Measuring baroreflex sensitivity from the gain function between arterial pressure and heart period

We tested an innovative approach for estimating baroreflex sensitivity (BRS) from the gain function between spontaneous oscillations of systolic arterial pressure (SAP) and heart period (HP). The major goal was to assess the practical implications of abandoning the classical coherence criterion (> or =0.5) as regards measurability of BRS, and agreement with values of BRS obtained using the phenylephrine test (Phe-BRS). We studied 19 normal subjects, 44 patients with a history of previous myocardial infarction (MI) and 45 patients with chronic heart failure (CHF). The experimental protocol included recording of SAP and HP for 10 min of supine rest, and evaluation of Phe-BRS. From resting SAP and HP, the gain and coherence functions were computed. The new BRS index was obtained in all subjects by averaging the gain function over the whole low-frequency band (0.04-0.15 Hz) (whole-band average BRS, WBA-BRS). WBA-BRS was 7.4 (5.8-10.8) ms/mmHg [median (25th-75th percentile)] in normal controls, 3.1 (1.4-5.4) ms/mmHg in MI patients (P<0.001 compared with normals) and 5.0 (3.2-6.9) ms/mmHg in CHF patients (P<0.01 compared with normals). Using the coherence criterion, BRS could be measured in only 43% and 49% of MI and CHF patients respectively, and the proportion of the low-frequency band contributing to the measurement was 21% (14-47%) and 29% (16-35%) respectively. The correlation between WBA-BRS and Phe-BRS was 0.47, 0.63 and 0.36 in the normal, MI and CHF groups respectively (all P<0.001). The relative bias of WBA-BRS was -5.2 ms/mmHg (P<0.001) in normals, -1.4 ms/mmHg (P=0.004) in MI patients and -1.0 ms/mmHg (P=0.11) in CHF patients. The limits of agreement were -13 to 2.6, -7.4 to 4.6 and -9.3 to 7.3 ms/mmHg in the normal, MI and CHF groups respectively. Thus the WBA-BRS method standardizes the computation of BRS among subjects, and dramatically increases its measurability in subjects with pathology compared with the classical spectral technique based on the coherence criterion. Compared with Phe-BRS, WBA-BRS tends to give negatively biased results. The correlation and the magnitude of the limits of agreement between the two methods are similar to those observed previously using coherence-based spectral methods.     

Comparison between spectral analysis and the phenylephrine method for the assessment of baroreflex sensitivity in chronic heart failure.

Baroreflex sensitivity assessed by means of the phenylephrine test plays a prognostic role in patients with previous myocardial infarction, but the need for drug injection limits the use of this technique. Recently, several non-invasive methods based on spectral analysis of systolic arterial pressure and heart period have been proposed, but their agreement with the phenylephrine test has not been investigated in patients with heart failure. The two methods (phenylephrine test and spectral analysis) were compared in a group of 49 patients with chronic congestive heart failure both at rest and during controlled breathing. The linear correlation and the limits of agreement between the phenylephrine test slope and the alpha-index [alpha(c); corrected by the coherence function between the interbeat interval (RR interval) and systolic arterial pressure] were evaluated. Only 16 patients had a measurable alpha-index at rest in both the low-frequency (LF) and high-frequency (HF) bands; the alpha(c)-index allowed measurements in all patients. It correlated moderately with the phenylephrine test slope at rest (r=0. 71 and P<0.001 in LF; r=0.57 and P<0.001 in HF) and during controlled breathing (r=0.51 and P<0.001 in LF; r=0.63 and P<0.001 in HF). Multivariate regression analysis showed that only alpha(c)LF during rest and alpha(c)HF during controlled breathing contributed significantly to baroreflex gain estimation. However, the agreement between methods was weak; the normalized limits of agreement and bias were -162 to 243% (0.46 ms/mmHg) for alpha(c)LF and -185 to 151% (-0.99 ms/mmHg) for alpha(c)HF. Thus the comparison between baroreflex sensitivity measurements obtained by the phenylephrine test and spectral analysis showed a moderate correlation between the two methods; however, despite the linear association, a consistent lack of agreement between the two techniques was found. Because both systematic and random factors contribute to the difference, these two techniques cannot be considered as alternatives for the assessment of heart failure.     

Cardiovascular autonomic control in endurance-trained and sedentary young women

This study aimed to investigate whether endurance-trained (ET) female athletes demonstrate differences in cardiovascular autonomic control compared with sedentary controls. Eighteen healthy eumenorrhoeic subjects, nine trained (22.4 +/- 3 years) and nine sedentary (21.0 +/- 1 years), volunteered for the study. Heart rate variability (HRV) and cardiovagal baroreflex sensitivity (BRS) measures were adopted to assess cardiac autonomic control. HRV was recorded for 30 min under both controlled (0.25 Hz) and spontaneous breathing conditions. Cardiovagal BRS was assessed using the Valsalva manoeuvre. Analysis of the HRV showed a longer R-R interval (1089 +/- 114 ms versus 865 +/- 100 ms; P<0.001) in the trained subject but only in the spontaneous breathing condition. Conversely, athletes exhibited higher normalized low frequency (LFnu, 44.2 +/- 8.5% versus 29.5 +/- 6.8%; P<0.001) and lower normalized high frequency (HFnu, 55.8 +/- 8.5% versus 69.9 +/- 7.7%; P<0.01) only during the controlled breathing condition, consequently the LF/HF ratio was also higher in the trained group in the same condition (0.83 +/- 0.3 versus 0.47 +/- 0.1, P<0.01). BRS was significantly lower in the ET group (7.95 +/- 4.0 ms mmHg(-1) versus 13.00 +/- 4.4 ms mmHg(-1), P<0.05). Further studies are necessary to elucidate the potential role of training and altered hormonal profile in the genesis of the observed differences in cardiovascular autonomic control between highly trained and sedentary control female subjects.     

Reproducibility of methods for assessing baroreflex sensitivity in normal controls and in patients with chronic heart failure.

Baroreflex sensitivity (BRS) conveys useful prognostic information in patients with heart disease, yet methods for its quantification suffer from poor reproducibility and test failure in some patients with heart failure. We set out to compare the short-term reproducibility and success rate of four different methods of assessing BRS in normal subjects and patients with chronic heart failure (CHF). A total of 31 patients with CHF and 18 normal controls underwent BRS testing using four techniques: (1) bolus phenylephrine (BRS(Phe)), (2) alpha-index in both low- and high-frequency bands (BRS(alphaLF) and BRS(alphaHF) respectively), (3) the sequence method (BRS(Seq)), and (4) a new 0.1 Hz controlled-breathing, time-domain analysis method (BRS(Cbr)). Each subject underwent two test episodes with each method on the same day. The average values for BRS in patients and controls respectively were: BRS(Phe), 4.4 (+/-4.4) ms/mmHg and 19.8 (+/-11.5) ms/mmHg; BRS(alphaLF), 5.6 (+/-4.1) ms/mmHg and 15.4 (+/-5.0) ms/mmHg; BRS(alphaHF), 7.1 (+/-7.0) ms/mmHg and 25.1 (+/-8.3) ms/mmHg; BRS(Seq), 7.7 (+/-6.3) ms/mmHg and 22.5 (+/-8.4) ms/mmHg; BRS(Cbr), 6.6 (+/-5.9) ms/mmHg and 22.8 (+/-10.8) ms/mmHg. The coefficients of variation (S.D. of the difference in repeated values divided by mean) in patients and controls respectively were: BRS(Phe), 85.6% and 52.2%; BRS(alphaLF), 65.9% and 33.7%; BRS(alphaHF), 99.7% and 52. 1%; BRS(Seq), 30.7% and 40.4%; BRS(Cbr), 30.7% and 19.6%. The numbers of test failures in patients were: BRS(Phen), 15; BRS(alphaLF), 7; BRS(alphaHF), 5; BRS(Seq), 14; BRS(Cbr), 1. Of the four techniques assessed for measuring BRS, the controlled breathing time-domain method yielded the best reproducibility and lowest failure rate in controls and in patients with CHF.     

Detection of elevated pulmonary capillary wedge pressure in elderly patients with various cardiac disorders by the Valsalva manoeuvre

In the present study, we assessed whether elevated (> or =15 mmHg) PCWP (pulmonary capillary wedge pressure) can be detected using the blood pressure response to the Valsalva manoeuvre in a group of elderly patients with various cardiac disorders, including atrial fibrillation and valvular heart disease, and healthy elderly controls. The Valsalva manoeuvre was performed in 93 patients (71+/-4 years) and 28 healthy controls (70+/-4 years) undergoing right-sided cardiac catheterization. Blood pressure was measured non-invasively with Finapres. PPR (pulse pressure ratio), the ratio of minimum pulse pressure during phase 2 and maximum pulse pressure during phase 1 of the Valsalva manoeuvre, was correlated with PCWP (r=0.63, P<0.001). The area under the receiver operator characteristic curve of PPR with elevated PCWP was 0.85 (P<0.001). For PPR=0.62, sensitivity for elevated PCWP was 80%, specificity was 79%, positive predictive value was 76% and negative predictive value was 83%. Correlation of PPR with PCWP and the ability of PPR to detect elevated PCWP was present in atrial fibrillation, heart failure and valvular heart disease. In conclusion, PPR is a sensitive and specific instrument to diagnose elevated PCWP non-invasively in a large group of elderly patients with various cardiac disorders. This makes the Valsalva manoeuvre a useful non-invasive tool for diagnosing heart failure, applicable in elderly patients with common cardiac disorders, such as atrial fibrillation and valvular heart disease.     

Baroreflex Sensitivity and Heart Rate Variability in Coronary Disease Compared to Dilated Cardiomyopathy

This study was designed to compare baroreceptor sensitivity and heart rate variability as measures of cardiac autonomic tone in patients with coronary disease (CAD, n = 49) and idiopathic dilated Cardiomyopathy (IDC, n = 130). Time domain heart rate variability, including SDNN, SDANN, and pNN50, was determined during 24-hour Holter ECG. Baroreflex sensitivity was analyzed nonivasively using the phenylephrine method. Baroreflex sensitivity and heart rate variability were comparable between patients with CAD versus IDC (baroreflex sensitivity: 6.1 ± 3 vs 6.9 ± 5 ms/mmHg; SDNN: 97 ± 40 vs 114 ± 41 ms; SDANN: 83 ± 33 vs 99 ± 41 ms; pNNSO: 3.9 ± 4 vs 9.6 ± 13 ms, P = NS for all comparisons). Likewise, a subgroup analysis of patients with a left ventricular ejection fraction (LVEF) ≤ 30% showed no significant difference in baroreceptor sensitivity and heart rate variability between IDC and CAD patients. Patients with CAD and an LVEF > 30% had a decreased heart rate variability but not a decreased baroreflex sensitivity compared to patients with IDC and LVEF > 30 % (baroreflex sensitivity: 6.4 ± 4 vs 8.3 ± 6 ms/mmHg, P = NS; SDNN: 98 ± 19 vs 128 ± 42 ms, P < 0.05; SDANN: 86 ± 21 vs 112 ± 43 ms, P < 0.05; pNN50: 4.2 ± 3 vs 12.3 ± 8 ms, P < 0.05). Patients with a markedly depressed LVEF show comparable alterations in cardiac autonomic tone whether they have CAD or IDC. Patients with CAD and preserved LV function, however, have a decreased heart rate variability compared to patients with IDC and preserved LV function. The prognostic significance of these findings will be determined prospectively in a large patient cohort at our institution.     

In aged men,central vessel transmural pressure is reduced by brief Valsalva manoeuvre during strength exercise

A brief Valsalva manoeuvre, lasting 2–3 s, performed by young healthy men during strength exercise reduces transmural pressure acting on intrathoracic arteries. In this study, we sought to verify this finding in older men. Twenty normotensive, prehypertensive and moderately hypertensive otherwise healthy men 46–69 years old performed knee extensions combined with inspiration or with brief Valsalva manoeuvre performed at 10, 20 and 40 mmHg mouth pressure. Same respiratory manoeuvres were also performed at rest. Non‐invasively measured blood pressure, knee angle, respiratory airflow and mouth pressure were continuously registered. In comparison to inspiration, estimated transmural pressure acting on thoracic arteries changed slightly and insignificantly during brief Valsalva manoeuvre at 10 and 20 mmHg mouth pressure. At 40 mmHg mouth pressure, transmural pressure declined at rest (?8·8 ± 11·4 mmHg) and during knee extension (?12·1 ± 11·9 mmHg). This decline ensued, as peak systolic pressure increase caused by this manoeuvre, was distinctly <40 mmHg. Only a main effect of mouth pressure was revealed (P<0·001) and neither exercise nor interaction between these factors, what suggests that transmural pressure decline, depended mainly on intrathoracic pressure developed during brief Valsalva manoeuvre. Resting blood pressure did not influence the effect of brief Valsalva manoeuvre on transmural pressure.     

Advanced analysis of spontaneous baroreflex sensitivity, blood pressure and heart rate variability in patients with dilated cardiomyopathy

Baroreflex sensitivity (BRS) is an important parameter in the classification of patients with reduced left ventricular function. This study aimed at investigating BRS in patients with dilated cardiomyopathy (DCM) and in healthy subjects (controls), as well as comparing the values of BRS parameters with parameters of heart rate variability (HRV) and blood pressure variability (BPV). ECG, continuous blood pressure and respiration curves were recorded for 30 min in 27 DCM patients and 27 control subjects. The Dual Sequence Method (DSM) includes the analysis of spontaneous fluctuations in systolic blood pressure and the corresponding beat-to-beat intervals of heart rate to estimate bradycardic, opposite tachycardic and delayed baroreflex fluctuations. The number of systolic blood pressure/beat-to-beat interval fluctuations in DCM patients was reduced in comparison with controls (DCM patients: male, 154.4+/-93.9 ms/mmHg; female, 93.7+/-40.5 ms/mmHg; controls: male, 245.5+/-112.9 ms/mmHg; female, 150.6+/-55.8 ms/mmHg, P<0.05). The average slope in DCM patients was lower than in controls (DCM, 5.3+/-1.9 ms/mmHg; controls, 8.0+/-5.4 ms/mmHg; P<0.05). Discriminant function analysis showed that, in the synchronous range of the standard sequence method, the DCM and control groups could be discriminated to only 76% accuracy, whereas the DSM gave an improved accuracy of 84%. The combination of six parameters of HRV, BPV and DSM gives an accuracy of classification of 96%, whereas six parameters of HRV and BPV could separate the two groups to only 88% accuracy. Thus the DSM leads to an improved characterization of autonomous regulation in order to differentiate between DCM patients and healthy subjects. BRS in DCM patients is significantly reduced and apparently less effective.     

Arrhythmia Risk Prediction in Idiopathic Dilated Cardiomyopathy Based on Heart Rate Variability and Baroreflex Sensitivity

This study examined the relation between heart rate variability (HRV) and baroreflex sensitivity (BRS) and subsequent major arrhythmic events (MAE), defined as sustained VT, VF or sudden death, in 263 patients with idiopathic dilated cardiomyopathy (IDC) in sinus rhythm. The predefined measure of HRV was the standard deviation of all normal-to-normal RR intervals (SDNN) on baseline 24-hour ambulatory ECG. BRS was determined by the phenylephrine method. Over 52 ± 21 months of follow-up, MAE occurred in 38 patients (14%). SDNN at baseline 24-hour ambulatory ECG (106 ± 46 vs 109 ± 45, ns) and BRS (7.9 ± 5.5 vs 7.7 ± 5.3 ms/mmHg, ns) were both similar in patients with versus without MAE during follow-up. In contrast, left ventricular ejection fraction was significantly lower in patients with versus without MAE (24%± 7% vs 31%± 10%, P < 0.019. Conclusions: Neither HRV nor BRS predicted MAE in patients with IDC.     

Time course of effects of cardiac resynchronization therapy in chronic heart failure: benefits in patients with preserved exercise capacity

Objectives: To assess in patients with chronic heart failure the effect of cardiac resynchronization therapy (CRT) over 12 months' follow-up the time course of the changes in functional and neurohormonal indices and to identify responders to CRT.
Methods: Eighty-nine patients (74.1 ± 1 years, left ventricular ejection fraction [LVEF] < 35%), QRS complex duration >150 ms, in stable New York Heart Association (NYHA) class III or IV on optimal medical treatment were prospectively randomized either in a control (n = 45) or CRT (n = 44) group and underwent clinical evaluation, cardiopulmonary exercise testing (CPET), 2D-Echo, heart rate variability (HRV), carotid baroreflex (BRS), and BNP assessments before and at 6- and 12-month follow-up.
Results: In the CRT group, improvement of cardiac indices and BNP concentration were evident at medium term (over 6 months) follow-up, and these changes persisted on a longer term (12 months) (all P < 0.05). Instead CPET indices and NYHA class improved after 12 months associated with restoration of HRV and BRS (all P < 0.05). We identified 26 responders to CRT according to changes in LVEF and diameters. Responders presented less depressed hemodynamic (LVEF 25 ± 1.0 vs 22 ± 0.1%), functional (peak VO₂ 10.2 ± 0.2 vs 6.9 ± 0.3 ml/kg/min), and neurohormonal indices (HRV 203.6 ± 15.7 vs 147.6 ± 10.ms, BRS 4.9 ± 0.2 vs 3.6 ± 0.3 ms/mmHg) (all P < 0.05). In the multivariate analysis, peak VO₂ was the strongest predictor of responders.
Conclusions: Improvement in functional status is associated with restoration of neurohormonal reflex control at medium term. Less depressed functional status (peak VO₂) was the strongest predictor of responders to CRT.     

Discrepancies between cardiovascular magnetic resonance and Doppler echocardiography in the measurement of transvalvular gradient in aortic stenosis: the effect of flow vorticity

Background

Valve effective orifice area EOA and transvalvular mean pressure gradient (MPG) are the most frequently used parameters to assess aortic stenosis (AS) severity. However, MPG measured by cardiovascular magnetic resonance (CMR) may differ from the one measured by transthoracic Doppler-echocardiography (TTE). The objectives of this study were: 1) to identify the factors responsible for the MPG measurement discrepancies by CMR versus TTE in AS patients; 2) to investigate the effect of flow vorticity on AS severity assessment by CMR; and 3) to evaluate two models reconciling MPG discrepancies between CMR/TTE measurements.

Methods

Eight healthy subjects and 60 patients with AS underwent TTE and CMR. Strouhal number (St), energy loss (EL), and vorticity were computed from CMR. Two correction models were evaluated: 1) based on the Gorlin equation (MPG_CMR-Gorlin); 2) based on a multivariate regression model (MPG_{CMR-Predicted}).

Results

MPG_CMR underestimated MPG_TTE (bias = −6.5 mmHg, limits of agreement from −18.3 to 5.2 mmHg). On multivariate regression analysis, St (p = 0.002), EL (p = 0.001), and mean systolic vorticity (p < 0.001) were independently associated with larger MPG discrepancies between CMR and TTE. MPG_CMR-Gorlin and MPG_TTE correlation and agreement were r = 0.7; bias = −2.8 mmHg, limits of agreement from −18.4 to 12.9 mmHg. MPG_{CMR-Predicted} model showed better correlation and agreement with MPG_TTE (r = 0.82; bias = 0.5 mmHg, limits of agreement from −9.1 to 10.2 mmHg) than measured MPG_CMR and MPG_CMR-Gorlin.

Conclusion

Flow vorticity is one of the main factors responsible for MPG discrepancies between CMR and TTE.     

Arterial baroreflex function determines the survival time in lipopolysaccharide-induced shock in rats

Lipopolysaccharide (LPS) mimics many of the effects of septic shock. LPS-induced death has been attributed to systemic hypotension, hyporeactiveness to vasoconstrictors, metabolic acidosis, and organ damage. However, there is no research directed to the involvement of the baroreflex sensitivity (BRS) in LPS-induced death. The purpose of this study was to evaluate the effect of BRS on the survival time after lethal LPS challenge. Four groups of rats were used. Each rat received an equivalent dose of intravenous LPS (50 mg/kg). It was found that the anesthetized sinoaortic-denervated (SAD) rats (representative of the lowest BRS, BRS = 0.022 +/- 0.015 ms/mmHg) survived the shortest time (36 +/- 11.1 min). The conscious SAD rats (BRS = 0.198 +/- 0.035 ms/mmHg) and the anesthetized sham-operated rats (BRS = 0.304 +/- 0.072 ms/mmHg) were alive a relatively long time (101 +/- 11.5 min and 110 +/- 12.4 min, respectively). The conscious sham-operated rats (BRS = 0.943 +/- 0.097 ms/mmHg) survived the longest time (148 +/- 6.5 min). These results demonstrated that arterial baroreflex function determined the survival time in the LPS-induced lethal shock.     

Effects of Aging on Reflex Autonomic Nervous Response Induced by Orthostatic Maneuvers

Background: Baroreflex sensitivity (BRS), exercise pressor reflex (EPR), and aging influence the autonomic nervous response associated with orthostatic maneuvers. Standing significantly increases heart rate (HR), with an initial increase (1.ΔHR) due to EPR and a secondary, more gradual increase (2.ΔHR) due to BRS. HR then decreases (3.ΔHR), which is also attributable to BRS. Thus far, however, few data are available regarding the interdependence of these variables.
Methods and Results: Ninety-five healthy volunteers (mean age 37 ± 11 years, range 10–70 years; 50 women) underwent continuous noninvasive measurements of beat-to-beat blood pressure, HR, and spontaneous BRS in the supine (10 minutes) and upright (10 minutes) positions. After tilt, 1.ΔHR, 2.ΔHR, and 3.ΔHR were calculated from the HR recording. From the 1^st to the 6^th decade BRS, 2.ΔHR and 3.ΔHR decreased with normal aging ([BRS 11.88 ± 7.97 ms/mmHg to 1.81 ms/mmHg, P = 0.006], 2.ΔHR [16.75 ± 3.40 beats to 5.33 ± 2.52 beats, P = 0.002], 3.ΔHR [52.25 ± 5.91 beats to 11.33 ± 4.04 beats, P < 0.001]). However, no such association was noted between 1.ΔHR and age (21.25 ± 9.35 beats to 12.00 ± 7.21 beats, ns). BRS while standing was correlated with 1.ΔHR (r = 0.432, P < 0.001).
Conclusions: EPR, in contrast to BRS, was not significantly influenced by normal aging. Furthermore, not only was BRS influenced by EPR, as is generally acknowledged, but EPR and BRS were interrelated. These observations offer new insights into the complex interactions of orthostasis-induced physiological autonomic reflexes associated with normal aging.     

Role of nitric oxide and oxidative stress in baroreceptor dysfunction in patients with chronic heart failure

Abnormalities of autonomic control of the cardiovascular system are seen in chronic heart failure (CHF) and confer a poor prognosis. Nitric oxide appears to be important in the regulation of baroreflex control in health and in disease states. The antioxidant vitamin C increases nitric oxide bioavailability in CHF. We evaluated the effects of vitamin C on baroreceptor sensitivity (BRS) by sequence analysis in 100 CHF patients and 44 control subjects. Groups of 55 CHF patients and 22 controls were randomly allocated to receive a single intravenous injection of vitamin C (2 g) or placebo. In addition, 45 CHF patients were randomly allocated to receive a 4-week course of oral vitamin C (4 g/day) or placebo. An age-related reference range for BRS was developed in 22 healthy controls matched for age and gender to the CHF group. BRS was significantly impaired in the CHF group compared with age-matched older controls and young controls (6.9 +/- 3.1, 12.5 +/- 4.9 and 21.7 +/- 9.1 mmHg/ms respectively; P < 0.001 between groups). Intravenous vitamin C acutely improved BRS in CHF patients by 24% (by 1.8 +/- 4.1 mmHg/ms; P < 0.05), but not in controls. There was no improvement in BRS in CHF patients given chronic oral vitamin C. Thus acute intravenous, but not chronic oral, vitamin C improved BRS in CHF patients. There was no effect of intravenous vitamin C in healthy subjects, suggesting that the mechanism was either by free radical scavenging or due to central effects.     

RR Variability and Baroreflex Sensitivity in Patients with Ventricular Tachycardia Associated with Normal Heart and Patients with Ischemic Heart Disease

Recent studies have suggested that disordered autonomic function, particularly the loss of protective vagal reflexes are associated with an increased incidence of arrhythmic deaths following myocardial infarction (MI). Heart rate variability (HRV) and baroreflex sensitivity (BRS) are measures of myocardial autonomic function and predict arrhythmic deaths post-Mi. Patients with ventricular tachycardia associated with a “normal heart” frequently have exercise-induced arrhythmia suggesting that the autonomic nervous system is important in the genesis of this form of ventricular tachycardia (VT). This study examines HRV and BRS in patients with VT associated with a “normal heart” and compares these values to patients post-Mi with and without evidence of arrhythmia. Twenty patients with VT associated with a “normal heart,” 16 patients with MI but without arrhythmia on follow-up, and 11 patients with MI and VT on follow-up were studied. HRV was measured from 24-hour Holter recordings and BRS was measured from plots of change in systolic blood pressure versus change in heart rate following an intravenous injection of 0.4–0.6 mg phenylephrine. HRV was significantly higher in the patients with VT associated with a normal heart (34.2 ± 10.8 msec) compared to the patients post-Mi, without (23.7 ± 6.7 msec) and with (14.8 ± 3.8 msec) arrhythmia (F = 9.2, P < 0.001) and these differences were unaffected by adjustment for age. Baroreflex sensitivity was also higher in patients with VT associated with a “normal heart” (10.1 ± 6.8 msec/mmHg) compared to patients post-Mi, without (6.1 ± 3.2 msec/mmHg) and with 3.2 ± 3.1 msec/mmHg) arrhythmia, (F = 7.2, P < 0.02), though statistical significance was lost after adjustment for age (F = 1.2, P = 0.3). We conclude that patients with VT associated with “normal hearts” have HRV and BRS that is higher than in patients post-MI. Alterations of autonomic tone are, therefore, unlikely to be important in VT associated with a “normal heart,” whereas these appear to be important in patients with arrhythmic events post-MI.     

Hand-carried echocardiography for assessment of left ventricular filling and ejection fraction in the surgical intensive care unit

Purpose

To better define the reliability of left ventricular ejection fraction (LVEF) and left ventricular filling, as determined by either hand-carried ultrasound (HCU) or formal transthoracic echocardiography (TTE), in the critically ill surgical patient.

Materials and Methods

Prospective cross-sectional study of 80 surgical intensive care unit patients with concomitant (<30 minutes apart) formal TTE and clinician-performed cardiac HCU. Visual estimates of LVEF and left ventricular filling (“underfilled” vs “normally filled”) were recorded, both by clinicians performing HCU and fellowship-trained echocardiographers.

Results

Bland-Altman plot analysis of LVEF estimates revealed good interobserver agreement between HCU and formal TTE (% LVEF mean bias, −2.2; with 95% limits of agreement, ±22.1). This was similar to agreement between independent echocardiography observers (% LVEF mean bias, 1.3; with 95% limits of agreement, ±21.0). However, assessments of left ventricular filling demonstrated only fair to moderate interobserver agreement (κ = 0.22-0.40). Of note, a greater percentage of the 5 standard acoustic windows were obtainable using formal TTE (72% vs 56%).

Conclusions

Formal TTE offers no advantage over HCU for determination of LVEF in critically ill surgical patients, even though the former allows for a more complete examination. However, estimations of left ventricular filling only demonstrate fair to moderate interrater agreement and thus should be interpreted with care when used as markers of volume responsiveness.     

An algorithm for real-time, continuous evaluation of left ventricular mechanics by single-beat estimation of arterial and ventricular elastance

We describe a computer algorithm that allows continuous, real-timeevaluation of ventricular elastance (Ees), arterial elastance (Ea), and theircoupling ratio in a clinical setting. In the conventional pressure-volumeanalysis of left ventricular (LV) contractility, invasive methods of volumedetermination and a significant, rapid preload reduction are required togenerate Ees. With the help of automated border detection by transesophagealechocardiography, and a technique of estimating peak LVisovolumic pressure, Ea and Ees were determined from a single cardiac beatwithout the need for preload reduction. A comparison of results obtained bya conventional approach and the new algorithm technique, showed goodcorrelation for Ea (r = 0.86, p < 0.001) and Ees(r = 0.74, p = 0.001). Bias analysis showed a bias (d) of1.47 mmHg/cm2 for Ea with a standard deviation (SD) of 7.03mmHg/cm 2, and upper (d+2SD) and lower (d–2SD)limits of agreement of 15.25 mmHg/cm2 and –12.31mmHg/cm2, respectively. Bias analysis showed a bias of–1.42 mmHg/cm2 for Ees with a SD of 4.88mmHg/cm2, and limits of agreement of 8.15mmHg/cm2 and –10.98 mmHg/cm2. Thealgorithms stability to artifacts was also analyzed by comparingmagnitudes of residuals of Ea and Ees from source signals with and withoutnoise. With Ea differing by an average of 1.036 mmHg/cm2 andEes differing by an average of 0.836 mmHg/cm2, the algorithmwas found to be stable to artifacts in the source signals.     

Evaluation of the 5-French saline paediatric gastric tonometer

Objective: To evaluate the paediatric 5-French (Fr) saline-filled gastric tonometer. Design: (a) In vitro comparison of saline bath reference pCO₂ with tonometric pCO₂ measured by normal saline-filled and phosphate-buffered saline-filled 5-Fr tonometers, and by a recirculating gas tonometer. ( b) In vivo comparison of gastric intramucosal pCO₂i, measured by normal saline-filled 5-Fr tonometer (NST) and simultaneously by recirculating gas tonometer (RGT) in ten paediatric intensive care patients. (c) In vivo comparison of pCO₂i measured simultaneously by 2 NST 5-Fr tonometers, before and after enteral feeding, in ten paediatric intensive care patients. Measurements and main results: (a) Twenty consecutive measurements of pCO₂ were made at constant reference pCO₂ of 19, 38, 56, and 75 mmHg (2.5, 5.0, 7.5, and 10.0 kPa), respectively. The NST tonometer underestimated reference pCO₂ by mean bias (limits of agreement) of 58 % (20 %), and the phosphate-buffered saline-filled tonometer by 6 % (26 %). The RGT showed mean bias 5.7 % with narrow limits of agreement (1.5 %). (b) In 50 paired (NST vs. RGT) in vivo measurements over pCO₂i range 23–73 mmHg (3.0–9.7 kPa), the NST underestimated RGT pCO₂i by a mean bias of 10 mmHg (1.3 kPa), with limits of agreement + /–10 mmHg (1.5 kPa). This resulted in NST consistently overestimating pHi and underestimating pCO₂ gap (both P < 0.001). (c) One hundred simultaneous paired NST measurements were assessed (50 without, and 50 with enteral feeding). The mean biases (limits of agreement) were identical in the fasted and fed states 0.4 ± 6 mmHg, with no difference between the fed and fasting states (P = 0.7). Conclusions: There are inherent problems in the methodology of saline tonometry, which adversely affect the accuracy and reliability of the 5-Fr paediatric gastric tonometer in comparison to recirculating gas tonometry. Received: 4 October 1999/Final revision received: 20 February 2000/Accepted: 25 February 2000     

Normal values of pulmonary capillary wedge pressure and the blood pressure response to the Valsalva manoeuvre in healthy elderly subjects

The blood pressure response to the Valsalva manoeuvre is related to pulmonary capillary wedge pressure (PCWP) and can be used to diagnose heart failure. However, this has never been studied specifically in the elderly, in whom the prevalence of heart failure is highest. Furthermore, normal values of the Valsalva manoeuvre are lacking. We aimed to obtain normal values of PCWP and the blood pressure response to the Valsalva manoeuvre in elderly subjects. Therefore, 28 healthy subjects, aged 70 +/- 4 years, performed Valsalva manoeuvres before and after anti-G garment inflation, which was used for temporary increase of PCWP. Before inflation, PCWP was 9.8 +/- 1.9 mmHg in supine and 8.9 +/- 2.1 in semi-recumbent position. From the blood pressure response, measured with Finapres, the systolic blood pressure ratio (SBPR), pulse pressure ratio (PPR), stroke volume ratio (SVR) and heart rate ratio (HRR) were calculated. In supine position, SBPR was 0.76 +/- 0.11, PPR 0.51 +/- 0.16, SVR 0.42 +/- 0.11, and HRR 1.17 +/- 0.12. Semi-recumbently, SBPR was 0.74 +/- 0.10, PPR 0.46 +/- 0.14, SVR 0.41 +/- 0.10, and HRR 1.24 +/- 0.23. After inflation of the anti-G garment, the areas under the Receiver Operator Characteristics curves of SBPR, PPR and SVR for elevated (> or = 15 mmHg) PCWP were >0.85 in supine position. In conclusion, this is the first study to obtain normal values of the blood pressure response to the Valsalva manoeuvre and PCWP in healthy elderly subjects, which is essential for the interpretation of patient data. The Valsalva manoeuvre showed significant discriminatory power in the detection of elevated PCWP, which underscores its potential in the non-invasive diagnosis of heart failure.     

Noninvasive Arrhythmia Risk Stratification in Idiopathic Dilated Cardiomyopathy: Design and First Results of the Marburg Cardiomyopathy Study

The Marburg Cardiomyopathy Study (MACAS) is a prospective, observational study designed to determine the value of the following potential noninvasive arrhythmia risk predictors in at least 200 patients with idiopathic dilated Cardiomyopathy (IDC) over a 5-year follow-up period: NYHA-class, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter, left bundle branch block and atrial fibrillation on ECG, QT/JT dispersion on 12-lead ECG, signal-averaged ECG, ventricular arrhythmias and heart rate variability (HRV) on 24-hour Hotter ECG, baroreflex sensitivity, and microvolt T wave alternans during exercise. This article describes the findings among the first 159 patients with IDCs enrolled in MACAS until May 1998 (40 women, 119 men;age:49 ± 12 years; LVEF: 32 ± 10%). Twenty-nine patients (18%) had atrial fibrillation and 130 patients (82%) were in sinus rhythm. Patients with sinus rhythm were further stratified according to LVEF < 30% (n = 54) versus LVEF ≥ 50% (n = 76). Compared to patients with LVEF ≥ 30%, patients with LVEF < 30% more often had left bundle branch block (43% vs 25%, P < 0.05), nonsustained VT (44% vs 22%, P < 0.05), decreased HRV (SDNN: 95 ± 39 vs 128 ± 42 ms, P < 0.01), decreased baroreflex sensitivity (5.6 ± 4 vs 8.3 ± 6 ms/mmHg, P < 0.01), and T wave alternans (59% vs 37%, P < 0.05). The prognostic significance of these findings will be determined by multivariate Cox analysis at the end of a 5-year follow-up. Primary endpoints in MACAS are overall mortality and arrhythmic events (i.e., sustained VT or VF, or sudden cardiac death).