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G D Pinna

Publications and source records attributed to G D Pinna.

At least 19 recordsLinked to original sources
PubMed2002

New criteria for estimating baroreflex sensitivity using the transfer function method.

Computer simulations were carried out to appraise three new criteria for the estimation of baroreflex sensitivity (BRS) using the transfer function method. The major goal was to identify a computation procedure able to overcome the intrinsic limitations of the classical coherence criterion. Four representative shapes of the gain function and three different average gains (2, 5 and 8 ms(mmHg)(-1) in the low-frequency (LF) band (0.04-0.15Hz) were considered. The signal-to-noise ratio was made to vary so that the peak coherence in the LF band changed from 0.15 to 0.9. All simulation parameters were derived from previous observations in healthy subjects and heart disease patients. The error of the estimated gain function was obtained from its confidence interval. BRS was computed as average gain in the LF band: (a) including in the average only those points having error < or = threshold (criterion 1, C1); (b) calculating the mean error in the band and accepting BRS measurements only when this error was < or = threshold (criterion 2, C2); (c) including in the average all points, regardless of the error (criterion 3, C3). The three criteria were compared in terms of measurability (percentage of measured BRS) and accuracy (bias and SD of BRS). Using C1 and C2, measurability dropped to 10% when the peak coherence in the LF band decreased, respectively, to 0.18-0.41 and to 0.26-0.53, depending on the shape and strength of the gain. In this condition (lower bound of measurability), worst bias and SD (average gain: 8 ms(mmHg)(-1)) were, respectively, 0.8 ms(mmHg)(-1) and 3.3ms(mmHg)(-1) (C1), and 0.1 ms(mmHg)(-1) and 1.0 ms(mmHg)(-1) (C2). C3, by definition, always ensured 100% measurability and showed bias and SD comparable with, or even lower than, C1 and C2, within the common range of measurable BRS. In the extreme condition of 0.15 coherence, bias and SD were, respectively, 1.7 ms(mmHg)(-1) and 2.3ms(mmHg)(-1) (average gain: 8ms(mmHg)(-1)). Hence, error checking (C1 and C2) dramatically reduced measurability and did not improve accuracy of BRS measurements compared with performing no error check (C3). In conditions of low signal-to-noise ratio and/or impaired baroreflex gain, leading to markedly reduced coherence, the simple average of the gain function in the LF band allows BRS to be estimated with accuracy adequate for clinical purposes.

Baroreflex↗
PubMed2002

RESP-24: a computer program for the investigation of 24-h breathing abnormalities in heart failure patients.

In this paper, we describe a computer program (RESP-24) specifically devised to assess the prevalence and characteristics of breathing disorders in ambulant chronic heart failure patients during the overall 24 h period. The system works on a single channel respiratory signal (RS) recorded through a Holter-like portable device. In the pre-processing stage RESP-24 removes noise, baseline drift and motion artefacts from the RS using a non-linear filter, enhances respiratory frequency components through high-pass filtering and derives an instantaneous tidal volume (ITV) signal. The core processing is devoted to the identification and classification of the breathing pattern into periodic breathing (PB), normal breathing or non-classifiable breathing using a 60 s segmentation, and to the identification and estimation of apnea and hypopnea events. Sustained episodes of PB are detected by cross analysis of both the spectral content and time behavior of the ITV signal. User-friendly interactive facilities allow all the results of the automatic analysis procedure to be edited. The final report provides a set of standard and non-standard parameters quantifying breathing abnormalities during the 24 h period, the night-time and the day-time, including the apnea/hypopnea index, the apnea index, the total time spent in apnea or in hypopnea and the prevalence of non-apneic and apneic PB. The accuracy of these measurements was appraised on a data set of 14 recordings, by comparing them with those provided by a trained analyst. The mean and standard deviation of the error of the automatic procedure were below respectively 6 and 8% of the reference value for all parameters considered and the mean total classification accuracy was 92%. In most cases, the individual error was <12%. We conclude that measurements provided automatically by the RESP-24 software are suitable for screening purposes and clinical trials, although a preventive check of signal quality should be recommended.

Apnea↗
PubMed2002

Left atrial function: bridge to central and hormonal determinants of exercise capacity in patients with chronic heart failure.

UNLABELLED: The stroke volume response to exercise is a critical determinant in meeting peripheral metabolic demands in patients with chronic hear failure. The Left atrium, by its position, is important in coupling right and left ventricles, to left preload reserve and to modulate sympathetic activity. We performed this study to investigate the relationship between exercise capacity and diastolic and systolic left atrium function in patients with chronic heart failure. METHODS: We considered 128 consecutive patients with severe chronic heart failure (EF < 35%) due to ischemic or idiopathic dilated cardiomyopathy. Cardiac output, right atrial pressure, pulmonary artery pressures and mean pulmonary wedge pressure (A, X, V, Y wedge pressures) were determined during right cardiac catheterization. By Echocardiography evaluation, we measured atrial pressures and volume during early and late left atrial systolic filling and we calculated left atrial chamber stiffness by this equation P = A*eKV1. (P = left atrial pressure; A = elastic constant (mmHg*ml); e = the base of the natural logarithm; V1 = left atrial volume (ml); K = left atrial chamber stiffness constant (ml-1) = ln (V/X)/(maximal--minimal left atrial volumes)). All patients performed cardiopulmonary exercise test with modified Noughton protocol. Plasma norepinephrine and Atrial natriuretic factor levels were determined. RESULTS: Maximal and minimal left atrial volumes were inversely related to oxygen consumption (r = -.44, p < .001; r = -.61, p < .001). At rest, no differences were found in plasma norepinephrine concentrations (309 +/- 152 pg/ml vs 309 +/- 394 pg/ml; p = ns) and systemic vascular resistance (1706 +/- 435 vs 1771 +/- 524 dynes/cm sec-5; p = ns) in patients with large or normal left atrial volumes. During exercise the chronotropic response increased less in patients with large atrial volumes (56 +/- 13 vs 45 +/- 14; p = .001). The left atrial chamber stiffness constant was inversely related to peak oxygen consumption and exercise time. Patients with different chamber stiffness showed statistical difference in peak VO2 (16 +/- 4 vs 11 +/- 3 ml/kg/min; p = .0001). Left atrial ejection fraction was directly related to peak oxygen consumption (r = 0.55), but the most strongly correlation was with atrial filling fraction (r = .67). CONCLUSIONS: This study demonstrates a strong relationship between left atrial function and exercise capacity in patients with chronic heart failure.

Chronic Disease↗
PubMed2001

Echo-Doppler mitral flow monitoring: an operative tool to evaluate day-to-day tolerance to and effectiveness of beta-adrenergic blocking agent therapy in patients with chronic heart failure.

OBJECTIVES: The goals of this study were: 1) to assess the predictive value of baseline mitral flow pattern (MFP) and its changes after loading manipulations as regards tolerance to and effectiveness of beta-adrenergic blocking agent treatment in patients with chronic heart failure (CHF); and 2) to analyze the prognostic implications of chronic MFP modifications after beta-blocker treatment. BACKGROUND: In patients with CHF, carvedilol therapy induces clinical and hemodynamic improvements. Individual management, clinical effectiveness and prognostic implications, however, remain unclear. The MFP changes induced by loading manipulations provide independent prognostic information. METHODS: Echo-Doppler was performed at baseline and after loading manipulations in 116 consecutive patients with CHF (left ventricular ejection fraction: 25 +/- 7%); 54 patients with a baseline restrictive MFP were given nitroprusside infusion; 62 patients with a baseline nonrestrictive MFP performed passive leg lifting. According to changes in MFP, we identified four groups: 17 with irreversible restrictive MFP (Irr-rMFP), 37 with reversible restrictive MFP (Rev-rMFP), 12 with unstable nonrestrictive MFP (Un-nrMFP) and 50 with stable nonrestrictive MFP (Sta-nrMFP). Carvedilol therapy (44 +/- 27 mg) was administered blind to results of loading maneuvers. After six months, MFP was reassessed and patients reclassified according to chronic MFP changes. During follow-up, tolerance to and effectiveness of treatment and major cardiac events (death, readmission and urgent transplantation) were considered. RESULTS: Changes of MFP after loading manipulations were more accurate than baseline MFP in predicting both tolerance to (p < 0.01) and effectiveness of (p < 0.05) carvedilol. After 26 +/- 14 months of follow-up, cardiac events had occurred in 23/102 patients (23%). The event rate in patients with chronic Irr-rMFP or Un-nrMFP was markedly higher than it was in those with Rev-rMFP or Sta-nrMFP. CONCLUSIONS: In our patients, tolerance to and effectiveness of carvedilol was predicted better by echo-Doppler MFP changes after loading manipulations than by baseline MFP. Chronic changes of MFP after therapy are strong predictors of major cardiac events.

Adrenergic beta-Antagonists↗
PubMed2001

Baroreflex sensitivity and heart rate variability in the identification of patients at risk for life-threatening arrhythmias: implications for clinical trials.

BACKGROUND: The need for accurate risk stratification is heightened by the expanding indications for the implantable cardioverter defibrillator. The Multicenter Automatic Defibrillator Implantation Trial (MADIT) focused interest on patients with both depressed left ventricular ejection fraction (LVEF) and the presence of nonsustained ventricular tachycardia (NSVT). Meanwhile, the prospective study Autonomic Tone and Reflexes After Myocardial Infarctio (ATRAMI) demonstrated that markers of reduced vagal activity, such as depressed baroreflex sensitivity (BRS) an heart rate variability (HRV), are strong predictors of cardiac mortality after myocardial infarction. METHODS AND RESULTS: We analyzed 1071 ATRAMI patients after myocardial infarction who had data on LVEF, 24-hour ECG recording, and BRS. During follow-up (21 +/- 8 months), 43 patients experienced cardiac death, 5 patients had episodes of sustained VT, and 30 patients experienced sudden death and/or sustained VT. NSVT, depressed BRS, or HRV were all significantly and independently associated with increased mortality. The combination of all 3 risk factor increased the risk of death by 22x. Among patients with LVEF<35%, despite the absence of NSVT, depressed BRS predicted higher mortality (18% versus 4.6%, P = 0.01). This is a clinically important finding because this grou constitutes 25% of all patients with depressed LVEF. For both cardiac and arrhythmic mortality, the sensitivity of lo BRS was higher than that of NSVT and HRV CONCLUSIONS: BRS and HRV contribute importantly and additionally to risk stratification. Particularly when LVEF is depressed, the analysis of BRS identifies a large number of patients at high risk for cardiac and arrhythmic mortalit who might benefit from implantable cardioverter defibrillator therapy without disproportionately increasing the number of false-positives.

Arrhythmias, Cardiac↗
PubMed2001

Reliability of transfer function estimates in cardiovascular variability analysis.

Transfer function (TF) analysis is a widely diffused technique in the assessment of the relationship between short-term cardiovascular variability signals, particularly blood pressure, heart rate and respiration. To guarantee the reliability of the estimates, a conventional threshold of 0.5 on the magnitude squared coherence (MSC) is commonly used, although (i) other analysis parameters play a role and (ii) lower values of MSC are frequently unavoidable in physiological systems. In this study, computer simulations are performed to assess the dependency of the bias and standard deviation (SD) of TF estimates on record length (RL), spectral window bandwidth (Bw) and MSC; to evaluate the accuracy of theoretical expressions for the computation of the confidence interval (CI) of the estimates; and to assess, in some representative situations, how faithfully observed TF shapes reproduce the underlying true functions in conditions of very low MSC. The accuracy of TF estimates increases non-linearly with increasing RL, and the benefit over 7 min is small. Using this RL, the relative bias for the TF modulus is < 10% for MSC > 0.2. Estimates of TF phase are unbiased. The SD of both the modulus and phase increases linearly as the MSC decrease to 0.4 and then, for lower MSC, increases markedly with nonlinear behaviour. Bw= 0.03Hz appears to be most suitable to reduce the error, preserving spectral resolution. CIs for the TF phase are highly reliable, whereas those for the modulus tend to be slightly narrower than the nominal value at high coherence values. Major features of the TF shape appear to be preserved in simulations with very low MSC. The major problem in TF estimation is the sharp increase in the variability of the measurements as the coherence decreases towards the lowest values. The combination of RL > or = 420s and Bw= 0.03Hz should be suggested in short-term cardiovascular variability studies. Although basic features of the true TF can be recovered even when the MSC is < 0.5, much greater values can be necessary when accurate point estimates are needed. Theoretical expressions for the computation of confidence intervals of the TF are adequate for practical purposes.

Blood Pressure↗
PubMed2001

Chronic infusion of dobutamine and nitroprusside in patients with end-stage heart failure awaiting heart transplantation: safety and clinical outcome.

BACKGROUND: in patients with severe heart failure additional therapeutic support with intravenous inotropic or vasodilator drugs is frequently employed in an attempt to obtain hemodynamic and clinical control. No data comparing the use and efficacy of chronic intravenous inotropic and vasodilator therapy in patients with advanced heart failure are available. AIMS: we evaluated, in a group of patients with advanced heart failure undergoing chronic infusion with dobutamine or nitroprusside, in addition to optimized oral therapy, (1) the safety of chronic infusion, (2) the efficacy of both drugs in managing unloading therapy and (3) clinical outcome of the two therapeutic strategies. METHODS: one hundred and thirteen patients receiving optimized oral therapy, in functional class III/IV with symptoms and signs of refractory heart failure and requiring additional pharmacological support with either intravenous dobutamine or nitroprusside were evaluated. Clinical and therapeutic management and clinical outcome of the two groups were considered. RESULTS: dobutamine was administered for 12 h/day for 20+/-23 days at a dosage of 7+/-3 microg/kg/min to 43 patients. The mean dose of nitroprusside was 0.76+/-0.99 microg/kg/min. The mean duration of use of this drug, administered as a 12-h/day infusion was 22+/-38 days. Nitroprusside infusion allowed greater doses of short-term ACE-inhibitors to be used compared to pre-infusion (ACE-inhibitor dose: 55+/-30 mg/day vs. 127+/-30 mg/day P<0.0001) and during dobutamine infusion (ACE-inhibitor dose: 85+/-47 mg/day vs. 127+/-30 mg/day P<0.002). Nitroprusside unlike dobutamine significantly improved the NYHA functional class. Of the 113 patients, 109 (97%) had a cardiac event during a mean follow-up of 337+/-264 days. Forty-four patients required hospitalization for worsening congestive heart failure, 45/113 (39%) patients died during the follow-up and 27/113 (24%) patients had a heart transplant in status one. Hospitalization, because of worsening heart failure was less frequent in the nitroprusside than in the dobutamine subgroup [29/51 (57%) vs. 19/22 (86%) P<0.02]. The overall mortality was 28% (20/70) in the nitroprusside group and 58% (25/43) in the dobutamine group (odds ratio 0.33 CI 0.16 to 0.73 P<0.006). In the group treated with nitroprusside, heart transplantation in status one was performed in 16/33 patients (48%), while in the dobutamine group this was done in 11/14 patients (78%) (odds ratio 0.25 CI 0.06-1.02 P<0.06). There was a significant reduction in the combined end-point of mortality/heart transplantation in status one in patients treated with nitroprusside compared to those treated with dobutamine (36/70 (51%) vs. 36/43 (84%) - (odds ratio 0.34 CI 0.14-0.80 P<0.01). The incidence of adverse events in the patients treated with nitroprusside was similar to that in those treated with dobutamine (20% vs. 17% P=ns). CONCLUSIONS: for patients awaiting heart transplantation chronic intermittent nitroprusside infusions are more effective and safer than dobutamine in relieving symptoms, facilitating unloading therapy management and improving survival. Whether chronic intermittent infusion of nitroprusside could represent a feasible medical strategy in out-patients with severe heart failure remains to be investigated.

Cardiac Output, Low↗
PubMed2001

Six-minute walking performance in patients with moderate-to-severe heart failure; is it a useful indicator in clinical practice?

AIMS: The 6-min walk test has been incorporated into studies on the efficacy of new therapies and into prognostic stratification for chronic heart failure patients. Firm conclusions on the usefulness of the test in clinical practice are still lacking. The aim of this study was to investigate (1) the correlation between walk test performance and standard indices of cardiac function and exercise capacity, and (2) the prognostic value of the walk test with respect to peak VO2 and NYHA class. METHODS AND RESULTS: Three hundred and fifteen chronic heart failure patients (age: 53+/-9 years, NYHA class: II (182), III (133)) underwent a functional evaluation and a 6-min walk test. Of these, 270 were followed-up for a minimum of 6 months (mean 387+/-177 days). Walked distance was 396+/-92 m. There was no significant correlation between distance walked and central haemodynamic data. Functional capacity, as measured by ergometry, correlated moderately with distance walked (duration: r=0.48, peak VO2: r=0.59, anaerobic threshold: r=0.54; all P<0.001). During follow-up, 46 patients died from cardiovascular causes and 12 were urgently transplanted. Either of these events were considered end points of the study. Survival analysis was performed from a continuous walk test and peak VO2 measurements or after categorization of (a) quartile segmentation, (b) cut-off points from the literature and (c) thresholds from receiver operating characteristic curves. At univariate survival analysis (Cox regression), the association of the walk test with survival was of significance (P=0.03, continuous variable), or borderline significance (0.05< or =P< or =0.1, after categorization). Peak VO2 was always significant, independent of the scale used (0.005< or =P< or =0.03). The strongest association was found for NYHA class (P<0.001), which showed the highest sensitivity and specificity for the prediction of the event (0.64 and 0.65, respectively). When walk test performance, continuous or categorized, was entered into a multivariate model with NYHA class or peak VO2, it lost any significant association with survival (P>0.76 in all models with NYHA class and P>0.27 in all models with peak VO2). CONCLUSION: In moderate-to-severe chronic heart failure patients, the 6-min walk test is not related to cardiac function and only moderately related to exercise capacity. Walking performance does not provide prognostic information which can complement or substitute for that provided by peak VO2 or NYHA class. Hence the test is of limited usefulness as a decisional indicator in clinical practice.

Adult↗
PubMed2001

Assessment of baroreflex sensitivity in patients with preserved and impaired left ventricular function by means of the Valsalva manoeuvre and the phenylephrine test.

The purpose of the present study was to assess the agreement between measurements of baroreflex sensitivity (BRS) obtained by the Valsalva manoeuvre and by the phenylephrine test in patients with previous myocardial infarction and different degrees of left ventricular dysfunction. Patients with a previous myocardial infarction were enrolled consecutively into two groups according to their left ventricular ejection fraction (LVEF): 40% (n=52). All patients underwent BRS assessment by the phenylephrine technique (Phe-BRS) and by the Valsalva manoeuvre, with the latter using both the overshoot part of phase IV (Ov-VM-BRS) and the whole of phase IV (IV-VM-BRS). The linear association between methods was assessed by correlation analysis and the agreement was evaluated by computing the bias and the limits of agreement. IV-VM-BRS and Ov-VM-BRS could not be computed in 26% and 39% of patients respectively. For both indices a much higher percentage of non-computable Valsalva manoeuvre slopes was found in the group of patients with LVEF 40% the results were: r=0.91 (P<0.001), bias=0.1 ms/mmHg (P=0.84) and limits of agreement from -4.8 to 5 ms/mmHg. When comparing Phe-BRS and IV-VM-BRS, we found r=0.67 (P=0.001), bias=-1.5 ms/mmHg (P=0.06) and limits of agreement from -8.8 to 5.7 ms/mmHg in the group of patients with LVEF 40%. Dichotomizing Ov-VM-BRS, the best cut-off value to identify patients with a Phe-BRS of <3 ms/mmHg was found to be 7 ms/mmHg, giving 100% sensitivity and 69% specificity. In conclusion, estimation of BRS by the Valsalva manoeuvre in post-myocardial infarction patients is limited by a large number of non-measurable results. When computable, measurements are well correlated with those obtained by Phe-BRS, but, because of large limits of agreement, the two methods cannot be used interchangeably. If used as a screening test for risk stratification, the Valsalva manoeuvre could reduce by about one-third the need for phenylephrine injection.

Adult↗
PubMed2000

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.

Adult↗
PubMed2000

Nonselective beta-adrenergic blocking agent, carvedilol, improves arterial baroflex gain and heart rate variability in patients with stable chronic heart failure.

OBJECTIVES: The purpose of this study was to investigate in a case-controlled study whether carvedilol increased baroreflex sensitivity and heart rate variability (HRV). BACKGROUND: In chronic heart failure (CHF), beta-adrenergic blockade improves symptoms and ventricular function and may favorably affect prognosis. Although beta-blockade therapy is supposed to decrease myocardial adrenergic activity, data on restoration of autonomic balance to the heart and, particularly, on vagal reflexes are limited. METHODS: Nineteen consecutive patients with moderate, stable CHF (age 54 +/- 7 years, New York Heart Association [NYHA] class II to III, left ventricular ejection fraction [LVEF] 24 +/- 6%), treated with optimized conventional medical therapy, received carvedilol treatment. Controls with CHF were selected from our database on the basis of the following matching criteria: age +/- 3 years, same NYHA class, LVEF +/- 3%, pulmonary wedge pressure +/- 3 mm Hg, peak volume of oxygen +/- 3 ml/kg/min, same therapy. All patients underwent analysis of baroreflex sensitivity (phenylephrine method) and of HRV (24-h Holter recording) at baseline and after six months. RESULTS: Beta-blockade therapy was associated with a significant improvement in symptoms (NYHA class 2.1 +/- 0.4 vs. 1.8 +/- 0.5, p < 0.01), systolic and diastolic function (LVEF 23 +/- 7 vs. 28 +/- 9%, p < 0.01; pulmonary wedge pressure 17 +/- 8 vs. 14 +/- 7 mm Hg, p < 0.05) and mitral regurgitation area (7.0 +/- 5.1 vs. 3.6 +/- 3.0 cm2, p < 0.01). No significant differences were observed in either clinical or hemodynamic indexes in control patients. Phenylephrine method increased significantly after carvedilol (from 3.7 +/- 3.4 to 7.1 +/- 4.9 ms/mm Hg, p < 0.01) as well as RR interval (from 791 +/- 113 to 894 +/- 110 ms, p < 0.001), 24-h standard deviation of normal RR interval and root mean square of successive differences (from 56 +/- 17 to 80 +/- 28 ms and from 12 +/- 7 to 18 +/- 9 ms, all p < 0.05), while all parameters remained unmodified in controls. During a mean follow-up of 19 +/- 8 months a reduced number of cardiac events (death plus heart transplantation, 58% vs. 31%) occurred in those patients receiving beta-blockade. CONCLUSIONS: Besides the well-known effects on ventricular function, treatment with carvedilol in CHF restores both autonomic balance and the ability to increase reflex vagal activity. This protective mechanism may contribute to the beneficial effect of beta-blockade treatment on prognosis in CHF.

Adrenergic beta-Antagonists↗
PubMed2000

Beta-blockade therapy in chronic heart failure: diastolic function and mitral regurgitation improvement by carvedilol.

BACKGROUND: In patients with chronic heart failure, the use of carvedilol therapy induces clinical and hemodynamic improvement. However, although the benefits of this beta-blocker have been established in patients with chronic heart failure, the mechanisms underlying them and the changes in left ventricular systolic function, diastolic function, and mitral regurgitation during long-term therapy remain unclear. OBJECTIVE: To identify the clinical and functional effects of carvedilol, focusing on diastolic function and mitral regurgitation variations. METHODS: Forty-five consecutive patients with chronic heart failure (ejection fraction 24% +/- 7%), 17 with dilated ischemic and 28 with nonischemic cardiomyopathy, were treated with carvedilol (mean dose 44 +/- 30 mg) and matched for clinical (New York Heart Association functional class and heart failure duration) and hemodynamic (cardiac index and pulmonary wedge pressure) characteristics to a control group. Clinical and echocardiographic variables were measured in the 2 groups at baseline and after 6 months and the results compared. RESULTS: After 6 months of treatment with carvedilol, left ventricular ejection fraction had increased from 24% +/- 7% to 29% +/- 9% (P <.0001); this change was caused by a reduction in end-systolic volume index (106 +/- 41 vs 93 +/- 37 mL/m(2); P <. 0001). Deceleration time of early diastolic filling increased (134 +/- 74 vs 196 +/- 63 ms; P <.0001). Seventeen of the 27 patients with demonstrated improvement of left ventricular diastolic filling moved from having a restrictive filling pattern to having a normal or pseudonormal left ventricular filling pattern. In the control group, no significant changes in deceleration time of early diastolic filling were found (139 +/- 74 vs 132 +/- 45 ms; P = not significant). The effective regurgitant orifice area decreased significantly in the carvedilol group but not in the control group. These changes were associated with a significant reduction of the mitral regurgitant stroke volume in the carvedilol group (50 +/- 25 vs 16 +/- 13 mL; P <.0001) but not in the control group (57 +/- 29 vs 47 +/- 24 mL; P = not significant). These changes of mitral regurgitation were closely associated with significant improvement of forward aortic stroke volume (r = -.57, P <.0001). These findings were not observed in patients in the control group. CONCLUSIONS: The results of this study show that long-term carvedilol therapy in patients with chronic heart failure was able to prevent or partially reverse progressive left ventricular dilatation. The effects on left ventricular remodeling were associated with a concomitant recovery of diastolic reserve and a decrease of mitral regurgitation, which have been demonstrated to be powerful prognostic predictors in such patients. Overall these findings provide important insights into the pathophysiologic mechanisms by which carvedilol improves the clinical course of patients with chronic heart failure.

Adrenergic beta-Antagonists↗
PubMed2000

Invasive and non-invasive determinants of pulmonary hypertension in patients with chronic heart failure.

BACKGROUND: In patients with chronic heart failure, pulmonary hypertension is an important predictive marker of adverse outcome. Its invasive and non-invasive determinants have not been evaluated. OBJECTIVE: This study was performed to evaluate hemodynamic determinants of pulmonary hypertension in chronic heart failure and to compare the predictive value of Doppler indices with that of invasively measured hemodynamic indices. METHODS: Right heart catheterization and transthoracic echo-Doppler were simultaneously performed in 259 consecutive patients with chronic heart failure (ejection fraction 24% +/- 7%) who were in sinus rhythm and receiving optimized medical therapy. Systolic pulmonary artery pressure (sPAP), cardiac index, transpulmonary gradient pressure, and pulmonary wedge pressure (PWP) were measured invasively. Left atrial and ventricular systolic and diastolic volumes, the ratio of maximal early to late diastolic filling velocities (E/A ratio), deceleration time (DT) and atrial filling fraction (AFF) of transmitral flow, systolic fraction of forward pulmonary venous flow (SFpvf), and mitral regurgitation were quantified by echo-Doppler. RESULTS: Patients with pulmonary hypertension had greater left atrial systolic and diastolic dysfunction, more left ventricular diastolic abnormalities, and greater hemodynamic impairment. The correlations between systolic left ventricular indices, mitral regurgitation, and sPAP were generally poor. Among invasive and non-invasive measurements, PWP (r = 0.89, p < 0.0001) and SFpvf (r = -0.68, p < 0.0001) showed the strongest correlation with sPAP. When we compared all patients with those without mitral regurgitation, the correlations between E/A ratio (r = 0.56 vs r = 0. 74, p < 0.002), SFpvf (r = -0.68 vs r = -0.84, p < 0.03), and systolic pulmonary artery pressure were significantly stronger. Multivariate analysis revealed that PWP was the strongest invasive independent predictor of systolic pulmonary artery pressure in patients with (R(2) = 0.87, p < 0.0001) and without (R(2) = 0.90, p < 0.0001) mitral regurgitation. A PWP > or= 18 mm Hg (odds ratio [95% CL], 142 (41-570) was strongly associated with systolic pulmonary hypertension. Among non-invasive variables DT, SFpvf, and AFF were identified as independent predictors of sPAP in patients with (R(2) = 0.56, p < 0.0001) and without (R(2) = 0.78, p < 0.0001) mitral regurgitation. A DT < 130 (odds ratio [95% CL], 3.5 (1.3-8.5), SFfvp < 40% (odds ratio [95% CL], 333 (41-1,007), and AFF < 30% (odds ratio [95% CL], 2 (1.3-7) most strongly predicted systolic pulmonary hypertension. CONCLUSIONS: The results of this study indicate that in patients with chronic heart failure, venous pulmonary congestion is an important determinant of systolic pulmonary artery hypertension. Hemodynamic and Doppler determinants showed similar predictive power in identifying systolic pulmonary artery hypertension.

Blood Flow Velocity↗
PubMed2000

Limitations of the computerized laryngeal analyzer (CLA) in the assessment of the swallowing mechanism.

This study was devised to assess the repeatability of measurements obtained from the Computerized Laryngeal Analyzer (CLA), a commercial system which monitors global laryngeal activity through a piezoelectric transducer positioned at the level of the thyroid cartilage. Twenty-two healthy subjects (37+/-7 yr) were asked to repeat three consecutive times the deglutition of three types of bolus: dry (saliva only), liquid (10 ml water) and solid (1 cm(3) biscuit). The whole recording session was repeated 4+/-3 days apart. Two parameters were considered: amplitude and duration of the deglutition. Both intra- and inter-sessions repeatability were assessed by the standard error of measurement. The amplitude measurements were often found to be clipped at 100 mV, making duration the only parameter suitable for analysis. The duration was homogenous for the three types of bolus and no trend effect was found either intra- or inter-sessions. Inter-sessions repeatability was significantly lower than the intra-session one (P<0.05). As a practical implication, a change in duration >/=1 s (=65% of the observed mean value) between two separate measurements is required in order to be 95% confident that it is not due to chance alone. We conclude that the observed limitations in the measurements provided by the CLA system, in conjunction with its intrinsic characteristic of providing only an uncalibrated measurement of global laryngeal activity, seriously question the possibility of using the CLA system either as a diagnostic tool or as a substitute of the gold standard method (videofluorography).

Adult↗
PubMed2000

Comparison between invasive and non-invasive measurements of baroreflex sensitivity; implications for studies on risk stratification after a myocardial infarction.

AIMS: The ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) study has proved the independent prognostic value of baroreflex sensitivity. A limitation of the traditional method of estimating baroreflex sensitivity by phenylephrine, is the need to monitor intra-arterial blood pressure. Our objective was to establish whether this invasive method of monitoring could be superseded by non-invasive methods, such as the Finapres device. METHODS AND RESULTS: Patients with three repeated invasive and non-invasive baroreflex sensitivity measurements were selected from the ATRAMI database (n = 454). The mean of these measurements was taken as the baroreflex sensitivity estimate. The repeatability of both methods (standard deviation of the three measurements) decreased with increasing baroreflex sensitivity. There was no constant bias between invasive and non-invasive measurements (0. 22+/-2.2 ms. mmHg(-1), P = 0.42). The linear correlation was very high (r = 0.91, P < 0.01). The normalized 95% limits of agreement were -0.5 and 0.52. On survival analysis, invasive and non-invasive baroreflex sensitivity gave similar prognostic information (likelihood ratio: 155.6 (P = 0.007) and 155.0 (P = 0.006); risk ratio: 0.79 and 0.81, respectively). According to the ATRAMI cut-off points, 85% of patients were classified concordantly by the two methods. None of the patients at high (low) risk with the invasive method were classified as low (high) risk class by the non-invasive method. CONCLUSION: Despite wide limits of agreement, invasive and non-invasive baroreflex sensitivity measurements are highly correlated and provide equivalent prognostic information.

Autonomic Nervous System↗
PubMed2000

Effect of beta-blockade on the premature ventricular beats/heart rate relation and heart rate variability in patients with coronary heart disease and severe ventricular arrhythmias.

We examined the effects of beta-blockers on the associations between heart rate and number of premature ventricular beats (PVBs) and on heart rate variability and myocardial ischemia in patients with coronary heart disease. After 2 weeks of run-in placebo treatment, 18 patients with coronary artery disease were randomized to a 7-day treatment with either propranolol (40 mg) three times a day or placebo. During run-in and after 7 days of treatment, patients underwent 24-hour Holter monitoring and exercise tests. We analyzed the 24-hour Holter recordings with customized software that computes the correlation between heart rate and occurrence of PVBs. We also computed spectral measures of heart rate variability on the same recordings. Propranolol caused a significant decrease in the log-transformed total number of PVBs recorded over 24 hours and during the day. The number of PVBs was much lower during the night than during the day both after placebo and after propranolol. There were no differences between the two treatments. During the day, there was a positive correlation between heart rate and the number of PVBs in all 18 patients. The mean correlation coefficients between heart rate and number of PVBs increased significantly after propranolol treatment both during the 24-hour monitoring (p < 0.05) and during the day (p < 0.05). The night-recorded correlation coefficients between heart rate and number of PVBs were not significantly different in the placebo versus propranolol group. Propranolol significantly increased the total power during the day. Placebo caused a significant decrease in the low-frequency band (LF) and a significant increase in the high-frequency band (HF) during the night compared with the day. During the day, propranolol significantly reduced LF power and increased HF power, with respect to placebo. After propranolol treatment, the values of LF and HF power during the day were comparable to those recorded at night. The LF/HF ratio decreased significantly after propranolol treatment with respect to placebo in the day and became similar to that recorded during sleep. Propranolol significantly reduced heart rate and systolic blood pressure at rest and at peak exercise and reduced signs of myocardial ischemia. Propranolol administration reduces PVBs in patients with coronary artery disease and severe ventricular arrhythmias possibly through an improvement of cardiac autonomic regulation and through anti-ischemic effects, antiarrhythmic effects, or both.

Adrenergic beta-Antagonists↗
PubMed2000

Cardiorespiratory interactions during periodic breathing in awake chronic heart failure patients.

We applied spectral techniques to the analysis of cardiorespiratory signals [instantaneous lung volume (ILV), instantaneous tidal volume (ITV), arterial O(2) saturation (Sa(O(2))) at the ear, heart rate (HR), systolic (SAP), and diastolic (DAP) arterial pressure] during nonapneic periodic breathing (PB) in 29 awake chronic heart failure (CHF) patients and estimated the timing relationships between respiratory and slow cardiovascular (<0.04 Hz) oscillations. Our aim was 1) to elucidate major mechanisms involved in cardiorespiratory interactions during PB and 2) to test the hypothesis of a central vasomotor origin of PB. All cardiovascular signals were characterized by a dominant (>/=84% of total power) oscillation at the frequency of PB (mean +/- SE: 0.022 +/- 0.0008 Hz), highly coherent (>/=0.89), and delayed with respect to ITV (ITV-HR, 2.4 +/- 0.72 s; ITV-SAP, 6.7 +/- 0.65 s; ITV-DAP, 3.2 +/- 0.61 s; P < 0.01). Sa(O(2)) was highly coherent with (coherence function = 0.96 +/- 0. 009) and almost opposite in phase to ITV. These findings demonstrate the existence of a generalized cardiorespiratory rhythm led by the ventilatory oscillation and suggest that 1) the cyclic increase in inspiratory drive and cardiopulmonary reflexes and 2) mechanical effects of PB-induced changes in intrathoracic pressure are the more likely sources of the HR and blood pressure oscillations, respectively. The timing relationship between ITV and blood pressure signals excludes the possibility that PB represents the effect of a central vasomotor rhythm.

Arteries↗