Giorgio Mazzuero

Augmented Peripheral Chemosensitivity as a Potential Input to Baroreflex Impairment and Autonomic Imbalance in Chronic Heart Failure

BACKGROUND The precise mechanisms responsible for the sympathetic overactivity and blunted baroreflex control in chronic heart failure (CHF) remain obscure. Augmented peripheral chemosensitivity has recently been demonstrated in CHF. We evaluated the relation between peripheral chemoreflex sensitivity and autonomic activity in patients with CHF. METHODS AND RESULTS We studied in 26 stable patients with CHF the peripheral chemosensitivity (ventilatory response to hypoxia using transient inhalations of pure nitrogen), autonomic balance (spectral analysis of heart rate variability [HRV]), and baroreflex sensitivity (bolus phenylephrine method and alpha index). To determine whether transient inactivation of peripheral chemoreceptors might influence autonomic balance, 12 patients underwent a second study during which they breathed 100% O2. Peripheral chemosensitivity correlated inversely with HRV power within the low-frequency band (0.04 to 0.15 Hz) (r=-.52, P=.006) and inversely with baroreflex sensitivity (r=-.60, P=.005). When the patients were divided into two groups according to the chemosensitivity of age-matched normal controls (above and below mean+2 SDs of chemosensitivity of control subjects), those above the normal range revealed more impaired autonomic balance, ie, lower baroreflex sensitivity (1.4 +/- 1.3 versus 5.0 +/- 1.5 ms/mm Hg, P<.0001) and depressed values of low-frequency power (2.5 +/- 1.8 versus 4.1 +/- 0.8 ln ms2, P<.005) compared with those with normal chemosensitivity. Transient hyperoxia did not alter heart rate or systolic pressure but resulted in an increase in HRV and an improvement in baroreflex sensitivity. CONCLUSIONS A link between increased peripheral chemosensitivity and impaired autonomic control, including baroreflex inhibition, is demonstrated. The clinical importance of this phenomenon warrants further investigation.

Detection and significance of a discrete very low frequency rhythm in RR interval variability in chronic congestive heart failure

Although in advanced chronic congestive heart failure (CHF) very low frequency (< 0.04 Hz, VLF) oscillations are prominent, the clinical importance and the physiologic basis of these rhythms have not been elucidated. To investigate the physiologic determinants of the VLF rhythms in RR interval variability, we studied 36 patients with stable, moderate to severe CHF (33 men, age: 58 +/- 8 years, ejection fraction 25 +/- 10%, peak oxygen consumption 18.1 +/- 4.6 ml/kg/min) and 12 age- and sex-matched controls using autoregressive spectral analysis of RR interval, blood pressure, and respiratory signals during controlled conditions. We quantified low frequency (LF) (0.04 to 0.15 Hz), high frequency (HF) (0.15 to 0.40 Hz), VLF, and total power (0 to 0.5 Hz), and calculated the coherence between systolic blood pressure and RR interval variability within each band. Peripheral chemosensitivity was assessed by the ventilatory response to hypoxia using transient inhalation of pure nitrogen. The influence of transient inactivation of peripheral chemoreceptors on the VLF rhythm was investigated by exposing 6 patients to hyperoxic (60% oxygen) conditions for 20 minutes. Twenty-three patients (64%) with CHF, but no controls, had a discrete VLF rhythm (0.019 +/- 0.008 Hz) in RR variability. The presence of VLF rhythm was not related to any difference in clinical parameters (etiology, New York Heart Association class, ejection fraction, oxygen uptake) but rather to a different pattern in RR interval and blood pressure variability: lower LF power (2.8 +/- 1.6 ms2 natural logarithm [ln]) compared either to patients without VLF (4.0 +/- 1.3 ms2 ln) or to controls (5.9 +/- 0.7 ms2 ln), higher percentage of power within VLF band (86.3 +/- 8.3% vs 77.5 +/- 7.9% and 61.5 +/- 14.1%) and a markedly impaired coherence between RR interval and systolic blood pressure variability within the LF band (0.26 +/- 0.10 vs 0.42 +/- 0.18 and 0.63 +/- 0.15, in patients with vs without VLF peak and controls, respectively). Patients with VLF had significantly increased hypoxic chemosensitivity, and hyperoxic conditions were able to decrease VLF power and abolish the VLF rhythm in 5 of 6 patients with CHF. Discrete VLF oscillations in RR variability are common in patients with advanced CHF and appear to be related to severely impaired autonomic regulation and suppression of baroreceptor function, with enhancement of hypoxic chemosensitivity. We hypothesize that this rhythm represents an enhanced chemoreflex harmonic oscillation in CHF patients, which may have application for arrhythmogenesis.

A comprehensive PC solution to heart rate variability analysis in mental stress

To assess the modifications of the sympathovagal balance induced by mental stress, a computerized system has been developed which is able to carry out a complete spectral analysis of the heart rate variability (HRV) signal. Based on a personal computer, it acquires ECG (electrocardiography), respiratory, and blood pressure signals for each step of a mental stress trial. The collected data are then processed and spectral analysis is carried out by conventional FFT. In addition, an autoregressive identification algorithm computes the power and central frequency of the spectra peaks, allowing automatic classification of low-frequency (LF) and high-frequency (HF) peaks. The analysis executed for each step of the trial allows the comparison of the various spectral responses corresponding to different stimulations. This system was tested on 32 recently infarcted subjects and results show a significant increment in LF peak (P<0.005) and a significant reduction in HF peak (P<0.05) during a mental arithmetic task. Preliminary results suggest that this method can be considered a useful technique for evaluating the autonomic response to mental stress.<<ETX>>

Is heart rate variability a reliable method to assess autonomic modulation in left ventricular dysfunction and heart failure?: Assessment of autonomic modulation with heart rate variability

Autonomic dysfunction seems to be involved in the progression and prognosis of congestive heart failure. Measurement of heart rate variability (HRV) provides a noninvasive method to obtain reliable and reproducible information on autonomic modulation of heart rate, but there is a difficulty in using HRV as a quantitative estimate of autonomic dysfunction in heart failure. This study was aimed at testing the hypothesis that abnormal modulation of heart rate assessed by power spectrum analysis may be present also in asymptomatic patients with left ventricular dysfunction and progress in patients with overt symptoms of congestive heart failure. HRV was measured in three groups of subjects: Group 1: 30 patients with chronic heart failure; Group 2: 21 patients with asymptomatic left ventricular dysfunction; and Group 3: 25 healthy volunteers as control group. HRV was evaluated by autoregressive spectral analysis with 600-beat ECG samples, while subjects were quietly recumbent (BSI), in conditions of controlled breathing (15 acts/min) (RSC) and passive orthostatism after tilting (80 degrees) (TLT). Patients in group 1 showed a reduction in the standard deviation of the R-R intervals (SDRR) (p<0.0003) and in the low frequency component (LF) (p<0.0001) compared to normal subjects. Low frequency component was not detectable in 11 patients of group I (p<0.0008). On RSC and TLT, group 1 failed to show any modification in the low frequency and high frequency components (HF) under any stimulation. Group 2 showed no modification at baseline evaluation, no increase in the high frequency component on RSC and in LF during TLT compared to controls (p<0.01 and p<0.0001 respectively). At baseline, group 1 had a lower SDRR (p<0.03) and LF (p<0.0001) vs. group 2, whereas during stimulation the two groups exhibited the same behaviour. In conclusion, reduced heart rate variability is specific for both asymptomatic and symptomatic post-ischemic left ventricular dysfunction. Our results suggest that frequency domain analysis of heart rate variability during a stimulation test allows a more accurate definition of the degree of autonomic control of heart rate.

Do alpha-index and phenylephrine test provide similar measurements of baroreflex sensitivity in cardiac patients with chronic heart failure?

To verify whether the phenylephrine test (PHE) and spectral analysis (alpha-index) provide similar measures of baroreflex sensitivity in patients with chronic heart failure due to left ventricular dysfunction, the authors evaluated by both methods a group of 40 patients during rest and controlled breathing (CB). R-R interval (RR), blood pressure (BP) and respiration were recorded in both conditions (600 heart beats), and bivariate spectral analysis was carried out. The alpha-index was measured when the magnitude squared coherence (MSC) between RR variability and systolic BP variability was >0.5 in the low frequency (/spl alpha/LF) and high frequency (/spl alpha/HF) bands; the mean /spl alpha/ was also computed. PHE followed immediately, with at least 3 injections during rest and one during CB. /spl alpha/LF could not be measured during both rest and CB in 40% of patients. The PHE slope could not be found in 7% of patients during rest and in 10% during CB. Regression analysis of the PHE slope vs /spl alpha/LF (r=0.61), /spl alpha/ HF (r=0.63) and /spl alpha/(r=0.67) showed a weak correlation during rest. No correlation was found during CB.

Baroreflex sensitivity in cardiac patients with chronic congestive heart failure: towards a non invasive assessment method

Spectral analysis of RR interval and systolic arterial pressure variability was applied for the non invasive assessment of the baroreflex gain in Congestive Chronic Heart Failure (CNF). Forty-nine CHF patients were studied during rest, controlled breathing and head-up tilt. The alpha index, a noninvasive measure of the overall gain of the RR to systolic arterial pressure (SAP) relationship, and a modified version called beta, incorporating the weighted coherence function, were computed in the low (LF) and high (NF) frequency bands by spectral analysis, and compared with the phenylephrine test slope. A linear model fitted on the beta index values during rest and controlled breathing showed a high correlation (r=0.93, Standard error of the estimation=2.5 ms/mmHg) with the phenylephrine test slope. In severe CNF patients the beta index proposed, evaluated during rest and controlled breathing, may improve the baroreflex gain estimation and provide a noninvasive assessment method that might be useful in gauging prognosis.

Impaired baroreflex sensitivity and nocturnal periodic breathing in patients with chronic heart failure

Nocturnal periodic breathing is a common finding in severe chronic heart failure (CHF). Patients (pts) with left ventricular dysfunction can exhibit impairment of baroreflex sensitivity (BRS) or heart rare variability (HRV). We studied 48 pts aged 57/spl plusmn/8 years with CHF in stable phase (EF=23/spl plusmn/6%). All pts underwent a sleep study to assess the occurrence of periodic breathing, and a phenylephrine test to evaluate BRS; 36 patients had also a 24 hour ambulatory electrocardiogram recording to measure HRV. Nocturnal periodic breathing was recorded in 75% of patients, BRS was markedly depressed in 60% of patients, HRV was reduced in 58% of patients. Significant correlations were found between %PB and left ventricle EF (p=0.016), BRS (p=0.0002), HRV (p=0.0001), and nocturnal oxygen desaturation (p=0.0001). Nocturnal periodic breathing is frequently associated with abnormal autonomic control of cardiac function in patients suffering from chronic heart failure.

Decreased heart rate variability and sudden death in amyotrophic lateral sclerosis

Sudden death is quite common terminal event in patients (pa) sulfering from AmyMrophic Lateral Sclerosis (ALS). To evaluate a possible autonomic imbalance in ALS. we studied 29 pts (19 M. 11 F) aged 33-74 yro (55~12). and 33 age-matched healthy subjects (Control). All pta had lower and upper motoneumn involvement. 13 had bulbar signs. We analized Heart Rote Variability (HRV) in time domain (standard deviation of mea” R-R interval. SD, and beaMvbeat mea” square difference. MSD) and in frequenq domain (autoregressive spectral analysis with automatic spectral decompz&tion recognizing low frequency. LF. and high frequency component HF. their ratio LFMF considered as a marker d syn~patho-vagai balance). W and Contml were evaluated at rest as well as during sympathetic and vagal enhancement by passive orthostatism (Tilt) and controlled breathing (CS) respectively. No p was taking any drug. Ftesults: RR( L MF ALS Rest 903:z 32511’.. 17f7”’ 4.1f4.0 Tilt 665*88.. . . . . 24*,()...... 1W”” 11.2fl2.v’ cs 799zt116”’ 3ok12’ ’ 15f7”’ 2.6f2.4” Control Rest 975k122 5M3 32zk12 2.ati.2 Tilt 759f103’” 36fl3”’ 18flS” lO.of12.0” CB 941f137 4tktlt” 27fll” 1.210.9” Tin&?dasvsR%& ‘~rn”~c31 *paav ALsrs c&l/ok *mar “.@O? “‘@&x7? -kS ots showed detxassad global HRV (lower SD1 with impaired vagal control (lower MSD. higher LF/F1F during CEi,. F?s with.bulbar signs had Ilk not diirent from pt

Decreased Heart Rate Variability in Patients With Chronic Obstructive Pulmonary Disease

free from bulbar signs. One year later. 16 pts wire died: their SD had bean lower than survived pts SD. both at rest (28k12 vs 37s msec, p<O.O5) and during passive otthcstatiom (2Oi7 vs 29f13 msec. p(O.05). Bulbar signs did not predict survival in this population. Four pts died from witnessed (and 2 unwitnessed) sudden death: their previous 24 hour ambulatory eledrocardiograrn had shown deeply depressed HRV with HF component virtually absent night and day. Thus. HRV seems to be depressed in ASL pts. particularly in sub@% with poor prognosis.