scholarly journals Clinical characteristics and outcomes in childhood-onset hypertrophic cardiomyopathy

2021 ◽  
Author(s):  
Nicholas A Marston ◽  
Larry Han ◽  
Iacopo Olivotto ◽  
Sharlene M Day ◽  
Euan A Ashley ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Natural History ◽  
Ventricular Arrhythmias ◽  
Composite Endpoint ◽  
Adult Onset ◽  
Childhood Onset ◽  
Ventricular Assist ◽  
Increased Risk ◽  
Age Of Diagnosis ◽  
Life Threatening

Abstract Aims Childhood-onset hypertrophic cardiomyopathy (HCM) is far less common than adult-onset disease, thus natural history is not well characterized. We aim to describe the characteristics and outcomes of childhood-onset HCM. Methods and results We performed an observational cohort study of 7677 HCM patients from the Sarcomeric Human Cardiomyopathy Registry (SHaRe). Hypertrophic cardiomyopathy patients were stratified by age at diagnosis [<1 year (infancy), 1–18 years (childhood), >18 years (adulthood)] and assessed for composite endpoints reflecting heart failure (HF), life-threatening ventricular arrhythmias, atrial fibrillation (AF), and an overall composite that also included stroke and death. Stratifying by age of diagnosis, 184 (2.4%) patients were diagnosed in infancy; 1128 (14.7%) in childhood; and 6365 (82.9%) in adulthood. Childhood-onset HCM patients had an ∼2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the 1st decade following baseline visit, but HF and AF becoming more common by the end of the 2nd decade. Sarcomeric variants were more common in childhood-onset HCM (63%) and carried a worse prognosis than non-sarcomeric disease, including a greater than two-fold increased risk of HF [HRadj 2.39 (1.36–4.20), P = 0.003] and 67% increased risk of the overall composite outcome [HRadj 1.67 (1.16–2.41), P = 0.006]. When compared with adult-onset HCM, childhood-onset was 36% more likely to develop life-threatening ventricular arrhythmias [HRadj 1.36 (1.03–1.80)] and twice as likely to require transplant or ventricular assist device [HRadj 1.99 (1.23–3.23)]. Conclusion Patients with childhood-onset HCM are more likely to have sarcomeric disease, carry a higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies. These findings provide insight into the natural history of disease and can help inform clinical risk stratification.

Abstract 14117: Clinical Characteristics and Cardiovascular Outcomes in Childhood-Onset Hypertrophic Cardiomyopathy

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nicholas A Marston ◽  
Larry Han ◽  
iacopo olivotto ◽  
Sharlene Day ◽  
Euan A Ashley ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Ventricular Arrhythmias ◽  
Composite Endpoint ◽  
Adult Onset ◽  
Childhood Onset ◽  
Ventricular Assist ◽  
Disease Biology ◽  
Increased Risk ◽  
Age Of Diagnosis ◽  
Life Threatening

Introduction: The prevalence of childhood-onset hypertrophic cardiomyopathy (HCM) is lower than adult-onset disease, thus natural history is not well characterized. We aim to describe the characteristics and outcomes of childhood-onset HCM. Methods: We performed an observational cohort study of 6345 HCM patients from the Sarcomeric Human Cardiomyopathy Registry (SHaRe) and Toronto's SickKids hospital. HCM patients were stratified by age at diagnosis (<1 year (infancy), 1-18 years (childhood), >18 years (adulthood)) and assessed for composite endpoints reflecting heart failure (HF), life-threatening ventricular arrhythmias, atrial fibrillation (AF), and an overall composite that also included stroke and death. Results: Based on defined age of diagnosis stratification, 173 (3%) patients were diagnosed in infancy, 909 (14%) in childhood, and 5263 (83%) in adulthood. Childhood-onset HCM patients had a 2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the 1st decade following diagnosis, and HF and AF more common by the end of the 2nd decade ( Fig, a ). Sarcomeric HCM was more common in childhood-onset HCM (62%) and carried a worse prognosis than non-sarcomeric disease, including a >2-fold increased risk of HF (HR adj 2.39 [1.36-4.20], p=0.003) and 67% increased risk of overall composite events (HR adj 1.67 [1.16-2.41], p=0.006). When compared to adult-onset HCM, childhood-onset was 36% more likely to develop life-threatening ventricular arrhythmias (HR adj 1.36 [1.03-1.80]) and twice as likely to require transplant or ventricular assist device (HR adj 1.99 [1.23-3.23]) ( Fig, b ). Conclusion: Patients with childhood-onset HCM are more likely to have sarcomeric disease, carry higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies. These findings provide insight into disease biology and can help improve the precision of risk prediction.

Abstract 15391: The Natural History of Asymptomatic and Mildly Symptomatic Obstructive Hypertrophic Cardiomyopathy: Insights From the Share Registry

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Monica Ahluwalia ◽  
Larry Han ◽  
iacopo olivotto ◽  
Euan A Ashley ◽  
Michelle Michels ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Natural History ◽  
Management Strategies ◽  
Composite Endpoint ◽  
Ventricular Outflow Tract ◽  
Left Ventricular ◽  
Increased Risk ◽  
Obstructive Hypertrophic Cardiomyopathy ◽  
Left Ventricular Outflow ◽  
History Of

Background: Contemporary studies are needed to determine the natural history of asymptomatic and mildly symptomatic patients with obstructive hypertrophic cardiomyopathy (oHCM). Methods: Patients with HCM, peak left ventricular outflow tract (LVOT) gradient ≥30 mm Hg (at rest, post-Valsalva, or exercise) and baseline NYHA I-II symptoms were identified using the multicenter Sarcomeric Human Cardiomyopathy Registry (SHaRe). Patients with prior atrial fibrillation (AF) or septal reduction therapies (SRT) were excluded. Incident outcomes, including the composite of NYHA III-IV symptoms, AF or SRT, were related to LVOT using Kaplan-Meier analysis (LVOT tertiles) and Cox proportion hazard models, controlling for age, sex, race, proband status, sarcomere status, hypertension and left atrial diameter. Results: At baseline, the 1048 patients who met inclusion criteria were 52.0 ± 16.1 yrs, 48.9% female, 34.9% sarcomere mutation +, with mean LVOT gradient 72 ± 39mm Hg. Over 8.6 years follow up (IQR 2.3, 13.6), progression to the composite endpoint ocurred in 530 (50.6%) and 92 (8.8%) died. Patients in the highest tertile of LVOT gradient (>84 mm Hg) were at increased risk of the composite endpoint (Figure). Every 10 mm Hg increase in LVOT gradient was associated with increased risk of incident NYHA III-IV HF (HR 1.04, 95% CI 1.00, 1.08, p=0.04), SRT (HR 1.07, 95% CI 1.04, 1.09, p<0.001) and the composite endpoint (HR 1.03, 95% CI 1.01, 1.06, p=0.003), but not incident AF (HR 1.02, p=0.39) or death (HR 0.99, p=0.3). Older age (HR 1.01, 95% CI 1.00-1.03, p=0.03), black race (HR 1.73, 95% CI 1.11-2.69, p=0.02) and sarcomere mutations (HR 1.27, 95% CI 1.02-1.59, p=0.03) were also associated with increased risk of the composite endpoint. Conclusions: In oHCM patients with NYHA I-II symptoms, the LVOT gradient appears to predict worsening symptoms and need for SRT, but not AF or overall survival. These findings have implications for refining management strategies for oHCM.

scholarly journals Age at Menarche and Asthma Onset Among US Girls and Women: Findings from NHANES, 2001-2018

2021 ◽  
Author(s):  
Li Cai ◽  
Lan Qiu ◽  
Yaqi Wang ◽  
Li Wu ◽  
Xiaojie Wu ◽  
...  
Keyword(s):  
Family Income ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Age At Menarche ◽  
Adult Onset ◽  
Childhood Onset ◽  
Early Menarche ◽  
Representative Study ◽  
Increased Risk ◽  
Menarche Age

Abstract Background: Findings on the association between early menarche and asthma onset remain inconsistent and the evidence in the US is lacking. Furthermore, there was no clear separation of childhood- and adult-onset asthma in previous studies. Therefore, we aim at quantitatively estimating the association of age at menarche with risk of childhood- and adult-onset asthma separately in US girls and women.Methods: We conducted a retrospective cohort study of 24,282 US girls and women aged less than 80 years by using continuous NHANES data in 2001-2018. Weighted Cox proportional-hazards regression models with censoring ages of 19 and 79 were used to separately estimate hazard ratios of childhood- and adult-onset asthma associated with age at menarche. Results: Each one-year increase of age at menarche was significantly associated with a 17% (HR [95%CI]: 0.83 [0.77, 0.90]) decrease in the risk of childhood-onset asthma. Compared with age at menarche of 12-14, we observed a 60% (HR [95%CI]: 1.60 [1.22, 2.09]) increased risk of childhood-onset asthma for early menarche (age at menarche <12 years) and 41% (HR [95%CI]: 0.59 [0.32, 1.08]) decreased risk for late menarche (age at menarche ≥15 years). Race, family income, education and family history of asthma did not modify these associations. No significant association between age at menarche and adult-onset asthma.Conclusions: In this US nationally representative study, we found that early menarche was associated with increased risk of childhood-onset asthma, but not adult-onset asthma. These findings help demonstrate early menarche may be a risk factor for childhood-onset asthma in US, indicating timely and effective management of special individuals with early menarche for preventing asthma.

scholarly journals Ion Channel Impairment and Myofilament Ca2+ Sensitization: Two Parallel Mechanisms Underlying Arrhythmogenesis in Hypertrophic Cardiomyopathy

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2789
Author(s):  
Lorenzo Santini ◽  
Raffaele Coppini ◽  
Elisabetta Cerbai
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Ventricular Arrhythmias ◽  
Early Stage ◽  
Sodium Current ◽  
Young Patients ◽  
Early Observation ◽  
Parallel Mechanisms ◽  
Cellular Mechanisms ◽  
Increased Risk ◽  
Repolarization Reserve

Life-threatening ventricular arrhythmias are the main clinical burden in patients with hypertrophic cardiomyopathy (HCM), and frequently occur in young patients with mild structural disease. While massive hypertrophy, fibrosis and microvascular ischemia are the main mechanisms underlying sustained reentry-based ventricular arrhythmias in advanced HCM, cardiomyocyte-based functional arrhythmogenic mechanisms are likely prevalent at earlier stages of the disease. In this review, we will describe studies conducted in human surgical samples from HCM patients, transgenic animal models and human cultured cell lines derived from induced pluripotent stem cells. Current pieces of evidence concur to attribute the increased risk of ventricular arrhythmias in early HCM to different cellular mechanisms. The increase of late sodium current and L-type calcium current is an early observation in HCM, which follows post-translation channel modifications and increases the occurrence of early and delayed afterdepolarizations. Increased myofilament Ca2+ sensitivity, commonly observed in HCM, may promote afterdepolarizations and reentry arrhythmias with direct mechanisms. Decrease of K+-currents due to transcriptional regulation occurs in the advanced disease and contributes to reducing the repolarization-reserve and increasing the early afterdepolarizations (EADs). The presented evidence supports the idea that patients with early-stage HCM should be considered and managed as subjects with an acquired channelopathy rather than with a structural cardiac disease.

scholarly journals The Burden of Ventricular Arrhythmias Following Left Ventricular Assist Device Implantation

2014 ◽  
Vol 3 (3) ◽  
pp. 145 ◽  
Author(s):  
Jan M Griffin ◽  
Jason N Katz ◽  
◽  
Keyword(s):  
Heart Failure ◽  
Left Ventricular Assist Device ◽  
Ventricular Assist Device ◽  
Ventricular Arrhythmias ◽  
Left Ventricular ◽  
Circulatory Support ◽  
Assist Device ◽  
Ventricular Assist ◽  
Increased Risk ◽  
Left Ventricular Assist

Few innovations in medicine have so convincingly and expeditiously improved patient outcomes more than the development of the left ventricular assist device (LVAD). Where optimal pharmacotherapy once routinely failed those with end-stage disease, the LVAD now offers considerable hope for the growing advanced heart failure population. Despite improvements in mortality, however, mechanical circulatory support is not without its limitations. Those supported with an LVAD are at increased risk of several complications, including infection, bleeding, stroke and arrhythmic events. While once considered benign, ventricular arrhythmias in the LVAD patient are being increasingly recognised for their deleterious influence on patient morbidity and quality of life. In addition, the often multifactorial aetiology to these episodes makes treatment difficult and optimal therapeutic management controversial. Novel strategies are clearly needed to better predict, prevent, and eradicate these arrhythmias in order to allow future generations of heart failure patients to reap the full benefits of LVAD implantation.

Abstract 12518: Ventricular Arrhythmias and Mortality After Left Ventricular Assist Devices Implantation: A Meta-Analysis

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Nader Makki ◽  
Olurotimi Mesubi ◽  
Curtis Steyers ◽  
Brian Olshansky
Keyword(s):  
Ventricular Arrhythmias ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Left Ventricular Assist Devices ◽  
Ventricular Assist ◽  
Increased Risk ◽  
Left Ventricular Assist ◽  
All Cause Mortality

Background: Ventricular arrhythmias (VAs) are among the most commonly reported adverse effects associated with left ventricular assist devices (LVADs). However, prevalence of VAs post-LVAD implantation, and their relation to all-cause mortality, remains to be elucidated. We conducted a meta-analysis and systematic review of observational studies with the primary objective of evaluating the risk of VAs after LVAD implantation and the risk of all-cause mortality in patients with LVADs who had VAs. Methods: We searched Medline, Embase and Cochrane Central from 2001 to 2014. Two reviewers independently searched,selected and assessed quality of included studies with differences resolved by consensus. Data were collected and analyzed using random and fixed-effect model, as appropriate, with inverse variance weighting. Results: Of 2,393 studies identified, 15 observational studies were eligible including 1,517 patients with a mean follow up of 201 days. An LVAD was associated with an increased risk of VA after implantation (OR = 2.21, 95% confidence interval [CI] 1.37-3.59, p<0.001).There was an increased risk of all-cause mortality in LVAD patients who had post-LVAD VA (OR = 1.91, 95% CI 1.18-3.11, p<0.001). Using meta-regression and sensitivity analyses to account for risk factors such as etiology of cardiomyopathy, duration of follow-up, destination LVAD versus bridge therapy and presence of an implantable cardioverter defibrillator at time of LVAD implantation did not change the results of our main analysis. Conclusions: LVADs are associated with an increased risk of VA and presence of VAs post LVAD implantation is associated with increased risk of all-cause mortality.

scholarly journals Cardiovascular, thromboembolic and renal outcomes in IgA vasculitis (Henoch-Schönlein purpura): a retrospective cohort study using routinely collected primary care data

2018 ◽  
Vol 78 (2) ◽  
pp. 261-269 ◽  
Author(s):  
Alexander Tracy ◽  
Anuradhaa Subramanian ◽  
Nicola J Adderley ◽  
Paul Cockwell ◽  
Charles Ferro ◽  
...  
Keyword(s):  
Primary Care ◽  
Chronic Kidney Disease ◽  
Cohort Study ◽  
Venous Thromboembolism ◽  
Kidney Disease ◽  
Iga Vasculitis ◽  
Adult Onset ◽  
Childhood Onset ◽  
Increased Risk ◽  
Schonlein Purpura

BackgroundIgA vasculitis (IgAV, Henoch-Schönlein purpura) is a small-vessel vasculitis most common in children but also occurring in adults. Case series have suggested that IgAV may be associated with cardiovascular disease and venous thromboembolism, but this has not been evaluated in population-based studies. Renal disease and hypertension are possible complications of the disease with unknown incidence.MethodsUsing a large UK primary care database, we conducted an open retrospective matched cohort study of cardiovascular, venous thrombotic and renal outcomes in adult-onset and childhood-onset IgAV. Control participants were selected at a 2:1 ratio, matched for age and sex. Adjusted HRs (aHRs) were calculated using Cox proportional hazards models.Results2828 patients with adult-onset IgAV and 10 405 patients with childhood-onset IgAV were compared with age-matched and sex-matched controls. There was significantly increased risk of hypertension (adult-onset aHR 1.42, 95% CI 1.19 to 1.70, p < 0.001; childhood-onset aHR 1.52, 95% CI 1.22 to 1.89, p < 0.001) and stage G3–G5 chronic kidney disease (adult-onset aHR 1.54, 95% CI 1.23 to 1.93, p < 0.001; childhood-onset aHR 1.89, 95% CI 1.16 to 3.07, p=0.010). There was no evidence of association with ischaemic heart disease, cerebrovascular disease or venous thromboembolism. All-cause mortality was increased in the adult-onset IgAV cohort compared with controls (aHR 1.27, 95% CI 1.07 to 1.50, p=0.006).ConclusionsPatients with IgAV are at increased risk of hypertension and chronic kidney disease (CKD) compared with individuals without IgAV; analysis restricted to adult-onset IgAV patients showed increased mortality. Appropriate surveillance and risk factor modification could improve long-term outcomes in these patients.

Awake and aware with ongoing ventricular fibrillation during LVAD treatment: is it possible?

2020 ◽  
Vol 13 (4) ◽  
pp. e234527
Author(s):  
Ingrid Hell Mott ◽  
Steen Hvitfeldt Poulsen ◽  
Brian Bridal Løgstrup
Keyword(s):  
Ventricular Fibrillation ◽  
Ventricular Arrhythmias ◽  
Left Ventricular ◽  
Ventricular Assist Devices ◽  
Left Ventricular Assist Devices ◽  
Randomised Trials ◽  
Ventricular Assist ◽  
Increased Risk ◽  
Left Ventricular Assist ◽  
Shed Light

Left ventricular assist devices (LVADs) are currently used as destination therapy or bridge to heart transplantation in patients with advanced chronic heart failure (CHF). It has been proved to reduce mortality and symptoms in these patients. Patients with advanced CHF are known to have increased risk of ventricular arrhythmias (ventricular tachycardia or ventricular fibrillation (VF)) despite the presence of LVAD. We report the case of patients with ongoing VF during LVAD treatment while being awake and aware. We discuss the challenges introduced along with the increasing use of LVAD treatment. The decision whether a patient with LVAD automatically should have an implantable cardioverter-defibrillator is challenging. Randomised trials are warranted to shed light on these challenging decisions.

scholarly journals RyR2 QQ2958 Genotype and Risk of Malignant Ventricular Arrhythmias

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Francesca Galati ◽  
Antonio Galati ◽  
Serafina Massari
Keyword(s):  
Ryanodine Receptor ◽  
Calcium Binding ◽  
Ventricular Arrhythmias ◽  
Receptor Gene ◽  
Developed Countries ◽  
Clinical Variable ◽  
Increased Risk ◽  
Common Causes ◽  
Life Threatening

Ventricular arrhythmias are one of the most common causes of death in developed countries. The use of implantable cardiac defibrillators is the most effective treatment to prevent sudden cardiac death. To date, the ejection fraction is the only approved clinical variable used to determine suitability for defibrillator placement in subjects with heart failure. The purpose of this study was to assess whether genetic polymorphisms found in the ryanodine receptor type 2 (Q2958R) and histidine-rich calcium-binding protein (S96A) might serve as markers for arrhythmias. Genotyping was performed in 235 patients treated with defibrillator for primary and secondary prevention of arrhythmias. No significant association was found between the S96A polymorphism and arrhythmia onset, whereas the QQ2958 genotype in the ryanodine receptor gene was correlated with an increased risk of life-threatening arrhythmias. Concurrent stressor conditions, such as hypertension, seem to increase this effect. Our findings might help to better identify patients who could benefit from defibrillator implantation.

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