Michal Fikrle

Abnormal Myocardial and Coronary Vasculature Development in Experimental Hypoxia

Oxygen availability is one of the necessary prerequisites for normal embryonic development. In our previous study we found that quail embryos incubated under hypoxic conditions (16% O2) die at embryonic day (ED) 9 with signs of heart failure. By ED4 and ED6 we found thinner ventricular wall and increased capillary density. We thus hypothesized that the cause of death would lie in severe myocardial and coronary maldevelopment. ED6 and 7 hypoxic hearts had thinner ventricular wall, especially left. There was a simultaneous increase in capillary density, most pronounced in the interventricular septum. This site corresponds to an area of tissue hypoxia and ensuing increased angiogenesis, and also formation of ventricular conduction system. Hypoxia had a positive effect on normal sequence of maturation of the conduction system evaluated by optical mapping at ED7. In sections from ED9 hypoxic hearts we found, in addition to thinner ventricular walls, irregularities in development of coronary tree (missing coronary ostia, absence of one coronary artery, and irregular arterial wall). This deficiency was due to decreased myocyte proliferation rather than to increased apoptosis. By Indian ink injection through the left ventricle we found in normoxic hearts regular coronary branching pattern, while in the hypoxic ones there was often only an irregular plexus. Embryonic hypoxia thus leads to increased capillarity and trabeculation to minimize diffusion distance. In the subsequent period there is a failure in organization of vascular plexus into normal vasculature, resulting in thin compact myocardium that likely leads to heart failure and embryonic death. Anat Rec, 2008.

The diagnostic performance of cardiac magnetic resonance in detection of myocardial involvement in AL amyloidosis

The non‐invasive assessment of amyloid heart disease may be challenging. Cardiac magnetic resonance (CMR) represents a method of choice for assessment of left ventricular (LV) morphology and function, and it also provides a unique possibility to evaluate the presence of amyloid deposition by the late gadolinium enhancement (LGE) technique. However, so far, published studies have not been consistent in terms of described LGE patterns associated with amyloid cardiomyopathy.

Contemporary Treatment of Amyloid Heart Disease

The amyloidoses represent a group of diseases characterized by extracellular deposition of abnormal protein, amyloid, which is formed by insoluble extracellular fibrils in β-pleated sheets. Although cardiac involvement may occur in all types of amyloidoses, clinically relevant amyloid cardiomyopathy is a typical feature of AL amyloidosis and transthyretin-related amyloidoses. Congestive heart failure represents the commonest manifestation of amyloid heart disease. Noninvasive imaging techniques, especially echocardiography and cardiac magnetic resonance, play a major role in the diagnosis of amyloid cardiomyopathy; however, histological confirmation and exact typing of amyloid deposits is necessary whether in extracardiac location or directly in the myocardium. Early diagnosis of amyloid heart disease is of utmost importance as the presence and especially the severity of cardiac involvement generally drives the prognosis of affected subjects and plays a major role in determining the intensity of specific treatment, namely in AL amyloidosis. The management of patients with amyloid heart disease is complex. Loop diuretics together with aldosterone antagonists represent the basis for influencing signs of congestion. In AL amyloidosis, high-dose chemotherapy followed by autologous stem cell transplantation is generally considered to be a front-line treatment option, if the disease is diagnosed at its early stage. The combination of mephalan with dexamethasone has been the standard therapy for severely affected individuals; however, the combinations with several novel agents including immunomodulatory drugs and bortezomibe have been tested in clinical trials with promising results. New therapeutic substances with the potential to slow or even stop the progression of transthyretin-related amyloidosis are also extensively studied.

New Therapeutic Aspects of Inflammatory Cardiomyopathy

Inflammatory cardiomyopathy is a term used for left ventricular systolic dysfunction associated with myocarditis. In order to establish definitely the diagnosis, an endomyocardial biopsy (EMB) must be performed. Based on the results of EMB analysis, specific treatment may be added to conventional heart failure therapy. Immunosuppressive therapy in patients with non-viral inflammatory cardiomyopathy has been shown to be effective, and there is also some evidence that antiviral or antimicrobial therapy may be beneficial.

Monitoring Cardiac Function During Idebenone Therapy in Friedreich's Ataxia

Friedreichs ataxia (FA) is associated with progressive cardiac hypertrophy resulting from a genetic abnormality in the frataxin gene. Cardiac involvement is the most common cause of death (59%) in FA patients. Cardiac related death occurs at a significantly younger age than non-cardiac related death. Idebenone is a short-chain quinone analogue with a potent free-radical scavenger action. This drug has the potential to preserve and even improve mitochondrial function.Studies on Idebenone treatment showed rather conflicting results on FA cardiomyopathy. The present article reviews the clinical features of FA cardiomyopathy, imaging techniques used to diagnose, follow and monitor therapy which aimed to revert FA cardiomyopathy.

Simplified apical four-chamber view evaluation of relative apical sparing of longitudinal strain in diagnosing AL amyloid cardiomyopathy

To assess the diagnostic utility of a simplified approach to relative apical sparing of longitudinal strain (RAS LS) using only an apical four‐chamber view (A4C) in patients with AL amyloid cardiomyopathy (ALAC).