DCM-PROGRESS: predicting end-stage heart failure in non-ischemic dilated cardiomyopathy patients.

Aims: Patients with non-ischemic dilated cardiomyopathy (DCM) are at considerable risk for end-stage heart failure (HF), requiring close monitoring to identify early signs of disease. We aimed to develop a model to predict the 5-years risk of end-stage HF, allowing for tailored patient monitoring and management. Methods and results: Derivation data were available from a Dutch cohort of 293 DCM patients, with external validation available from a Czech Republic cohort of 235 DCM patients. Candidate predictors spanned patient and family histories, ECG and echocardiogram measurements, and biochemistry. End-stage HF was defined as a composite of death, heart transplantation, or implantation of a ventricular assist device. Lasso and sigmoid kernel support vector machine (SVM) algorithms were trained using cross-validation. During follow-up 65 (22%) of Dutch DCM patients developed end-stage HF, with 27 (11%) cases in the Czech cohort. Out of the two considered models, the lasso model (retaining NYHA class, heart rate, systolic blood pressure, height, R-axis, and TAPSE as predictors) reached the highest discriminative performance (testing c-statistic of 0.85, 95%CI 0.58; 0.94), which was confirmed in the external validation cohort (c-statistic of 0.75, 95%CI 0.61; 0.82), compared to a c-statistic of 0.69 for the MAGGIC score. Both the MAGGIC score and the DCM-PROGRESS model slightly over-estimated the true risk, but were otherwise appropriately calibrated. Conclusion: We developed a highly discriminative risk-prediction model for end-stage HF in DCM patients. The model was validated in two countries, suggesting the model can meaningfully improve clinical decision-making.

[Diastolic dysfunction in the elderly subjects. Disease or a physiological manifestation of ageing?]. / Diastolická dysfunkce levé komory ve vyssím veku. Nemoc, nebo fyziologický projev stárnutí?

AIM: The purpose of this summary paper is to discuss the current knowledge of the impact of age on diastolic function of the left ventricle. Data from the literature: Reports published till this time have convincingly demonstrated a significant relationship of age to diastolic function of the left ventricle. Ageing is a physiological process accompanied by structural changes in both myocardium and arterial bed resulting in worsening of parameters characterizing the left ventricular diastolic function. This "physiological" diastolic dysfunction in the elderly subjects can be explained by the deterioration of passive left ventricular filling properties and by worsening of left ventricular relaxation. The detailed analysis of published reports shows problems in distiguishing this "physiological" diastolic dysfunction resulting from physiological tissue ageing from "pathological" diastolic dysfunction reflecting a disease of cardiovascular system. CONCLUSION: To interprete correctly values of parameters quantifying diastolic function of the left ventricle, one should take into account the age of subjects under the examination. Further studies are necessary to distinguish exactly "physiological" deterioration of diastolic function associated with ageing from really "pathological" diastolic dysfunction in the elderly subjects.

The effect of regular physical activity on the left ventricle systolic function in patients with chronic coronary artery disease.

The purpose of this study was to assess the influence of aerobic training on the left ventricular (LV) systolic function. Thirty patients with stable coronary artery disease, who had participated in the conducted 3-month physical training, were retrospectively divided into 2 cohorts. While patients in the cohort I (n=14) had continued training individually for 12 months, patients in the cohort II (n=16) had stopped training after finishing the conducted program. Rest and stress dobutamine/atropine echocardiography was performed in all patients before the training program and 1 year later. The peak systolic velocities of mitral annulus (Sa) were assessed by tissue Doppler imaging for individual LV walls. In addition, to determine global LV systolic longitudinal function, the four-site mean systolic velocity was calculated (Sa glob). According to the blood supply, left ventricular walls were divided into 5 groups: A- walls supplied by nonstenotic artery; B- walls supplied by coronary artery with stenosis ≤50 %; C- walls supplied by coronary artery with stenosis 51-70 %; D- walls with stenosis of supplying artery 71-99 %; and E- walls with totally occluded supplying artery. In global systolic function, the follow-up values of Sa glob in cohort I were improved by 0.23±0.36 as compared with baseline values at rest, and by 1.26±0.65 cm/s at the maximal load, while the values of Sa glob in cohort II were diminished by 0.53±0.22 (p=NS), and by 1.25±0.45 cm/s (p<0.05), respectively. Concerning the resting regional function, the only significant difference between cohorts in follow-up changes was found in walls E: 0.37±0.60 versus -1.76±0.40 cm/s (p<0.05). At the maximal load, the significant difference was found only in walls A (0.16±0.84 versus -2.67±0.87 cm/s; p<0.05). Patients with regular 12-month physical activity improved their global left ventricle systolic function mainly due to improvement of contractility in walls supplied by a totally occluded coronary artery.

Association of polymorphisms of zinc metalloproteinases with clinical response to stem cell therapy.

AIM: The purpose of this study was to assess the associations of polymorphisms in two metalloproteinase genes-metalloproteinase-2 (MMP-2) and angiotensin converting enzyme (ACE)-with clinical response to autologous transplantation of mononuclear bone marrow cells (MBMC) in patients with acute myocardial infarction. METHODS: The double centre study included 48 patients with a first acute myocardial infarction treated with primary coronary angioplasty, stent implantation and transplantation of MBMC. According to the changes in perfusion defect size, left ventricle ejection fraction, end-systolic volume and peak systolic velocity of the infracted wall (dSaMI) after cell therapy, the patients were retrospectively divided into group A (responders) and group B (non-responders). Genomic DNA was isolated from peripheral leukocytes by a standard technique using proteinase K. Three MMP-2 promoter (-1575G/A, -1306C/T and -790T/G) as well as I/D ACE gene polymorphisms were detected by PCR methods with restriction analyses (when necessary) according to standard protocols. RESULTS: Of the 48 patients who received MBMC transplantation, 17 responded to the therapy. There were no significant differences in the prevalence of matrix metalloproteinase-2 triple genotype GGCCTT between responder/non-responder groups (71% versus 61%, p=0.375). Similarly, no differences in either genotype distribution or allelic frequencies of I/D ACE polymorphism between responders and non-responders to the cell therapy were observed (p=0.933). Compared to patients with ACE genotype ID or DD, the patients with ACE II genotype significantly improved in regional systolic LV function of the infarcted wall after implantations of MBMC (dSaMI - 0.4 versus 1.4 cm/s, p=0.037). CONCLUSION: In our study, the ACE genotype II was associated with improvement of regional systolic LV function of the infarcted wall after implantations of MBMC. The detected polymorphism in matrix metalloproteinase-2 gene was not associated with clinical response to cell therapy.

Association of the eNOS 4a/b and -786T/C polymormphisms with coronary artery disease, obesity and diabetes mellitus.

The aim was to assess the relationship between eNOS 4a/b and -786T/C polymorphisms with coronary artery disease (CAD), obesity and diabetes mellitus. Total number of 1313 patients underwent coronary angiography, 939 had significant CAD (stenosis of > or = 1 coronary artery > or = 50%), 222 had smooth coronary arteries. Patients with insignificant atherosclerosis were excluded, the study finally comprised 1161 patients. The analysis of eNOS 4a/b and -786T/ C polymorphisms was performed by polymerase chain reaction. No significant interaction was found between -786T/C polymorphism and solitary CAD or CAD with diabetes and obesity. For 4a/b polymorphism, genotypes aa+ab were almost three times more frequent in diabetic patients without CAD versus patients without CAD and without diabetes--OR 2.79; P = 0.009, Pcorr = 0.03. In 4a/b polymorphism and CAD with obesity and diabetes: bb genotype was significantly more frequent: in patients with CAD, diabetes and obesity in comparison with obese diabetic patients without CAD (OR = 3.63, Pcorr = 0.05); in non-diabetic non-obese patients with CAD, versus diabetic and obese patients without CAD (OR = 3.38, Pcorr = 0.05); in obese non-diabetic patients without CAD vs. obese diabetic patients without CAD (OR = 5.91, Pcorr = 0.01); in patients without CAD, obesity and diabetes vs. obese diabetic patients without CAD (OR = 3.59, Pcorr = 0.05). The eNOS 4a/b polymorphism has significant association with diabetes mellitus in CAD-negative patients, and with CAD in combination with obesity and diabetes mellitus. No association between 4a/b or -786T/C polymorphism and solitary CAD was found.

[Monitoring functional disorders of microcirculation using laser doppler flowmetry in patients with chronic venous insufficiency class 2 according to CEAP classification before and after varicose veins surgery]. / Sledování funkcních poruch mikrocirkulace laser dopplerem u pacientu s chronickou zilní nedostatecností trídy 2 dle CEAP klasifikace pred a po operaci varixu.

INTRODUCTION: Laser Doppler flowmetry is a sensitive modern method for evaluating the function of small veins which allows for the detection and assessment of early pathological changes in microcirculation. The method uses a low power laser beam which is emitted into the tissue where it is reflected and further recollected and analysed. The objective of the study was to compare laser Doppler flowmetry parameters for patients with chronic venous insufficiency (class 2 according to CEAP, primary varices) prior to and 1 month after surgery of varicose veins. METHODOLOGY AND PATIENT SAMPLE: The examination was performed by a Periflux laser Doppler apparatus made by Perimed. Blood flow was examined on the dorsal side of foot fingers. A total of 42 patients were examined prior to and one month following the varicose veins surgery, of whom 28 women and 14 men. The mean age of the patient sample was 49 years. A 45 minute pre-op and post-op recording of the limb was made for each patient. The protocol consisted of a 10 minute recording in rest, followed by a 4 minute ischemisation of the limb with the use of a blood pressure measuring cuff, subsequent release of the cuff, a 15 minute recording of the reperfusion and a test of vasodilatation using nitrate, and a 10 minute recording following vasodilatation. Evaluation was performed for a 4 minute period at the end of the initial rest period, for reperfusion after the release of the cuff and for the interim period of rest immediately preceding the application of nitrate, and finally for a 5 minute period after nitrate application. Statistical evaluation was performed for data acquired during the movement of blood elements and data acquired in the frequency analysis of the movement of the blood vessel wall. 3 variables were chosen for the statistical evaluation of the blood cell movement data: "the area under the curve", "the mean value of the deviation" and "the percentage change" in the different phases of the measurement, i.e. as compared with the rest recording: comparing the ischemisation and the rest recordings, comparing the vasodilatation and the rest recordings, and comparing the restitution and the rest recordings. The above variables were not assessed as absolute numbers but as the difference of values before and after the surgery. The above differences were tested in the Wilcoxon test. The intensity of blood vessel movements in the frequency range from 0.008 to 0.200 Hz and 0.210-0.420 Hz was evaluated in frequency analyses. RESULTS: Significant differences in peripheral microcirculation in lower limbs were found in the evaluation of data acquired during the movement of the different blood elements before and after varicose vein surgery (p = NS). On the contrary, evaluation of frequency analysis for both the operated and non-operated limb shows a decrease in spontaneous arterial reactivity after varicose vein surgery. This decrease is statistically significant in the frequency range from 0.102 to 0.228 on operated limbs after the removal of a varix in a T1 test (i. e. after reperfusion) as compared with the values before the surgery (p < 0.05). CONCLUSION: Varicose vein surgery results in the reduction of spontaneous vasomotion in the periphery of the operated limb.

[Interval and continuous training in cardiovascular rehabilitation]. / Intervalový a kontinuální trénink v kardiovaskulární rehabilitaci.

The objective of the study was to evaluate the physiological effectiveness and the influence of two modifications of aerobic training (interval and continuous) on the physical performance in the patients with coronary heart disease. 38 males with coronary heart disease (age 60 +/- 10.2 years) passed three months training programme of 60 min 3 times a week (10 min of warm up phase, 25 min of aerobic phase, 15 min of resistance training, 10 min of relaxing phase). Patients with coronarographically verified stenosis > 50% luminal diameter and/or left ventricular ejection fraction lower than 40 % (n = 22) had in terms of aerobic phase interval training prescribed (30 second work phases with work load intensity on the level of anaerobic threshold alternating with 60 second recovery phases with intensity of 5 W); other patients (n = 16) passed aerobic phase of the programme with continual work load of intensity on the level of ventilatory anaerobic threshold. After the determination of three month rehabilitation programme the maximal achieved performance as well as aerobic capacity evaluated by spiroergometric examination statistically significantly increased in the group of patients with interval training and also in the group with continuous training. Despite the group with interval training performed 2.5-3 times less work in each training unit (p < 0.01), the performance and aerobic capacity parameters after the termination of three month programme did not statistically significantly differ from the group with continuous training. The advantage of the continuous training is a possibility to achieve an improvement also in the patients with left ventricular dysfunction and chronic coronary heart disease who could have worse tolerance of the continual work load.

[Combined training in patients with systolic left ventricular dysfunction]. / Kombinovaný trénink u nemocných se systolickou dysfunkcí levé komory srdecní.

The objective of the work was to evaluate the effect of eight-week combined training on the performance, aerobic capacity and basic haemodynamic parameters in patients with systolic dysfunction of the left ventricle and to assess its safety. The investigation comprised 26 patients, men mean age (x +/- SD) 61.8 +/- 11.1 years with coronarographically verified chronic ischaemic heart disease and with a left ventricular ejection fraction lower than 40% (EF 35 +/- 4%). Before the beginning and after completion of the rehabilitation programme (eight weeks) a spiroergometric examination was made, up to the symptom-limited maximum. Fitness elements were included after 2 weeks of aerobic training. The lesson lasted 60 mins. and included warming up (10 mins.), aerobic load on an ergometer with an intensity of the load at the level of the anaerobic threshold (20 mins.), the stage of fitness training on a combined training machine (20 mins) and the relaxation stage (10 mins). In the fitness stage the patients started to exercise at the 30% level, after two weeks at the 60% level 1-RM (one repetition maximum) The results showed after eight-week combined training a significant (p < 0.05) increase of the maximum achieved performance (from 104 +/- 27 to 132 +/- 32 W) in patients with systolic left ventricular dysfunction. There was a significant increase in the capacity of the transport system expressed by the value of the maximum oxygen uptake (from 1545 +/- 312 to 1740 +/- 359 ml.min-1) and MET (from 5.3 +/- 1.3 to 6.0 +/- 1.4). There was a significant decrease of the blood pressure at rest, systolic and diastolic, and of the baseline value of the heart rate at rest and of the "product rate, pressure"--RPP. Changes in the EF were not significant.

[Effect of physical training on the magnitude of left ventricular ischaemic dysfunction in patients with chronic ischaemic heart disease]. / Vliv telesného tréninku na velikost ischemické dysfunkce levé komory u nemocných s chronickou ischemickou chorobou srdecní.

Twenty-two patients with chronic ischaemic heart disease (IHD) and reversible myocardial ischaemia after a load as recorded by single photon emission computed tomography (SPECT) participated in an eight-week rehabilitation programme. Before exercise their efficiency was tested by spiroergometric examinatin and the patients were randomized into two groups. Group A (10 patients) took exercise at the level of the anaerobic threshold (high intensity training), group B (12 patients) trained at the level of the 60 % anaerobic threshold (low intensity training). The exercise unit including the warming up and relaxation stage lasted 50 minutes and was repeated three times per week. Before and after the rehabilitation programme in all patients spiroergometry was performed as well as exercise pulsed tissue Doppler echocardiography to evaluate regional systolic and diastolic left ventricular function in the ischaemic area, localized beforehand by the SPECT. The following parameters were evaluated by echocardiograpphy: the peak velocity of motion in the ischaemic area in systole (Si), the peak velocity of motion in the ischaemic area in early diastole (Ei) ad in atrial contraction (Ai), and the ratio Ei/Ai was calculated. With the exception of the decline of the value at rest Ai from 8.4 +/- 1.3 cm/sec to 7.3 +/- 1.3 cm/s (p < 005) in the exercising group A none of the parameters of left ventricular regional function changed significantly after an eight-week rehabilitation programme. The maximal performance achieved in spiroergometry increased however after rehabilitation in group A (from 145 +/- 36 W to 162 +/- 39 W, p < 0.01) as well as in group B (from 112 +/- 36W to 122 +/- 36W, p < 0.05). I It may be concluded that a rehabilitation programme of high and low intensity improved the load tolerance during spiroergometry but did not lead to significant improvement of regional systolic and diastolc left ventricular function in the area of reversible ischaemia.

[Correlation of a change in the amplitude of the R wave during ergometry with the finding of significant stenosis of the coronary artery]. / Korelace zmeny amplitudy R kmitu pri ergometrii s nálezem významné stenózy koronární tepny.

The authors evaluated retrospectively 224 patients with ischaemic heart disease. These patients were subjected to an ergometric loading test on a bicycle ergometer followed by angiography of the coronary arteries. With regard to the site of the increased amplitude of R waves during the loading test the patients were divided into seven groups which were sub-divided further according to the coronarographic finding. The authors investigated the assumption that patients with pathological changes of R waves above the anterior wall suffer from afflictions of the ramus interventricularis anterior, patients with changes above the lateral wall of the ramus circuflexus and patients with increased R waves above the inferior wall of the right coronary artery. From the work ensues that no localization of increased amplitudes of R waves during the loading test has a statistically significant correlation with the coronarographic finding.

[Can we determine which coronary artery is affected by the localization of ST depression? Comparison of ergometric and coronarographic results]. / Dokázeme podle lokalizace ST depresí urcit postizenou koronární tepnu? Srovnání ergometrických a koronarografických výsledku.

The authors evaluated retrospectively 206 patients with ischaemic heart disease. These patients were subjected to an ergometric loading test on a bicycle ergometer followed by angiography of the coronary arteries. With regard to the site of the ST depressions during the loading test the patients were divided into 7 groups which were further subdivided according to the coronographic finding. The authors investigated the hypothesis that patients with depressions of the ST segment above the anterior wall suffer from an affection of the ramus interventricularis anterior, patients with depressions of ST above the lateral wall from affection of the ramus circumflexus and patients with depressions above the lower wall have an affection of the right coronary artery. From the work ensues that no site of the ST depression correlates significantly with the coronary finding. The correlation is not statistically significant even when we compare the site of ST depressions with the affection of one artery regardless of the affection of the other coronaries.

[The ergometry stress test in patients with stenosis of the left main coronary artery]. / Ergometrický zátezový test u nemocných se stenózou kmene levé vencité tepny.

In 168 patients with ischaemic heart disease an ergometric loading test on a bicycle ergometer was made before coronarography. A total of 19 patients had on coronarography a finding of significant stenosis of the lumen of the trunk of the left coronary artery--group A. These patients were compared with a control group of 20 patients with confirmed coronary heart disease (narrowing of the diameter of the lumen by 50 or more percent) without affection of the trunk of the left coronary artery-group B. As to the investigated parameters of the ergometric test the two groups differed significantly in the total time of the load (group A: 6.21 minutes, group B: 7.94 minutes, p < 0.05), while in all other parameters--total amount of performed work, sum of depressions of the ST segments during a maximum load, time of onset of stenocardias, time since development of 1 mm depressions of the ST segment, maximal depression of the ST segment in lead V5 and number of leads with ST depressions above 1 mm--no significant difference was found. From the work ensues that from the ergometric loading test the finding of stenosis of the left coronary artery on coronarography cannot be predicted.