cats with hypertrophic obstructive cardiomyopathy (HOCM). However, there are various hemodynamic responses to beta-blockers. This retrospective study aimed to explore the relationship between the response to carvedilol and the presence of geometric abnormalities. Medical records were reviewed for 16 cats diagnosed with HOCM. Cats were divided into two groups based on the velocity of the left-ventricular outflow-tract after carvedilol treatment (responder: eight cats, non-responder: eight cats). Baseline intergroup comparison revealed that anterior mitral valve leaflet length and diastolic left-ventricular posterior-wall thickness were significantly greater in the non-responder group. Longer anterior mitral valve leaflet and thicker left-ventricular posterior-wall may cause poor response to carvedilol. Thus, these properties may predict a lack of response to carvedilol therapy.

Analytical validation of platelet microparticle quantification in cats.

Cardiogenic embolism (CE) in cats is a devastating condition primarily associated with hypertrophic cardiomyopathy (HCM). Hypercoagulability may pose a risk for thrombus formation; however, no single test can predict CE development. Platelet microparticles (PMPs) released from platelet membranes are associated with thrombosis in humans. The aims were to validate flow cytometric PMP quantification in cats analytically and, in a pilot study, evaluate the procoagulant annexin V (AnV) positive PMP concentration in healthy cats and cats with asymptomatic HCM. With CD61 as a platelet marker, CD61+ AnV+ PMPs (0.3-1.0μm) were quantified in citrated whole blood (WB) and platelet-poor plasma (PPP) using flow cytometry. Analyses were performed in 6 healthy cats and 5 cats with asymptomatic HCM. The coefficient of variation (CV) for duplicate (intra-assay) and parallel (inter-assay) analyses were calculated. PMP concentrations were quantified with acceptable intra-assay CV for WB (CD61+ /AnV- ; 2.4%, 0.2%-8.4% (median, range), CD61+ /AnV+ ; 3.8%, 0.1%-12.5%) and PPP (CD61+ /AnV- ; 5.0%, 0.7%-12.8%, CD61+ /AnV+ ; 7.4%, 0.5%-15.3%), and acceptable inter-assay CV for WB in 10/11 cats (CD61+ /AnV- ; 6.2%, 1.4%-13.3%, CD61+ /AnV+ ; 6.4%, 0.7%-17.2%), but unacceptable for PPP (CD61+ /AnV- ; 15.6%, 5.8%-42.7%, CD61+ /AnV+ ; 27.8%, 8.4%-77.1%). For WB PMP concentrations, the pilot data demonstrated no differences between healthy cats and cats with asymptomatic HCM (4/5 with left ventricular outflow obstruction) for either the CD61+ /AnV- or the CD61+ /AnV+ PMPs. Only WB PMP concentrations could be quantified reliably in cats in a clinical setting. PMP concentrations did not differ between healthy and asymptomatic HCM cats in this pilot study.

Diagnostic utility of cardiac troponin I in cats with hypertrophic cardiomyopathy.

BackgroundCardiac troponin I (cTnI) is useful for assessing hypertrophic cardiomyopathy (HCM) in cats.ObjectiveTo measure plasma cTnI concentrations in healthy cats and evaluate the clinical utility of cTnI in determining the severity of HCM.AnimalsClinically healthy cats (n = 88) and cats with HCM (n = 93).MethodsMulticenter prospective study. Cats with HCM, including hypertrophic obstructive cardiomyopathy at various stages, were diagnosed using echocardiography. Plasma cTnI concentrations were analyzed by a commercial laboratory. Receiver‐operating characteristic curve analysis was used to evaluate the accuracy of plasma cTnI concentrations to detect HCM.ResultsThe median cTnI concentration was 0.027 ng/mL (interquartile range, 0.012‐0.048 ng/mL) in healthy cats. Concentrations were significantly higher in diseased cats than in healthy controls, and concentrations were significantly higher in cats with heart failure than in asymptomatic cats. A plasma cTnI concentration of 0.163 ng/mL had a sensitivity of 62.0% and specificity of 100% when used to distinguish normal cats from asymptomatic HCM cats without left atrial dilatation. A cutoff of 0.234 ng/mL had high sensitivity (95.0%) and specificity (77.8%) for assessing heart failure. The areas under the receiver‐operating characteristic curves were 0.85 and 0.93, respectively.Conclusions and Clinical ImportanceIncreased cTnI concentrations reflect the severity of HCM. If other causes of cardiac injury are ruled out, plasma cTnI concentration may be useful for predicting the severity of HCM in cats.

Analysis of cardiac troponin C gene TNNC1 c. G175C mutation in a Chinese pedigree with familial hypertrophic cardiomyopathy and the correlation between genotype and phenotype

Objective: To investigate the genotype-phenotype correlation in Chinese familial hypertrophic cardiomyopathy (HCM )focusing on the cardiac troponin C gene TNNC1 c. G175C mutation. Methods: All family members of a Chinese pedigree with hypertrophic cardiomyopathy admitted in Third People's Hospital of Qingdao in February 2005 and 200 healthy volunteers were included in this study. The coding exons of 30 hypertrophic cardiomyopathy associated genes were identified by whole exons amplification and high-throughput sequencing in the proband, and the identified mutation were further detected through bi-directional Sanger sequencing in all family members and 200 healthy volunteers. Pedigree analysis included clinical manifestation, physical examination, ECG and echocardiogram. Results: A missense mutation c. G175C was identified in the TNNC1 gene in 2 family members, which resulted in a glutamic acid (E) to glutamine (Q) exchange at amino acid residue 59. A mutation c. A1319G was identified in the MYLK2 gene in 1 family member, which resulted in a lysine (K) to arginine (R) exchange at amino acid residue 440. These mutations were absent in 200 healthy controls. The proband carried the two kinds of mutations and expressed various clinical manifestations of heart failure and had history of ventricular tachycardia, paraxial atrial fibrillation, pacemaker implantation, electrocardiogram showed right bundle branch block and echocardiography examination evidenced thickened interventricular septum (23.3 mm) and apex and reduced wall motion of these segments. The daughter of the proband carried the TNNC1 c. G175C mutation and was also diagnosed with asymptomatic HCM by echocardiography with thickened interventricular septum (19 mm) and apex (15 mm). Conclusion: The novel missense mutation of TNNC1 c. G175C might be the disease-causing gene mutation in this Chinese pedigree with familiar HCM.

Effects of clopidogrel therapy on whole blood platelet aggregation, the Plateletworks® assay and coagulation parameters in cats with asymptomatic hypertrophic cardiomyopathy: a pilot study

ABSTRACTBackground: Although scientific evidence is limited, clopidogrel is frequently used as prophylaxis for arterial thromboembolism in cats with hypertrophic cardiomyopathy (HCM).Objectives: Evaluating effects of clopidogrel therapy in asymptomatic cats with HCM on (1) conventional whole blood aggregation (WBA), (2) alternative platelet aggregation assessed with tubes of the Plateletworks® assay and (3) standard coagulation parameters.Animals and methods: Prospective, randomized, double-blind, placebo-controlled pilot study. Fourteen asymptomatic HCM cats were randomly allocated to receive placebo (n = 5) or clopidogrel (18.75 mg/cat q24h, n = 9) as part of a larger study. Aggregation responses (to 20 µM adenosine diphosphate (ADP) and 10 µg/ml collagen) in WBA and the Plateletworks® assay and standard coagulation parameters were evaluated at baseline and after seven days of therapy.Results: Clopidogrel therapy significantly reduced aggregation responses to ADP and collagen in the Plateletworks® agonists tubes (ADP and collagen: P < 0.001), but did not significantly reduce aggregation responses to ADP and collagen in the WBA technique (ADP: P = 0.07, collagen: P = 0.30). Clopidogrel therapy did not show a significant effect on prothrombin time, activated partial thromboplastin time, antithrombin, D-dimers and fibrinogen concentrations.Conclusion and clinical importance: Clopidogrel therapy at a dose of 18.75 mg/cat q24h for seven days causes a significant decrease in in vitro platelet aggregation evaluated with the Plateletworks® assay, without affecting standard coagulation parameters in cats with asymptomatic HCM.

Ambulatory electrocardiogram recordings in cats with primary asymptomatic hypertrophic cardiomyopathy.

Objectives The aims of the study were to determine the heart rate, rhythm, number of ventricular premature complexes (VPCs) and atrial premature complexes (APCs) in unsedated cats with asymptomatic hypertrophic cardiomyopathy (HCM), using 24 h ambulatory electrocardiogram (ECG) (Holter) in the home environment and to compare the results with those from healthy control cats. Methods Fifteen privately owned cats with asymptomatic HCM entered the study. Data from 23 healthy cats, previously published by our group, were used as the control. Clinical examination, measurement of blood pressure, echocardiographic examination, Holter recordings and biochemical analyses were performed in all cats. Holter recordings were obtained in the home environment. Results Three-lead ECGs of good quality were obtained from 15 cats with HCM. The median heart rate was 145 (interquartile range [IQR] 137-184) beats per minute for the cats with HCM. All cats with HCM presented with normal sinus rhythm; 60% of cats had intermittent sinus arrhythmia. Median number of VPCs was 3 (IQR 1-17). Three cats had APCs and three cats had both escape beats and intermittent sinus arrhythmia. Conclusions and relevance Asymptomatic cats with HCM had few VPCs and APCs on 24 h ambulatory ECG in the home environment. Intermittent sinus arrhythmia was observed in 60% of cats with HCM. The present study shows that the heart rate and the number of VPCs and APCs in cats with asymptomatic HCM are similar to that found in healthy control cats.

Stratification du risque de la mort subite dans la cardiomyopathie hypertrophique en 2016

Patients with hypertrophic cardiomyopathy (HCM) are at an increased risk of death from many causes and sudden cardiac death is one of them. The study of the sudden cardiac death of patients with HCM has allowed the identification of risk factors and among them major risk factor are: family history of sudden cardiac death, the occurrence of syncope/dizziness, the existence of non-sustained ventricular tachycardia an abnormal blood pressure response during stress test, presence of severe left ventricular hypertrophy≥30mm. Risk stratification for sudden cardiac death is essential, for symptomatic or asymptomatic HCM patients. Two approaches are possible: the classical approach or risk stratification methods with major risk factors and the new approach using the risk-calculator recommended by the ESC. Both methods are not in opposition but complementary. The risk stratification in hypertrophic cardiomyopathy should be still improved to be sure that only the most high-risk patients receive an implantable cardiac defibrillator.

Characteristic Clinical Features and Survival in Cats with Symptomatic Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is recognized as the most common feline cardiac disease. Several studies have evaluated the population characteristics and survival time of cats with HCM; however, these reports included large numbers of asymptomatic HCM. The purpose of this study was to evaluate the characteristics and survival time of cats with symptomatic HCM admitted to emergency service. Medical records were examined to verify clinical diagnosis of HCM. Asymptomatic cats diagnosed with HCM were also excluded from the study. From a total of 13 cats, eight were classified in the arterial thromboembolism (ATE) group while the other five were in the congestive heart failure (CHF) group. Middle-aged (6 years, range 1.4~7 years) male cats (53.8%) were included in this study. Pelvic limb paralysis, depression, and respiratory distress were common clinical signs found in symptomatic HCM cats. Hematologic evaluation found that enzymes related to muscle damage and tissue necrosis were elevated in both groups and highly elevated in the ATE group. Left atrium was remarkably enlarged in ATE group cats. The median survival time of cats in the ATE group was significantly shorter than that of cats in the CHF group (P=0.002). Prospective investigation based on a large population would be required to clarify the effects of various factors on prognosis of HCM cats.

Quantification and significance of diffuse myocardial fibrosis and diastolic dysfunction in childhood hypertrophic cardiomyopathy.

The purpose of this study was to evaluate the presence of diffuse myocardial fibrosis in children and adolescents with hypertrophic cardiomyopathy (HCM) and to assess associations with echocardiographic and clinical parameters of disease. While a common end point in adults with HCM, it is unclear whether diffuse myocardial fibrosis occurs early in the disease. Cardiac magnetic resonance (CMR) estimation of myocardial post-contrast longitudinal relaxation time (T1) is an increasingly used method to estimate diffuse fibrosis. T1 measurements were taken using standard multi-breath-hold spoiled gradient echo phase-sensitive inversion-recovery CMR before and 15 min after the injection of gadolinium. The tissue-blood partition coefficient was calculated as a function of the ratio of T1 change of myocardium compared with blood. An echocardiogram and blood brain natriuretic peptide (BNP) levels were obtained on the day of the CMR. Twelve controls (mean age 12.8 years; 7 male) and 28 patients with HCM (mean age 12.8 years; 21 male) participated. The partition coefficient for both septal (0.27 ± 0.17 vs. 0.13 ± 0.09; p = 0.03) and lateral walls (0.22 ± 0.09 vs. 0.07 ± 0.10; p < 0.001) was increased in patients compared with controls. Eight patients had overt areas of late gadolinium enhancement (LGE). These patients did not show increased partition coefficient compared with those without LGE (0.27 ± 0.15 vs. 0.27 ± 0.19 and 0.22 ± 0.09 vs. 0.22 ± 0.09; p = 0.95 and 0.98, respectively). However, patients who were symptomatic (dyspnea, arrhythmia and/or chest pain) had higher lateral wall partition coefficient than asymptomatic HCM patients (0.27 ± 0.08 vs. 0.17 ± 0.08; p = 0.006). Similarly, patients with raised BNP (>100 pg/ml) had raised lateral wall coefficients (0.27 ± 0.07 vs. 0.20 ± 0.07; p = 0.03), as did those with traditional risk factors for sudden death (0.27 ± 0.06 vs. 0.18 ± 0.08; p = 0.007). Diffuse fibrosis, measured by the partition coefficient technique, is demonstrable in children and adolescents with HCM. Markers of fibrosis show an association with symptoms and raised serum BNP. Further study of the prognostic implication of this technique in young patients with HCM is warranted.

Heart rate and arrhythmia frequency of normal cats compared to cats with asymptomatic hypertrophic cardiomyopathy

ObjectivesTo compare heart rate and arrhythmia frequency and complexity in a normal population of cats to a population of cats with hypertrophic cardiomyopathy (HCM). Animals17 cats with HCM and 15 cats with normal echocardiograms. MethodsResults for echocardiography, electrocardiography, Doppler blood pressure, and 24-h Holter monitoring were compared between groups. ResultsThere was no difference in heart rate between HCM cats and normal cats regardless of modality used. All (17/17) HCM cats had ventricular arrhythmias (geometric mean 124 complexes/24 h) with 82% (14/17) exhibiting complex arrhythmias (couplets, triplets, or ventricular tachycardia). Most (14/15) normal cats had ventricular arrhythmias (geometric mean 4 complexes/24 h), but only 20% (3/15) exhibited complexity. HCM cats had significantly more total ventricular complexes, ventricular premature complexes and accelerated idioventricular rhythm than normal cats (P < 0.0001, P < 0.0001, and P = 0.01, respectively). Eighty eight percent (15/17) of HCM cats had supraventricular arrhythmias (geometric mean 9 complexes/24 h) with 23% (4/17) exhibiting complexity. Sixty percent (9/15) of normal cats had supraventricular arrhythmias (geometric mean 1 complex/24 h) with 13% (2/15) exhibiting complexity. Cats with hypertrophic cardiomyopathy had significantly more supraventricular complexes than normal cats (P = 0.0148). ConclusionCats with asymptomatic HCM have more frequent and complex ventricular and supraventricular arrhythmias than normal cats but do not have different overall heart rates compared to normal cats. Further studies are needed to determine if these arrhythmias are associated with an increased risk of sudden cardiac death or influence long-term survival.