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Biomedical subjects

D Harrington

Publications and source records attributed to D Harrington.

At least 55 records · Page 3Linked to original sources
PubMed1998

MOPP/ABV hybrid chemotherapy for advanced Hodgkin's disease significantly improves failure-free and overall survival: the 8-year results of the intergroup trial.

PURPOSE: To compare the efficacy of sequential mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) followed by doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) versus the MOPP/ABV hybrid regimen in advanced-stage Hodgkin's disease. PATIENTS AND METHODS: A total of 737 patients with previously untreated stages III2A, IIIB, IVA, or IVB Hodgkin's disease and patients in first relapse after radiotherapy were prospectively randomized to sequential MOPP-ABV or MOPP/ABV hybrid. Of 691 eligible patients, 344 received the sequential regimen and 347 received the hybrid. RESULTS: The overall response rate was 95%, with complete responses (CRs) in 79%: 83% on the MOPP/ABV hybrid and 75% on the sequential MOPP-ABVD arm (P = .02). With a median follow-up time of 7.3 years, the 8-year failure-free survival (FFS) rates were 64% for MOPP/ABV hybrid and 54% far sequential MOPP-ABVD (P = .01; 0.69 relative risk of failure, comparing MOPP/ABV hybrid v MOPP-ABVD). The 8-year overall survival rate was significantly better for the MOPP/ABV hybrid (79%) as compared with sequential MOPP-ABVD (71%) (P = .02; relative risk, 0.65). MOPP/ABV hybrid had significantly more life-threatening or fatal neutropenia and pulmonary toxicity than the sequential MOPP-ABVD arm, which was associated with significantly greater thrombocytopenia. Nine cases of acute myelogenous leukemia or myelodysplasia were reported on the sequential regimen as compared with only one on the hybrid (P = .01). CONCLUSION: MOPP/ABV hybrid chemotherapy was significantly more effective than sequential MOPP-ABVD. FFS and overall survival were significantly improved on the hybrid arm, which was also associated with a lower incidence of acute leukemia or myelodysplasia.

Adolescent↗
PubMed1998

Elevation of conjugated cis-9, trans-11-octadecadienoic acid in bovine milk because of dietary supplementation.

Cows on pasture were fed full fat soybeans (toasted, flaked, and pelleted) or ground full fat rapeseeds to investigate effects on cis-9, trans-11-octadecadienoic acid in milk. Three herds of 16 cows each that were on pasture were fed 3.1 kg/d of unmolassed beet pulp (control), 3.0 kg/d of rapeseed concentrate, or 3.1 kg/d of a soybean supplement. The concentration of cis-9, trans-11-octadecadienoic acid in the milk of cows fed the rapeseed and soybean supplements was significantly higher than in the milk of cows fed the control diet during the feeding trial. Over the trial, the cis-9, trans-11-octadecadienoic acid concentration in the milk of individual cows varied from 6.8 to 25.7 mg/g of fat in the control herd, from 10.6 to 33.5 mg/g of fat in the herd fed the rapeseed concentrate, and from 8.8 to 30.5 mg/g of fat in the herd fed the soybean supplement. The concentration of cis-9, cis-12-octadecadienoic acid, the substrate for cis-9, trans-11-octadecadienoic acid synthesis in the rumen, was 4.9 g/100 g of fatty acid methyl esters in the milk fat of cows fed the soybean supplement, 2.5 g/100 g of fatty acid methyl esters in the milk fat of cows fed the rapeseed concentrate, and 2.3 g/100 g of fatty acid methyl esters in the milk fat of the control cows. Milk yield and milk constituent yields were not affected by supplementation of either full fat soybeans or rapeseeds compared with controls, but milk protein concentration was significantly reduced by both oilseed supplements.

Animals↗
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

Nonsurgical septal reduction for hypertrophic obstructive cardiomyopathy: outcome in the first series of patients.

BACKGROUND: Some patients with hypertrophic obstructive cardiomyopathy may gain symptomatic relief from a reduction in the extent of obstruction to left ventricular outflow. We present the outcome of the first series of patients treated with an alternative method of gradient reduction using catheter techniques. METHODS AND RESULTS: Eighteen patients were treated with selective intracoronary alcohol injection to induce localized septal infarction. Patients underwent echocardiographic measurement of left ventricular dimensions and Doppler echocardiographic evaluation of left ventricular outflow tract gradients before the procedure, on the first postoperative day, and at a median follow-up of 3 months after the procedure. In addition, patients underwent exercise testing and symptom evaluation before and 3 months after nonsurgical septal reduction. There was a significant reduction in left ventricular outflow tract obstruction after the procedure (preprocedure, 67 mm Hg [95% CI, 48 to 87 mm Hg]; postprocedure, 25 mm Hg [95% CI, 16 to 34 mm Hg]; P=.0006), which persisted at 3-month follow-up (22 mm Hg [95% CI, 12 to 32 mm Hg]; P=.001). This was associated with a significant improvement in symptoms. There was a small but not significant increase in exercise capacity (n=10; preprocedure, 418 seconds [95% CI, 273 to 563 seconds]; postprocedure, 452 seconds [95% CI, 283 to 621 seconds). Left ventricular dimensions were not significantly altered by nonsurgical septal reduction. CONCLUSIONS: Nonsurgical septal reduction significantly reduces left ventricular outflow tract obstruction and improves symptoms in some patients with hypertrophic obstructive cardiomyopathy. The technique may provide an alternative to surgical myomectomy in selected patients.

Adolescent↗
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

Skeletal muscle function and its relation to exercise tolerance in chronic heart failure.

OBJECTIVES: This study sought to define the relation between muscle function and bulk in chronic heart failure (HF) and to explore the association between muscle function and bulk and exercise capacity. BACKGROUND: Skeletal muscle abnormalities have been postulated as determinants of exercise capacity in chronic HF. Previously, muscle function in chronic HF has been evaluated in relatively small numbers of patients and with variable results, with little account being taken of the effects of muscle wasting. METHODS: One hundred male patients with chronic HF and 31 healthy male control subjects were studied. They were matched for age (59.0 +/- 1.0 vs. 58.7 +/- 1.7 years [mean +/- SEM]) and body mass index (26.6 +/- 0.4 vs. 26.3 +/- 0.7 kg/m2). We assessed maximal treadmill oxygen consumption (VO2), quadriceps maximal isometric strength, fatigue (20-min protocol, expressed in baseline maximal strength) and computed tomographic cross-sectional area (CSA) at midthigh. RESULTS: Peak VO2 was lower in patients (18.0 +/- 0.6 vs. 33.3 +/- 1.4 ml/min per kg, p < 0.0001), although both groups achieved a similar respiratory exchange ratio at peak exercise (1.15 +/- 0.01 vs. 1.19 +/- 0.03, p = 0.13). Quadriceps (582 vs. 652 cm2, p < 0.05) and total leg muscle CSA (1,153 vs. 1,304 cm2, p < 0.005) were lower in patients with chronic HF. Patients were weaker than control subjects (357 +/- 12 vs. 434 +/- 18 N, p < 0.005) and also exhibited greater fatigue at 20 min (79.1% vs. 92.1% of baseline value, p < 0.0001). After correcting strength for quadriceps CSA, significant differences persisted (5.9 +/- 0.2 vs. 7.0 +/- 0.3 N/cm2, p < 0.005), indicating reduced strength per unit muscle. In patients, but not control subjects, muscle CSA significantly correlated with peak absolute VO2 (R = 0.66, p < 0.0001) and is an independent predictor of peak absolute VO2. CONCLUSIONS: Patients with chronic HF have reduced quadriceps maximal isometric strength. This weakness occurs as a result of both quantitative and qualitative abnormalities of the muscle. With increasing exercise limitation there is increasing muscle weakness. This progressive weakness occurs predominantly as a result of loss of quadriceps bulk. In patients, this muscular atrophy becomes a major determinant of exercise capacity.

Case-Control Studies↗
PubMed1997

Hibernating myocardium: clinical and functional response to revascularisation.

OBJECTIVE: We assessed the effects of coronary bypass grafting on left ventricular (LV) function, exercise capacity and symptom profile in patients with LV impairment and evaluated the role of identifying myocardial hibernation in a prospective non-randomised study. METHODS: Of 120 patients screened, 47 patients with LV ejection fraction < 35% and three vessel coronary artery disease were studied. All underwent stress/redistribution and separate day rest/redistribution T1-201 imaging together with cine MRI at enrolment, and cine MRI at follow-up. Group 1, 30 patients undergoing bypass surgery, underwent symptom limited treadmill exercise testing with peak VO2 measurement, and symptom profile evaluation less than 3 months before, and 3-6 months after operation. Revascularisation was assessed by post-operative T1-201 imaging and repeat coronary angiography. Group 2, 17 patients treated on medical therapy alone underwent symptom profile assessment at enrolment and follow-up for those who survived. Segmental hibernation was defined as the equivalent of greater than 50% of maximal T1-201 uptake where wall motion was severely impaired on resting imaging. Patients were considered to be hibernating where two of nine LV segments fulfilled these criteria. RESULTS: In group 1, five patients died (17%), peri-or post-operatively, two defaulted and 23 attended follow-up studies. In group 2, three patients died prior to follow-up (18%). In the surgical group there was an increase in mean LVEF from 24.0 +/- 8% to 29.7 +/- 11% (P < 0.05) while in the medical group there was a fall from 25.7 +/- 10% to 20.6 +/- 8% (P < 0.05). In group 1, the mean NYHA dyspnoea grade improved from 2.7 to 1.4 while in the medical group it was unchanged, 2.6 to 2.5. In patients with myocardial hibernation identified pre-operatively, 18/19 (95%) improved LVEF after CABG compared with 2/4 (50%) of patients without hibernation. 17/19 (86%) patients with hibernation improved NYHA dyspnoea class compared with 2/4 (50%) of patients without. 60/93 (65%) of hibernating segments improved function after revascularisation while 47/53 (89%) hibernating segments showed no improvement on medical therapy alone. CONCLUSION: In patients with severe LV impairment with myocardial hibernation, coronary artery bypass grafting improves both global and regional systolic LV function, and symptom profile. Medical treatment of patients with LV impairment and myocardial hibernation does not improve LV contractile function or symptoms. Both surgical and medical therapy carry a high mortality rate.

Adult↗
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↗
PubMed1997

Mechanisms of exercise intolerance in congestive heart failure.

A major aim in treating patients with chronic heart failure is to improve exercise capacity and quality of life. Experimental evidence does not support the view that central hemodynamic disturbance is the sole determinant of exercise capacity. Rather, multiple other factors including abnormalities of ventilatory control, the lungs, the peripheral circulation, and skeletal muscle appear to combine to generate symptoms and limit exercise.

Exercise Test↗
PubMed1997

Exercise capacity in chronic heart failure is related to the aetiology of heart disease.

OBJECTIVE: To assess whether the underlying aetiology of chronic heart failure is a predictor of exercise performance. SETTING: Tertiary referral centre for cardiology. PATIENTS AND OUTCOME MEASURES: Retrospective study of maximum exercise testing with metabolic gas exchange measurements in 212 patients with chronic heart failure who had undergone coronary angiography. Echocardiography and radionucleide ventriculography were used to determine indices of left ventricular function, and coronary arteriography was used to determine whether the cause of chronic heart failure was ischaemic heart disease (n = 122) or dilated cardiomyopathy (n = 90). RESULTS: The cardiomyopathy group was younger (mean (SD) age 58.45 (11.66) years v 61.49 (7.42); p = 0.02) but there was no difference between the groups in ejection fraction or fractional shortening. Peak oxygen consumption (VO2) was higher in the dilated group, while the slope relating carbon dioxide production and ventilation (VE/VCO2 slope) was the same in both groups. Both groups achieved similar respiratory exchange ratios at peak exercise, suggesting that there was near maximum exertion. There was a relation between peak VO2 and age (peak VO2 = 33.9-0.267*age; r = 0.36; p < 0.001). After correcting for age, the peak achieved VO2 was still greater in the cardiomyopathy group than in the ischaemic group (p < 0.002). CONCLUSIONS: Exercise performance for a given level of cardiac dysfunction appears to vary with the aetiology of heart failure. Thus the two diagnostic categories should be considered separately in relation to abnormalities of exercise physiology. The difference may in part account for the worse prognosis in ischaemic patients.

Cardiomyopathy, Dilated↗
PubMed1997

Chemoreceptor dependence of very low frequency rhythms in advanced chronic heart failure.

Factors responsible for very low frequency oscillations (VLF; cycle > 30 s) in the cardiovascular system remain obscure. We tested the hypothesis that increased peripheral chemosensitivity is important in the pathogenesis of VLF oscillations in patients with chronic heart failure (CHF). Fourteen male patients with stable, moderate to severe CHF (age 60 +/- 1.1 yr, ejection fraction 23 +/- 11%) and reproducible VLF oscillations in heart rate underwent a protocol consisting of three consecutive 20-min phases during which they breathed air, hyperoxia (O2 via mask, 60% O2 concn), and air again. Autoregressive spectral analysis of R-R intervals, blood pressure, and respiration was used to quantify total oscillatory power (TP), VLF, low (0.04-0.15 Hz)- and high (0.15-0.40Hz)-frequency power, and the coherence between these signals. Peripheral chemosensitivity was studied by assessing the ventilatory response to hypoxia using transient inhalations of pure N2. Discrete VLF rhythms were seen in R-R intervals in all 14 patients, in blood pressure in 7 of 14, and in respiration in 8 of 14 patients. A significant coherence (> 0.5) between heart rate and systolic blood pressure within the VLF band with mean phase value of -140 degrees, suggesting an antibaroreflex relationship, was seen in six subjects. Transient hyperoxia abolished the VLF oscillations in most subjects (12 of 14 in R-R intervals) and decreased R-R variability power within the VLF band. This response significantly correlated with peripheral chemoreceptor sensitivity (r = 0.77, P = 0.014). This study suggests that in CHF, enhanced peripheral chemoreceptor activity may facilitate slow oscillations in the cardiorespiratory signals.

Aged↗
PubMed1996

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

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

Autonomic Nervous System↗