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Role of echocardiography in the evaluation of functional and structural changes of the myocardium
Rob, Daniel ; Linhart, Aleš (advisor) ; Pudil, Radek (referee) ; Málek, Filip (referee)
Echocardiography plays a key role in the evaluation of functional and structural changes of the heart. Fabry disease (FD) is a genetic (X-linked) lysosomal storage disease caused by mutations in the gene for alpha-galactosidase A. Cardiovascular involvement is a major cause of morbidity and mortality in FD. The aim of our work was to refine the diagnosis and risk stratification of Fabry cardiac involvement using echocardiography. In the first part of our retrospective project, we analysed the relationship between the uric acid level, development, and progression of left ventricular (LV) hypertrophy and adverse events. Our results showed a strong relationship between uric acid level and progression of LV hypertrophy, mortality, and cardiovascular events. Uric acid can be used as a marker of cardiovascular risk in FD. In the second part of our retrospective project, we analysed the diagnostic value of tissue doppler imaging (TDI) of mitral annular velocities in Fabry cardiomyopathy. Despite the lower TDI mitral annular velocities in FD, the overlap with the general population is too large to allow reliable diagnosis of FD in routine clinical practice. In the prospective study, we analysed the prevalence, characteristics, prognosis and validity of the current echocardiographic criteria for heart...
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Pathophysiology of intraventricular electrical activation and its relation to cardiac resynchronization therapy
Sedláček, Kamil ; Wichterle, Dan (advisor) ; Linhart, Aleš (referee) ; Čurila, Karol (referee)
The QRS complex shortening by cardiac resynchronization therapy (CRT) has been associated with improved outcomes. We hypothesized that (1) the absence of QRS duration (QRSd) prolongation by right ventricular septal pacing may indicate a complete left bundle branch block (cLBBB), and (2) that the interval between the right-ventricular pacing stimulus and left-ventricular lead electrogram (RVP-LV) is a better predictor of the electrocardiographic effect of CRT than the interval Q-LV. We prospectively collected 12-lead surface ECG and intracardiac electrograms during CRT implant procedures. Digital ECG and intracardiac recordings were edited and manually measured. The outcome measure was the QRS duration change induced by CRT (deltaCRT). Several outcome predictors were investigated: native QRS duration (QRSd), cLBBB (as defined by Strauss), Q-LV and RVP-LV intervals, and a newly proposed index defined by the difference between the right-ventricle-paced QRSd and native QRSd (deltaRVP). We included 133 consecutive patients in the study and found that the baseline QRSd, deltaRVP, and Q-LV represent strong independent predictors of electrocardiographic response to CRT (deltaCRT). DeltaRVP correlates tightly with the CRT effect on QRSd and outperforms predictive value of the ECG-based cLBBB. Strong...
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Role of echocardiography in cardiac resynchronization therapy
Marek, Josef ; Linhart, Aleš (advisor) ; Mandysová, Eva (referee) ; Ozábalová, Eva (referee)
Cardiac resynchronization therapy (CRT) is an established treatment of patients with heart failure with reduced ejection fraction associated with QRS complex prolongation. However, about 30% of patients do not respond to CRT favorably, more so patients with shorter QRS duration and QRS morphology other than typical left bundle branch block. Echocardiography plays a crucial role in management of all those patients. Echocardiographic assessment of myocardial mechanics can quantitate myocardial deformation and find myocardial segments that are latest mechanically activated in a dyssynchronously contracting left ventricle. Left ventricular (LV) lead placement in this area is associated with clinical response to CRT. On the other hand, lead placement within a scar has been associated with bad prognosis. The aim of this work was to investigate whether left ventricular lead placed close to the site of latest mechanical activation is beneficial especially in patients with shorter QRS durations or atypical QRS morphology. This has been done by analyzing data of the randomized trial STARTER, which compared echo-guided LV lead navigation to routine empirical lead placement. The STARTER trial proved clinical benefit of echo-guided LV lead placement towards the site of latest mechanical activation. In our...
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Therapeutic vasculogenesis in patients with critical leg ischemia
Skalická, Lenka ; Linhart, Aleš (advisor) ; Neužil, Petr (referee) ; Roztočil, Karel (referee)
PhD Aims: The aim of our study was to evaluate an efficacy and safety of intra-arterial injection of bone marrow mononuclear cells (BMMCs) in patients with chronic critical limb ischemia (CLI) Methods.In average 400ml bone marrow blood was harvested from posterior iliac crests in 24 CLI patients. BMMCs were obtained from the blood by standard procedure used for bone marrow transplantation. After digital subtraction angiography was performed in each patient, BMMCs were injected into arteries of 28 limbs. Primary outcome was the efficacy of BMMCs injection measured as a successfull healing of limb defects, a change of Fontain ischemia grade and a rate of high limb amputations. Secondary outcomes were a safety of the BMMCs injections, changes in angiographic findings after BMMCs injections and changes in quality of life (questionnaire SF-36). Results: After one year follow-up all patients were alive and 2 patients have undergone high limb amputation. Out of 14 limb defects, eleven have been healed completely and the average Fontain ischemia grade has changed from baseline value of 3.5 to 2.0 after one year (P<0.0001). Angiographic findings have improved in all examined segments of limb vessels. One year after the procedure patients have reported significant improvement. Conclusion: The intra-arterial...
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The impact of positive inotropic and antiarrhythmic drugs on cardiovascular system
Kočková, Radka ; Linhart, Aleš (advisor) ; Janoušek, Jan (referee) ; Štengl, Milan (referee)
Heart rate changes mediate the embryotoxic effect of antiarrhythmic drugs in the chick embryo A significant increase in cardiovascular medication use during pregnancy has occurred in recent years but only limited evidence on its safety profile is available. We hypothesized that drug-induced bradycardia is the leading mechanism of developmental toxicity. We tested metoprolol, carvedilol, or ivabradine for embryotoxicity and their acute effect on chick embryonic model. We used video microscopy and ultrasound biomicroscopy. Significant dose-dependent mortality was achieved in embryos injected with carvedilol and ivabradine. In ED4 embryos, metoprolol, carvedilol and ivabradine reduced the heart rate by 33%, 27%, and 55%, respectively, compared to controls (6%). In ED8 embryos this effect was more pronounced with a heart rate reduction by 71%, 54%, 53%, respectively (controls 36%). Cardiac output decreased in all tested groups but only proved significant in the metoprolol group in ED8 embryos. The number of -adrenergic receptors showed a downward tendency during embryonic development but a negative chronotropic effect of tested drugs was increasingly pronounced with embryonic maturity. This effect was associated with reduced cardiac output in chick embryos, probably leading to premature death....
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Specofics of Acute Mocardial Infarction in Young Adults.
Dostálová, Gabriela ; Linhart, Aleš (advisor) ; Moťovská, Zuzana (referee) ; Vítovec, Jiří (referee)
Univerzita Karlova 1. lékařská fakulta Studijní program: Doktorské studium biomedicíny 1. LF UK Studijní obor: Oborová rada Fyziologie a patofyziologie člověka MUDr. Gabriela Dostálová Disertační práce Vybrané aspekty akutního infarktu myokardu u mladých nemocných Specifics of Acute Myocardial Infarction in Young Adults Školitelé: prof. MUDr. A. Linhart, DrSc., doc. MUDr. D. Karetová, CSc. Praha 2017 Abstract Coronary heart disease is the leading cause of death in adults in the western world. Myocardial infarction can represent the lethal manifestation of coronary heart disease leading to sudden cardiac death. Although myocardial infarction mainly occurs in patients older than 45 years, the young population can be affected as well. Despite the relatively low incidence of myocardial infarction in the young population, the mortality rates and long-term disability make acute myocardial infarction in young patients an important clinical issue. Consequences of myocardial infraction usually have great impact on the young patient's psychology, ability to work and the overall quality of life. The management of young myocardial infarction patients should differ at least slightly from the older ones. Young patients usually have a different risk factor profile, clinical presentation, and prognosis in comparison with...
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The impact of positive inotropic and antiarrhythmic drugs on cardiovascular system
Kočková, Radka ; Linhart, Aleš (advisor) ; Janoušek, Jan (referee) ; Štengl, Milan (referee)
Heart rate changes mediate the embryotoxic effect of antiarrhythmic drugs in the chick embryo A significant increase in cardiovascular medication use during pregnancy has occurred in recent years but only limited evidence on its safety profile is available. We hypothesized that drug-induced bradycardia is the leading mechanism of developmental toxicity. We tested metoprolol, carvedilol, or ivabradine for embryotoxicity and their acute effect on chick embryonic model. We used video microscopy and ultrasound biomicroscopy. Significant dose-dependent mortality was achieved in embryos injected with carvedilol and ivabradine. In ED4 embryos, metoprolol, carvedilol and ivabradine reduced the heart rate by 33%, 27%, and 55%, respectively, compared to controls (6%). In ED8 embryos this effect was more pronounced with a heart rate reduction by 71%, 54%, 53%, respectively (controls 36%). Cardiac output decreased in all tested groups but only proved significant in the metoprolol group in ED8 embryos. The number of -adrenergic receptors showed a downward tendency during embryonic development but a negative chronotropic effect of tested drugs was increasingly pronounced with embryonic maturity. This effect was associated with reduced cardiac output in chick embryos, probably leading to premature death....
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Pathophysiology of cardiorenal interaction in patients with type 2 diabetes mellitus
Pecková, Marie ; Horáčková, Miroslava (advisor) ; Teplan, Vladimír (referee) ; Linhart, Aleš (referee)
Patients with type 2 diabetes mellitus (DM) suffer often from cardirenal syndrome because of high prevalence of cardiac and renal insufficiency. Functional deterioration of both organs depends on the compensation of DM, arterial hypertension and other metabolic parameters. We asked a question when did the cardiorenal interaction develop and which factors influenced its development. We examined 82 patients with type 2 DM with optimally corrected arterial hypertension, with well compensated diabetic metabolic disorder, without any clinical signs of heart disease and with normal or mild-to-moderate decrease in glomerular filtration rate according to MDRD equation (eGFR). We analysed the associations between eGFR and echocardiographic parameters of left ventricular (LV) diastolic function E' and E/E' on the basis of linear regression and multivariate analysis. According to multivariate analysis eGFR was significantly associated with E' and E/E' either. We assessed the association between E' and GFR by cluster analysis that divided whole cohort into two subgroups on the basis of the value E' = 7.1 cm s-1 . We analysed the associations between the parameters of LV diastolic function, eGFR and other parameters separately in both subgroups. We found out, that cardiorenal interaction (significant association...
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Therapeutic vasculogenesis in patients with critical leg ischemia
Skalická, Lenka ; Linhart, Aleš (advisor) ; Neužil, Petr (referee) ; Roztočil, Karel (referee)
PhD Aims: The aim of our study was to evaluate an efficacy and safety of intra-arterial injection of bone marrow mononuclear cells (BMMCs) in patients with chronic critical limb ischemia (CLI) Methods.In average 400ml bone marrow blood was harvested from posterior iliac crests in 24 CLI patients. BMMCs were obtained from the blood by standard procedure used for bone marrow transplantation. After digital subtraction angiography was performed in each patient, BMMCs were injected into arteries of 28 limbs. Primary outcome was the efficacy of BMMCs injection measured as a successfull healing of limb defects, a change of Fontain ischemia grade and a rate of high limb amputations. Secondary outcomes were a safety of the BMMCs injections, changes in angiographic findings after BMMCs injections and changes in quality of life (questionnaire SF-36). Results: After one year follow-up all patients were alive and 2 patients have undergone high limb amputation. Out of 14 limb defects, eleven have been healed completely and the average Fontain ischemia grade has changed from baseline value of 3.5 to 2.0 after one year (P<0.0001). Angiographic findings have improved in all examined segments of limb vessels. One year after the procedure patients have reported significant improvement. Conclusion: The intra-arterial...
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