Gender differences in prevalence and prognostic value of fragmented QRS complex

Background: Fragmented QRS (fQRS) on 12-lead electrocardiogram(ECG) is associated with scarred myocardium and adverse outcome. However, the data on gender differences in terms of its prevalence and prognostic value is sparse. The aim of this study was to evaluate whether gender differences in fQRS exist among subjects drawn from populations with different risk profiles. Methods: We analyzed fQRS from 12-lead ECG in 953 autopsy-confirmed victims of sudden cardiac death (SCD) (78% men; 67.0 +/- 11.4 yrs), 1900 coronary artery disease (CAD) patients with angiographically confirmed stenosis of >= 50% (70% men; 66.6 +/- 9.0 yrs, 43% with previous myocardial infarction [MI]), and in 10,904 adults drawn from the Finnish adult general population (52% men; 44.0 +/- 8.5 yrs). Results: Prevalence of fQRS was associated with older age, male sex and the history and severity of prior cardiac disease of subjects. Among the general population fQRS was more commonly found among men in comparison to women (20.5% vs. 14.8%, p <0.001). The prevalence of fQRS rose gradually along with the severity of prior cardiac disease in both genders, yet remained significantly higher in the male population: subjects with suspected or known cardiac disease (25.4% vs. 15.8% p <0.001), CAD patients without prior MI (39.9% vs. 26.4%, p <0.001), CAD patients with prior MI (42.9% vs. 31.2%, p <0.001), and victims of SCD (56.4% vs. 44.4%, p <0.001). Conclusions: The prevalence of QRS fragmentation varies in different populations. The fragmentation is clearly related to the underlying cardiac disease in both genders, however women seem to have significantly lower prevalence of fQRS in each patient population in comparison to men. (C) 2020 The Authors. Published by Elsevier Inc.Peer reviewe

Characteristics of undiagnosed coronary artery disease in sudden cardiac death:autopsy findings and genetics

Abstract Sudden cardiac death (SCD) remains a major health problem worldwide, and a great proportion of victims do not have a previously diagnosed heart disease. Especially in older population, the majority of SCDs are caused by coronary artery disease (CAD); however, the burden of CAD among the young has also been noted. The aim of this thesis was to study the characteristics of SCDs associated with CAD, especially in younger victims and in those with no prior history of heart disease. The study population consisted of 5,869 SCD victims from Northern Finland who underwent medicolegal autopsy between the years 1998–2017. In Study I, CAD was found to be the most common cause of SCD. At autopsies, a prior silent myocardial infarction (SMI) was detected in about 42% of the victims without a clinical history of CAD, and it was associated with myocardial hypertrophy and SCD during physical activity. A prior electrocardiogram was abnormal in 67% of the SCD victims with a previous SMI. In Study II, 10% of the study population were found to be aged under 50 years and the most common cause of SCD among these young SCD victims was CAD. In about 90% of the cases SCD occurred in the absence of previously diagnosed CAD, but at least one known cardiovascular risk factor was present in over half of the victims. Despite the young age, advanced heart disease was a common finding at autopsies. In Study III, the genetic background of cardiac hypertrophy was investigated in SCD victims with single-vessel CAD without a previously diagnosed heart disease. Possible disease-causing variants were detected in 8% of the study victims, while variants of uncertain significance existed in about 40% of the study victims. All detected variants were in myocardial structure protein coding genes. In Study IV, temporal trends in the incidence and characteristics of SCDs were studied in subjects under 40 years of age. The incidence of SCD decreased during the years 1998–2017. Most SCDs in this age group were due to non-ischemic myocardial diseases, and the incidence of CAD-related SCD decreased. The findings of this thesis increase the understanding of CAD-related SCDs, especially among younger population. In addition, Studies I and III provide novel information on the role of SMIs and genetics in the risk of SCD among victims without a previously diagnosed CAD.Tiivistelmä Sydänperäinen äkkikuolema on edelleen merkittävä terveysongelma maailmanlaajuisesti, ja suurella osalla uhreista ei ole aiemmin todettua sydänsairautta. Etenkin iäkkäillä suurin osa äkkikuolemista johtuu sepelvaltimotaudista, mutta sen taakka myös nuoremmilla on tiedostettu. Tämän väitöskirjatutkimuksen tavoitteena oli tutkia sepelvaltimotautiin liittyvien äkkikuolemien tunnuspiirteitä erityisesti nuoremmilla uhreilla sekä niillä, joilla ei ole aiemmin todettua sydänsairautta. Tutkimusjoukkoon kuului 5869 sydänperäisen äkkikuoleman uhria Pohjois-Suomesta, joille tehtiin ruumiinavaus vuosina 1998–2017. Tutkimuksessa I sepelvaltimotaudin todettiin olevan yleisin äkkikuoleman syy. Ruumiinavauksissa aiemmin sairastettu hiljainen sydäninfarkti todettiin 42 %:lla uhreista, joilla ei ollut aiemmin diagnosoitua sepelvaltimotautia, ja se oli yhteydessä sydämen hypertrofiaan sekä äkkikuolemaan fyysisen rasituksen aikana. Ennen kuolemaa nauhoitettu sydänsähkökäyrä oli poikkeava 67 %:lla uhreista, joilla todettiin aiemmin sairastettu hiljainen sydäninfarkti. Tutkimuksessa II havaitsimme, että 10 % tutkimusjoukostamme oli alle 50-vuotiaita ja sepelvaltimotautioli heillä yleisin äkkikuoleman syy. Noin 90 %:ssa tapauksista äkkikuolema esiintyi ilman aiempaa tietoa sepelvaltimotaudista, mutta yli puolella oli ainakin yksi tiedossa oleva sydän- ja verisuonisairauksien riskitekijä. Nuoresta iästä huolimatta pitkälle edennyt sydänsairaus oli yleinen löydös ruumiinavauksissa. Tutkimuksessa III tutkimme sydämen hypertrofian geneettistä taustaa äkkikuoleman uhreilla, joilla oli yhden suonen sepelvaltimotauti ilman aiemmin diagnosoitua sydänsairautta. Löysimme todennäköisesti sydänsairautta aiheuttavia geenimuutoksia 8 %:lla tutkituista uhreista, ja 40 %:lla todettiin merkitykseltään epäselvä geenimuutos. Geenimuutokset todettiin sydänlihasproteiineja koodaavissa geeneissä. Tutkimuksessa IV tutkimme alle 40-vuotiaiden äkkikuolemien ilmaantuvuuden ja tunnuspiirteiden ajallisia kehityssuuntia. Äkkikuolemien ilmaantuvuus väheni vuosina 1998–2017. Suurin osa äkkikuolemista tässä ikäryhmässä johtui ei-iskeemisistä sydänsairauksista, ja sepelvaltimotautiperäisten kuolemien ilmaantuvuus väheni. Tämän väitöstutkimuksen havainnot lisäävät ymmärrystä sepelvaltimoperäisistä äkkikuolemista erityisesti nuoremman väestön keskuudessa. Lisäksi tutkimuksissa I ja II saatiin uutta tietoa hiljaisten sydäninfarktien ja genetiikan roolista äkkikuoleman riskissä uhreilla, joilla ei ole aiemmin diagnosoitua sepelvaltimotautia

Increasing air temperature relative to water temperature makes the mixed layer shallower, reducing phytoplankton biomass in a stratified lake

The depth of the mixed layer is a major determinant of nutrient and light availability for phytoplankton in stratified waterbodies. Ongoing climate change influences surface waters through meteorological forcing, which modifies the physical structure of fresh waters including the mixed layer, but effects on phytoplankton biomass are poorly known. To determine the responses of phytoplankton biomass to the depth of the mixed layer, light availability and associated meteorological forcing, we followed daily changes in weather and water column properties in a boreal lake over the first half of a summer stratification period. Phytoplankton biomass increased with the deepening of the mixed layer associated with high wind speeds and low air temperature relative to the temperature of the mixed layer (Tair−Tmix < 0), whereas heatwave conditions—shallow mixed layer driven by high Tair−Tmix value and low wind speed—reduced the biomass. Improving light availability from low to moderate light conditions increased the phytoplankton biomass, while the highest light availability was associated with low phytoplankton biomass. Our study demonstrates that the climatic impact-drivers wind speed and Tair−Tmix are major drivers of mixed layer depth, which controlled phytoplankton biomass during the early summer stratification period. Our study suggests that increasing air temperature relative to water temperature and declining wind speeds have potential to lead to reduced phytoplankton biomass due to a shallower mixed layer during the first half of the stratification period in non-eutrophic lakes with sufficient light availability.peerReviewe

Temporal trends in the incidence and characteristics of sudden cardiac death among subjects under 40 years of age in Northern Finland during 1998–2017

Abstract Background: Although the mean age of sudden cardiac death (SCD) victims has increased during recent decades, overall incidence has remained relatively stable. Small but very important proportion of SCDs occur in subjects under 40 years of age and temporal trends in the incidence and characteristics of SCD in this age-group are not well known. Methods: The Fingesture study has prospectively gathered data from 5,869 consecutive autopsy verified SCD victims in Northern Finland during 1998–2017. On the basis of Finnish law, all who die unexpectedly undergo autopsy. Results: Out of total 5,869 SCDs, 160 occurred in subjects under 40 years of age (3%) indicating a total incidence of 2.9/100,000/year. Incidence decreased during the study period: 4.0/100,000/year (n = 50) in 1998–2002, 3.7/100,000/year (n = 45) in 2003–2007, 2.5/100,000/year (n = 36) in 2008–2012, and 1.5/100,000/year (n = 29) in 2013–2017. Coronary artery disease (CAD) was the cause of death in 46 SCD victims (29%). Among nonischemic causes, most common were obesity-related hypertrophic myocardial disease (24%), primary myocardial fibrosis (19%), and hypertensive myocardial disease (6%). The incidence of SCD caused by CAD decreased as follows: 1.5/100,000/year in 1998–2002, 1.2/100,000/year in 2003–2007, 0.6/100,000/year in 2008–2012, and 0.2/100,000/year in 2013–2017. Proportion of male gender (81%) and obesity as a comorbidity (body mass index >30 kg/m², 40%) remained relatively stable during the period (p = 0.58 and p = 0.79, respectively). Conclusions: The incidence of SCD in subjects under 40 years of age has decreased in Northern Finland during 1998–2017. According to autopsy data, most of the deaths are due to nonischemic myocardial diseases and relative proportion of CAD has decreased

Sudden cardiac death after alcohol intake:classification and autopsy findings

Abstract Alcohol is known to have an immediate effect on cardiac rhythm, and previous studies have found that a notable proportion of sudden cardiac deaths (SCD) occur after alcohol intake. The objective of the present study was to investigate the association between the timing of alcohol intake and SCD. Our study population is drawn from the Fingesture study, which includes 5869 consecutive SCD cases from Northern Finland who underwent medicolegal autopsy 1998–2017. Toxicological analysis was performed if there was any suspicion of toxic exposure, or if there was no obvious immediate cause of SCD at autopsy. We found that 1563 (27%) of all SCD victims had alcohol in blood or urine at autopsy (mean age (61 ± 10 years, 88% male). Eighty-six percent of alcohol-related SCD victims had higher urine alcohol concentration than blood alcohol concentration, referring to the late-stage inebriation. These results suggest that the majority of alcohol-related SCDs occur at the late stage of inebriation

Coronary artery disease as the cause of sudden cardiac death among victims &lt; 50 years of age

Abstract Coronary artery disease (CAD) is the most common cause of sudden cardiac death (SCD). Atherosclerosis increases with age, but also many victims of SCD in young and middle-aged population have CAD at autopsy. The purpose of this study was to determine the characteristics and autopsy findings of SCD due to CAD among victims of SCD under the age of 50. Fingesture is a population-based study consisting of consecutive series of victims of autopsy verified SCD in Northern Finland between the years 1998 to 2017 (n = 5,869). Histological examinations were part of all autopsies and a toxicology investigation was performed if needed. Analyses included information accumulated from death certificates, medical records, autopsy data, standardized questionnaire to the closest family members of the victims of SCD and police reports of the conditions of the death. Overall, 10.4% of all SCDs occurred among victims under the age of 50 years (610 victims). Most common underlying cause of SCD among these younger SCD victims was CAD (43.6%). The prevalence of CAD as the cause of SCD became more common in young SCD victims after the age of 35 years. The mean age of ischemic SCD victims was 44±5 years and most were men (89.5%). Most victims (90.2%) had no clinical diagnosis of CAD, however 33.8% had an autopsy evidence of silent myocardial infarction. SCD occurred during physical activity in 24.1%. Three-vessel disease was detected in 44.4% of the study victims. Cardiac hypertrophy (58.3%) and myocardial fibrosis (82.6%) were also common. At least 1 cardiovascular risk factor was present in 64.7% of SCD victims. In conclusion, most SCDs among victims &lt; 50 years of age are due to CAD

Clinical implementation of 4-dihydroxyborylphenylalanine synthesised by an asymmetric pathway

Boron neutron capture therapy (BNCT) is an experimental therapeutic modality combining a boron pharmaceutical with neutron irradiation. 4-Dihydroxyborylphenylalanine (L-BPA) synthesised via the asymmetric pathway by Malan and Morin [Synlett. 167-168 (1996)] was developed to be the boron containing pharmaceutical in the first series of Finnish BNCT clinical trials. The final product was >98.5% chemically pure L-BPA with L-phenylalanine and L-tyrosine as the residual impurities. The solubility of L-BPA was enhanced by complex formation with fructose (BPA-F). The pH and osmolarity of the BPA-F preparation is in the physiological range. Careful attention was given to the pharmaceutical quality of the BPA-F preparations. Prior to starting clinical trials the acute toxicity of L-BPA was studied in male albino Sprague-Dawley rats. In accordance with earlier studies no adverse effects were observed. After completion of the development work L-BPA solution was administered to brain tumour patients in conjunction with clinical studies for development and testing of BPA-based BNCT. No clinically significant adverse events attributable to the L-BPA i.v. infusions were observed. We conclude that our synthesis development, complementary preclinical and clinical observations justify the safe use of L-BPA up to clinical phase III studies with L-BPA produced by the asymmetric pathway, originally presented by Malan and Morin in 1996. © 2002 Elsevier Science B.V. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe