[AL-amyloidosis with cardiac involvement. Diagnostic capabilities of non-invasive methods].

There are presented the literature data and a description of the clinical course of the disease in isolated/predominant cardiac amyloidosis. Amyloid cardiomyopathy is the most common phenocopy of hypertrophic cardiomyopathy. The modern possibilities of non-invasive diagnostics using osteoscintigraphy for the differential diagnosis between amyloid cardiomyopathy caused by AL- and transthyretin amyloidosis are described in detail.

[Transthyretin amyloidosis in a cohort of old and very old patients with chronic heart failure].

BACKGROUND: Life-time diagnostics of wild type transthyretin amyloidosis (ATTR(wt)-amyloidosis) is virtually absent, even though ATTR(wt)-amyloidosis is an underestimated cause for morbidity and mortality, particularly in the older age group. AIM: To study incidence, demographic characteristics, and morpho-functional features of ATTR(wt)-amyloidosis in patients with FC IV CHF and LV hypertrophy > 15 mm according to autopsy data. MATERIALS AND METHODS: Postmortem reports were retrospectively analyzed for patients (n=141; 19 % males, 81 % females) of cardiology departments aged ≥69 with the underlying CHF syndrome. From all formalin-fixed fragments of the myocardium embedded in paraffin were prepared 5-7 mkm cuts, which were stained with Congo red (Sigma, USA) and viewed under normal and polarized light. Immunohistochemical analysis was also performed using antibodies to AA-amyloid, transthyretin, kappa and lambda-light chains of immunoglobulins. RESULTS: deposits were found in both old and very old persons aged 91.25±9.67, mostly in women due to shorter life span of men. In different FCs associated with LV hypertrophy, according to autopsy data amyloid deposits were observed in virtually every fifth deceased (21 % of cases). The amount of myocardial amyloid deposits was generally small (56 % of cases had (+) and 27 % had (++) amyloid deposits); 17 % of cases had considerable amyloid deposits (7 % had (+++) and 10 % had (++++)). The presence of amyloid deposits did not influence indexes of myocardial hypertrophy, such as ventricular septum thickness, LV posterior wall thickness, and heart mass. In the presented cases we observed focal amyloid deposition in the myocardium typical for old age-related amyloidosis; in 97 % cases, amyloid was located in the interstitium, around cardiomyocytes and in 3 % of cases - exclusively around blood vessels. CONCLUSION: ATTR (wt)-amyloidosis was detected in every fifth patient in the old and very old cohort, primarily in women (83 %), and was not diagnosed during the life time. Characteristic morphological manifestations of ATTR(wt)-amyloidosis were focal amyloid deposits mostly in the myocardial interstitium.

CHARACTERISTICS OF AMYLOID DEPOSITS DETECTED IN THE INTERNAL ORGANS OF mdx MICE.

The dystrophin-deficient mdx mouse is the most commonly used experimental model of Duchenne muscular dystrophy (DMD). Although the amyloid has been shown in the muscle biopsies of patients with different types of muscular dystrophies, there are no data on the amyloid accumulations in the biopsy of DMD patients or mdx mouse. Therefore, the aim of the present study was to testify the hypothesis of probable accumulation of amyloid in the visceral organs of mdx mouse. Specimens of myocardium, kidneys, and liver of male and female mdx mice aged from 2 months to 1.5 years (n = 9) were used in the study. The histochemical staining with Congo red demonstrated amyloid accumulations in the studied organs of the mdx mice. Morphology and localization of the found accumulations were described in details and analyzed. The mass-spectrometric study determined the vitronectin and apolipoprotein A-II as the most probable components of the amyloid accumulations in the mdx mouse.

How can we block sympathetic overactivity? Effects of rilmenidine and atenolol in overweight hypertensive patients.

The aim of the present study was to evaluate effects of long-term treatment with rilmenidine compared with atenolol on lipid and glucose metabolism and cardiovascular remodelling in hypertension. In total, 37 patients with hypertension were randomised to rilmenidine 1-2 mg/day or atenolol 50-100 mg/day for 26 weeks. Standard oral glucose tolerance test with a parallel measurement of insulin and glucose levels was performed. The 'areas under the curve' (AUC) for insulin and glucose were calculated. Plasma lipids, left ventricular mass index (LVMI), and intima-media thickness (IMT) were measured. Brachial artery diameter during reactive hyperaemia was used to test endothelium-dependent vasodilatation (EDVD). Blood pressure reduction was equally achieved in both treatment arms. The fasting glucose level increased in the atenolol group from 4.8+/-0.6 to 5.2+/-0.7 mmol/l (P<0.01). The AUC of glucose in rilmenidine group decreased from 860+/-93 to 737+/-66 mmol/min/l (P<0.05), and in the atenolol group it increased from 937+/-86 to 989+/-88 mmol/min/l (P<0.05). Rilmenidine showed a positive effect on lipid levels, whereas in the atenolol group a significant decrease of high-density lipoprotein cholesterol was observed. Left ventricular mass index decreased with rilmenidine by 9.6% and by 6.9% with atenolol (P<0.05). Intima-media thickness significantly decreased in the rilmenidine group. Endothelium-dependent vasodilatation slightly increased on in the rilmenidine group, while on in the atenolol group it remained unchanged. Our data suggest that in hypertensive patients central inhibition of sympathetic drive can produce favourable effects on glucose and lipid metabolism compared with standard beta-blockade with a similar antihypertensive efficacy. Rilmenidine also provides beneficial effects on cardiovascular remodelling and altered endothelial function in hypertension.

[Variants of heart remodeling in essential hypertension: prevalence and determinants].

AIM: To study myocardial remodeling (MR) in hypertensive patients with normal and excessive body mass, to analyse MR features depending on clinical and hemodynamic parameters. MATERIAL AND METHODS: Structural-functional conditions of the myocardium were studied with echocardiography, and determination of left ventricular remodeling (LVR) type was made in 734 untreated hypertensive patients aged 19-76 years. RESULTS: Patients with essential hypertension (EH) stage I had mostly excentric left ventricular hypertrophy (LVH). The number of patients with concentric LVH increases with age, disease severity. This type of LVH occurs more frequently in males than in females. In females, LVH severity depends, primarily, on the degree of obesity. If EH combines with obesity, structural alterations of the myocardium are more prominent than in isolated pathology. In android obesity, LVH is more frequent. CONCLUSION: In EH, structural alterations of the heart and a LVR variant are determined, besides arterial pressure, by such factors as age and gender, duration of EH, obesity, its degree and kind.

Effect of 24-week treatment with telmisartan on myocardial structure and function: relationship to insertion/deletion polymorphism of the angiotensin-converting enzyme gene.

The aim of the present study was to assess the effect of treatment with the angiotensin II receptor blocker telmisartan for 24 weeks on myocardial structure and function in patients with essential hypertension, and the relationship between this effect and the structural polymorphism of the angiotensin-converting enzyme (ACE) gene. Thirty-five patients with essential hypertension and left ventricular hypertrophy (LVH) without other associated morbidity were included in an open-label, non-comparative study. The patients were treated with telmisartan 40-80 mg once daily. In the final analysis, there were 29 patients who received the full course of treatment and were evaluated echocardiographically before and after treatment by the same blinded investigator, and myocardial structure and function were analysed. The myocardial mass of the left ventricle was determined in M-mode. Assessment of diastolic function of transmitral blood flow was performed using pulsed Doppler echocardiography. All patients were genotyped for insertion/deletion (I/D) polymorphism of the ACE gene. Telmisartan produced a significant reduction in left ventricular mass index from 140.4 +/- 48.6 to 128.7 +/- 40.6 g/m2 that was accompanied by an improvement in characteristics of diastolic function. The decrease in LVH was more significant in the ID genotype group than in the II and DD groups. Thus, prolonged treatment with telmisartan is accompanied by an improvement in myocardial structure, expressed as a reduction in left ventricular mass and function that is more marked in patients with ID genotype of the ACE gene.

Prevalence and determinants of left ventricular hypertrophy and remodelling patterns in hypertensive patients: the St. Petersburg study.

OBJECTIVE: The primary aim of the present study was to determine the prevalence of left ventricular hypertrophy (LVH) in hypertensive patients with the use of different threshold values and also to assess the distribution of left ventricular (LV) geometry patterns verified by two different methods of relative wall thickness (RWT) calculation. The secondary aim was to evaluate the impact of different demographic determinants into prevalence of LVH and remodelling patterns. PATIENTS AND METHODS: A cross-sectional study in a population-based sample of 734 essential hypertensives from the primary care clinic was undertaken. Echocardiography was performed and analysed by trained observers. The LV posterior wall thickness (PWd), interventricular septum (IVSd) and LV mass index (LVMI) were measured. The following criteria for LVH definition were used: LVMI >125 g/m2 and 134/110 g/m2, and >131/110 and 116/104 g/m2 in males/females, respectively. The RWT was calculated as a 2PWd/LVDD or PWd + IVSd/LVDD, where LVDD is the LV internal dimension at the end of diastole. The values exceeding 0.45 were considered evidence for concentric remodelling. RESULTS: Prevalence of LVH ranged from 52.2 to 72.2% by the use of different threshold for LVH definition. It was shown that the LVH estimation without sex-specific criteria underestimates the prevalence of LVH in women and overestimates it in men. The prevalence of concentric LVH and concentric remodelling was higher when the IVSd was included in the RWT calculation. Only one-quarter of patients were free from morphological alterations and eccentric LVH was as frequently observed as concentric LVH. Sex, obesity stage and type as well as hypertension level and duration contributed to LVH level and remodelling pattern. CONCLUSIONS: The use of different threshold values can significantly influence the assessment of prevalence of LVH in hypertension. The "mild" criteria, to our opinion, can overestimate the prevalence of structural LV remodelling, while implementation of sex-specific criteria for the definition of LVH increases the sensitivity of the method. In any way, eccentric LVH is as common for hypertension as a concentric LVH, the proportion of the latter increasing with age and more frequently observed in males. Concomitant obesity, in particular abdominal, significantly increases LVH prevalence.

[Clinical efficacy of carvedilol in patients with severe cardiac insufficiency]. / Klinicheskaia éffektivnost' karvedilola u bol'nykh s tiazheloi serdecnoi nedostatochnost'iu.

AIM: To assess clinical response to carvedilol in long-term treatment of cardiac failure (CF). MATERIAL AND METHODS: 34 patients with CF (NYHA functional class III-IV) were observed for 6 months. 25 of them received standard therapy combined with carvedilol, 9 patients received only standard therapy. RESULTS: Carvedilol produced positive changes in the disease functional class, left ventricular ejection fraction, stabilisation of echo-CG parameters and cardiothoracic index, resulted in prolongation of 6-min walk distance. Discontinuation of carvedilol therapy enhances CF symptoms. CONCLUSION: Long-term therapy with carvedilol inhibits CF progression.

[Comparative study of the level of cardiomyocyte hypertrophy in patients suffering from ischemic heart disease with normal arterial pressure and in hypertension]. / Sravnitel'noe issledovanie urovenei gipertrofii kardiomiotesitov patsientov, stradaiushchikh ishemicheskoi bolezn'iu serdtsa pri normal'nom arterial'nom davlenii i v sostoianii gipertenzii.

A study was performed on the human atrial myocytes, isolated by means of alkaline dissociation of bioptates, obtained in clinics during open heart surgery, from two groups of patients. The first group consisted of 8 men aged from 40 to 62 years, with ischemic heart disease and normal arterial blood pressure. The second group involved 10 men, aged from 43 to 67 years, with ischemic heart disease and arterial hypertension. The nuclear DNA and the total protein in the cytoplasm of isolated cardiomyocytes were revealed by means of the two consecutive tests: the Feulgen and Naphthol yellow S staining. DNA and protein contents were determined by two wave-length scanning cytophotometry. It is ascertained that the temperate arterial hypertension exerted no appreciable influence on the polyploidy level of atrial myocytes, which correlated with the age of patient; in both groups (coefficients 0.7 and 0.4 for the first and second groups, resp.). The myocyte areas correlate with their ploidy (coefficients--0.7 and 0.7, accordingly). The protein contents in myocytes also correlate with their ploidy (0.5 and 0.7). The average protein content in myocytes of patients in the second group is higher than in the first group, the difference is most distinct when calculating the protein quantity per 2c-genome (717 +/- 34 a. u. and 517 +/- 51 a. u., resp.). A comparison of cytochemical and morphometric indices with some clinical findings obtained by means of echocardiography allowed to reveal the presence of correlative connections among them. The protein contents in myocytes correlate with the left ventricle mass (coefficients 0.6 and 0.5 for the first and second groups, resp.). The correlation between the rate of transmitral blood flow and myocyte ploidy (0.8 and 0.9), and the correlation between the myocyte area and the rate of transmitral blood flow (0.8 and 0.8) look convincing.

[Changes in the cytochemical and morphometric characteristics of the myocytes in the right heart of the rat in adrenal-regeneration hypertension]. / Izmeneniia tsitokhimicheskikh i morfometricheskikh kharakteristik miotsitov pravykh otdelov serdtsa krysy pri adrenalregeneratornoi gipertenzii.

A study was made on myocytes of the right atrium and the right ventricle of rats with experimental arterial hypertension due to adrenal regeneration. The nuclear DNA and the total protein in the cytoplasm were revealed using two consecutive tests: the Feulgen reaction and Napththol yellow S staining. A two-wavelength scanning cytophotometry was used for measuring DNA and protein contents. It has been ascertained that the polyploidy levels in the myocytes of the right atrium and the right ventricle, measured 6, 12 and 26 weeks after nephradrenalectomy by the Skelton technique, differ from the control level negligibly. A small increase in the share of tetraploid myocytes occurred in 12 weeks in the right atrium, and in 26 weeks in the right ventricle. The mean nuclear volume in atrial myocytes decreased gradually within 12 weeks, to increase afterwards but did not reach to control level in 26 weeks. The cytoplasm volume of atrial myocytes decreased in 6 weeks, and then was seen to increase gradually approaching the norm within 26 weeks. At the same time the mean cytoplasm volume of ventricular myocytes, which remained practically unchanged within 6 weeks, decreased within 12 weeks more than twice as compared to the control level, but in 26 weeks started to rise, although less quickly than the volume of atrial myocytes. The common protein content was seen to decrease 6 weeks after the operation both in atrial and ventricular myocytes, then gradually approached the control within 26 weeks, these changes in atrial myocytes being sharper than in ventricular myocytes.

[The effect of adrenal-regeneration hypertension on protein-nucleic acid metabolism in rat atrial cardiomyocytes]. / Vliianie adrenalregeneratornoi gipertenzii na belkovo-nukleinovyi obmen v predserdnykh kardiomiotsitakh krys.

A study was made on cardiomyocytes of the left atrium of rats with experimental arterial hypertension due to adrenal regeneration. The nuclear DNA and the total protein in the cytoplasm were revealed using two consecutive tests: the Feulgen reaction, and Naphthol yellow S staining. The two-wavelength scanning cytophotometry was used for measuring DNA and protein contents. It has been ascertained that the polyploidy level in the nuclei of the left atrium myocytes, measured 6 and 9 weeks after nephradrenalectomy, remained the same as in the intact animals. The increase in the share of tetra- and octaploid nuclei occurred by 12 weeks. The mean nuclear volume decreased gradually throughout 9 weeks and subsequently was seen to increase, but by 12 weeks it did not yet reach the control level. The cytoplasm volume decreased by 6 weeks, then started to increase by 9 weeks to reach almost the standard level. The common protein content in the atrial myocytes decreases also by 6 weeks, but restores more rapidly than the volume, and reaches the standard level by 9 weeks, exceeding the same by 12 weeks. Thus, the prolonged hyperfunction of the atrial cardiomyocytes, associated with arterial hypertension, results in their hypertrophy which becomes apparent both in the increased polyploidy and in the augmented protein mass of the cells.

Atrial and digitalis-like natriuretic hormones in essential hypertension under functional loading.

To assess the relation of the two natriuretic hormones, atrial natriuretic peptide (ANP) and digitalis-like natriuretic factor (DLF), to hypertension, levels of ANP and DLF were measured under basal conditions and after salt and water loading in 31 normal subjects and 36 and 57 patients with Stage I or II essential hypertension (EH). DLF levels were higher in normal women than men; in EH-II patients, DLF levels were elevated among men but subnormal in women (P less than .02) and rose with water loading in both genders. In all groups ANP levels tended to be higher in women. Water loading increased ANP levels in EH-I patients (P less than .001) and caused less marked increases of ANP in control and EH-II women and men. ANP also tended to increase with salt loading. Both DLF and ANP were related to blood pressure in the subject groups (r = 0.75 to 0.96 and r = 0.27 to 0.75, respectively) and were also related to each other (r = 0.20 to 0.47). The role of ANP and DLF in hypertension are likely to be compensatory and directed against water-electrolyte metabolism disorders associated with elevated arterial pressure.

[Natriuretic hormones (atrial and digitalis-like) in patients with arterial hypertension during exercise]. / Natriureticheskie gormony (predserdnyi i digitalisopodobnyi) u bol'nykh s arterial'noi gipertenziei v usloviiakh funktsional'nykh nagruzok.

Blood levels of natriuretic hormones (atrial natriuretic peptide and digitalis-like natriuretic factor) were measured in 93 patients with Stages I and II essential hypertension and 31 healthy individuals. The baseline level of digitalis-like natriuretic factor was higher in the patients with Stage II essential hypertension than in the healthy individuals. This parameter was normal in the patients with Stage I hypertension. The concentration of atrial natriuretic peptide was not greatly different in the patients from that in the healthy persons. Water and salt loads were reported to affect the blood levels of natriuretic hormones. The levels of the hormones were shown to be correlated between them and with blood pressures and the activity of the renin-angiotension-aldosterone system. It was suggested that the natriuretic hormones might play a compensatory role in the pathogenesis of essential hypertension.