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BACKGROUND: Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration is elevated in patients with pulmonary hypertension (PH); however, its role in the detection of PH associated with lung disease is not well established. AIM: The aim of this study was to assess the value of NT-proBNP in the detection of PH in patients with end-stage lung disease (esLD) referred for lung transplantation. MATERIALS AND METHODS: The study population consisted of 65 patients: 37 with idiopathic pulmonary fibrosis (IPF), 20 with chronic obstructive pulmonary disease, and 8 patients with other interstitial lung diseases (75% men, mean age 53.3 ± 9.5 years). Serum concentration of NT-proBNP was assessed with an immunoradiometric assay kit. The mean pulmonary artery pressure (mPAP) was measured using a Swan-Ganz catheter. PH was defined as mPAP ≥ 25 mm Hg. RESULTS: Median NT-proBNP concentrations were significantly higher in patients with PH than in patients without PH: 139 (49-1236) pg/mL vs 67 (38-116) pg/mL, respectively; P = .016. Receiver operating characteristic (ROC) analysis revealed that NT-proBNP concentration higher than 131.5 pg/mL was a predictor of PH with good specificity (81%) and positive predictive value (78.9%) but low sensitivity (55.6%) and negative predictive value (58.6%). The area under the ROC curve of serum NT-proBNP concentration for PH was 0.71 (95% confidence interval 0.57-0.85, P = .039). CONCLUSION: Serum concentration of NT-proBNP may be useful in the diagnosis of PH in patients with esLD referred for lung transplantation.

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BACKGROUND: Pulmonary hypertension (PH) is a common complication in end-stage lung disease (esLD). The aim of this study was to establish the best threshold values for mean, systolic, and diastolic artery pressure (mPAP, dPAP, and sPAP, respectively) to identify patients with esLD referred for lung transplantation and to predict 1-year prognosis. METHODS: Sixty-five patients were enrolled in the study (75% men) with a mean age of 53.3 ± 9.5 years; 31% had chronic obstructive pulmonary disease (COPD), 57% had idiopathic pulmonary fibrosis (IPF), and 12% had interstitial lung diseases (ILDs). The mean period of observation was 14.4 ± 5 months. We assessed invasively mPAP, dPAP, and sPAP, as well as pulmonary capillary wedge pressure (PCWP), using a Swan-Ganz catheter. Receiver-operating characteristic (ROC) curves were constructed to identify the best cutoff points for mPAP, dPAP, and sPAP to predict survival. The study endpoint was defined as 1-year mortality before transplantation. Survival analysis was completed according to the Kaplan-Meier method. RESULTS: During follow-up, 30 (46.1%) patients died and 19 (29%) underwent lung transplantation. Based on ROC curve analysis, we estimated mPAP ≥30 mm Hg, dPAP ≥20 mm Hg, and sPAP ≥44 mm Hg as the best threshold values with the highest sensitivity (70%, 70%, and 73%, respectively) and specificity (76%, 69%, and 72%, respectively) and the acceptable area under curve (0.67, 0.68, and 0.72, respectively). The negative predictive values for mPAP, dPAP, and sPAP were higher than the positive predictive values (79%, 77%, and 81% vs 67%, 61%, and 64%, respectively). We also constructed Kaplan-Meier curves for mPAP, dPAP, and sPAP threshold values. There were significant differences in 1-year survival between patients with and without PH for mPAP, dPAP, and sPAP threshold values (P = .005, P = .035, and P < .001; respectively). CONCLUSION: Elevated mPAP, dPAP, and sPAP are related to worse prognosis in patients with esLD referred for lung transplantation.

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Tissue Doppler imaging (TDI) can be useful in the evaluation of right ventricular (RV) regional dysfunction due to pulmonary diseases. The aim of the study was to assess RV dysfunction in patients with severe interstitial lung diseases (ILD), using both TDI and conventional transthoracic echocardiography (TTE). The study group consisted of 40 consecutive patients with end-stage ILD referred for lung transplantation (LT). Eighteen of them, mean age 47 +/-12 yr, who fulfilled the ATS/ERS criteria for LT (mean forced vital capacity (FVC) 1.4 +/-0.8 l, mean diffusing capacity for carbon dioxide (DLCO) <50% of predicted) constituted the active group, and 22 age-matched patients (mean age 49 +/-12 yr), who did not fulfill these criteria, were placed in the waiting group for LT. We found that among the TDI parameters, the longitudinal peak systolic strain rate (SR) measured at the RV outflow tract, was significantly more negative (-1.1 +/-0.3 vs. -3.2 +/-1.2 s(-1), P=0.03) and the time to peak velocity (TpVEL) in the medial and apical septal segments were shorter (129.9 +/-47.9 vs. 159.2 +/-38.1 ms, P=0.018 and 126.8 +/-44.3 vs. 154.6 +/-40.9 ms, P=0.019) in the patients from the active than those from the waiting group. TTE showed that patients from the active group had significantly lower values of tricuspid annulus plane systolic excursion (TAPSE) (14.3 +/-3.3 vs. 20.6 +/-6.2 mm, P=0.0003) and pulmonary artery acceleration time (PVAT) (70.3 +/-23.3 vs. 96.9 +/-12.4 ms, P=0.0001)compared with those from the waiting group. No other differences were found for other parameters of RV function between the examined groups. In conclusion, severity of lung disease in patients with ILD influences RV systolic dysfunction, which is reflected in both TDI and conventional echocardiographic parameters.

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Nitric oxide is present in the exhaled air. Factors affecting the level of exhaled nitric oxide (exNO), except for smoking, are not well defined. In this study we seek to determine whether age, gender, body mass index (BMI), part of the day, or time after a meal could modulate exNO levels. exNO was examined by the use of a chemiluminescence method in 100 subjects - 31 women (19 nonsmokers and 12 smokers) and 69 males (55 nonsmokers and 14 smokers). Forty four subjects took medications due to stable coronary disease, 22 were after heart transplantation, and 34 did not take any drugs. We found that exNO levels did not differ either between the whole groups of women and men or between smokers and nonsmokers of either respective group (4.91 +/-2.38 vs. 6.27 +/-4.23 ppb; 3.21 +/-1.16 vs. 3.71 +/-1.55 ppb; 5.98 +/-2.35 vs. 6.92 +/-4.45 ppb). The correlation of exNO with age in the whole population was weak (r=0.23; P=0.02) and insignificant in the smoking and nonsmoking subgroups. Likewise, correlations of exNO with BMI, part of the day, or time after a meal were insignificant in whole population as well as the subgroups. We conclude that the aforementioned factors are not able to confound the measurement of exNO in the population studied.

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A retrospective analysis of all cases when cyclosporine (CyA) was replaced with sirolimus (SIR) to avoid the renal toxicity of CyA late after heart transplant (OHT) was discontinued due to advanced renal impairment in all five heart transplant recipients (four men, 1 women; age 41 years, range 38-45; time after OHT 5 years, range 4-14). The serum creatinine level at the time of SIR introduction, which was 298 micromol/L (range 217-676), had remained stable for the 6 months prior to conversion. Target SIR trough levels were 12-20 ng/mL. In four patients the last dose of CyA was immediately followed by the first dose of SIR, whereas in one patient CyA was tapered gradually in the presence of low-dose SIR. Deterioration of renal function with signs of fluid overload and increased serum creatinine levels (Delta: 77, 33-150 micromol/L) was observed in all patients. Two patients required dialysis during SIR treatment including one case of pulmonary edema requiring emergency hemodialysis. None of four biopsies showed significant rejection. Four patients were converted back to low-dose CyA (including the two patients requiring dialysis during SIR therapy); one was maintained on mycophenolate mofetil. The creatinine level at the time of SIR discontinuation was (range 250-753) micromol/L, 448. Eventually, all patients required dialysis. In conclusion, replacement of cyclosporine with sirolimus in heart transplant recipients with severe renal impairment late after transplantation may accelerate renal failure.

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Bioprosthetic heart valve, derived from human or animal tissues is a commercial, implantable valve characterised by good haemodynamic parameters, low haemolysis ratio and satisfactory durability. Until now, its wide-spread therapeutic use has been limited by the progressing leaflet calcification. The aim of the paper is to present the benefits, adverse reactions as well as problems associated with the improvement of this bioprosthesis.

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The circadian heart rate course was assessed in 3 groups of patients with left ventricular ejection fraction (LVEF) 10-15%, 20-25% and 30-35%. The study comprised 36 persons. In 9 patients heart failure was due to MI and in 17--to dilated cardiomyopathy. Those with atrial fibrillation, ventricular tachycardia, supraventricular tachycardia, diabetes, valvular heart diseases and with central system disorders were excluded from the study. Left ventricular ejection fraction was evaluated by echocardiography. Heart rate, calculated as a mean value every 5 minutes, was taken in patients during 24 hour recordings. For each patient separately, mean value of all measurement was calculated. Then a ratio of each actual value to the mean value was calculated. This ratio was defined as relative heart rate; [formula: see text] Circadian heart rate courses were approximated by Fourier row: [formula: see text]. The 24 harmonics were analyzed. Statistically significant differences in circadian courses were closed to amplitudes of 1st, 12th, 13th, 14th, 16th, 18th harmonics. Using test of variance homogeneity it has been demonstrated that variability of amplitudes of 12th and 17th harmonics as well as phase of 5th harmonic depend on left ventricular ejection fraction.

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Investigations were carried out in 74 persons (32 female and 42 male, mean age: 39.7 +/- 10.0 years, range: 16 to 68 years) free of diseases known to affect autonomic function. After a quarter of rest in quite, air conditioned room, while on voluntary breathing in supine, and later on in vertical position, time-series of a few minutes of successive R-R intervals were collected in each person and than stored for further off line analysis. Multivariate autoregressive modeling approach with parametric decomposition of peaks has given a basis for computation of spectral power of heart rate variability. In each body position 150 seconds long, stationary epoch of R-R intervals free of ectopy and artifacts were selected, and spectral power were calculated in three frequency bands: very low frequency (VLF): below 0.03 Hz (rejected from further analysis), low frequency (LF): from 0.03 to 0.15 Hz, and high frequency (HF): 0.15 to 0.35 Hz. Than, computed powers were expressed in either absolute units, or as normalized values, that is as percentages of total power less VLF. Breathing was also monitored in each case and spectral characteristics of its frequency also given in ranges defined for heart rate variability. In vertical, as compared to supine position, mean R-R interval decreased: 856 +/- 119 ms vs. 695 +/- 111 ms (p < 0.0005). The power of LF increased: 8.1 +/- 7.3 BPM2 vs. 19.2 +/- 14.6 BPM2, (p < 0,005), and simultaneously the power of HF dropped: 4.7 +/- 3.6 BPM2 vs. 2.7 +/- 2.5 BPM2, (p < 0.0005). In normalized units LF power enhanced: 63 +/- 385 vs. 87 +/- 42%, (p < 0.0005), and HF dropped: 36.7 +/- 32% vs. 12.3 +/- 12%, (p < 0.0005). Autonomic balance expressed as LF/HF ratio was higher in vertical position: 2.0 +/- 1.6 vs. 11.0 +/- 8.7, (p < 0.0005). In 73 out of 74 subjects (98.6%) the power of LF increased, and in 71 (95.9%)-decreased. In one person who had lower power of LF in vertical than supine position, the increase of HF power was noticed. Mean percentage increase of LF in the whole group was 209.4 +/- 243%, but after rejection of the result mention above the mean value increased to 218 +/- 22.1%. Mean percentage decrease of HF power in the whole group was 34.7 +/- 37.7%, and increased to 39.5 +/- 26.9% after rejection of three results with changes in opposite direction. Mean values of respiratory power did not change with switching of posture neither in LF:14.4 +/- 6.6% vs. 17.8 +/- 7.1%, (NS), nor in HF: 77.7 +/- 9.2% vs. 73.6 +/- 12.1%, (NS).

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The clinical symptoms of migraine point to autonomic disturbances, especially to disrupted regulation of the circulatory system and autonomic balance. Searching for more accurate autonomic system studies we turned to the spectral analysis of cardiac rhythm changes, that allows to estimate the autonomic balance in sinus node. 44 patients with migraine were studied and the results were compared with those obtained in 74 healthy subjects. The reduced influence of both sympathetic and parasympathetic part of autonomic system on the sinus rhythm in migraine patients was found. The autonomic balance is shifted to the parasympathetic innervation side in patients with migraine.

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The autonomic impairment, which is the frequent complication of end-stage renal failure, may eventually trigger numerous crippling consequences. It is doubtful if standard dialysis techniques may effectively treat once developed autonomic lesions. Renal transplantation seems to be much more efficient. The article points out the discrepancies in symptoms attributable to autonomic impairment and results of autonomic testing, discusses also differences between somatic and autonomic nervous system involvement in uremic patients. The one of the most important part of the article describes the practical approach to the patient with severely symptomatic uremic autonomic neuropathy. Finally the authors articulate their proposals for further research on uremic autonomic neuropathy.

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Autonomic impairement is associated with poor prognosis in many diseases. The article (first of three parts) critically reviews arguments found in the literature showing autonomic dysfunction in chronic renal failure patients. The autonomic nervous system problems will become of great clinical relevance considering increasing number and age of uremic patients being dialysed worldwide.

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Autonomic impairment is associated with poor prognosis in many diseases. The pathogenesis of the uremic autonomic neuropathy has not been convincingly established, so the article reviews available information on factors involved in its development, furthermore the authors put forward their own hypothetical scheme of the pathogenesis. The last section outlines the methods most commonly used for its diagnosis and finally the authors discuss symptoms suggestive of this neuropathy in clinical setting.

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Spectral analysis of hart rhythm variability makes possible assessment of the state (power) of autonomic innervation of the heart. The reported study was carried out in 40 patients (22 women) with migraine. The studies were done in times between migraine attacks. The control group comprised 62 clinically healthy subjects. In most patients (over 61%) the sympathetic and parasympathetic innervation of the heart was weaker than in healthy subjects and the index of automatic equilibrium in the sinus node was lower than in controls.

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