Ischemic peripheral arterial disease and recurrent iliofemoral venous thrombosis in a 24-year-old man with antiphospholipid syndrome.

The following is a case report of a young man with antiphospholipid syndrome, present with a recurrent iliofemoral venous thrombosis and premature peripheral arterial disease. This case report highlights the high risk of recurrent thrombosis upon discontinuation of anticoagulation therapy, particularly in the presence of persistent spontaneously increased aPTT and a high antiphospholipid antibody titer. The case report also reviews the potential of endovascular treatment of iliac vein thrombosis and points out the good 24-month patency rates of stents implanted into the pelvic vein region.Key words: antiphospholipid syndrome - iliofemoral deep vein thrombosis - recurrent thrombosis - accelerated atherosclerosis - peripheral arterial disease.

[Acute myocardial infarction in young patients--severe failures in the system of acute and secondary care]. / Akutní infarkt myokardu u mladých nemocných - závazné nedostatky v systému akutní a následné péce.

INTRODUCTION: The incidence of cardiovascular (CV) diseases and acute myocardial infarction (AMI) in Czech Republic is de-clining. In spite of this in a proportion of patients AMI occurs in young age. The aim of our project was to assess the character of risk factors, precipitating diseases and the quality of care in young AMI survivors. METHODS: We included 132 patients (97 men and 35 women) in whom AIM with ST elevations occurred before age of 45 years in men and age of 50 years in women. Several results were compared to a control group composed of 84 healthy volunteers of comparable age. We assessed the course of the disease, extent of coronary involvement, subsequent therapy and control of risk factors after 3 years from the index event. RESULTS: Smoking represented the main risk factor - 85% patents were active smokers at the time of AMI and 9% were former smokers, 64% patients had a positive family history of CV disease. We found a higher prevalence of dyslipidemia history in men. In spite of high rate of statin use, laboratory examination during follow-up revealed higher triglyceride values and low levels of HDL-cholesterol in both genders. All together 23% of patients had a history of provoking underlying disease or precipitating factors (inflammatory diseases, malignancies, combined thrombophilias, drug abuse). In total 95% of patients underwent coronary angiography during the acute phase of AMI, the median time from pain onset to intervention was 9 hours. Most patients had single vessel disease, 14% had even coronary angiogram without clinically significant stenosis. The subsequent care was satisfactory concerning the rate of drug prescriptions. However, target lipid values were not reached in 78% patients and blood pressure targets in 37%. CONCLUSIONS: In patients who suffered AMI in young age, risk factors are dominated by smoking and positive family history of CV diseases. One fifth of patients suffer from other underlying disease (inflammatory disease, malignancies, combined thrombophilia) or have another precipitating factor (febrile disease, drug abuse). The acute care seems unsatisfactory due to late arrival of most patients to catheterization laboratories (underestimation of the disease, incorrect initial diagnosis). Subsequent therapy is well composed but lacks in intensity.

Fabry disease - Vascular manifestations.

Fabry disease (FD) is an X-linked disorder of glycosphingolipid metabolism caused by the deficient activity of alpha-galactosidase A which results in the accumulation of neutral glycosphingolipids in various tissues leading particularly to vasculopathy, cardiomyopathy, neuropathy, and chronic kidney disease. It results in substantial morbidity and premature death in affected patients. Although there are some signs and symptoms suggestive of FD including painful crisis, angiokeratomas, and corneal changes, the majority of FD complications are non-specific (left ventricular hypertrophy, conduction abnormalities, vascular spasms, proteinuria, renal insufficiency), which is why FD still remains largely underdiagnosed. The mechanism by which accumulating glycosphingolipids cause multiorgan disorder is not yet completely understood as it cannot be explained by pure substrate storage. Besides standard therapy of different medical problems in FD patients, specific enzyme replacement therapy has been introduced in the last few years.

A new strategy for the treatment of atherothrombosis - inhibition of inflammation.

Improvement in the prognosis of patients at risk of atherothrombotic events is based on three pillars - slowing down the process of atherogenesis (i.e. the development of atherosclerotic plaque), stabilizing the current atherosclerotic plaque, and reducing the risk of thrombotic occlusion in cases with unstable atherosclerotic plaque. The current prophylaxis has so far taken into consideration the adjustment of several risk factors, including dyslipidemia, arterial hypertension, smoking, and diabetes through lifestyle changes or pharmacological therapies. An essential part of prophylaxis is the anti-thrombotic strategy, especially anti-platelet therapy. Recently, a new pathway has been developed, based on reducing the activity of the inflammatory process with NLRP3 inflammasome, specifically a monoclonal antibody against interleukin 1beta (canakinumab). The efficacy and safety of this treatment, in secondary prevention, were documented in the CANTOS study. Other therapeutic procedures, including suppression of the inflammatory component of atherogenesis, are at the stage of clinical assessment.

Intravascular ultrasound assessment of coronary artery involvement in Fabry disease.

AIM: We used intravascular ultrasound (IVUS) to characterize coronary artery involvement in patients with Fabry disease (FD). METHODS: Nine FD patients (5 women) were matched to 10 control patients (5 women) chosen from our IVUS database. Standard volumetric IVUS analyses were performed along with assessment of plaque echodensity. RESULTS: Plaques in FD patients were diffuse and hypoechogenic compared with more focal and more echogenic lesions in control patients. Echogenicity of plaques was significantly lower in FD patients (median 30.7 +/- 12.9 vs 55.9 +/- 15.7, p = 0.0052, mean 37.2 +/- 15.6 vs 66.2 +/- 13.3, p = 0.0014). Diffusiveness was assessed as differences between mean and median plaque burden versus the plaque burden in each of the analysed cross-sections. These differences were lower in FD vs controls (5.8 +/- 4.8 vs 8.7 +/- 6.6, p < 0.001 for mean, and 5.8 +/- 4.9 vs 8.8 +/- 7.3, p < 0.001 for median) indicating a more diffuse involvement. The occurrence of lipid cores was significantly higher in FD patients than in controls (2.4 +/- 1.5 vs 1.0 +/- 0.94, p = 0.02). CONCLUSION: IVUS showed diffuse hypoechogenic plaques in patients with FD. The explanation may be higher lipid content in plaques and accumulation of glycosphingolipid in smooth-muscle and endothelial cells.

Natural history of the respiratory involvement in Anderson-Fabry disease.

BACKGROUND: Anderson-Fabry disease (AFD) is an X-linked disorder caused by deficient activity of enzyme alpha-galactosidase A, resulting in the accumulation of glycosphingolipids within lysosomes. Pulmonary involvement in AFD has previously been documented, but until now has been studied only in a few series of patients without any longitudinal follow-up. The aim of this study was to compare spirometric changes in AFD patients with a matched control population and to follow the subsequent progression of the disease. MATERIALS AND METHODS: Fifty individuals (27 women, 23 men, mean age 40 +/- 14 years) with AFD from 14 families underwent a static spirometric examination under standard conditions. A set of indices was compared with that of the control population. Out of this cohort, 39 individuals not receiving enzyme replacement therapy were longitudinally evaluated (median follow-up time 24 months). RESULTS: A clinically significant reduction in spirometric parameters, corresponding to mild to severe airway obstruction, was observed in 26% of women and 61% of men. During the serial follow-up, a significant (p < 0.05) age-dependent reduction of predicted %FVC and %FEV1 values was observed in male patients, while the influence of age was not seen in female patients. The %FEF(25-75) values decreased by similar degrees in men and women and in older and younger patients, indicating that progressive bronchial disease affects the small airways first. CONCLUSIONS: We have demonstrated a clinically relevant age- and sex-dependent progressive pulmonary involvement in AFD patients. The effects of enzyme replacement therapy on pulmonary involvement remain to be demonstrated.

[Prevention of thrombembolic disease in internal medicine]. / Prevence trombembolické nemoci ve vnitrním lékarství.

Although deep vein thrombosis is often considered to be associated with recent surgery, 50-70% of symptomatic thrombembolic events occur in nonsurgical patients. Hospitalization for acute medical illness is independently associated with about eightfold increase in relative risk for venous thrombosis. Thus correct evaluation of risks for thrombembolic disease in individual inpatient and appropriate prophylaxis offers the opportunity to improve the prognosis of acutely ill patient. The most efficient and easy way of pharmacologic prophylaxis is subcutaneous administration of low molecular weight heparin. Only in minority of patients mechanical methods of prevention are sufficient. The optimal duration of thromboprohylaxis in medical patients is unknown and we have to evaluate the changing conditions in each patient.

Arterial stiffening contributes to impairment of cerebrovascular reactivity in patients with coronary artery disease without carotid stenosis.

Impaired cerebrovascular reactivity (CVR), an important risk factor for future stroke, is affected by a presence carotid stenosis. However, in some cases CVR can be impaired in the absence of carotid stenosis due to several poorly characterized mechanisms. We hypothesized that arterial stiffening as observed in coronary heart disease (CHD) could be associated with alteration in CVR in CHD patients without carotid stenosis. The study population consisted of patients referred for coronary angiography without significant carotid stenosis (<50 %). CVR was evaluated by breath holding index (BHI) measured with transcranial color code duplex ultrasound. Arterial stiffness was assessed by pulse wave velocity (PWV) measured by the oscillometric method. The extent of coronary atherosclerosis was quantified by Gensini score (GS). Out of 186 subjects, sixty-two patients fulfilled the inclusion and exclusion criteria. BHI decreased with increasing PWV (r = -0.47, p<0.001). Decrease in BHI was significantly inversely associated with GS (r = -0.61, p<0.001). GS was associated with PWV (p<0.001). In conclusion, impaired CVR was associated with increased arterial stiffening in CHD patients in the absence of significant carotid stenosis. Thus, we speculate that increased arterial stiffness may at least partially contribute to the pathophysiology of CVR alteration in coronary artery disease.

Randomized double-blind comparison of isosorbide dinitrate and nifedipine in variant angina pectoris.

The antianginal and anti-ischemic effect of isosorbide dinitrate (ISDN), 120 mg once daily, and nifedipine, 20 mg twice daily, both in slow-release formulations, were compared in 17 patients with variant angina pectoris in a randomized, double-blind trial. The design included a placebo run-in period and two 6-week crossover periods of active treatment. Mean frequency of angina decreased significantly from 43 attacks per week during the placebo period to 4 per week with ISDN and 8 with nifedipine (p less than 0.001). Sublingual nitroglycerin consumption decreased significantly from 37 tablets per week with placebo to 3 tablets per week with ISDN and 7 with nifedipine (p less than 0.001). Both drugs reduced the silent and symptomatic ST-segment deviations on ambulatory electrocardiographic recording and increased maximal exercise tolerance. Episodes of coronary spasm could be provoked, by hyperventilation, in all patients during the placebo phase but in no patient during therapy with either active drug. Thus, both ISDN and nifedipine, in their slow-release formulations, are effective in the treatment of variant angina pectoris.

[Takayasu's disease associated with autoimmune thyroiditis and celiac disease. Clinical course and limitations of treatment]. / Association de la maladie de Takayasu avec la thyroïdite auto-immune et la maladie coeliaque. Déroulement de la maladie et limites du traitment.

Takayasu's arteritis is a non-specific form of vasculitis involving the aorta, its main branches and pulmonary arteries. It is a rare disease in our country, contrasting with the high prevalence in Southeast Asia, Africa and South America. We discuss the course of the disease in our patient who was a young women who developed Takayasu's arteritis associated with autoimmune thyroiditis and malabsorption syndrome due to celiac sprue. Long-term immunosuppressive therapy contributed to stabilizing the associated diseases, but did not stop the progression of the vascular lesions. The main adverse outcome in our patient was the development of severe renovascular hypertension. Bilateral renal artery stenosis was treated by angioplasty with stent implantation. Based on literature reports, the association of Takayasu's disease with multiple autoimmune disorders is a rare event. However, it would appear that the arteritis was the limiting disease for prognosis in our patient.

[Decreasing the occurrence of arrhythmia during coronary spasm by the early administration of nitrates]. / Snízení výskytu arytmií v prubehu koronárního spazmu vcasným podáním nitrátu.

Variant angina is frequently accompanied by serious arrhythmias. The aim of our study was to verify the role of early nitrate administration in prevention of these arrhythmias. We compared arrhythmias occurrence in the course of 104 episodes of chest pain with ST elevation during which short acting nitrate was not administered (group I) and 114 episodes with administration of 2.5 mg isosorbit dinitrate (ISDN) spray (group II). Serious arrhythmias occurred in spontaneous episodes in 41 cases (39%) and in episodes with early ISDN administration in 15 cases (13%). Particular types of arrhythmias were as follows: ventricular premature beats in group I 32 and in group II only 12, supraventricular premature beats 4, resp. 3, A-V block IInd or IIIrd degree 5, resp. 1, ventricular tachycardia 5, resp. 0, junctional bradycardia 0, resp. 1. In conclusion, early administration of nitrates at the very beginning of stenocardia during coronary spasm can prevent or reduce the occurrence of serious arrhythmias.

[Catheterization therapy of thromboembolic arterial occlusions of the lower extremities]. / Katetrizacní lécba trombembolických uzáveru tepen dolních koncetin.

Thromboembolic occlusions of peripheral arteries may threaten the vitality of extremities and sometimes patients life. Till recently the main therapeutic method was Fogarty surgical thromboembolectomy. A less invasive procedure is systemic (intravenous) and local (intraarterial) thrombolysis. All these method have, however, certain disadvantages. A new approach to the treatment for acute and subacute occlusions of peripheral arteries represents catheter thromboembolectomy, which involves the following: a) Aspiration of thromboembolic material--percutaneous thrombembolextraction (PTEE), b) Local infiltration thrombolysis where the catheter penetrates through the occlusion while simultaneously administering a fibrinolytic agent, c) PTA of residual stenosis in case of thrombotic occlusion. A combination of these methods of treatment for thromboembolic occlusions of peripheral arteries is very effective and enables to use a small amount of thrombolytic agent. The thrombosis and the underlying atherosclerotic stenosis are resolved during the same session.

[Comparison of isosorbide dinitrate and nifedipine in the treatment of variant angina pectoris. Randomized study]. / Srovnání isosorbid dinitrátu a nifedipinu v lécbe variantní anginy pectoris. Randomizovaná studie.

The effects of isosorbide dinitrate single dose 120 mg daily and nifedipine 20 mg twice daily were studied in 17 patients with variant angina pectoris due to coronary artery spasm. After a placebo phase the patients were randomized to treatment with either isosorbide dinitrate or nifedipine. After six weeks the patients were crossovered for another six weeks period of treatment. There was significant decrease of number of angina attacks during both treatment regimens. Using 24 hours Holter monitoring we also proved significant decrease of number of ST segment elevation or depression, either symptomatic or asymptomatic. There was increase of performed work during exercise tests after both treatment periods. The efficacy of Isoket 120 mg and Adalat Retard 2 x 20 mg daily in the treatment of patients with active variant angina pectoris was comparable in our study. 3 patients suffered untolerable headache during isosorbide dinitrate phase and had to terminate treatment after first day only.

[Thrombotic complications in patients with malignant diseases]. / Trombotické komplikace u nemocných s maligním onemocnením.

The incidence of thromboembolic disease (TED) in malignant diseases is high and is often the cause of death in these patients. The most important thrombogenic factors are changes of the coagulation system, venostasis, changes in the function and structure of the endothelium and the influence of specific anti-tumour therapy. The most frequent clinical manifestation is phlebothrombosis of the lower extremity. Diagnostic procedures in detection of thrombosis do not differ fundamentally from standard procedures (clinical examination, duplex sonography, phlebography, possibly pulmonary scintigraphy). More intensive prophylaxis of TED is necessary under certain conditions (surgical treatment, immobilization, chemotherapy). Therapeutic patterns with heparins, possibly thrombolytics, are common but subsequent anticoagulation treatment must be provided as long as the active stage of the neoplastic disease persists, in particular if the patient is treated with cytostatics. When anticoagulation treatment is contraindicated and there is a general favourable prognosis, implantation of caval filters is an adequate provision. New findings indicate the possible anti-tumourous action of low-molecular heparins, but these are only initial observations.

[New trends in pharmacotherapy of cardiovascular diseases]. / Nové trendy farmakoterapie kardiovaskulárních chorob.

There has not been a year that would not have brought something new, often upheaval in the field of cardiovascular pharmacotherapy during last decades. This overview addresses the perspectives that may be expected in the treatment of cardiovascular diseases in the coming years. As for the field of dyslipidemy treatment there are some new options of blocking cholesterol resorption at the enterocyte level opening up in the field of dyslipidemy treatment (e.g. brush border transport system inhibitors, inhibitors of esterification or bind to apolipoprotein), further big revolution may be foreseen in the field of the stimulation of peroxysomal receptors controlling the lipids and glycides metabolism. It is also the field of antithrombotic drugs where we encounter the series of innovative approaches as the inhibitors of receptors facilitating the thrombocyte adhesion, new direct thrombin inhibitors or tissue factor blockers. There is no significant advance in the field of arrhythmias pharmacology, that field is completely posessed by electro-impulse therapy and ablative methods. On the contrary, great perspectives may be foreseen in the field of heart failure therapy. Along with the new methods moderating hyperactivated regulation mechanisms (e.g. renin or vasopeptidases inhibitors) promising is the field of the new inotropics active without increasing the supply of calcium (calcium sensitizers, the stimulators of sarcoplasmatic calcium ATPase). In the field of diuretics there may be expected the introduction of adiuretin blockers (akvaretics). Finally the last promising field is represented by the drugs intervening the metabolism of non-cellular matrix which are expected primarily to have a positive influence on the ventricle remodellation.

[Cardiac manifestation of Fabry's disease: current knowledge]. / Kardiální manifestace Fabryho choroby: soucasné znalosti.

Fabry's disease is a rare lysosomal storage disease caused by the X-linked defect of the enzyme alpha-galactosidase A leading to the intracellular accumulation of glycosphingolipids in various organs and tissues. Cardiac involvement is frequent and, in individuals with some residual enzyme activity, may be the sole manifestation of the disease. Hemizygous men are generally more seriously affected than heterozygous women. The dominant cardiac manifestations include myocardial hypertrophy of the left ventricle, which, in some patients, mimics hypertrophic cardiomypathy. Left ventricular systolic function is usually preserved, on the other hand mild to moderate diastolic dysfunction is regularly detected. Valvular abnormalities are frequently noted. However, hemodynamically significant lesions are rare. Conduction system involvement leads initially to the shortening of atrioventricular conduction, in later stages, with a progression of the disease, antrioventricular blocks and various forms of supraventricular and ventricular arrhythmias appear. Myocardial ischemia in Fabry disease has in most cases a functional origin due to endothelial dysfunction of coronary arteries and also due to the increase oxygen demand of hypertrophied myocardium. The results of so far performed studies with enzyme replacement therapy are promising in preventing further deterioration and even improving function of affected organs.

[Noninvasive diagnosis of coronary spasm]. / Moznosti neinvazivní diagnostiky koronárních spazmu.

The objective of this work was to compare the sensitivity of non-invasive tests used for the diagnosis of variant angina pectoris (VAP). In a group of 38 patients with VAP the authors compare the sensitivity of the cold test (CT), hyperventilation test (HT), handgrip (HG), bicycle ergometry (BE) and a newly suggested combination of hyperventilation with HG and BE resp. The authors evaluated first the sensitivity of ST elevations which are an entirely specific sign and in particular denivelization of ST (by depression or elevation) which is a less specific sign. The sensitivity of different tests was as follows: CT 5% and 5% resp., HT 18% and 39% resp., HG 13% and 29% resp., BE 26% and 66% resp., HV+HG 37% and 63% resp., HV+BE 50% and 87% resp. Then the authors assessed the sensitivity of repeated examinations HV+HG 47% and evaluation during denivelization of ST 63%, HV+BE 66% and 89% resp. The authors evaluated moreover the sensitivity of ST elevations in patients according to the activity of the disease. Patients with at least five stenocardias per week had a higher sensitivity, as compared with patients with less frequent attacks: HV+HG 42% and 25% resp., HV+BE 60% and 33% resp. The highest sensitivity was found in a combination of HV+BE. Repetition of the test in case of a negative result increased markedly the sensitivity, a higher sensitivity was found also in patients with more frequent stenocardias.

[Occurrence and prognosis of silent ischemia]. / Výskyt a prognóza nemé ischémie.

The authors assessed in a group of 486 asymptomatic middle-aged men (50-60 years) the prevalence of silent myocardial ischaemia. For screening they used the exercise test on a bicycle ergometer and in men with a positive test the presence of silent ischaemia was confirmed by perfusion scintigraphy with thallium-201 or by. The prevalence of silent ischaemia was compared with the incidence of angina angiography, myocardial infarction and sudden deaths in a similar group of 1419 men followed up for 10 years in the same department. In patients with a confirmed diagnosis of silent ischaemia the prognosis was monitored, as well as possible clinical manifestations of IHD, in the course of 4-7 years of the investigation. The presence of silent ischaemia was confirmed in 32 men, i.e. 6.6%. As compared with other forms of IHD, silent ischaemia was detected almost equally frequently as myocardial infarction and as compared with angina pectoris it was observed twice as frequently. In the course of the investigation period two patients were subjected to a revascularization (CABC or PTCA). In the remaining group of 30 patients who underwent conservative treatment two patients died (sudden deaths), seven developed angina and five myocardial infarctions (incl. one clinically silent).