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Biomedical subjects

P Ponikowski

Publications and source records attributed to P Ponikowski.

At least 37 records · Page 2Linked to original sources
PubMed1999

Effects of amiodarone on the P-wave triggered signal-averaged electrocardiogram in patients with paroxysmal atrial fibrillation and coronary artery disease.

The effects of a 6-week treatment with amiodarone on the P-wave triggered signal-averaged electrocardiogram in patients with paroxysmal atrial fibrillation and coronary artery disease have been studied. Amiodarone favorably influences P-wave triggered signal-averaged electrocardiographic parameters, predominantly in patients in whom amiodarone is effective in preventing paroxysmal atrial fibrillation.

Aged↗
PubMed1999

A neural link to explain the "muscle hypothesis" of exercise intolerance in chronic heart failure.

BACKGROUND: In chronic heart failure the cause of exercise limitation is still unclear: ergoreceptors, muscle afferents sensitive to exercise metabolites, are proposed as a neural link between muscular abnormalities and the limited exercise responses in this syndrome. METHODS: In 92 stable patients with heart failure (34 in New York Heart Association class I, 27 in class II, and 31 in class III) and 28 age-matched normal controls, we assessed exercise tolerance (maximal upright bicycle) and ergoreflex activity (2 dynamic hand grips: one control and one followed by 3 minutes of local circulatory occlusion to isolate the ergoreflex component by metabolite trapping). RESULTS: Patients, with respect to the controls, showed reduced exercise tolerance (peak VO2: 20 vs 33 mL/kg/min), increased ergoreflex effects on ventilation (9 vs 4 L/min), systolic pressure (37 vs 13 mm Hg), and leg vascular resistance (45 vs 22 units) (all P <.005); with the progression of the symptoms, a progressive increase in ergoreflex contribution to the ventilatory response to exercise was observed. The indexes of exercise limitation during arm and leg exercise (ie, peak VO 2, V/VCO2 slope) correlated highly with the ergoreflex contribution to ventilatory response during handgrip test ( r </= 0.7, P <.0001) but weakly with left ventricular ejection fraction (r </= 0.5). CONCLUSION: In chronic heart failure, the overactivity of the ergoreflex is related to a degree of functional limitation and appears, through direct ventilatory and cardiovascular responses, to contribute to the abnormal responses to exercise, explaining the "muscle hypothesis."

Aged↗
PubMed1999

The impact of cachexia on cardiorespiratory reflex control in chronic heart failure.

BACKGROUND: The mechanism of persistent neurohormonal and cardiorespiratory reflex abnormalities in chronic heart failure remain unclear. Also, why chronic heart failure patients who develop cachexia demonstrate a particularly abnormal neurohormonal profile and have a high risk of death is not known. Impaired reflex control within the cardiac and respiratory systems, and abnormal heart rate variability have both been linked to a poor outcome. Muscle reflexes may contribute to persistent neurohormonal overactivity in wasted patients. Thus, we hypothesized that patients with cardiac cachexia might exhibit particularly profound abnormalities in cardiorespiratory reflexes and heart ratevariability. METHODS AND RESULTS: We investigated 39 chronic heart failure patients: 13 with cardiac cachexia (non-intentional, non-oedematous, documented weight loss of >7.5% of previous normal weight over more than 6 months), and 26 non-cachectic chronic heart failure patients matched according to the severity of chronic heart failure (all men, mean age: 59 vs 60 years, NYHA functional class: 2.6 vs 2.5, peak O(2)consumption: 16.2 vs 16.8 ml. kg(-1). min(-1), left ventricular ejection fraction: 23 vs 24%, all P>0.2 for cachectic vs non-cachectic). In the assessment of the cardiorespiratory reflex control we investigated: cardiac sympathovagal balance (using spectral analysis of heart rate variability to derive low (LF, 0. 04-0.15Hz) and high frequency (HF, 0.15-0.4Hz) components), baroreflex sensitivity (using the phenylephrine method), and peripheral chemosensitivity (using the transient hypoxic method). There was a severely abnormal pattern of cardiorespiratory reflex control in patients with cachexia compared with non-cachectic patients. The former group exhibited severely impaired autonomic reflex control, characterized by an abnormal profile of heart rate variability (reduced LF component), and depressed baroreflex sensitivity (P=0.0001 and P=0.02, respectively, vs non-cachectics). Patients with cachexia also demonstrated an increased peripheral chemosensitivity (0.91 vs0.46 l. min(-1). %SaO(2)(-1), P<0.001, cachectic vs non-cachectic, respectively). In the correlation analyses the degree of impairment in the reflex control was more closely related to wasting, and to the level of neurohormonal activation (as measured by the levels of epinephrine and norepinephrine) than to conventional markers of the severity of heart failure. CONCLUSIONS: Chronic heart failure patients who developed cardiac cachexia demonstrate an abnormal reflex control within the cardiovascular and respiratory systems. The nature of the link between this phenomenon and hormonal changes and the poor prognosis of cachectic chronic heart failure patients warrants further investigation.

Cachexia↗
PubMed1999

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.

Adult↗
PubMed1998

Impaired baroreflex sensitivity and sympathovagal balance in syndrome X.

Alterations of autonomic nervous control of cardiac function have been described in syndrome X. The characteristics, however, of the autonomic control of the cardiovascular system in patients with syndrome X have not been adequately studied; thus, the aim of the present study was to investigate the role of baroreceptor sensitivity and sympathovagal balance in syndrome X. The study group included 12 patients with syndrome X, 12 age- and sex-matched control patients with coronary artery disease, and 12 age- and sex-matched controls with no evidence of heart disease. Baroreceptor sensitivity was evaluated by calculating the regression line relating phenylephrine-induced increases in systolic blood pressure to the attendant changes in the RR interval. Sympathovagal balance was assessed by using heart rate variability in the time and frequency domain and measuring plasma norepinephrine at rest and during incremental bicycle exercise. Baroreceptor sensitivity was significantly reduced in syndrome X compared with that in control normal subjects (7.4 +/- 1.2 vs 16.8 +/- 2.3 ms/mm Hg; p < 0.02). This was associated with a significantly lower percentage of adjacent normal RR intervals that differ by >50 ms, lower root-mean-square of the difference of adjacent RR intervals, and lower logarithmic value of the high-frequency component in patients with syndrome X compared with normal subjects. A nonsignificant trend toward lower baroreceptor sensitivity was found in patients with syndrome X compared with control ischemic patients (7.4 +/- 2 vs 12.2 +/- 1.3 ms/mm Hg). A nonsignificant trend toward a higher value of the low- to high-frequency ratio was also observed in patients with syndrome X than in both control groups. No difference was detected in norepinephrine levels either at rest or during exercise or in the exercise-induced norepinephrine increase between the 3 groups. No difference was also observed between ischemic patients and normal subjects in either baroreceptor sensitivity or heart rate variability measurements. A significant correlation (r = 0.80, p < 0.01) was found between baroreceptor sensitivity and the high-frequency component in normal controls but not for other measurements of autonomic function in the 3 groups. In conclusion, patients with syndrome X have an altered autonomic control of the cardiovascular system characterized by impaired baroreceptor sensitivity and reduced heart rate variability. Abnormal autonomic regulation of the cardiovascular system may be of pathophysiologic importance in syndrome X.

Baroreflex↗
PubMed1998

Overview and meta-analysis of randomised trials of amiodarone in chronic heart failure.

Unlike other antiarrhythmic class I drugs, amiodarone showed in preliminary studies, benefits also in patients with left ventricular dysfunction. These positive results have induced the development of large randomised controlled studies: their results are reviewed and the controversial points are discussed. In a meta-analysis of randomised controlled trials the use of amiodarone in heart failure was associated with an approximate 20 to 25% reduction in deaths. However, amiodarone was also associated with a 120 to 124% increase in side effects.

Amiodarone↗
PubMed1998

Ventilatory response to exercise correlates with impaired heart rate variability in patients with chronic congestive heart failure.

In chronic congestive heart failure (CHF) an overactivity of muscle ergoreceptors and peripheral chemoreceptors may lead to an increased ventilatory response to exercise and contribute to the autonomic imbalance. The analysis of heart rate variability (HRV), which is a reliable method of studying autonomic regulations within the cardiovascular system, showed depressed HRV indexes in CHF, but predictors of abnormal HRV pattern in CHF remain controversial. Considering a common mechanism involved in generation of both abnormal ventilation and autonomic dysfunction in CHF, we hypothesized that impaired ventilation may be better than other variables of CHF severity in determining HRV parameters. Seventy-two patients with CHF (57+/-9 years, ejection fraction: 28+/-11%) underwent cardiopulmonary exercise testing; the relation between ventilation and carbon dioxide production (VE/VCO2) was used as an index of the ventilatory response to exercise. Time and frequency-domain measurements of HRV were derived from 24-hour electrocardiographic monitoring. Patients had reduced exercise tolerance with abnormal ventilatory response (peak oxygen consumption [VO2max]: 17.8+/-5.5 ml/kg/min, VE/VCO2: 36.0+/-9.8). Correlations were found between HRV measures and etiology, New York Heart Association (NYHA) functional class, and VO2max, but the strongest relation was observed for VE/VCO2 slope (r values from -0.33 to -0.65, p <0.01). In the multiple regression analysis only VE/VCO2 was found to correlate independently with all HRV measurements. To investigate the role of peripheral chemoreceptor overactivity as the mechanism of autonomic imbalance and the increased ventilatory response to exercise, we assessed peripheral chemosensitivity in 22 patients (mean value of peripheral chemosensitivity: 0.62+/-0.34 L/min/%SaO2, significantly higher than in normal controls, mean value: 0.29+/-0.20 L/min/%SaO2 in our laboratory). The activity of the peripheral chemoreflex inversely correlated with all parameters of HRV. Increased ventilatory response to exercise correlated with depressed HRV measures in patients with CHF better than other clinical variables. An important role of the increased peripheral chemosensitivity in this relation may be relevant, being also a potential link between functional severity and sympathovagal imbalance in CHF.

Administration, Inhalation↗
PubMed1998

[The influence of ischemia provoked by dobutamine and exercise on presence of late potentials in patients after myocardial infarction].

UNLABELLED: The aim of this study was to examine the influence of transient exercise- and dobutamine-induced myocardial ischemia on time domain parameters of signal-averaged ECG (SAECG) and presence of late potentials (LP) in patients after myocardial infarction (MI). The investigation covered 85 patients after healing of MI, divided into two groups. Group I (24 males and 2 females, mean age 56.8 +/- 6.4 yrs) had exercise-induced ischemia and group II consisted of 59 patients (51 males and 8 females, mean age 58.3 +/- 8.5 years) with ischemia provoked by the intravenous dobutamine stress-testing. In each patient 2-D echocardiography, 24-h ambulatory Holter ECG, coronary arteriography were performed before stress testing. The ischemia was proven by using Tc-99m MIBI myocardial perfusion and standard 12-lead ECG monitoring. Recordings of SAECG were registered at rest and during ischemia under influence of stress-testing. The following time-domain parameters of SAECG were analysed: the root-mean-square voltage of the last 40 and 50 ms of the filtered QRS complex (RMS40, 50), total time duration of filtered QRS (t-QRS) and duration of signal lower than 40 muV (LPD). LP were detected when two or three of following criteria's had been registered: RMS 40 < 20 muV, t-QRS > 114ms, LPD > 38s. There was no statistically significant differences in all time domain parameters of SAECG between records at the baseline and during ischemia in each study group. At the baseline LP have been registered in 11.5% and in 15% patients, respectively of group I and group II. On the top of ischemia during treadmill exercise stress-testing LP have been recorded in 27% subjects. Under influence of dobutamine-provoked ischemia LP have been registered in 25% patients. CONCLUSIONS: Exercise- and dobutamine-induced ischemia triggers development of LP in small grade in post-infarction patients.

Coronary Angiography↗
PubMed1998

[Recording of atrial and ventricular signal averaged ECGs in patients with mitral valve prolapse syndrome].

The aim of the study was to assess the time-domain parameters of atrial signal-averaged ECG (ASAECG) and ventricular signal-averaged ECG (SAECG) in patients with mitral valve prolapse (MVP) and healthy ones. Fifty patients with MVP (15 men, 35 women, mean age--37.1 +/- 8.9 years) and 50 healthy controls (36 men, 14 women, mean age 38.2 +/- 4.7 years) were studied). The following time-domain parameters of ASAECG were analysed: the root mean square voltage of the terminal 10, 20, 30 ms of filtered P wave (RMS10, 20, 30) and the total duration of filtered P wave (PWD). The atrial late potentials (ALP) were defined as the presence: RMS10 < 4 microV i PWD > 123 ms. As the time-domain parameters of SAECG we analysed: the root mean square voltage of the terminal 40, 50 ms of the filtered QRS (RMS 40, 50), the total filtered QRS duration (t-QRS) and the low-amplitude signal duration < 40 microV in the terminal QRS (LPD). The ventricular late potentials (VLP) were defined as the presence of at least two of the following criteria: t-QRS > 114 ms, RMS 40 < 20 microV i LPD > 38 ms. There was no difference in the time-domain parameters of ASAECG between patients with MVP and controls: RMS 10: 4.5 +/- 1.8 microV vs 4.8 +/- 1.9 microV, RMS 20: 6.3 +/- 2.2 microV vs 6.1 +/- 2.2 microV, RMS 30: 8.3 +/- 2.5 microV vs 7.1 +/- 2.7 microV and PWD 113 +/- 11.7 ms vs 116 +/- 15.2 ms, respectively. Three patients with MVP (6%) and 5 controls (10%) revealed ALP. THE time-domain parameters of SAECG did not differ in patients with MVP and controls: RMS 40: 40.2 +/- 29.1, microV vs 35.5 +/- 18.2 microV, RMS 50: 68.2 +/- 40.1 microV vs 64.4 +/- 33.6 microV and t-QRS-101.4 +/- 10.7 ms vs 101.8 +/- 10.9 ms i LPD--28.7 +/- 10.0 ms vs 28.3 +/- 10.0 ms, respectively. VLP were found in 7 patients with MVP (14%) and 5 controls (10%). Our findings suggest that time-domain parameters of ASAECG and SAECG could not differentiate patients with MVP and healthy ones. Moreover, the presence of ALP and VLP in MVP group did not correlate with supraventricular and ventricular arrhythmias recorded on ambulatory ECG.

Adult↗
PubMed1997

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.

Aged↗
PubMed1997

Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia.

BACKGROUND: The role of hormonal and cytokine abnormalities in the development of cardiac cachexia remains obscure. METHODS AND RESULTS: Healthy control subjects (n=16) and patients with chronic heart failure (CHF), classified clinically as cachectic (8% to 35% weight loss over > or = 6 months before study, n=16) or noncachectic (n=37), were assessed for markers of disease severity (maximal oxygen consumption, left ventricular ejection fraction, NYHA functional class). These markers were compared with plasma concentrations of potentially important anabolic and catabolic factors. The degree of neurohormonal activation and catabolic/anabolic imbalance was closely related to wasting but not to conventional measures of the severity of heart failure. Compared with control subjects and noncachectic patients, cachectic patients had reduced plasma sodium and increased norepinephrine, epinephrine (all P<.0001), cortisol, tumor necrosis factor (TNF)-alpha (both P<.002), and human growth hormone (P<.05). Insulin-like growth factor-1, testosterone, and estrogen were similar in all groups. Insulin was increased only in the noncachectic patients (P<.005 versus control subjects). Dehydroepiandrosterone was reduced in the cachectic patients (P<.02 versus control subjects). Insulin, cortisol, TNF-alpha, and norepinephrine correlated independently with wasting in CHF (P<.05; multiple regression of these four factors versus percent ideal weight, R2=.50, P<.0001). CONCLUSIONS: Cachexia is more closely associated with hormonal changes in CHF than conventional measures of the severity of CHF. This study suggests that the syndrome of heart failure progresses to cardiac cachexia if the normal metabolic balance between catabolism and anabolism is altered.

Aged↗
PubMed1997

Depressed heart rate variability as an independent predictor of death in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

After acute myocardial infarction, depressed heart rate variability (HRV) has been proven to be a powerful independent predictor of a poor outcome. Although patients with chronic congestive heart failure (CHF) have also markedly impaired HRV, the prognostic value of HRV analysis in these patients remains unknown. The aim of this study was to investigate whether HRV parameters could predict survival in 102 consecutive patients with moderate to severe CHF (90 men, mean age 58 years, New York Heart Association [NYHA] class II to IV, CHF due to idiopathic dilated cardiomyopathy in 24 patients and ischemic heart disease in 78 patients, ejection fraction [EF], 26%; peak oxygen consumption, 16.9 ml/kg/min) after exclusion of patients in atrial fibrilation with diabetes or with chronic renal failure. In the prognostic analysis (Cox proportional-hazards model, Kaplan-Meier survival analysis), the following factors were investigated: age, CHF etiology, NYHA class, EF, peak oxygen consumption, presence of ventricular tachycardia on Holter monitoring, and HRV measures derived from 24-hour electrocardiography monitoring, calculated in the time (standard deviation of all normal RR intervals [SDNN], standard deviation of 5-minute RR intervals [SDANN], mean of all 5-minute standard deviations of RR intervals [SD], root-mean-square of difference of successive RR intervals [rMSSD], and percentage of adjacent RR intervals >50 ms different [pNN50]) and frequency domain (total power [TP], power within low-frequency band [LF], and power within high-frequency band [HF]). During follow-up of 584 +/- 405 days (365 days in all who survived), 19 patients (19%) died (mean time to death: 307 +/- 315 days, range 3 to 989). Cox's univariate analysis identified the following factors to be predictors of death: NYHA (p = 0.003), peak oxygen consumption (p = 0.01), EF (p = 0.02), ventricular tachycardia on Holter monitoring (p = 0.05), and among HRV measures: SDNN (p = 0.004), SDANN (p = 0.003), SD (p = 0.02), and LF (p = 0.003). In multivariate analysis, HRV parameters (SDNN, SDANN, LF) were found to predict survival independently of NYHA functional class, EF, peak oxygen consumption, and ventricular tachycardia on Holter monitoring. The Kaplan-Meier survival curves revealed SDNN < 100 ms to be a useful risk factor; 1-year survival in patients with SDNN < 100 ms was 78% when compared with 95% in those with SDNN > 100 ms (p = 0.008). The coexistence of SDNN < 100 ms and a peak oxygen consumption < 14 ml/kg/min allowed identification of a group of 18 patients with a particularly poor prognosis (1-year survival 63% vs 94% in the remaining patients, p <0.001). We conclude that depressed HRV on 24-hour ambulatory electrocardiography monitoring is an independent risk factor for a poor prognosis in patients with CHF. Whether analysis of HRV could be recommended in the risk stratification for better management of patients with CHF needs further investigation.

Aged↗
PubMed1997

Wasting as independent risk factor for mortality in chronic heart failure.

BACKGROUND: Wasting in chronic heart failure (CHF) has long been known but is little investigated. We sought to find out whether the cachectic state in CHF provides additional prognostic information about all-cause mortality. METHODS: Between June, 1993, and May, 1995, we studied 171 consecutive patients with CHF (mean age 60 years [SD 11; range 27-86]; 17 female). We assessed exercise capacity (peak oxygen consumption; mean 17.5 mL kg-1 min-1 [6.7]), functional status (New York Heart Association [NYHA] class: 21 class I, 63 class II, 68 class III, 19 class IV), and left-ventricular ejection fraction (mean 30% [SD 15]; n = 115). The cachectic status was defined prospectively as a non-intentional documented weight loss of at least 7.5% of previous normal weight (28 patients; range 9-36% or 6-30 kg) during at least 6 months. The Cox proportional-hazards model was used to assess the association of variables with survival, and Kaplan-Meier cumulative survival plots were constructed to estimate the influence of risk factors. FINDINGS: At the end of follow-up in November, 1996, 49 patients had died (after a mean 324 days [SD 283]). The mean follow-up of the survivors was 834 days (SD 186; range 549-1269). The cachectic state was predictive of 18-month mortality independent of age, NYHA class, left-ventricular ejection fraction, and peak oxygen consumption. Mortality in the cachectic patients (n = 28) was 18% at 3 months, 29% at 6 months, 39% at 12 months, and 50% at 18 months. Patients who had a peak oxygen consumption below 14 mL kg-1 min-1 (n = 53) had mortality at 3, 6, 12, and 18 months of 19%, 30%, 40%, and 51%. 18-month survival was 23% (95% CI 0-46) for the 13 patients with both of these risk factors (cachexia and low peak oxygen consumption) compared with 93% (88-98) in those (n = 103) with neither risk factor (p < 0.0001). INTERPRETATION: The cachectic state is a strong independent risk factor for mortality in patients with CHF. Combined with a low peak oxygen consumption, it identifies a subset of patients at extremely high risk of death. Assessment of cachexia should be included in transplant programmes and studies that investigate the effect of interventions by survival analyses.

Adult↗
PubMed1997

Effects of dihydrocodeine on chemosensitivity and exercise tolerance in patients with chronic heart failure.

OBJECTIVES: We sought to test the hypothesis that suppression of chemosensitivity (respiratory response to arterial blood gases) with dihydrocodeine may improve dyspnea and exercise tolerance in patients with chronic heart failure. BACKGROUND: Exertional dyspnea is a common limiting symptom in patients with chronic heart failure. The mechanisms underlying this symptom are not fully understood but may be related to increased ventilation caused, in part, by the augmentation of chemosensitivity. Suppression of chemosensitivity with mild opiates may thus improve this symptom as well as exercise tolerance. METHODS: Twelve men with chronic heart failure (mean [+/-SE] age 65.5 +/- 1.5 years, range 58 to 75; left ventricular ejection fraction 21.3 +/- 3.0%, range 8 to 39) received placebo or dihydrocodeine (1 mg/kg body weight) on two separate days in a randomized, double-blind design. One hour later, hypoxic and hypercapnic chemosensitivities were assessed using the transient inhalations of pure nitrogen and the rebreathing of 7% carbon dioxide in 93% oxygen, followed by treadmill cardiopulmonary exercise testing. The symptoms of dyspnea and fatigue during the exercise test were assessed using a modified Borg scale from 0 to 10. RESULTS: There was a significant fall in hypoxic and hypercapnic chemosensitivities with dihydrocodeine administration compared with placebo (0.447 +/- 0.096 vs. 0.746 +/- 0.104 liter/min per percent arterial oxygen saturation, p = 0.005; 2,480 +/- 0.234 vs. 2.966 +/- 0.283 liter/min per mm Hg, p = 0.01, respectively). Exercise duration was prolonged from 455 +/- 27 s on placebo to 512 +/- 27 s (p = 0.001) with dihydrocodeine, and peak oxygen consumption increased from 18.0 +/- 0.6 to 19.7 +/- 0.6 ml/kg per min (p = 0.002). The ventilatory response to exercise, characterized by the regression slope relating minute ventilation to carbon dioxide output, decreased from 34.19 +/- 2.35 to 30.85 +/- 1.91 (p = 0.01). With dihydrocodeine administration, the change in the modified Borg score for dyspnea was -0.80 (p = 0.003) at 6 min and -0.33 (p = 0.52) at peak exercise, whereas that for fatigue did not change significantly. Arterial oxygen saturation was maintained during exercise despite dihydrocodeine administration (99.3% at rest vs. 98.9% at peak exercise, p = 0.21). CONCLUSIONS: Augmented chemosensitivity is important in the pathophysiology of chronic heart failure. Its suppression with dihydrocodeine was associated with a reduction of exercise ventilation, an improvement in exercise tolerance and a decrease in breathlessness. Pharmacologic modulation of chemosensitivity may benefit patients with chronic heart failure and merits further investigation.

Aged↗
PubMed1997

Clinical correlates and prognostic significance of the ventilatory response to exercise in chronic heart failure.

OBJECTIVES: This study sought to investigate the clinical characteristics of patients with chronic heart failure and an increased ventilatory response to exercise and to examine the prognostic usefulness of this response. BACKGROUND: The ventilatory response to exercise is increased in many patients with chronic heart failure and may be characterized by the regression slope relating minute ventilation to carbon dioxide output (VE-VCO2 slope) during exercise. METHODS: One hundred seventy-three consecutive patients (155 men; mean [+/-SD] age 59.8 +/- 11.5 years; radionuclide left ventricular ejection fraction [LVEF] 28.4 +/- 14.6%) underwent cardiopulmonary exercise testing (peak oxygen consumption 18.5 +/- 7.3 ml/kg per min; VE-CO2 slope 34.8 +/- 10.6) over a 2-year period. Using 1.96 standard deviations above the mean VE-VCO2 slope of 68 healthy age-matched subjects (mean slope 26.3 +/- 4.1), we defined a high ventilatory response to exercise as a slope >34. RESULTS: Eighty-three patients (48%) had an increased VE-VCO2 slope (mean 43.1 +/- 8.9). There was a difference in age (62.2 vs. 57.3 years, p = 0.005), New York Heart Association functional class (2.9 vs. 2.1, p < 0.001), LVEF (24.7 vs. 31.9%, p = 0.0016), peak oxygen consumption (14.9 vs. 21.7 ml/kg per min, p < 0.0001) and radiographic cardiothoracic ratio (0.58 vs. 0.55, p = 0.002) between these patients and those with a normal slope. In the univariate Cox proportional hazards model, the E-VCO2 slope was an important prognostic factor (p < 0.0001). In the multivariate Cox analyses using several variables (age, peak oxygen consumption, VE-VCO2 slope and LVEF), the VE-VCO2 slope gave additional prognostic information (p = 0.018) beyond peak oxygen consumption (p = 0.022). Kaplan-Meier survival curves at 18 months demonstrated a survival rate of 95% in patients with a normal VE-VCO2 slope compared with 69% in those with a high slope (p < 0.0001). CONCLUSIONS: A high VE-VCO2 slope selects patients with more severe heart failure and is an independent prognostic marker. The VE-VCO2 slope may be used as a supplementary index in the assessment of patients with chronic heart failure.

Aged↗
PubMed1997

Clinical characteristics of chronic heart failure patients with an augmented peripheral chemoreflex.

AIMS: The peripheral chemoreflex may be augmented in chronic heart failure and may play a role in its pathophysiology including the mediation of exercise hyperpnoea and sympathetic activation. The objective of this study was to characterize the patients with an augmented peripheral chemoreflex. METHODS AND RESULTS: Peripheral chemoreflex sensitivity was assessed by measuring the ventilatory response to hypoxia using transient inhalations of pure nitrogen in 50 patients with chronic heart failure (age 58.7 +/- 12.1 (SD) years; radionuclide left ventricular ejection fraction 26.5 +/- 13.0%). The peripheral chemoreflex of 12 healthy controls with similar demographic characteristics was 0.272 +/- 0.201l.min-1.%Sao(2)-1 compared with 0.673 +/- 0.410l. min-1.%Sao(2)-1 (P < 0.0001) in the chronic heart failure patients. Using 2 standard deviations above the mean level of the controls peripheral chemoreflex sensitivity as the upper limit of normal, we defined an augmented chemoreflex as greater than 0.6751.min-1.%Sao(2)-1. Twenty of the chronic heart failure patients (40%) demonstrated such an augmented peripheral chemoreflex. Compared with patients with peripheral chemoreflex sensitivity within the normal range, they had a reduced peak oxygen consumption during cardiopulmonary exercise (15.1 +/- 4.4 vs 18.5 +/- 5.8 ml.kg-1.min-1, P = 0.02), reduced radionuclide left ventricular ejection fraction (21.8 +/- 11.8 vs 29.4 +/- 13.1%, P = 0.046) and were in a worse New York Heart Association functional class (2.8 vs 2.4, P = 0.05). The ventilatory response to exercise, as characterized by the regression slope relating minute ventilation to carbon dioxide output during exercise, was also higher (40.48 +/- 9.32 vs 34.54 +/- 7.19, P = 0.02), consistent with the role of the peripheral chemoreflex in mediating exercise hyperpnoea. There was also an increased proportion of patients with non-sustained ventricular tachycardia in the group with an augmented peripheral chemoreflex (61% vs 21%, chi-squared 7.08, P < 0.01). No difference was seen in the age, height, weight and lung function measurements of these patients compared with the normal chemoreflex group. CONCLUSION: An augmented peripheral chemoreflex is a common finding in chronic heart failure patients, one associated with increasing severity and with the exercise hyperpnoea seen in the condition. That there was an excess of patients with non-sustained ventricular tachycardia in the group with an augmented peripheral chemoreflex may be related to the chemoreflex-driven sympathetic stimulation. The peripheral chemoreflex may be important in the pathophysiology of chronic heart failure, both in terms of symptoms and exercise limitation.

Case-Control Studies↗