scholarly journals Friedreich’s ataxia-associated childhood hypertrophic cardiomyopathy: a national cohort study

2021 ◽  
pp. archdischild-2021-322455
Author(s):  
Gabrielle Norrish ◽  
Thomas Rance ◽  
Elena Montanes ◽  
Ella Field ◽  
Elspeth Brown ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cohort Study ◽  
Hypertrophic Cardiomyopathy ◽  
Cardiac Death ◽  
Friedreich’S Ataxia ◽  
Left Ventricular ◽  
Friedreich's Ataxia ◽  
Atrial Arrhythmia ◽  
Primary Study

ObjectiveHypertrophic cardiomyopathy (HCM) is an important predictor of long-term outcomes in Friedreich’s ataxia (FA), but the clinical spectrum and survival in childhood is poorly described. This study aimed to describe the clinical characteristics of children with FA-HCM.Design and settingRetrospective, longitudinal cohort study of children with FA-HCM from the UK.Patients78 children (<18 years) with FA-HCM diagnosed over four decades.InterventionAnonymised retrospective demographic and clinical data were collected from baseline evaluation and follow-up.Main outcome measuresThe primary study end-point was all-cause mortality (sudden cardiac death, atrial arrhythmia-related death, heart failure-related death, non-cardiac death) or cardiac transplantation.ResultsThe mean age at diagnosis of FA-HCM was 10.9 (±3.1) years. Diagnosis was within 1 year of cardiac referral in 34 (65.0%) patients, but preceded the diagnosis of FA in 4 (5.3%). At baseline, 65 (90.3%) had concentric left ventricular hypertrophy and 6 (12.5%) had systolic impairment. Over a median follow-up of 5.1 years (IQR 2.4–7.3), 8 (10.5%) had documented supraventricular arrhythmias and 8 (10.5%) died (atrial arrhythmia-related n=2; heart failure-related n=1; non-cardiac n=2; or unknown cause n=3), but there were no sudden cardiac deaths. Freedom from death or transplantation at 10 years was 80.8% (95% CI 62.5 to 90.8).ConclusionsThis is the largest cohort of childhood FA-HCM reported to date and describes a high prevalence of atrial arrhythmias and impaired systolic function in childhood, suggesting early progression to end-stage disease. Overall mortality is similar to that reported in non-syndromic childhood HCM, but no patients died suddenly.

Abstract 13812: Pulmonary Function Predicts Cardiac Function, Structure & Clinical Outcome in Chronic Heart Failure: Results From the Myovasc Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Marc W Heidorn ◽  
Felix Müller ◽  
Stefanie Steck ◽  
Alexander Schuch ◽  
Sven O Tröbs ◽  
...  
Keyword(s):  
Heart Failure ◽  
Clinical Outcome ◽  
Pulmonary Function ◽  
Cardiac Death ◽  
Independent Predictor ◽  
Left Ventricular ◽  
Study Endpoint ◽  
Primary Study ◽  
Increased Risk

Introduction: A growing body of evidence suggests a relevance of pulmonary function in the pathophysiology of heart failure (HF). Comprehensive data on the role of forced expiratory volume in 1 second (FEV1) in the development & progression of HF is limited. Hypothesis: Given this background, we hypothesized, that (FEV1) is associated with deteriorated left ventricular (LV) functional as well as structural status, & predicts specific clinical outcome in HF. Methods: Data from the MyoVasc Study (n=3,289) were analysed. Comprehensive clinical phenotyping including body plethysmography for the evaluation of FEV1 & standardized echocardiography were performed during a five-hour investigation in a dedicated study center. Worsening of HF (comprising transition from asymptomatic to symptomatic HF, HF hospitalization, & cardiac death) was assessed during a structured follow-up with subsequent validation & adjudication of endpoints. Results: Information on FEV1 was available in 2,998 individuals (age 35-84 years; 34.1% female, mean FEV1 92.4[% predicted]). In multivariable regression analysis adjusted for age, sex, height, cardiovascular risk factors (CVRF) & clinical profile, FEV1 per-1SD was an independent predictor of reduced LV ejection fraction (β:-1.6[95%CI -2.0;-1.3]), elevated E/E’-ratio (β:0.82[0.64;0.99]), & increased LV mass/Height 2.7 (β:1.6[1.1;2.1]) (for all, P<0.001). During a median follow-up of 2.3 (interquartile range 1.1; 4.0) years, FEV1 per-1SD predicted worsening of HF (hazard ratio(HR) 1.46[1.30;1.65], P<0.001) independent of age, sex, height, CVRF & comorbidities. This finding was consistent among the single components of the primary study endpoint: FEV1 per-1SD predicted an increased risk for transition to symptomatic HF (HR 1.57[1.19;2.06]), HF hospitalization (HR 1.35[1.16;1.57]) & for cardiac death (HR 1.84[1.49;2.26]) (for all, P<0.001). FEV1 per-1SD remained an independent predictor of worsening of HF after additional adjustment for NT-proBNP (HR 1.25[1.08;1.45], P=0.002). Conclusion: Impaired FEV1 is directly linked to the pathophysiology of HF & represents a strong & independent predictor of HF outcome highlighting its potential value to advance risk prediction in HF.

scholarly journals POSTERS (2)96CONTINUOUS VERSUS INTERMITTENT MONITORING FOR DETECTION OF SUBCLINICAL ATRIAL FIBRILLATION IN HIGH-RISK PATIENTS97HIGH DAY-TO-DAY INTRA-INDIVIDUAL REPRODUCIBILITY OF THE HEART RATE RESPONSE TO EXERCISE IN THE UK BIOBANK DATA98USE OF NOVEL GLOBAL ULTRASOUND IMAGING AND CONTINUEOUS DIPOLE DENSITY MAPPING TO GUIDE ABLATION IN MACRO-REENTRANT TACHYCARDIAS99ANTICOAGULATION AND THE RISK OF COMPLICATIONS IN PATIENTS UNDERGOING VT AND PVC ABLATION100NON-SUSTAINED VENTRICULAR TACHYCARDIA FREQUENTLY PRECEDES CARDIAC ARREST IN PATIENTS WITH BRUGADA SYNDROME101USING HIGH PRECISION HAEMODYNAMIC MEASUREMENTS TO ASSESS DIFFERENCES IN AV OPTIMUM BETWEEN DIFFERENT LEFT VENTRICULAR LEAD POSITIONS IN BIVENTRICULAR PACING102CAN WE PREDICT MEDIUM TERM MORTALITY FROM TRANSVENOUS LEAD EXTRACTION PRE-OPERATIVELY?103PREVENTION OF UNECESSARY ADMISSIONS IN ATRIAL FIBRILLATION104EPICARDIAL CATHETER ABLATION FOR VENTRICULAR TACHYCARDIA ON UNINTERRUPTED WARFARIN: A SAFE APPROACH?105HOW WELL DOES THE NATIONAL INSTITUTE OF CLINICAL EXCELLENCE (NICE) GUIDENCE ON TRANSIENT LOSS OF CONSCIOUSNESS (T-LoC) WORK IN A REAL WORLD? AN AUDIT OF THE SECOND STAGE SPECIALIST CARDIOVASCULAT ASSESSMENT AND DIAGNOSIS106DETECTION OF ATRIAL FIBRILLATION IN COMMUNITY LOCATIONS USING NOVEL TECHNOLOGY'S AS A METHOD OF STROKE PREVENTION IN THE OVER 65'S ASYMPTOMATIC POPULATION - SHOULD IT BECOME STANDARD PRACTISE?107HIGH-DOSE ISOPRENALINE INFUSION AS A METHOD OF INDUCTION OF ATRIAL FIBRILLATION: A MULTI-CENTRE, PLACEBO CONTROLLED CLINICAL TRIAL IN PATIENTS WITH VARYING ARRHYTHMIC RISK108PACEMAKER COMPLICATIONS IN A DISTRICT GENERAL HOSPITAL109CARDIAC RESYNCHRONISATION THERAPY: A TRADE-OFF BETWEEN LEFT VENTRICULAR VOLTAGE OUTPUT AND EJECTION FRACTION?110RAPID DETERIORATION IN LEFT VENTRICULAR FUNCTION AND ACUTE HEART FAILURE AFTER DUAL CHAMBER PACEMAKER INSERTION WITH RESOLUTION FOLLOWING BIVENTRICULAR PACING111LOCALLY PERSONALISED ATRIAL ELECTROPHYSIOLOGY MODELS FROM PENTARAY CATHETER MEASUREMENTS112EVALUATION OF SUBCUTANEOUS ICD VERSUS TRANSVENOUS ICD- A PROPENSITY MATCHED COST-EFFICACY ANALYSIS OF COMPLICATIONS & OUTCOMES113LOCALISING DRIVERS USING ORGANISATIONAL INDEX IN CONTACT MAPPING OF HUMAN PERSISTENT ATRIAL FIBRILLATION114RISK FACTORS FOR SUDDEN CARDIAC DEATH IN PAEDIATRIC HYPERTROPHIC CARDIOMYOPATHY: A SYSTEMATIC REVIEW AND META-ANALYSIS115EFFECT OF CATHETER STABILITY AND CONTACT FORCE ON VISITAG DENSITY DURING PULMONARY VEIN ISOLATION116HEPATIC CAPSULE ENHANCEMENT IS COMMONLY SEEN DURING MR-GUIDED ABLATION OF ATRIAL FLUTTER: A MECHANISTIC INSIGHT INTO PROCEDURAL PAIN117DOES HIGHER CONTACT FORCE IMPAIR LESION FORMATION AT THE CAVOTRICUSPID ISTHMUS? INSIGHTS FROM MR-GUIDED ABLATION OF ATRIAL FLUTTER118CLINICAL CHARACTERISATION OF A MALIGNANT SCN5A MUTATION IN CHILDHOOD119RADIOFREQUENCY ASSOCIATED VENTRICULAR FIBRILLATION120CONTRACTILE RESERVE EXPRESSED AS SYSTOLIC VELOCITY DOES NOT PREDICT RESPONSE TO CRT121DAY-CASE DEVICES - A RETROSPECTIVE STUDY USING PATIENT CODING DATA122PATIENTS UNDERGOING SVT ABLATION HAVE A HIGH INCIDENCE OF SECONDARY ARRHYTHMIA ON FOLLOW UP: IMPLICATIONS FOR PRE-PROCEDURE COUNSELLING123PROGNOSTIC ROLE OF HAEMOGLOBINN AND RED BLOOD CELL DITRIBUTION WIDTH IN PATIENTS WITH HEART FAILURE UNDERGOING CARDIAC RESYNCHRONIZATION THERAPY124REMOTE MONITORING AND FOLLOW UP DEVICES125A 20-YEAR, SINGLE-CENTRE EXPERIENCE OF IMPLANTABLE CARDIOVERTER DEFIBRILLATORS (ICD) IN CHILDREN: TIME TO CONSIDER THE SUBCUTANEOUS ICD?126EXPERIENCE OF MAGNETIC REASONANCE IMAGING (MEI) IN PATIENTS WITH MRI CONDITIONAL DEVICES127THE SINUS BRADYCARDIA SEEN IN ATHLETES IS NOT CAUSED BY ENHANCED VAGAL TONE BUT INSTEAD REFLECTS INTRINSIC CHANGES IN THE SINUS NODE REVEALED BY I (F) BLOCKADE128SUCCESSFUL DAY-CASE PACEMAKER IMPLANTATION - AN EIGHT YEAR SINGLE-CENTRE EXPERIENCE129LEFT VENTRICULAR INDEX MASS ASSOCIATED WITH ESC HYPERTROPHIC CARDIOMYOPATHY RISK SCORE IN PATIENTS WITH ICDs: A TERTIARY CENTRE HCM REGISTRY130A DGH EXPERIENCE OF DAY-CASE CARDIAC PACEMAKER IMPLANTATION131IS PRE-PROCEDURAL FASTING A NECESSITY FOR SAFE PACEMAKER IMPLANTATION?

EP Europace ◽  
2016 ◽  
Vol 18 (suppl 2) ◽  
pp. ii36-ii47
Author(s):  
T. Philippsen ◽  
M. Orini ◽  
C.A. Martin ◽  
E. Volkova ◽  
J.O.M. Ormerod ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Ventricular Tachycardia ◽  
Hypertrophic Cardiomyopathy ◽  
Pacemaker Implantation ◽  
Left Ventricular ◽  
Day Case ◽  
Single Centre ◽  
Subcutaneous Icd

Abstract 17263: Pre-Clinical Left Ventricular Myocardial Remodeling in Patients With Friedreich’s Ataxia: A Cardiac MRI Study

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Karen A Takazaki1 ◽  
Thiago Quinaglia A. C. Silva ◽  
Alberto Martinez ◽  
Tomas Neilan ◽  
Ravi SHAH ◽  
...  
Keyword(s):  
Heart Failure ◽  
Volume Fraction ◽  
Extracellular Volume ◽  
Extracellular Volume Fraction ◽  
Friedreich’S Ataxia ◽  
Left Ventricular ◽  
Friedreich's Ataxia ◽  
Intracellular Water ◽  
Lv Mass ◽  
Burn Out

Background: Heart Failure (HF) is the most common cause of death in Friedreich’s ataxia (FRDA), an inherited mitochondrial disease. Myocardial fibrosis is a well-documented histopathological feature among FRDA patients with HF. Objectives: In this study we will investigate the myocardial extracellular volume fraction (ECV) and intracellular water lifetime (τ ic ), using T1-weighted CMR imaging, in a cohort of patients with FRDA without signs of heart failure. We will also investigate whether myocardial tissue phenotyping by CMR can highlight particular characteristics of LV remodeling in FRDA’s cardiomyopathy, beyond those currently assessed with imaging-based classification of disease severity. Methods: Twenty-six FRDA’s patients (age 26.6±9.3 years, 15 women) without signs of HF, and 10 healthy controls (32.6±7.3 years, 5 women) underwent cardiac magnetic resonance (CMR) studies for assessment of left ventricular (LV) function, myocardial T1, late gadolinium enhancement (LGE), extracellular volume fraction (ECV), and intracellular water-lifetime (τ ic ) as marker of cardiomyocyte size. Neurological decline was determined using the FRDA rating scale (FARS 3). Results: FRDA patients had normal LV ejection fraction (LVEF: 67.66±11.4 vs. 63.9±9.0, P=0.311), larger LV mass index (LVMASSi: 61.03±22.1 vs. 45±4.2g/m 2 , P<0.001), and decreased LV end-diastolic volume index (LVEDVi 53.42±12 vs. 75.7±16.1, P=0.002), compared with controls. ECV and τ ic , were increased in FRDA patients (ECV: 0.36±0.05 vs. 0.25±0.02, P<0.0001; τ ic : 0.13±0.07 vs. 0.06±0.03, P=0.001). ECV was positively associated with LV mass-to-volume ratio (r=0.628, P<0.001). FARS 3 correlated positively with disease duration (r=0.669, P<0.001), and negatively with τ ic , (r=0.478, P=0.039). LVMASSi and cardiomyocyte mass-index [(1–ECV)LVMASSi] declined with age, indicating that LV hypertrophy may transition to a “burn-out” phase with LV atrophy. Conclusions: LV hypertrophy in FRDA reflects an expansion of the myocardial interstitium and an increase in cardiomyocyte size. In contrast, the neurological decline was more likely with decreasing cardiomyocyte size, possibly an early sign of myocardial “burn-out” in FRDA.

Abstract 19346: Peak Oxygen Consumption Predicts Outcome in Hypertrophic Cardiomyopathy

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Carla Contaldi ◽  
Raffaella Lombardi ◽  
Alessandra Giamundo ◽  
Sandro Betocchi
Keyword(s):  
Heart Failure ◽  
Oxygen Consumption ◽  
Hypertrophic Cardiomyopathy ◽  
Nyha Class ◽  
Left Ventricular ◽  
Exercise Intolerance ◽  
Peak Oxygen Consumption ◽  
Class Iii ◽  
Asymptomatic Patients

Introduction: Peak oxygen consumption (VO 2 ) has a strong and independent prognostic value in systolic heart failure; in contrast no data support its prognostic role in hypertrophic cardiomyopathy (HCM). Hypothesis: We assess if peak VO 2 is a long-term predictor of outcome in HCM. Methods: We studied 92 HCM patients (40±15 years). Peak VO 2 was expressed as percentage (%) of the predicted value. Follow up was 76±57 months. The primary composite endpoint (CE) was atrial fibrillation, progression to NYHA class III or IV, myotomy-myectomy (MM), heart transplantation (HT) and cardiac death. An ancillary endpoint (HFE) included markers of heart failure (progression to NYHA class III or IV, MM and HT). Results: At baseline, 62% of patients were asymptomatic, 35% NYHA class II and 3% NYHA class III; 26% had left ventricular outflow tract obstruction. During follow up, 30 patients met CE with 43 events. By multivariate Cox survival analysis, we analyzed 2 models, using the CE, and in turn HFE. For CE, maximal left atrial diameter (LAD) (HR: 1.12; 95% CI: 1.04 to 1.22), maximal wall thickness (MWT) (HR: 0.14; 95% CI: 1.04 to 1.23) and % predicted peak VO 2 (HR: -0.03; 95% CI: 0.95 to 0.99) independently predicted outcome (overall, p<0.0001). For HFE, maximal LAD (HR:0.31; 95% CI: 1.09 to 1.70), MWT (HR: 0.35; 95% CI: 1.08 to 1.84) and % predicted peak VO 2 (HR: -0.06; 95% CI: 0.89 to 0.98) independently predicted outcome (overall, p<0.0001). Only 19% of mildly symptomatic or asymptomatic patients with % predicted peak VO 2 >80% had events, as opposed to 53% of them with % predicted peak VO 2 < 55% (p= 0.04). Event-free survival for both endpoints was significantly lower in patients with % predicted peak VO 2 < 55% as compared to those with it between 55 and 80 and >80% , Figure. Conclusion: In mildly or asymptomatic patients severe exercise intolerance may precede clinical deterioration. In HCM, peak VO 2 provides excellent risk stratification with a high event rate in patients with % predicted value <55%.

Abstract 13943: Hypertrophic Cardiomyopathy with Left Ventricular Apical Aneurysm Represents a High-Risk Subgroup Necessitating Aggressive Preventive Therapy: A Long-term Follow-Up Study

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Ethan J Rowin ◽  
Barry J Maron ◽  
Tammy S Haas ◽  
John R Lesser ◽  
Mark S Link ◽  
...  
Keyword(s):  
Heart Failure ◽  
Hypertrophic Cardiomyopathy ◽  
High Risk ◽  
Sudden Death ◽  
Left Ventricular ◽  
Increased Risk ◽  
Long Term Follow Up ◽  
Apical Aneurysm

Background: Increasing penetration of high spatial resolution cardiovascular magnetic resonance (CMR) imaging into routine cardiovascular practice has resulted in more frequent identification of a subset of hypertrophic cardiomyopathy (HCM) patients with thin-walled, scarred left ventricular (LV) apical aneurysms. Prior experience involved relatively small numbers of patients with short follow-up and therefore the risk associated with this subgroup remains incompletely defined. Therefore, we assembled a large HCM cohort with LV apical aneurysms and long-term follow-up in order to clarify clinical course and prognosis. Methods and Results: Of 2,400 HCM patients, 60 (2.5%) were identified by CMR with LV apical aneurysm, 24 to 86 years of age, including 19 (32%) <45 years old; 70% male, and followed for 5.6 ± 3.5 years. Over the follow-up period, 24 patients experienced 31 adverse disease-related complications including: appropriate implantable cardioverter-defibrillator discharge for VT/VF (n=11), received or listed for heart transplant (n=6), heart failure death (n=5), nonfatal thromboembolic events (n=4), resuscitated out-of-hospital cardiac arrest (n=3), and sudden death (n=2). In addition, an intracavitary thrombus was identified in the apical aneurysm in 9 patients without a thromboembolic history. Combined HCM-related death and aborted life threatening event rate was 8.6% per year, nearly 6-fold greater than the 1.5% annual mortality rate reported in the general HCM population. Conclusions: Patients with LV apical aneurysms represent a high-risk subgroup within the diverse HCM spectrum, associated with substantial increased risk for disease-related morbidity and mortality, including advanced heart failure, thromboembolic stroke and sudden death. Identification of this unique HCM phenotype should prompt consideration for primary prevention ICD, and anticoagulation for stroke prophylaxis.

scholarly journals Head-to-head comparison of NT-proBNP and soluble ST2 for long-term prognosis of patients with hypertrophic cardiomyopathy

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
G Cediel Calderon ◽  
H Resta ◽  
P Codina ◽  
E Santiago-Vacas ◽  
M Domingo ◽  
...  
Keyword(s):  
Heart Failure ◽  
Hypertrophic Cardiomyopathy ◽  
Primary Endpoint ◽  
Left Ventricular ◽  
Functional Class ◽  
Left Ventricular Ejection ◽  
Nyha Functional Class ◽  
C Statistic

Abstract Background N-terminal pro-brain natriuretic peptide (NT-proBNP) predicts mortality and the development of heart failure (HF) in hypertrophic cardiomyopathy (HCM), however, evidence regarding soluble interleukin-1 receptor-like 1 (ST2) in this population is lacking. Purpose To assess the ST2 and NT-proBNP significance for risk stratification of patients with HCM during long-term follow-up. Methods We prospectively enrolled a cohort of consecutive patients with HCM admitted to an ambulatory HF Unit in a Tertiary University Hospital. All patients had clinical and echocardiographic evaluation and measurement of NT-proBNP and ST2 at inclusion. The primary endpoint was the composite of all-cause death or HF-related hospitalization. Results 103 patients were enrolled, 68% (n=70) males with a median (IQR) age of 60 (50–71) years. The median (IQR) of ST2 was 31.5 (IQR: 24.5 – 40.7) pg/mL. During a median follow-up of 2.5 years, 17 patients had the primary endpoint. Both, NT-proBNP and ST2 (both log-transformed) were associated with the primary endpoint in the univariable analyses (p&lt;0.01). However, after adjustment by age, sex, NYHA functional class and left ventricular ejection fraction (LVEF), this association remained statistically significant only for ST2 (HR: 4.62, 95% CI 1.80–11.87, p=0.001 vs HR: 1.57, 95% CI 0.97–2.54, p=0.068 for NT-proBNP). The addition of ST2 to a clinical model (age, sex, NYHA functional class and LVEF) increased the Harrel's C statistic from 0.70 to 0.76, while the addition of NT-proBNP increase this C-statistic only to 0.73. Conclusions ST2 appears to be a valuable biomarker for the prediction of death and heart failure related hospitalization in patients with HCM, outperforming the prognostic value of NT-proBNP. Future research should delve into this association. FUNDunding Acknowledgement Type of funding sources: None.

P1243Comparison of long-term clinical course and outcome of MYBPC3 - versus MYH7 - related hypertrophic cardiomyopathy

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
C Fumagalli ◽  
E Fedele ◽  
M Beltrami ◽  
N Maurizi ◽  
S Passantino ◽  
...  
Keyword(s):  
Heart Failure ◽  
Hypertrophic Cardiomyopathy ◽  
Diastolic Dysfunction ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Septal Myectomy ◽  
Lv Dysfunction ◽  
Instrumental Records

Abstract Introduction The presence of sarcomere mutations is a powerful predictor of heart failure-related outcomes in Hypertrophic Cardiomyopathy (HCM). However, whether the prevalence of left ventricular (LV) dysfunction differs in patients with mutations in the two most prevalent HCM-associated genes (i.e. MYBPC3 and MYH7) is unclear. Purpose To ascertain lifetime trends in prevalence of LV dysfunction in HCM associated with pathogenic or likely-pathogenic MYBPC3 versus MYH7 mutations. Methods Clinical and instrumental records of 402 HCM patients with MYBPC3 (N=251) or MYH7 (N=151) mutations were retrospectively reviewed. Presence of systolic dysfunction (ejection fraction [EF] <50%) and diastolic dysfunction (Grade II and III) were assessed for each patient. In vitro analysis of septal myectomy samples was performed to further compare electro-mechanic properties of MYBC3 and MYH7 patients. Results Patients were diagnosed at a mean age of 39±17 years and 63% were men. At first evaluation MYBPC3-HCM patients were less frequently obstructive (15% vs 26% in MYH7; p=0.005) and had lower LVEF (61±11% vs 64±9%; p=0.01). Prevalence of diastolic dysfunction increased with age and was lowest in MYBPC3 patients <40 years at diagnosis (19.5% vs 35.4% in MYH7, p=0.043). At a mean follow-up (FU) of 13±11 years, patients developed comparable left atrium enlargement (MYBPC3 52±29 ml/m2 vs 41±18 at baseline, p<0.001; MYH7 54±25ml/m2 vs 45±22, p=0.003). Prevalence of diastolic dysfunction was also similar. MYBPC3 patients had lower LVEF at final evaluation (61±11% vs 64±9% in MYH7, p=0.01) with greater prevalence of overt systolic dysfunction (EF<50%, MYBPC3 vs MYH7: 15% vs 5%, OR: 2.3 95% CI: 1.2–5.8, p=0.013). No significant differences were observed in terms of NYHA class change, atrial fibrillation, stroke, heart failure, appropriate ICD intervention or cardiovascular death. However, prevalence of NSVT was higher for MYBPC3 (39% vs 14% in MYH7, p<0.0001). At Cox multivariable analysis independent predictors of systolic dysfunction at follow-up were MYBPC3 positive status (HR 2.53 95% CI: 1.09–5.82, p=0.029) and age at initial evaluation (HR 1.03 95% CI 1.00–1.06, p=0.027). In vitro cross-sectional evaluation of myocardial samples taken during septal myectomy at different ages showed a decline in contraction-relaxation properties after age 40 in MYPBC3 carriers, but preserved function in MYH7 patients (Figure). Kinetic of myosin cross-bridges Conclusions In HCM patients, mutations in the MYBPC3 gene and early diagnosis are associated with slowly progressing systolic impairment leading to overt dysfunction in 15% compared to 5% in MYH7-HCM. However, outcome was similar in the two subsets. These differences in lifetime myocardial performance between the two most common HCM-associated genes suggest diverse pathways of disease progression, potentially amenable to requiring different molecular approaches.

Abstract 2954: Short-term Effects of High Dose Idebenone on Left Ventricular Mass and Function in a Pediatric Cohort with Friedreich’s Ataxia

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Jonathan F Plehn ◽  
Keren Hasbani ◽  
Ken Horton ◽  
Inez Ernst ◽  
Andrew E Arai ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Left Ventricular Mass ◽  
Friedreich’S Ataxia ◽  
Left Ventricular ◽  
Friedreich's Ataxia ◽  
High Dose ◽  
Short Term ◽  
Short Term Treatment ◽  
Tissue Velocity ◽  
Ventricular Mass

Background: Early mortality in Friedreich’s Ataxia (FA) is believed to commonly result from an underlying hypertrophic cardiomyopathy which may be caused by increases in reactive oxygen species. Antioxidant therapy could result in slowing of disease progression or regression of left ventricular mass (LVM). Methods: We tested the hypothesis that high dose idebenone could lead to regression of LVM and LV functional improvement in 48 pediatric subjects with genetically-confirmed FA (23 females, 25 males, mean age=13.4 years) randomly assigned to weight-stratified low (4 – 8 mg/kg), medium (10–20 mg/kg) or high (30–50 mg/kg) doses of idebenone or placebo. Cardiac magnetic resonance imaging (MRI) and echocardiographic (echo) two-dimensional and Doppler analysis blinded to treatment assignment were performed at baseline and after 6 months of therapy. Results: At baseline, increased LVM indexed by height 2.7 was observed in 44%, LV concentric remodeling (relative wall thickness >0.39) in 83% and impaired early relaxation by Doppler tissue velocity (E’) in 88% of subjects as determined by age-adjusted, normative echo data. MRI-determined LVM (n=45 subjects) was inversely related to measures of LV relaxation including E’ (p<0.0001), color Doppler flow propagation (p<0.007) and isovolumic relaxation time (p<0.005) but not mitral deceleration time. LVM also correlated with peak lateral systolic tissue velocity (p=0.002) but not LV ejection fraction. At 6 months combined, idebenone-assigned subjects demonstrated a 1.3 ± 1.6 % reduction of LVM vs. baseline which compared to an 8.9 ± 4.0% LVM increase in placebo subjects (p=.007). By Fisher’s test, LVM regression was observed only in the high and intermediate dose groups (p≤0.05 and p≤0.01) with a trend toward regression in the low dose group (p=0.056). No effects on diastolic relaxation or systolic functional parameters were observed after 6 months of idebenone treatment. Conclusions: Hypertrophic cardiomyopathy and associated diastolic functional impairment is highly prevalent in pediatric FA patients with moderate neurologic impairment. Short term treatment with high dose idebenone appears to result primarily in blunting of LV mass progression but not to detectable improvements in LV function.

Residual inflammation is a major determinant of myocardial recovery and cardiovascular outcome in takotsubo patients

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
L Lachmet-Thebaud ◽  
B Marchandot ◽  
K Matsushita ◽  
C Sato ◽  
C Dagrenat ◽  
...  
Keyword(s):  
Heart Failure ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Cardiovascular Outcome ◽  
Left Ventricular Ejection ◽  
Funding Source ◽  
Ventricular Ejection Fraction ◽  
Cox Regression Analysis ◽  
The Impact

Abstract Background Recent insights have emphasized the importance of myocardial and systemic inflammation in Takotsubo Syndrome (TTS). Objective In a large registry of unselected patients, we sought to evaluate whether residual high inflammatory response (RHIR) could impact cardiovascular outcome after TTS. Methods Patients with TTS were retrospectively included between 2008 and 2018 in three general hospitals. 385 patients with TTS were split into three subgroups, according to tertiles of C-reactive protein (CRP) levels at discharge (CRP&lt;5.2 mg/l, CRP range 5.2 to 19 mg/l, and CRP&gt;19 mg/L). The primary endpoint was the impact of RHIR, defined as CRP&gt;19 mg/L at discharge, on cardiac death or hospitalization for heart failure. Results Follow-up was obtained in 382 patients (99%) after a median of 747 days. RHIR patients were more likely to have a history of cancer or a physical trigger. Left ventricular ejection fraction (LVEF) at admission and at discharge were comparable between groups. By contrast, RHIR was associated with lower LVEF at follow-up (61.7 vs. 60.7 vs. 57.9%; p=0.004) and increased cardiac late mortality (0% vs. 0% vs. 10%; p=0.001). By multivariate Cox regression analysis, RHIR was an independent predictor of cardiac death or hospitalization for heart failure (hazard ratio: 1.97; 95% confidence interval: 1.11 to 3.49; p=0.02). Conclusions RHIR was associated with impaired LVEF recovery and was evidenced as an independent factor of cardiovascular events. All together these findings underline RHIR patients as a high-risk subgroup, to target in future clinical trials with specific therapies to attenuate RHIR. Main results Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): GERCA (Groupe pour l'Enseignement, la prévention et la Recherche Cardiovasculaire en Alsace)

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