Gender differences in prevalence and prognostic value of fragmented QRS complex

Background: Fragmented QRS (fQRS) on 12-lead electrocardiogram(ECG) is associated with scarred myocardium and adverse outcome. However, the data on gender differences in terms of its prevalence and prognostic value is sparse. The aim of this study was to evaluate whether gender differences in fQRS exist among subjects drawn from populations with different risk profiles. Methods: We analyzed fQRS from 12-lead ECG in 953 autopsy-confirmed victims of sudden cardiac death (SCD) (78% men; 67.0 +/- 11.4 yrs), 1900 coronary artery disease (CAD) patients with angiographically confirmed stenosis of >= 50% (70% men; 66.6 +/- 9.0 yrs, 43% with previous myocardial infarction [MI]), and in 10,904 adults drawn from the Finnish adult general population (52% men; 44.0 +/- 8.5 yrs). Results: Prevalence of fQRS was associated with older age, male sex and the history and severity of prior cardiac disease of subjects. Among the general population fQRS was more commonly found among men in comparison to women (20.5% vs. 14.8%, p <0.001). The prevalence of fQRS rose gradually along with the severity of prior cardiac disease in both genders, yet remained significantly higher in the male population: subjects with suspected or known cardiac disease (25.4% vs. 15.8% p <0.001), CAD patients without prior MI (39.9% vs. 26.4%, p <0.001), CAD patients with prior MI (42.9% vs. 31.2%, p <0.001), and victims of SCD (56.4% vs. 44.4%, p <0.001). Conclusions: The prevalence of QRS fragmentation varies in different populations. The fragmentation is clearly related to the underlying cardiac disease in both genders, however women seem to have significantly lower prevalence of fQRS in each patient population in comparison to men. (C) 2020 The Authors. Published by Elsevier Inc.Peer reviewe

Sudden death due to non-ischemic myocardial diseases:genetics and electrocardiographic characteristics

Abstract Approximately 10–20% of all deaths occur unexpectedly and suddenly due to underlying cardiac disease, i.e. sudden cardiac death (SCD). Non-ischemic myocardial diseases cause one in every five SCD cases and most of these cases occur without prior diagnosis of cardiac disease. The aim of this thesis was to investigate the electrocardiographic characteristics and genetic background of non-ischemic myocardial diseases leading to SCD. The study population included a total of 5,869 SCD victims from Northern Finland and 10,864 Finnish subjects from general population. In the I study, we found that early repolarization (ER) in the inferolateral leads of 12-lead ECG was a more common finding among victims of non-ischemic SCD than in general population. In the II study, we investigated the genetic background of non-ischemic SCD victims with primary myocardial fibrosis (PMF) as the cause of death. Likely disease-causing variants existed in 10% of the study subjects. The variants were predominantly in myocardial structure protein-coding genes that are generally associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. In the III study we found that 10% of the SCD victims with presumably acquired hypertrophic cardiac disease carried likely disease-causing genetic variants in myocardial genes. This suggests that rare genetic variants may play a role in SCD among patients with either hypertension or obesity-related cardiac disease. In study IV, we investigated the ECG characteristics of various amounts of myocardial fibrosis in SCD victims. The results suggest that fibrotic accumulation in the myocardium manifests as QRS prolongation, QRS fragmentation, pathologic Q waves and T wave abnormalities. In conclusion, the results of this thesis introduce genetic vulnerability in the development of life-threatening non-specific non-ischemic myocardial diseases and highlight the priority of meticulous post-mortem investigations in the case of unexpected SCD. Studies I and IV also demonstrated that life-threatening non-ischemic cardiomyopathies express ECG abnormalities before clinical symptoms. Consequently, detection and treatment of such cardiac diseases may be possible before the devastating event.Tiivistelmä Noin 10–20 % kaikista kuolemista on odottamattomia ja tapahtuu äkillisesti sydänsairaudesta johtuen. Erilaiset sydänlihassairaudet kattavat noin viidesosan kaikista sydänperäisistä äkkikuolemista ja yli puolet niistä on piilevän sydänsairauden ensimmäisiä oireita. Tämän väitöstutkimuksen tarkoitus on löytää kyseisten sydänlihassairauksien ilmentymiä 12-kanavaisesta EKG:stä sekä selvittää tautien geneettistä taustaa. Tutkimusaineisto käsittää 5869 äkillisesti sydänsairauteen kuollutta sekä 10864 yleistä väestöä edustavaa henkilöä. Ensimmäisessä tutkimuksessa huomasimme, että EKG:n inferolateraalisissa kytkennöissä esiintyvä varhainen repolarisaatio oli sydänlihassairauteen äkillisesti kuolleilla yleisempää kuin yleisessä väestössä. Toisessa tutkimuksessa tarkoituksemme oli selvittää äkkikuolemaan johtavan primaarin sydänlihasfibroosin geneettistä taustaa. Todennäköisesti tautia aiheuttavia geenimuutoksia löytyi 10 prosentilla tutkituista. Geenimuutokset olivat pääasiassa sydänlihasproteiineja koodaavissa geeneissä, joiden on todettu aiheuttavan sekä hypertrofista että dilatoivaa kardiomyopatiaa ja arytmogeenista oikean kammion kardiomyopatiaa. Kolmannessa tutkimuksessa huomasimme, että 10 % näennäisesti hankittuun hypertrofiseen sydänlihassairauteen äkkikuollutta kantoikin todennäköisesti sydänsairautta aiheuttavia geenimuutoksia sydänlihasproteiineja koodaavissa geeneissä. Näin ollen muutokset sydänlihasproteiineja koodaavissa geeneissä mahdollisesti muokkaavat korkeaan verenpaineeseen tai lihavuuteen liittyvän sydänlihassairauden luonnetta, mikä lisää äkkikuoleman riskiä. Neljännessä tutkimuksessamme selvitimme eriasteisiin sydänlihaksen sidekudoskertymiin liittyviä EKG-poikkeavuuksia. Tutkimuksessa kävi ilmi, että lisääntyvä fibroosi liittyy QRS-ajan pitenemiseen, patologisiin Q-aaltoihin, QRS-kompleksin solmuuntumiseen sekä T-aallon muutoksiin. Äkkikuolemaan johtavia sydänlihassairauksia olisi mahdollista epäillä ennen oireilua/kuolemaa EKG-poikkeavuuksien perusteella. Sidekudoskertymään liittymätön varhainen repolarisaatio on lisäksi merkki lisääntyneestä äkkikuolemariskistä. Tutkimuksessamme selvisi lisäksi, että geeniperimällä voi olla merkittävä vaikutus myös epäspesifien äkkikuolemia aiheuttavien sydänlihassairauksien kehittymisessä

Sudden cardiac death after alcohol intake:classification and autopsy findings

Abstract Alcohol is known to have an immediate effect on cardiac rhythm, and previous studies have found that a notable proportion of sudden cardiac deaths (SCD) occur after alcohol intake. The objective of the present study was to investigate the association between the timing of alcohol intake and SCD. Our study population is drawn from the Fingesture study, which includes 5869 consecutive SCD cases from Northern Finland who underwent medicolegal autopsy 1998–2017. Toxicological analysis was performed if there was any suspicion of toxic exposure, or if there was no obvious immediate cause of SCD at autopsy. We found that 1563 (27%) of all SCD victims had alcohol in blood or urine at autopsy (mean age (61 ± 10 years, 88% male). Eighty-six percent of alcohol-related SCD victims had higher urine alcohol concentration than blood alcohol concentration, referring to the late-stage inebriation. These results suggest that the majority of alcohol-related SCDs occur at the late stage of inebriation

Temporal trends in the incidence and characteristics of sudden cardiac death among subjects under 40 years of age in Northern Finland during 1998–2017

Abstract Background: Although the mean age of sudden cardiac death (SCD) victims has increased during recent decades, overall incidence has remained relatively stable. Small but very important proportion of SCDs occur in subjects under 40 years of age and temporal trends in the incidence and characteristics of SCD in this age-group are not well known. Methods: The Fingesture study has prospectively gathered data from 5,869 consecutive autopsy verified SCD victims in Northern Finland during 1998–2017. On the basis of Finnish law, all who die unexpectedly undergo autopsy. Results: Out of total 5,869 SCDs, 160 occurred in subjects under 40 years of age (3%) indicating a total incidence of 2.9/100,000/year. Incidence decreased during the study period: 4.0/100,000/year (n = 50) in 1998–2002, 3.7/100,000/year (n = 45) in 2003–2007, 2.5/100,000/year (n = 36) in 2008–2012, and 1.5/100,000/year (n = 29) in 2013–2017. Coronary artery disease (CAD) was the cause of death in 46 SCD victims (29%). Among nonischemic causes, most common were obesity-related hypertrophic myocardial disease (24%), primary myocardial fibrosis (19%), and hypertensive myocardial disease (6%). The incidence of SCD caused by CAD decreased as follows: 1.5/100,000/year in 1998–2002, 1.2/100,000/year in 2003–2007, 0.6/100,000/year in 2008–2012, and 0.2/100,000/year in 2013–2017. Proportion of male gender (81%) and obesity as a comorbidity (body mass index >30 kg/m², 40%) remained relatively stable during the period (p = 0.58 and p = 0.79, respectively). Conclusions: The incidence of SCD in subjects under 40 years of age has decreased in Northern Finland during 1998–2017. According to autopsy data, most of the deaths are due to nonischemic myocardial diseases and relative proportion of CAD has decreased

Blood alcohol levels in Finnish victims of non-ischaemic sudden cardiac death

Abstract Introduction: Non-ischaemic heart disease (NIHD) is the underlying pathology in∼20% of all sudden cardiac deaths (SCDs). Heavy drinking is known to be associated with SCD due to ischaemic heart disease, but studies on association of recent alcohol consumption and SCD in patients with NIHD are scarce. We evaluated the blood alcohol levels of autopsy verified non-ischaemic SCD victims. Methods: Study population was derived from the Finnish Genetic Study of Arrhythmic Events (Fingesture) (n = 5869, mean age 65 ± 12, 79% males). All deaths occurred in Northern Finland during 1998–2017. All victims underwent a medico-legal autopsy. Subjects of SCD due to ischaemic heart disease were excluded. Results: A total of 1301 (mean age 57 ± 12, 78% males) victims of SCD due to NIHD were included in the study. The blood ethanol level was elevated in 543 (42%) subjects, out of which the blood alcohol level was ≥0.10%in 339 (62%) subjects and ≥0.15%in 252 (46%) subjects. Male SCD victims had alcohol in blood more frequently compared to females (45% versus 31%, p &lt; .001). Conclusion: Elevated blood alcohol level is common in SCD victims due to NIHD, especially in males. Recent alcohol consumption might contribute to the subsequent SCD in many non-ischaemic SCD victims

Electrocardiographic associations with myocardial fibrosis among sudden cardiac death victims

Abstract Objective: A major challenge in reducing the incidence of sudden cardiac death (SCD) is the identification of patients at risk. Myocardial fibrosis has a substantial association with SCD risk but is difficult to identify among general populations. Our aim was to find electrocardiographic (ECG) markers of myocardial fibrosis among SCD victims. Methods: Study population was acquired from the Fingesture study, which has gathered data from 5869 consecutive autopsied SCD victims in Northern Finland between 1998 and 2017. The degree of fibrosis was determined in histological samples taken from the heart during autopsy and was categorised into four groups: (1) no fibrosis, (2) scattered mild fibrosis, (3) moderate patchy fibrosis and (4) substantial fibrosis. We were able to collect ECGs from 1100 SCD victims. Results: The mean age of the study subjects was 66±13 years and 75% were male. QRS duration in ECG correlated with the degree of fibrosis (p&lt;0.001, β=0.153). Prevalence of fragmented QRS complex, pathological Q waves and T wave inversions correlated with increased degree of fibrosis (p&lt;0.001 in each). Depolarisation abnormalities were observed both in ischaemic and non-ischaemic heart disease. Repolarisation abnormalities reached statistical significance only among ischaemic SCD victims. An abnormal ECG was observed in 75.3% of the subjects in group 1, 73.7% in group 2, 88.5% in group 3 and 91.7% in group 4 patients (p&lt;0.001). Conclusions: Myocardial fibrosis was associated with QRS prolongation, deep Q waves, T wave inversions and QRS fragmentation. The results provide potentially useful non-invasive early recognition of patients with fibrotic cardiomyopathy and risk of SCD

Causes and characteristics of unexpected sudden cardiac death in octogenarians/nonagenarians

Abstract Introduction: The risk for sudden cardiac death (SCD) increases with ageing. Methods: We evaluated causes and characteristics of unexpected SCD in SCD victims aged ≥ 80 years in a consecutive series of 5,869 SCD victims in Northern Finland. All the victims underwent medico-legal autopsy as medico-legal autopsy is mandatory in cases of unexpected sudden death in Finland. All the non-cardiac deaths such as pulmonary embolism and cerebral hemorrhage were excluded from the study, as were unnatural deaths such as intoxications. Results: Among SCD victims ≥ 80 years, 91.0% of SCDs were due to ischemic heart disease (IHD) determined in autopsy and 9.0% due to non-ischemic heart disease (NIHD), whereas among those &lt; 80 years, only 72.6% of SCDs were due to IHD and 27.4% due to NIHD (P &lt; .001). Severe fibrosis in myocardium was more common whereas heart weight and liver weight, body mass index and abdominal fat thickness, were lower among SCD victims aged ≥ 80 years than among victims aged &lt; 80 years. In those with IHD as etiology of SCD, at least 75% stenosis in one or more major coronary vessels was more common in SCD victims aged ≥ 80 years than among victims aged &lt; 80 years (P = .001). SCD victims 80 years or older were less likely to die during physical activity than those under 80 years old (5.6% vs. 15.9%, P &lt; .001). Dying in sauna was more common among those ≥ 80 years than among those &lt; 80 years (5.5% vs. 2.6%, P &lt; .001). Conclusion: In victims of unexpected SCD aged ≥ 80 years, the autopsy-based etiology of SCD was more commonly IHD than in those aged &lt; 80 years. In SCD victims aged ≥ 80 years, severe fibrosis in myocardium, representing arrhythmic substrate, was more common than in the younger ones