Heart Rate Variability and Dispersion of QT Interval in Patients With Vulnerability to Ventricular Tachycardia and Ventricular Fibrillation After Previous Myocardial Infarction

Objectives. This study was designed to compare QT dispersion measured from the standard 12-lead electrocardiogram and 24-h heart rate variability in patients with vulnerability to either ventricular tachycardia or ventricular fibrillation after a previous myocardial infarction. Background. Increased QT interval dispersion and reduced heart rate variability have been shown to be associated with vulnerability to ventricular tachyarrhythmias, but the data have mainly been pooled from patients with presentation of stable ventricular tachycardia and ventricular fibrillation. Methods. QT dispersion and time domain and two-dimensional vector analysis of heart rate variability were studied in 30 survivors of ventricular fibrillation with a previous myocardial infarction and with inducible unstable ventricular tachyarrhythmia by programmed electrical stimulation and in 30 postinfarction patients with clinical and inducible stable monomorphic sustained ventricular tachycardia. Both of these patient groups were matched, with respect to age, gender and left ventricular ejection fraction, with an equal number of postinfarction control patients without a history of arrhythmic events or inducible ventricular tachyarrhythmia and arrhythmia-free survival during a follow-up period of 2 years. Forty-five age-matched healthy subjects served as normal control subjects. Results. Standard deviation of all sinus intervals and long-term continuous RR interval variability analyzed from Poincaré plots were reduced in patients with vulnerability to ventricular fibrillation (p < 0.001 for both), but not in patients with ventricular tachycardia (p = NS for both), compared with postinfarction control subjects. Corrected QT (QTc) dispersion was significantly broader both in patients with ventricular fibrillation (p < 0.001) and in those with ventricular tachycardia (p < 0.05) than in matched postinfarction control subjects. Heart rate variability performed better than QTc dispersion in predicting vulnerability to ventricular fibrillation. Conclusions. Increased QT dispersion is associated with vulnerability to both ventricular tachycardia and ventricular fibrillation. Low heart rate variability is specifically related to susceptibility to ventricular fibrillation but not to stable monomorphic ventricular tachycardia, suggesting that the autonomic nervous system modifies the presentation of life-threatening ventricular arrhythmias

Cardiac remodeling from middle age to senescence

Abstract Background: The data on cardiac remodeling outside the scope of myocardial infarction and heart failure are limited. Methods: A cohort of middle-aged hypertensive subjects with age- and gender-matched control subjects without hypertension (n = 1,045, aged 51 ± 6 years) were randomly selected for the OPERA study (Oulu Project Elucidating Risk of Atherosclerosis study). The majority of those who were still alive after more than 20 years of follow-up underwent thorough re-examinations. Results: Left ventricular mass index (LVMI) increased significantly from 106.5 ± 27.1 (mean ± SD) to 114.6 ± 29.1 g/m² (p &lt; 0.001), the thickness of the left ventricular posterior wall (LVPW) from 10.0 ± 1.8 to 10.6 ± 1.7 mm (p &lt; 0.001), fractional shortening (FS) from 35.0 ± 5.7 to 38.4 ± 7.2 % (p &lt; 0.001), and left atrial diameter (LAD) from 38.8 ± 5.2 to 39.4 ± 6.7 mm (p = 0.028) during the 20-year follow-up. After multivariate adjustments, hypertension treated with antihypertensive medication and male gender predicted a smaller increase in the thickness of LVPW (p = 0.017 to &lt;0.001). Baseline higher fasting plasma insulin level, larger intima media thickness of the carotid artery, greater height and antihypertensive medication (p = 0.046–0.002) predicted a smaller (less favorable) change of FS. The increase of LAD was associated with higher baseline diastolic blood pressure (p = 0.034) and greater height (p = 0.006). Conclusion: Aging from middle age to senescence increases the echocardiographic indexes of LVMI, LVPW thickness, FS and LAD. Several baseline factors are associated with these changes

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

Association between birth characteristics and cardiovascular autonomic function at mid-life

Abstract Background: Low birth weight is associated with an increased risk of cardiovascular diseases in adulthood. As abnormal cardiac autonomic function is a common feature in cardiovascular diseases, we tested the hypothesis that low birth weight may also be associated with poorer cardiac autonomic function in middle-aged subjects. Methods: At the age of 46, the subjects of the Northern Finland Birth Cohort 1966 were invited to examinations including questionnaires about health status and life style and measurement of vagally-mediated heart rate variability (rMSSD) from R-R intervals (RRi) and spontaneous baroreflex sensitivity (BRS) in both seated and standing positions. Maternal parameters had been collected in 1965–1966 since the 16th gestational week and birth variables immediately after delivery. For rMSSD, 1,799 men and 2,279 women without cardiorespiratory diseases and diabetes were included and 902 men and 1,020 women for BRS. The analyses were adjusted for maternal (age, anthropometry, socioeconomics, parity, gestational smoking) and adult variables (life style, anthropometry, blood pressure, glycemic and lipid status) potentially confounding the relationship between birth weight and autonomic function. Results: In men, birth weight correlated negatively with seated (r = -0.058, p = 0.014) and standing rMSSD (r = -0.090, p&lt;0.001), as well as with standing BRS (r = -0.092, p = 0.006). These observations were verified using relevant birth weight categories (&lt;2,500 g; 2,500–3,999 g; ≥4,000 g). In women, birth weight was positively correlated with seated BRS (r = 0.081, p = 0.010), but none of the other measures of cardiovascular autonomic function. These correlations remained significant after adjustment for potential confounders (p&lt;0.05 for all). Conclusions: In men, higher birth weight was independently associated with poorer cardiac autonomic function at mid-life. Same association was not observed in women. Our findings suggest that higher, not lower, birth weight in males may contribute to less favourable cardiovascular autonomic regulation and potentially to an elevated cardiovascular risk in later life

Association of non-shockable initial rhythm and psychotropic medication in sudden cardiac arrest

Abstract Background: Asystole (ASY) and pulseless electrical activity (PEA) have a poor outcome during sudden cardiac arrest (SCA). Psychotropic medication has been associated with a risk for sudden cardiac death (SCD). Our aim was to study the association of psychotropic medication with ASY/PEA during SCA. Methods and results: A total of 659 SCA subjects were derived from the emergency data of Oulu University Hospital (2007–2012). Subjects with non-cardiac origin of SCA and over 30-minute delay to rhythm recording were excluded. Population included 222 subjects after exclusions (mean age 64 ± 14 years, 78% males). Initial rhythm was ventricular fibrillation (VF) or ventricular tachycardia (VT) in 123 (55%), ASY in 67 (30%) and PEA in 32 (14%) subjects. The delay (collapse to rhythm recording) was similar in VF/VT and ASY/PEA subjects (median 8 min [1st–3rd quartile 3–12 min] versus 10 [0–14] minutes, p = 0.780). Among VF/VT subjects underlying cardiac disease was more often ischemic compared to ASY/PEA subjects (85% versus 68%, p = 0.003). Psychotropic medication was associated with ASY/PEA rhythm (OR 3.18, 95%CI 1.40–7.23, p = 0.006) after adjustment for gender, age and underlying cardiac disease. Subsequently, antipsychotics (OR 4.27, 95%CI 1.28–14.25, p = 0.018) were more common in the ASY/PEA group. Benzodiazepines and antidepressants were not associated with ASY/PEA. Conclusion: Psychotropic medication and especially antipsychotics are associated with non-shockable rhythm during SCA and may lower the possibility of survival from the event. This might partly explain the risk of SCD related to psychotropic medication

Genetic contributions to the expression of acquired causes of cardiac hypertrophy in non-ischemic sudden cardiac death victims

AbstractThe contribution of genetic variants to non-ischemic sudden cardiac death (SCD) due to acquired myocardial diseases is unclear. We studied whether SCD victims with hypertension/obesity related hypertrophic myocardial disease harbor potentially disease associated gene variants. The Fingesture study has collected data from 5869 autopsy-verified SCD victims in Northern Finland. Among SCD victims, 740 (13%) had hypertension and/or obesity as the most likely explanation for myocardial disease with hypertrophy and fibrosis. We performed next generation sequencing using a panel of 174 cardiac genes for 151 such victims with the best quality of DNA. We used 48 patients with hypertension and hypertrophic heart as controls. Likely pathogenic variants were identified in 15 SCD victims (10%) and variants of uncertain significance (VUS) were observed in additional 43 SCD victims (28%). In controls, likely pathogenic variants were present in two subjects (4%; p = 0.21) and VUSs in 12 subjects (25%; p = 0.64). Among SCD victims, presence of potentially disease-related variants was associated with lower mean BMI and heart weight. Potentially disease related gene variants are common in non-ischemic SCD but further studies are required to determine specific contribution of rare genetic variants to the extent of acquired myocardial diseases leading to 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

Genetic variants associated with sudden cardiac death in victims with single vessel coronary artery disease and left ventricular hypertrophy with or without fibrosis

Abstract Objective: Cardiac hypertrophy with varying degrees of myocardial fibrosis is commonly associated with coronary artery disease (CAD) related sudden cardiac death (SCD), especially in young victims among whom patterns of coronary artery lesions do not entirely appear to explain the cause of SCD. Our aim was to study the genetic background of hypertrophy, with or without fibrosis, among ischemic SCD victims with single vessel CAD. Methods: The study population was derived from the Fingesture study, consisting of all autopsy-verified SCDs in Northern Finland between the years 1998 and 2017 (n = 5,869). We carried out targeted next-generation sequencing using a panel of 174 genes associated with myocardial structure and ion channel function in 95 ischemic-SCD victims (mean age 63.6 ± 10.3 years; 88.4% males) with single-vessel CAD in the absence of previously diagnosed CAD and cardiac hypertrophy with or without myocardial fibrosis at autopsy. Results: A total of 42 rare variants were detected in 43 subjects (45.3% of the study subjects). Five variants in eight subjects (8.4%) were classified as pathogenic or likely pathogenic. We observed 37 variants of uncertain significance in 39 subjects (40.6%). Variants were detected in myocardial structure protein coding genes, associated with arrhythmogenic right ventricular, dilated, hypertrophic and left ventricular non-compaction cardiomyopathies. Also, variants were detected in ryanodine receptor 2 (RYR2), a gene associated with both cardiomyopathies and catecholaminergic polymorphic ventricular tachycardias. Conclusions: Rare variants associated with cardiomyopathies, in the absence of anatomic evidence of the specific inherited cardiomyopathies, were common findings among CAD-related SCD victims with single vessel disease and myocardial hypertrophy found at autopsies, suggesting that these variants may modulate the risk for fatal arrhythmias and SCD in ischemic disease

Genetic contributions to the expression of acquired causes of cardiac hypertrophy in non-ischemic sudden cardiac death victims

Abstract The contribution of genetic variants to non-ischemic sudden cardiac death (SCD) due to acquired myocardial diseases is unclear. We studied whether SCD victims with hypertension/obesity related hypertrophic myocardial disease harbor potentially disease associated gene variants. The Fingesture study has collected data from 5869 autopsy-verified SCD victims in Northern Finland. Among SCD victims, 740 (13%) had hypertension and/or obesity as the most likely explanation for myocardial disease with hypertrophy and fibrosis. We performed next generation sequencing using a panel of 174 cardiac genes for 151 such victims with the best quality of DNA. We used 48 patients with hypertension and hypertrophic heart as controls. Likely pathogenic variants were identified in 15 SCD victims (10%) and variants of uncertain significance (VUS) were observed in additional 43 SCD victims (28%). In controls, likely pathogenic variants were present in two subjects (4%; p = 0.21) and VUSs in 12 subjects (25%; p = 0.64). Among SCD victims, presence of potentially disease-related variants was associated with lower mean BMI and heart weight. Potentially disease related gene variants are common in non-ischemic SCD but further studies are required to determine specific contribution of rare genetic variants to the extent of acquired myocardial diseases leading to SCD

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