Background: Chronic heart failure is caused by several cardiac conditions. Heart failure can consist of forward failure and/or backward failure, which can affect the right ventricle as well as the left. The main symptoms are fatigue, dyspnea, and oedema. Modern medical treatment has improved the prognosis. Physical activity increases muscle strength, enhances quality of life, and reduces the risk of hospitalisation. Nurses need to be perceptive towards the persons’ experiences to support their health and well-being. Aim: The aim of this study was to describe older persons’ experiences of living with chronic heart failure. Method: A qualitative literature-based study was used in which 13 qualitative articles were analysed. The results were interpreted to obtain new themes. Results: Three main themes were discovered: “To not recognize your own body”, “To find hope and meaning” and “To maintain self-care ability”. The first main theme consisted of two subthemes: “Fatigue leads to physical limitations” and “To feel despair and fear”. The second main theme consisted of three subthemes: “To continue living”, “Motivation to self-care” and “Desire for normality”. Two subthemes emerged from the third main theme: “To need support from family” and “The importance of information and a person-centered care”. Conclusion: Chronic heart failure affected the persons’ lives mentally, physically, and socially.They felt alienated in terms of themselves and their bodies. Support from family and friends,and person-centered information provided by the nurse, had an important role concerning selfcare.

Bakgrund: Hjärtsvikt är en global och livslång sjukdom som medför symptom som förändrar livssituationen. Fysiska och känslomässiga påfrestningarna visar sig vara faktorer som försvårar vardagen. Samsjuklighet av andra sjukdomar är vanligt förekommande och bidrar till ökade risker att dö. Med hjälp av läkemedel och en förändrad livsstil kan symptomen lindras, öka livskvalitén, samt minska sjukhusinläggningar och mortalitet. Syfte: att beskriva patienters upplevelse av att leva med hjärtsvikt. Metod: En kvalitativ litteraturstudie baserad på kvalitativa artiklar sökta i databaserna CINAHL och PubMed. Utifrån relevanta indexord samt inklusions- och exklusionskriterier har lämplig data identifierats. Artiklarna har kvalitetsgranskats och analyserats utifrån en manifest innehållsanalys. Resultat: Patienter som lever med hjärtsvikt upplever fysiska begränsningar som reducerar deras förmåga att arbeta och utföra sociala aktiviteter. Det bidrar till social isolering och ett förändrat liv, vilket bidrar till negativa känslor. Existentiella tankar om liv och död uppdagas, som kan leda till depressiva symptom. De negativa känslorna kan hanteras med hjälp av acceptans från religion och socialt stöd vilket ökar patienternas livskvalité trots svår sjukdom. Slutsats: Hjärtsvikt medför fysiska och sociala begränsningar som hindrar patienter från att utöva aktiviteter. Social isolering och depressiva symptom uppdagas, vilket är faktorer som bidrar till lidande. Acceptans och socialt stöd visar sig göra sjukdomen mer hanterbar.

Vid en ekokardiografisk undersökning läggs fokus främst på klaffunktion, hjärtrumsstorlek och vänstersidans systoliska funktion. Vänstersidans diastoliska funktion har dock börjat få större betydelse, men upplevs ofta vara svårbedömd. Höger kammare har en komplex anatomi med ett trabekulerat myokardie och är otillgängligt placerad i bröstkorgen, vilket gör den svårare att bedöma än vänster kammare. 1995 publicerades ett index för bedömning av hjärtats kombinerade systoliska och diastoliska funktion, myocardial performance index (MPI). Syftet med studien var att undersöka om MPI kan vara en användbar och kompletterande metod vid bedömning av systolisk och diastolisk funktion i höger respektive vänster kammare. I den aktuella studien ingick 33 personer i åldrarna 21–80. MPI beräknades med pulsad vävnadsdoppler under en hjärtcykel. MPI jämfördes mot traditionella ekokardiografiska mätmetoder som speglar systolisk och diastolisk funktion för vänster respektive höger kammare. Normalfördelnings-, korrelations- och överrensstämmelseanalyser utfördes. För vänstersidig kammarfunktion sågs en signifikant korrelation mellan MPI och MAPSE. Ingen eller dålig överensstämmelse sågs mellan MPI och samtliga traditionella mätmetoder för systolisk funktion. För högersidig kammarfunktion sågs en starkt signifikant korrelation mellan MPI och FAC samt TAPSE. Mindre god överensstämmelse sågs mellan högersidans MPI och FAC samt TAPSE. För MPI och E/e’ sågs ingen signifikant korrelation hos vare sig vänster eller höger kammare och en sämre överensstämmelse än om klassificeringen hade gjorts rent slumpmässigt. Användbarheten av MPI för bedömning av vänster kammarfunktion anses, baserat på aktuell studie, vara låg. MPI kan vara användbart vid bedömning av höger kammares systoliska funktion, men inte avseende diastolisk funktion.

Background: Thoracic aortic aneurysms and dissections (TAAD) have a genetic component with an estimated 20-25% of the patients having a positive family history. An aneurysm often precedes a dissection. Acute aortic dissections are associated with high mortality and morbidity, even when operated on. Complications due to prophylactic surgery are considerably fewer. Therefore, patients at risk for dissection should be identified, followed-up and evaluated for prophylactic intervention. Aims: 1. To establish reference values for ascending (AoA) and descending aortic (AoD) diameters measured by computed tomography. 2. To study the effectiveness of phenotypic cascade screening in families with an inherited form of thoracic aortic aneurysms and dissections (FTAAD) and to address questions that arise when screening for a genetic disorder is applied. 3. To study the agreement of aortic diameters obtained by TTE and MRI and to study aortic stiffness in individuals from families with FTAAD. 4. To perform exome sequencing in order to identify pathogenic sequence variants causing FTAAD, to characterize the phenotype, and to compare thoracic aortic diameter and stiffness in mutation carriers and non-carriers. Results: Paper I: The diameter of the thoracic aorta increased by 0.17 mm (0.12 – 0.20 mm) per year. The mean sex-related difference in diameter was 1.99 mm (1.28 – 2.60 mm) with men having larger aortas than women. The mean difference in aortic diameter per unit BMI was 0.27 mm (0.14 – 0.44 mm). Upper normal limits for the AoA can be calculated by the formula D (mm)=31+0.16*age and for the AoD by D (mm)=21+0.16*age. Paper II: Of 106 individuals from families with FTAAD but without known thoracic aortic disease, 19 individuals (18%) were identified to have a dilated AoA. The expected number of individuals in this group with an autosomal dominant disease would have been 40 (p<0.0001). In first-degree relatives younger than 40, we found only one individual with a dilated aorta although the expected number of individuals with disease causing mutation would have been 10. Paper III: Of 116 individuals investigated, 21 were identified with thoracic aortic dilatation and 95 individuals with normal thoracic aortic diameter. Aortic stiffness increased with age and diameter. The individuals with aortic dilatation were older than those without (49 vs. 37 years, p=0.001) and showed lower aortic elastic properties. The diameters measured by TTE and MRI correlated strongly (r2=0.93). The mean difference in diameters between the two methods was 0.72 mm (95% CI 0.41-1.02) with TTE giving larger diameters than MRI. Paper IV: From exome sequencing and segregation analysis, a 2-bp deletion in the MYLK gene (c.3272_3273del) was identified to cause FTAAD. The age and the aortic diameter at dissection or rupture varied in the family members. We did not find any differences in aortic diameter, aortic stiffness, or pulse wave velocity between carriers and non-carriers. Conclusions: Thoracic aortic diameter increases with age, and sex and body size are also associated with the diameter. In FTAAD, screening identifies family members with a previously unknown aortic dilatation. However, a normal aortic diameter does not exclude an individual from being a carrier of FTAAD. TTE can be used in follow-up for the ascending aorta. Individuals identified to have a dilated thoracic aorta have increased aortic stiffness compared to individuals with normal thoracic aortic diameter. The MYLK mutation (c.3272_3273del) causes thoracic aortic dissections with variable clinical expression. No differences in aortic stiffness were identified between MYLK mutation carriers and non-carriers.

Although vasovagal syncope (VVS) is a common clinical condition the mechanisms behind VVS remain elusive. Upright posture is the major trigger of VVS and lower limb blood pooling affecting cardiac output has been proposed as a major determinant. The overall aim of this thesis was twofold. First, to develop new methodology for calculating limb venous compliance. Second, to study lower limb venous volume load and cardiovascular responses during hypovolemic circulatory stress caused by lower body negative pressure (LBNP) in healthy women and women with VVS, emphasizing compensatory mechanisms to maintain central blood volume. Net fluid filtration was associated with an underestimation ofvenous compliance. This could be accounted for with a correctionmodel. Further, a new venous wall model made it possible to adopt thevenous pressure-volume curve through the entire pressure range andthus provide a valid characterization of venous compliance. Calf blood pooling was similar between the groups and was not associated with tolerance to hypovolemic circulatory stress. Venous compliance was reduced at low venous pressures in VVS and correlated with decreased tolerance to circulatory stress. VVS women displayed attenuated sympathetic vasoconstrictor responses during graded circulatory stress, and mobilization of arm capacitance blood as well as capillary fluid absorption from extra- to intravascular space were reduced. Accordingly, more pronounced reductions in cardiac output were found in VVS. Thus, reduced compensatory mechanisms to maintain cardiac output could contribute to the pathogenesis oforthostatic VVS. In healthy women, rapid pooling in the lower limb was associated with higher tolerance to circulatory stress and more efficient cardiovascular responses, in part due to speed-dependent baroreflex-mediated sympathetic activation. In VVS however, rapid lower limb blood pooling was associated with lower tolerance and deficient cardiovascular responses. No speed-dependent baroreflexmediated sympathetic activation was found in VVS, indicating welldefined differences in cardiovascular regulation already in the initial responses to orthostatic stress.

This thesis focused on the acute management of patients with ST-segment elevation myocardial infarction (STEMI) in an effort to provide information that may improve outcome. The aim was to evaluate the efficacy and safety of bivalirudin versus unfractionated heparin (UFH) in STEMI patients during primary PCI. Furthermore, to provide pharmacodynamic data of novel ways of ticagrelor administration compared to standard tivcagrelor. Additionally, to identify subgroups of patients, such as women who may derive greater benefit from specific antithrombotic strategies due to their risk/benefit profile. Finally, to evaluate current formulas for estimation of renal function in the acute phase of STEMI. In Paper I, all STEMI patients in Sweden between 2008 and 2014, treated with primary PCI and UFH or bivalirudin were included in our analysis. Of the total population of 23 800 patients, 8 783 (36.9%) were included in the UFH group and 15 017 (63.1%) in the bivalirudin group. Concomitant GPI administration was 68.5% in the UFH arm compared to 3.5% in the bivalirudin arm (p<0.01).The adjusted incidence of 30-day mortality was not significant different between the two groups (UFH vs bivalirudin, adjusted HR 0.94; 95% CI 0.82 -1.07). The adjusted risk for 1-year mortality, 30-day and 1-year stent thrombosis and re-infarction did not differ significantly between the two groups. In contrast, patients treated with UFH had a significantly higher incidence of major in-hospital bleeding (adjusted OR 1.62; 95%CI 1.30 -2.03). In Paper II pharmacodynamic data of chewed or crushed ticagrelor compared to standard ticagrelor loading dose (LD) was assessed in 99 patients with stable angina. Platelet reactivity (PR) was assessed with VerifyNow before, 20 and 60 minutes after LD. High Residual platelet reactivity (HRPR) was defined as > 208 P2Y12 reaction units (PRU). Chewed ticagrelor tablets resulted in significantly lower PRU values compared to crushed or integral tablets at 20 and 60 minutes. Crushed ticagrelor LD resulted in significantly lower PRU values compared to integral tablets at 20 minutes whereas no difference was observed at 60 minutes. At 20 minutes, no patients had HRPR with chewed ticagrelor compared to 68% with integral and 30% with crushed ticagrelor LD (p<0.01). In Paper III we presented a pre-specified gender analysis of the ATLANTIC trial including 1 862 STEMI patients that were randomly assigned to pre-hospital versus in-hospital administration of 180mg ticagrelor. Women were older and had higher TIMI risk score. Women had a 3-fold higher risk for all-cause mortality compared to men (5.7% vs 1.9%, HR 3.13, 95% CI 1.78 – 5.51). However, after adjustment for baseline characteristics, the difference was lesser and no longer significant (HR 1.98, 95% CI 0.97 – 4.04). Female gender was not an independent predictor of risk for bleeding after multivariable adjustments (BARC type 3-5 HR 1.52, 95% CI 0.74-3.09). There was no interaction between gender and efficacy or safety of randomised treatment. In Paper IV, forty patients with PCI- treated STEMI were included between November 2011 and February 2013. We validated the performance of the Cockcroft-Gault (CG), the Modification of Diet in Renal Disease (MDRD-IDMS), the Chronic Kidney Disease Epidemiology (CKD-EPI) and the Grubb relative cystatin C (rGCystC) equations for estimation of GFR against measured GFR (mGFR) during the index hospitalisation for STEMI. MDRD-IDMS and CKD-EPI demonstrated a good performance to estimate GFR with accuracy within 30% (P30) 82.5% vs 82.5%, respectively. CKD was best classified by CKD-EPI (Kappa 0.83). CG showed the worst performance with the lowest P30. The rG-CystC equation had a marked bias of -17.8% and significantly underestimated mGFR (p=0.03). Conclusions – In STEMI patients treated with primary PCI, bivalirudin should be preferred in patient at high risk for bleeding. With crushed or chewed ticagrelor tablets a more rapid platelet inhibition may be achieved, compared with standard integral tablets. In STEMI patients, fast and potent platelet inhibition with chewed ticagrelor may reduce the risk of early stent thrombosis and patients treated with a less aggressive antithrombotic strategy, such as UFH or bivalirudin monotherapy, may derive a greater benefit. Although gender differences in adverse outcomes could mainly be explained by older age and clustering of comorbidities in women, a bleedreduction strategy in women with high risk characteristics is warranted in order to improve their outcome. Regardless the choice of antithrombotic strategy, dose adjustment of drugs cleared by kidneys based on GFR estimation is of crucial importance. MDRD and CKD-EPI should be the formulas used for estimation of GFR in STEMI patients

Background: The twisting motion of the left ventricle (LV), with clockwise rotation at the base and counter clockwise rotation at the apex during systole, is a vital part of LV function. Even though LV rotation has been studied for decades, the rotation pattern has not been described in detail. By the introduction of speckle tracking echocardiography measuring rotation has become easy of access. However, the axis around which the LV rotates has never before been assessed. The aims of this thesis were to describe the rotation pattern of the LV in detail (study I), to assess RV apical rotation (study II), develop a method to assess the rotation axis (study III) and finally to study the effect of regional ischemia to the rotation pattern of the LV (study IV). Methods: Healthy humans were examined in study I-III and the final study populations were 40 (60±14 years), 14 (62±11 years) and 39 (57±16 years) subjects, respectively. In study IV six young pigs (32-40kg) were studied. Standard echocardiographic examinations were performed. In study IV the images were recorded before and 4 minutes after occlusion of left anterior descending coronary artery (LAD). Rotation was measured in short axis images by using a speckle tracking software. By development of custom software, the rotation axis of the LV was calculated at different levels in every image frame throughout the cardiac cycle. Results: Study I showed significant difference in rotation between basal and apical rotations, as well as significant differences between segments at basal and mid ventricular levels. The rotation pattern of the LV was associated with different phases of the cardiac cycle. Study II found significant difference in rotation between the LV and the RV. RV rotation was heterogeneous and bi-directional, creating a ´tightening belt action´ to reduce it circumference. Study III indicated that the new method could assess the rotation axis of the LV. The motion of the rotation axes in healthy humans displayed a physiological and consistent pattern. Study IV found a significant difference in the rotation pattern, between baseline and after LAD occlusion, by measuring the rotation axes, but not by conventional measurements of rotation. AV-plane displacement and wall motion score (WMS) were also significantly changed after inducing regional ischemia. Conclusion: There are normally large regional differences in LV rotation, which can be associated anatomy, activation pattern and cardiac phases, indicating its importance to LV function. In difference to the LV, the RV did not show any functional rotation. However, its heterogeneous circumferential motion could still be of importance to RV function and may in part be the result of ventricular interaction. The rotation axis of the LV can now be assessed by development of a new method, which gives a unique view of the rotation pattern. The quality measurements and results in healthy humans indicate that it has a potential clinical implication in identifying pathological rotation. This was supported by the experimental study showing that the rotation axis was more sensitive than traditional measurements of rotation and as sensitive as AV-plane displacement and WMS in detecting regional myocardial dysfunction.

Despite the currently recommended dual antiplatelet treatment (DAT) with aspirin and P2Y12 inhibition in patients with coronary artery disease (CAD) there is a risk of adverse clinical outcome. Pharmacodynamic (PD) poor response to clopidogrel occurs in ~ 30% of clopidogrel-treated patients and is associated with an increased risk of recurrent thrombotic events. The aims of this thesis were to compare the PD and pharmacokinetic effects of clopidogrel 600 mg loading dose (LD)/ 75 mg standard maintenance dose (MD) with the novel P2Y12 inhibitor prasugrel 60 mg LD/10 mg MD, in 110 patients with CAD. The mechanisms behind clopidogrel poor response were investigated by assessing the pharmacodynamics after adding clopidogrel active metabolite (AM) and genotyping for variation in CYP-genes involved in thienopyridine metabolism. In another study, we compared the on-clopidogrel platelet reactivity of patients with stent thrombosis (ST) (n=48) or myocardial infarction (MI) (n=30) while on DAT and their matched controls (n=50 + 28). Prasugrel achieved a faster and greater P2Y12-mediated platelet inhibition than clopidogrel measured with light transmission aggregometry, VASP and VerifyNow® P2Y12. Prasugrel’s greater platelet inhibition was associated with higher exposure of AM. The addition of clopidogrel AM led to maximal platelet inhibition in all subjects, suggesting that prasugrel’s greater antiplatelet effect was related to more efficient AM generation compared to that of clopidogrel. Lower levels of AM as well as less platelet inhibition were seen in clopidogrel-treated patients with reduced-metabolizer genotype CYP2C19 compared to those with normal genotype. Patients with ST while on DAT showed higher on-clopidogrel platelet reactivity compared to matched stented controls. Patients with spontaneous MI after stenting did not. In conclusion, these results showed a high rate PD poor response to a high bolus dose of clopidogrel because of a partly genetically caused lower generation of AM which could be overcome by prasugrel treatment. In patients after coronary stenting, clopidogrel poor response was related to ST but not to spontaneous MI, illustrating difficulties in optimizing treatment with clopidogrel based on platelet function or genetic testing in individual patients.

The overall aim of this thesis was to describe patients’ and spouses’ experiences of suspected acute myocardial infarction in the pre-hospital phase. A descriptive survey study was conducted to identify various factors influencing patient delay in 381 patients with suspected myocardial infarction hospitalised at a Coronary Care Unit (I) and ambulance utilisation among 110 myocardial infarction patients (II). In order to obtain a deeper understanding of the myocardial infarction patients’ own conceptions about the event, an interview study with a phenomenographic approach was conducted with 15 strategically selected myocardial infarction patients (III), within 72 hours after admission to hospital. Finally, the pre-hospital experiences of 15 spouses of myocardial infarction patients were also studied through interviews with a phenomenographic approach, within 48 hours after the affected partner’s admittance to hospital (IV). The results showed that 59% of the patients with suspected acute myocardial infarction delayed > 1 hour after onset of symptoms. The most common reasons given for delay in seeking hospital admittance were: (1) Did not consider the symptoms as to be severe enough that they warranted hospital care, (2) thought the symptoms to be temporary and that they would disappear, (3) the chest pain was more of a dull pain, (4) or, as one third of the patients chose to do, contacted the general practitioner instead of going directly to the hospital (I). Furthermore, as a first action, 59% consulted their spouse for advice about what to do henceforth. The most common reason for additional delay when the decision to go to hospital had already been taken was that the myocardial infarction patients stated that they were unaware of the advantages of a rapid decision-making process. Sixty percent went by ambulance, but it was the spouse (40%) or the personnel at the general practitioner’s office (32%) who called the emergency service number, rather than the patient him/her self (5%). The most frequently given reasons for not choosing ambulance, were that the patients did not perceive their symptoms as being serious enough to require ambulance transportation (43%), followed by that they had not thought about ambulance as an alternative at all (38%). As a third reason for not going by ambulance, the patients stated that it was unnecessary to call an ambulance when being affected by symptoms related to a myocardial infarction (26%). The patients who called an ambulance differed in some respects from those who went by private alternatives; patients with large infarctions (ST-Elevation Myocardial Infarction) went by ambulance more frequently, as did patients suffering from nausea and severe chest pain (II). The patients expressed in the interviews how the interaction with others, described as the need for supportive environment, worries for the family and the utilisation of the health-care resources, was of great importance in the pre-hospital phase. Likewise, symptom awareness, with earlier experiences of a similar situation to compare with, denying the seriousness of the situation and the use of different self-care strategies, were important in order to manage the situation. Vulnerability, expressed as anxiety and a lack of control, also influenced the decision-making process in the pre-hospital phase (III). Spouses seemed to have a strong influence on the course of events when their partner suffered an acute myocardial infarction and it emerged from the interviews how the spouses in many cases were influenced into sharing the denial of the affected partner by respecting his/her independence. The spouses accepted the partner’s need for control; took earlier marital roles and experiences into account; restraining own emotions and seeking agreement with their partners, contributing to delay. However, being resourceful by sharing the experience; having knowledge; understanding the severity; being rational and consulting others when needed, seemed to have a positive influence on the decision time in the pre-hospital phase (IV). Conclusion: The reasons for delaying or not in the pre-hospital phase, as well as the reasons for utilising the ambulance services or not, varied considerably between individuals. Earlier experiences of MI did not influence what actions to take; instead patients’ feelings, emotional attitudes to MI symptoms, inadequate coping strategies, and spouses’ influences were important components in the pre-hospital phase.

The overall aims of this thesis were to elucidate the circulatory responses to ultra-endurance exercise (Adventure Racing), and furthermore, to contribute to the clarification of the so called “exercise-induced cardiac fatigue” in relation to said exercise. An Adventure race (AR) varies in duration from six hours to over six days, in which the participants have to navigate through a number of check-points over a pre-set course, using a combination of three or more endurance/outdoor sports, e.g., cycling, running, and kayaking. This thesis is based on the results from four different protocols; 12- and 24-h (n = 8 and 9, respectively) in a controlled setting with fixed exercise intensity, and 53-h and 5-7-day (n = 15 in each) in field setting under race conditions. The subjects in all protocols were experienced adventure racing athletes, competitive at elite level. Study I and II address the circulatory responses and cardiovascular drift, using methods for monitoring heart rate (HR), oxygen uptake (VO2), cardiac output (non-invasive re-breathing) and blood pressure, during ergometer cycling at fixed steady state work rate at periods before, during and after the ultra-endurance exercise. In Study III and IV we examined the possible presence of exercise-induced cardiac fatigue after a 5-7-day AR, from two different perspectives. In Study III analyses were performed with biochemical methods to determine circulating levels of cardiac specific biomarkers (i.e., creatine kinase isoenzyme MB (CK-MB), troponin I, B-type natriuretic peptide (BNP) and N-terminal prohormonal B-type natriuretic peptide (NT-proBNP)). We also made an attempt to relate increases in biomarkers to rated relative performance. In Study IV we used tissue velocity imaging (TVI) (VIVID I, GE VingMed Ultrasound, Norway) to determine whether the high workload (extreme duration) would induce signs of functional cardiac fatigue similar to those that occur in skeletal muscle, i.e., decreased peak systolic velocities. Using conventional echocardiography we also evaluated whether the hearts of experienced ultra-endurance athletes are larger than the normal upper limit. The central circulation changed in several steps in response to ultra-endurance exercise. Compared to initial levels, VO2 was increased at every time-point measured. The increase was attributed to peripheral adaptations, confirmed by a close correlation between change in VO2 and change in arteriovenous oxygen difference. The first step of the circulatory response was typical of normal (early) cardiovascular drift, with increased HR and concomitantly decreased stroke volume (SV) and oxygen pulse (VO2/HR), occurring over the first 4-6 h. The second step, which continued until approximately 12h, included reversed HR-drift, with normalisation of SV and VO2/HR. When exercise continued for 50 h a late cardiovascular drift was noted, characterised by increased VO2/HR, (indicating more efficient energy distribution), decreased peripheral resistance, increased SV, and decreased work of the heart. Since cardiac output was maintained at all-time points we interpret the changes as physiologically appropriate adaptations. Our findings in Study III point towards a distinction between the clinical/pathological and the physiological/exercise-induced release of cardiac biomarkers. The results imply that troponin and CKMB lack relevance in the (healthy) exercise setting, but that BNP, or NT-proBNP adjusted for exercise duration, might be a relevant indicator for impairment of exercise performance. High levels of NTproBNP, up to 2500 ng · l -1 , can be present after ultra-endurance exercise in healthy athletes without any subjective signs or clinical symptoms of heart failure. However, these high levels of NT-proBNP seemed to be associated with decreased relative exercise performance, and might be an indicator of the cardiac fatigue that has previously been described after endurance exercise. Study IV revealed that the sizes of the hearts (left ventricle) of all of our ultra-endurance athletes were within normal limits. The measurements of peak systolic velocities showed (for group average) no signs of cardiac fatigue even after 6 days of continuous exercise. This discrepancy between ours and other studies, involving e.g., marathon or triathlon, might reflect the fact that this type of exercise is performed at relatively low average intensity, suggesting that the intensity, rather than the duration, of exercise is the primary determinant of cardiac fatigue. / Physiology of Adventure Racing