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The carotid artery wall moves longitudinally along the length of the vessel, although little is known about what causes this motion, or what health information it represents. The overarching purpose of this dissertation was to investigate the regulation of carotid artery longitudinal wall motion (CALM) in humans, as well as how CALM can be used to infer information about arterial health. Through observational and experimental designs, we tested evidence for a structural ventricular-vascular coupling effect, which postulates that systolic anterograde CALM is influenced by the forward blood shear rate while systolic retrograde CALM is influenced by left ventricular rotation, although the data suggests a moderate influence of left ventricular rotation, and minimal influence of shear rate. In cross-sectional analyses, we demonstrated that diastolic CALM variables are better related to age and health status compared to systolic CALM displacement and that this relationship was independent of traditional measures of arterial stiffness. These experimental and observational results directed the use of diastolic CALM as a potential indicator of arterial health in subsequent studies, due to the relative independence from systolic events. While there was no effect of 12-weeks of exercise training in healthy men on diastolic CALM variables, we observed increased systolic retrograde CALM and diastolic CALM acceleration in men with a history of resistance exercise training compared to sedentary men, suggesting an effect of habitual exercise training. Our novel findings suggest that CALM is regulated by a complex system, in part related to both arterial wall structure and ventricular-vascular coupling, and may have clinical value in complimenting measures of traditional arterial stiffness in humans. Future studies should examine whether local changes to arterial wall structure or indirect changes in regulatory control dictate differences in CALM with aging and with chronic exercise training, before integrating CALM into routine measurement of arterial health. / Thesis / Doctor of Philosophy (PhD) / We have known for a long time that arteries expand in order to absorb pressure; however, only recently have we identified that arteries also move longitudinally along the length of the arterial wall. The overarching purpose of this dissertation was to study what causes carotid artery longitudinal wall motion (CALM), and how we can use this information to understand arterial health. We demonstrated that CALM is partly controlled through the forward blood velocity wave and left ventricular rotation of the heart, and that diastolic CALM is uniquely related to aging and health status, but is not impacted by exercise training in healthy men. There are many aspects of CALM that need to be examined before wide-spread use, though our results indicate that CALM represents a new way of studying arterial health, which has the potential to complement traditional measures of cardiovascular disease risk in humans.

L’hypertension artérielle chronique induit une hypertrophie ventriculaire gauche, à l’origine d’une dysfonction diastolique caractérisée par des troubles de la relaxation, de la compliance et du remplissage ventriculaires gauches, le tout aggravé par toute augmentation de la fréquence cardiaque. Le couplage contraction-relaxation physiologique implique, en cas de préservation dans ce contexte d’hypertrophie ventriculaire gauche, que cette dysfonction diastolique s’accompagne d’une dysfonction systolique. Ainsi, ce travail de thèse s’est attaché (1) à caractériser la fonction ventriculaire gauche et le couplage contraction-relaxation à l’aide de la mesure de la torsion et la détorsion, (2) à étudier les mécanismes cellulaires impliqués dans le couplage contraction-relaxation et (3) à explorer les effets d’une stratégie thérapeutique visant à réduire la fréquence cardiaque sur la torsion et la détorsion du ventricule gauche dans un modèle d’hypertension artérielle chronique et d’hypertrophie ventriculaire induites chez le porc chroniquement instrumenté par la perfusion continue d’angiotensine II pendant 28 jours. A J28, la torsion et la détorsion étaient diminuées et la détorsion également retardée au sein du cycle cardiaque, alors que la fraction d’éjection ventriculaire gauche était préservée. Le couplage contraction-relaxation était préservé, tant au niveau du ventricule gauche qu’à l’échelon cardiomyocytaire, suggérant que toute dysfonction diastolique devrait faire rechercher une dysfonction systolique. A J28, ces anomalies fonctionnelles s’accompagnaient d’une diminution de l’expression de la SERCA2a et de sa protéine régulatrice le phospholamban. Des anomalies du récepteur de la ryanodine de type 2 étaient aussi observées avec son hyperphosphorylation et la dissociation de sa protéine régulatrice calstabine 2, à l’origine de fuites calciques systoliques et diastoliques. Ce dernier pourrait ainsi jouer un rôle clé dans la préservation du couplage contraction-relaxation et représenter l’intégrateur entre les anomalies ventriculaire gauche systolique et diastolique observées. Enfin, la réduction pharmacologique de la fréquence cardiaque à J28 par l’ivabradine, un inhibiteur sélectif des canaux If, permettait d’améliorer, en partie par des effets fréquence-indépendants dont les mécanismes cellulaires restent à élucider, tant les anomalies ventriculaire gauche diastolique que systolique, avec une amélioration des temps de contraction et de relaxation isovolumiques, de la torsion et de la détorsion ainsi que du remplissage du ventricule gauche. En l’absence d’hypertrophie ventriculaire gauche, la réduction de la fréquence cardiaque à des valeurs inférieures à 60 batt/min s’accompagnait d’un effet délétère fréquence-dépendant, à l’origine d’une altération isolée de la fonction diastolique caractérisée par une diminution de la détorsion du ventricule gauche et une augmentation de la pression télédiastolique ventriculaire gauche. La caractérisation de la fonction ventriculaire gauche et l’étude du couplage contraction-relaxation par la mesure de la torsion et de la détorsion en cas de décompensation cardiaque restent à déterminer. / Chronic hypertension induces left ventricular (LV) hypertrophy, resulting in abnormalities in LV relaxation, passive stiffness and filling. The higher the heart rate, the more pronounced the LV diastolic dysfunction. Moreover, in the normal heart, there is a tight coupling between LV contraction and relaxation, implying that in case of preserved contraction-relaxation coupling during LV hypertrophy, there is no diastolic dysfunction without systolic dysfunction. Thus, the three main objectives of this thesis were to investigate 1) the LV function and contraction-relaxation coupling with LV twist and untwist, which represent LV myocardial deformation during systole and diastole, 2) the cellular mechanisms of the LV contraction-relaxation coupling and 3) the effects effects of heart rate reduction on LV twist and untwist in the context of chronic hypertension and LV hypertrophy. All experiments were conducted in a pig model of chronic hypertension and LV hypertrophy induced by four weeks of continuous angiotensin II infusion. Chronic angiotensin II infusion decreased LV twist and untwist but also delayed LV untwist in the cardiac cycle, whereas the LV ejection fraction was preserved. The contraction-relaxation coupling was preserved as illustrated by the strong relationship between LV twist and untwist. The contraction-relaxation coupling was also preserved at the level of cardiomyocytes. This implies that LV hypertrophy is associated with concomitant LV diastolic and systolic dysfunction despite preserved LV ejection fraction. Thus, LV diastolic dysfunction is always accompanied by LV systolic dysfunction, i.e., the discovery of LV diastolic dysfunction with preserved ejection fraction might imply the track of LV systolic dysfunction. At the cellular level, LV systolic and diastolic dysfunctions were associated to aberrant calcium handling with a remodelling of the type 2 ryanodine receptor calcium release channel (RyR2), i.e., PKA-hyperphosphorylation and depletion of calstabin 2 (FKBP12.6). RyR2 were leaky and hypersensitive to cytosolic calcium, during both the contraction and the relaxation phases. Since both LV systolic and diastolic dysfunctions were associated to leaky and hypersensitive RyR2 channels, it might suggest considering RyR2 as an integrator contributing to control contraction-relaxation coupling during chronic hypertension and LV hypertrophy. Finally, we investigated the effects of heart rate reduction induced by ivabradine, an If-channel blocker, which does not modify atrioventricular or LV conduction and is devoid of any intrinsic negative inotropic or lusitropic effects. In the context of chronic hypertension and LV hypertrophy, ivabradine improved both LV systolic and diastolic functions, as attested by the improvement in contraction and relaxation times, LV twist and untwist as well as LV filling. Heart-rate independent effects of ivabradine, i.e., pleiotropic effects, participate to its beneficial effect. However, the cellular mechanisms of these beneficial effects of ivabradine were not elucidated and require further investigations. In normal heart, when heart rate was reduced to a low level (approximately <60 beats/min) with ivabradine, LV twist was not affected but LV diastolic function was altered as suggested by decreased LV untwist parameters and increased LV end-diastolic pressure. Investigation of contraction-relaxation coupling during decompensation from stable LV hypertrophy remains a goal to achieve.

Doctor Pharmaceuticae - DPharm / An aqueous extract prepared from the leaves and smaller stems of Leonotis leonurus was used to investigate the potential effects on certain cardiovascular parameters, such as left ventricular systolic pressure, end-diastolic pressure, developed pressure, heart rate, cardiac work and coronary perfusion pressure in isolated rat hearts. Hearts were perfused at constant flow for 3min using the modified Langendorf! perfused model of the heart. Effects of adrenaline and digoxin solutions on the isolated heart were compared to that of the plant extract. Adrenaline produced both positive inotropic and chronotropic effects. Adrenaline increased (p<O.Ol) the left ventricular systolic pressure and hence the left ventricular developed pressure by 40.6% and 43.9% at peak, and 24.3% and 31.9%, after 3min, respectively. Simultaneously, the heart rate and the cardiac work were increased (p<0.01) by 22.5% and 89.4% at peak, and 24.6% and 63%, after 3rnin, respectively. There were no significant effects on the left ventricular diastolic pressure and the coronary perfusion pressure. Digoxin solution (2.5ng/ml) significantly (p<O.Ol) increased the left ventricular systolic pressure by 5.1% after 3min and the left ventricular diastolic pressure by 9.7% at peak and 5.3% after 3min. The heart rate was significantly (p<O.OI) decreased by 3.7% at peak. The cardiac work was increased by 4.5% after 3rnin. Digoxin did not significantly affect the left end diastolic pressure and the coronary perfusion pressure. The extract of Leonons leonurus at O.lmg/ml increased (p<O.OI) the left ventricular systolic pressure and hence the left ventricular diastolic pressure by 9.7% and 10.7% at peak, and 5.4% and 5.5% after 3rnin, respectively. The cardiac work was increased (p<O.Ol) by 10.1% at peak. Leonotis leonurus (0.1mg/ml) did not significantly affect the left ventricular end diastolic pressure, the heart rate and the coronary perfusion pressure. At 0.5mg/ml, the left ventricular systolic pressure and hence the left ventricular diastolic pressure were increased (p<0.01) by 14.8% and 15.4% at peak and 7.4% and 7.8% after 3rnin, respectively with a corresponding decrease (p<O.OI) in the coronary perfusion pressure of 8.5% at peak and 4.4% after 3rnin. The cardiac work was increased (p<O.OI) by 13.6% at peak and 5.2% after 3rnin. The extract at 1.0mg/ml increased (p<O.Ol) the left ventricular systolic pressure and hence the left ventricular diastolic pressure by 25.4% and 29.4% at Peak, and 23.1% and 26.3% after 3rnin, respectively. The heart rate was reduced (p<O.OI) by 34.7% at peak and 28.3% after 3min. The cardiac work and the coronary perfusion pressure were decreased (p<O.OI) by 15.9% and 12.1% at Peak and 3.3% and 11.4% after 3rnin. However, at 2.0mg/ml, the left ventricular systolic pressure and the left ventricular diastolic pressure were increased (p<O.OI) by 14.9% at peak. The left ventricular diastolic pressure was decreased (p<O.OI)by 9.8% over the 3rnin. The heart rate was drastically decreased (p<O.OI) by 42.7% after 3rnin. The cardiac work was reduced (p<O.Ol) by 48.8% over the 3min period. Also, the coronary perfusion pressure was decreased (p<0.01) by 16.9% at peak. Thus, Leonatis leonurus produced both positive inotropic and negative chronotropic effects after 3min perfusion, accompanied by a decreased coronary perfusion pressure. Thus, it appears that the extract seemed to contain certain constituents associated with positive inotropic and negative chronotropic agents as wel! as constituents associated with coronary vasodilation. However, at the higher concentration, it seemed to contain some constituents associated with toxic effects on the isolated heart. Therefore, further studies are needed to isolate the various constituents and examine their possible pharmacological effects on the heart individually before it could be considered safe to recommend this plant for its use in the treatment of cardiovascular disease.

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

Introdução. Pacientes com insuficiência cardíaca submetidos à ventriculectomia parcial esquerda apresentam melhora na função sistólica do ventrículo esquerdo em repouso, porém continuam apresentando limitação funcional. Objetivo. Para melhor compreender os mecanismos desta limitação funcional, estudamos a função sistólica e diastólica do ventrículo esquerdo em repouso e durante exercício submáximo em pacientes submetidos a ventriculectomia parcial esquerda e em pacientes com insuficiência cardíaca não operados, pareados para capacidade funcional máxima e submáxima. Métodos. Foram estudados 9 pacientes submetidos previamente a ventriculografia parcial esquerda (VPE) e 9 pacientes com insuficiência cardíaca não operados previamente (IC). Todos os pacientes foram submetidos inicialmente a um teste cardiopulmonar para determinação do consumo de oxigênio no limiar anaeróbio (LA) e de pico (VO2 pico). Após, foram estudados através da ventriculografia radioisotópica e analisadas a fração de ejeção (FE) e a taxa máxima de enchimento (TME) do ventrículo esquerdo, em repouso e exercício na intensidade do LA. Resultados. Os grupos apresentaram capacidade funcional semelhante avaliada pelo VO2 pico (VPE: [média ± DP] 13,1 ± 3,3 ml/kg.min; IC: 14,1 ± 3,6 ml/kg.min; P > 0,05) e LA (VPE: 7,9 ± 1.3 ml/kg.min; IC: 8,5 ± 1,6 ml/kg.min; P > 0,05). A frequência cardíaca máxima foi maior no grupo IC em comparação ao grupo da VPE (VPE: 119 ± 20 bpm; IC: 149 ± 21 bpm; P < 0.05) A FE em repouso era mais elevada no grupo VPE (VPE: 40 ± 12 %; IC: 32 ± 9 %; P < 0,0125), entretanto a FE elevou-se do repouso ao LA apenas no grupo IC (VPE: 44 ± 17 %; IC: 39 ± 11 %; P < 0,0125). A TME foi semelhante em repouso (VPE: 1,41 ± 0,55 VDF/s; IC: 1,39 ± 0,55 VDF/s; P > 0,05) e aumentou na intensidade do LA similarmente em ambos os grupos (VPE: 2,28 ± 0,55 VDF/s; IC: 2,52 ± 1,07 VDF/s; P < 0,0125). Conclusão. Pacientes submetidos a ventriculectomia parcial esquerda apresentam uma o limiar anaeróbio (LA) resposta anormal da função sistólica do ventrículo esquerdo ao exercício na intensidade do LA e uma resposta cronotrópica diminuida ao exercício máximo. Essas respostas anormais podem contribuir para a limitada capacidade ao exercício destes pacientes, a despeito da melhora na função ventricular sistólica em repouso. / Background. Patients with heart failure who have undergone partial left ventriculectomy improve resting left ventricular systolic function, but maintain limited functional capacity. Objective. In order to better understand the mechanisms associated with this limitation, we studied the systolic and diastolic left ventricular function at rest and during submaximal exercise in patients with previous partial left ventriculectomy and in patients with heart failure who had not been operated, matched for maximal and submaximal exercise capacity. Methods: Nine patients with heart failure who were previously submitted to partial left ventriculectomy (PLV) were compared with a group of 9 patients with heart failure who had not been operated. All patients performed a cardiopulmonary exercise testing with measurement of peak oxygen uptake (VO2 peak) and anaerobic threshold (AT). In a second evaluation, radionuclide left ventriculography was performed to analyze ejection fraction (EF) and peak filling rate (PFR) at rest and during exercise at the intensity corresponding to the AT. Results: Groups presented similar exercise capacity evaluated by VO2peak (PLV: [mean ± SD] 13.1 ± 3.3 mL/Kg.min; HF: 14.1 ± 3.6 mL/Kg.min; P > 0.05) and AT (PLV: 7.9 ± 1.3 mL/Kg.min; HF: 8.5 ± 1.6 mL/Kg.min; P > 0.05). Maximal heart rate was higher in the HF group when compared to the PLV group (PLV: 119 ± 20 bpm; HF: 149 ± 21 bpm; P < 0.05). EF at rest was higher in the PLV group (PLV: 40 ± 12 %; HF: 32 ± 9 %; P < 0.0125), however EF increased from rest to AT only in the HF group (PLV: 44 ± 17 %; HF: 39 ± 11 %; P < 0.0125). PFR was similar at rest (PLV: 1.41 ± 0.55 EDV/sec; HF: 1.39 ± 0.55 EDV/sec; P > 0.05) and increased in both groups at the AT intensity (PLV: 2.28 ± 0.55 EDV/sec; HF: 2.52 ± 1.07 EDV/sec; P < 0,0125). Conclusion: Patients who had partial left ventriculectomy present an abnormal response of left ventricular systolic function to exercise at the AT intensity and an impaired chronotropic response to maximal exercise. These abnormal responses may contribute to the limited exercise capacity of these patients, despite the improvement in resting left ventricular systolic function.

Introdução. Pacientes com insuficiência cardíaca submetidos à ventriculectomia parcial esquerda apresentam melhora na função sistólica do ventrículo esquerdo em repouso, porém continuam apresentando limitação funcional. Objetivo. Para melhor compreender os mecanismos desta limitação funcional, estudamos a função sistólica e diastólica do ventrículo esquerdo em repouso e durante exercício submáximo em pacientes submetidos a ventriculectomia parcial esquerda e em pacientes com insuficiência cardíaca não operados, pareados para capacidade funcional máxima e submáxima. Métodos. Foram estudados 9 pacientes submetidos previamente a ventriculografia parcial esquerda (VPE) e 9 pacientes com insuficiência cardíaca não operados previamente (IC). Todos os pacientes foram submetidos inicialmente a um teste cardiopulmonar para determinação do consumo de oxigênio no limiar anaeróbio (LA) e de pico (VO2 pico). Após, foram estudados através da ventriculografia radioisotópica e analisadas a fração de ejeção (FE) e a taxa máxima de enchimento (TME) do ventrículo esquerdo, em repouso e exercício na intensidade do LA. Resultados. Os grupos apresentaram capacidade funcional semelhante avaliada pelo VO2 pico (VPE: [média ± DP] 13,1 ± 3,3 ml/kg.min; IC: 14,1 ± 3,6 ml/kg.min; P > 0,05) e LA (VPE: 7,9 ± 1.3 ml/kg.min; IC: 8,5 ± 1,6 ml/kg.min; P > 0,05). A frequência cardíaca máxima foi maior no grupo IC em comparação ao grupo da VPE (VPE: 119 ± 20 bpm; IC: 149 ± 21 bpm; P < 0.05) A FE em repouso era mais elevada no grupo VPE (VPE: 40 ± 12 %; IC: 32 ± 9 %; P < 0,0125), entretanto a FE elevou-se do repouso ao LA apenas no grupo IC (VPE: 44 ± 17 %; IC: 39 ± 11 %; P < 0,0125). A TME foi semelhante em repouso (VPE: 1,41 ± 0,55 VDF/s; IC: 1,39 ± 0,55 VDF/s; P > 0,05) e aumentou na intensidade do LA similarmente em ambos os grupos (VPE: 2,28 ± 0,55 VDF/s; IC: 2,52 ± 1,07 VDF/s; P < 0,0125). Conclusão. Pacientes submetidos a ventriculectomia parcial esquerda apresentam uma o limiar anaeróbio (LA) resposta anormal da função sistólica do ventrículo esquerdo ao exercício na intensidade do LA e uma resposta cronotrópica diminuida ao exercício máximo. Essas respostas anormais podem contribuir para a limitada capacidade ao exercício destes pacientes, a despeito da melhora na função ventricular sistólica em repouso. / Background. Patients with heart failure who have undergone partial left ventriculectomy improve resting left ventricular systolic function, but maintain limited functional capacity. Objective. In order to better understand the mechanisms associated with this limitation, we studied the systolic and diastolic left ventricular function at rest and during submaximal exercise in patients with previous partial left ventriculectomy and in patients with heart failure who had not been operated, matched for maximal and submaximal exercise capacity. Methods: Nine patients with heart failure who were previously submitted to partial left ventriculectomy (PLV) were compared with a group of 9 patients with heart failure who had not been operated. All patients performed a cardiopulmonary exercise testing with measurement of peak oxygen uptake (VO2 peak) and anaerobic threshold (AT). In a second evaluation, radionuclide left ventriculography was performed to analyze ejection fraction (EF) and peak filling rate (PFR) at rest and during exercise at the intensity corresponding to the AT. Results: Groups presented similar exercise capacity evaluated by VO2peak (PLV: [mean ± SD] 13.1 ± 3.3 mL/Kg.min; HF: 14.1 ± 3.6 mL/Kg.min; P > 0.05) and AT (PLV: 7.9 ± 1.3 mL/Kg.min; HF: 8.5 ± 1.6 mL/Kg.min; P > 0.05). Maximal heart rate was higher in the HF group when compared to the PLV group (PLV: 119 ± 20 bpm; HF: 149 ± 21 bpm; P < 0.05). EF at rest was higher in the PLV group (PLV: 40 ± 12 %; HF: 32 ± 9 %; P < 0.0125), however EF increased from rest to AT only in the HF group (PLV: 44 ± 17 %; HF: 39 ± 11 %; P < 0.0125). PFR was similar at rest (PLV: 1.41 ± 0.55 EDV/sec; HF: 1.39 ± 0.55 EDV/sec; P > 0.05) and increased in both groups at the AT intensity (PLV: 2.28 ± 0.55 EDV/sec; HF: 2.52 ± 1.07 EDV/sec; P < 0,0125). Conclusion: Patients who had partial left ventriculectomy present an abnormal response of left ventricular systolic function to exercise at the AT intensity and an impaired chronotropic response to maximal exercise. These abnormal responses may contribute to the limited exercise capacity of these patients, despite the improvement in resting left ventricular systolic function.

Introdução. Pacientes com insuficiência cardíaca submetidos à ventriculectomia parcial esquerda apresentam melhora na função sistólica do ventrículo esquerdo em repouso, porém continuam apresentando limitação funcional. Objetivo. Para melhor compreender os mecanismos desta limitação funcional, estudamos a função sistólica e diastólica do ventrículo esquerdo em repouso e durante exercício submáximo em pacientes submetidos a ventriculectomia parcial esquerda e em pacientes com insuficiência cardíaca não operados, pareados para capacidade funcional máxima e submáxima. Métodos. Foram estudados 9 pacientes submetidos previamente a ventriculografia parcial esquerda (VPE) e 9 pacientes com insuficiência cardíaca não operados previamente (IC). Todos os pacientes foram submetidos inicialmente a um teste cardiopulmonar para determinação do consumo de oxigênio no limiar anaeróbio (LA) e de pico (VO2 pico). Após, foram estudados através da ventriculografia radioisotópica e analisadas a fração de ejeção (FE) e a taxa máxima de enchimento (TME) do ventrículo esquerdo, em repouso e exercício na intensidade do LA. Resultados. Os grupos apresentaram capacidade funcional semelhante avaliada pelo VO2 pico (VPE: [média ± DP] 13,1 ± 3,3 ml/kg.min; IC: 14,1 ± 3,6 ml/kg.min; P > 0,05) e LA (VPE: 7,9 ± 1.3 ml/kg.min; IC: 8,5 ± 1,6 ml/kg.min; P > 0,05). A frequência cardíaca máxima foi maior no grupo IC em comparação ao grupo da VPE (VPE: 119 ± 20 bpm; IC: 149 ± 21 bpm; P < 0.05) A FE em repouso era mais elevada no grupo VPE (VPE: 40 ± 12 %; IC: 32 ± 9 %; P < 0,0125), entretanto a FE elevou-se do repouso ao LA apenas no grupo IC (VPE: 44 ± 17 %; IC: 39 ± 11 %; P < 0,0125). A TME foi semelhante em repouso (VPE: 1,41 ± 0,55 VDF/s; IC: 1,39 ± 0,55 VDF/s; P > 0,05) e aumentou na intensidade do LA similarmente em ambos os grupos (VPE: 2,28 ± 0,55 VDF/s; IC: 2,52 ± 1,07 VDF/s; P < 0,0125). Conclusão. Pacientes submetidos a ventriculectomia parcial esquerda apresentam uma o limiar anaeróbio (LA) resposta anormal da função sistólica do ventrículo esquerdo ao exercício na intensidade do LA e uma resposta cronotrópica diminuida ao exercício máximo. Essas respostas anormais podem contribuir para a limitada capacidade ao exercício destes pacientes, a despeito da melhora na função ventricular sistólica em repouso. / Background. Patients with heart failure who have undergone partial left ventriculectomy improve resting left ventricular systolic function, but maintain limited functional capacity. Objective. In order to better understand the mechanisms associated with this limitation, we studied the systolic and diastolic left ventricular function at rest and during submaximal exercise in patients with previous partial left ventriculectomy and in patients with heart failure who had not been operated, matched for maximal and submaximal exercise capacity. Methods: Nine patients with heart failure who were previously submitted to partial left ventriculectomy (PLV) were compared with a group of 9 patients with heart failure who had not been operated. All patients performed a cardiopulmonary exercise testing with measurement of peak oxygen uptake (VO2 peak) and anaerobic threshold (AT). In a second evaluation, radionuclide left ventriculography was performed to analyze ejection fraction (EF) and peak filling rate (PFR) at rest and during exercise at the intensity corresponding to the AT. Results: Groups presented similar exercise capacity evaluated by VO2peak (PLV: [mean ± SD] 13.1 ± 3.3 mL/Kg.min; HF: 14.1 ± 3.6 mL/Kg.min; P > 0.05) and AT (PLV: 7.9 ± 1.3 mL/Kg.min; HF: 8.5 ± 1.6 mL/Kg.min; P > 0.05). Maximal heart rate was higher in the HF group when compared to the PLV group (PLV: 119 ± 20 bpm; HF: 149 ± 21 bpm; P < 0.05). EF at rest was higher in the PLV group (PLV: 40 ± 12 %; HF: 32 ± 9 %; P < 0.0125), however EF increased from rest to AT only in the HF group (PLV: 44 ± 17 %; HF: 39 ± 11 %; P < 0.0125). PFR was similar at rest (PLV: 1.41 ± 0.55 EDV/sec; HF: 1.39 ± 0.55 EDV/sec; P > 0.05) and increased in both groups at the AT intensity (PLV: 2.28 ± 0.55 EDV/sec; HF: 2.52 ± 1.07 EDV/sec; P < 0,0125). Conclusion: Patients who had partial left ventriculectomy present an abnormal response of left ventricular systolic function to exercise at the AT intensity and an impaired chronotropic response to maximal exercise. These abnormal responses may contribute to the limited exercise capacity of these patients, despite the improvement in resting left ventricular systolic function.

Studium of the clinical impact of different forms of cardiac resynchronization therapy by patients with chronic heart failure MUDr. Lucie Burianová ABSTRACT: Introduction: Biventricular (BiV) pacing decreases mortality and improves quality of life of patients with severe heart failure. Haemodynamic and short time clinical studies suggest that isolated leftventricular pacing could have the same effect. Aims: Compare the effect of BiV and leftventricular pacing by subjects with dilated cardiomyopathy and severe heart failure with the attention to signs of dyssynchrony and remodelation of the left chamber. In methodical substudy compare the results of left chamber volumes and ejection fraction (EF LK) measured by CT angiography and 2-dimensional echocardiography with use of contrast agent (K-ECHO). Methods: Patients indicated for cardiac resynchronization therapy were randomized for either BiV or leftventricular pacing. After implantation of the device they were examinated clinically and by echocardiography every 3 months in the period of one year. Four years from the onset of the study the major adverse events in both groups were evaluated. The results of left chamber volumes and EF LK measured by K-ECHO and CT angiography were compared. Results: We enrolled 33 patients. We found clinical improvement in both...

Studium of the clinical impact of different forms of cardiac resynchronization therapy by patients with chronic heart failure MUDr. Lucie Burianová ABSTRACT: Introduction: Biventricular (BiV) pacing decreases mortality and improves quality of life of patients with severe heart failure. Haemodynamic and short time clinical studies suggest that isolated leftventricular pacing could have the same effect. Aims: Compare the effect of BiV and leftventricular pacing by subjects with dilated cardiomyopathy and severe heart failure with the attention to signs of dyssynchrony and remodelation of the left chamber. In methodical substudy compare the results of left chamber volumes and ejection fraction (EF LK) measured by CT angiography and 2-dimensional echocardiography with use of contrast agent (K-ECHO). Methods: Patients indicated for cardiac resynchronization therapy were randomized for either BiV or leftventricular pacing. After implantation of the device they were examinated clinically and by echocardiography every 3 months in the period of one year. Four years from the onset of the study the major adverse events in both groups were evaluated. The results of left chamber volumes and EF LK measured by K-ECHO and CT angiography were compared. Results: We enrolled 33 patients. We found clinical improvement in both...