Idiopathic Hypertrophic Cardiomyopathy Research Articles

Prevalence and phenotypes associated with ALPK3 null variants in a large French multicentric cohort: Confirming its involvement in hypertrophic cardiomyopathy.

Biallelic disease-causing variants in the ALPK3 gene were first identified in children presenting with a severe cardiomyopathy. More recently, it was shown that carriers of heterozygous ALPK3 null variants are at risk of developing hypertrophic cardiomyopathy (HCM) with an adult onset. Since the number of reported ALPK3 patients is small, the mutational spectrum and clinical data are not fully described. In this multi-centric study, we described the molecular and clinical spectrum of a large cohort of ALPK3 patients. Genetic testing using targeted next generation sequencing was performed in 16 183 cardiomyopathy index cases. Thirty-six patients carried at least one null ALPK3 variant. The five paediatric patients carried two ALPK3 variants, all presented an HCM phenotype with severe outcomes (one transplantation, one heart failure and one cardiac arrest). The 31 adult patients carried heterozygous variants and the main phenotype was HCM (n = 26/31); including 15% (n = 4) presented with an apical or a concentric form of hypertrophy. Reporting a large cohort of ALPK3 patients, this collaborative work confirmed a strong association with HCM and suggesting his screening in the context of idiopathic HCM.

Long-term outcomes and risk factors for reoperation after subaortic stenosis resection in children and adults

Abstract Background Sub-valvular aortic stenosis (SAS) is an extremely heterogeneous form of left ventricular outflow tract (LVOT) obstruction, which can lead to aortic valve damage. Although corrective surgery is considered the most effective treatment, rates of recurrence and reoperation are still high. Previous studies have focused on predictors of reoperation in several subgroups of patients with SAS, but rarely in the whole population of patients with SAS. Purpose We sought to describe long-term outcomes after SAS resection and to determine the predictors of reoperation after successful primary resection. Methods We retrospectively reviewed the records of patients who underwent SAS resection between 1994 and 2021 at our institution with at least 12 months’ follow-up. Patients with a single-ventricle physiology and idiopathic hypertrophic cardiomyopathy were excluded. Demographic, surgical and echocardiographic data were analyzed. Outcomes were reoperation after successful primary resection, death and morbidities, including postoperative complete heart block and aortic regurgitation (AR) grade at latest follow-up. Results Seventy-six patients (paediatric, n = 72 and adult, n = 4) who underwent SAS resection were included in the analysis. Median length of postoperative follow-up was 11.1 years (IQR range: 7.3 – 15.7 years), with two late deaths. Reoperation due to recurrent obstruction or severe AR occurred in 24 patients (31.6%). Median time to reoperation was 7.5 years (IQR range: 3.6 – 11 years). Overall freedom from reoperation at 5 years and 10 years was 84.6% and 69.1% respectively. Gender and association with other cardiac defects did not differ significantly between those with reoperation and those without. In multivariate analysis, independent predictors of reoperation were age at first surgery younger than 5 years (HR 3.54, 95% CI 1.06 – 11.83; P = 0.040) and tunnel-type lesions (HR 4.42, 95% CI 1.70 – 11.51; P = 0.002). Three patients (3.9%) had complete heart block and required placement of an implantable pacemaker. Following SAS resection, progression of AR was common (39/68, 57.3%) but only 5 patients (7.3%) developed sufficient regurgitation to require surgical repair or replacement. Conclusions Reoperation is not infrequent after surgical relief of SAS and reaches a plateau after 10 years. Younger age at first surgery and tunnel-type SAS independently predict reoperation. Progression of AR after corrective surgery of SAS is common, but fortunately only a minority of patients develop hemodynamically significant AR requiring reintervention.

Postmortem Diagnostic Imaging to Evaluate Idiopathic Hypertrophic Cardiomyopathy in a Roborovski Hamster

Idiopathic cardiomyopathy in hamsters can cause death due to cardiac failure. The current case study investigated the capability of imaging to reveal possible cardiomyopathy in a dead hamster. To this end, the cadaver of a 6-month-old male Roborovski dwarf hamster, which showed acute respiratory symptoms a few days before its death, was examined by virtopsy to discover the cause of death. Postmortem radiography was not efficient enough to evaluate the heart due to postmortem lung atelectasis that increases lung opacity and diminishes the contrast between lung and heart. Postmortem computed tomography can be helpful for the assessment of cardiac size. Consistent with postmortem echocardiographic studies, an increased thickness of the left ventricular parietal wall and the interventricular septum and dilation of the left atrium were observed. Thus, hypertrophic cardiomyopathy was determined by imaging and confirmed by the conventional necropsy approach. It showed that the cause of death was acute cardiac failure following idiopathic hypertrophic cardiomyopathy.

Magnitude of the Potential Screening Gap for Fabry Disease in Manitoba: A Population-Based Retrospective Cohort Study.

Fabry disease is a rare disorder caused by the deficient activity of α-galactosidase A (GLA) that often leads to organ damage. Fabry disease can be treated with enzyme replacement or pharmacological therapy, but due to its rarity and nonspecific manifestations, it often goes undiagnosed. Mass screening for Fabry disease is impractical; however, a targeted screening program for high-risk individuals may uncover previously unknown cases. Our objective was to use population-level administrative health databases to identify patients at high risk of Fabry disease. Retrospective cohort study. Population-level health administrative databases housed at the Manitoba Centre for Health Policy. All residents of Manitoba, Canada, between 1998 and 2018. We ascertained the evidence of GLA testing in a cohort of patients at high risk of Fabry disease. Individuals without a hospitalization or prescription indicative of Fabry disease were included if they had evidence of 1 of 4 high-risk conditions for Fabry disease: (1) ischemic stroke <45 years of age, (2) idiopathic hypertrophic cardiomyopathy, (3) proteinuric chronic kidney disease or kidney failure of unknown cause, or (4) peripheral neuropathy. Patients were excluded if they had known contributing factors to these high-risk conditions. Those who remained and had no prior GLA testing were assigned a 0% to 4.2% probability of having Fabry disease depending on their high-risk condition and sex. After applying exclusion criteria, 1386 individuals were identified as having at least 1 high-risk clinical condition for Fabry disease in Manitoba. There were 416 GLA tests conducted during the study period, and of those, 22 were conducted in individuals with at least 1 high-risk condition. This leaves a screening gap of 1364 individuals with a high-risk clinical condition for Fabry disease in Manitoba who have not been tested. At the end of the study period, 932 of those individuals were still alive and residing in Manitoba, and if screened today, we expect between 3 and 18 would test positive for Fabry disease. The algorithms we used to identify our patients have not been validated elsewhere. Diagnoses of Fabry disease, idiopathic hypertrophic cardiomyopathy, and peripheral neuropathy were only available via hospitalizations and not physician claims. We were only able to capture GLA testing processed through public laboratories. Patients identified to be at high risk of Fabry disease by the algorithm did not undergo GLA testing due to a clinical rationale that we were unable to capture. Administrative health databases may be a useful tool to identify patients at higher risk of Fabry disease or other rare conditions. Further directions include designing a program to screen high-risk individuals for Fabry disease as identified by our administrative data algorithms.

Mitral valve abnormalities in decedents of sudden cardiac death due to hypertrophic cardiomyopathy and idiopathic left ventricular hypertrophy

Abstract Background The sole identification of left ventricular hypertrophy (LVH) in a young individual that died suddenly may often lead to an erroneous diagnosis of hypertrophic cardiomyopathy (HCM). Emerging data suggests that idiopathic LVH (ILVH) and HCM may be separate entities. Aim We aimed to report on the prevalence and nature of mitral valve (MV) abnormalities, in a cohort of sudden cardiac death (SCD) victims with a post-mortem examination consistent with HCM and ILVH. Methods We reviewed 6860 consecutive cases of SCD referred to our specialist cardiac pathology centre between 1994 and 2020. SCD was defined as death from a cardiovascular cause within 12 hours of apparent well-being. HCM was defined by the presence of LVH, in the absence of abnormal loading conditions and characterised by myocyte disarray at histology. ILVH was defined as unexplained LVH (heart weight &amp;gt;500 g in males and &amp;gt;400 g in females) and left ventricular (LV) wall thickness &amp;gt;15mm, in the absence of myocardial disarray or secondary causes of LVH. The MV was examined for patency, circumference, thickening, nodularity, ballooning, bulging between cords, perforation, and the presence of impact lesions in the LV outflow tract (LVOT) and aortic outlet. Results Of the total cases of SCD, 264 (4%) were due to HCM (mean age 41±18 years, 78% males, LV maximal wall thickness 19±6 mm) (Figure 1). Ante-mortem symptoms were reported in 44 (17%) cases and for the majority (n=217, 82%) HCM was established at post-mortem. Death was attributed to ILVH in 253 (3%) cases (mean age 43±16 years, 80% males, LV maximal wall thickness 18±4 mm). MV abnormalities were found in 58 (22%) decedents with HCM (mean age 38±17 years; 72% males) and in 13 (5%) decedents with ILVH (mean age 55±15 years; 77% male), p&amp;lt;0.001. Amongst the 58 (22%) cases with HCM and MV abnormalities, 15 (6%) cases had multiple MV abnormalities. These included impact lesions associated with thickening of the anterior leaflet of the MV (n=39) and degenerative changes (n=34) such as bulging and ballooning; and thickening and nodularity. Decedents with HCM exhibiting MV abnormalities were younger than decedents with a normal MV (38±17 versus 45±19 years; p=0.08). Among the 253 decedents with ILVH, 13 (5%) cases exhibited MV abnormalities, which largely included degenerative changes (n=12). Among decedents with HCM and ILVH exhibiting MV abnormalities, the former was significantly younger (38±17 versus 55±15; p=0.001). Myocardial fibrosis was observed in 162 (61%) cases of HCM and 99 (39%) cases of ILVH, p&amp;lt;0.001. Conclusions MV abnormalities are over four-fold more common in individuals with HCM than those with ILVH and may be considered as additional macroscopic features to differentiate between these two entities. Furthermore, the inherent descriptive terminologies used when assessing the MV, support a greater emphasis on the standardisation and quantification of MV abnormalities as part of the autopsy in victims of SCD. Funding Acknowledgement Type of funding sources: Other. Main funding source(s): Acknowledgements: We thank the charitable organisation, Cardiac Risk in the Young (CRY) who fund and support the CRY Cardiovascular Pathology Unit and CRY database.

Mitral valve abnormalities in decedents of sudden cardiac death due to hypertrophic cardiomyopathy and idiopathic left ventricular hypertrophy.

Mitral valve abnormalities in decedents of sudden cardiac death due to hypertrophic cardiomyopathy and idiopathic left ventricular hypertrophy.

Thirty-year outcome in children with hypertrophic cardiomyopathy based on the type

BackgroundWe reviewed the long-term outcome of children with hypertrophic cardiomyopathy (HCM) based on the type. MethodsWe reviewed the medical records of 100 patients (male 54 female 46) with HCM at our hospital between 1977 and 2015. The survival and cardiac event-free survival rates were calculated by the Kaplan–Meier method. ResultsThe age at the time of the diagnosis ranged from 0 to 15 years with a median of 8 years. The number of patients with Noonan syndrome and hypertrophic obstructive cardiomyopathy (HOCM), idiopathic HCM (i-HCM), and secondary HCM (s-HCM) was 13, 13, 65, and 9 respectively. A dilated phase of HCM occurred in 24 patients. Nineteen (79 %) of the 24 patients died of heart failure, and two underwent a heart transplantation. Eight (33 %) of the 24 patients had s-HCM. The median age when a dilated phase occurred was 15 years old, and the median interval from the initial diagnosis to the dilated phase was 8 years. The median time from the diagnosis of a dilated phase to death was 1.6 years. Sudden death and implantable cardioverter defibrillator implantations occurred in 6 and 11 patients at around 15 years old, respectively. The 20-year survival rates were as follows: Noonan syndrome 84 %; HOCM 82 %; i-HCM 71 %; and s-HCM 17 %. Overall, the survival rates at 10, 20, and 30 years were 83 % (95 % confidence interval 73–89), 69 % (58–78), and 63 % (50–74), respectively. The overall cardiac event-free survival rates at 10, 20, and 30 years were 57 % (47–67), 39 % (31–50), and 32 % (21–44), respectively. ConclusionThe long-term outcome in children with HCM was poor, and the outcome of s-HCM was very poor. The occurrence of a dilated phase worsened the outcome in HCM patients. Sudden death and d-HCM often occurred at around 15 years old.

Abstract 12022: Cardiac Rehabilitation for Patients With Idiopathic Hypertrophic Cardiomyopathy

Introduction: Cardiac rehabilitation (CR) is strongly recommended for patients with cardiovascular diseases, but a few studies on exercise training for hypertrophic cardiomyopathy (HCM) are reported. Objective: The aim of this study is to clarify whether supervised CR could improve the long-term prognosis of patients with HCM. Methods: Our multicenter cohort study included 590 idiopathic HCM patients recruited into supervised CR with anaerobic threshold (AT) level from 2004 to 2018, who were divided into two groups according to CR duration; CR until discharge (non-CR group) and continuous outpatient CR after discharge (CR group). Mortality and major adverse cardiovascular events (MACE) were compared between the groups by Kaplan-Meier and Cox hazard analyses. Results: Follow-up period after registration was 3.4±2.6 years. Patients in CR group were older and their ejection fraction (EF) was lower than those in non-CR group (68±12 versus 62±19 years; p&lt;0.01 and 57±17 versus 63±15%; p&lt;0.001, respectively). The HCM patients in CR group had worse survival and relatively higher risk of MACE than those in non-CR group by Kaplan-Meier analysis (log rank, p=0.01 and p=0.08, respectively). However, the risk of death and MACE was similar between two groups by Cox hazard analysis adjusted by age, gender, hypertension, dyslipidemia, diabetes, smoking, EF, beta blockers, angiotensin-converting-enzyme inhibitors, angiotensin receptor blockers and statins (p=0.16 and p=0.64, respectively). Conclusions: Exercise with AT level for HCM patients did not significantly increase mortality, but continuous CR for patients with HCM should be carefully considered.

Calmodulinopathies: throwing back the veil on the newest life-threatening genetic arrhythmia syndrome.

This review provides a basic understanding of the calmodulin gene and its role in calcium homeostasis. We outline the functional effects and clinical expression of CALM mutations and review disease expression and management. Calmodulinopathies are rare life-threatening arrhythmia syndromes affecting young individuals. They are caused by mutations in any of the three genes (CALM 1-3) that encode calmodulin (CaM), a ubiquitously expressed Ca signaling protein with multiple targets that in the heart, modulates several ion channels. Patients express varied phenotypes: long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, sudden death, idiopathic ventricular fibrillation, hypertrophic cardiomyopathy, or mixed disease. This is severe disease. Over half of 2019 International Calmodulin Registry patients experienced recurrent cardiac events despite management strategies that included: monotherapy and combination therapy with beta blockers, sodium channel blockers, other antiarrhythmics, sympathetic denervation, and pacing. Induced pluripotent stem cell-derived cardiomyocytes from patients harboring CALM mutations have provided a platform for better understanding pathogenic mechanisms and avenues for therapy. Calmodulinopathies are among the more novel inherited arrhythmia syndromes. These are rare but highly lethal diseases with diverse clinical expressions. The practicing electrophysiologist should be aware these conditions, how to recognize them clinically, and understand the challenges in management.

Genetic study of pediatric hypertrophic cardiomyopathy in Egypt.

Paediatric cardiomyopathy is a progressive and often lethal disorder and the most common cause of heart failure in children. Despite their severe outcomes, their genetic etiology is still poorly characterised. The current study aimed at uncovering the genetic background of idiopathic primary hypertrophic cardiomyopathy in a cohort of Egyptian children using targeted next-generation sequencing. The study included 24 patients (15 males and 9 females) presented to the cardiomyopathy clinic of Cairo University Children's Hospital with a median age of 2.75 (0.5-14) years. Consanguinity was positive in 62.5% of patients. A family history of hypertrophic cardiomyopathy was present in 20.8% of patients. Ten rare variants were detected in eight patients; two pathogenic variants (8.3%) in MBPC3 and MYH7, and eight variants of uncertain significance in MYBPC3, TTN, VCL, MYL2, CSRP3, and RBM20.Here, we report on the first national study in Egypt that analysed sarcomeric and non-sarcomeric variants in a cohort of idiopathic paediatric hypertrophic cardiomyopathy patients using next-generation sequencing. The current pilot study suggests that paediatric hypertrophic cardiomyopathy in Egypt might have a particular genetic background, especially with the high burden of consanguinity. Including the genetic testing in the routine diagnostic service is important for a better understanding of the pathophysiology of the disease, proper patient management, and at-risk detection. Genome-wide tests (whole exome/genome sequencing) might be better than the targeted sequencing approach to test primary hypertrophic cardiomyopathy patients in addition to its ability for the identification of novel genetic causes.

Epidemiology of Pediatric Hypertrophic Cardiomyopathy in a 10-Year Medicaid Cohort.

The epidemiologic data for pediatric hypertrophic cardiomyopathy (HCM)needs to be periodically updated as diagnostic techniques and management strategies improve. Herein, the incidence, prevalence, andmortality rates of pediatric HCM in a population-based treatment system are described. Patients aged ≤ 17years and diagnosed with HCM on service visits over a 10-year period in one state Medicaid database (2007-2016) were analyzed. The cohort included 137 unique patients; 64.2% were male; 40.9% were African American; 42.3% were first diagnosed ≤ 24months. The accrued 10-year prevalence rate for pediatric HCM was 1.2/1,000,000 and the annual incidence rate (CY 2010) was 1.3/100,000. Cardiac-related mortality was 2.9% in those who died cohort (N = 10); 70.0% of those who died were ≤ 13months of age. Arrhythmia was diagnosed in 30.7% of the cohort, heart failure in 12.4%, and low birth weight in 8.8%. Inborn errors of metabolism were diagnosed in 8.0% of the cohort; malformation syndromes in 13.1%, and neuromuscular disorders in 2.9%; therefore, 75.9% were classified as idiopathic HCM. Our findings are somewhat higher than extant study estimates but update and augment them in representing a Southeast US statewide service system.

Sleep Disordered Breathing in Hypertrophic Cardiomyopathy

There is a paucity of scientific knowledge regarding the presence and nature of sleep disordered breathing (SDB) amongst patients with hypertrophic cardiomyopathy (HCM). SDB may contribute to morbidity and mortality in patients with HCM. The goal of this study was to characterize SDB among HCM patients and evaluate treatment patterns of, and adherence to, positive airway pressure (PAP) therapies. An additional aim was to characterize if PAP therapy was associated with mortality in patients with HCM. Retrospective review of consecutive adults with idiopathic HCM undergoing polysomnography (PSG) at the Mayo Clinic over a 10 year period. Type of PAP therapy and PAP adherence were obtained if PAP therapy was prescribed. Ninety-four patients with HCM underwent PSG (age 56.3 ± 12.4 years; 62 males, [66%]). Median follow-up was 6 years. Most patients (n = 75, 80%) had obstructive sleep apnea (OSA), followed by a combination of obstructive and central sleep apnea (n = 6; 6%), and central sleep apnea (n = 1; 1%). Twenty-four percent (n = 18) of patients with OSA had treatment emergent central sleep apnea. The rest (n = 12, 13%) had normal PSG studies. Continuous PAP (n = 60) was the most commonly prescribed PAP modality followed by adaptive servo-ventilation (ASV; n = 10). For those patients with known adherence (n = 43), adherence was greater than 4 h a night for greater than 70% of the days for a majority of patients (n = 36; 83%). Mortality was not associated with SDB, PAP treatment or PAP adherence over the 10 year period. SDB is highly prevalent in patients with HCM. Continuous PAP therapy was the most common PAP therapy and PAP adherence was high. There was no association between SDB and mortality in this limited data set of patients with HCM.

The clinical use of the MOGE(S) classification in the differential diagnosis between idiopathic hypertrophic cardiomyopathy and its phenocopies

Aim . To determine the relation between idiopathic hypertrophic cardiomyopathy (HCM) and HCM phenocopies, as well as to study the etiological pattern of HCM phenocopies in patients of the North-Western region of Russia in different age groups. Material and methods . The study included 321 patients with left ventricular hypertrophy ≥15 mm according to an echocardiography. All the necessary clinical, laboratory and instrumental diagnostic methods for verification of HCM and HCM phenocopies was carried out. In the diagnosis, the MOGE(S) classification was used. Results . At a young age, idiopathic HCM accounts for 92% (n=62), HCM phenocopies — 8% (Danon disease (n=1 (2%)), isolated cardiac sarcoidosis (n=1 (2%)) and systemic AL amyloidosis (n=3(4%)). Idiopathic HCM is also found in the vast majority of middle-aged patients — in 85% of cases (n=86). HCM phenocopies (15%) were in isolated cardiac sarcoidosis (n=3 (3%)), systemic amyloidosis variants (n=12 (12%)) — AL amyloidosis with predominant cardiac injury (n=11,11%), hereditary transthyretin amyloidosis (n=1,1%). Of the 153 examined patients with HCM aged ≥60 years old, 85% (n=131) were diagnosed with idiopathic HCM. HCM phenocopies were detected in 15% of cases (n=22). In the etiological pattern of HCM phenocopies, transthyretin amyloidosis was 10%: non-hereditary transthyretin amyloidosis — 6% (n = 9), hereditary transthyretin amyloidosis — 4% (n=6); AL amyloidosis — 4% (n=6). In 1 patient, acromegalic cardiomyopathy (1%) was verified. In this article, we present 3 clinical cases that demonstrate the difficulty of differential diagnosis between idiopathic HCM and various HCM phenocopies. Conclusion . In all age groups, idiopathic HCM predominates. Lysosomal storage diseases classify as rare diseases. Isolated cardiac injury with amyloidosis and sarcoidosis is widely met but less often diagnosed. We determined a high frequency of isolated cardiac injury with amyloidosis under the age of 45 years. The etiological pattern of HCM phenocopies in the elderly is represented mainly by transthyretin cardiomyopathic amyloidosis of hereditary and non-hereditary variants.

Case Study: Dilated Cardiomyopathy Evolves into Apical-Variant Hypertrophic Cardiomyopathy

Introduction Apical-variant hypertrophic cardiomyopathy (HCM) is a form of HCM in which hypertrophy is limited to the left-ventricular apex. Apical-variant HCM is rarely obstructive, though there is still an increased risk of atrial fibrillation, myocardial infarction, and sudden cardiac death (SCD). Apical-variant HCM has not previously been described in a patient with a prior diagnosis of dilated cardiomyopathy (DCM). Case A 53-year-old female with a history of hypertension and type-II diabetes mellitus presented with progressive dyspnea on exertion, fatigue and lower extremity swelling. Family history was significant for SCD of her mother at age 45. An initial transthoracic echocardiogram (TTE) showed DCM with an ejection fraction (EF) 15% and left ventricular end diastolic dimension (LVEDD) of 6.8 cm. The patient was placed on guideline-directed medical therapy (GDMT) and ultimately received cardiac resynchronization therapy with a defibrillator (CRT-D). One year later, EF was 25% with LVEDD 7.1 cm (Figure 1). A subsequent TTE two years later showed resolution of DCM with EF 55% and LVEDD of 5.1 cm. However, a new finding on this TTE was apparent: the apex demonstrated a spade-like shape on contraction consistent with apical-variant HCM (Figure 2). The patient underwent genetic testing but no genetic cause of either DCM or HCM was identified. Discussion HCM is caused by autosomal-dominant inheritance of a defective gene in sarcomere proteins. DCM and HCM are linked in that some etiologies of DCM are driven by sarcomeric protein abnormalities. DCM is also a rare phenotypical variant of HCM generally occurring very late in the disease and evolving from an initially hypertrophic myocardium. The opposite, in which DCM evolves into apical-variant HCM, to the best of our knowledge, has not been described in the literature. This relationship, as well as a family history of early SCD, suggest an inherited sarcomeric disorder manifesting as two discrete phenotypes within the same individual. This evolution may be due to treatment with GDMT, or it may be a rare expression of the disease's natural history. Only a fraction of cases of idiopathic DCM and HCM have an identifiable genetic cause and, thus, lacking an identified mutation does not preclude an inherited cardiomyopathy.

Prevalence and clinical significance of red flags in patients with hypertrophic cardiomyopathy

IntroductionWe sought to determine prevalence and predictive accuracy of clinical markers (red flags, RF), known to be associated with specific systemic disease in a consecutive cohort of patients with hypertrophic cardiomyopathy (HCM). MethodsWe studied 129 consecutive patients (23.7 ± 20.9 years, range 0–74 years; male/female 68%/32%). Pre-specified RF were categorized into five domains: family history; signs/symptoms; electrocardiography; imaging; and laboratory. Sensitivity (Se), specificity (Sp), negative predictive value (NPV), positive predictive value (PPV), and predictive accuracy of RF were analyzed in the genotyped population. ResultsIn the overall cohort of 129 patients, 169 RF were identified in 62 patients (48%). Prevalence of RF was higher in infants (78%) and in adults >55 years old (58%). Following targeted genetic and clinical evaluation, 94 patients (74%) had a definite diagnosis (sarcomeric HCM or specific causes of HCM). We observed 14 RF in 13 patients (21%) with sarcomeric gene disease, 129 RF in 34 patients (97%) with other specific causes of HCM, and 26 RF in 15 patients (45%) with idiopathic HCM (p < 0.0001). Non-sarcomeric causes of HCM were the most prevalent in ages <1yo and > 55yo. Se, Sp, PPV, NPV and PA of RF were 97%, 70%, 55%, 98% and 77%, respectively.Single and clinical combination of RF (clusters) had an high specificity, NPV and predictive accuracy for the specific etiologies (syndromes/metabolic/infiltrative disorders associated with HCM). ConclusionsAn extensive diagnostic work up, focused on analysis of specific diagnostic RF in patients with unexplained LVH facilitates a clinical diagnosis in 74% of patients with HCM.

Danon Disease: A Challenging Case with Diagnosis of Hypertrophic Cardiomyopathy

: Danon disease is an X-linked dominant glycogen storage disease characterized by cardiomyopathy, skeletal myopathy, and intellectual disability. Danon disease has a rapidly progressive natural course, hence early diagnosis is crucial to achieve a proper management plan. This case concerns a 30-year-old male of Danon disease presenting with symptoms and signs of systolic heart failure, with no intellectual impairment and skeletal muscle involvement at presentation. Thus, he was initially misdiagnosed and managed as idiopathic sarcomeric hypertrophic cardiomyopathy. To the best of our knowledge, this is the first report of Danon disease in Iran, further implicating previous cases overlooked by local cardiologists.

Left Ventricular Relaxation Half-Time as a Predictor of Cardiac Events in Idiopathic Dilated Cardiomyopathy and Hypertrophic Cardiomyopathy With Left Ventricular Systolic and/or Diastolic Dysfunction

Diastolic dysfunction preceding systolic dysfunction is considered an important interaction in cardiomyopathy with poor prognosis. The aim of this study was to compare left ventricular (LV) isovolumic relaxation with the other parameters as a potential prognostic marker for patients with idiopathic dilated cardiomyopathy (IDC) and hypertrophic cardiomyopathy (HC). A total of 145 patients with IDC and 116 with HC were evaluated for hemodynamic parameters; LV pressure was directly measured by a micromanometer catheter, and relaxation half-time (T1/2) was used to determine LV isovolumic relaxation. The median follow-up period was 4.7 years. The mean ages of the patients with IDC and HC were 52.0 ± 12.0 and 57.1 ± 12.4 years, respectively. Each patient group was further divided into 2 groups based on the median value of T1/2: (1) <41.0 ms (D-L group) and ≥41.0 ms (D-H group) (2) <38.5 ms (H-L group) and ≥38.5 ms (H-H group). Kaplan-Meier analysis showed a significantly higher probability of cardiac events in the D-H group than in the D-L group (p = 0.001) and in the H-H group than in the H-L group (p = 0.028). Further, Cox proportional hazard regression analysis revealed that T1/2 was an independent predictor of cardiac events for patients with IDC (hazard ratio 1.109; p = 0.007) and HC (hazard ratio 1.062; p = 0.041). In conclusion, regardless of the type of cardiomyopathy, T1/2 as a measure of LV isovolumic relaxation function was found to be associated with the occurrence of cardiac events.

Risk factors for lethal arrhythmic events in children and adolescents with hypertrophic cardiomyopathy and an implantable defibrillator: An international multicenter study

Predictors of risk of lethal arrhythmic events (LAE) is poorly understood and may differ from adults in children with hypertrophic cardiomyopathy (HCM). The purpose of this study was to determine predictors of LAE in children with HCM. A retrospective data collection was performed on 446 children and teenagers 20 years and younger (290 [65%] male; mean age 10.1 ± 5.7 years) with idiopathic HCM from 35 centers. Patients were classified as group 1 (HCM with LAE) if having a secondary prevention implantable cardioverter-defibrillator (ICD) or primary prevention ICD with appropriate interventions or group 2 (HCM without LAE) if having a primary prevention ICD without appropriate interventions. There were 152 children (34%) in group 1 and 294 (66%) in group 2. Risk factors for group 1 by univariate analysis wereseptal thickness, posterior left ventricular (LV) wall thickness, lower LV outflow gradient, and Q wave > 3 mm in inferior electrocardiographic leads. Factors not associated with LAE were family history of SCD, abnormal blood pressure response to exercise, and ventricular tachycardia on ambulatory electrocardiographic monitoring. Risk factors for SCD by multivariate analysis were age at ICD placement (hazard ratio [HR] 0.9; P = .0025), LV posterior wall thickness z score (HR 1.02; P < .005), and LV outflow gradient < 30 mm Hg (HR 2.0; P < .006). LV posterior wall thickness z score ≥ 5 was associated with LAE. Risk factors for LAE appear different in children compared to adults. Conventional adult risk factors were not significant in children. Further prospective studies are needed to improve risk stratification for LAE in children with HCM.

Markers Of Arrhythmia In Patients With Left Ventricular Outflow Tract Stenosis And Coartation Of Aort

Objective: Arrhythmias due to congenital heart diseases are found to be the second most common cause of mortality after ischemic heart diseases in several studies . Coarctation of the aorta , hypertrophic cardiomyopathy and aort stenosis increase afterload of the left ventricle and as a result of this, they cause an increase in wall stress in the early and hypertophy of the wall in the late phase. This condition leads a corruption in ventricular and atrial conduction and predisposes to arrhythmias . In this study, we intended to examine the risks with indicators like P dis, QT dis, Tp-e for arrhythmias in diseases with left ventricular outflow tract stenosis in children. Method: 101 patients with with left ventricular outflow tract stenosis ( coarctation of the aorta, idiopathic hypertrophic subaortic stenosis , hypertrophic cardiomyopathy and aortic stenosis ) in pediatric age group who were diagnosed between 2008-2014 in Dr . Behçet Uz Children’s Training and Research Hospital were included in this study. 110 healthy children were included in this study as a control group. Pdis, corrected QT, QT dis ve Tp-e and Tp-e /QT indices in both groups were were calculated and compared using standard 12 -lead ECG. Results: P max, corrected QT, Pdis, QTdis, Tp-e and Tp-e/QT in patient group were found to be significantly higher than the control group . There was no difference between sub- groups of patient group according to Pmax, corrected QT, P dis, QT dis, Tp-e and Tp-e/QT. There was also no difference between beta blocker users and non-users according to P max, corrected QT, P dis, QT dis, Tp-e and Tp-e/QT. Conclusions: High P max, corrected QT, P dis, QT dis, Tp-e and Tp-e/QT in the patient group showed the risk for ventricular arrhythmias and atrial fibrillation in patients with left ventricular outflow tract stenosis .

Outcomes in Pediatric Hypertrophic Cardiomyopathy Patients with Reduced Systolic Ventricular Function

Purpose Our aim was to determine the transplant-free survival for pediatric hypertrophic cardiomyopathy (HCM) patients with decreased left ventricular (LV) systolic function and identify risk factors for change in function. Methods There were 177 patients (<18 years old) identified in our centre's Heart Failure Database diagnosed with HCM between January 1, 2001 and July 1, 2017. Patients with at least mildly reduced LV systolic function on quantitative and/or qualitative assessment were compared to those with normal function. Changes in ejection fraction (EF) over time for the entire HCM cohort were analyzed using a linear regression model adjusted for repeated measures and risk factors associated with change were identified. Results Reduced LV function was observed in 31 patients (17.5%) of which 19 (61%) were male and 22 (71%) had idiopathic HCM. Median age at diagnosis was 1.2 years (IQR 0.06-10.2) and at follow-up was 6.0 years (IQR 1.2-14.6). The 7-year transplant-free survival for patients with reduced systolic function was 41% (95% CI 30-52%) compared with 92% (95% CI 90-94%) for patients with normal function (p<.0001). Factors associated with a decline in EF were increased LV posterior wall thickness z-score and intensive care unit (ICU) admission. LV outflow tract obstruction was associated with an increase in EF (Table 1). Conclusion Pediatric HCM patients with reduced LV systolic function have a significantly worse transplant-free survival than those with normal LV function. The presence of increased LV posterior wall thickness or admission to the ICU are independent predictors of worsening LV function over time. Our aim was to determine the transplant-free survival for pediatric hypertrophic cardiomyopathy (HCM) patients with decreased left ventricular (LV) systolic function and identify risk factors for change in function. There were 177 patients (<18 years old) identified in our centre's Heart Failure Database diagnosed with HCM between January 1, 2001 and July 1, 2017. Patients with at least mildly reduced LV systolic function on quantitative and/or qualitative assessment were compared to those with normal function. Changes in ejection fraction (EF) over time for the entire HCM cohort were analyzed using a linear regression model adjusted for repeated measures and risk factors associated with change were identified. Reduced LV function was observed in 31 patients (17.5%) of which 19 (61%) were male and 22 (71%) had idiopathic HCM. Median age at diagnosis was 1.2 years (IQR 0.06-10.2) and at follow-up was 6.0 years (IQR 1.2-14.6). The 7-year transplant-free survival for patients with reduced systolic function was 41% (95% CI 30-52%) compared with 92% (95% CI 90-94%) for patients with normal function (p<.0001). Factors associated with a decline in EF were increased LV posterior wall thickness z-score and intensive care unit (ICU) admission. LV outflow tract obstruction was associated with an increase in EF (Table 1). Pediatric HCM patients with reduced LV systolic function have a significantly worse transplant-free survival than those with normal LV function. The presence of increased LV posterior wall thickness or admission to the ICU are independent predictors of worsening LV function over time.