Reproducibility of the six-minute walking test in chronic heart failure patients.

The six-minute walking test (WT) is used in trials and clinical practice as an easy tool to evaluate the functional capacity of chronic heart failure (CHF) patients. As WT measurements are highly variable both between and within individuals, this study aims at assessing the contribution of the different sources of variation and estimating the reproducibility of the test. A statistical model describing WT measurements as a function of fixed and random effects is proposed and its parameters estimated. We considered 202 stable CHF patients who performed two baseline WTs separated by a 30 minute rest; 49 of them repeated the two tests 3 months later (follow-up control). They had no changes in therapy or major clinical events. Another 31 subjects performed two baseline tests separated by 24 hours. Collected data were analysed using a mixed model methodology. There was no significant difference between measurements taken 30 minutes and 24 hours apart (p = 0.99). A trend effect of 17 (1.4) m (mean (SE)) was consistently found between duplicate tests (p < 0.001). REML estimates of variance components were: 5189 (674) for subject differences in the error-free value; 1280 (304) for subject differences in spontaneous clinical evolution between baseline and follow-up control, and 266 (23) for the within-subject error. Hence, the standard error of measurement was 16.3 m, namely 4 per cent of the average WT performance (403 m) in this sample. The intraclass correlation coefficient was 0.96. We conclude that WT measurements are characterized by good intrasubject reproducibility and excellent reliability. When follow-up studies > or = 3 months are performed, unpredictable changes in individual walking performance due to spontaneous clinical evolution are to be expected. Their clinical significance, however, is not known.

Loading manipulations improve the prognostic value of Doppler evaluation of mitral flow in patients with chronic heart failure.

BACKGROUND: Mitral flow velocity patterns (MFVPs) evaluated by Doppler echocardiography are strong predictors of survival in various cardiac diseases. However, MFVPs may change over time according to loading conditions. We performed this prospective study to assess whether changes in MFVP induced by loading manipulations provided additional prognostic information in 173 patients with chronic heart failure. METHODS AND RESULTS: Simultaneous Doppler echocardiographic and right-sided hemodynamic recordings were obtained at baseline in all patients, during nitroprusside infusion in the 98 patients who had a baseline restrictive (early-to-late flow velocity ratio > 1 and deceleration time < or = 130 ms) MFVP, and during passive leg lifting in the 75 patients who had a baseline nonrestrictive MFVP. Patients were categorized, according to changes in MFVP, into four groups: 61 patients with an irreversible restrictive, 37 with a reversible restrictive, 48 patients with a stable nonrestrictive, and 27 patients with an unstable nonrestrictive MFVP. Fifty patients experienced major cardiac events. Cox analysis revealed that MFVP was a strong predictor of events and that the response to loading manipulations improved its prognostic value. Patients with an irreversible restrictive MFVP had a higher event rate (51%) than patients with a reversible restrictive MFVP (19%). Among patients with a baseline nonrestrictive MFVP, those with a stable nonrestrictive MFVP had the lowest event rate (6%), whereas the event rate was 33% in patients with an unstable nonrestrictive MFVP. CONCLUSIONS: In patients with chronic heart failure, MFVPs provide independent prognostic information. Their prognostic value can be further increased by assessment of the changes induced in them by loading manipulations.

Mitral flow velocity changes after 6 months of optimized therapy provide important hemodynamic and prognostic information in patients with chronic heart failure.

Transmitral flow velocity patterns evaluated by Doppler echocardiography provide important hemodynamic and prognostic information in various cardiac conditions. However, these patterns may change over time, and so far the hemodynamic and prognostic significance of these changes has not been established. Accordingly, we performed this study to determine the hemodynamic and prognostic value of changes in transmitral flow velocity patterns after 6 months of optimized medical treatment in patients with chronic heart failure due to ischemic or nonischemic dilated cardiomyopathy. Ninety-eight consecutive patients with chronic heart failure underwent a clinical examination, a cardiopulmonary exercise test, and simultaneous Doppler echocardiographic and hemodynamic studies at baseline and after 6 months, patients were followed up for 12 +/- 7 months. Cardiac death and heart transplantation while patients were in critical condition were considered events. A restrictive pattern was defined by an early-to-late peak diastolic velocity ratio > 1 and an early diastolic deceleration time < or = 130 msec. Patients were grouped according to their mitral flow pattern at baseline and its changes after chronic optimized therapy. No significant changes in clinical, ergometric, and hemodynamic variables were found after 6 months in the 49 patients who had a persistent restrictive transmitral flow pattern or the 24 patients who had a persistent nonrestrictive transmitral flow pattern. In the 19 patients who had a restrictive pattern at baseline that reverted into a nonrestrictive pattern, this change was accompanied by a highly significant reduction in pulmonary wedge pressure (from 25 +/- 7 mm Hg to 11 +/- 3 mm Hg) and by an increase in exercise capacity, whereas in the 6 patients who had a nonrestrictive pattern that became restrictive, hemodynamic features markedly deteriorated. Seventeen of the 21 events occurred in the 49 patients (event rate 35%) with a persistent restrictive pattern, whereas the event rate was much lower in the 19 patients with a reversible restrictive pattern (5%) and in the 24 patients with a persistent nonrestrictive pattern (4%). Two (33%) of the 6 patients in whom a restrictive pattern developed had events. Cox analysis revealed that a restrictive transmitral flow pattern (p = 0.0068) and peak rate of oxygen consumption (p = 0.0056) detected at the late examination were significantly related to cardiac events. These results show that in patients with chronic heart failure, changes in transmitral flow patterns after chronic optimized therapy are correlated with changes in pulmonary wedge pressure, are accompanied by changes in functional capacity, and provide relevant independent prognostic information.

Comparison of Doppler echocardiography with thermodilution for assessing cardiac output in advanced congestive heart failure.

Noninvasive cardiac output estimation by Doppler echocardiography was compared with thermodilution and Fick oxygen methods in 73 patients with advanced chronic congestive heart failure due to dilated cardiomyopathy. In these patients, Doppler echocardiographic measurements showed a closer agreement with Fick measurements than that of thermodilution.

Concomitant factors of decompensation in chronic heart failure.

The concomitant factors implicated in 328 nonfatal decompensations of 304 patients with congestive heart failure were: arrhythmias in 24%, infections in 23%, poor compliance in 15%, angina in 14%, iatrogenic factors in 10%, and other causes in 5% of cases. New York Heart Association class and right atrial pressure significantly related to the occurrence of decompensation. Poor compliance and angina were unpredictable, infection was related to pulmonary wedge pressure, iatrogenic factors were predicted by the more advanced functional classes, whereas arrhythmias were more frequent in patients with renal failure.

Effects of record length selection on the accuracy of spectral estimates of heart rate variability: a simulation study.

To evaluate the effects of record length selection on the accuracy of spectral estimates of heart rate variability (HRV), a simulation study was carried out using a set of 58 signals obtained by autoregressive (AR) fitting a representative sample of real HRV signals. Four record lengths of 180, 300, 420, and 540 s were considered. Spectral estimation was performed by both the Blackman-Tukey (B-T) and AR methods. Accuracy was assessed for: 1) point spectral estimates, by computing the normalized averaged bias (NAB) and variance (NAV); and 2) the most commonly used spectral parameters [total power (TP) and the powers in the bands: very low frequency (VLF) (0 divided by 0.04 Hz), low frequency (LF) (0.04 divided by 0.15 Hz), and high frequency (HF) (0.15 divided by 0.45 Hz)], by computing the normalized bias (NB) and variance (NV). The results are: whatever the record length considered, the 90th percentiles (90P) of the NAB were < 10%, whereas those of the NB were < 9% for TP, LF, and HF powers, and < 14% for the VLF power, in both methods. The NAV was proportional to the reciprocal of record length, showing high 90P values for the shortest record length (26.4% for B-T and 44.2% for AR). The NV showed the same trend but 90P values were much lower (< 8% for TP, LF, and HF powers and < 19% for VLF power, in both methods). In the final part of the paper a procedure for the computation of approximate upper bounds of the relative absolute error of spectral measures at each record length, based on the knowledge of the NB and NV, is presented.

Doppler evaluations of left ventricular diastolic filling and pulmonary wedge pressure provide similar prognostic information in patients with systolic dysfunction after myocardial infarction.

Previous studies have demonstrated that in patients with various types of cardiac diseases and left ventricular dysfunction, left ventricular filling patterns assessed by Doppler of mitral flow are correlated to ventricular filling pressure, the prognostic value of which is well known. The current study was carried out to determine the prognostic importance of a noninvasive evaluation of left ventricular filling by Doppler of mitral flow in patients with systolic dysfunction after myocardial infarction and to compare its value with that of pulmonary wedge pressure. One hundred seven patients with a left ventricular ejection fraction < 40% were studied 3 to 12 weeks after myocardial infarction. All patients underwent a complete clinical examination, a standard two-dimensional and Doppler echocardiographic examination, and right-sided heart catheterization at rest and during a cardiopulmonary bicycle exercise test. Early and late diastolic peak flow velocities, their ratio, and the deceleration time of early diastolic velocity were measured from pulsed-wave Doppler of mitral flow. Follow-up data were obtained for 101 patients. During a mean period of 25 (median 21, range 12 to 60) months cardiac events (death, heart transplantation, or heart failure requiring hospitalization) occurred in 43 (42%) patients. Patients with cardiac events during follow-up were in a worse functional class and had a more impaired exercise capacity and higher capillary pulmonary wedge pressure at baseline examination. Among Doppler echocardiographic variables, in patients with cardiac events a greater early to late diastolic peak velocity ratio of mitral flow (1.9 +/- 0.9 pl/min vs 1.2 +/- 0.8 pl/min, p < 0.001) and a shorter early diastolic deceleration time (112 +/- 35 vs 145 +/- 42 msec, p < 0.001) were found. Cox analysis revealed that the combination of early to late diastolic peak flow velocity ratio of mitral flow and New York Heart Association functional class were the strongest noninvasive independent predictors of cardiac events. One-year event-free probability of survival was 90% in patients with an early to late diastolic peak velocity ratio < or = 1 (all but 1 in New York Heart Association functional class I or II) but was significantly less in patients with an early to late diastolic peak velocity ratio > 1 (64% in functional class I or II and 36% functional class III). Similar results were obtained when mean pulmonary wedge pressure was considered instead of the ratio between peak flow velocities of mitral flow.(ABSTRACT TRUNCATED AT 400 WORDS)

Cardiac and vascular sources of peripheral thromboembolism in patients with atrial fibrillation. A combined transesophageal and vascular ultrasonographic study.

Atrial fibrillation is associated with an increased risk of peripheral thromboembolism. Although emboli arising from the left atrium are the most probable causes of peripheral ischemic events, coexistent vascular mechanisms may play a role in the genesis of thromboembolism. To assess the prevalence and the relative role of cardiac and vascular sources of thromboembolism in patients with atrial fibrillation 101 consecutive patients with (group 1: 47 patients) and without (group 2: 54 patients) recent thromboembolism were studied by transesophageal echocardiography and ultrasound duplex scanning of carotid arteries. Left atrial thrombosis was found in 19 (40%) group 1 patients and in 3 (5%) group 2 patients. Left atrial thrombosis and/or spontaneous echocardiographic contrast were significantly more frequent in group 1 patients than in group 2 (70% vs 20%, p < 0.001). Stepwise regression analysis revealed that they were the only independent predictors of thromboembolism (p = 0.018, p = 0.0003 respectively). Among clinical and transthoracic echocardiographic variables, left atrial diameter (p = 0.022), rheumatic mitral stenosis (p = 0.0058) and absence of significant mitral regurgitation (p = 0.027) emerged as independent predictors of left atrial thrombosis and/or spontaneous echocardiographic contrast. When transesophageal parameters were also entered into the analysis, the only independent predictor was low blood flow velocity within the left atrial appendage (p = 0.0001). Vascular sources (obstructive carotid arteries plaques, non-obstructive ulcerated carotid plaques and thoracic aortic atherosclerotic debris) were found in 30.6% of patients. Their prevalence was not significantly different in the two groups (34% in group 1, 27% in group 2). Vascular and cardiac sources coexisted in 23% of patients with thromboembolism. Seven of the 10 patients with more severe vascular lesions (i.e., obstructive carotid artery lesions or pedunculated mobile aortic debris) were from group 1 and 5 of them had negative cardiac results. In conclusion, these results indicate that a cardioembolic mechanism due to blood stasis within the left atrium is involved in most of the atrial fibrillation-related thromboembolic events. In patients with atrial fibrillation vascular sources are not infrequent and may be involved in the genesis of ischemic events in some patients. Transesophageal echocardiography may be useful in identifying subgroups of patients with atrial fibrillation who are at high thromboembolic risk.

Familial aggregation of blood pressure in a paediatric population.

Familial aggregation of blood pressure in childhood and the difference between males and females were studied in a random sample of a nursery and school-age population in Milan. Age, sex, height, weight, skinfold thicknesses and heart rate were obtained. Blood pressure was measured in accordance with the recommendations of the Task Force of Blood Pressure Control in Children. After adjusting for age, significant correlation coefficients were found between mother and son (r = 0.17 and r = 0.11), mother and daughter (r = 0.11 and r = 0.15), and father and son (r = 0.16 and r = 0.17) for systolic and diastolic pressure, respectively; the father-daughter correlations were not statistically different (r = 0.08 and r = 0.03). Multiple regression analysis underlined the difference between males and females; height was an important determinant in the males and body weight in the females. In conclusion, anthropometric measurements should be considered in evaluations of blood pressure status. Our results suggest important differences between males and females. The BP pattern of the parents also seems more important for sons, and there seems to be a lower correlation between fathers and daughters.

Mortality in an area contaminated by TCDD following an industrial incident.

The mortality experience of the population, aged 20-74 years, living in an area contaminated by TCDD after an industrial accident in 1976, was examined in the period 1976-1986 and compared with the mortality of the population of the surrounding noncontaminated territory. People who left the area during the study period were followed up, and vital status was successfully ascertained for over 99% of the cohort members. An increased mortality, from chronic ischemic heart disease (males) and hypertensive disease (females), which could not be explained in terms of chance, confounding, or bias, was noted in the exposed population. The stressful experience of the population in the aftermath of the disaster was deemed relevant to the interpretation of these findings. Overall, cancer mortality was not increased. Suggestive increases, however, were seen for melanoma, brain cancer, soft tissue sarcomas and certain hematologic neoplasms, whereas mortality from breast cancer and cancer of the liver was noticeably decreased. Further research is in progress in order to thoroughly investigate the association, if any, of cancer occurrence with TCDD contamination.

Ten-year mortality study of the population involved in the Seveso incident in 1976.

In 1976, an accidental explosion in a plant near Seveso, Italy, caused the contamination of a populated area by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The area was subdivided into three zones (A, B, and R) having decreasing mean levels of TCDD soil contamination. This study examines the mortality between 1976 and 1986 among the subjects, aged 20-74 years, who were resident in the area since the accident (n = 556 in zone A, n = 3,920 in zone B, n = 26,227 in zone R). Subjects' exposure was classified by residence. A referent cohort of 167,391 subjects who lived in the immediate surroundings was concurrently examined. Vital status ascertainment was successful for over 99% of the subjects. Increased mortality from cardiovascular causes was found; incident-related stressors were considered more relevant to increased mortality than was TCDD exposure. Mortality from several cancers was elevated. The increases in biliary cancer (females), brain cancer, and lymphatic and hemopoietic neoplasms (particularly leukemia in males) did not appear to result from chance, confounding, or information/comparison bias. However, no definite patterns related to exposure classification were apparent. Merely suggestive increases in soft tissue tumors and melanoma were also noted. Liver and breast cancer mortality tended to be below expectations. Interpretation is hampered by the short observation period, small number of deaths from certain causes, and poor exposure definition. Further research is in progress.