P1247FLNC pathogenic variants in patients with various cardiomyopathies:prevalence and genotype-phenotype correlations

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F Ader ◽  
P De Groote ◽  
P Reant ◽  
D Dupin-Deguine ◽  
C Rambaud ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Pathogenic Variant ◽  
Pathogenic Variants ◽  
History Of ◽  
Custom Panel ◽  
Few Data ◽  
First Time

Abstract Background/Introduction Pathogenic variants FLNC encoding filamin C have been firstly reported to cause myopathies, and were recently linked to isolated cardiac phenotypes.However, few data on phenotype-genotype correlation are available. Purpose Our aim was to estimate the prevalence of FLNC pathogenic variants in cardiomyopathies and to study the relations between phenotype and genotype. Methods DNAs from a cohort of 1150 unrelated index-patients with an isolated cardiomyopathy (700 hypertrophic, 300 dilated, 50 restrictive cardiomyopathies, and 100 left ventricle non-compactions) have been sequenced on a custom panel of 52 cardiomyopathy disease-causing genes. Results A FLNC pathogenic variant was identified in 28 patients corresponding to a prevalence ranging from 1 to 8% depending on the cardiomyopathy subtypes. Truncating variants were always identified in patients with dilated cardiomyopathy, while missense or in-frame variants were found in other phenotypes. This work reported for the first time a left ventricular non-compaction associated with FLNC pathogenic variant. In the cohort, nine patients (32%) were implanted with an automatic defibrillator. In 7 families (25%), history of sudden cardiac death (SCD) before 50 years was reported. A personal or family history of sudden cardiac death (SCD) was significantly higher in patients with truncating variants than in patients carrying missense variants (p=0.01). Four patients died of cardiac cause including 3 from SCD and 1 from heart failure. Conclusion This work highlights the role of FLNC in cardiomyopathies. A correlation between the type of the variant and the cardiomyopathy subtype was observed as well as with SCD risk. These new data should be taken into consideration for patient's management and primary prevention of sudden cardiac death. Acknowledgement/Funding La ligue contre la Cardiomyopathie

Supplementary role of left ventricular global longitudinal strain for predicting sudden cardiac death in hypertrophic cardiomyopathy

2021 ◽  
Author(s):  
Hyun-Jung Lee ◽  
Hyung-Kwan Kim ◽  
Sang Chol Lee ◽  
Jihoon Kim ◽  
Jun-Bean Park ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Sudden Cardiac Death ◽  
Risk Score ◽  
Primary Endpoint ◽  
Cardiac Death ◽  
Longitudinal Strain ◽  
Global Longitudinal Strain ◽  
Left Ventricular ◽  
C Statistic

Abstract Aims We investigated the prognostic role of left ventricular global longitudinal strain (LV-GLS) and its incremental value to established risk models for predicting sudden cardiac death (SCD) in patients with hypertrophic cardiomyopathy (HCM). Methods and results LV-GLS was measured with vendor-independent software at a core laboratory in a cohort of 835 patients with HCM (aged 56.3 ± 12.2 years) followed-up for a median of 6.4 years. The primary endpoint was SCD events, including appropriate defibrillator therapy, within 5 years after the initial evaluation. The secondary endpoint was a composite of SCD events, heart failure admission, heart transplantation, and all-cause mortality. Twenty (2.4%) and 85 (10.2%) patients experienced the primary and secondary endpoints, respectively. Lower absolute LV-GLS quartiles, especially those worse than the median (−15.0%), were associated with progressively higher SCD event rates (P = 0.004). LV-GLS was associated with an increased risk for the primary endpoint, independent of the LV ejection fraction, apical aneurysm, and 2014 European Society of Cardiology (ESC) risk score [adjusted hazard ratio (aHR) 1.14, 95% confidence interval (CI) 1.02–1.28] or 2011 American College of Cardiology/American Heart Association (ACC/AHA) risk factors (aHR 1.18, 95% CI 1.05–1.32). LV-GLS was also associated with a higher risk for the composite secondary endpoint (aHR 1.06, 95% CI 1.01–1.12). The addition of LV-GLS enhanced the performance of the ESC risk score (C-statistic 0.756 vs. 0.842, P = 0.007) and the 2011 ACC/AHA risk factor strategy (C-statistic 0.743 vs. 0.814, P = 0.007) for predicting SCD. Conclusion LV-GLS is an important prognosticator in patients with HCM and provides additional information to established risk stratification strategies for predicting SCD.

Congenital absence of pericardium: a nomad heart

2014 ◽  
Vol 25 (7) ◽  
pp. 1415-1417
Author(s):  
Liliana Marta ◽  
António M. Ferreira ◽  
Katya R. Santos
Keyword(s):  
Family History ◽  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Congenital Absence ◽  
Medical Attention ◽  
Cardiac Malformation ◽  
Cardiac Defect ◽  
History Of

AbstractCongenital pericardial absence is a rare cardiac defect. Although most patients are asymptomatic, recognising this condition is clinically important as it can cause serious complications. We report the case of an asymptomatic 33-year-old woman seeking medical attention due to a family history of sudden cardiac death. The investigation led us to the diagnosis of congenital absence of the pericardium. The role of imaging in the diagnosis of this rare cardiac malformation is briefly discussed.

scholarly journals Dissociation of hemodynamic and electrocardiographic indexes of myocardial ischemia in pigs with hibernating myocardium and sudden cardiac death

2013 ◽  
Vol 304 (12) ◽  
pp. H1697-H1707 ◽  
Author(s):  
Matthew F. Pizzuto ◽  
Gen Suzuki ◽  
Michael D. Banas ◽  
Brendan Heavey ◽  
James A. Fallavollita ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Diastolic Pressure ◽  
Left Ventricular ◽  
Hibernating Myocardium ◽  
Sympathetic Activation ◽  
Premature Ventricular Contractions ◽  
Severe Coronary Artery ◽  
Artery Disease

Many survivors of sudden cardiac death (SCD) have normal global ventricular function and severe coronary artery disease but no evidence of symptomatic ischemia or infarction before the development of lethal ventricular arrhythmias, and the trigger for ventricular tachycardia (VT)/ventricular fibrillation (VF) remains unclear. We sought to identify the role of spontaneous ischemia and temporal hemodynamic factors preceding SCD using continuous telemetry of left ventricular (LV) pressure and the ECG for periods up to 5 mo in swine ( n = 37) with hibernating myocardium who experience spontaneous VT/VF in the absence of heart failure or infarction. Hemodynamics and ST deviation at the time of VT/VF were compared with survivors with hibernating myocardium as well as sham controls. All episodes of VT/VF occurred during sympathetic activation and were initiated by single premature ventricular contractions, and the VT degenerated into VF in ∼ 30 s. ECG evidence of ischemia was infrequent and no different from those that survived. Baseline hemodynamics were no different among groups, but LV end-diastolic pressure during sympathetic activation was higher at the time of SCD (37 ± 4 vs. 26 ± 4 mmHg, P < 0.05) and the ECG demonstrated QT shortening (155 ± 4 vs. 173 ± 5 ms, P < 0.05). The week before SCD, both parameters were no different from survivors. These data indicate that there are no differences in the degree of sympathetic activation or hemodynamic stress when VT/VF develops in swine with hibernating myocardium. The transiently elevated LV end-diastolic pressure and QT shortening preceding VT/VF raises the possibility that electrocardiographically silent subendocardial ischemia and/or mechanoelectrical feedback serve as a trigger for the development of SCD in chronic ischemic heart disease.

scholarly journals 683 Cor in memoria posterorum: role of familial screening in sudden death syndrome

2021 ◽  
Vol 23 (Supplement_G) ◽  
Author(s):  
Chiara Chiti ◽  
Vanda Parisi ◽  
Maddalena Graziosi ◽  
Elena Biagini
Keyword(s):  
Sudden Cardiac Death ◽  
Left Ventricle ◽  
Cardiac Death ◽  
Structural Damage ◽  
Family Members ◽  
Anterior Wall ◽  
Left Ventricular ◽  
Arrhythmogenic Cardiomyopathy ◽  
Therapeutic Implications

Abstract A 14-year-old boy suddenly died during a school lesson. His familial history was negative for sudden cardiac death and no comorbidities were reported. As part of Emilia Romagna regional network for sudden cardiac death, the heart was examined at our Cardiovascular Pathology Unit. The molecular autopsy revealed extensive lymphocytic macrophage left ventricle myocarditis (infero-lateral and anterior wall) in various evolutive stages. Genetic testing with next-generation sequencing was performed on DNA isolated from explanted heart samples (178 candidate genes for channelopathies and cardiomyopathies were analysed) and it showed a frameshift pathological mutation in the filamine C gene (FLNC c.8034delC p. Cys2679fsTer6) which induces protein premature termination. In order to screen family members, we evaluated the father, 53-year-old, asymptomatic and with an unremarkable cardiology history. The ECG showed sinus rhythm, HR 60 b.p.m., normal atrioventricular conduction, QRS fragmentation and negative T waves in the inferior leads. The echocardiogram revealed left ventricle mild dilation (79 mL/m2) with global hypokinesia (EF 45%), while right ventricle was normal for size and kinetics. A cardiac MRI confirmed left ventricular dilation and hypokinesia with diffuse LGE with circumferential mesocardial distribution mainly in the middle-baseline site, which reflected structural damage (fibrosis). The 24-h Holter ECG did not record arrhythmias. The genetic test was then performed and the same FLNC frameshift mutation was identified. We thus suspected familial arrhythmogenic cardiomyopathy involving left ventricle with pathological filamine C mutation and an ICD was recommended. Other family members had no pathological findings. Filamine C mutations are associated with many type of cardiomyopathy. A possible association between some mutated variants and certain subtypes of cardiomyopathy has been highlighted. In particular, the frameshift variant is associated with an increased arrhythmic risk, particularly when dilated forms are considered. Recent studies have identified a correlation with arrhythmogenic cardiomyopathy, although the role of these mutated variants has not yet been fully defined. This clinical case underlines the importance of multidisciplinary approach in cases of sudden cardiac death, consisting of autopsy, genetic and clinical evaluation, in order to identify any forms of familial cardiomyopathy and activate a systematic screening in family members with important prognostic and therapeutic implications. Data about our regional structural network for sudden cardiac death will also be shown.

The role of implantable cardioverter-defibrillators and sudden cardiac death prevention: indications, device selection, and outcome

2019 ◽  
Vol 41 (21) ◽  
pp. 2003-2011 ◽  
Author(s):  
Ilan Goldenberg ◽  
David T Huang ◽  
Jens Cosedis Nielsen
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Current Knowledge ◽  
Left Ventricular ◽  
Cardiac Resynchronization ◽  
Implantable Cardioverter Defibrillators ◽  
Icd Implantation ◽  
Device Selection ◽  
Cardioverter Defibrillators

Abstract Multiple randomized multicentre clinical trials have established the role of the implantable cardioverter-defibrillator (ICD) as the mainstay in the treatment of ventricular tachyarrhythmias and sudden cardiac death (SCD) prevention. These trials have focused mainly on heart failure patients with advanced left ventricular dysfunction and were mostly conducted two decades ago, whereas a more recent trial has provided conflicting results. Therefore, much remains to be determined on how best to balance the identification of patients at high risk of SCD together with who would benefit most from ICD implantation in a contemporary setting. Implantable cardioverter-defibrillators have also evolved from the simple, defibrillation-only devices implanted surgically to more advanced technologies of multi-chamber devices, with physiologic bradycardic pacing, including cardiac resynchronization therapy, atrial and ventricular therapeutic pacing algorithms, and subcutaneous ICDs. These multiple options necessitate individualized approach to device selection and programming. This review will focus on the current knowledge on selection of patients for ICD treatment, device selection and programming, and future directions of implantable device therapy for SCD prevention.

scholarly journals The role of the electrocardiographic phenotype in risk stratification for sudden cardiac death in childhood hypertrophic cardiomyopathy

2021 ◽  
Author(s):  
Gabrielle Norrish ◽  
Cristian Topriceanu ◽  
Chen Qu ◽  
Ella Field ◽  
Helen Walsh ◽  
...  
Keyword(s):  
Hypertrophic Cardiomyopathy ◽  
Sudden Cardiac Death ◽  
Risk Stratification ◽  
Risk Score ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Predictive Values ◽  
Arrhythmic Event ◽  
Ecg Abnormalities

Abstract Aims The 12-lead electrocardiogram (ECG) is routinely performed in children with hypertrophic cardiomyopathy (HCM). An ECG risk score has been suggested as a useful tool for risk stratification, but this has not been independently validated. This aim of this study was to describe the ECG phenotype of childhood HCM in a large, international, multi-centre cohort and investigate its role in risk prediction for arrhythmic events. Methods and results Data from 356 childhood HCM patients with a mean age of 10.1 years (±4.5) were collected from a retrospective, multi-centre international cohort. Three hundred and forty-seven (97.5%) patients had ECG abnormalities at baseline, most commonly repolarization abnormalities (n = 277, 77.8%); left ventricular hypertrophy (n = 240, 67.7%); abnormal QRS axis (n = 126, 35.4%); or QT prolongation (n = 131, 36.8%). Over a median follow-up of 3.9 years (interquartile range 2.0–7.7), 25 (7%) had an arrhythmic event, with an overall annual event rate of 1.38 (95% CI 0.93–2.04). No ECG variables were associated with 5-year arrhythmic event on univariable or multivariable analysis. The ECG risk score threshold of &gt;5 had modest discriminatory ability [C-index 0.60 (95% CI 0.484–0.715)], with corresponding negative and positive predictive values of 96.7% and 6.7% Conclusion In a large, international, multi-centre cohort of childhood HCM, ECG abnormalities were common and varied. No ECG characteristic, either in isolation or combined in the previously described ECG risk score, was associated with 5-year sudden cardiac death risk. This suggests that the role of baseline ECG phenotype in improving risk stratification in childhood HCM is limited.

scholarly journals Unique clinical features and long term follow up of survivors of sudden cardiac death in an Asian multicenter study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Pang-Shuo Huang ◽  
Jen-Fang Cheng ◽  
Wen-Chin Ko ◽  
Shu-Hsuan Chang ◽  
Tin-Tse Lin ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Asia Pacific ◽  
Left Ventricular Ejection ◽  
Arrhythmic Death ◽  
Long Term Follow Up ◽  
History Of

AbstractThere has been no long-term clinical follow-up data of survivors or victims of sudden cardiac death (SCD). The Taiwan multi-center sudden arrhythmia death syndrome follow-up and clinical study (TFS-SADS) is a collaborative multi-center study with median follow-up time 43 months. In this cohort, the clinical characteristics of these SADS patients were compared with those with ischemic heart disease (IHD). In this SCD cohort, around half (42%) were patients with IHD, which was different from Caucasian SCD cohorts. Among those with normal heart, most had Brugada syndrome (BrS). Compared to those with SADS, patients with IHD were older, more males and more comorbidities, more arrhythmic death, and lower left ventricular ejection fraction. In the long-term follow-up, patients with SADS had a better survival than those with IHD (p < 0.001). In the Cox regression analysis to identify the independent predictors of mortality, older age, lower LVEF, prior myocardial infarction and history of out-of-hospital cardiac arrest were associated with higher mortality and beta blocker use and idiopathic ventricular fibrillation or tachycardia (IVF/IVT) with a better survival during follow-up. History of prior MI was associated with more arrhythmic death. Several distinct features of SCD were found in the Asia–Pacific region, such as higher proportion of SADS, poorer prognosis of LQTS and better prognosis of IVF/IVT. Patients with SADS had a better survival than those with IHD. For those with SADS, patients with channelopathy had a better survival than those with cardiomyopathy.

scholarly journals Case reports of a c.475G>T, p.E159* lamin A/C mutation with a family history of conduction disorder, dilated cardiomyopathy and sudden cardiac death

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Tetsuro Yokokawa ◽  
Shohei Ichimura ◽  
Naoko Hijioka ◽  
Takashi Kaneshiro ◽  
Akiomi Yoshihisa ◽  
...  
Keyword(s):  
Family History ◽  
Sudden Cardiac Death ◽  
Left Ventricular Ejection Fraction ◽  
Ejection Fraction ◽  
Cardiac Death ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
History Of ◽  
Conduction Disorder

Abstract Background Patients with some mutations in the lamin A/C (LMNA) gene are characterized by the presence of dilated cardiomyopathy (DCM), conduction abnormalities, ventricular tachyarrhythmias (VT), and sudden cardiac death (SCD). Various clinical features have been observed among patients who have the same LMNA mutation. Here, we show a family with cardiac laminopathy with a c.475G > T, p.E159* LMNA mutation, and a family history of conduction disorder, DCM, VT, and SCD. Case presentation A proband (female) with atrial fibrillation and bradycardia was implanted with a pacemaker in her fifties. Twenty years later, she experienced a loss of consciousness due to polymorphic VT. She had a serious family history; her mother and elder sister died suddenly in their fifties and sixties, respectively, and her nephew and son were diagnosed as having DCM. Genetic screening of the proband, her son, and nephew identified a nonsense mutation (c.475G > T, p.E159*) in the LMNA gene. Although the proband’s left ventricular ejection fraction remained relatively preserved, her son and nephew’s left ventricular ejection fraction were reduced, resulting in cardiac resynchronization therapy by implantation of a defibrillator. Conclusions In this family with cardiac laminopathy with a c.475G > T, p.E159* LMNA mutation, DCM, SCD, and malignant VT occurred. Clinical manifestation of various atrial and ventricular arrhythmias and heart failure with reduced ejection fraction occurred in an age-dependent manner in all family members who had the nonsense mutation. It appears highly likely that the E159* LMNA mutation is related to various cardiac problems in the family of the current report.

scholarly journals Sudden cardiac death risk in contact sports increased by myocarditis: a case series

2021 ◽  
Vol 5 (3) ◽  
Author(s):  
Grégoire Massoullié ◽  
Baptiste Boyer ◽  
Vincent Sapin ◽  
Frédéric Jean ◽  
Marius Andronache ◽  
...  
Keyword(s):  
Sudden Cardiac Death ◽  
Cardiac Death ◽  
Chest Trauma ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Loss Of Consciousness ◽  
Contact Sports ◽  
Blunt Impact ◽  
Life Threatening ◽  
History Of

Abstract Background Myocarditis is a known cause of sudden cardiac death of the athlete. The impact of direct chest trauma in at-risk sports or activities in patients with a history of myocarditis has never been demonstrated or studied. We report herein two cases of life-threatening ventricular arrhythmia secondary to non-penetrating blunt chest trauma while playing contact sports. Case summary The first patient, a 26-year-old man described a brief loss of consciousness after having received blunt impact to the chest (typical intensity) while playing a rugby match. The loss of consciousness was total and proceeded by rapid and regular palpitations. He had a history of viral myocarditis 10 years prior with a fibrotic sequalae in the inferolateral wall on cardiac magnetic resonance imaging (left ventricular ejection fraction 71%). Right apical ventricular pacing induced a sustained monomorphic ventricular tachycardia reproducing the patient’s symptoms. A subcutaneous implantable cardioverter-defibrillator was implanted. The second patient is a 22-year-old professional rugby player with no known notable history. During a match, a direct blow to the chest wall was followed by a cardiac arrest. A ventricular fibrillation was cardioverted to pulseless electrical activity. Patient died despite cardiopulmonary resuscitation. An autopsy identified a myocardial sequela of fibrosis with no acute inflammatory remodelling compatible with a previous myocarditis. Discussion Myocarditis may increase the risk of life-threatening ventricular arrhythmias caused by blunt impact to the chest, particularly in contact sports. Screening and prevention measures should be considered to reduce this risk.

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