Risk of sudden cardiac death associated with QRS, QTc, and JTc intervals in the general population

BACKGROUND QRS duration and corrected QT (QTc) interval have been associated with sudden cardiac death (SCD), but no data are available on the significance of repolarization component (JTc interval) of the QTc interval as an independent risk marker in the general population. OBJECTIVE In this study, we sought to quantify the risk of SCD associated with QRS, QTc, and JTc intervals. METHODS This study was conducted using data from 3 population cohorts from different eras, comprising a total of 20,058 individuals. The follow-up period was limited to 10 years and age at baseline to 30-61 years. QRS duration and QT interval (Bazett's) were measured from standard 12-lead electrocardiograms at baseline. JTc interval was defined as QTc interval - QRS duration. Cox proportional hazards models that controlled for confounding clinical factors identified at baseline were used to estimate the relative risk of SCD. RESULTS During a mean period of 9.7 years, 207 SCDs occurred (1.1 per 1000 person-years). QRS duration was associated with a significantly increased risk of SCD in each cohort (pooled hazard ratio [HR] 1.030 per 1-ms increase; 95% confidence interval [CI] 1.017-1.043). The QTc interval had borderline to significant associations with SCD and varied among cohorts (pooled HR 1.007; 95% CI 1.001-1.012). JTc interval as a continuous variable was not associated with SCD (pooled HR 1.001; 95% CI 0.996-1.007). CONCLUSION Prolonged QRS durations and QTc intervals are associated with an increased risk of SCD. However, when the QTc interval is deconstructed into QRS and JTc intervals, the repolarization component (JTc) appears to have no independent prognostic value.Peer reviewe

Risk of sudden cardiac death associated with QRS, QTc, and JTc intervals in the general population

BackgroundQRS duration and corrected QT (QTc) interval have been associated with sudden cardiac death (SCD), but no data are available on the significance of repolarization component (JTc interval) of the QTc interval as an independent risk marker in the general population.ObjectiveIn this study, we sought to quantify the risk of SCD associated with QRS, QTc, and JTc intervals.MethodsThis study was conducted using data from 3 population cohorts from different eras, comprising a total of 20,058 individuals. The follow-up period was limited to 10 years and age at baseline to 30–61 years. QRS duration and QT interval (Bazett’s) were measured from standard 12-lead electrocardiograms at baseline. JTc interval was defined as QTc interval – QRS duration. Cox proportional hazards models that controlled for confounding clinical factors identified at baseline were used to estimate the relative risk of SCD.ResultsDuring a mean period of 9.7 years, 207 SCDs occurred (1.1 per 1000 person-years). QRS duration was associated with a significantly increased risk of SCD in each cohort (pooled hazard ratio [HR] 1.030 per 1-ms increase; 95% confidence interval [CI] 1.017–1.043). The QTc interval had borderline to significant associations with SCD and varied among cohorts (pooled HR 1.007; 95% CI 1.001–1.012). JTc interval as a continuous variable was not associated with SCD (pooled HR 1.001; 95% CI 0.996–1.007).ConclusionProlonged QRS durations and QTc intervals are associated with an increased risk of SCD. However, when the QTc interval is deconstructed into QRS and JTc intervals, the repolarization component (JTc) appears to have no independent prognostic value.</p

Sudden cardiac death, cardiac mortality, and morbidity in women:electrocardiographic risk markers

Abstract Cardiovascular disease is the leading cause of death in both genders worldwide, and coronary artery disease (CAD) is the most common cause of cardiovascular death. Often the first manifestation of CAD, especially in women, is sudden cardiac death (SCD). Studies concerning gender difference in electrocardiographic (ECG) risk markers for adverse cardiac outcomes are scarce. The aim of this thesis was to study ECG risk markers in women with different risk profiles. In Study I, causes of death, autopsy findings, and ECG risk markers were studied in consecutive series of 5,869 SCD victims who underwent medicolegal autopsy. Non-ischemic SCD was more common in women, and especially the role of primary myocardial fibrosis as a cause of death was pronounced. Women were more likely to lack prior ECG abnormalities. Only the prevalence of ECG left ventricular hypertrophy (LVH) was higher in female SCD victims than in their male counterparts. In Study II, gender differences in the prevalence and prognostic value of QRS fragmentation (fQRS) were studied in 10,264 middle-aged subjects with and without known cardiac disease, in 1,900 CAD patients with and without previous myocardial infarction, and in 1,101 autopsy verified SCD victims. The prevalence of fQRS was considerably lower in women than in men in each population, and fQRS had prognostic value for adverse cardiac event only in male subjects with known cardiac disease. In Study III, gender differences in ECG risk markers for heart failure hospitalization were studied in 10,864 middle-aged subjects. Only ECG LVH predicted future heart failure hospitalization in women, but not in men. In Study IV, gender differences in the prevalence and prognostic value of different ECG markers for cardiac death were studied in three large samples of Finnish middle-aged general population containing a total of 20,310 subjects. The prevalence of all endpoints was considerably higher in men than in women. Women had more often normal electrocardiogram compared to men. ECG LVH was the only ECG variable which had a greater prognostic value for cardiac death in women than in men. Inferolateral T wave inversions, prolonged QRS duration and inferolateral early repolarization increased the risk of cardiac death only in men. Overall, the results of this thesis contribute to a growing understanding of the different ECG risk profiles of men and women.Tiivistelmä Sekä miehillä että naisilla sydän- ja verisuonisairaudet ovat maailmanlaajuisesti yleisin kuolinsyy, joista sepelvaltimotaudin osuus kuolemaan johtavana sairautena on suurin. Erityisesti naisilla sydänperäinen äkkikuolema on usein sepelvaltimotaudin ensimmäinen ilmentymä. Tutkimuksia sukupuolieroista 12-kytkentäisen sydänfilmin (EKG) riskitekijöissä on tehty vähän. Tämän väitöstutkimuksen tavoitteena oli tutkia EKG-riskimarkkereita erilaisen riskiprofiilin omaavilla naisilla. Tutkimuksessa I analysoitiin 5 869 sydänperäisen äkkikuoleman uhrin kuolinsyy ja ruumiinavauslöydökset sekä 1 101 uhrin EKG. Ei-iskeeminen äkkikuolema oli tyypillisempi naisilla, joilla kuolinsyynä korostui erityisesti primaari sydänlihaksen fibroosi. Naisten EKG oli miehiä useammin tulkittavissa normaaliksi, ja ainoastaan vasemman kammion hypertrofia (LVH) oli tyypillisempi löydös äkkikuolleilla naisilla kuin miehillä. Tutkimuksessa II tarkasteltiin sukupuolieroja QRS-kompleksin fragmentoitumisen (fQRS) esiintyvyydessä ja ennustavuudessa 10 264 keski-ikäisellä terveellä ja sydänsairaalla suomalaisella, 1 900 sepelvaltimotautipotilaalla sekä 1 101 ruumiinavatulla sydänperäisen äkkikuoleman uhrilla. fQRS:n esiintyvyys oli jokaisessa populaatiossa korkeampi miehillä, ja ennusteellista merkitystä epäsuotuisalle sydäntapahtumalle havaittiin ainoastaan miehillä, joilla oli tiedossa oleva sydänsairaus. Tutkimuksessa III tutkittiin sukupuolieroja EKG-muuttujien ennustavuudessa sydämen vajaatoiminnan sairaalahoitojaksoille 10 864 keski-ikäisellä suomalaisella tutkittavalla. Ainoastaan LVH ennusti tulevaa sydämen vajaatoiminnan sairaalajaksoa naisilla, mutta ei miehillä. Tutkimus IV käsitteli sukupuolieroja EKG-muuttujien ennustearvossa sydänkuolemalle kolmessa suuressa suomalaisessa keski-ikäistä perusväestöä kuvaavassa aineistossa, jotka yhdessä sisältävät 20 310 tutkittavaa. Kaikki päätetapahtumat olivat yleisempiä miehillä kuin naisilla. Naisilla EKG oli miehiä useammin normaali. Ainoastaan LVH:lla oli tulevan sydänkuoleman kannalta suurempi ennustemerkitys naisilla kuin miehillä. Inferolateraaliset T-aallon inversiot, pidentynyt QRS-kesto ja inferolateraalinen varhainen repolarisaatio nostivat sen sijaan sydänkuoleman riskiä vain miehillä. Kokonaisuudessaan tämän väitöstutkimuksen tulokset lisäävät osaltaan tietämystä naisten ja miesten erilaisesta EKG-riskiprofiilista sydäntapahtumille

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

Electrocardiographic risk markers for heart failure in women versus men

Abstract Heart failure (HF) is one of the leading causes of hospitalization in the Western world. Women have a lower HF hospitalization rate and mortality compared with men. The role of electrocardiography as a risk marker of future HF in women is not well known. We studied association of electrocardiographic (ECG) risk factors for HF hospitalization in women from a large middle-aged general population with a long-term follow-up and compared the risk profile to men. Standard 12-lead ECG markers were analyzed from 10,864 subjects (49% women), and their predictive value for HF hospitalization was analyzed. During the follow-up (30 ± 11 years), a total of 1,743 subjects had HF hospitalization; of these, 861 were women (49%). Several baseline characteristics, such as age, body mass index, blood pressure, and history of previous cardiac disease predicted the occurrence of HF both in women and men (p &lt;0.001 for all). After adjusting for baseline variables, ECG sign of left ventricular hypertrophy (LVH) (p &lt;0.001), and atrial fibrillation (p &lt;0.001) were the only baseline ECG variables that predicted future HF in women. In men, HF was predicted by fast heart rate (p = 0.008), T wave inversions (p &lt;0.001), abnormal Q-waves (p = 0.002), and atrial fibrillation (p &lt;0.001). Statistically significant gender interactions in prediction of HF were observed in ECG sign of LVH, inferolateral T wave inversions, and heart rate. In conclusion, ECG sign of LVH predicts future HF in middle-aged women, and T wave inversions and elevated heart rate are associated with HF hospitalization in men

Impact of age and sex on the long-term prognosis associated with early repolarization in the general population

Abstract Background: Early repolarization (ER) has been linked to the risk of sudden cardiac death (SCD) in the general population, although controversy remains regarding risks across various subgroups. Objective: The purpose of this study was to investigate whether age and sex influence the prognostic significance of ER. Methods: We evaluated the 12-lead electrocardiograms of 6631 Finnish general population subjects age ≥30 years (mean age 50.1 ± 13.9 years; 44.5% men) for the presence of ER (J-point elevation ≥0.1 mV in ≥2 inferior/lateral leads) and followed them for 24.4 ± 10.3 years. We analyzed the association between ER and the risk of SCD, cardiac death, and all-cause mortality in subgroups according to age (&lt;50 or ≥50 years) and sex. Results: ER was present in 367 of the 3305 subjects age &lt;50 years and in 426 of 3326 subjects ≥50 years. ER was not associated with any of the endpoints in the entire study population. After adjusting for clinical factors, ER was associated with SCD (hazard ratio [HR] 1.88; 95% confidence interval [CI] 1.16–3.07) in subjects &lt;50 but not in older subjects (interaction between ER and age group, P = .048). In the younger subgroup, women with ER had a high risk of SCD (HR 4.11; 95% CI 1.41–12.03), whereas among men ER was not associated with SCD. Finally, ER was not associated with cardiac mortality or all-cause mortality in either age group. Conclusion: ER is associated with SCD in subjects younger than 50 years, particularly in women, but not in subjects 50 years and older

Prevalence and prognostic significance of negative U-waves in a 12-lead electrocardiogram in the general population

Abstract Negative U-waves are a relatively rare finding in an electrocardiogram (ECG), but are often associated with cardiac disease. The prognostic significance of negative U-waves in the general population is unknown. We evaluated 12-lead ECGs of 6,518 adults (45% male, mean age 50.9 ± 13.8 years) for the presence of U-waves, and followed the subjects for 24.5 ± 10.3 years. Primary end points were all-cause mortality, cardiac mortality, and sudden cardiac death; secondary end point was hospitalization due to cardiac causes. Negative U-waves (amplitude ≥0.05 mV) were present in 231 subjects (3.5%), minor negative (amplitude &lt;0.05 mV) or discordant U-waves in 1,004 subjects (15.4%), normal positive U-waves in 3,950 (60.6%) subjects, and no U-waves were observed in 603 subjects (9.3%). In 730 subjects (11.2%), U-waves were unassessable. When adjusted for age and gender, negative U-waves were associated with all end points (p &lt;0.01). In an analysis adjusted for multiple demographic and clinical factors, in men, negative U-waves were associated with increased risk of all-cause mortality (hazard ratio [HR] 1.60; 95% confidence interval [CI] 1.26 to 2.03; p &lt;0.001), cardiac mortality (HR 1.74; 95% CI 1.26 to 2.39; p = 0.001), and cardiac hospitalization (HR 1.67; 95% CI 1.27 to 2.18; p &lt;0.001), but not with sudden cardiac death, whereas women did not show a significant association to any of the end points (p &gt;0.30). In conclusion, negative U-waves are associated with adverse events in the general population. In men, this association is independent of cardiovascular risk factors

Plaque histology and myocardial disease in sudden coronary death:the Fingesture study

Abstract Aims: At least 50% of deaths due to coronary artery disease (CAD) are sudden cardiac deaths (SCDs), but the role of acute plaque complications on the incidence of sudden death in CAD is somewhat unclear. The present study aimed to investigate plaque histology and concomitant myocardial disease in sudden coronary death. Methods and results: The study population is derived from the Fingesture study, which has collected data from 5869 consecutive autopsy-verified SCD victims in Northern Finland (population ≈600 000) between 1998 and 2017. In this substudy, histological examination of culprit lesions was performed in 600 SCD victims whose death was due to CAD. Determination of the cause of death was based on the combination of medical records, police reports, and autopsy data. Plaque histology was classified as either (i) plaque rupture or erosion, (ii) intraplaque haemorrhage, or (iii) stable plaque. The mean age of the study subjects was 64.9 ± 11.2 years, and 82% were male. Twenty-four per cent had plaque rupture or plaque erosion, 24% had an intraplaque haemorrhage, and 52% had a stable plaque. Myocardial hypertrophy was present in 78% and myocardial fibrosis in 93% of victims. The presence of myocardial hypertrophy or fibrosis was not associated with specific plaque histology. Conclusions: Less than half of sudden deaths due to CAD had evidence of acute plaque complication, an observation which is contrary to historical perceptions. The prevalence of concomitant myocardial disease was high and independent of associated plaque morphology