Publications by authors named "Jari Laurikka"

84 Publications

Epitranscriptomics of Ischemic Heart Disease-The IHD-EPITRAN Study Design and Objectives.

Int J Mol Sci 2021 Jun 21;22(12). Epub 2021 Jun 21.

Heart and Lung Center, Helsinki University Hospital, 00029 Helsinki, Finland.

Epitranscriptomic modifications in RNA can dramatically alter the way our genetic code is deciphered. Cells utilize these modifications not only to maintain physiological processes, but also to respond to extracellular cues and various stressors. Most often, adenosine residues in RNA are targeted, and result in modifications including methylation and deamination. Such modified residues as -6-methyl-adenosine (mA) and inosine, respectively, have been associated with cardiovascular diseases, and contribute to disease pathologies. The Ischemic Heart Disease Epitranscriptomics and Biomarkers (IHD-EPITRAN) study aims to provide a more comprehensive understanding to their nature and role in cardiovascular pathology. The study hypothesis is that pathological features of IHD are mirrored in the blood epitranscriptome. The IHD-EPITRAN study focuses on mA and A-to-I modifications of RNA. Patients are recruited from four cohorts: (I) patients with IHD and myocardial infarction undergoing urgent revascularization; (II) patients with stable IHD undergoing coronary artery bypass grafting; (III) controls without coronary obstructions undergoing valve replacement due to aortic stenosis and (IV) controls with healthy coronaries verified by computed tomography. The abundance and distribution of mA and A-to-I modifications in blood RNA are charted by quantitative and qualitative methods. Selected other modified nucleosides as well as IHD candidate protein and metabolic biomarkers are measured for reference. The results of the IHD-EPITRAN study can be expected to enable identification of epitranscriptomic IHD biomarker candidates and potential drug targets.
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http://dx.doi.org/10.3390/ijms22126630DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8235045PMC
June 2021

The Effect of Atrial Fibrillation on the Long-Term Mortality of Patients with Acute Coronary Syndrome: The TACOS Study.

Cardiology 2021;146(4):508-516. Epub 2021 Jun 16.

Faculty of Medicine and Health Technology, Finnish Cardiovascular Research Center, Tampere University, Tampere, Finland.

Introduction: Atrial fibrillation (AF) is a frequent finding in acute coronary syndrome (ACS), but there is conflicting scientific evidence regarding its long-term impact on patient outcome. The aim of this study was to survey and compare the ≥10-year mortality of ACS patients with sinus rhythm (SR) and AF.

Methods: Patients were divided into 2 groups based on rhythm in their 12-lead ECGs: (1) SR (n = 788) at hospital admission and discharge (including sinus bradycardia, physiological sinus arrhythmia, and sinus tachycardia) and (2) AF/atrial flutter (n = 245) at both hospital admission and discharge, or SR and AF combination. Patients who failed to match the inclusion criteria were excluded from the final analysis. The main outcome surveyed was long-term all-cause mortality between AF and SR groups during the whole follow-up time.

Results: Consecutive ACS patients (n = 1,188, median age 73 years, male/female 58/42%) were included and followed up for ≥10 years. AF patients were older (median age 77 vs. 71 years, p < 0.001) and more often female than SR patients. AF patients more often presented with non-ST-elevation myocardial infarction (69.8 vs. 50.4%, p < 0.001), had a higher rate of diabetes (31.0 vs. 22.8%, p = 0.009), and were more often using warfarin (32.2 vs. 5.1%, p < 0.001) or diuretic medication (55.1 vs. 25.8%, p < 0.001) on admission than patients with SR. The use of warfarin at discharge was also more frequent in the AF group (55.5 vs. 14.8%, p < 0.001). The rates of all-cause and cardiovascular mortality were higher in the AF group (80.9 vs. 50.3%, p < 0.001, and 73.8 vs. 69.6%, p = 0.285, respectively). In multivariable analysis, AF was independently associated with higher mortality when compared to SR (adjusted HR 1.662; 95% CI: 1.387-1.992, p < 0.001).

Conclusion: AF/atrial flutter at admission and/or discharge independently predicted poorer long-term outcome in ACS patients, with 66% higher mortality within the ≥10-year follow-up time when compared to patients with SR.
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http://dx.doi.org/10.1159/000516369DOI Listing
June 2021

The effect of postoperative complications on health-related quality of life and survival 12 years after coronary artery bypass grafting - a prospective cohort study.

J Cardiothorac Surg 2021 Jun 14;16(1):173. Epub 2021 Jun 14.

Department of Cardio-Thoracic Surgery, Tays Heart Hospital, Tampere University Hospital, Tampere, Finland.

Background: Despite the steady improvements in survival and operative safety, postoperative complications still remain a significant cause of morbidity and mortality after coronary artery bypass grafting (CABG). However, less is known on the impact of postoperative complications on health-related quality of life (QoL). The main objective of our study was to investigate the impact of postoperative complications on long-term QoL and survival after CABG surgery.

Methods: Data of 508 patients, who underwent isolated CABG was prospectively collected. The RAND-36 Health Survey (RAND-36) was used to evaluate patients' QoL status preoperatively, 1 year and 12 years after the surgery. Predefined postoperative complications were reported during primary and secondary hospital stay. QoL and survival analysis were performed primarily on three patient groups: patients with and without complications and patients with major adverse cardiac and cerebrovascular events (MACCE).

Results: In total 205(40%) of 508 patients had at least one postoperative complication and 73 (14%) experienced MACCE. Patients' thirty-day, 1-year and 10-year survival rates were, 99, 98, 84% without complications, 97, 95, 72% with complications, and 90, 89, 64% with MACCE, respectively (log-rank p < 0.001). Patients without complications showed significant(p < 0.05) improvements in seven and patients with complications in five out of eight RAND-36 QoL dimensions. All patient groups showed significant improvements in RAND-36 summary scores compared with preoperative values. Patients with complications and especially with MACCE had more profound decline in their RAND-36 summary scores while patients without complications maintained their health status best.

Conclusions: Despite the constant deterioration, both patients with and without complications showed improvements even 12 years after CABG compared with preoperative state. Postoperative complications and especially MACCE were associated with impaired long-term QoL.
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http://dx.doi.org/10.1186/s13019-021-01527-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8200795PMC
June 2021

Genome-wide analysis identifies novel susceptibility loci for myocardial infarction.

Eur Heart J 2021 03;42(9):919-933

Division Heart & Lungs, Department of Cardiology, University Medical Center Utrecht, Utrecht University, 3584 CX Utrecht, the Netherlands.

Aims: While most patients with myocardial infarction (MI) have underlying coronary atherosclerosis, not all patients with coronary artery disease (CAD) develop MI. We sought to address the hypothesis that some of the genetic factors which establish atherosclerosis may be distinct from those that predispose to vulnerable plaques and thrombus formation.

Methods And Results: We carried out a genome-wide association study for MI in the UK Biobank (n∼472 000), followed by a meta-analysis with summary statistics from the CARDIoGRAMplusC4D Consortium (n∼167 000). Multiple independent replication analyses and functional approaches were used to prioritize loci and evaluate positional candidate genes. Eight novel regions were identified for MI at the genome wide significance level, of which effect sizes at six loci were more robust for MI than for CAD without the presence of MI. Confirmatory evidence for association of a locus on chromosome 1p21.3 harbouring choline-like transporter 3 (SLC44A3) with MI in the context of CAD, but not with coronary atherosclerosis itself, was obtained in Biobank Japan (n∼165 000) and 16 independent angiography-based cohorts (n∼27 000). Follow-up analyses did not reveal association of the SLC44A3 locus with CAD risk factors, biomarkers of coagulation, other thrombotic diseases, or plasma levels of a broad array of metabolites, including choline, trimethylamine N-oxide, and betaine. However, aortic expression of SLC44A3 was increased in carriers of the MI risk allele at chromosome 1p21.3, increased in ischaemic (vs. non-diseased) coronary arteries, up-regulated in human aortic endothelial cells treated with interleukin-1β (vs. vehicle), and associated with smooth muscle cell migration in vitro.

Conclusions: A large-scale analysis comprising ∼831 000 subjects revealed novel genetic determinants of MI and implicated SLC44A3 in the pathophysiology of vulnerable plaques.
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http://dx.doi.org/10.1093/eurheartj/ehaa1040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7936531PMC
March 2021

Inspiratory training and immediate lung recovery after resective pulmonary surgery: a randomized clinical trial.

J Thorac Dis 2020 Nov;12(11):6701-6711

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Background: Prompt and uneventful recovery after resective pulmonary surgery benefits patients by decreasing length and total costs of hospital stay. Postoperative physiotherapy has been shown to be advantageous for patient recovery in several studies and lately inspiratory muscle training (IMT) physiotherapy has been used also in thoracic patients. This randomized controlled trial intended to evaluate whether IMT is an efficient and feasible method of physiotherapy compared to water bottle positive expiratory physiotherapy (PEP) immediately after lung resections.

Methods: Forty-two patients were randomly allocated into two intervention groups: water bottle PEP (n=20) and IMT group (n=22). Patients were given physiotherapeutic guidance once a day and patients were also instructed to do independent exercises. Measurements of pulmonary function were compared between the treatment groups according to intention to treat by using two-way repeated measures analysis of variances at three time points (preoperative, first postoperative day, and second postoperative day). Walking distance was measured at first and second postoperative day and similarly, evaluation of postoperative air leak during exercises was performed. Physiotherapy was modified or temporarily interrupted, if necessary, because of the air leak.

Results: Postoperative pulmonary function tests were equal between the intervention groups. Air leak was relatively common after lung resections: 31% of all patients had mild or moderate/severe air leak at first postoperative day and 14% of all patients had mild to severe air leak at second postoperative day respectively. There were no statistically significant differences in occurrence of air leak between intervention groups, but water resistance had to be reduced or physiotherapy discontinued significantly more often among the water bottle PEP group patients (P=0.01). Walking distance improved slightly faster in the IMT group between the first and the second postoperative day when compared to the water bottle PEP group, but the difference between the groups was not statistically significant.

Conclusions: IMT physiotherapy is equally effective to water bottle PEP training in postoperative physiotherapy after lung resection surgery evaluated with pulmonary function tests and walking distance. In addition, IMT physiotherapy is safe and more feasible form of physiotherapy during postoperative air leak compared to water bottle PEP.
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http://dx.doi.org/10.21037/jtd-20-1668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711407PMC
November 2020

Pleural infection-an indicator of morbidity and increased burden on health care.

Interact Cardiovasc Thorac Surg 2020 10;31(4):513-518

Department of Cardio-Thoracic Surgery, Tays Heart Hospital, Tampere University Hospital, Tampere, Finland.

Objectives: Patients with pleural infections frequently have several comorbidities and inferior long-term survival. We hypothesized that these patients represent a vulnerable cohort with high rates of hospitalization and frequent use of healthcare services. This study aims to ascertain the need for and causes of treatment episodes after pleural infections during long-term follow-up.

Methods: Patients treated for pleural infections at Tampere University Hospital between January 2000 and December 2008 (n = 191, 81% males, median age 58 years) were included and compared to a demographically matched population-based random sample of 1910 controls. Seventy percent of the pleural infections were caused by pneumonias and 80% of the patients underwent surgery. Information regarding later in-hospital periods and emergency room and out-patient clinic visits, as well as survival data, was obtained from national registries and compared between patients and controls.

Results: Patients treated for pleural infections had significantly higher rates of hospitalizations (8.19 vs 2.19), in-hospital days (88.5 vs 26.6), emergency room admissions (3.18 vs 1.45), out-patient clinic visits (41.1 vs 11.8) and procedures performed (1.26 vs 0.55) per 100 patient-months when compared to controls during 5-year follow-up, in addition to having increased mortality (30% vs 11%), P-value <0.00001 each. Particularly, episodes due to respiratory and digestive diseases, malignancies and mental disorders were more frequent. The patients' comorbidities, such as alcoholism or chronic pulmonary disease, were associated with more frequent use of healthcare services.

Conclusions: Patients treated for pleural infections have high rates of hospitalizations, emergency room admissions and out-patient clinic visits during follow-up.
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http://dx.doi.org/10.1093/icvts/ivaa147DOI Listing
October 2020

Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.

Circulation 2020 Aug 13;142(6):546-555. Epub 2020 Jul 13.

Department of Cardiology, Division Heart and Lungs (V.T., A.F.S., J.v.S., A.O.K., F.W.A.), UMC Utrecht, Utrecht University, the Netherlands.

Background: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD.

Methods: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality.

Results: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; =28%; -heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity.

Conclusions: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.045526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493828PMC
August 2020

High Occurrence of Thrombo-Embolic Complications During Long-Term Follow-up After Pleural Infections-A Single-Center Experience with 536 Consecutive Patients Over 17 Years.

Lung 2020 08 30;198(4):671-678. Epub 2020 Jun 30.

Department of Cardio-Thoracic Surgery, Tays Heart Hospital, Tampere University Hospital, Ensitie 4, 33520, Tampere, Finland.

Purpose: Pleural infections are associated with significant inflammation, long hospitalizations, frequent comorbidities, and are often treated operatively-all of which are consequential risk factors for thrombo-embolic complications. However, their occurrence following the treatment of pleural infection is still unknown. The aim of the study was to ascertain the early and long-term occurrence of thrombo-embolic events in patients treated for pleural infections.

Methods: The study included all patients that were treated for pleural infections in Tampere University Hospital between January 2000 and December 2016. Data regarding later treatment episodes due to pulmonary embolisms and/or deep vein thromboses as well as survival data were requested from national registries. The rates were also compared to a demographically matched reference population adjusted for age, sex, and the location of residence.

Results: The final study population comprised 536 patients and 5318 controls (median age 60, 78% men). The most common etiology for pleural infection was pneumonia (73%) and 85% underwent surgical treatment for pleural infection. The occurrence of thrombo-embolic complications in patients and controls was 3.8% vs 0.1% at three months, 5.0% vs 0.4% at one year, 8.8% vs 1.0% at three years, and 12.4% vs 1.8% at five years, respectively, p < 0.001 each. Female sex, advanced age, chronic lung disease, immunosuppression, video-assisted surgery, and non-pneumonic etiology were associated with a higher incidence of thrombo-embolism.

Conclusions: The occurrence of thrombo-embolic events-particularly pulmonary embolism but also deep vein thrombosis-was significant in patients treated for pleural infections, both initially and during long-term follow-up.
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http://dx.doi.org/10.1007/s00408-020-00374-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374478PMC
August 2020

Serum apolipoprotein A-I concentration differs in coronary and peripheral artery disease.

Scand J Clin Lab Invest 2020 Sep 3;80(5):370-374. Epub 2020 Jun 3.

Center for Vascular Surgery and Interventional Radiology, Tampere University Hospital, Tampere, Finland.

Coronary artery and peripheral artery diseases represent different clinical outcomes of atherosclerosis and despite sharing common risk factors the ultimate reasons determining disease presentation are still unclear. The present study sought to define and compare the serum lipid and apolipoprotein profiles of patients undergoing coronary artery bypass grafting and those treated invasively for symptomatic lower extremity peripheral artery disease. Altogether 218 coronary and 280 peripheral artery disease patients treated between 2013 and 2014 in the Tampere University Hospital, Tampere, Finland, with available lipid measurements within two years prior to the intervention were retrospectively analysed. The Extended Friedewald formula neural network model was used to obtain apolipoprotein and lipoprotein subfraction values. Patients undergoing coronary artery bypass surgery had a clear male predominance (82% versus 53%,  < 0.001), lower median age (69 versus 74 years,  < 0.001) and a lower prevalence of smoking (18% versus 32%,  = 0.001) and pulmonary disease (12% versus 20%,  = 0.023) compared to peripheral artery disease patients. There were some differences in the serum lipid profiles between the study groups in the univariable analyses. When controlling for the statistically significant differences in age, sex, urgency of treatment and comorbidities between the groups in a multivariable logistic regression model, higher serum concentrations of apolipoprotein A-I were significantly and independently associated with coronary artery disease (OR 1.11 for 0.01 g/L increase,  = 0.044). In conclusion, patients undergoing coronary artery bypass grafting appear to have higher apolipoprotein A-I levels when compared to patients treated for peripheral artery disease.
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http://dx.doi.org/10.1080/00365513.2020.1746974DOI Listing
September 2020

The prognostic significance of a positive or isoelectric T wave in lead aVR in patients with acute coronary syndrome and ischemic ECG changes in the presenting ECG - Long-term follow-up data of the TACOS study.

J Electrocardiol 2020 May - Jun;60:131-137. Epub 2020 Apr 12.

Faculty of Medicine and Health Technology, Tampere University, Finland; Heart Center, Tampere University Hospital, Finland.

Background: A positive T wave in lead aVR (aVRT+) is an independent prognostic predictor of cardiovascular mortality in the general population as well as in cardiovascular disease.

Subjects And Methods: We evaluated the prognostic impact of aVRT+ in an ECG recorded as close to hospital discharge as possible in acute coronary syndrome patients (n = 527). We divided the patients into three categories based on the findings in the admission ECG: ST elevation, global ischemia and other ST/T changes.

Results: In the whole study population, and in all the three ECG subgroups, the 10-year all-cause mortality rate was higher in the aVRT+ group than in the aVRT- group. In Cox regression analysis, the age and gender adjusted hazard ratio (HR) for aVRT+ to predict all-cause mortality in the whole study population was 1.43 (95% confidence interval [CI] 1.12-1.83; p = 0.004). To predict cardiovascular mortality, the age and gender adjusted HR for aVRT+ was 1.54 (95% CI 1.14-2.07; p = 0.005) in the whole study population and 2.07 (95% CI 1.07-4.03; p = 0.032) in the category with other ST/T changes.

Conclusion: In ACS patients with or without ST elevation, but with ischemic ST/T changes in their presenting ECG, a positive or isoelectric T wave in lead aVR in an ECG recorded in the subacute in-hospital stage is associated with all-cause and cardiovascular mortality during long-term follow-up. Clinicians should pay attention to this simple ECG finding at hospital discharge.
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http://dx.doi.org/10.1016/j.jelectrocard.2020.04.009DOI Listing
June 2021

Risk of symptomatic venous thromboembolism after abdominal aortic aneurysm repair in long-term follow-up of 1021 consecutive patients.

J Vasc Surg Venous Lymphat Disord 2021 01 20;9(1):54-61. Epub 2020 Apr 20.

Department of Cardio-Thoracic Surgery, Tays Heart Hospital, Tampere University Hospital, Tampere, Finland. Electronic address:

Objective: Venous thromboembolism (VTE), including deep venous thrombosis and pulmonary embolism (PE), is an infrequent but consequential and potentially preventable complication after major surgical procedures. The aim of the study was to describe the long-term occurrence of symptomatic VTE in patients undergoing abdominal aortic aneurysm (AAA) repair and to ascertain patient-specific risk factors as well as to compare the rate with that of a reference population.

Methods: The study included all patients who had undergone endovascular or open AAA repair, both elective and urgent/acute cases, at the Tampere University Hospital (Finland) between February 2001 and December 2016; 59% of patients had undergone endovascular and 41% open repair, and 23% of all cases had required urgent or emergency treatment. Information about later treatment episodes for symptomatic VTE and survival data were obtained from national registries. The reference population was obtained from national registries with a random sample of inhabitants matched for age, sex, and location of residence with a 4:1 ratio and was analyzed similarly.

Results: Altogether, 1021 patients and 4065 controls were included (88% male; median age, 74 years in both groups). The high-risk period for VTE lasted for approximately 3 months, and during that time, its occurrence was highest in patients with coronary disease (2.5%), after open repair (2.4%), and in an urgent or emergency setting (2.6%), whereas the rate was low after endovascular aneurysm repair (1.0%). The cumulative incidence of VTE at 3 months, 1 year, 3 years, and 5 years was 1.1%, 1.6%, 2.7%, and 4.5% in patients and 0.1%, 0.3%, 1.0%, and 1.8% in the reference population, respectively (P < .001 each). Most VTE events were PE in the patient group. The 5-year mortality rates were 37.9% in patients and 23.8% in controls (P < .001).

Conclusions: The incidence of symptomatic VTE, particularly PE, after AAA repair is significant, in both short-term and long-term follow-up. Open surgery, acute setting, and concomitant coronary disease appear to increase the risk.
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http://dx.doi.org/10.1016/j.jvsv.2020.03.016DOI Listing
January 2021

The incidence and long-term outcomes of esophageal perforations in Finland between 1996 and 2017 - a national registry-based analysis of 1106 esophageal perforations showing high early and late mortality rates and better outcomes in patients treated at high-volume centers.

Scand J Gastroenterol 2020 Apr 1;55(4):395-401. Epub 2020 Apr 1.

Department of Gastroenterology and Alimentary Tract Surgery, Tampere University Hospital, Tampere, Finland.

Esophageal perforations cause severe life-threatening diseases with significant mortality and morbidity. The national incidence and long-term prognosis of these patients is incompletely described in the current literature. Information regarding each treatment episode for esophageal perforations that had occurred in Finland between 1996 and 2017 and survival data of each patient was obtained from national registries. The occurrence of the disease, related interventions, the number and type of later treatment episodes, as well as the prognosis of these patients was analyzed. The total number of patients with esophageal perforations was 1106 (median age 65, 38% female) and the median follow-up time was 113 months. The overall incidence of the disease was 0.95 (95% CI ± 0.12) per 100,000 person years with male predominance and a trend for slightly increasing occurrence. Esophageal cancer was present in 5.8% of cases. Altogether 41% of patients underwent invasive treatment (31% endoscopic stenting, 69% surgery). Particularly stenting was more frequent later in the series. The median number of disease-related hospitalizations was two and later out-patient clinic visits four. The overall 30-day, 90-day, 1-year and 5-year mortality rates were 14%, 22%, 31% and 46%, respectively, and significantly higher in malignancy-associated cases. There were no clear improvements in the mortality rates over the study period, but the prognosis was better in patients that were treated in higher volume hospitals. There is a slightly increasing trend in the occurrence of esophageal perforations. Contemporary treatment is less invasive with similar results. Patients treated in high-volume hospitals have better prognosis.
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http://dx.doi.org/10.1080/00365521.2020.1746392DOI Listing
April 2020

Early postoperative statin administration does not affect the rate of atrial fibrillation after cardiac surgery.

Eur J Cardiothorac Surg 2020 06;57(6):1154-1159

Department of Cardio-Thoracic Surgery, Tays Heart Hospital, Tampere University Hospital, Tampere, Finland.

Objectives: Postoperative atrial fibrillation is the most frequent complication after cardiac surgery, and the use of statins in preventing them is being extensively studied. The aim of this study was to investigate whether a pause in the administration of statins affects the occurrence of atrial fibrillation after cardiac surgery in a prospective randomized and controlled setting.

Methods: A total of 301 patients without chronic atrial fibrillation with prior statin medication scheduled for elective or urgent cardiac surgery involving the coronary arteries and/or heart valves were prospectively recruited and randomized for statin re-initiation on either the first (immediate statin group) or the fifth (late statin group) postoperative day, using the original medication and dosage. The immediate statin group comprised 146 patients and the late statin group 155 patients. Except for a somewhat higher rate of males (85% vs 73%, P = 0.016) in the immediate statin group, the baseline characteristics and the distribution of procedures performed within the groups were comparable. The occurrence of postoperative atrial fibrillation and the clinical course of the patients were compared between the groups.

Results: The incidence of atrial fibrillation was 46% and the median delay after surgery before the onset of atrial fibrillation was 3 days in both groups (P = NS). No differences were observed in the frequency of the arrhythmia in any subgroup analyses or in other major complications or clinical parameters. No adverse effects related to early statin administration were detected.

Conclusions: Early re-initiation of statins does not appear to affect the occurrence of postoperative atrial fibrillation.

Clinical Trial Registration: European Union Drug Regulating Authorities Clinical Trials Database (EudraCT)-2016-001655-44.
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http://dx.doi.org/10.1093/ejcts/ezz365DOI Listing
June 2020

A device for measuring sternal bone connectivity using vibration analysis techniques.

Proc Inst Mech Eng H 2020 Jan 15;234(1):81-90. Epub 2019 Nov 15.

Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Objectives: Stability of bone splitting sternotomy is essential for normal healing after open cardiac surgery. Mechanical vibration transmittance may offer a means for early detection of separation of bone (diastasis) in the sternotomy and prevent further complications. This article describes the technical implementation and validation of vibration analysis-based prototype device built for measuring sternal bone connectivity after sternotomy.

Methods: An in-house built measurement system, sternal vibration device, consisting of actuator, sensor, and main controller and signal acquisition unit was designed and manufactured. The system was validated, and three different test settings were studied in mockups (polylactide rods in ballistic gel) and in two human sternums: intact, stable wire fixation, and unstable wire fixation with a gap mimicking bone diastasis. The transmittance of vibration stimulus across the median sternotomy was measured.

Results: The validation showed that the force produced by the actuator was stable, and the sensor could be calibrated to precisely measure the acceleration values. The vibration transmittance response to material cut and sternotomy was evident and detectable in the 20 Hz to 2 kHz band. The transmittance decreased when the connectivity between the sternal halves became unstable. The trend was visible in all the settings.

Conclusion: Technical solutions and description of validation process were given. The device was calibrated, and the vibration transmittance analysis differentiated intact and cut polylactide rod. In the sternum, intact bone, wire fixation with exact apposition, and with a gap were identified separately. Although further studies are needed to assess the accuracy of the method to detect different levels of diastases, the method appears to be feasible.
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http://dx.doi.org/10.1177/0954411919884802DOI Listing
January 2020

Model selection for metabolomics: predicting diagnosis of coronary artery disease using automated machine learning.

Bioinformatics 2020 03;36(6):1772-1778

Department of Biostatistics, Epidemiology and Informatics, Institute for Biomedical Informatics, University of Pennsylvania, Philadelphia, PA, USA.

Motivation: Selecting the optimal machine learning (ML) model for a given dataset is often challenging. Automated ML (AutoML) has emerged as a powerful tool for enabling the automatic selection of ML methods and parameter settings for the prediction of biomedical endpoints. Here, we apply the tree-based pipeline optimization tool (TPOT) to predict angiographic diagnoses of coronary artery disease (CAD). With TPOT, ML models are represented as expression trees and optimal pipelines discovered using a stochastic search method called genetic programing. We provide some guidelines for TPOT-based ML pipeline selection and optimization-based on various clinical phenotypes and high-throughput metabolic profiles in the Angiography and Genes Study (ANGES).

Results: We analyzed nuclear magnetic resonance-derived lipoprotein and metabolite profiles in the ANGES cohort with a goal to identify the role of non-obstructive CAD patients in CAD diagnostics. We performed a comparative analysis of TPOT-generated ML pipelines with selected ML classifiers, optimized with a grid search approach, applied to two phenotypic CAD profiles. As a result, TPOT-generated ML pipelines that outperformed grid search optimized models across multiple performance metrics including balanced accuracy and area under the precision-recall curve. With the selected models, we demonstrated that the phenotypic profile that distinguishes non-obstructive CAD patients from no CAD patients is associated with higher precision, suggesting a discrepancy in the underlying processes between these phenotypes.

Availability And Implementation: TPOT is freely available via http://epistasislab.github.io/tpot/.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btz796DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703753PMC
March 2020

Association of Chromosome 9p21 With Subsequent Coronary Heart Disease Events.

Circ Genom Precis Med 2019 04 21;12(4):e002471. Epub 2019 Mar 21.

Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital (M.H.).

Background: Genetic variation at chromosome 9p21 is a recognized risk factor for coronary heart disease (CHD). However, its effect on disease progression and subsequent events is unclear, raising questions about its value for stratification of residual risk.

Methods: A variant at chromosome 9p21 (rs1333049) was tested for association with subsequent events during follow-up in 103 357 Europeans with established CHD at baseline from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) Consortium (73.1% male, mean age 62.9 years). The primary outcome, subsequent CHD death or myocardial infarction (CHD death/myocardial infarction), occurred in 13 040 of the 93 115 participants with available outcome data. Effect estimates were compared with case/control risk obtained from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) including 47 222 CHD cases and 122 264 controls free of CHD.

Results: Meta-analyses revealed no significant association between chromosome 9p21 and the primary outcome of CHD death/myocardial infarction among those with established CHD at baseline (GENIUS-CHD odds ratio, 1.02; 95% CI, 0.99-1.05). This contrasted with a strong association in CARDIoGRAMPlusC4D odds ratio 1.20; 95% CI, 1.18-1.22; P for interaction <0.001 compared with the GENIUS-CHD estimate. Similarly, no clear associations were identified for additional subsequent outcomes, including all-cause death, although we found a modest positive association between chromosome 9p21 and subsequent revascularization (odds ratio, 1.07; 95% CI, 1.04-1.09).

Conclusions: In contrast to studies comparing individuals with CHD to disease-free controls, we found no clear association between genetic variation at chromosome 9p21 and risk of subsequent acute CHD events when all individuals had CHD at baseline. However, the association with subsequent revascularization may support the postulated mechanism of chromosome 9p21 for promoting atheroma development.
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http://dx.doi.org/10.1161/CIRCGEN.119.002471DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6625876PMC
April 2019

Subsequent Event Risk in Individuals With Established Coronary Heart Disease.

Circ Genom Precis Med 2019 04 21;12(4):e002470. Epub 2019 Mar 21.

Department of Pharmacotherapy and Translational Research, Centre for Pharmacogenomics (Y.G., R.M.C.-D., J.A.J.), University of Florida, Gainesville.

Background: The Genetics of Subsequent Coronary Heart Disease (GENIUS-CHD) consortium was established to facilitate discovery and validation of genetic variants and biomarkers for risk of subsequent CHD events, in individuals with established CHD.

Methods: The consortium currently includes 57 studies from 18 countries, recruiting 185 614 participants with either acute coronary syndrome, stable CHD, or a mixture of both at baseline. All studies collected biological samples and followed-up study participants prospectively for subsequent events.

Results: Enrollment into the individual studies took place between 1985 to present day with a duration of follow-up ranging from 9 months to 15 years. Within each study, participants with CHD are predominantly of self-reported European descent (38%-100%), mostly male (44%-91%) with mean ages at recruitment ranging from 40 to 75 years. Initial feasibility analyses, using a federated analysis approach, yielded expected associations between age (hazard ratio, 1.15; 95% CI, 1.14-1.16) per 5-year increase, male sex (hazard ratio, 1.17; 95% CI, 1.13-1.21) and smoking (hazard ratio, 1.43; 95% CI, 1.35-1.51) with risk of subsequent CHD death or myocardial infarction and differing associations with other individual and composite cardiovascular endpoints.

Conclusions: GENIUS-CHD is a global collaboration seeking to elucidate genetic and nongenetic determinants of subsequent event risk in individuals with established CHD, to improve residual risk prediction and identify novel drug targets for secondary prevention. Initial analyses demonstrate the feasibility and reliability of a federated analysis approach. The consortium now plans to initiate and test novel hypotheses as well as supporting replication and validation analyses for other investigators.
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http://dx.doi.org/10.1161/CIRCGEN.119.002470DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6629546PMC
April 2019

Vibration transmittance measures sternotomy stability - a preliminary study in human cadavers.

J Cardiothorac Surg 2019 Jan 7;14(1). Epub 2019 Jan 7.

Department of Cardiothoracic Surgery, Tampere Heart Hospital Co., Ensitie 4, FI-33520, Tampere, Finland.

Background: Stability is essential for the normal healing of a sternotomy. Mechanical vibration transmittance may provide a new means of early detection of diastasis in the sternotomy and thus enable the prevention of further complications. We sought to confirm that vibration transmittance detects sternal diastasis in human tissue.

Methods: Ten adult human cadavers (8 males and 2 females) were used for sternal assessments with a device constructed in-house to measure the transmittance of a vibration stimulus across the median sternotomy at the second, third, and fourth costal cartilage. Intact bone was compared to two fixed bone junctions, namely a stable wire fixation and an unstable wire fixation with a 10 mm wide diastasis mimicking a widely rupturing sternotomy. A generalized Linear Mixed Model with the lme function was used to determine the ability of the vibration transmittance device to differentiate mechanical settings in the sternotomy.

Results: The transmitted vibration power was statistically significantly different between the intact chest and stable sternotomy closure, stable and unstable closure, as well as intact and unstable closure (t-values and p-values respectively: t = 6.87, p < 0.001; t = 7.41, p < 0.001; t = 14.3, p < 0.001). The decrease of vibration transmittance from intact to stable at all tested costal levels was 78%, from stable to unstable 58%, and from intact to unstable 91%. The vibration transmittance power was not statistically significantly different between the three tested costal levels (level 3 vs. level 2; level 4 vs. level 2; level 4 vs. level 3; t-values and p-values respectively t = - 0.36, p = 0.723; t = 0.35, p = 0.728; t = 0.71, p = 0.484).

Conclusions: Vibration transmittance analysis differentiates the intact sternum, wire fixation with exact apposition, and wire fixation with a gap. The gap detection capability is not dependent on the tested costal level. The method may prove useful in the early detection of sternal instability and warrants further exploration.
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http://dx.doi.org/10.1186/s13019-018-0823-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6323770PMC
January 2019

Biomarker Glycoprotein Acetyls Is Associated With the Risk of a Wide Spectrum of Incident Diseases and Stratifies Mortality Risk in Angiography Patients.

Circ Genom Precis Med 2018 11;11(11):e002234

Research Programs Unit, Diabetes and Obesity, University of Helsinki, Finland. (P.W.).

Background: Integration of systems-level biomolecular information with electronic health records has led to recent interest in the glycoprotein acetyls (GlycA) biomarker-a serum- or plasma-derived nuclear magnetic resonance spectroscopy signal that represents the abundance of circulating glycated proteins. GlycA predicts risk of diverse outcomes, including cardiovascular disease, type 2 diabetes mellitus, and all-cause mortality; however, the underlying detailed associations of GlycA's morbidity and mortality risk are currently unknown.

Methods: We used 2 population-based cohorts totaling 11 861 adults from the Finnish general population to test for an association with 468 common incident hospitalization and mortality outcomes during an 8-year follow-up. Further, we utilized 900 angiography patients to test for GlycA association with mortality risk and potential utility for mortality risk discrimination during 12-year follow-up.

Results: New associations with GlycA and incident alcoholic liver disease, chronic renal failure, glomerular diseases, chronic obstructive pulmonary disease, inflammatory polyarthropathies, and hypertension were uncovered, and known incident disease associations were replicated. GlycA associations for incident disease outcomes were in general not attenuated when adjusting for hsCRP (high-sensitivity C-reactive protein). Among 900 patients referred to angiography, GlycA had hazard ratios of 4.87 (95% CI, 2.45-9.65) and 5.00 (95% CI, 2.38-10.48) for 12-year risk of mortality in the fourth and fifth quintiles by GlycA levels, demonstrating its prognostic potential for identification of high-risk individuals. When modeled together, both hsCRP and GlycA were attenuated but remained significant.

Conclusions: GlycA was predictive of myriad incident diseases across many major internal organs and stratified mortality risk in angiography patients. Both GlycA and hsCRP had shared and independent contributions to mortality risk, suggesting chronic inflammation as an etiological factor. GlycA may be useful in improving risk prediction in specific disease settings.
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http://dx.doi.org/10.1161/CIRCGEN.118.002234DOI Listing
November 2018

Multi-ethnic genome-wide association study for atrial fibrillation.

Nat Genet 2018 06 11;50(9):1225-1233. Epub 2018 Jun 11.

Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
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http://dx.doi.org/10.1038/s41588-018-0133-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6136836PMC
June 2018

The effect of obesity on long-term survival and health-related quality of life after coronary artery bypass grafting: a 12-year follow-up.

Coron Artery Dis 2018 08;29(5):378-383

Department of Cardiothoracic Surgery, Heart Center, Tampere University Hospital.

Objective: The proportion of obese patients undergoing coronary artery bypass graft (CABG) surgery is increasing. In this study, our main objective was to assess the effect of obesity on long-term mortality and changes in quality of life (QoL) after GABG.

Materials And Methods: Data of 508 patients who underwent isolated GABG were prospectively collected. RAND-36 Health Survey (RAND-36) was used as an indicator of QoL. BMI was used to assess obesity, and the analysis was based primarily on two patient groups: BMI less than 30 kg/m (408 patients) and BMI of at least 30 (100 patients). All assessments were made preoperatively and repeated 1 and 12 years after CABG surgery. The follow-up of the cohort was complete in 95 and 84% of the alive patients at 1 and 12 years, respectively.

Results: Thirty-day, 1-year, and 10-year survival rates were 99.0, 97.0, and 78.0%, respectively, in the obese and 98.0, 96.8, and 79.2%, respectively, in the nonobese group. Obese showed significant (P<0.05) improvements only in four and nonobese in seven of eight RAND-36 dimensions of QoL. In both obese and nonobese patients, improved RAND-36 physical component summary and mental component summary scores were seen in comparison with the preoperative values. Yet, obese patients had a more pronounced diminution in their physical component summary and mental component summary scores, whereas nonobese patients maintained their physical and mental health status better.

Conclusion: Despite an on-going decline in 12 years after the CABG, both patient groups showed improvements in their health status in comparison with preoperative values. Obese patients gained less benefit in terms of QoL dimension, but there was no significant difference in overall mortality in the long-term follow-up.
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http://dx.doi.org/10.1097/MCA.0000000000000622DOI Listing
August 2018

Pulmonary vascular resistance index during coronary artery bypass surgery with aprotinin.

Scand J Clin Lab Invest 2017 Sep 2;77(5):315-320. Epub 2017 May 2.

a Department of Cardiothoracic Surgery , Heart Center, Tampere University Hospital and University of Tampere , Tampere , Finland.

Low pulmonary vascular resistance index (PVRI) reflects favorable redundant pulmonary circulation following coronary artery bypass grafting with cardiopulmonary bypass surgery (CPB). This randomized study investigated whether aprotinin given in different modalities impacts PVRI after coronary artery bypass grafting. A total of 40 patients undergoing coronary artery bypass grafting were randomized to four groups according to aprotinin dose: (1) high dose, (2) early low dose, (3) late low dose, and (4) without aprotinin. Oxygenation index, pulmonary shunt, alveolar-arterial oxygen gradient and PVRI were determined. PVRI was calculated as the transpulmonary pressure gradient divided by cardiac index multiplied by 80. The results showed that PVRI remained relative low in all patients provided aprotinin regardless of treatment dosage; PVRI increased at 4 h after restarting ventilation after CPB in patients without aprotinin as compared with aprotinin (266 ± 137, 266 ± 115, 244 ± 86 vs. 386 ± 121, dynes-s-cm, respectively, p = .047). Elevated postoperative PVRI was predictive for patients without aprotinin (AUC 0.668; SE 0.40; p < .0001; CI 0.590-0.746). There were no statistical differences in oxygenation index, pulmonary shunt or alveolar-arterial oxygen gradient between the groups. In conclusion, aprotinin maintains a low PVRI in elective patients with healthy lungs during CPB. We suggest that aprotinin maintains pulmonary arterial endothelial integrity.
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http://dx.doi.org/10.1080/00365513.2017.1318446DOI Listing
September 2017

Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation.

Nat Genet 2017 Jun 17;49(6):946-952. Epub 2017 Apr 17.

Institute for Stroke and Dementia Research, Klinikum der Universität München, Ludwig-Maximilians-Universität, Munich, Germany.

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery.
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http://dx.doi.org/10.1038/ng.3843DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585859PMC
June 2017

Incidence, presentation and risk factors of late postoperative pericardial effusions requiring invasive treatment after cardiac surgery.

Interact Cardiovasc Thorac Surg 2017 06;24(6):835-840

Department of Cardio-Thoracic Surgery, Heart Hospital, Tampere University Hospital, Tampere, Finland.

Objectives: Occurrence and risk factors of late postoperative pericardial effusions requiring invasive treatment, i.e. pretamponade and tamponade, following cardiac surgery are incompletely described in current literature. The purpose of this study was to define the incidence and presentation of late pretamponade and tamponade as well as to outline significant predisposing factors.

Methods: A cohort of 1356 consecutive cardiac surgery patients treated in a tertiary academic centre between January 2013 and December 2014 was followed up for 6 months after surgery. Pericardial effusion was considered late when presenting after the 7th postoperative day. The incidence, timing and risk factors, as well as symptoms and clinical findings associated with late pretamponade and tamponade in patients surviving at least 7 days was analysed.

Results: Of 1308 patients included in the analysis, 81 (6.2%) underwent invasive treatment for late postoperative pericardial effusion, 27 (2.1%) for pretamponade and 54 (4.1%) for tamponade, respectively, with a median delay of 11 (range 8-87) days after the primary operation. Haemodynamic instability was present in 34.6%, signs of cardiac chamber compression in 54.3% and subjective symptoms, mostly dyspnoea, in 56.8% of patients, respectively. Treated patients were younger, had lower EuroSCORE-II rating, less coronary disease, better cardiac function, higher preoperative haemoglobin values and had mostly undergone elective surgery involving cardiac valves. In multivariable analysis, independent risk factors were single valve surgery and high preoperative haemoglobin level, whereas age 60-69 years was associated with lower risk.

Conclusions: Younger, generally healthier patients undergoing valve surgery are at greatest risk for developing late tamponade or pretamponade.
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http://dx.doi.org/10.1093/icvts/ivx011DOI Listing
June 2017

Electrocardiographic findings during balloon angioplasty of the left circumflex coronary artery - influence of location of the ischemic segments with respect to the obtuse margin of the left ventricle.

J Electrocardiol 2017 Jan - Feb;50(1):102-110. Epub 2016 Jun 21.

Heart Center, Department of Cardiology, Tampere University Hospital, and School of Medicine, University of Tampere, Finland. Electronic address:

Background: Acute left circumflex coronary artery (LCx) occlusion is not easily detected by the standard 12-lead electrocardiogram (ECG).

Methods: In 16 patients continuous ECG recording was performed during balloon occlusion. The treated lesions were divided into proximal and distal based on the location of the ischemic segments with respect to the left obtuse margin of the heart.

Results: Mean ΔST (=ST amplitude during inflation - pre-inflation ST) ≥0.5mm in both leads I and aVL predicted a proximal occlusion site with sensitivity of 62.5% (95% confidence interval [CI] 24.9-91.5%), specificity 100% (95% CI 63.1-100%), positive predictive value 100% (95% CI 47.8-100%), and negative predictive value 72.7% (95% CI 39-94%). In lead III, mean ΔST was +0.3mm in the distal and -0.2mm in the proximal group, respectively (p=0.036).

Conclusions: ST elevation in leads I and aVL is associated with myocardial ischemia at or proximal to the left obtuse margin.
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http://dx.doi.org/10.1016/j.jelectrocard.2016.06.004DOI Listing
November 2017

Increasing Occurrence of Postoperative Atrial Fibrillation in Contemporary Cardiac Surgery.

J Cardiothorac Vasc Anesth 2016 Oct 12;30(5):1302-7. Epub 2016 Feb 12.

Department of Cardiothoracic Surgery, Heart Hospital, Tampere University Hospital, Tampere, Finland.

Objective: Patients referred for cardiac surgery are increasingly older, with a higher prevalence of significant comorbidities and undergoing more extensive surgery. The aim of the study was to ascertain the incidence and presentation of postoperative atrial fibrillation in contemporary patients.

Design: A prospective single-center study.

Setting: A tertiary academic center.

Participants: Between January 2013 and December 2014, 1,356 consecutive patients (72% male, median age 68), including urgent and emergency cases, were analyzed. Preoperative paroxysmal atrial fibrillation was present in 163 (12%) and chronic in 156 (12%) patients.

Interventions: No interventions.

Measurements And Main Results: Of the 1,164 patients without chronic atrial fibrillation and surviving at least 5 days, 599 (51%) developed postoperative atrial fibrillation, 43% after bypass, 55% after single valve, 74% after multiple valve, 66% after combined bypass and valve, and 54% after aortic procedures, p<0.001, respectively. In 29%, the duration of postoperative atrial fibrillation was less than 48 hours and did not recur, whereas in 71% the arrhythmia persisted for at least 48 hours or recurred during hospitalization. Patients with postoperative atrial fibrillation were significantly older, had a higher prevalence of previous atrial fibrillation and hypertension, larger left atrium, and required longer hospitalization with increased rates of reoperations and infectious complications.

Conclusions: The authors report high, 10% to 20% greater than previously described, occurrence of postoperative atrial fibrillation in contemporary patients undergoing cardiac surgery. Most patients with postoperative atrial fibrillation experienced prolonged duration or recurrence of the arrhythmia. The type of surgery, advanced age, and previous atrial fibrillation were the most important risk factors.
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http://dx.doi.org/10.1053/j.jvca.2016.02.013DOI Listing
October 2016

Rational Autologous Cell Sources For Therapy of Heart Failure - Vehicles and Targets For Gene and RNA Therapies.

Curr Gene Ther 2016 ;16(1):21-33

Faculty of Medicine, Department of Pharmacology, P.O. Box 63 (Haartmaninkatu 8), FI-00014 University of Helsinki, Finland.

This review focuses on the possibilities for intraoperative processing and isolation of autologous cells, particularly atrial appendage-derived cells (AADCs) and cellular micrografts, and their straightforward use in cell transplantation for heart failure therapy. We review the potential of autologous tissues to serve as sources for cell therapy and consider especially those tissues that are used in surgery but from which the excess is currently discarded as surgical waste. We compare the inculture expanded cells to the freshly isolated ones in terms of evidence-based cost-efficacy and their usability as gene- and RNA therapy vehicles. We also review how financial and authority-based decisions and restrictions sculpt the landscape for patients to participate in academic-based trials. Finally, we provide an insight example into AADCs isolation and processing for epicardial therapy during coronary artery bypass surgery.
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http://dx.doi.org/10.2174/1566523216666160104141809DOI Listing
November 2016

Symptoms of Sternal Nonunion Late after Cardiac Surgery.

Thorac Cardiovasc Surg 2017 Jun 24;65(4):325-331. Epub 2015 Apr 24.

Department of Cardiothoracic Surgery, Heart Center Co., Tampere University Hospital, Tampere, Finland.

 A cohort of patients having symptoms of sternal nonunion late after sternotomy was studied to find out whether the complaints were related to true sternal nonunion or decreased bone density.  A survey was mailed to 2,053 cardiac surgical patients operated in our institution between July 2007 and June 2010. The patients were requested about symptoms referring to sternal instability. A group of symptomatic individuals as well as 1:1 age- and time-matched asymptomatic controls were examined with sternal palpation, ultrasound during standardized sternal pressure provocation, and computed tomography (CT).  The number of patients replied in the survey was 1,918 (93.4%); 2.3% (44 patients) reported sensation of movement or clicking in sternum during body movements and during coughing. Symptomatic patients living within 200 km to the hospital (21) and their asymptomatic controls (21) were selected for further clinical and imaging studies. Mean period between the initial operation and the examinations was 36 (22-56) months. Sternal palpation pain was significantly associated with reported symptoms suggestive of sternal nonunion (odds ratio [OR] 22.0; 95% confidence interval [CI] 2.5-195); however, none of the patients had clinically unstable sternum or nonunion in the sternal imaging. The symptoms of sternal instability were more frequent in patients whose bone mineralization rate (as measured with T-scores) was higher.  Symptoms suggestive of sternal nonunion were experienced by 2.3%. However, their symptoms did not correlate with CT scans or provocation ultrasound although palpation pain was evident. Thus the pain is derived from nonmechanical etiologies. Higher bone mineralization rate correlated with abnormal symptoms of sternal wound.
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http://dx.doi.org/10.1055/s-0035-1549360DOI Listing
June 2017

Adipocytokine resistin correlates with oxidative stress and myocardial injury in patients undergoing cardiac surgery.

Eur J Cardiothorac Surg 2014 Oct 30;46(4):729-36. Epub 2014 Jan 30.

The Immunopharmacology Research Group, University of Tampere School of Medicine and Tampere University Hospital, Tampere, Finland.

Objectives: Adipocytokines are hormones regulating energy metabolism and appetite and according to recent reports also inflammatory responses including ischaemia-reperfusion injury. Based on experimental data, we hypothesized that the levels of adipocytokines adiponectin, adipsin, leptin and/or resistin would correlate with myocardial injury, inflammation and oxidative stress during cardiac surgery.

Methods: Thirty-two patients undergoing an elective on-pump coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass (CPB) were recruited into the study. Blood samples were collected after the induction of anaesthesia, and at the onset of CPB, 1 and 15 min after the removal of aortic cross-clamp and 4 and 24 h after the onset of CPB. Samples were analysed for levels of four adipocytokines (adiponectin, adipsin, leptin and resistin) and markers of oxidative stress [myeloperoxidase (MPO) and 8-isoprostane], inflammation [interleukin-6 (IL-6)] and myocardial injury [troponin T (TnT)].

Results: Adiponectin and adipsin concentrations declined, while leptin and resistin levels increased significantly by 24 h after the onset of the operation. Interestingly, basal levels of resistin (r = 0.41, P = 0.020) as well as the maximal increase occurring in resistin levels during the 24-h follow-up (r = 0.49, P = 0.005) correlated positively with TnT release. In addition, the reperfusion-induced elevation in resistin levels correlated positively with oxidative stress measured as increases in MPO concentrations.

Conclusions: As an original finding, we report here that resistin levels correlate with oxidative stress and myocardial injury in patients undergoing cardiac surgery. In addition, leptin levels were increased on the first postoperative day, but only minor declines were found in adiponectin and adipsin levels. Resistin has been implicated in unfavourable metabolic, cardiovascular and inflammatory responses: it may thus serve as a useful biomarker or a drug target in conditions complicated by ischaemia-reperfusion injury.
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http://dx.doi.org/10.1093/ejcts/ezt634DOI Listing
October 2014
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