Andrea Passantino

Comparison Between Noninvasive Indices of Baroreceptor Sensitivity and the Phenylephrine Method in Post–Myocardial Infarction Patients

BACKGROUND Depressed baroreflex sensitivity obtained by means of a phenylephrine test plays a prognostic role in patients with a previous myocardial infarction. Our purpose was to evaluate the correlation and agreement between the baroreflex sensitivity obtained with phenylephrine and that obtained by two noninvasive methods: the alpha-index and sequence analysis. METHODS AND RESULTS The alpha-index was measured by means of the spectral analysis of RR and systolic blood pressure variabilities in both the high- and low-frequency bands; sequences were identified from simultaneously recorded time series in which the RR and systolic blood pressure concurrently increased or decreased. Noninvasive baroreflex sensitivity tests were performed during both spontaneous and controlled respiration. Fifty-two consecutive patients with recent myocardial infarction underwent the analyses. Although the correlations between phenylephrine and either of the noninvasive methods were always significant, those found during controlled respiration had the highest r values (r=.70). However, the limits of agreement calculated by means of the Bland and Altman method were wide for both noninvasive methods. CONCLUSIONS The results obtained by means of noninvasive baroreflex sensitivity assessments should not be used in clinical practice as an alternative to those obtained by the phenylephrine method.

Short- and long-term reproducibility of time and frequency domain heart rate variability measurements in normal subjects

OBJECTIVE To obtain data relating to the reproducibility of the time and frequency domain measurements obtained from 10-min ECG recordings. METHODS Eighteen normal volunteers underwent evaluations of time and frequency domain heart rate variability 2 weeks and 7 months after baseline analysis. The time domain parameters were mean NN, the standard deviation of NN intervals, the percentage of successive NN intervals > 50 ms and the root mean square successive difference of NN intervals. The frequency domain evaluations (total power, low frequency, and high frequency) were made by means of both the Fast Fourier Transform algorithm (FFT) and the autoregressive method (AR) from 10-min ECG recordings made under three different conditions: rest, controlled respiration, and after a passive head-up tilt test. Reproducibility was evaluated by means of the interclass correlation coefficient (ICC), comparing baseline values with the results obtained at the second week and the seventh month. Time domain evaluation were also made from 10-min ECG. RESULTS All of the time domain measurements had an ICC > or = 0.75, except for the standard deviation of NN intervals, which had an ICC of 0.57. The frequency domain parameters obtained by means of either FFT or AR showed similar reproducibility. Low frequency was reproducible under all three conditions, total power only at rest, and high frequency only during controlled respiration. CONCLUSION The reproducibility of frequency domain parameters depends on the analysed condition. These results are of primary importance when the effects of drugs or other interventions on heart rate variability are under investigation.

Effect of respiratory rate on the relationships between RR interval and systolic blood pressure fluctuations: a frequency-dependent phenomenon

OBJECTIVE The aims of this study were to determine the relationships between oscillations in systolic blood pressure and heart period at different breathing frequencies and to investigate the role of sympathetic contribution to this relationship. METHODS Fourteen healthy volunteers underwent three randomized periods of controlled breathing at 6, 10 and 16 breaths/min. ECG (RR), respiratory signal (RESP) and systolic blood pressure (SBP) were continuously recorded. The component of RR and SBP oscillations related to respiration (RRResp and SBPResp) was defined by means of uni- and bivariate spectral analysis. The squared coherence (K2) and phase between RR and RESP, and RR and SBP (RR-SBP) were also assessed. When the K2 of RR-SBP in the respiratory band was > 0.5, we considered the phase and calculated the closed-loop gain between the two signals. Seven subjects were also studied after chronic metoprolol treatment. RESULTS Although the mean values of RR and SBP did not differ between the three periods of breathing, the higher the respiratory rate, the smaller the RRResp and SBPResp. The phase was always negative (SBPResp changes preceded RRResp changes), thus suggesting a baroreflex link. The higher the respiratory rate, the lower the gain and phase. Pharmacological beta-adrenoceptor blockade increased the gain and shifted the phase, but the relationships found at baseline between the respiratory rate and both the gain and phase remained unchanged. CONCLUSIONS The effect of breath rate on the relationship between heart rate and systolic pressure variabilities is a frequency-dependent phenomenon that is also independent of the sympathetic drive.

The cardiorenal anaemia syndrome in systolic heart failure: prevalence, clinical correlates, and long-term survival

We sought to assess the prevalence and clinical correlates of cardiorenal anaemia (CRA) syndrome in systolic heart failure and the relationship between renal dysfunction and anaemia on hard clinical outcomes.

Percent achieved of predicted peak exercise oxygen uptake and kinetics of recovery of oxygen uptake after exercise for risk stratification in chronic heart failure

To investigate whether percent achieved of predicted peak exercise oxygen uptake (%VO2max) and recovery of oxygen consumption after exercise may provide prognostic information in chronic heart failure (CHF), we prospectively studied 196 patients with mild to moderate CHF. The following variables were examined: age, etiology of CHF, functional class, ejection fraction (EF), peak exercise oxygen uptake normalized for body weight (VO2max), %VO2max, time to reach 50% of the peak oxygen uptake after exercise (T1/2VO2max), presence of nonsustained ventricular tachycardia (NSVT) and inability to take ACE-inhibitors. VO2max was the most powerful predictor of cardiac death (P<0.0001). Other independent predictors of death were EF, T1/2VO2max, NSVT and inability to take ACE-inhibitors. The discriminatory accuracy of VO2max for cardiac death was not significantly greater than that of %VO2max. In conclusion, the determination of %VO2max does not enhance risk stratification in CHF whereas the kinetics of oxygen consumption after exercise can provide prognostic information.

Dependency of premature ventricular contractions on heart rate

To identify a method for characterizing the dynamic behavior of ventricular arrhythmias at different heart rates, 201 consecutive patients with frequent premature ventricular contractions (PVCs) underwent two 24-hour electrocardiographic monitoring periods. The percentage of PVCs for each cycle length was calculated and then analyzed by linear regression analysis. On the basis of the significance of the p value, and the positive or negative value of the slope, we identified three trends: a tachycardia-enhanced pattern (p < 0.01, slope negative), a bradycardia-enhanced pattern (p < 0.01, slope positive), and an indifferent pattern (p > 0.01). During the first monitoring period, a tachycardia-enhanced pattern was present in 56 patients (28%), a bradycardia-enhanced pattern was present in 49 patients (24%), and an indifferent pattern was present in 96 patients (48%). This relationship was reproducible in 41 of the patients with a tachycardia-enhanced pattern (73%), in 29 of the patients with a bradycardia-enhanced pattern (59%), and in 70 patients with an indifferent pattern (72%). In conclusion, it is possible to identify a spontaneous trend between the incidence of ventricular arrhythmias and the length of the preceding cardiac cycle that seems to remain stable over time.

Clinical utility of N-terminal pro-B-type natriuretic peptide for risk stratification of patients with acute decompensated heart failure. Derivation and validation of the ADHF/NT-proBNP risk score

BACKGROUND NT-proBNP has been associated with prognosis in acute decompensated heart failure (ADHF). Whether NT-proBNP provides additional prognostic information beyond that obtained from standard clinical variables is uncertain. We sought to assess whether N-terminal pro-B-type natriuretic peptide (NT-proBNP) determination improves risk reclassification of patients with ADHF and to develop and validate a point-based NT-proBNP risk score. METHODS This study included 824 patients with ADHF (453 in the derivation cohort, 371 in the validation cohort). We compared two multivariable models predicting 1-year all-cause mortality, including clinical variables and clinical variables plus NT-proBNP. We calculated the net reclassification improvement (NRI) and the integrated discrimination improvement (IDI). Then, we developed and externally validated the NT-proBNP risk score. RESULTS One-year mortalities for the derivation and validation cohorts were 28.3% and 23.4%, respectively. Multivariable predictors of mortality included chronic obstructive pulmonary disease, estimated glomerular filtration rate, sodium, hemoglobin, left ventricular ejection fraction, and moderate to severe tricuspid regurgitation. Adding NT-proBNP to the clinical variables only model significantly improved the NRI (0.129; p=0.0027) and the IDI (0.037; p=0.0005). In the derivation cohort, the NT-proBNP risk score had a C index of 0.839 (95% CI: 0.798-0.880) and the Hosmer-Lemeshow statistic was 1.23 (p=0.542), indicating good calibration. In the validation cohort, the risk score had a C index of 0.768 (95% CI: 0.711-0.817); the Hosmer-Lemeshow statistic was 2.76 (p=0.251), after recalibration. CONCLUSIONS The NT-proBNP risk score provides clinicians with a contemporary, accurate, easy-to-use, and validated predictive tool. Further validation in other datasets is advisable.

Diastolic Dysfunction and Baroreflex Sensitivity in Hypertension

The determinants of diastolic dysfunction in patients with systemic hypertension are not completely known. To evaluate the possible role of age, arterial blood pressure, and baroreflex heart rate response impairment in causing diastolic dysfunction, we studied 61 patients (42 male; mean+/-SD age, 43.9+/-12 years) with newly recognized and therefore previously untreated systemic hypertension. Diastolic dysfunction was evaluated by means of Doppler echocardiography (and diagnosed as such when the early to atrial peak velocity ratio corrected to heart rate was <1), arterial blood pressure by 24-hour ambulatory monitoring, and baroreflex heart rate response by means of the spectral technique (alpha index) during paced (0.27 Hz) and spontaneous breathing (in a supine position and during tilt). Nineteen patients had diastolic dysfunction, the most powerful predictor of which was age (r=-0.63, P<0.001). The patients with diastolic dysfunction had significantly lower values for spectral baroreflex gain in the high-frequency band than those without (5.2+/-3 versus 8.4+/-5 ms/mm Hg during paced breathing, P<0.05; 7. 4+/-4 versus 13.3+/-7 ms/mm Hg in a supine position, P<0.05; 4.3+/-4 versus 5+/-2 ms/mm Hg during tilt, P<NS). Ambulatory blood pressure values were not significantly different in the patients with (137+/-14 and 89+/-9 mm Hg) and without (144+/-11 and 82+/-24 mm Hg) diastolic dysfunction. In conclusion, age and impaired baroreflex heart rate response (but not pressure overload) are determinants of left ventricular diastolic dysfunction in patients with newly recognized and untreated systemic hypertension.

Predicting mortality in patients with acute heart failure: Role of risk scores

Acute heart failure is a leading cause of hospitalization and death, and it is an increasing burden on health care systems. The correct risk stratification of patients could improve clinical outcome and resources allocation, avoiding the overtreatment of low-risk subjects or the early, inappropriate discharge of high-risk patients. Many clinical scores have been derived and validated for in-hospital and post-discharge survival; predictive models include demographic, clinical, hemodynamic and laboratory variables. Data sets are derived from public registries, clinical trials, and retrospective data. Most models show a good capacity to discriminate patients who reach major clinical end-points, with C-indices generally higher than 0.70, but their applicability in real-world populations has been seldom evaluated. No study has evaluated if the use of risk score-based stratification might improve patient outcome. Some variables (age, blood pressure, sodium concentration, renal function) recur in most scores and should always be considered when evaluating the risk of an individual patient hospitalized for acute heart failure. Future studies will evaluate the emerging role of plasma biomarkers.

Assessment of cardiac vagal activity in patients with hyperthyroidism

Previous studies suggested that in patients with hyperthyroidism an autonomic imbalance and in particular a lower than normal vagal activity might be present. To verify this hypothesis we have evaluated the respiratory sinus arrhythmia (RSA, a measure of cardiac vagal activity) in ten hyperthyroid patients and in ten normal subjects. RSA was calculated from the power of the spectral component of the heart rate variability in high frequency band (HF-RR) during both spontaneous (supine and passive head-up tilt) and controlled breathing (supine). During controlled breathing the phase relation between heart rate and respiratory has been computed. The hyperthyroid patients showed a higher heart rate in all three conditions (P<0.001) and higher spontaneous respiratory rate in supine position (centered frequency of HF-RR: 0.342+/-0.015 vs 0.262+/-0.016 Hz; P<0.001). No difference was found in hyperthyroid patients compared to controls in terms of the HF-RR power in normalized units both during spontaneous breathing (supine, 43+/-8.3 vs 39.7+/-6.7%; tilt 18.8+/-5.9 vs 19.3 vs 4.1%; mean+/-SE) and controlled breathing (45.4+/-7.1 vs 48.9+/-6.9%). No difference was found also in terms of the phase relationship between the heart rate and the respiratory signals (77.5+/-32.3 vs 77.5+/-28.1, degrees). Hyperthyroid patients seem not to have an impaired cardiac vagal activity.