MYBPC3Δ25bp intronic deletion in hypertrophic cardiomyopathy patients and healthy Iranian population

Background: Hypertrophic cardiomyopathy is a common genetic cardiovascular disease with autosomal dominant inheritance and MYBPC3 gene has been frequently linked to its pathogenesis. Since, carriers of the 25 nucleotides deletion located on intron 32 of the MYBPC3 are at increased risk of heart disease we aimed to investigate this variant in hypertrophic cardiomyopathy patients and healthy population. Methods: DNA was extracted from 350 Blood samples including 42 hypertrophic cardiomyopathies and 308 healthy subjects and the region containing the deletion was amplified by PCR method. PCR products were analyzed on agarose gel and genotyping results were recorded. Results: Genetic counseling results revealed that 26.2% of patients were sporadic cases vs 59.5% with positive family history and there was a history of sudden cardiac death in the first degree relatives of 42.3% of the patients. Genotyping results showed that all samples had a single band of 198 bp, indicating no MYBPC3Δ25bp variant in HCM patients as well as 308 controls. Bioinformatics assessments revealed that MYBPC3Δ25bp had a frequency of 0.00438 on Iranome database with the highest incidence reported in the Baloch population. Conclusion: Since hypertrophic cardiomyopathy is related to sudden cardiac death, population studies in terms of predisposing factors are of particular importance. Our study results showed that MYBPC3Δ25bpshould not be considered as risk factor in the patients of northwest of Iran. However, according to the bioinformatics findings and reports of neighboring countries, it is suggested that MYBPC3Δ25bp to be studied in the eastern and southern Iranian hypertrophic cardiomyopathy patients.

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Does the Age of Sudden Cardiac Death in Family Members Matter in Brugada Syndrome?

Journal of the American Heart Association ◽

10.1161/jaha.120.019788 ◽

2021 ◽

Author(s):

Pattara Rattanawong ◽

Jakrin Kewcharoen ◽

Chanavuth Kanitsoraphan ◽

Timothy Barry ◽

Anusha Shanbhag ◽

...

Keyword(s):

Family History ◽

Sudden Cardiac Death ◽

Brugada Syndrome ◽

Cardiac Death ◽

Meta Analysis ◽

Positive Family History ◽

Family Members ◽

Increased Risk ◽

History Of ◽

Risk Predictor

Background Brugada syndrome is an inherited cardiac channelopathy associated with major arrhythmic events (MAEs). The presence of a positive family history of sudden cardiac death (SCD) as a risk predictor of MAE remains controversial. We aimed to examine the association between family history of SCD and MAEs stratified by age of SCD with a systematic review and meta‐analysis. Methods and Results We searched the databases of MEDLINE and EMBASE from January 1992 to January 2020. Data from each study were combined using the random‐effects model. Fitted metaregression was performed to evaluate the association between the age of SCD in families and the risk of MAE. Twenty‐two studies from 2004 to 2019 were included in this meta‐analysis involving 3386 patients with Brugada syndrome. The overall family history of SCD was not associated with increased risk of MAE in Brugada syndrome (pooled odds ratio [OR], 1.11; 95% CI, 0.82–1.51; P =0.489, I 2 =45.0%). However, a history of SCD in family members of age younger than 40 years of age did increase the risk of MAE by ≈2‐fold (pooled OR, 2.03; 95% CI, 1.11–3.73; P =0.022, I 2 =0.0%). When stratified by the age of cut point at 50, 45, 40, and 35 years old, a history of SCD in younger family member was significantly associated with a higher risk of MAE (pooled OR, 0.49, 1.30, 1.51, and 2.97, respectively; P =0.046). Conclusions A history of SCD among family members of age younger than 40 years was associated with a higher risk of MAE.

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Diagnosis of Brugada Syndrome, a Rare Inherited Arrhythmogenic Disorder

Dubai Medical Journal ◽

10.1159/000507572 ◽

2020 ◽

Vol 3 (2) ◽

pp. 70-73

Author(s):

Juwairiya Syed Iqbaluddin ◽

Fathima Murthuza ◽

Sumaiya Iqbal

Keyword(s):

Family History ◽

Sudden Cardiac Death ◽

Brugada Syndrome ◽

Cardiac Death ◽

Genetic Disorder ◽

Positive Family History ◽

Provocation Test ◽

Increased Risk ◽

History Of ◽

Electrocardiogram Ecg

Brugada syndrome (BrS) is a rare, autosomal dominant genetic disorder with mutation in the SCN5A gene. It is associated with an increased risk of arrhythmias and sudden cardiac death. BrS can be diagnosed by characteristic electrocardiogram (ECG) findings and significant events, such as syncope, palpitations, nocturnal respiratory agonia, and family history of sudden cardiac death below the age of 45 years. Special investigations, such as electrophysiology study, ajmaline provocation test, and genetic testing, play an important role in its diagnosis. This case report describes a patient who presented with chest pain and dizziness along with a positive family history of sudden cardiac deaths below the age of 45 years. He was discovered to have type 2 Brugada pattern on ECG, and by ajmaline provocation test, the type 1 pattern was unmasked, which established a definitive diagnosis of BrS. The patient was then advised for an implantable cardioverter-defibrillator. This case highlights the need for physicians to be competent in identifying patients with BrS in order to provide the necessary management and prevent fatal outcomes.

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N-terminal pro-brain natriuretic peptide and sudden cardiac death in hypertrophic cardiomyopathy

Heart ◽

10.1136/heartjnl-2020-317701 ◽

2020 ◽

pp. heartjnl-2020-317701

Author(s):

Guixin Wu ◽

Jie Liu ◽

Shuiyun Wang ◽

Shiqin Yu ◽

Ce Zhang ◽

...

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Sudden Cardiac Death ◽

Brain Natriuretic Peptide ◽

Natriuretic Peptide ◽

Cardiac Death ◽

Cardiac Fibrosis ◽

Discrimination Performance ◽

Net Reclassification Improvement ◽

C Statistic ◽

Increased Risk

ObjectiveElevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with heart failure-related death in hypertrophic cardiomyopathy (HCM), but the relationship between NT-proBNP level and sudden cardiac death (SCD) in HCM remains undefined.MethodsThe study prospectively enrolled 977 unrelated patients with HCM with available NT-proBNP results who were prospectively enrolled and followed for 3.0±2.1 years. The Harrell’s C-statistic under the receiver operating characteristic curve was calculated to evaluate discrimination performance. A combination model was constructed by adding NT-proBNP tertiles to the HCM Risk-SCD model. The correlation between log NT-proBNP level and cardiac fibrosis as measured by late gadolinium enhancement (LGE) or Masson’s staining was analysed.ResultsDuring follow-up, 29 patients had SCD. Increased log NT-proBNP levels were associated with an increased risk of SCD events (adjusted HR 22.27, 95% CI 10.93 to 65.63, p<0.001). The C-statistic of NT-proBNP in predicting SCD events was 0.80 (p<0.001). The combined model significantly improved the predictive efficiency of the HCM Risk-SCD model from 0.72 to 0.81 (p<0.05), with a relative integrated discrimination improvement of 0.002 (p<0.001) and net reclassification improvement of 0.67 (p<0.001). Furthermore, log NT-proBNP levels were significantly correlated with cardiac fibrosis as detected either by LGE (r=0.257, p<0.001) or by Masson’s trichrome staining in the myocardium (r=0.198, p<0.05).ConclusionNT-proBNP is an independent predictor of SCD in patients with HCM and may help with risk stratification of this disease.

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Abstract 14760: Myocardial Scarring by Magnetic Resonance Predicts Sudden Cardiac Death in Pediatric Patients With Hypertrophic Cardiomyopathy

Circulation ◽

10.1161/circ.142.suppl_3.14760 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Lars Grosse-Wortmann ◽

Laurine van der Wal ◽

Aswathy Vaikom House ◽

Lee Benson ◽

Raymond Chan

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Hypertrophic Cardiomyopathy ◽

Sudden Cardiac Death ◽

Cardiac Death ◽

Pediatric Patients ◽

Risk Markers ◽

C Statistic ◽

Increased Risk ◽

Traditional Risk Factors

Introduction: Cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE) has been shown to be an independent predictor of sudden cardiac death (SCD) in adults with hypertrophic cardiomyopathy (HCM). The clinical significance of LGE in pediatric HCM patients is unknown. Hypothesis: LGE improves the SCD risk prediction in children with HCM. Methods: We retrospectively analyzed the CMR images and reviewed the outcomes pediatric HCM patients. Results: Amongst the 720 patients from 30 centers, 73% were male, with a mean age of 14.2±4.8 years. During a mean follow up of 2.6±2.7 years (range 0-14.8 years), 34 experienced an episode of SCD or equivalent. LGE (Figure 1A) was present in 34%, with a mean burden of 14±21g, or 2.5±8.2g/m2 (6.2±7.7% of LV myocardium). The presence of ≥1 adult traditional risk factor (family history of SCD, syncope, LV thickness >30mm, non-sustained ventricular tachycardia on Holter) was associated with an increased risk of SCD (HR=4.6, p<0.0001). The HCM Risk-Kids score predicted SCD (p=0.002). The presence of LGE was strongly associated with an increased risk (HR=3.8, p=0.0003), even after adjusting for traditional risk factors (HR adj =3.2, p=0.003) or the HCM Risk-Kids score (HR adj =3.5, p=0.003). Furthermore, the burden of LGE was associated with increased risk (HR=2.1/10% LGE, p<0.0001). LGE burden remained independently associated with an increased risk for SCD after adjusting for traditional risk factors (HRadj=1.5/10% LGE, p=0.04) or HCM Risk-Kids (HRadj=1.9/10% LGE, p=0.0018, Figure 1B). The addition of LGE burden improved the predictive model using traditional risk markers (C statistic 0.67 vs 0.77, p=0.003) and HCM Risk-Kids (C statistic 0.68 vs 0.74, p=0.045). Conclusions: Quantitative LGE is an independent risk factor for SCD in pediatric patients with HCM and improves the performance of traditional risk markers and the HCM Risk-Kids Score for SCD risk stratification in this population.

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The Potential of Late Gadolinium Enhancement to Serve as a Predictor of Ventricular Arrhythmias in Hypertrophic Cardio-myopathy Patients

The Open Hypertension Journal ◽

10.2174/1876526201608010001 ◽

2016 ◽

Vol 8 (1) ◽

pp. 1-11

Author(s):

Thomas D. Gossios ◽

Georgios K. Efthimiadis ◽

Theodoros D. Karamitsos ◽

Thomas Zegkos ◽

Vasilios G. Athyros ◽

...

Keyword(s):

Late Gadolinium Enhancement ◽

Hypertrophic Cardiomyopathy ◽

Sudden Cardiac Death ◽

Sudden Death ◽

Cardiac Death ◽

Large Scale ◽

Small Subset ◽

Gadolinium Enhancement ◽

Inherited Cardiomyopathy ◽

Increased Risk

Hypertrophic cardiomyopathy, the most common inherited cardiomyopathy is well known to be the leading cause of sudden cardiac death in young people. However, amongst the population of patients, a small subset bears increased risk of sudden cardiac death and would benefit from implantation of a defibrillator, currently recognized utilizing a series of established risk factors. This risk stratification model is hampered by low positive predictive value. Therefore, novel predictors of sudden death are sought. The advent of cardiac magnetic resonance and late gadolinium enhancement has allowed accurate quantification of regional fibrosis, a key element of hypertrophic cardiomyopathy, pathophysiologically linked to increased arrhythmogenicity. We sought to review currently available data on the utility of late gadolinium enhancement to serve as a novel predictor of arrhythmias and sudden death. In conclusion, significantly diverse methodological approaches and subsequent findings between available studies on the topic have hampered such use, highlighting the need for uniformly designed large scale, prospective studies in order to clarify which aspects of myocardial fibrosis could serve as predictors of arrhythmic events.

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Sudden Cardiac Death in Athletes: What Sport-Rehabilitation Specialists Need to Know

Journal of Sport Rehabilitation ◽

10.1123/jsr.12.3.259 ◽

2003 ◽

Vol 12 (3) ◽

pp. 259-271 ◽

Cited By ~ 1

Author(s):

Christian C. Evans ◽

Sandra L. Cassady

Keyword(s):

Sudden Cardiac Death ◽

Los Angeles ◽

Health Care Professionals ◽

Cardiac Death ◽

Signs And Symptoms ◽

Data Sources ◽

Los Angeles Times ◽

Increased Risk ◽

History Of ◽

Artery Disease

Objective:To describe the underlying conditions that predispose athletes to sudden cardiac death (SCD) and review signs and symptoms that indicate an athlete is at risk.Data Sources:MEDLINE, theLos Angeles TimesandTriathlon Timesarchives, and other sources identified in the references of articles initially located therein. A total of 43 references were included.Conclusions:Most cases of SCD in younger athletes (≤35 years) are attributable to multiple hereditary conditions, with familial hyper-trophic cardiomyopathy being the primary cause, whereas the major cause of SCD in older athletes (>35 years) is coronary artery disease. Health-care professionals evaluating athletes should pay particular attention to past medical and family history. Items in an athlete’s screening that suggest increased risk include a history of chest pain, syncope, excessive shortness of breath, irregular heart rate or murmur, or a history of SCD in an immediate family member.

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Sudden Cardiac Death in Three Generations of the Same Family: A case report

Cardiovascular Journal ◽

10.3329/cardio.v8i1.24779 ◽

2015 ◽

Vol 8 (1) ◽

pp. 73-77

Author(s):

MM Zahurul Alam Khan ◽

Abdul Wadud Chowdhury ◽

Tunaggina Afrin Khan ◽

Md Gaffar Amin ◽

Md Nur Alam ◽

...

Keyword(s):

Heart Failure ◽

Young Adults ◽

Case Report ◽

Hypertrophic Cardiomyopathy ◽

Sudden Cardiac Death ◽

Cardiac Death ◽

Premature Death ◽

Young Person ◽

Current Case ◽

History Of

Every one of us has heard about tragic and sudden death of a healthy young person and which is often stated as inexplicable. The current case report focuses on a 20 year old young man with hypertrophic cardiomyopathy facing premature death with history of similar sudden premature death of his grandmother, father and brother. Hypertrophic cardiomyopathy is the commonest cause of sudden cardiac death in young adults and is also an important substrate for heart failure disability at any age.Cardiovasc. j. 2015; 8(1): 73-77

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Higher serum urate levels are associated with an increased risk for sudden cardiac death

The Journal of Rheumatology ◽

10.3899/jrheum.210139 ◽

2021 ◽

pp. jrheum.210139

Author(s):

Lisandro D. Colantonio ◽

Richard J. Reynolds ◽

Tony R. Merriman ◽

Angelo Gaffo ◽

Jasvinder A. Singh ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Racial Differences ◽

Cardiac Death ◽

Cohort Analysis ◽

Serum Urate ◽

Hazard Ratio ◽

Baseline Serum ◽

Serum Urate Level ◽

Increased Risk ◽

History Of

Objective Determine the association of serum urate levels with sudden cardiac death and incident coronary heart disease (CHD), separately, among adults without a history of CHD. Methods We conducted a case-cohort analysis of Black and White participants ≥45 years of age enrolled in the REason for Geographic And Racial Differences in Stroke (REGARDS) study without a history of CHD at baseline between 2003 and 2007. Participants were followed for sudden cardiac death or incident CHD (i.e., myocardial infarction or death from CHD excluding sudden cardiac death) through December 31, 2013. Baseline serum urate was measured in a random sample of participants (n=840) and among participants who experienced sudden cardiac death (n=235) or incident CHD (n=851) during follow-up. Results Participants with higher serum urate levels were older and more likely to be male or Black. The crude hazard ratio (95%CI) per 1 mg/dL higher serum urate level was 1.26 (1.14-1.40) for sudden cardiac death and 1.17 (1.09-1.26) for incident CHD. After adjustment for age, gender, race, and cardiovascular risk factors, the hazard ratio (95%CI) per 1 mg/dL higher serum urate level was 1.19 (1.03-1.37) for sudden cardiac death and 1.05 (0.96-1.15) for incident CHD. Hazard ratios for sudden cardiac death were numerically higher among participants 45-64 versus ≥65 years of age, without versus with diabetes, and among those of White versus Black race, although p-values for effect modification were all ≥0.05. Conclusion Higher serum urate levels were associated with an increased risk for sudden cardiac death but not with incident CHD.

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Abstract P110: High Serum Urate Levels are Associated With an Increased Risk for Sudden Cardiac Death in the Reasons for Geographic and Racial Differences in Stroke (regards) Study

Circulation ◽

10.1161/circ.141.suppl_1.p110 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Lisandro D Colantonio ◽

Richard Reynolds ◽

Tony Merriman ◽

Angelo Gaffo ◽

Jasvinder A Singh ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Racial Differences ◽

Cardiac Death ◽

Statistical Power ◽

Cohort Analysis ◽

Large Population ◽

Serum Urate ◽

Increased Risk ◽

History Of ◽

Regards Study

Background: Higher serum urate (SU) levels were shown to causally increase the risk for sudden cardiac death (SCD) in a Mendelian randomization analysis of white adults, most of whom had coronary heart disease (CHD). It is unclear if these results are generalizable to more racially diverse adults without CHD. Objective: To assess the risk for SCD and incident CHD associated with SU levels in adults without a history of CHD using data from a large, population-based cohort of US black and white men and women ≥45 years of age, the REason for Geographic And Racial Differences in Stroke (REGARDS) study. Methods: We conducted a case-cohort analysis of REGARDS study participants without a history of CHD at baseline between 2003 and 2007. Participants were followed for SCD or incident CHD (i.e., myocardial infarction or CHD death excluding SCD) from baseline through December 31, 2013. Baseline SU levels were measured in a random sample of participants (n=840) and among 235 participants with SCD and 851 participants with incident CHD. Results: Participants with higher SU levels were older and more likely to be black and male. The crude hazard ratio (95%CI) per 1 mg/dL higher SU level was 1.26 (1.14, 1.40) for SCD and 1.17 (1.09, 1.26) for incident CHD. Analyses modeling SU levels using splines supported that these associations were linear. After multivariable adjustment, higher SU levels remained associated with an increased risk for SCD, but not for incident CHD ( Table ). There was no effect modification in the association of SU levels with SCD or incident CHD by either age, gender, race or chronic kidney disease. However, the increased risk for SCD associated with higher SU levels was present in whites but not among blacks. Limitations: The study has limited statistical power for subgroup comparisons. Race differences in the association between SU levels and SCD require further investigation. Conclusions: In adults without a history of CHD, higher SU levels appear to be an independent risk factor for SCD, but no association was detected with incident CHD.

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Elevated Level of Troponin but Not N-Terminal Probrain Natriuretic Peptide Is Associated with Increased Risk of Sudden Cardiac Death in Hypertrophic Cardiomyopathy Calculated According to the ESC Guidelines 2014

Disease Markers ◽

10.1155/2017/9417908 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5 ◽

Cited By ~ 9

Author(s):

Renata Rajtar-Salwa ◽

Rafał Hładij ◽

Paweł Petkow Dimitrow

Keyword(s):

Hypertrophic Cardiomyopathy ◽

Sudden Cardiac Death ◽

Natriuretic Peptide ◽

Cardiac Death ◽

Troponin I ◽

Increased Risk ◽

Echocardiographic Examination ◽

Esc Guidelines ◽

The Relationship ◽

High Sensitive Troponin

The aim of this study was to assess the relationship between biomarkers (high-sensitive troponin I [hs-TnI], N-Terminal probrain natriuretic peptide [NT-proBNP]) and calculated 5-year percentage risk score of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM). Methods. In 46 HCM patients (mean age 39 ± 7 years, 24 males and 22 females), echocardiographic examination, including the stimulating maneuvers to provoke maximized LVOT gradient, had been performed and next ECG Holter was immediately started. After 24 hours, the ECG Holter was finished and the hs-TnI and NT-proBNP have been measured. Patients were divided according to 1/value of both biomarkers (hs-TnI-positive and hs-TnI-negative subgroups) and 2/(NT-proBNP lower and higher subgroup divided by median). Results. In comparison between 19 patients (hs-TnI positive) versus 27 patients (hs-TnI negative), the calculated 5-year percentage risk of SCD in HCM was significantly greater (6.38 ± 4.17% versus 3.81 ± 3.23%, P<0.05). In comparison between higher NT-proBNP versus lower NT-proBNP subgroups, the calculated 5-year percentage risk of SCD in HCM was not significantly greater (5.18 ± 3.63% versus 4.14 ± 4.18%, P>0.05). Conclusions. Patients with HCM and positive hs-TnI test have a higher risk of SCD estimated according to SCD calculator recommended by the ESC Guidelines 2014 than patients with negative hs-TnI test.

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