Yes / We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9Hz. Action potential waveforms recorded at 1Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na+-channel blocker (5μM) ranolazine or the intracellular Ca2+ buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller inMCTmyocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus, our study links electrical restitution remodeling to a defining mechanical characteristic of heart failure, the reduced ability to respond to an increase in demand.

The general purpose of this thesis is to establish the ability of Speckle Tracking Echocardiography (STE) in assessing left atrial (LA) response to pressure and volume overload respectively in aortic stenosis (AS) and mitral regurgitation (MR), and to evaluate its accuracy in predicting LA and right ventricular (RV) fibrosis in patients with end-stage heart failure (HF) undergoing heart transplantation (HTx). I demonstrated that assessment of left ventricular (LV) long axis systolic velocity and amplitude of excursion is more sensitive than simple determination of ejection fraction (EF) for revealing the beneficial impact of MR surgery on overall LV systolic performance. Severe symptomatic AS is associated with LA enlargement and compromised mechanical function with a high incidence of peri-operative atrial fibrillation (AF). Valve replacement reverses these abnormalities and regains normal atrial function, a behaviour which is directly related to the severity of pre-operative LV outflow tract obstruction. Early identification of LA size and function disturbances, as shown by myocardial strain measurements might contribute to better patient’s recruitment for a safe valve replacement. In late stage HF patients, the right ventricle is enlarged, with reduced systolic function due to significant myocardial fibrosis. RV free wall myocardial deformation is the most accurate function measure that correlates with the extent of RV myocardial fibrosis and functional capacity. In patients with preserved EF, severe MR masks LV and LA myocardial dysfunction and correlates with symptoms and post-operative cavity function instability. Three months after MVR, the underlying myocardial disturbances are unmasked suggesting that most pre-operative measurements are subject to loading conditions. Finally LA volume and PALS remain the main predictors of post-operative AF, thus should be used for stratifying surgical risk. STE has been shown to accurately determine the severity of impairment of LA myocardial function shown by suppressed PALS which was the strongest predictor of the presence and extent of fibrosis, over and above other structure and function parameters. These findings may assist in better stratifying patients with end stage HF and identifying particularly those requiring HTx.

The general purpose of this thesis is to establish capability and accuracy of speckle tracking echocardiography (STE) in assessing left atrial (LA), left ventricular (LV) and right ventricular (RV) function and their correlation with myocardial fibrosis, filling pressure and clinical outcomes in advanced heart failure (HF) patients before and after heart transplantation (HT). I demonstrated that HT recipients had impaired LV twist dynamics in the form of reduced rotation twist angle and untwist rate but time to peak twist was not different from the age matched controls and other cardiac surgical patients. With a longitudinal study conducted on patients with refractory HF, the best prognostic power has been shown by RV strain analysis. Among the indexes of LV function, the LV ejection fraction (LVEF) demonstrated the lowest diagnostic accuracy; instead LV global circumferential strain (GCS) showed a better sensitivity and specificity than LV global longitudinal strain (GLS). When analyzing the relationship between different severity of myocardial fibrosis and LV cavity function, the strongest function parameter that correlated with severity of myocardial fibrosis was GLS. In contrast, none of diastolic LV function or even measures of exercise capacity correlated with myocardial fibrosis. In patients with end-stage HF, global peak atrial longitudinal strain (PALS), an index of atrial reservoir function was dependent by pulmonary capillary wedge pressure (PCWP) and LV fibrosis, but not influenced by LV systolic function. Results from this study confirm previous evidence of correlation between impaired global PALS and increased PCWP.

Introdução: A Doença Pulmonar Obstrutiva Crônica (DPOC) está freqüentemente associada a comorbidades crônicas como a doença cardiovascular, o diabetes mellitus e a hipertensão. O presente estudo tem por objetivo investigar as alterações morfológicas e funcionais no coração secundárias ao enfisema pulmonar em ratos diabéticos. Métodos: Ratos Wistar machos adultos (200 ± 20 g, n = 36) foram destinados à avaliação ecocardiográfica, análise morfométrica do coração e pulmões e análise da taxa de sobrevida. O diabetes mellitus foi induzido por aloxana (42 mg/kg, iv) 10 dias antes da indução do enfisema pulmonar por instilação de elastase (0,25 UI/100 g de peso corpóreo). Um grupo de ratos diabéticos recebeu tratamento com insulina NPH (4 UI antes da elastase, seguido de 2 UI/dia, 50 dias). Os experimentos foram realizados 50 dias após a instilação. Resultados: Ratos diabéticos e respectivos controles instilados com elastase apresentaram aumentos similares no diâmetro médio alveolar, cujos valores correlacionam-se positivamente com aumentos na espessura da parede (p=0,0022), na área da cavidade (p=0,0001) e espessura dos cardiomiócitos (p=0,0001) do ventriculo direito (VD). Ratos tornados diabéticos por injeção de aloxana exibiram redução na espessura da parede do ventrículo esquerdo (VE), no septo interventricular (IV) e na espessura dos cardiomiócitos. Estas variáveis morfométricas associaram-se à redução da fração de encurtamento do VE (p < 0,05) e a aumento no tempo de relaxamento isovolumétrico do VE (p < 0,05). A taxa de sobrevida reduziu-se de 80% em ratos diabéticos a 40% em ratos diabéticos instilados com elastase (p < 0,05). Conclusões: O diabetes por aloxana em ratos não modifica a hipertrofia do VD secundária ao enfisema pulmonar, porém induz disfunção ventricular esquerda. A manifestação de ambas as doenças, diabetes mellitus e enfisema pulmonar, reduz substancialmente a taxa de sobrevida, enfatizando a condição de comorbidade na coexistência de diabetes e DPOC / Background: Chronic Obstructive Pulmonary Disease (COPD) is often associated with chronic comorbid conditions of cardiovascular disease, diabetes mellitus and hypertension. This study aimed to investigate morphological and functional alterations of the heart secondary to chronic emphysema in diabetic rats. Methods: Adult male Wistar rats (200 ± 20 g, n=36) were used for echocardiographic measurements, morphometric analyses of the heart and lungs, and survival rate. Diabetes mellitus was induced by alloxan (42 mg/kg, iv) 10 days before the induction of pulmonary emphysema by the instillation of elastase (0.25 IU/100 g body weight). A group of diabetic rats was treated with NPH insulin (4 IU before elastase, plus 2 IU/day, 50 days). Experiments were performed 50 days after instillation. Results: Both elastase-instilled diabetic rats and matching controls exhibited similar increases in mean alveolar diameter, which are positively correlated with increases in RV wall thickness (p=0.0022), cavity area (p=0.0001), and cardiomyocyte thickness (p=0.0001). Alloxan-diabetic rats demonstrated a reduction in left ventricular (LV) wall, IV septum, and cardiomyocyte thickness, associated with a reduction in LV fractional shortening (p<0.05), and an increase in LViv relaxation time (p < 0.05). Survival rate decreased from 80% in diabetic rats to 40% in elastase-instilled diabetic rats. Conclusions: Alloxan diabetes did not affect RV hypertrophy secondary to chronic emphysema, but induced LV dysfunction. The association of diabetes and emphysema substantially reduced the survival rate, emphasizing the comorbid condition of the coexistence of diabetes and COPD

Introdução: A Doença Pulmonar Obstrutiva Crônica (DPOC) está freqüentemente associada a comorbidades crônicas como a doença cardiovascular, o diabetes mellitus e a hipertensão. O presente estudo tem por objetivo investigar as alterações morfológicas e funcionais no coração secundárias ao enfisema pulmonar em ratos diabéticos. Métodos: Ratos Wistar machos adultos (200 ± 20 g, n = 36) foram destinados à avaliação ecocardiográfica, análise morfométrica do coração e pulmões e análise da taxa de sobrevida. O diabetes mellitus foi induzido por aloxana (42 mg/kg, iv) 10 dias antes da indução do enfisema pulmonar por instilação de elastase (0,25 UI/100 g de peso corpóreo). Um grupo de ratos diabéticos recebeu tratamento com insulina NPH (4 UI antes da elastase, seguido de 2 UI/dia, 50 dias). Os experimentos foram realizados 50 dias após a instilação. Resultados: Ratos diabéticos e respectivos controles instilados com elastase apresentaram aumentos similares no diâmetro médio alveolar, cujos valores correlacionam-se positivamente com aumentos na espessura da parede (p=0,0022), na área da cavidade (p=0,0001) e espessura dos cardiomiócitos (p=0,0001) do ventriculo direito (VD). Ratos tornados diabéticos por injeção de aloxana exibiram redução na espessura da parede do ventrículo esquerdo (VE), no septo interventricular (IV) e na espessura dos cardiomiócitos. Estas variáveis morfométricas associaram-se à redução da fração de encurtamento do VE (p < 0,05) e a aumento no tempo de relaxamento isovolumétrico do VE (p < 0,05). A taxa de sobrevida reduziu-se de 80% em ratos diabéticos a 40% em ratos diabéticos instilados com elastase (p < 0,05). Conclusões: O diabetes por aloxana em ratos não modifica a hipertrofia do VD secundária ao enfisema pulmonar, porém induz disfunção ventricular esquerda. A manifestação de ambas as doenças, diabetes mellitus e enfisema pulmonar, reduz substancialmente a taxa de sobrevida, enfatizando a condição de comorbidade na coexistência de diabetes e DPOC / Background: Chronic Obstructive Pulmonary Disease (COPD) is often associated with chronic comorbid conditions of cardiovascular disease, diabetes mellitus and hypertension. This study aimed to investigate morphological and functional alterations of the heart secondary to chronic emphysema in diabetic rats. Methods: Adult male Wistar rats (200 ± 20 g, n=36) were used for echocardiographic measurements, morphometric analyses of the heart and lungs, and survival rate. Diabetes mellitus was induced by alloxan (42 mg/kg, iv) 10 days before the induction of pulmonary emphysema by the instillation of elastase (0.25 IU/100 g body weight). A group of diabetic rats was treated with NPH insulin (4 IU before elastase, plus 2 IU/day, 50 days). Experiments were performed 50 days after instillation. Results: Both elastase-instilled diabetic rats and matching controls exhibited similar increases in mean alveolar diameter, which are positively correlated with increases in RV wall thickness (p=0.0022), cavity area (p=0.0001), and cardiomyocyte thickness (p=0.0001). Alloxan-diabetic rats demonstrated a reduction in left ventricular (LV) wall, IV septum, and cardiomyocyte thickness, associated with a reduction in LV fractional shortening (p<0.05), and an increase in LViv relaxation time (p < 0.05). Survival rate decreased from 80% in diabetic rats to 40% in elastase-instilled diabetic rats. Conclusions: Alloxan diabetes did not affect RV hypertrophy secondary to chronic emphysema, but induced LV dysfunction. The association of diabetes and emphysema substantially reduced the survival rate, emphasizing the comorbid condition of the coexistence of diabetes and COPD

Echocardiography is a well established technique when evaluating the size and function of the heart. One of the most common ways to measure the size of the right ventricle (RV) is to measure the RV outflow tract 1(RVOT1). Several ways to measure RVOT1 are described in the literature.These ways were compared with echocardiography on 27 healthy subjects.The result showed significant differences in RVOT1, depending on the way it was measured, concluding that the same site, method and body positionshould be used when comparing RVOT1 in the same subject over time.One parameter to evaluate the RV diastolic function (RVDF) is to measure the RV isovolumetric relaxation time (RV-IVRT), a sensitive marker ofRV dysfunction. There are different ways to measure this. In this thesis two ways of measuring RV-IVRT and their time intervals were compared in 20 patients examined with echocardiography. There was a significant difference between the two methods indicating that they are not measuring the same interval.Another way to assess the RVDF is to measure the maximal early diastolicvelocity (MDV) in the long-axis direction. MDV can be measured bydifferent methods, hence 29 patients were examined and MDV was measured according to two methods. There was a good correlation but a poor agreement between the two methods meaning that reference values cannot be used interchangeably.Takotsubo cardiomyopathy is characterized by apical wall motion abnormalities without coronary stenosis. The pathology of this condition remains unclear. To evaluate biventricular changes in systolic long-axisfunction and diastolic parameters in the acute phase and after recovery, 13 patients were included and examined with echocardiography at admission and after recovery. The results showed significant biventricular improvementof systolic long-axis function while most diastolic parameters remainedunchanged.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Dans un premier temps, nous avons observé la chronologie des altérations de la biogenèse et de la fonction mitochondriale dans les ventricules droit (VD) et gauche (VG) et le muscle gastrocnémien (GAS) dans un modèle animal d’hypertension artérielle pulmonaire (HTAP). Nous avons constaté une diminution précoce des facteurs impliqués dans la biogénèse mitochondriale du GAS. Plus tard, les mêmes anomalies apparaissaient dans le VD. Au stade décompensé de l’insuffisance cardiaque droite s’ajoutaient une diminution de la protéine PGC-1 , de l’activité de la citrate-synthase et de la respiration mitochondriale. L’expression des ARNm et la respiration mitochondriale du VG n’étaient pas modifiées de façon significative.Dans un deuxième temps, nous avons étudié l’effet de l’entraînement en mode excentrique sur le même modèle d’HTAP. La survie des rats entraînés n’était pas différente de celle des rats sédentaires et la tolérance hémodynamique évaluée par échocardiographie et cathétérisme cardiaque a été bonne. Le bénéfice de l’entraînement s’est traduit par une augmentation de la vitesse maximale de course dans les deux groupes entraînés, malades et témoins. / We assessed the time courses of mitochondrial biogenesis factors and respiration in the right ventricle (RV), gastrocnemius (GAS) and left ventricle (LV) in a model of pulmonary-hypertensive (PH) rats induced by monocrotaline (MT). The expression of the studied genes was decreased early in the MT GAS. At 4 weeks, the MT GAS and MT RV showed decreased mRNA levels whatever the stage of disease, but PGC-1 protein and citrate-synthase activity were significantly reduced only atthe decompensated stage. The functional result was a significant fall in mitochondrial respiration at the decompensated stage in the RV and GAS. The mRNA expression and mitochondrial respiration were not significantly modified in the MT LV. Secondly, we assessed the effects of eccentric exercise training (ECCt) in MT rats with PH. ECCt was initiated 2 weeks after MT injection for 4 weeks. The trained MT rats survival was not different from that of sedentary rats. ECCt was not detrimental on hemodynamic condition estimated by echocardiography and right heart catheterization. Maximal speed significantly increased in trained rats. The mRNA expression of mitochondrial biogenesis factors were not significantly modified in skeletal muscle and in RV.

Contexte: Le syndrome de détresse respiratoire aigüe (SDRA) est associé à une dysfonction vasculaire pulmonaire. Objectifs: Préciser le retentissement cardiaque de cette dysfonction vasculaire pulmonaire en recherchant la fréquence et le pronostic du foramen ovale perméable, du passage transpulmonaire de bulles en échographie de contraste, du cœur pulmonaire aigu (CPA), de la dysfonction systolique ventriculaire droite ainsi que de la déformation ventriculaire gauche au cours du SDRA. Nous avons aussi évalué la tolérance hémodynamique de la ventilation en Pression Expiratoire Positive (PEP) élevée. Méthodes: Les explorations étaient menées par échographie trans-œsophagienne (ETO) traditionnelle et en signature acoustique. Résultats: La faisabilité de l'ETO en décubitus ventral est bonne. Le foramen ovale perméable, détecté chez 19% des patients, est associé à une moins bonne réponse à l'augmentation de la PEP et à un recours aux thérapeutiques de sauvetage plus fréquent. Le passage de bulles transpulmonaire ne rend pas compte du seul shunt intra-pulmonaire anatomique, et dépend plus des conditions hémodynamiques (augmentation du débit cardiaque associée au sepsis) que de la ventilation. Le CPA, retrouvé chez 22% des patients, est associé à une pression motrice plus élevée, et au sepsis ; il est fréquemment associé à une insuffisance circulatoire, avec une mortalité plus élevée à J28. La quantification de la déformation ventriculaire gauche systolique par l'index d'excentricité est un bon marqueur de CPA, mais pas la dysfonction contractile ventriculaire droite évaluée en signature acoustique. Enfin, nous n'avons pas retrouvé de lien robuste entre la tolérance hémodynamique et l'efficacité respiratoire (recrutement alvéolaire) des niveaux de PEP élevés, sous réserve d'un nombre limité de patients. Conclusion: Les conséquences cardiaques de la dysfonction vasculaire pulmonaire restent fréquentes et associées à un pronostic péjoratif, avec des implications respiratoires et circulatoires. / Context: Acute respiratory distress syndrome (ARDS) leads to pulmonary vascular dysfunction Aims: We assessed cardiac consequences of pulmonary vascular dysfunction by detecting patent foramen ovale and transpulmonary bubbles transit using contrast echocardiography, acute cor pulmonale, right ventricle systolic dysfunction and left ventricle deformation during ARDS. We also assessed hemodynamic tolerance of high positive end expiratory pressure (PEEP). Methods: Transesophageal echocardiography (TEE) was performed with standard measurements and speckle tracking. Results: TEE could be safely performed in prone position. Patent foramen ovale was detected in 19% of patients, and was associated with a poor oxygenation response to PEEP, and greater use of adjunctive interventions. Transpulmonary bubbles transit was not solely related to anatomical intrapulmonary shunt, but was merely influenced by hemodynamic status (increased cardiac output associated with sepsis). Acute cor pulmonale occurred in 22% of patients, and was associated with a higher driving pressure and with sepsis; it was often associated with circulatory failure, with higher day-28 mortality. Left ventricle systolic deformation (evaluated by eccentricity index) but not right ventricle contractile impairment (evaluated with speckle tracking) was associated with acute cor pulmonale. Finally, we did not find a robust relation between hemodynamic tolerance and alveolar recruitment with higher PEEP levels, but the limited number of patients restricted the power of the analysis. Conclusion: Cardiac consequences of pulmonary vascular dysfunction remain frequent and associated with a poorer prognosis, with respiratory and circulatory implications.

Hintergrund: Die gegenwärtigen Richtlinien zur Herzinsuffizienzbehandlung schenken der Beurteilung des rechten Ventrikels nur wenig Aufmerksamkeit, da nur begrenzte Daten zu Determinanten der rechtsventrikulären Funktion und den Mechanismen, die zu seiner Insuffizienz führen bzw. der Beziehung zu den Ergebnissen zur Verfügung stehen. Fragestellung: Es war die Aufgabe der Studie, die Prävalenz der rechtsventrikulären Dysfunktion (RVD) zu bestimmen, klinische und hämodynamische Korrelate zu identifizieren und die Beziehung zu kardialer Mortalität bei Herzinsuffizienz mit reduzierter linksventrikulärer Ejektionsfraktion (LVEF) hervorgerufen durch die nicht-ischämische Kardiomyopathie (NICM) einzuschätzen. Methoden: In dieser prospektiv angelegten Studie wurden 423 Patienten mit kardiovaskulärer Magnetresonanztomographie (CMR) untersucht. Zudem wurde bei 100 Patienten zeitnah zur CMR-Untersuchung eine Rechtsherzkatheteruntersuchung durchgeführt. Die kardiale Mortalität wurde als Studienendpunkt definiert. Ergebnisse: Während einer medianen Nachbeobachtungszeit von 6,2 Jahren (IQR: 2,9 bis 7,6) starben 101 (24 %) der Patienten aufgrund eines kardialen Versagens. Es stellte sich heraus, dass die rechtsventrikuläre Ejektionsfraktion (RVEF) ein starker Prädiktor für kardiale Mortalität nach Anpassung an Alter, NYHA-Klasse, systolischen Blutdruck, Herzfrequenz, Natrium und Kreatininserumspiegel, Myokardnarbe und linksventrikuläre Ejektionsfraktion (LVEF) ist. Patienten, die im Quintil mit der niedrigsten RVEF waren, hatten ein fast fünffach so hohes kardiales Mortalitätsrisiko im Vergleich zum höchsten Quintil (Hazard Ratio [95%-Konfidenzintervall (CI)]: 4,68 [2,43-9,02]; p<0,0001). Die RVEF hatte eine positive Korrelation zur LVEF (r=0,60; p=<0,0001), und eine umgekehrte Korrelation zum rechten Vorhofdruck (r=−0,32; p=0,001), mittleren pulmonalarteriellen Druck (r=−0,34, p=0,0005), transpulmonalen Gradienten (r=−0,28; p=0,006), aber keine mit dem pulmonalarteriellen Verschlussdruck (r=−0,15; p=0,13). In der multivariablen logistischen Regressionsanalyse des CMR und der klinischen und hämodynamischen Daten waren die LVEF (Odds Ratio [95%-CI]: 0,85 [0,78-0,92], p<0,0001), der transpulmonale Gradient (Odds Ratio [95%-CI]: 1,20 [1,09-1,32], p=0,0003) und der systolische Blutdruck (Odds Ratio [95%-CI]: 0,97 [0,94-0,99], p=0,02) die stärksten Prädiktoren für die RVD. Schlussfolgerungen: Die Untersuchung der RVEF mit CMR liefert wichtige prognostische Informationen unabhängig von etablierten Risikofaktoren bei Herzinsuffizienzpatienten. RVD steht in einer starken Verbindung mit beiden Kenngrößen der intrinsischen myokardialen Kontraktilität und der erhöhten Nachlast durch eine pulmonalvaskuläre Dysfunktion.:Inhaltsverzeichnis Abkürzungsverzeichnis 1 Einleitung 1.1 Einführung in die Problemstellung der vorliegenden Arbeit 1.2 Nicht-ischämische Kardiomyopathie 1.3 Die Bedeutung des rechten Ventrikels für die Entwicklung der Herzinsuffizienz 1.4 Magnetresonanztomographie als Untersuchungsmethode 1.4.1 Einführung in die CMR 1.4.2 Allgemeine Grundlagen der MRT 1.4.3 True Fast Imaging with Steady-State Precession (TrueFISP) 1.4.4 Turbo Fast Low-Angle Shot (Turbo-FLASH) 1.5 Rechtsherzkatheter als Standarduntersuchung 1.6 Ziele der Studie 2 Patienten und Methoden 2.1 Patientenpopulation 2.2 Untersuchungsprotokoll MRT 2.2.1 Untersuchungstechnik 2.2.2 Bildanalyse 2.3 Rechtsherzkatheteruntersuchung 2.4 Verlaufsuntersuchung 2.5 Statistische Analyse 3. Ergebnisse 3.1 Basischarakteristika 3.2 Ergebnisse der Nachfolgeuntersuchung 3.3 Zusammenhang zwischen rechtsventrikulärer Dysfunktion und kardialer Mortalität 3.4 Prädiktoren der kardialen Mortalität 3.5 Bestimmungsfaktoren der rechtsventrikulären Dysfunktion 4 Diskussion 4.1 Ergebnisdiskussion 4.2 Grenzen der Studie 4.3 Schlussfolgerungen der Diskussion 4.4 Perspektiven 4.4.1 Kompetenz bei der Patientenbehandlung und Fähigkeiten der Prozedur 4.4.2 Ausblick für die zukünftige Behandlung 5 Zusammenfassung 6 Literaturverzeichnis Abbildungsverzeichnis Tabellenverzeichnis Eidesstattliche Erklärungen Einhaltung der gesetzlichen Regeln Danksagung / Background: Current heart failure (HF) management guidelines place little emphasis on right ventricular (RV) assessment, due to limited available data on determinants of RV function and mechanisms leading to its failure, and relation to outcomes. Objective: To determine the prevalence of RV dysfunction (RVD), identify clinical and hemodynamic correlates, and assess the relation to cardiac mortality in HF with reduced left ventricular ejection fraction (LVEF) from non-ischemic cardiomyopathy (NICM). Methods: This study prospectively examined 423 patients with cardiovascular magnetic resonance (CMR). Right-heart catheterization was performed in 100 patients. The prespecified study endpoint was cardiac mortality. Results: During a median follow-up time of 6.2 years (IQR: 2.9 to 7.6) 101 (24%) patients died of cardiac causes. RVEF was a strong independent predictor of cardiac mortality after adjustment for age, HF functional class, systolic blood pressure, heart rate, serum sodium and creatinine levels, myocardial scar, and LVEF. Patients with the lowest quintile of RVEF had a near five-fold higher cardiac mortality risk compared to the highest quintile (hazard ratio [95% confidence interval (CI)]: 4.68 [2.43-9.02], p<0.0001). RVEF was positively correlated with LVEF (r=0.60, p=<0.0001), and inversely correlated with right atrial pressure (r=−0.32, p=0.001), mean pulmonary artery pressure (r=−0.34, p=0.0005), transpulmonary gradient, (r=−0.28, p=0.006) but not with pulmonary wedge pressure (r=−0.15, p=0.13). In multivariable logistic regression analysis of CMR, clinical, and hemodynamic data, LVEF, transpulmonary gradient, and systolic blood pressure were the strongest predictors of RVD (odds ratio [95% CI]: 0.85 [0.78-0.92], p<0.0001; 1.20 [1.09-1.32], p=0.0003; 0.97 [0.94-0.99], p=0.02, respectively). Conclusion: CMR assessment of RVEF provides important prognostic information independent of established risk factors in HF patients. RVD is strongly associated with both indices of intrinsic myocardial contractility and increased afterload from pulmonary vascular dysfunction.:Inhaltsverzeichnis Abkürzungsverzeichnis 1 Einleitung 1.1 Einführung in die Problemstellung der vorliegenden Arbeit 1.2 Nicht-ischämische Kardiomyopathie 1.3 Die Bedeutung des rechten Ventrikels für die Entwicklung der Herzinsuffizienz 1.4 Magnetresonanztomographie als Untersuchungsmethode 1.4.1 Einführung in die CMR 1.4.2 Allgemeine Grundlagen der MRT 1.4.3 True Fast Imaging with Steady-State Precession (TrueFISP) 1.4.4 Turbo Fast Low-Angle Shot (Turbo-FLASH) 1.5 Rechtsherzkatheter als Standarduntersuchung 1.6 Ziele der Studie 2 Patienten und Methoden 2.1 Patientenpopulation 2.2 Untersuchungsprotokoll MRT 2.2.1 Untersuchungstechnik 2.2.2 Bildanalyse 2.3 Rechtsherzkatheteruntersuchung 2.4 Verlaufsuntersuchung 2.5 Statistische Analyse 3. Ergebnisse 3.1 Basischarakteristika 3.2 Ergebnisse der Nachfolgeuntersuchung 3.3 Zusammenhang zwischen rechtsventrikulärer Dysfunktion und kardialer Mortalität 3.4 Prädiktoren der kardialen Mortalität 3.5 Bestimmungsfaktoren der rechtsventrikulären Dysfunktion 4 Diskussion 4.1 Ergebnisdiskussion 4.2 Grenzen der Studie 4.3 Schlussfolgerungen der Diskussion 4.4 Perspektiven 4.4.1 Kompetenz bei der Patientenbehandlung und Fähigkeiten der Prozedur 4.4.2 Ausblick für die zukünftige Behandlung 5 Zusammenfassung 6 Literaturverzeichnis Abbildungsverzeichnis Tabellenverzeichnis Eidesstattliche Erklärungen Einhaltung der gesetzlichen Regeln Danksagung