Novel Genetic Variants Associated with Primary Myocardial Fibrosis in Sudden Cardiac Death Victims.

Myocardial fibrosis is a common finding in victims of sudden cardiac death (SCD). Whole exome sequencing was performed in 127 victims of SCD with primary myocardial fibrosis as the only pathological finding. These cases are derived from the Fingesture study which has collected data from autopsy-verified SCD victims in Northern Finland. A computational approach was used to identify protein interactions in cardiomyocytes. Associations of the identified variants with cardiac disease endpoints were investigated in the Finnish national genetic study (FinnGen) dataset. We identified 21 missense and one nonsense variant. Four variants were estimated to affect protein function, significantly associated with SCD/primary myocardial fibrosis (Fingesture) and associated with cardiac diseases in Finnish population (FinnGen). These variants locate in cartilage acidic protein 1 (CRATC1), calpain 1 (CAPN1), unc-45 myosin chaperone A (UNC45A) and unc-45 myosin chaperone B (UNC45B). The variants identified contribute to function of extracellular matrix and cardiomyocytes.

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

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. CONCLUSION: 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.

Long-term cardiac surveillance and outcomes of COVID-19 patients.

Acute cardiac manifestions of COVID-19 have been well described, while chronic cardiac sequelae remain less clear. Various studies have shown conflicting data on the prevalence of new or worsening cardiovascular disease, myocarditis or cardiac dysrhythmias among patients recovered from COVID-19. Data are emerging that show that patients recovering from COVID-19 have an increased incidence of myocarditis and arrhythmias after recovery from COVID-19 compared with the control groups without COVID-19. The incidence of myocarditis after COVID-19 infection is low but is still significantly greater than the incidence of myocarditis from a COVID-19 vaccine. There have been several studies of athletes who underwent a variety of screening protocols prior to being cleared to return to exercise and competition. The data show possible, probable or definite myocarditis or cardiac injury among 0.4-3.0% of the athletes studied. Recent consensus statements suggest that athletes with full recovery and absence of cardiopulmonary symptoms may return to exercise and competition without cardiovascular testing. In conclusion, patients with COVID-19 may be expected to have an increased risk of cardiovascular disease, myocarditis or arrhythmias during the convalescent phase. Fortunately, the majority of patients, including athletes may return to their normal activity after recovery from COVID 19, in the absence of persisting cardiovascular symptoms.

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.

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

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.

Association of SGLT2 inhibitors with arrhythmias and sudden cardiac death in patients with type 2 diabetes or heart failure: A meta-analysis of 34 randomized controlled trials.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce hospitalizations and death from heart failure (HF), but their effect on arrhythmia expression has been poorly investigated. OBJECTIVE: The purpose of this study was to evaluate the association of SGLT2is with arrhythmias in patients with type 2 diabetes mellitus (T2DM) or HF. METHODS: We searched PubMed and ClinicalTrials.gov. Two independent investigators identified randomized double-blind trials that compared SGLT2is with placebo or active control for adults with T2DM or HF. Primary outcomes were incident atrial arrhythmias, ventricular arrhythmias (VAs), and sudden cardiac death (SCD). RESULTS: We included 34 randomized (25 placebo-controlled and 9 active-controlled) trials with 63,166 patients (35,883 SGLT2is vs 27,273 control: mean age 53-67 years; 63% male). Medications included canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin. Except for 1 study of HF, all patients had T2DM. Follow-up ranged from 24 weeks to 5.7 years. The cumulative incidence of events was low: 3.6, 1.4, and 2.5 per 1000 patient-years for atrial arrhythmias, VAs and SCD, respectively. SGLT2i therapy was associated with a significant reduction in the risk of incident atrial arrhythmias (odds ratio 0.81; 95% confidence interval 0.69-0.95; P = .008) and the "SCD" component of the SCD outcome (odds ratio 0.72; 95% confidence interval 0.54-0.97; P = .03) compared with control. There was no significant difference in incident VA or the "cardiac arrest" SCD component between groups. CONCLUSION: SGLT2is are associated with significantly reduced risks of incident atrial arrhythmias and SCD in patients with T2DM. Prospective trials are warranted to confirm the antiarrhythmic effect of SGLT2is and whether this is a class or drug-specific effect.

Genetic Variants Associated With Sudden Cardiac Death in Victims With Single Vessel Coronary Artery Disease and Left Ventricular Hypertrophy With or Without Fibrosis.

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.

Osteopontin and LDLR Are Upregulated in Hearts of Sudden Cardiac Death Victims With Heart Failure With Preserved Ejection Fraction and Diabetes Mellitus.

Background: Diabetes mellitus (DM) is associated with increased risk of sudden cardiac death (SCD), particularly in patients with heart failure with preserved ejection fraction (HFpEF). However, there are no known biomarkers in the population with DM and HFpEF to predict SCD risk. Objectives: This study was designed to test the hypothesis that osteopontin (OPN) and some proteins previously correlated with OPN, low-density lipoprotein receptor (LDLR), dynamin 2 (DNM2), fibronectin-1 (FN1), and 2-oxoglutarate dehydrogenase-like (OGDHL), are potential risk markers for SCD, and may reflect modifiable molecular pathways in patients with DM and HFpEF. Methods: Heart tissues were obtained at autopsy from 9 SCD victims with DM and HFpEF and 10 age and gender-matched accidental death control subjects from a Finnish SCD registry and analyzed for the expression of OPN and correlated proteins, including LDLR, DNM2, FN1, and OGDHL by immunohistochemistry. Results: We observed a significant upregulation in the expression of OPN, LDLR, and FN1, and a marked downregulation of DNM2 in heart tissues of SCD victims with DM and HFpEF as compared to control subjects (p < 0.01). Conclusions: The dysregulated protein expression of OPN, LDLR, FN1, and DNM2 in patients with DM and HFpEF who experienced SCD provides novel potential modifiable molecular pathways that may be implicated in the pathogenesis of SCD in these patients. Since secreted OPN and soluble LDLR can be measured in plasma, these results support the value of further prospective studies to assess the predictive value of these plasma biomarkers and to determine whether tuning expression levels of OPN and LDLR alters SCD risk in patients with DM and HFpEF.

Network meta-analysis of His bundle, biventricular, or right ventricular pacing as a primary strategy for advanced atrioventricular conduction disease with normal or mildly reduced ejection fraction.

INTRODUCTION: Although right ventricular pacing (RVP) may impair ventricular function, it is commonly used for advanced atrioventricular block (AVB) and normal or mildly reduced ejection fraction (EF). We aimed to compare His bundle pacing (HBP), biventricular pacing (BiVP), and RVP for advanced AVB in patients with normal or mildly reduced EF. METHODS AND RESULTS: MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials.gov, Scopus, and Web of Science were searched. Outcomes were all-cause death, heart failure hospitalizations (HFH), EF, left ventricular volumes, 6-minute walk test, and QRS duration. HBP or BiVP was compared with RVP. Subsequently, network meta-analysis compared the three pacing options. Our protocol was registered in PROSPERO (CRD42018094132). Six studies compared BiVP and RVP (704 vs 614 patients) and four compared HBP and RVP (463 vs 568 patients). Follow-up was 6 months to 5 years. There was significantly lower mortality and HFH with HBP or BiVP as compared with RVP (odds ratio [OR], 0.66, [0.51-0.85], P = .002; OR, 0.61 [0.45-0.82], P < .001, respectively]. HBP or BiVP also showed significant increase in EF and decrease in QRS duration (mean difference [MD], 5.27 [3.86-6.69], P < .001; MD -42.2 [-51.2 to -33.3], P < .001, respectively). In network meta-analysis, HBP and BiVP were associated with significantly improved survival compared to RVP, with surface under the cumulative ranking curve (SUCRA) probability of 79.4%, 69.4%, and 1.2% for HBP, BiVP, and RVP, respectively. For HFH, SUCRA probability was 91.5%, 57.2%, and 1.3%, respectively. CONCLUSION: HBP or BiVP were the superior strategies to reduce all-cause death and HFH for advanced AVB with normal or mildly reduced EF, with no significant difference between BiVP and HBP.

Electrocardiographic associations with myocardial fibrosis among sudden cardiac death victims.

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<0.001, ß=0.153). Prevalence of fragmented QRS complex, pathological Q waves and T wave inversions correlated with increased degree of fibrosis (p<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<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.

Genetic determinants of responsiveness to mesenchymal stem cell injections in non-ischemic dilated cardiomyopathy.

BACKGROUND: Non-ischemic dilated cardiomyopathy (NIDCM) responds variably to intramyocardial injection of mesenchymal stem cells (MSCs). We hypothesized that NIDCM genotype may influence responsiveness to MSC therapy and performed genotyping on all patients in the POSEIDON-DCM trial. METHODS: POSEIDON-DCM patients (n = 34) underwent genetic sequence analysis and deletion/duplication testing. The results were classified as positive for pathological variants (PV+; n = 8), negative for any variants (V-; n = 6), or as variants of uncertain significance (VUS; n = 20). All outcomes of therapy were analysed for each category of genetic results. FINDINGS: The 3 groups were indistinguishable at baseline with regard to ejection fraction (EF), demographics, medication use, or functional parameters. V- patients had an increase in EF at 12 months: +13.6% (IQR = +7.8%; +20.5%; p = 0.002), compared with VUS (+6.5%; IQR = +0.9%, +11.1%; p = 0.005) and PV+(-5.9%; IQR = -12.7%, +1.0; p = 0.2; p = 0.01 between groups). Six-minute walk distance improved in V- patients, but not in VUS and PV+. V- patients improved MLHFQ, compared to the other 2 groups, which did not improve over time. EPCCFUs increased by 9.7 ±â€¯1.9 in V- (p = 0.009) compared to VUS and PV+ patients. V- patients had one-year survival (100%) compared with VUS (85%) and PV+ (40%; p = 0.015 log-rank). Similarly, MACE rates were lower in V- (0%) than PV+ (61.9%) or VUS (42.2%; p = 0.021 log-rank). INTERPRETATION: Our findings support the concept that the genetic profile of NIDCM patients plays a role in responsiveness to MSC therapy, with V- patients more likely to benefit and the converse for PV+. This observation emphasizes the need for further genetic studies, because of important implications for the management of NIDCM syndromes.

A meta-analysis of arrhythmia endpoints in randomized controlled trials of transendocardial stem cell injections for chronic ischemic heart disease.

INTRODUCTION: The electrophysiologic impact of cell-based therapy on the injured myocardium remains highly controversial. We aimed to perform a meta-analysis of studies comparing arrhythmia burden following transendocardial stem cell therapy vs placebo in patients with chronic ischemic heart disease (CIHD). METHODS AND RESULTS: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched. No restriction of stem cell type was specified. The outcomes included sustained supraventricular or ventricular arrhythmias (VAs), sudden cardiac death (SCD), and resuscitated sudden cardiac arrest (SCA). Effect sizes were reported as odds ratio (OR) and 95% CI. Poisson regression was used to account for zero-events data. Twelve randomized trials that included 736 patients (384 in the cell therapy group and 352 in the placebo group) were analyzed. Six different cell types were used. Follow-up ranged from 6 to 12 months. There was a significant decrease in risk of SCD in the cell therapy group, (FE OR, 0.19 [0.04, 0.93]; P = .04). In subgroup analysis, there was a significantly lower risk of SCD or resuscitated SCA in the cell therapy group limited to studies that did not use skeletal myoblasts, (FE OR, 0.23 [0.06, 0.83]; P = .03). There was no significant difference in the incidence of sustained VA between groups (FE OR, 0.91 [0.47, 1.77]; P = .8), even after stratifying by cell type. There was no difference in supraventricular arrhythmias between groups. CONCLUSION: Nonskeletal myoblast transendocardial cell therapy was associated with a significantly lower risk of SCD or resuscitated SCA compared to control, with no proarrhythmic effects.

Association of Silent Myocardial Infarction and Sudden Cardiac Death.

Importance: Myocardial infarction in the absence of major or unrecognized symptoms are characterized as silent (SMI). The prevalence of SMI among individuals who experience sudden cardiac death (SCD), with or without concomitant electrocardiographic (ECG) changes, has not previously been described in detail from large studies to our knowledge. Objective: To determine the prevalence of SMI in individuals who experience SCD without a prior diagnosis of coronary artery disease (CAD) and to detect ECG abnormalities associated with SMI-associated SCD. Design, Setting, and Participants: This case-control study compared autopsy findings, clinical characteristics, and ECG markers associated with SMI in a consecutive cohort of individuals in the Finnish Genetic Study of Arrhythmic Events (Fingesture) study population who were verified to have had SCD. The Fingesture study consists of individuals who had autopsy-verified SCD in Northern Finland between 1998 and 2017. Individuals who had SCD with CAD and evidence of SMI were regarded as having had cases; those who had SCD with CAD without SMI were considered control participants. Analyses of ECG tests were carried out by investigators blinded to the SMI data. Data analysis was completed from October 2018 through November 2018. Main Outcomes and Measures: Silent MI was defined as a scar detected by macroscopic and microscopic evaluation of myocardium without previously diagnosed CAD. Clinical history was obtained from medical records, previously recorded ECGs, and a standardized questionnaire provided to the next of kin. The hypothesis tested was that SMI would be prevalent in the population who had had SCD with CAD, and it might be detected or suspected from findings on ECGs prior to death in many individuals. Results: A total of 5869 individuals were included (2459 males [78.8%]; mean [SD] age, 64.9 [12.4] years). The cause of SCD was CAD in 4392 individuals (74.8%), among whom 3122 had no history of previously diagnosed CAD. Two individuals were excluded owing to incomplete autopsy information. An ECG recorded prior to SCD was available in 438 individuals. Silent MI was detected in 1322 individuals (42.4%) who experienced SCD without a clinical history of CAD. The participants with SMI were older than participants without MI scarring (mean [SD] age, 66.9 [11.1] years; 65.5 [11.6] years; P < .001) and were more often men (1102 of 1322 [83.4%] vs 1357 of 1798 [75.5%]; P < .001). Heart weight was higher in participants with SMI (mean [SD] weight, 483 [109] g vs 438 [106] g; P < .001). In participants with SMI, SCD occurred more often during physical activity (241 of 1322 [18.2%] vs 223 of 1798 [12.4%]; P < .001). A prior ECG was abnormal in 125 of the 187 individuals (66.8%) who had SCD after SMI compared with 139 of 251 (55.4%) of those who had SCD without SMI (P = .02). Conclusions and Relevance: Many individuals who experienced SCD associated with CAD had a previously undetected MI at autopsy. Previous SMI was associated with myocardial hypertrophy and SCD during physical activity. Premortem ECGs in a subset with available data were abnormal in 67% of the individuals who had had a SCD after an SMI.

Usefulness of Single Nucleotide Polymorphisms as Predictors of Sudden Cardiac Death.

The pathophysiology of sudden cardiac death (SCD) remains incompletely understood. Genetic mutations can create a favorable substrate for SCD. Our aim is to evaluate the evidence of single nucleotide polymorphisms (SNPs) as predictors of SCD. We searched the Medline database (2000 to 2017) and selected all case-control or cohort studies that reported associations between SNPs and SCD. Our search terms included "polymorphisms" and "sudden death." We collected the study design, population ethnic background, gene testing strategy, the association between the SNP and SCD, and the cardiovascular comorbidities of the population. Our search yielded 723 studies, of which we included 24 based upon our inclusion criteria. The studies had a total population of 78,165 participants, with a median age of 62.5 years (IQR 56 to 66) and 35% (IQR 13 to 32) were female. Almost all studies were conducted in white patients of European descent and the most commonly used genetic strategy was candidate gene panels. Fifteen of the studies had a case-control design that included SCD patients without known heart disease as the comparison group and the other 9 studies included patients with heart failure and coronary artery disease. The studies evaluated 53 SNPs and the most common genetic loci were SCN5A, RyR2, CASQ2, NOSA1P, and AGTR. SNPs with the 3 strongest statistically significant ORs >1 were: rs6684209 of CASQ2 (odds ratio [OR] 19), rs3814843 of CALM1 (OR 5.5), and rs35594137 of GJA5 (OR 3.6). In Conclusion, many SNPs are associated with SCD, with the strongest associations seen in SNPs of genes related to intracellular calcium handling. These findings were generated primarily using a candidate gene strategy in white patients with European descent.

Prediabetes and Risk for Cardiac Death Among Patients With Coronary Artery Disease: The ARTEMIS Study.

OBJECTIVE: To compare cardiac mortality in patients with CAD and prediabetes with that in CAD patients with normal glycemic status and type 2 diabetes. RESEARCH DESIGN AND METHODS: The Innovation to Reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study included patients with CAD after revascularization (79%), optimal medical therapy, or both. Patients had type 2 diabetes (n = 834), impaired glucose tolerance (IGT; n = 314), impaired fasting glucose (IFG; n = 103), or normal glycemic status (n = 697) as defined on the basis of the results of an oral glucose tolerance test. The primary end point was cardiac death. Major adverse cardiac event (MACE: cardiac death, heart failure, or acute coronary syndrome) and all-cause mortality were secondary end points. RESULTS: During a mean ± SD follow-up of 6.3 ± 1.6 years, 101 cardiac deaths, 385 MACEs, and 208 deaths occurred. Patients with IGT tended to have 49% lower adjusted risk for cardiac death (P = 0.069), 32% lower adjusted risk for all-cause mortality (P = 0.076), and 36% lower adjusted risk for MACE (P = 0.011) than patients with type 2 diabetes. The patients with IFG had 82% lower adjusted risk for all-cause mortality (P = 0.015) than the patients with type 2 diabetes, whereas risks for cardiac death and MACE did not differ significantly between the two groups. The adjusted risks for cardiac death, MACE, and all-cause mortality among patients with IGT and IFG did not significantly differ from those risks among patients with normal glycemic status. CONCLUSIONS: Cardiac mortality or incidence of MACE in patients with CAD with prediabetes (i.e., IGT or IFG after revascularization, optimal medical therapy, or both) does not differ from those values in patients with normal glycemic status.

Sudden Cardiac Death in Women.

BACKGROUND: Despite recent progress in profiling of risk for sudden cardiac death (SCD) and prevention and intervention of cardiac diseases, SCD remains a major cause of death. Among women, the incidence of SCD is significant, but lower than in men, particularly in the premenopausal and early postmenopausal years. Possibly, as a consequence of the difference in population burden, the mechanisms and risk markers of SCD are not as well defined for women. The aim of this study was to determine the autopsy findings and causes of death among women in a large SCD population. Additionally, we sought to classify prior ECG characteristics in male and female subjects with SCD. METHODS: The Fingesture study has systematically collected clinical and autopsy data from subjects with SCD in Northern Finland between 1998 and 2017. The cohort consists of 5869 subjects with SCD. Previously recorded ECGs were available and analyzed in 1101 subjects (18.8% of total population; and in 25.3% of women). RESULTS: Female subjects with SCD were significantly older than men: 70.1±13.1 years versus 63.5±11.8 years (mean ± standard deviation, P<0.001). The most frequently identified cause of death was ischemic heart disease in both sexes: 71.7% among women versus 75.7% among men, P=0.005. In contrast, women were more likely to have nonischemic cause of SCD than men (28.3% versus 24.3%, P=0.005). The prevalence of primary myocardial fibrosis was higher among women (5.2%, n=64) than in men (2.6%, n=120; P<0.001). Female subjects with SCD were more likely to have normal prior ECG tracings (22.2% versus 15.3% in men, P<0.001). A normal ECG was even more common among nonischemic female subjects with SCD (27.8% versus 16.2% in men, P=0.009). However, ECG markers of left ventricular hypertrophy, with or without repolarization abnormalities, were more common among women (8.2%; 17.9%) than in men (4.9%; 10.6%, P=0.036; P<0.001, respectively). CONCLUSIONS: Women were considerably older at the time of SCD and more commonly had nonischemic causes. Women were also more likely to have a prior normal ECG than men, but an increased marker for SCD risk based on ECG criteria for left ventricular hypertrophy with repolarization abnormalities was more commonly observed in women.