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1.
JAMA Cardiol ; 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31290935

RESUMO

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.

2.
Eur Heart J ; 40(37): 3121-3128, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31230070

RESUMO

AIMS: The present study was done to assess the role of sudden cardiac death (SCD) among the presenting manifestations of and fatalities from cardiac sarcoidosis (CS). METHODS AND RESULTS: We analysed altogether 351 cases of CS presenting from year 1998 through 2015 in Finland. There were 262 patients with a clinical diagnosis and treatment of CS, 27 patients with an initial lifetime diagnosis of giant cell myocarditis that was later converted to CS, and 62 cases detected at autopsy and identified by screening >820 000 death certificates from the national cause-of-death registry. The total case series comprised 253 females and 98 males aged on average 52 years at presentation. High-grade atrioventricular block was the most common first sign of CS (n = 147, 42%) followed by heart failure (n = 58, 17%), unexpected fatal (n = 38) or aborted (n = 12) SCD (14%), and sustained ventricular tachycardia (n = 48, 14%). Severe coronary artery disease was found at autopsy concomitant with CS in four of the 38 cases presenting with fatal SCD. Of all deaths recorded till the end of 2015, 64% (n = 54/84) were unexpected SCDs from CS that had either been silent during life or defied all attempts at diagnosis. The Kaplan-Meier estimate (95% CI) of survival from symptom onset was 85% (80-90%) at 5 years and 76% (68-84%) at 10 years. CONCLUSION: Together fatal and aborted SCD constitute 14% of the presenting manifestations of CS. Nearly two-thirds of all fatalities from CS are caused by undiagnosed granulomas in the heart.

3.
Nat Commun ; 10(1): 1252, 2019 03 19.
Artigo em Inglês | MEDLINE | ID: mdl-30890702

RESUMO

Clonal hematopoiesis driven by somatic heterozygous TET2 loss is linked to malignant degeneration via consequent aberrant DNA methylation, and possibly to cardiovascular disease via increased cytokine and chemokine expression as reported in mice. Here, we discover a germline TET2 mutation in a lymphoma family. We observe neither unusual predisposition to atherosclerosis nor abnormal pro-inflammatory cytokine or chemokine expression. The latter finding is confirmed in cells from three additional unrelated TET2 germline mutation carriers. The TET2 defect elevates blood DNA methylation levels, especially at active enhancers and cell-type specific regulatory regions with binding sequences of master transcription factors involved in hematopoiesis. The regions display reduced methylation relative to all open chromatin regions in four DNMT3A germline mutation carriers, potentially due to TET2-mediated oxidation. Our findings provide insight into the interplay between epigenetic modulators and transcription factor activity in hematological neoplasia, but do not confirm the putative role of TET2 in atherosclerosis.


Assuntos
Aterosclerose/genética , Metilação de DNA/genética , Proteínas de Ligação a DNA/genética , Haploinsuficiência , Doença de Hodgkin/genética , Proteínas Proto-Oncogênicas/genética , Adulto , Aterosclerose/patologia , Células Cultivadas , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Proteínas de Ligação a DNA/metabolismo , Epigênese Genética , Feminino , Finlândia , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Hematopoese/genética , Doença de Hodgkin/sangue , Doença de Hodgkin/patologia , Humanos , Masculino , Fenótipo , Cultura Primária de Células , Proteínas Proto-Oncogênicas/metabolismo , RNA Interferente Pequeno/metabolismo , Sequenciamento Completo do Genoma
5.
Artigo em Inglês | MEDLINE | ID: mdl-30445634

RESUMO

Context: PCOS is associated with many traditional cardiovascular disease risk factors, but it is unclear whether PCOS is an independent risk factor for hypertension. Objective: To investigate in a population-based set-up whether PCOS associates with the risk of hypertension independently of body-mass-index (BMI), and with cardiovascular manifestations. Design: Cross-sectional assessments in the Northern Finland Birth Cohort 1966 at ages 31 and 46. Setting: General community. Participants: Women who reported both oligo/amenorrhea and hirsutism at age 31 and/or diagnosis of PCOS by age 46 (self-reported PCOS [srPCOS], n=279) and women without PCOS symptoms or diagnosis (n=1577). Intervention: None. Main Outcome Measures: Blood pressure (BP), BMI, cardiovascular manifestations. Results: Use of antihypertensive medication was significantly more common in women with srPCOS. At age 31, women with srPCOS had significantly higher systolic (SBP) and diastolic BP (DBP) than control women (SBP: normal-weight: 119.9±13.2 vs. 116.9±11.4mmHg, P=0.017; overweight/obese: 126.1±14.3 vs. 123.0±11.9mmHg, P=0.031; and DBP: normal-weight: 75.5±10.0 vs. 72.4±9.6mmHg, P=0.003; overweight/obese: 80.7±11.8 vs. 78.0±10.6mmHg, P=0.031). At age 46, srPCOS was significantly associated with hypertension (AOR=1.56 [1.14-2.13]) independently of BMI, and with higher cardiovascular morbidity (6.8% vs. 3.4%, P=0.011). Hypertensive srPCOS displayed consistent, unfavorable changes in cardiac structure and function compared with controls. Conclusion: Women with srPCOS displayed higher BP compared with controls already at early age and srPCOS was associated with hypertension independently of overweight/obesity. srPCOS was associated with increased cardiovascular morbidity in premenopausal women, suggesting that cardiovascular disease risk factors should be screened and efficiently managed early enough in women with PCOS.

6.
Circ Arrhythm Electrophysiol ; 11(8): e006145, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30354309

RESUMO

BACKGROUND: Symptomatic high-grade atrioventricular block (AVB) is the most common and often the only presenting manifestation (lone AVB) of cardiac sarcoidosis. Implantation of an intracardiac cardioverter defibrillator instead of a pacemaker is recommended, but the true risk of fatal arrhythmia, one incident to lone AVB in particular, remains poorly known. METHODS: We used Myocardial Inflammatory Diseases in Finland Study Group Registry to analyze the presentations, left ventricular (LV) function, pacemaker therapy, and ventricular arrhythmias in cardiac sarcoidosis. From year 1988 to 2015, altogether 325 cases of cardiac sarcoidosis were diagnosed in Finland. Of them, 143 patients (112 women, mean age 52 years) presented with Mobitz II second degree or third degree AVB in the absence of other explanatory cardiac disease. RESULTS: Concomitant with AVB at presentation, 20 patients had either ventricular tachycardia or severe LV dysfunction with ejection fraction <35% and 29 patients had nonsevere LV dysfunction (ejection fraction, 35%-50%) while 90 patients presented with AVB alone. During a median of 2.8 years' follow-up, 23 sudden cardiac deaths (fatal or aborted) and 19 ventricular tachycardias were recorded as arrhythmic end point events. Their composite 5-year incidence (95% confidence interval) was 56% (36%-88%) in the AVB subgroup with ventricular tachycardia or severe LV dysfunction versus 24% (12%-49%) in the subgroup with nonsevere LV dysfunction and 24% (15%-38%) with lone AVB ( P=0.019). The 5-year incidence of sudden cardiac death was 34% (16%-71%), 14% (6%-35%), and 9% (4%-22%) in the respective subgroups ( P=0.060). CONCLUSIONS: The risk of sudden cardiac death is significant in cardiac sarcoidosis presenting with high-grade AVB with or without ventricular tachycardia or LV dysfunction. The consensus recommendation to implant an intracardiac cardioverter defibrillator whenever permanent pacing is needed seems well-founded.

7.
Circulation ; 137(25): 2716-2726, 2018 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-29915098

RESUMO

BACKGROUND: Myocardial fibrosis is a common postmortem finding among young individuals with sudden cardiac death. Because there is no known single cause, we tested the hypothesis that some cases of myocardial fibrosis in the absence of identifiable causes (primary myocardial fibrosis [PMF]) are associated with genetic variants. METHODS: Tissue was obtained at autopsy from 4031 consecutive individuals with sudden cardiac death in Northern Finland, among whom PMF was the only structural finding in 145 subjects with sudden cardiac death. We performed targeted next-generation sequencing using a panel of 174 genes associated with myocardial structure and ion channel function when autopsies did not identify a secondary basis for myocardial fibrosis. All variants with an effect on protein and with a minor allele frequency <0.01 were classified as pathogenic or variants of uncertain significance on the basis of American College of Medical Genetics consensus guidelines. RESULTS: Among the 96 specimens with DNA passing quality control (66%), postmortem genetic tests identified 24 variants of known or uncertain significance in 26 subjects (27%). Ten were pathogenic/likely pathogenic variants in 10 subjects (10%), and 14 were variants of uncertain significance in 11 genes among 16 subjects (17%). Five variants were in genes associated with arrhythmogenic right ventricular cardiomyopathy, 6 in hypertrophic cardiomyopathy-associated genes, and 11 in dilated cardiomyopathy-associated genes; 2 were not associated with these disorders. Four unique variants of uncertain significance cosegregated among multiple unrelated subjects with PMF. No pathogenic/likely pathogenic variants were detected in ion channel-encoding genes. CONCLUSIONS: A large proportion of subjects with PMF at autopsy had variants in genes associated with arrhythmogenic right ventricular cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy without autopsy findings of those diseases, suggesting that PMF can be an alternative phenotypic expression of structural disease-associated genetic variants or that risk-associated fibrosis was expressing before the primary disease. These findings have clinical implications for postmortem genetic testing and family risk profiling.

8.
Int J Cardiol ; 243: 389-395, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28571618

RESUMO

Patients in the latest stages of heart failure are severely compromised, with poor quality of life and frequent hospitalizations. Heart transplantation and left ventricular assist device implantation are viable options only for a minority, and intermittent or continuous infusions of positive inotropes may be needed as a bridge therapy or as a symptomatic approach. In these settings, levosimendan has potential advantages over conventional inotropes (catecholamines and phosphodiesterase inhibitors), such as sustained effects after initial infusion, synergy with beta-blockers, and no increase in oxygen consumption. Levosimendan has been suggested as a treatment that reduces re-hospitalization and improves quality of life. However, previous clinical studies of intermittent infusions of levosimendan were not powered to show statistical significance on key outcome parameters. A panel of 45 expert clinicians from 12 European countries met in Rome on November 24-25, 2016 to review the literature and envision an appropriately designed clinical trial addressing these needs. In the earlier FIGHT trial (daily subcutaneous injection of liraglutide in heart failure patients with reduced ejection fraction) a composite Global Rank Score was used as primary end-point where death, re-hospitalization, and change in N-terminal-prohormone-brain natriuretic peptide level were considered in a hierarchical order. In the present study, we tested the same end-point post hoc in the PERSIST and LEVOREP trials on oral and repeated i.v. levosimendan, respectively, and demonstrated superiority of levosimendan treatment vs placebo. The use of the same composite end-point in a properly powered study on repetitive levosimendan in advanced heart failure is strongly advocated.


Assuntos
Cardiotônicos/administração & dosagem , Conferências de Consenso como Assunto , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Hidrazonas/administração & dosagem , Piridazinas/administração & dosagem , Administração Oral , Ensaios Clínicos como Assunto/métodos , Ensaios Clínicos como Assunto/normas , Esquema de Medicação , Europa (Continente)/epidemiologia , Medicina Baseada em Evidências/normas , Medicina Baseada em Evidências/tendências , Insuficiência Cardíaca/diagnóstico , Humanos , Infusões Intravenosas , Roma/epidemiologia , Simendana
9.
Artigo em Inglês | MEDLINE | ID: mdl-27301265

RESUMO

BACKGROUND: Coronary artery disease is identified in ≈80% of victims of sudden cardiac death (SCD). Because the prevention strategies and public awareness have changed during the past decades, we studied the temporal trends in the pathogenesis of SCD. METHODS AND RESULTS: FinGesture (n=4031) is a prospective study designed to classify the phenotype and genotype profiles of SCD in a consecutive series of victims of SCD in Northern Finland. On the basis of Finnish law, all subjects who die suddenly undergo autopsy. We analyzed the characteristics of SCD victims and autopsy findings in 1998 to 2002, 2003 to 2007, and 2008 to 2012. Among victims of SCD as a first cardiac event (n=2697), the proportion with coronary artery disease decreased during the 2008 to 2012 time period, compared with the 2 preceding 5-year periods: 74.0% in 1998 to 2002, 73.1% in 2003 to 2007, and 66.4% in 2008 to 2012 (P<0.001). Proportion of SCDs associated with hypertensive heart disease with left ventricular hypertrophy in the absence of coronary artery disease increased from 1.7% in 1998 to 2002 to 5.8% in 2003 to 2007 and 8.9% in 2008 to 2012 (P<0.001). Similarly, myocardial fibrosis in the absence of myocarditis or left ventricular hypertrophy, or other known pathogeneses, was 6.7% in the past 5-year period compared with 2 previous 5-year periods (3.7% and 4.0%; P<0.001 between 1998-2002 and 2008-2012 and between 2003-2007 and 2008-2012). CONCLUSIONS: The proportion of SCDs attributable to coronary artery disease, in the absence of a history of heart disease, has decreased, whereas the proportion associated with hypertensive heart disease and idiopathic fibrosis has increased during the past 15 years.


Assuntos
Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/etiologia , Autopsia , Causas de Morte , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/epidemiologia , Feminino , Finlândia/epidemiologia , Genótipo , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Hipertrofia Ventricular Esquerda/complicações , Hipertrofia Ventricular Esquerda/epidemiologia , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Prospectivos , Fatores de Risco
10.
Ann Med ; 48(1-2): 111-7, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26838936

RESUMO

BACKGROUND: Epilepsy is associated with sudden death, but the reasons for this association are not well known. Objective We studied the role of antiepileptic drugs (AEDs) as a factor contributing to sudden cardiac death (SCD) in The Finnish Study of the Genotype and Phenotype Characteristics of Sudden Cardiac Death (FinGesture). METHODS AND RESULTS: The FinGesture study compares the characteristics of victims of SCD caused by an autopsy-verified acute coronary event (cases) vs. survivors of an acute coronary event (ACS) (controls). The study population comprised 3737 cases (mean age 64 ± 12 y) and 3081 controls (mean age 66 ± 12 y). The use of AED was obtained from death certificates, autopsy/hospital records, national drug imbursement register, and interviews with the relatives. AEDs were more commonly used by the victims of SCD vs. controls (5.5% vs. 2.2%, adjusted odds ratio 2.7, 95% CI; 1.9-3.9; p < 0001). The use of AED for non-epilepsy indications was also more common in the cases than in controls (1.5% vs. 1.0%, p = 0.005). CONCLUSION: A higher rate of AED was observed in victims of SCD than in a control group of ACS patients. Concomitant use of AED could be responsible for a small fraction of deaths due to acute coronary events. Key message Epilepsy has been associated with sudden cardiac death. The use of antiepileptic drugs seems to be associated with an increased risk of sudden cardiac death during a coronary event. Physicians should be aware of the risk related to antiepileptic drugs especially when used for other reasons than epilepsy.


Assuntos
Síndrome Coronariana Aguda/mortalidade , Anticonvulsivantes/administração & dosagem , Morte Súbita Cardíaca/epidemiologia , Epilepsia/tratamento farmacológico , Idoso , Anticonvulsivantes/efeitos adversos , Autopsia , Estudos de Casos e Controles , Morte Súbita Cardíaca/etiologia , Epilepsia/mortalidade , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
11.
Europace ; 18(7): 1006-9, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26552693

RESUMO

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.


Assuntos
Álcoois/sangue , Morte Súbita Cardíaca/epidemiologia , Infarto do Miocárdio/sangue , Infarto do Miocárdio/complicações , Idoso , Autopsia , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
12.
Am J Cardiol ; 116(6): 960-4, 2015 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-26209113

RESUMO

Evaluation and treatment of cardiac sarcoidosis (CS) suffer from lack of sensitive and easily repeatable markers of disease activity. We studied measurements of high-sensitivity cardiac troponin T or troponin I (hs-cTnT/I) taken at presentation and during treatment in 62 patients with new-onset CS (48 women, mean age 49 years). Hs-cTnT was measured in 50 patients and was elevated (>13 ng/L) at presentation in 26 of them (52%). Hs-cTnI was measured in the remaining 12 patients and was elevated (>0.04 ng/mL) in 7 of them (58%). Left ventricular ejection fraction averaged 43 ± 14% in association with elevated hs-cTnT/I (n = 33) versus 53 ± 10% with normal hs-cTnT/I (n = 29; p = 0.001). Hs-cTnT/I was remeasured after 4 weeks of steroid therapy in 38 patients and was normalized in 16 of the 24 (67%) with an elevated pretreatment concentration and remained normal in the rest of the 14 patients (p <0.001). During follow-up (median, 17 months), cardiac death (n = 2), aborted sudden death (n = 5), sustained ventricular tachycardia (n = 8), or new complete atrioventricular block (n = 1) was recorded in 11 of 33 patients with elevated hs-cTnT/I versus in 5 of 29 with normal hs-cTnT/I (log-rank p = 0.068). Two-year event-free Kaplan-Meier cardiac survival estimate (95% confidence interval) was 67% (48% to 81%) with elevated hs-cTnT/I versus 93% (76% to 99%) with normal hs-cTnT/I. In CS, circulating hs-cTnT/I may help clinicians evaluate disease activity and treatment response. Their prognostic value remains tentative pending more follow-up data.


Assuntos
Cardiomiopatias/tratamento farmacológico , Glucocorticoides/uso terapêutico , Prednisona/uso terapêutico , Sarcoidose/tratamento farmacológico , Troponina I/sangue , Troponina T/sangue , Adulto , Biomarcadores/sangue , Cardiomiopatias/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sarcoidose/sangue , Resultado do Tratamento
13.
Ann Med ; 47(3): 263-8, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25861828

RESUMO

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.


Assuntos
Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/patologia , Exercício/fisiologia , Idoso , Autopsia , Causas de Morte , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/patologia , Morte Súbita Cardíaca/etiologia , Feminino , Finlândia/epidemiologia , Cardiopatias/mortalidade , Cardiopatias/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/mortalidade , Isquemia Miocárdica/patologia , Estudos Prospectivos , Fatores de Risco
14.
Circulation ; 131(7): 624-32, 2015 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-25527698

RESUMO

BACKGROUND: This study was designed to assess the epidemiology, characteristics, and outcome of cardiac sarcoidosis (CS) in Finland. METHODS AND RESULTS: We identified in retrospect all adult (>18 years of age) patients diagnosed with histologically confirmed CS in Finland between 1988 and 2012. A total of 110 patients (71 women) 51±9 years of age (mean±SD) were found and followed up for outcome events to the end of 2013. The annual detection rate of CS increased >20-fold during the 25-year period, reaching 0.31 in 1×10(5) adults between 2008 and 2012. The 2012 prevalence of CS was 2.2 in 1×10(5). Nearly two thirds of patients had clinically isolated CS. Altogether, 102 of the 110 patients received immunosuppressive therapy, and 56 received an intracardiac defibrillator. Left ventricular function was impaired (ejection fraction <50%) in 65 patients (59%) at diagnosis and showed no overall change over 12 months of steroid therapy. During follow-up (median, 6.6 years), 10 patients died of a cardiac cause, 11 patients underwent transplantation, and another 11 patients suffered an aborted sudden cardiac death. The Kaplan-Meier estimates for 1-, 5-, and 10-year transplantation-free cardiac survival were 97%, 90%, and 83%, respectively. Heart failure at presentation predicted poor outcome (log-rank P=0.0001) with a 10-year transplantation-free cardiac survival of only 53%. CONCLUSIONS: The detection rate of CS has increased markedly in Finland over the last 25 years. With current therapy, the prognosis of CS appears better than generally considered, but patients presenting with heart failure still have poor long-term outcome.


Assuntos
Cardiomiopatias/diagnóstico , Cardiomiopatias/epidemiologia , Sarcoidose/diagnóstico , Sarcoidose/epidemiologia , Adulto , Idoso , Cardiomiopatias/terapia , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sarcoidose/terapia , Taxa de Sobrevida/tendências , Resultado do Tratamento
15.
Ann Med ; 46(5): 318-23, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24813458

RESUMO

AIMS: Idiopathic myocardial fibrosis (IMF) was observed to be the most prevalent autopsy finding in the victims of sudden cardiac death (SCD) under the age of 40 years in the FinGesture cohort. To elucidate further the mechanisms of IMF, we examined the collagen composition from the myocardial samples taken from the victims of IMF-associated SCD. METHODS: Eighteen cases with IMF as a cause of death, confirmed by autopsy, were selected for the analysis. Controls (n = 27) included were cases in whom no cardiac or non-cardiac disease could be found as a cause of unexpected death at autopsy. In addition to conventional histological examination, immunohistochemical staining of procollagens I and III (PINP and PIINP), mature collagen III (IIINTP), and the cross-linked collagen I degradation product (ICTP) were performed. RESULTS: Increased accumulation of PINP was observed in the fibrotic tissue of the IMF cases in comparison with control samples. In contrast, type III collagen was not as frequently expressed in the fibrotic areas. CONCLUSION: Myocardial accumulation of PINP in the victims of IMF-associated SCD indicates increased type I collagen synthesis. Future studies on the role of circulating type I collagen biomarkers are needed to study further the implications of the described association.


Assuntos
Cardiomiopatias/complicações , Colágeno Tipo I/biossíntese , Morte Súbita Cardíaca/etiologia , Miocárdio/patologia , Adolescente , Adulto , Idoso , Autopsia , Cardiomiopatias/patologia , Feminino , Fibrose , Finlândia , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
16.
Circ Arrhythm Electrophysiol ; 5(4): 757-61, 2012 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-22787009

RESUMO

BACKGROUND: Recent studies have identified the presence of familial clustering of ischemic sudden cardiac death (SCD) as a clinical expression of coronary artery disease. The purpose of this study was to determine whether nonischemic SCD has a similar familial background, which would be evidence of a genetic predisposition. METHODS AND RESULTS: The retrospective case-control study included (1) consecutive victims of nonischemic SCD (n=223), (2) consecutive victims of ischemic SCD (n=596), whose deaths and diagnosis were verified at medicolegal autopsy, and (3) control subjects without heart disease (n=475). In each study group, the family history of SCD among the first-degree relatives was determined and verified from death certificates. The prevalence of SCD in ≥1 first-degree relative was significantly higher in victims of ischemic (34.2%) than nonischemic SCD (13.4%; P<0.001) or controls (17.6%; P<0.001). The history of SCD in first-degree relatives did not differ from controls in nonischemic SCD victims (P=0.155). In a subgroup analysis of victims of ischemic SCD, the prevalence of family history of SCD in first-degree relatives did not differ between those with or without a prior infarct scar at autopsy (33.1% versus 29.9%, respectively; P=0.222). CONCLUSIONS: Ischemic SCD has a strong familial background both in cases with and without a prior myocardial infarction. The family history of SCD is not significantly increased in victims of nonischemic SCD, suggesting a larger role of sporadic occurrence than inherited traits as the cause of nonischemic SCD.


Assuntos
Morte Súbita Cardíaca/epidemiologia , Cardiopatias/mortalidade , Isquemia Miocárdica/mortalidade , Adulto , Idoso , Análise de Variância , Autopsia , Distribuição de Qui-Quadrado , Finlândia/epidemiologia , Predisposição Genética para Doença , Cardiopatias/diagnóstico , Cardiopatias/genética , Hereditariedade , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Infarto do Miocárdio/genética , Infarto do Miocárdio/mortalidade , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/genética , Razão de Chances , Linhagem , Fenótipo , Prevalência , Medição de Risco , Fatores de Risco
17.
Eur Heart J ; 33(6): 745-51, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21920969

RESUMO

AIMS: Psychotropic medication increases cardiac mortality, but the reasons for this association are not clear. We studied the role of psychotropic drugs as a triggering factor of sudden cardiac death (SCD) during an acute coronary event. METHODS AND RESULTS: The use of medication was compared between victims of SCD and survivors of an acute coronary event in a case-control study including a consecutive series of victims of SCD (n= 1814, mean age 65 ± 11 years) verified to be due to an acute coronary event at medico-legal autopsy and consecutive series of patients surviving an acute myocardial infarction (AMI; n= 1171, mean age 66 ± 12 years). The medication history was obtained from autopsy/hospital records and interviews with relatives of SCD victims and AMI patients. The use of antipsychotics [9.7 vs. 2.4%, odds ratio (OR) 4.4, 95% confidence interval (CI) 2.9-6.6; P< 0.001] and antidepressants (8.6 vs. 5.5%, OR: 1.6, 95% CI: 1.2-2.2; P= 0.003) was more common in the SCD than AMI group, but the use of benzodiazepines did not differ between the groups (11.7 vs. 13.2%; P= 0.270). The use of antipsychotics remained as a significant risk factor for SCD after adjustment for confounding variables (OR: 3.4, 95% CI: 1.8-6.5; P< 0.001). Combined use of phenothiazines and any antidepressant was associated with a very high risk of SCD (OR: 18.3, 95% CI: 2.5-135.3; P< 0.001). CONCLUSION: The use of psychotropic drugs, especially combined use of antipsychotic and antidepressant drugs, is strongly associated with an increased risk of SCD at the time of an acute coronary event.


Assuntos
Doença das Coronárias/induzido quimicamente , Morte Súbita Cardíaca/etiologia , Transtornos Mentais/tratamento farmacológico , Psicotrópicos/efeitos adversos , Idoso , Antipsicóticos/efeitos adversos , Estudos de Casos e Controles , Ritmo Circadiano , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo
18.
Heart Rhythm ; 8(10): 1570-5, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21740887

RESUMO

BACKGROUND: Previous data have shown that various nonischemic cardiac diseases account for about 20% of sudden cardiac deaths (SCDs) and that dilated and hypertrophic cardiomyopathy (CM) are major causes of nonischemic SCD. OBJECTIVE: The purpose of this study was to define the prevalence and causes of SCD due to nonischemic CM in the current era given the substantial change in the diagnosis and treatment of cardiac diseases and in lifestyle patterns. METHODS: A total of 2661 consecutive victims of SCD from among a population of approximately 470,000 inhabitants in the Province of Oulu, Northern Finland, were included in the study. The causes of deaths were determined from the uniformly required autopsies of SCD victims in Finland, plus available medical records and standardized questionnaires. RESULTS: Nonischemic cause of SCD was found in 579 victims (21.8% of all the SCDs). Mean age (± SD) was 55 (±12) years; 78% were males. After subgrouping the nonischemic SCDs into various categories, SCDs associated most closely with obesity (23.7%), followed by alcoholic CM (19.0%), hypertensive CM (15.5%), and fibrotic CM (13.6%). Fibrotic CM was the most common association with SCD in subjects younger than 40 years (28.3%), whereas alcoholic CM was the most common cause of death in subjects between 40 and 59 years of age (25.8%). CONCLUSION: CM related to obesity, fibrotic CM, and alcoholic CM are commonly associated with nonischemic SCD in the current era. The association of SCD with fibrotic CM is notably frequent among victims younger than 40 years.


Assuntos
Morte Súbita Cardíaca/etiologia , Adulto , Alcoolismo/complicações , Alcoolismo/epidemiologia , Análise de Variância , Autopsia , Cardiomiopatias/complicações , Cardiomiopatias/epidemiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/epidemiologia , Causas de Morte , Distribuição de Qui-Quadrado , Feminino , Finlândia/epidemiologia , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Inquéritos e Questionários
19.
PLoS Genet ; 7(6): e1002158, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21738491

RESUMO

Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000-300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10(-10)). The risk allele, while ancestral, has a frequency of ~1.4%, suggesting strong negative selection and increases risk for SCD by 1.92-fold per allele (95% CI 1.57-2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006).


Assuntos
Cromossomos Humanos Par 2/genética , Morte Súbita Cardíaca , Grupo com Ancestrais do Continente Europeu/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Adulto , Idoso , Alelos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Contração Miocárdica/genética , Polimorfismo de Nucleotídeo Único/genética
20.
Cardiovasc Diabetol ; 9: 42, 2010 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-20731869

RESUMO

BACKGROUND: The beta-1 adrenergic receptor (beta1AR) 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. METHODS: The 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. RESULTS: The 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. CONCLUSIONS: The data suggest an association between the beta1AR 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.


Assuntos
Complicações do Diabetes/genética , Hipertrofia Ventricular Esquerda/genética , Infarto do Miocárdio/genética , Receptores Adrenérgicos beta 1/genética , Idoso , Complicações do Diabetes/mortalidade , Ecocardiografia Doppler , Feminino , Variação Genética , Genótipo , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/mortalidade , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Polimorfismo Genético , Estrutura Terciária de Proteína , Receptores Adrenérgicos beta 1/química , Fatores de Risco
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