<p>The aim was to study pathophysiological mechanisms and risk factors for developing atrial fibrillation (AF) after coronary artery bypass grafting (CABG), and the effect of thoracic epidural anaesthesia (TEA).</p><p>The study comprised 141 patients undergoing CABG, including 45 patients randomised for TEA intra- and postoperatively. All patients underwent 24-hour Holter monitoring pre- and postoperatively for the analysis of arrhythmias and heart rate variability (HRV). Catecholamines and neuropeptides (reflecting sympathetic and parasympathetic activity), atrial peptides and echocardiographically assessed atrial arias were obtained pre- and postoperatively.</p><p>Logistic regression analysis identified body mass index (BMI), maximum supraventricular beats (SPB) per minute, and total amount of cardioplegia as independent predictors of postoperative AF. Patients developing AF showed limited diurnal variation of HRV preoperatively. All HRV parameters decreased significantly in all patients postoperatively. The significant postoperative increase in atrial areas and atrial peptides did not differ between patients developing AF and those who did not. TEA had no effect on the incidence of postoperative AF, but resulted in lower heart rate, less increase in adrenaline levels, and decreased neuropeptide levels (reflecting sympathetic and parasympathetic activity). AF was initiated by an SPB in 72.4% of non-TEA and 100% of TEA treated patients, whereas changes in heart rate only, before onset, were seen in 17.2% non-TEA patients.</p><p>The observed risk factors, SPB and cardioplegia, may both induce electrophysiological changes known to increase the susceptibility to AF. The observed postoperative atrial dilatation and autonomic imbalance, indicated by HRV and neuropeptide levels, may further favour the development of AF. The observation that a majority of postoperative AF was initiated by a premature atrial contraction supports our hypothesis that latent atrial foci may be a major trigger mechanism of postoperative AF.</p>

The aim was to study pathophysiological mechanisms and risk factors for developing atrial fibrillation (AF) after coronary artery bypass grafting (CABG), and the effect of thoracic epidural anaesthesia (TEA). The study comprised 141 patients undergoing CABG, including 45 patients randomised for TEA intra- and postoperatively. All patients underwent 24-hour Holter monitoring pre- and postoperatively for the analysis of arrhythmias and heart rate variability (HRV). Catecholamines and neuropeptides (reflecting sympathetic and parasympathetic activity), atrial peptides and echocardiographically assessed atrial arias were obtained pre- and postoperatively. Logistic regression analysis identified body mass index (BMI), maximum supraventricular beats (SPB) per minute, and total amount of cardioplegia as independent predictors of postoperative AF. Patients developing AF showed limited diurnal variation of HRV preoperatively. All HRV parameters decreased significantly in all patients postoperatively. The significant postoperative increase in atrial areas and atrial peptides did not differ between patients developing AF and those who did not. TEA had no effect on the incidence of postoperative AF, but resulted in lower heart rate, less increase in adrenaline levels, and decreased neuropeptide levels (reflecting sympathetic and parasympathetic activity). AF was initiated by an SPB in 72.4% of non-TEA and 100% of TEA treated patients, whereas changes in heart rate only, before onset, were seen in 17.2% non-TEA patients. The observed risk factors, SPB and cardioplegia, may both induce electrophysiological changes known to increase the susceptibility to AF. The observed postoperative atrial dilatation and autonomic imbalance, indicated by HRV and neuropeptide levels, may further favour the development of AF. The observation that a majority of postoperative AF was initiated by a premature atrial contraction supports our hypothesis that latent atrial foci may be a major trigger mechanism of postoperative AF.

In Part I we found that the CYP2C9 genotype appears to influence the diastolic blood pressure response to the angiotensin II-receptor antagonist irbesartan in patients with hypertension and left ventricular hypertrophy. Those with the *1/*2 genotype (slower metabolism) responded better than those with the *1/*1 genotype (normal metabolism), likely due to a slower elimination of the drug. We further found that a +9/-9 exon 1 polymorphism of the B2 bradykinin receptor gene – shown to affect mRNA expression - appears to influence the regression of left ventricular mass during therapy with irbesartan or the beta-blocker atenolol in the same patients. Subjects with the -9/-9 genotype (higher mRNA expression) had a greater regression than carriers of the +9 allele. In Part II we found that women on digoxin therapeutic drug monitoring have higher serum digoxin concentrations (SDCs) as compared to men (1.54±0.04 [nmol/L±SE] vs 1.20±0.05 [nmol/L±SE], p&lt;0.001), which could be of importance since an SDC &gt;1.4 nmol/L has been associated with increased mortality. We further found that coadministration of P-glycoprotein inhibitors with digoxin was common (47%) among the same patients, and that the SDC increased in a stepwise fashion with the number of P-glycoprotein inhibitors (20-60%). Lastly, we found that patients admitted to Swedish coronary care units with atrial fibrillation without heart failure and who had been given digoxin had a higher 1-year mortality than those not given digoxin (RR 1.44 [95% CI 1.29-1.60], adjustment made for potential confounders). In conclusion, Part I represents a further step in the pharmacogenomic prospect of tailoring antihypertensive therapy. Part II indicates that heightened attention to the digoxin-dose is warranted in women, that there is a need for awareness about P-glycoprotein interactions with digoxin, and that long-term therapy with digoxin is an independent risk factor for death among patients with atrial fibrillation without heart failure.

The overall aim of this thesis was to study the influence of physical activity on health. Risks and benefits of physical activity is of particular interest since there is a global trend of less physical activity among youths and adults. In order to investigate this aim we used a database from a large cross country ski race, Vasaloppet, with participants with a wide age range, and with both elite athletes and ordinary people who exercise and promote their health. The most serious risk of strenuous exercise is sudden death and it is challenging to identify preventive effects of major endemic diseases. Using epidemiological methodology we studied 200 000 Vasaloppet skiers and compared them with the general population. Based on personal identification numbers we added data from Swedish national personal and health registers, clinical registers as the cancer register, Swedeheart, or Swedish stroke register, and socioeconomic information from Statistics Sweden. In the Vasaloppet database we collected data on age, gender, finish time and number of races during the period 1989 to 2010. We evaluated risk of death during the race in two papers (I,II). During 90 years of annual races, cardiac arrest occurred in 20 skiers, of which five survived. The death rate is in average two per 100 000 skiers. We also studied the association with cancer incidence (paper III). The overall reduction of cancer was modest among skiers compared with the general population, but for cancers related to lifestyle the risks were markedly lower. We investigated the risk for recurrent myocardial infarction and found a 30% reduction among skiers (paper IV). In paper V we showed that skiers with a first stroke have a lower incidence of all-cause death. The skiers had a higher frequency of atrial fibrillation but had less severe stroke and no increased risk of recurrent stroke. Thus our data suggest that a lifestyle with a high level of physical activity may work as a protection after a cardiovascular event. Summary: The short excess mortality in endurance physical activity is by far outweighed by the long term protective effect of exercise in cardiovascular diseases and cancer.

Postoperative atrial fibrillation (AF) after cardiac surgery with cardiopulmonary bypass (CPB) remains unresolved problem. Some authors noticed that there were changes in electrolyte balance after coronary artery bypass grafting (CABG) surgery with CPB. The changes in serum magnesium level and their relation with the rate of postoperative AF are usually analyzed in scientific publications. The aim of the study has been to estimate the relationship between the rate of postoperative AF and the changes in serum electrolyte concentration and their urinary excretion after CABG surgery with CPB. The goals: 1) To estimate the rate and the character of postoperative AF and its influence on haemodynamics after CABG surgery. 2) To estimate changes in serum K+, Na+, Mg++, Ca++, Cl–, P– concentration and compare them between the patients who received, and who did not receive magnesium sulphate supplementation during the surgery. 3)To estimate changes of urinary excretion of K+, Na+, Mg++, Ca++, Cl–, P– and compare them between the patients who received, and who did not receive magnesium sulphate supplementation during the surgery. 3) To evaluate the effects of intraoperatively infused magnesium sulphate on the rate of postoperative AF in the early postoperative period. In our study the rate of postoperative AF was 27.4 %. AF in 91.3 % of cases was tachyarrhythmic, but haemodynamic remained stabile. Serum Mg++ level was > 1.05 mmol/l during the suregry in all patients. The infusion of... [to full text]

The aim of present study was to investigate the prognostic value of plasma and atrial tissue expression of prothrombotic, proinflammatory and extracellular matrix turnover indices for the development of atrial fibrillation (AF) after on-pump coronary artery bypass grafting (CABG) surgery and to describe atrial ultrastructural changes in patients suffering from severe coronary artery disease. Methods: Blood samples were obtained from peripheral vein (PV) and from intracardiac chambers (right atrium (RA), right atrial appendage (RAA), left atrium (LA) and left atrial appendage (LAA)) amongst 100 consecutive patients undergoing elective on-pump CABG. Biomarker (high sensitivity C reactive protein (hs-CRP), interleukin 6 (IL-6), von Willebrand factor (vWF), tissue factor (TF), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1)) concentrations were related to incident AF (in 30 days after CABG). The RAA and LAA tissues were tested for expression of vWF, TF, IL-6, MMP-9 and TIMP-1 using immunohistochemistry. The ultrastructure of the RAA and LAA in 20 patients was examined by electron microscopy. Results: Levels of plasma vWF, TF, hs-CRP, MMP-9 and TIMP-1 differ in-between various intracardiac sampling sites. Higher plasma hs-CRP levels in the PV, RAA and LA, higher plasma IL-6 levels in the RAA, LA and LAA and higher plasma MMP-9 levels in the LAA are associated with postoperative AF. An increased expression of vWF by the LAA is a risk... [to full text] / Tyrimo tikslas – išaiškinti prognostinę kraujo plazmoje ir prieširdžių audinyje nustatomų prokoaguliacinių, prouždegiminių citokinų ir ekstraląstelinio matrikso degradacijos žymenų vertę pooperacinio prieširdžių virpėjimo (PV) išsivystymui pacientams, kuriems atliekama izoliuota AVJO su dirbtine kraujo apytaka (DKA) bei aprašyti šių pacientų prieširdžių audinio ultrastruktūros pakitimus. Metodai: Kraujo mėginiai paimti iš 5 skirtingų 100 pacientų, kuriems buvo atliekama izoliuota AVJO su DKA, vietų: periferinio kraujo (PK), dešiniojo prieširdžio (DP), dešiniojo prieširdžio ausytės (DPA), kairiojo prieširdžio (KP), kairiojo prieširdžio ausytės (KPA). Kraujo plazmos citokinai (von Willebrand faktorius (vWF), audinių faktorius (AF), didelio jautrumo C reaktyvus baltymas (dj-CRB), interleukinas 6 (IL-6), matrikso metaloproteinazė 9 (MMP-9) bei matrikso metaloproteinazių audinių inhibitorius 1 (TIMP-1)) tirti imunofermentiniais metodais. DPA ir KPA biopsijos tirtos imunohistocheminiais metodais dėl vWF, AF, IL-6, MMP-9 bei TIMP-1 ekspresijos. DPA ir KPA ultrastruktūros pakitimai ištirti 20-iai pacientų elektroninės mikroskopijos būdu. Rezultatai: Nustatėme, kad plazmos vWF, AF, MMP-9, TIMP-1 ir dj-CRB koncentracijos skiriasi įvairiose prieširdžių vietose. Didesnės plazmos dj-CRB koncentracijos PK, DPA ir KP, taip pat plazmos IL-6 koncentracijos DPA, KP ir KPA bei plazmos MMP-9 koncentracija KPA buvo susiję su pooperacinio PV kilimu. vWF žymesnė ekspresija KPA buvo susijusi su PV... [toliau žr. visą tekstą]

Tyrimo tikslas – išaiškinti prognostinę kraujo plazmoje ir prieširdžių audinyje nustatomų prokoaguliacinių, prouždegiminių citokinų ir ekstraląstelinio matrikso degradacijos žymenų vertę pooperacinio prieširdžių virpėjimo (PV) išsivystymui pacientams, kuriems atliekama izoliuota AVJO su dirbtine kraujo apytaka (DKA) bei aprašyti šių pacientų prieširdžių audinio ultrastruktūros pakitimus. Metodai: Kraujo mėginiai paimti iš 5 skirtingų 100 pacientų, kuriems buvo atliekama izoliuota AVJO su DKA, vietų: periferinio kraujo (PK), dešiniojo prieširdžio (DP), dešiniojo prieširdžio ausytės (DPA), kairiojo prieširdžio (KP), kairiojo prieširdžio ausytės (KPA). Kraujo plazmos citokinai (von Willebrand faktorius (vWF), audinių faktorius (AF), didelio jautrumo C reaktyvus baltymas (dj-CRB), interleukinas 6 (IL-6), matrikso metaloproteinazė 9 (MMP-9) bei matrikso metaloproteinazių audinių inhibitorius 1 (TIMP-1)) tirti imunofermentiniais metodais. DPA ir KPA biopsijos tirtos imunohistocheminiais metodais dėl vWF, AF, IL-6, MMP-9 bei TIMP-1 ekspresijos. DPA ir KPA ultrastruktūros pakitimai ištirti 20-iai pacientų elektroninės mikroskopijos būdu. Rezultatai: Nustatėme, kad plazmos vWF, AF, MMP-9, TIMP-1 ir dj-CRB koncentracijos skiriasi įvairiose prieširdžių vietose. Didesnės plazmos dj-CRB koncentracijos PK, DPA ir KP, taip pat plazmos IL-6 koncentracijos DPA, KP ir KPA bei plazmos MMP-9 koncentracija KPA buvo susiję su pooperacinio PV kilimu. vWF žymesnė ekspresija KPA buvo susijusi su PV... [toliau žr. visą tekstą] / The aim of present study was to investigate the prognostic value of plasma and atrial tissue expression of prothrombotic, proinflammatory and extracellular matrix turnover indices for the development of atrial fibrillation (AF) after on-pump coronary artery bypass grafting (CABG) surgery and to describe atrial ultrastructural changes in patients suffering from severe coronary artery disease. Methods: Blood samples were obtained from peripheral vein (PV) and from intracardiac chambers (right atrium (RA), right atrial appendage (RAA), left atrium (LA) and left atrial appendage (LAA)) amongst 100 consecutive patients undergoing elective on-pump CABG. Biomarker (high sensitivity C reactive protein (hs-CRP), interleukin 6 (IL-6), von Willebrand factor (vWF), tissue factor (TF), matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of matrix metalloproteinase 1 (TIMP-1)) concentrations were related to incident AF (in 30 days after CABG). The RAA and LAA tissues were tested for expression of vWF, TF, IL-6, MMP-9 and TIMP-1 using immunohistochemistry. The ultrastructure of the RAA and LAA in 20 patients was examined by electron microscopy. Results: Levels of plasma vWF, TF, hs-CRP, MMP-9 and TIMP-1 differ in-between various intracardiac sampling sites. Higher plasma hs-CRP levels in the PV, RAA and LA, higher plasma IL-6 levels in the RAA, LA and LAA and higher plasma MMP-9 levels in the LAA are associated with postoperative AF. An increased expression of vWF by the LAA is a risk... [to full text]

Atrial fibrillation is the most prevalent form of cardiac arrhythmia. Studies in animal modelshave provided important insights into arrhythmia mechanisms. However, to date, we do not dispose ofanimal models of spontaneous atrial arrhythmia.Thus, we aimed to develop a model of spontaneous atrial arrhythmia in rats and to assesspathophysiological mechanisms of these arrhythmias by using a multidisciplinary approach. We alsoaimed to assess the presence and the extent of inflammation and endothelial dysfunction, incriminatedin atrial fibrillation-related complications such as stroke, in atrial fibrillation patients.The animal study describes the first animal model of spontaneous atrial arrhythmias. We alsoprovide evidence that multiple mechanisms participate in arrhythmia occurrence in this model,particularly autonomic imbalance with relative vagal hyperactivity, left atrial endocardial fibrosis, anddecreased left atrial expression of the Pitx2 gene. In our clinical study, we found high levels ofvascular endothelial growth factor and von Willebrand factor in atrial fibrillation patients compared tosinus rhythm controls. These results suggest specific thromboembolic risk patterns according to theclinical form of arrhythmia and highlight a parallel evolution of atrial fibrillation and endothelialdysfunction. These results add new insights into the understanding of atrial arrhythmias. This new animalmodel could facilitate studies of pathophysiological mechanisms involved in atrial arrhythmias andallow assessment of efficacy and toxicity of therapeutic agents in a setting that faithfully reproducesthe clinical presentation of the arrhythmia

Objectif: Déterminer si l’efficacité de l’amiodarone pour le maintien du rythme sinusal varie selon la fonction systolique ventriculaire gauche. Contexte: Malgré un profil de sécurité établi en insuffisance cardiaque, nous ignorons si l’efficacité de l’amiodarone et son impact sur différentes issues cardiovasculaires sont modulés par la fonction ventriculaire gauche. Méthode: Nous avons effectué une analyse combinée de 3307 patients (âgés de 68,0±0,9 ans ; 31,1% de femmes) recrutés dans les études AFFIRM et AF-CHF qui ont été randomisés au contrôle du rythme par l’amiodarone (N=1107) ou au contrôle de la fréquence cardiaque (N=2200). Résultats: Chez les patients sous amiodarone, la survie sans fibrillation auriculaire était de 84% et de 45% à 1 et 5 ans respectivement, sans égard à la fraction d’éjection ventriculaire gauche (P=0,8754, ajusté). De façon similaire, la proportion moyenne ajustée de temps en fibrillation auriculaire (15,0±1,8%) n’a pas été influencée par la fraction d’éjection (P=0,6094). Durant le suivi, 1963 patients (59,4%) ont requis au moins une hospitalisation, incluant 1401 (42,6%) patients hospitalisés pour cause cardiovasculaire. Les taux ajustés d’hospitalisation pour toutes causes et pour cause cardiovasculaire étaient similaires entre les patients sous amiodarone et ceux dans le groupe de contrôle de la fréquence dans l’ensemble de la population ainsi que dans les sous-groupes de patients avec et sans dysfonction ventriculaire gauche sévère. De façon similaire, les taux ajustés de mortalité globale et cardiovasculaire étaient similaires entre chez les patients sous amiodarone et ceux traités par le contrôle de la fréquence dans l’ensemble de la population ainsi que dans les sous-groupes de patients avec et sans dysfonction ventriculaire gauche sévère. Conclusions: L’efficacité de l’amiodarone pour le maintien du rythme sinusal n’est pas influencée par la fonction ventriculaire gauche. Le contrôle du rythme avec l’amiodarone s’associe à des taux de mortalité et d’hospitalisation comparables au contrôle de la fréquence à la fois chez les patients avec et sans dysfonction ventriculaire gauche sévère. / Objectives: To determine whether amiodarone’s efficacy in maintaining sinus rhythm varies according to left ventricular systolic function. Background: Despite amiodarone’s established safety profile in heart failure, it is unknown whether its impact on cardiovascular outcomes is modulated by ventricular function. Methods: We conducted a pooled analysis of 3307 patients (age 68.0±0.9 years; 31.1% female) enrolled in AFFIRM and AF-CHF trials who were randomized to rhythm control with amiodarone (N=1107) or rate control (N=2200). Results: In amiodarone-treated patients, freedom from recurrent atrial fibrillation was 84% and 45% at 1 and 5 years, respectively, with no differences according to left ventricular function (adjusted P=0.8754). Similarly, the adjusted mean proportion of time in atrial fibrillation (15.0±1.8%) did not vary according to ventricular function (P=0.6094). During follow-up, 1963 (59.4%) patients required at least one hospitalization, with 1401 (42.6%) patients hospitalized for a cardiovascular reason. Adjusted all-cause and cardiovascular hospitalization rates were similar with amiodarone versus rate control in the overall population and in subgroups of patients with and without severe left ventricular dysfunction. Similarly adjusted all-cause and cardiovascular mortality rates were similar with amiodarone versus rate control, overall and in subgroups of patients with and without severe left ventricular dysfunction. Conclusions: Amiodarone’s efficacy in maintaining sinus rhythm and reducing the burden of atrial fibrillation is similar in patients with and without left ventricular dysfunction. Rhythm control with amiodarone was associated with similar mortality and hospitalisation rates when compared to rate control in patients with and without severe left ventricular dysfunction.

Aptikus minimalius PAL simptomus, yra labai svarbūs diagnostiniai, greitai atliekami neinvaziniai tyrimo metodai (kulkšnies-žasto indeksas, nykščio indeksas, ėjimo testas, segmentinių slėgio gradientų matavimas ir kt.). Ambulatorinėje grandyje retai matuojamas kulkšnies-žasto indeksas riboja galimybę nustatyti PAL kiek galima anksčiau, numatyti galimas gyvybiškai svarbių organų kraujagyslines komplikacijas, laiku siųsti pacientą konsultuoti angiochirurgui. Mažai tyrinėtu alternatyvaus neinvazinio impedanso pletizmografijos tyrimu galima nustatyti ne tik periferinių arterijų ligos simptomus, bet vienu metu įvertinti eilę kitų parametrų. Darbo tikslas buvo nustatyti neinvazinio impedanso pletizmografijos metodo efektyvumą kojų arterinei kraujotakai įvertinti ir šį metodą palyginti su kitais neinvaziniais bei invaziniais diagnostikos metodais. Tyrimo metu nustatyta statistiškai reikšminga kulkšnies-žasto indekso bei impedanso pletizmografijos parametrų sąsaja pacientams, sergantiems lėtiniu prieširdžių virpėjimu, lyginant su pacientais neturinčiais šio ritmo sutrikimo, nustatyta impedanso pletizmografijos - bangos viršūnės laiko parametro sąsaja su angiografiškai aptikta kraujagyslės okliuzijos vieta. Pagrindinio impedanso pletizmografijos parametro (bangos viršūnės laiko) specifiškumas yra 96 proc., jautrumas – 73 proc. atsižvelgiant į KŽI pokyčius, o lyginant su angiografija – jautrumas 100 proc., specifiškumas – 50 proc. Taigi, neinvazinis impedanso pletizmografijos... [toliau žr. visą tekstą] / In cases of observing even the slightest PAD symptoms, rapid non-invasive diagnostic test methods become extremely important (the ankle-brachial index, thumb index, walking test, measurement of segmental pressure gradients, etc.). in an outpatient setting , the ankle-brachial index (ABI) is rarely measured, thus limiting the opportu¬nities for the earliest possible detection of PAD, prediction of vascular com¬plications of vital organs, and timely referral of the patient for a con¬sultation with an angiosurgeon. An alternative non-invasive test method of impedance plethysmo¬graphy, which has been little investigated so far, allows both detection of symptoms of peripheral arterial disease and concurrent assessment of a number of other parameters. The aim of the study is to assess the efficiency of a non-invasive method of impedance plethysmography in diagnosing arterial circulation disorders in the legs, and to compare this method with other non-invasive and invasive diagnostic methods of peripheral arterial disease. A significant correlation between the Ankle-Brachial Index and the im¬pedance plethysmography parameters was established in subjects with permanent atrial fibrillation, but not in subjects without this rhythm disorder. During the study, an obvious correlation between the Crest Time in¬ter¬val measured by the impedance plethysmography method and the vas¬¬cular occlusion site shown on angiography was established. Specificity of the impedance plethysmography... [to full text]