abstract: Heart failure is a major worldwide health concern and is the leading cause of hospitalization among elderly Americans. Approximately 50% of those diagnosed with heart failure have heart failure with preserved ejection fraction (HFPEF). HFPEF presents a therapeutic dilemma because pharmacological strategies that are effective for the treatment of heart failure and reduced ejection fraction have failed to show benefit in HFPEF. Long term moderate intensity exercise programs have been shown to improve diastolic function in patients HFPEF. High intensity interval training (HIIT) has been shown to improve diastolic function in patients with heart failure and reduced ejection fraction. However, the effects of high intensity interval training in patients with HFPEF are unknown. Fourteen patients with HFPEF were randomized to either: (1) a novel program of high-intensity aerobic interval training (n = 8), or (2) a commonly prescribed program of moderate-intensity (MOD) aerobic exercise training (n = 6). Before and after four weeks of exercise training, patients underwent a treadmill graded exercise test for the determination of peak oxygen uptake (VO2peak), a brachial artery reactivity test for assessment of endothelium-dependent flow-mediated dilation (BAFMD), aortic pulse wave velocity assessment as an index of vascular stiffness and two-dimensional echocardiography for assessment of left ventricular diastolic and systolic function. I hypothesized that (1) high-intensity aerobic interval training would result in superior improvements in FMD, aortic pulse wave velocity, VO2peak, diastolic function and, (2) changes in these parameters would be correlated with changes in VO2peak. The principal findings of the study were that a one month long high intensity interval training program resulted in significant improvements in diastolic function as measured by two-dimensional echocardiography [pre diastolic dysfunction (DD) grade - 2.13 + 0.4 vs. post DD grade - 1.25 + 0.7, p = 0.03]. The left atrial volume index was reduced in the HIIT group compared to MOD ( - 4.4 + 6.2 ml/m2 vs. 5.8 + 10.7 ml/m2, p = 0.02). Early mitral flow (E) improved in the HIIT group (pre - 0.93 + 0.2 m/s vs. post - 0.78 + 0.3 m/s, p = 0.03). A significant inverse correlation was observed between change in BAFMD and change in diastolic dysfunction grade (r = - 0.585, p = 0.028) when all the data were pooled. HIIT appears to be a time-efficient and safe strategy for improving diastolic function in patients with heart failure and preserved ejection fraction. These data may have implications for cardiovascular risk reduction in this population. / Dissertation/Thesis / Ph.D. Exercise and Wellness 2012

No description available.

Introduktion: Vid ekokardiografi används ultraljudsvågor med frekvens över 20 000Hz. Ultraljudssändare med piezoelektriska kristaller används för att generera ljudvågor som skickas ut i kroppen, reflekteras och sedan återvänder till kristallerna för att skapa en ultraljudsbild. Ejektionsfraktionen uttrycker hur stor del av den diastoliska volymen som pumpas ut i kroppen under systole och är en viktig parameter vid bedömning av den globala systoliska funktionen. Den rekommenderade metoden Simpsons biplan jämförs med Philips automatiska funktion a2Dq, som utgår ifrån speckle tracking principen, för bedömning av ejektionsfraktionen. Material och metod: 32 hjärtfriska testpersoner mellan 20–43 år inkluderades i tvärsnittsstudien. Apikala 4- och 2-kammarbilder insamlades ifrån testpersonerna och användes för beräkning av ejektionsfraktionen. Den manuella metoden Simpsons biplan grundas på operatörens utlinjering av endokardiet. Den automatiska funktionen a2Dq utgår ifrån 53 hjärtmodeller och placerar en region of interest automatiskt. Den semiautomatiska funktionen används genom att operatören modifierar region of interest men inte längden av vänsterkammaren. Resultat: Resultatet visade att det inte förelåg någon signifikant skillnad i mätvärdena av ejektionsfraktionen mellan de tre mätprinciperna. Den semiautomatiska och manuella metoden som är operatörsberoende hade likvärdiga mätresultat. Den automatiska funktionen erhöll totalt 6 mätvärden som hamnade utanför normalgränserna. Diskussion: Automatiska funktioner för bedömning av ejektionsfraktionen utvecklas snabbt och kräver utvärderingar. Automatiska mätningar har påvisats vara fördelaktiga då de inte är så tidskrävande som den manuella Simsons biplanmetoden. Tidsaspekten framhävs i de flesta studier dock på bekostnad av säkra mätresultat. Observationerna i denna studie påvisar att den automatiska funktionen inte är säker nog för användning. Konklusion: Enligt observationer ifrån denna studien rekommenderas att den automatiska funktionen ifrån Philips inte används. / Introduction: Ultrasound are soundwaves with frequencies above 20 000Hz. Piezoelectric crystals are used to generate sound waves that can be transmitted into the tissue and reflected back to the crystals to obtain an ultrasound image. The ejection fraction expresses how much blood the left ventricle pumps out with each contraction and is an important parameter for assessment of the hearts global systolic function. The recommended method Simpson´s biplane to assess ejection fraction is compared with Philips automatic function a2Dq, which is based on the principle of speckle tracking. Material and method: The study population included 32 tests subjects with age between 20-43 years old. The test subjects had no records of earlier heart pathologies. Apical 4- and 2-chamber images were collected for the purpose to measure the ejection fraction. The manual method Simpson´s biplane is based on the sonographers manual tracking of the endocardial border. The automatic function a2Dq is based on 53 heart models with different anatomy and physiology and applies a region of interest automatically along the endocardial border. The semi-automatic function allows the sonographer to adjust the region of interest but not the length of the chamber. Result: The result showed that there was no significant difference in the measured values of ejection fraction between the three different techniques. The semi-automatic and Simpson´s biplane method showed equivalent results. The automatic function showed a wide variance of measurements which resulted with a total of 6 measurement ended up below the normal values for ejection fraction. Discussion: Automatic functions for assessing the ejection fraction rapidly develops and requires validations. Automatic functions have shown to be advantageous as the are not as time-consuming as the manual Simpson´s biplane method. In most studies, however, the time aspect is emphasized at the expense of correct measurements results. The observations in this study show that the automatically function a2Dq from Philips are not providing correct measurements. Conclusion: According to observations in this study, it´s recommended that the automatic function from Philips shouldn’t be used.

Background: Heart Failure (HF) is a frequent cause of mortality and recurrent hospitalization. Although HF databases are assembled based on left ventricular (LV) ejection fraction, patients without LV ejection fraction determination are not further analyzed. Objective: The purpose of this study is to characterize patient attributes and outcomes in this group-HF with unknown Ejection Fraction (HFunEF). Methods: We queried the electronic medical record from a community-based university practice for patients with a HF diagnosis. We included patients with >60 days follow-up and had interpretable Doppler-echocardiograms. We recorded demographic, Doppler-echocardiographic, and outcome variables (up to 2083 days). Results: There were 820 patients: 269 with HF with preserved Ejection Fraction (HFpEF), 364 with HF with reduced Ejection Fraction (HFrEF), of which 231 had a LV ejection fraction=40-49% and 133 had a LV ejection fraction<40%, and 187 with HFunEF. As compared to patients with HFunEF, HFpEF patients were younger, had a higher coronary disease and hyperlipidemia prevalence. Patients with HFrEF had more prevalent coronary disease, myocardial infarction, and hyperlipidemia. Patients with HFunEF were more likely to be seen by non-cardiology providers. All-cause mortality (ACM) was greater in HFunEF patients than patients with HFpEF (Hazard Ratio (HR)=1.60 (1.16-2.29), p=0.004). Furthermore, HF readmission rates were lower in HFunEF as compared to HFpEF (HR=0.33 (0.27-0.54), p<0.0001) and HFrEF (HR=0.30 (0.028-0.50), p<0.0001). Conclusion: Patients with HFunEF have greater ACM and lower HF re-admission than other HF phenotypes. Adherence to core measures, including LV ejection fraction assessment, may improve outcomes in this cohort of patients.

No description available.

Remarkable advances have been made in the treatment of cardiovascular diseases (CVD), however, CVD still accounts for the most deaths in industrialized nations. Ischemic heart disease (IHD) can lead to acute coronary syndrome (ACS) (myocardial infarction [MI]). The standard of care is reperfusion therapy followed by pharmacological intervention to attenuate clinical symptoms related to the MI. While survival from MI has dramatically increased with the implementation of reperfusion therapy, these individuals will inevitably suffer progressive pathological remodeling leaving them predispose to develop heart failure (HF). HF is a clinical syndrome defined as the impairment of the heart to maintain organ perfusion at rest and/or during times of exertion (i.e. exercise intolerance). Clinically, this is accompanied by dyspnea, pulmonary or splanchnic congestion and peripheral edema. Physiologically, there is neurohormal activation through the classical β–adrenergic and PKA–dependent signalin / Physiology

Background and aims Heart failure (HF) is a major cause of serious morbidity and death in the population and one of the leading medical causes of hospitalization among people older than 60 years. The aim of this thesis was to describe how to create and how to analyze a Heart Failure Registry with emphasis on Anemia and Quality of Life. (Paper I) We described the creation of the Swedish Heart Failure Registry (SwedeHF) as an instrument, which may help to optimize the handling of HF patients and show how the registry can be used to improve the management of patients with HF. (Paper II) In order to show how to analyze a HF registry we investigated the prevalence of anemia, its predictors, and its association with mortality and morbidity in a large cohort of unselected patients with HFrEF included in the SwedeHF, and to explore if there are subgroups of HF patients identifying high--‐risk patients in need of treatment. (Paper III) In order to show another way of analyzing a HF registry we assessed the prevalence of, associations with, and prognostic impact of anemia in patients with HFmrEF and HFpEF. (Paper IV) Finally we examined the usefulness of EQ--‐ 5D as a measure of patient--‐reported outcomes among HF patients using different analytical models and data from the SwedeHF, and comparing results about HRQoL for patients with HFpEF and HFrEF. Methods An observational study based on the SwedeHF database, consisting of about 70 variables, was undertaken to describe how a registry is created and can be used (Paper I). One comorbidity (anemia) was applied to different types of HF patients, HFrEF (EF &lt;40%) (II) and HFmrEF (EF 40--‐49% ) or HFpEF (&gt; 50%) (III) analyzing the data with different statistical methods. The usefulness of EQ--‐5D as measure of patient--‐ reported outcomes was studied and the results about HRQoL were compared for patients with HFpEF and HFrEF (IV). Results In the first paper (Paper I) we showed how to create a HF registry and presented some characteristics of the patients included, however not adjusted since this was not the purpose of the study. In the second paper (Paper II) we studied anemia in patients with HFrEF and found that the prevalence of anemia in HFrEF were 34 % and the most important independent predictors were higher age, male gender and renal dysfunction. One--‐year survival was 75 % with anemia vs. 81 % without (p&lt;0,001). In the matched cohort after propensity score the hazard ratio associated with anemia was for all--‐cause death 1.34. Anemia was associated with greater risk with lower age, male gender, EF 30--‐39%, and NYHA--‐class I--‐II. In the third paper (Paper III) we studied anemia in other types of HF patients and found that the prevalence in the overall cohort in patients with EF &gt; 40% was 42 %, in HFmrEF 38 % and in HFpEF (45%). Independent associations with anemia were HFpEF, male sex, higher age, worse New York Heart Association class and renal function, systolic blood pressure &lt;100 mmHg, heart rate ≥70 bpm, diabetes, and absence of atrial fibrillation. One--‐year survival with vs. without anemia was 74% vs. 89% in HFmrEF and 71% vs. 84% in HFpEF (p&lt;0.001 for all). Thus very similar results in paper II and III but in different types of HF patients. In the fourth paper (Paper IV) we studied the usefulness of EQ--‐5D in two groups of patients with HF (HFpEF and HFrEF)) and found that the mean EQ--‐5D index showed small reductions in both groups at follow--‐up. The patients in the HFpEF group reported worsening in all five dimensions, while those in the HFrEF group reported worsening in only three. The Paretian classification showed that 24% of the patients in the HFpEF group and 34% of those in the HFrEF group reported overall improvement while 43% and 39% reported overall worsening. Multiple logistic regressions showed that treatment in a cardiology clinic affected outcome in the HFrEF group but not in the HFpEF group (Paper IV). Conclusions The SwedeHF is a valuable tool for improving the management of patients with HF, since it enables participating centers to focus on their own potential for improving diagnoses and medical treatment, through the online reports (Paper I). Anemia is associated with higher age, male gender and renal dysfunction and increased risk of mortality and morbidity (II, III). The influence of anemia on mortality was significantly greater in younger patients in men and in those with more stable HF (Paper II, III). The usefulness of EQ--‐5D is dependent on the analytical method used. While the index showed minor differences between groups, analyses of specific dimensions showed different patterns of change in the two groups of patients (HFpEF and HFrEF). The Paretian classification identified subgroups that improved or worsened, and can therefore help to identify needs for improvement in health services (Paper IV).

Résumé: Mise en contexte : Les infarctus antérieurs avec élévation du segment ST (IMAEST) causent fréquemment une dysfonction ventriculaire gauche. Une diminution de la fraction d’éjection du ventricule gauche (FeVG) est associée à une augmentation du risque d’accident vasculaire cérébral (AVC). Les lignes directrices recommandaient jusqu’à récemment (Classe I, niveau d’évidence C) l’anticoagulation des patients qui, après un IMAEST, étaient jugés à haut risque d’embolie systémique tels que les infarctus étendus ou de la paroi antérieure. Généralement, ces patients reçoivent une anticoagulation d’une durée de trois mois en combinaison avec une double thérapie antiplaquettaire pour au moins quatre semaines. Si les anomalies régionales de la contractilité se normalisaient avant trois mois, la durée de l’anticoagulation pourrait potentiellement être écourtée. La cinétique de récupération des infarctus antérieurs revascularisés par angioplastie primaire est mal décrite. Objectif : Chez des patients ayant subi un IMAEST de la paroi antérieure revascularisés par angioplastie primaire, évaluer si la FeVG et la récupération de l’akinésie antérieure et apicale est différente à un mois et trois mois post infarctus. Méthode : De façon prospective, nous avons recruté 42 patients présentant une FEVG de 45% ou moins et une akinésie de la paroi antérieure ou apicale lors de l’échocardiographie réalisée 48 heures post IMAEST. Des échocardiographies étaient obtenues à un mois et trois mois post IMAEST. Chaque échocardiographie était interprétée par deux cardiologues indépendants à l’aveugle des données cliniques. Résultats : Lorsque comparée à la FeVG à 48 heures post IMAEST, la FeVG à un mois s’était déjà améliorée de façon significative (38% à 42%, p=0.03). Il n’y avait pas d’amélioration significative supplémentaire entre un mois et trois mois (42% à 44%, p=NS). La dynamique des segments apicaux et antérieurs s’améliorait de façon significative entre 48 heures et un mois, mais aussi entre un mois et trois mois. Conclusion : Vu l’amélioration significative de la FeVG et de l’akinésie antérieure et apicale à un mois post IMAEST, il pourrait être justifié de ré-évaluer la FeVG plus précocement chez les patients anticoagulés pour cette indication afin de minimiser la durée de l’anticoagulation et le risque de saignement qui y est associé. / Abstract: Background: Anterior ST-elevation myocardial infarction (STEMI) frequently causes left ventricular dysfunction. Worsening left ventricular ejection fraction (LVEF) is associated a higher stroke rate. Prior guidelines recommended anticoagulation for patients after STEMI who are at high risk for systemic emboli and specified that large or anterior myocardial infarctions (MI) are part of that group (Class I, level of Evidence C). The 2013 Guidelines made it a Class IIB recommendation and restricted the recommendation to those with anterior or apical akinesia and dyskinesia. These patients are usually given three months of anticoagulation. If the regional wall motion abnormalities were to normalize earlier, the duration of anticoagulation could be shortened. However, the kinetics of recovery after an anterior MI revascularized with primary percutaneous intervention are not well described. Objective: To evaluate if LVEF and apical and anterior akinesia recuperation is different at one month and three months after STEMI in patients treated with primary percutaneous angioplasty. Methods: We prospectively recruited 42 patients who had a LVEF of 45% or less and apical or anterior akinesia on echocardiography at 48 hours post STEMI. Echocardiography was repeated one month and three months post STEMI. Each echocardiogram was interpreted by two different cardiologists who were blinded to clinical information. Results: When compared to 48 hours post STEMI, LVEF at one month had already improved significantly (38% to 42%, p=0.03) and there was no further significant improvement at three months (44%, p=NS). Anterior and apical akinesia decreased significantly between the 48 hours and one month echocardiograms, but also between one month and three months. Conclusion: Given that LVEF and anterior/apical akinesia improve significantly within the first post STEMI month, it may be worth re-evaluating the LVEF earlier in patients in whom the decision was made to start anticoagulation for that indication in order to minimize the duration of anti-coagulation and the associated bleeding risk.

On estime qu'approximativement 20 millions de personnes dans le monde souffrent d'insuffisance cardiaque et la prévalence de cette pathologie ne cesse d'augmenter avec le vieillissement croissant de la population. L'évaluation de la fonction ventriculaire gauche par la mesure de la fraction d'éjection permet en fait de distinguer deux populations distinctes de patients insuffisants cardiaques : l'une avec et l'autre sans altération de la fraction d'éjection, encore dénommées respectivement Heart Failure with Reduced Ejection Fraction (IC-FEr) et Heart Failure with Preserved Ejection Fraction (IC-FEp). On ne sait pas aujourd'hui si ces deux entités représentent deux pathologies distinctes ou, au contraire, deux entités intimement liées. L'IC-FEp est actuellement observée chez environ 40 à 50% des patients présentant une insuffisance cardiaque et son évolution est semblable à celle des patients IC-FEr.Le concept d'IC-FEp soulève toutefois des difficultés conceptuelles : d'une part car la notion d'une fraction d'éjection préservée implique la connaissance de sa valeur de base et d'autre part, les valeurs dites "normales" de la fraction d'éjection sont encore à établir. Par ailleurs, la vision mécanique du cœur comme une pompe hémodynamique ou musculaire conditionne la compréhension de la physiopathologie de la IF-FEp.Dans ce contexte, nous avons mis au point un modèle porcin de dysfonction diastolique avec éjection préservée secondaire à une hypertension artérielle induite par une perfusion continue d'angiotensine II pendant 28 jours. Dans ces conditions, nous avons démontré une altération de la fonction ventriculaire gauche alors même que l'éjection était préservée. Ceci était objectivé par 1) une augmentation paradoxale des durées relatives de contraction et de relaxation isovolumiques, 2) des réponses inappropriées des phases isovolumiques du cycle cardiaque à des augmentations de la fréquence et de l'inotropisme cardiaques et 3) une étroite relation entre ces deux phases isovolumiques (couplage contraction-relaxation). L'inadéquation entre les niveaux de fréquence cardiaque et des phases isovolumiques nous a amené à évaluer les effets de la modulation pharmacologique de la fréquence cardiaque sur le couplage contraction-relaxation. Ainsi la réduction sélective de la fréquence cardiaque par l'administration d'ivabradine, un inhibiteur des canaux If, a réduit significativement la durée de ces deux phases et favorisé le remplissage. Cependant, cette normalisation n'était qu'apparente puisque le ratio entre la contraction et la relaxation isovolumiques restait augmenté à J28, en défaveur de la contraction isovolumique.En conclusion, le développement d'une dysfonction diastolique avec une éjection préservée s'accompagne d'une dysfonction systolique qui entrave une réponse adéquate du myocarde à un stress dans un contexte d'hypertension chronique. / Approximately 20 millions individuals in the world experience heart failure symptoms; heart failure prevalence is continuously rising with population aging. Left ventricular function evaluation by the ejection fraction allows distinguishing two different patient sets: one with and one other without ejection fraction alteration, respectively named Heart Failure with Reduced Ejection Fraction (HF-rEF) and Heart Failure with Preserved Ejection Fraction (HF-pEF). It is unknown if these two clinical presentations represent two different pathologies or two manifestations of the same clinical entity. HF-pEF is found in about 40-50% of patients with heart failure and its evolution is similar to that of patients with HF-rEF.However, several conceptual difficulties deal with the HFpEF: on one hand, talking about preserved ejection fraction implies the knowledge of its basal value; on the other, the normality needs to be established. Moreover, considering the heart either as a hemodynamic pump or as a muscular pump may modify the understanding of HFpEF physiopathology.We therefore set up a swine model of diastolic dysfunction with preserved ejection induced by chronic hypertension, which was obtained by continuous perfusion of angiotensin II during 28 days. In these conditions, we clearly demonstrated a LV function impairment, while the ejection phase parameters remained preserved. The LV impairment is demonstrated by: 1) the paradox increase of the relative durations of isovolumic contraction and relaxation; 2) the blunted responses of the isovolumic phases of cardiac cycle to heart rate augmentation and cardiac inotropisme; 3) a straight relationship between these two isovolumic phases (contraction-relaxation relationship).The mismatch between the heart rate and the isovolumic phases behaviour led us to investigate the possible effects of the heart rate pharmacological modulation on the contraction-relaxation coupling. The selective reduction of the heart rate by ivabradine administration (a selective If channel inhibitor) was able to significantly reduce the isovolumic contraction and relaxation phases' durations, thus improving filling phase dynamics. Anyway, this “normalisation” was only apparent, because the contraction to relaxation ratio was increased at day 28, to the detriment of the isovolumic contraction.In conclusion, chronic hypertension induces a diastolic dysfunction with a preserved ejection fraction paralleled by a systolic dysfunction which is responsible of a blunted myocardial response to stress.

Left ventricular (LV) volumes and ejection fraction (EF) are important predictors of cardiac morbidity and mortality. LV volumes provide valuable prognostic information which isparticularly useful in the selection of therapy or determination of the optimal time for surgery. Two-dimensional (2D) echocardiography is the most widely used non-invasive method forassessment of cardiac function, 2D echocardiography has however several limitations inmeasuring LV volumes and EF since the formulas for quantifications are based on geometricalassumptions. Three-dimensional (3D) echocardiography has been available for almost twodecades, although the use of this modality has not gained wide spread acceptance. 3D echocardiography can overcome the above mentioned limitation in LV volume and EF evaluation since it is not based on geometrical assumption. 3D echocardiography has been shownin several studies to be more accurate and reproducible with low inter- and intraobservervariability in comparison to 2D echocardiography regarding the measurements of LV volumesand EF. The overall aim of the thesis was to evaluate the feasibility and accuracy of 3D echocardiography based-methods in the clinical context. In Study I the feasibility of 3D echocardiography was investigated for determination of LV volumes and EF using parasternal, apical and subcostal approaches. The study demonstrated that the apical 3D echocardiography view offers superior visualization. Study II tested the possibility of creating flow-volume loops to differentiate patients with valvular abnormalities from normal subjects. There were significant differences in the pattern from flow-volume loops clearly separating the groups. In Study III the visual estimation, “eyeballing” of EF was evaluated with two- and tri-plane echocardiography in comparison to quantitative 3D echocardiography. The study confirmed that an experienced echocardiographer can, with a high level of agreement estimate EF both with two- and tri-plane echocardiography. Study IV exposed the high accuracy of stroke volume and cardiac output determination using a3D biplane technique by planimetrically tracing the left ventricular outflow tract and indicating that an assumption of circular left ventricular outflow tract is not reliable. In Study V, two 3D echocardiography modalities, single-beat and four-beat ECG-gated 3D echocardiography were evaluated in patients having sinus rhythm and atrial fibrillation. Thesingle-beat technique showed significantly lower inter-and intraobserver variability in LV volumes and EF measurements in patients having atrial fibrillation in comparison to four-beat ECG-gated acquisition due to absence of stitching artifact. All studies demonstrated good results suggesting 3D echocardiography to be a feasible andaccurate method in daily clinical settings. / degree of Medical DoctorQC 20100629