Juhani Junttila

Sudden cardiac death during physical exercise: Characteristics of victims and autopsy findings

Abstract Objective. To provide data on the risk factors and characteristics of subjects who experience sudden cardiac death (SCD) during physical exercise. Methods and results. We assessed the characteristics and the medico-legal autopsy findings of SCD victims who had experienced a witnessed fatal cardiac arrest at rest (n = 876) or in relation to physical exercise (n = 328) in the Finnish Study of Genotype and Phenotype Characteristics of SCD (FinGesture). A total of 876 (73%) witnessed SCDs occurred at rest (R group) and 328 (27%) during or immediately after physical exercise (PE group). Male gender was more common in the PE group compared to the R group (309/328, 94% versus 678/876, 77%, P < 0.001). Coronary artery disease was a more common structural heart disease than non-ischemic disease at autopsy when SCD was exercise-triggered (299/328, 91% versus 657/876, 75%, P < 0.001). Myocardial scarring and cardiac hypertrophy were more commonly found at autopsy in the PE group (194/328, 59% versus 370/876, 42%, P < 0.001; 243/328, 74% versus 585/876, 67%, P = 0.012, respectively). Skiing, cycling, and snow shoveling were the most common modes of exercise at the time of SCD. Conclusions. SCD during or immediately after exercise is related to male gender, ischemic heart disease, cardiac hypertrophy, and myocardial scarring.

Association of the beta-1 adrenergic receptor carboxyl terminal variants with left ventricular hypertrophy among diabetic and non-diabetic survivors of acute myocardial infarction

BackgroundThe beta-1 adrenergic receptor (β1AR) plays a fundamental role in the regulation of cardiovascular functions. It carries a nonsynonymous single nucleotide polymorphism in its carboxyl terminal tail (Arg389Gly), which has been shown to associate with various echocardiographic parameters linked to left ventricular hypertrophy (LVH). Diabetes mellitus (DM), on the other hand, represents a risk factor for LVH. We investigated the possible association between the Arg389Gly polymorphism and LVH among non-diabetic and diabetic acute myocardial infarction (AMI) survivors.MethodsThe study population consisted of 452 AMI survivors, 20.6% of whom had diagnosed DM. Left ventricular parameters were measured with two-dimensional guided M-mode echocardiography 2-7 days after AMI, and the Arg389Gly polymorphism was determined using a polymerase chain reaction-restriction fragment length polymorphism assay.ResultsThe Arg389 homozygotes in the whole study population had a significantly increased left ventricular mass index (LVMI) when compared to the Gly389 carriers (either Gly389 homozygotes or Arg389/Gly389 heterozygotes) [62.7 vs. 58.4, respectively (p = 0.023)]. In particular, the Arg389 homozygotes displayed thicker diastolic interventricular septal (IVSd) measures when compared to the Gly389 carriers [13.2 vs. 12.3 mm, respectively (p = 0.004)]. When the euglycemic and diabetic patients were analyzed separately, the latter had significantly increased LVMI and diastolic left ventricular posterior wall (LVPWd) values compared to the euglycemic patients [LVMI = 69.1 vs. 58.8 (p = 0.001) and LVPWd = 14.2 vs. 12.3 mm (p < 0.001), respectively]. Furthermore, among the euglycemic patients, the Arg389 homozygotes displayed increased LVMI and IVSd values compared to the Gly389 carriers [LVMI = 60.6 vs. 56.3, respectively (p = 0.028) and IVSd = 13.1 vs. 12.0 mm, respectively (p = 0.001)]. There was no difference in the LVMI and IVSd values between the diabetic Arg389 homozygotes and Gly389 carriers.ConclusionsThe data suggest an association between the β1AR Arg389Gly polymorphism and LVH, particularly the septal hypertrophy. The Arg389 variant appears to confer a higher risk of developing LVH than the corresponding Gly389 variant among patients who have suffered AMI. This association cannot be considered to be universal, however, since it does not appear to exist among diabetic AMI survivors.

Association of sST2 and hs-CRP levels with new-onset atrial fibrillation in coronary artery disease

BACKGROUND The data on biomarkers as predictors of atrial fibrillation (AF) in patients with coronary artery disease (CAD) are limited. METHODS A total of 1946 patients with CAD were recruited to the ARTEMIS study. At baseline, the study patients underwent clinical and echocardiographic examinations and had laboratory tests. The patients (n=1710) with the information about the occurrence of new-onset AF during the follow-up were included in the present analysis. RESULTS During 5.7±1.5years of follow-up, 143 (8.4%) patients developed a new-onset AF. Higher values of soluble ST2 (sST2) (20.2±10.8 vs. 17.5±7.2ng/mL, p=0.005), high-sensitivity troponin T (hs-TnT) (11.9±10.2 vs. 10.3±8.3ng/L, p=0.005), high-sensitivity C-reactive protein (hs-CRP) (3.3±5.9 vs. 2.0±4.4mg/L, p<0.001) and brain natriuretic peptide (BNP) (85.6±77.5 vs. 64.9±73.5ng/L, p<0.001) had significant associations with the occurrence of new-onset AF. In the Cox clinical hazards model, higher age (p=0.004), greater weight (p=0.045), larger left atrial diameter (p=0.001), use of asthma/chronic obstructive pulmonary disease medication (p=0.001) and lack of cholesterol lowering medication (p=0.008) had a significant association with the increased risk of AF. When the biomarkers were tested in the Cox clinical hazards model, sST2 (HR=1.025, 95% CI=1.007-1.043, p=0.006) and hs-CRP (HR=1.027, 95% CI=1.008-1.047, p=0.006) retained their significant power in predicting AF. CONCLUSION A biomarker of fibrosis, sST2, and a biomarker of inflammation, hs-CRP, predict the risk of occurrence of new-onset AF in patients with CAD. These biomarkers contributed to the discrimination of the AF risk model, but did not improve it markedly.

Blood alcohol in victims of sudden cardiac death in northern Finland

AIMS Momentary intake of large quantity of alcohol provokes ventricular ectopic activity increasing electrical instability. The present study was aimed to assess the prevalence of alcohol intake prior to a sudden cardiac death (SCD) event. METHODS AND RESULTS Victims of unexpected SCD [n = 2363, age 61 ± 12 years, males 1940 (82%)] included in the Finnish study of genotype and phenotype profiles of SCD (FINGESTURE) had a thorough interview of family members, medico-legal autopsy, and determination of blood alcohol concentration. Because of the Finnish law, all unexpected deaths undergo medico-legal autopsy. Patients who were admitted to a hospital due to an acute myocardial infarction [n = 128, age 63 ± 10 years, males 100 (78%)] served as controls. Based on autopsy findings, 1691 of these victims had ischaemic heart disease (IHD) and were included in the present analysis. A total of 646 (38%) SCD victims with IHD had a blood ethanol concentration above 0‰. Of these victims with blood alcohol test positive, 41% (n = 264) had blood ethanol concentration ≥1.5‰ and 56% (n = 362) ≥1‰. Male SCD victims had more frequently alcohol in blood than the females (40 vs. 27%, P < 0.001, respectively). None of the controls, who gave a consent for the blood ethanol concentration determination (n = 88), had alcohol in blood. Of the controls, 40 (31%) declined to participate in the study and give the consent for blood alcohol testing. CONCLUSION Almost 4 of 10 of the victims of unexpected SCD have evidence of alcohol intake before the fatal event in the northern Finland autopsy population.

Heart Rate Turbulence and T-Wave Alternans in Patients with Coronary Artery Disease: The Influence of Diabetes.

Patients with diabetes mellitus (DM) have a higher risk of sudden cardiac death. Factors associated with the risk profiles of coronary artery disease (CAD) patients with DM are not well established. Heart rate turbulence (HRT) and T‐wave alternans (TWA) are often used to predict arrhythmia events.

Leptin predicts short-term major adverse cardiac events in patients with coronary artery disease

Abstract Introduction: Leptin is an adipose tissue-derived hormone associated with cardiovascular risk factors. We examined whether leptin predicts major adverse cardiac events (MACE) in coronary artery disease (CAD) patients. Methods: Fasting plasma leptin levels were measured in 1327 male and 619 female CAD patients. The patients were followed up for two years. The primary endpoint (MACE) was the composite of a hospitalisation for congestive heart failure (CHF) or a cardiac death. The secondary endpoint was the composite of an acute coronary syndrome (ACS) or a stroke. Results: In regression analysis including established risk variables, high leptin levels were associated with a significantly increased risk of MACE (HR 3.37; 95%CI 1.64–6.90; p = 0.001) and ACS or stroke (HR 1.95; 95%CI 1.29–2.96; p = 0.002). Adding leptin to the risk model for MACE increased the C-index from 0.78 (95%CI 0.71–0.85) to 0.81 (0.74–0.88) and improved classification (NRI 0.36; 95%CI 0.13–0.60; p = 0.002) and discrimination of the patients (IDI 0.016; 95%CI 0.001–0.030; p = 0.031). Conclusions: High plasma leptin levels predict short-term occurrence of CHF or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible harmful effects of leptin should be thoroughly investigated. Key messages Leptin is a peptide hormone secreted mainly by adipose tissue. It has been associated with several cardiovascular risk factors. High leptin levels predict the short-term occurrence of congestive heart failure or cardiac death and ACS or stroke in patients with CAD independently of established risk factors. The possible detrimental effects of leptin on the cardiovascular system should be thoroughly investigated.

Novel 6p21.3 Risk Haplotype Predisposes to Acute Coronary Syndrome

Background—The HLA-DRB1*01 allele of the human leukocyte antigen has been associated with acute coronary syndrome. Genome-wide association studies have revealed associations with human leukocyte antigen and non–human leukocyte antigen genes of 3 major histocompatibility complex gene classes but not at allelic level. Methods and Results—We conducted a large-scale genetic analysis on a case–control cohort comprising 5376 acute coronary syndrome cases and 4852 unrelated controls from 4 populations of 2 European countries. We analyzed the risk candidate allele of HLA-DRB1*01 by genomic real-time polymerase chain reaction together with high-density single nucleotide polymorphisms of the major histocompatibility complex to precisely identify risk loci for acute coronary syndrome with effective clinical implications. We found a risk haplotype for the disease containing single nucleotide polymorphisms from BTNL2 and HLA-DRA genes and the HLA-DRB1*01 allele. The association of the haplotype appeared in 3 of the 4 populations, and the direction of the effect was consistent in the fourth. Coronary samples from subjects homozygous for the disease-associated haplotype showed higher BTNL2 mRNA levels (r=0.760; P<0.00001).We localized, with immunofluorescence staining, BTNL2 in CD68-positive macrophages of the coronary artery plaques. In homozygous cases, BTNL2 blocking, in T-cell stimulation assays, enhanced CD4+FOXP3+ regulatory T cell proliferation significantly (blocking versus nonblocking; P<0.05). Conclusions—In cases with the risk haplotype for acute coronary syndrome, these results suggest involvement of enhanced immune reactions. BTNL2 may have an inhibitory effect on FOXP3+ T cell proliferation, especially in patients homozygous for the risk alleles. Clinical Trial Registration—https://www.clinicaltrials.gov; Unique Identifier: NCT00417534.

Response to Letter from Barra et al Based on “Association of Early Repolarization and Sudden Cardiac Death During an Acute Coronary Event” by Tikkanen et al

We thank Dr Barra and his colleagues for their interest and comments about our study,1 which presented an association between early repolarization pattern (ERP) and sudden cardiac death during an acute coronary event. We concur with the authors on several topics with minor viewpoint divergences. First, the authors of the letter point out the differences between the studied groups. This is obviously a regrettable downside of the nature of our observational cross-sectional study. We did recognize this limitation, and therefore performed additional analyses with subjects without documented coronary artery disease or prior coronary event. Within these subjects, the results remained essentially the same. However, as the authors of the letter state, it is true that a reliable comparison would require less preventive treatment in the control group. In their letter, Barra and colleagues next discuss the possibility of peri-infarction block and remote myocardial scarring underlying …

Electrocardiogram as a predictor of sudden cardiac death in middle-aged subjects without a known cardiac disease

Background Abnormal 12‑lead electrocardiogram (ECG) findings and proposing its ability for enhanced risk prediction, majority of the studies have been carried out with elderly populations with prior cardiovascular diseases. This study aims to denote the association of sudden cardiac death (SCD) and various abnormal ECG morphologies using middle-aged population without a known cardiac disease. Methods In total, 9511 middle-aged subjects (mean age 42 ± 8.2 years, 52% males) without a known cardiac disease were included in this study. Risk for SCD was assessed after 10 and 30-years of follow-up. Results Abnormal ECG was present in 16.3% (N = 1548) of subjects. The incidence of SCD was distinctly higher among those with any ECG abnormality in 10 and 30-year follow-ups (1.7/1000 years vs. 0.6/1000 years, P < 0.001; 3.4/1000 years vs. 1.9/1000 years, P < 0.001). At 10-year point, competing risk multivariate regression model showed HR of 1.62 (95% CI 1.0–2.6, P = 0.05) for SCD in subjects with abnormal ECG. QRS duration ≥ 110 ms, QRST-angle > 100°, left ventricular hypertrophy, and T-wave inversions were the most significant independent ECG risk markers for 10-year SCD prediction with up to 3-fold risk for SCD. Those with ECG abnormalities had a 1.3-fold risk (95% CI 1.07–1.57, P = 0.007) for SCD in 30-year follow-up, whereas QRST-angle > 100°, LVH, ER ≥ 0.1 mV and ≥0.2 mV were the strongest individual predictors. Subjects with multiple ECG abnormalities had up to 6.6-fold risk for SCD (P < 0.001). Conclusion Several ECG abnormalities are associated with the occurrence of early and late SCD events in the middle-age subjects without known history of cardiac disease.

High-sensitivity troponin predicts coronary disease outcomes in type 2 diabetes but yields no benefit in selecting patients for revascularisation

Commentary on: Everett BM, Brooks MM, Vlachos HE, et al., BARI 2D Study Group. Troponin and cardiac events in stable ischemic heart disease and diabetes. N Engl J Med 2015;373:610–20.[OpenUrl][1][CrossRef][2][PubMed][3] High-sensitivity troponin (hs-TnT) assays have been developed for early recognition of patients with acute coronary syndrome (ACS). Additionally, hs-TnT has been shown to be a feasible tool for assessing risk among patients with heart failure. Even though efforts have been made to improve prognosis among patients with coronary artery disease (CAD) with high-risk features, most adverse events occur in patients without these features. Therefore, novel risk markers for ‘intermediate risk’ participants are needed. Recent evidence presents hs-TnT as a promising marker for adverse events among patients with stable CAD.1 ,2 The pathophysiological background for these findings and therapeutic … [1]: {openurl}?query=rft.jtitle%253DN%2BEngl%2BJ%2BMed%26rft.volume%253D373%26rft.spage%253D610%26rft_id%253Dinfo%253Adoi%252F10.1056%252FNEJMoa1415921%26rft_id%253Dinfo%253Apmid%252F26267622%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1056/NEJMoa1415921&link_type=DOI [3]: /lookup/external-ref?access_num=26267622&link_type=MED&atom=%2Febmed%2F21%2F3%2F100.atom