Atrial natriuretic factor during exercise in patients with congestive heart failure

In order to evaluate the potential relationship between atrial pressure development and release of atrial natriuretic factor (ANF), 33 patients with congestive heart failure were investigated with right-sided heart catheterization during supine graded bicycle exercise. Resting plasma ANF levels were higher in patients with heart failure as compared with normal controls, 75.1 +/- 45.6 pmol/l vs 12.3 +/- 6.2 pmol/l (mean +/- SD, N = 33 and N = 42, respectively) and correlated with right atrial, pulmonary arterial and pulmonary capillary wedge pressures. During exercise, central pressures rose steeply with a simultaneous increase in plasma ANF in all patients. Plasma ANF levels correlated with heart rate at a workload of 25 w, to pulmonary arterial and pulmonary capillary wedge pressure at 50 w, and to pulmonary capillary wedge pressure at 75 w. The increments in ANF levels between the different workloads during exercise did not correlate with the corresponding increments in pressure values. In congestive heart failure, the capability of ANF secretion in consequence to pressure stimuli is preserved, and left atrial pressure seems to be the major stimulus for ANF release during exercise.     

Ventilatory drive during exercise in congestive heart failure

Background: Continuous increases in the ventilatory equivalent for carbon dioxide (the ratio of minute ventilation to carbon dioxide production, an index of ventilatory drive) during exercise in patients with congestive heart failure would suggest that factors other than carbon dioxide excessively stimulate ventilation during exercise, and may be an important factor in exercise-related dyspnea and fatigue in these patients.Methods and Results: Eighty-five patients with congestive heart failure and 17 normal control subjects underwent symptom-limited exercise testing with gas-exchange analysis. Patients were divided into four functional classes (A–D, Weber's classification) based on peak exercise oxygen consumption. In all heart failure patient groups and in control subjects the ventilatory equivalent for carbon dioxide decreased (P < .005, class D; P < .0001, all other groups) from rest to anaerobic threshold. Three isolated patients showed a continuous increase in ventilatory drive during exercise (mean peak oxygen consumption 13.7 mL/kg/ min). In the lowest functional class (D) the ventilatory equivalent for carbon dioxide was greater than in all other groups at rest, at anaerobic threshold, and at peak exercise (P < .01).Conclusions: In all heart failure groups and in normal control subjects ventilatory drive, as determined by the ventilatory equivalent for carbon dioxide, decreases during exercise. Continuous increases in ventilatory drive during exercise are infrequently seen, suggesting that factors other than carbon dioxide production do not excessively stimulate ventilation in heart failure patients during exercise.     

Neurohumoral activation during exercise in congestive heart failure

Neurohumoral factors were assessed in 14 subjects with chronic, stable New York Heart Association functional class II or III congestive heart failure and nine comparably aged normal subjects at rest and during moderate (50 W) and strenuous (100 W) upright exercise. Heart failure was associated with elevated plasma renin activity and plasma antidiuretic hormone (ADH) concentrations at rest. However, plasma renin activity almost doubled (from 4.7 +/- 0.6 to 8.4 +/- 1.1 ng/ml per hour) during strenuous exercise in subjects with heart failure, and changed only minimally in normal control subjects. Plasma ADH concentration did not change during exercise in the presence of heart failure, but rose in normal subjects during strenuous exercise to levels comparable to those of subjects with heart failure. Similar plasma osmolality values were present in both groups. Circulating norepinephrine concentrations were insignificantly elevated by heart failure both at rest and during exercise, and plasma epinephrine concentrations were similar. These findings suggest independent neurohumoral activation during exercise in the presence of congestive heart failure, with predominant activation of the renin-angiotensin-aldosterone axis.     

Ventilatory markers during exercise for congestive heart failure

The exaggerated ventilatory response in patients with heart failure is clearly multifactorial and complex beyond a mere reduction in pulmonary blood flow. Pulmonary dysfunction, including ventilation-perfusion mismatching, decreased lung compliance, restriction, airway obstruction, decreased diffusion capacity, and decreases in respiratory muscle strength and endurance, contributes to an inefficient breathing pattern and increased work of breathing. This is further compounded by the limited ability of the failing heart to meet the metabolic demands of the respiratory muscles, leading to underperfusion and ischemia.Although VO2max has important implications with regard to functional capacity, exercise test personnel must be knowledgeable concerning the clinical physiology of ventilation during exercise in the patient with heart failure. Ventilatory markers, as Arena and coworkers have demonstrated, are most indicative of disease severity and enhance the prognostic value of the test results.     

Mechanisms of periodic breathing during exercise in patients with chronic heart failure

BACKGROUND: Periodic breathing (PB) in heart failure (HF) is attributed to many factors, including low cardiac output delaying the time it takes pulmonary venous blood to reach the central and peripheral chemoreceptors, low lung volume, lung congestion, augmented chemoreceptor sensitivity, and the narrow difference between eupneic carbon dioxide tension and apneic/hypoventilatory threshold. METHODS AND RESULTS: We measured expired gases, ventilation, amplitude, and duration of PB in 23 patients with PB during progressive exercise tests done with 0 mL, 250 mL, or 500 mL of added dead space. Periodicity of PB remained constant despite heart rate, oxygen consumption, and minute ventilation increasing. Within each PB cycle, starting from the beginning of exercise, the largest (peak) tidal volume approached maximum observed tidal volume, while the smallest (nadir) tidal volume increased as exercise power output increased. PB ceased when nadir tidal volume reached peak tidal volume. End-tidal carbon dioxide increased with added dead space, and PB ceased progressively earlier during the exercise done with increased dead space. CONCLUSION: Circulatory delay does not contribute to the PB observed in exercising HF patients. The pattern of gradually increasing nadir tidal volume during exercise and the effect of dead space on both PB ceasing and end-tidal carbon dioxide suggest that low tidal volume and carbon dioxide apnea threshold are important contributors to PB that occurs during exercise in HF.     

Autonomic abnormalities in congestive heart failure patients with sleep-disordered breathing

BackgroundThe increasing prevalence of chronic heart failure is affecting patients' longevity, quality of life, and health resources, despite advances in management. Recognizing and treating comorbid illnesses is critical. Risk factors such as hypertension and diabetes are treated, but less importance is placed on the role of sleep apnea in heart failure.Methods and ResultsThere is a discrepancy between the growing evidence on the potential adverse influence of sleep apnea on heart failure (and vice versa) and incorporating its treatment as part of the management strategy for chronic heart failure. Apneic episodes during sleep can lead to profound disturbances to the sympathetic and parasympathetic nervous system.ConclusionsThis review explores the impact of sleep disordered breathing in patients with chronic heart failure, focusing on the autonomic nervous system.     

Causes of breathing inefficiency during exercise in heart failure

BackgroundPatients with heart failure (HF) develop abnormal pulmonary gas exchange; specifically, they have abnormal ventilation relative to metabolic demand (ventilatory efficiency/minute ventilation in relation to carbon dioxide production [V_E/VCO₂]) during exercise. The purpose of this investigation was to examine the factors that underlie the abnormal breathing efficiency in this population.Methods and ResultsFourteen controls and 33 moderate-severe HF patients, ages 52 ± 12 and 54 ± 8 years, respectively, performed submaximal exercise (～65% of maximum) on a cycle ergometer. Gas exchange and blood gas measurements were made at rest and during exercise. Submaximal exercise data were used to quantify the influence of hyperventilation (PaCO₂) and dead space ventilation (V_D) on V_E/VCO₂. The V_E/VCO₂ relationship was lower in controls (30 ± 4) than HF (45 ± 9, P < .01). This was the result of hyperventilation (lower PaCO₂) and higher V_D/V_T that contributed 40% and 47%, respectively, to the increased V_E/VCO₂ (P < .01). The elevated V_D/V_T in the HF patients was the result of a tachypneic breathing pattern (lower V_T, 1086 ± 366 versus 2003 ± 504 mL, P < .01) in the presence of a normal V_D (11.5 ± 4.0 versus 11.9 ± 5.7 L/min, P = .095).ConclusionsThe abnormal ventilation in relation to metabolic demand in HF patients during exercise was due primarily to alterations in breathing pattern (reduced V_T) and excessive hyperventilation.     

Relative attenuation of sympathetic drive during exercise in patients with congestive heart failure

Patients with congestive heart failure have been considered to have augmented sympathetic drive both at rest and during dynamic exercise. The augmentation observed during exercise may be related to the state of near exhaustion experienced by patients with heart failure at relatively low work loads. To compare the response of the sympathetic nervous system to exercise in normal subjects and patients with heart failure when they are working in a comparable physiologic frame of reference, the data for both groups can be expressed as percent peak oxygen consumption achieved (percent peak VO2) rather than as a function of absolute oxygen consumption (VO2). Ten healthy control subjects and 31 patients with chronic clinical class II and III heart failure were studied during upright maximal bicycle exercise. Eighteen of the 31 patients had primary cardiomyopathy and 13 had ischemic cardiomyopathy. The average ejection fraction at rest was 24 +/- 10% (+/- SD) in the group with heart failure. Heart rate, systolic blood pressure, VO2 and plasma norepinephrine levels were measured at rest and throughout exercise. When the data were expressed as a function of percent peak VO2 achieved, patients with heart failure demonstrated a flatter slope (p = 0.004) than normal in the response of plasma norepinephrine to exercise, indicating a relative blunting of sympathetic drive. This was accompanied by attenuated heart rate (p = 0.001) and blood pressure (p less than 0.001) responses. These differences were not apparent when the data are expressed as a function of absolute VO2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hemodynamic responses during leg press exercise in patients with chronic congestive heart failure.

To increase muscle mass and strength in patients with chronic congestive heart failure (CHF), there is a need for implementing resistance exercises in exercise training programs. This study sought to assess the safety of rhythmic strength exercise with respect to left ventricular function in 9 patients with stable CHF, compared with 6 stable coronary patients with mild left ventricular dysfunction (control group). With use of right-sided catheterization, changes in left ventricular function were assessed during double leg press exercise at loads of 60% and 80% of maximum voluntary contraction. The exercise sessions lasted 14 minutes each, divided into work and recovery phases of 60/120 seconds. In CHF, during exercise at a 60% load, there was a significant increase in heart rate (mean +/- SEM 90 +/- 4 beats/min; p <0.05), mean arterial blood pressure (95 +/- 3 mm Hg; p <0.01), diastolic pulmonary artery pressure (20.2 +/- 2.7 mm Hg; p <0.01), and cardiac index (3 +/- 0.3 L/m2/min; p <0.05). Additionally, during leg press exercise at an 80% load, there was a significant decrease in systemic vascular resistance (1,086 +/- 80 dynes x s x cm(-5); p <0.001), an increased cardiac index (3.4 +/- 0.1; p <0.001), and left ventricular stroke work index (75 +/- 5 g x m/m2; p <0.01), suggesting enhanced left ventricular function. Compared with controls, in CHF the magnitude of changes in hemodynamic parameters during exercise, demonstrated at a 60% load, was significantly smaller (systemic vascular resistance: [mean] 1,613 --> 1000 vs 1472 --> 1,247 dynes x s x cm(-5); cardiac index: 2.4 --> 3 vs 2.8 --> 4.4 L/m2/min, and stroke work index: 60 --> 69 vs 114 --> 155 g x m/m2; p <0.05 each). Nevertheless, changes indicated an enhanced contractile function of the left ventricle in CHF. This study demonstrates stability of left ventricular function during resistance exercise in well-compensated CHF patients with optimal drug therapy, as well as the appropriateness of the chosen mode and intensity applied as these factors relate to cardiovascular stress. This conclusion cannot be extrapolated to patients with less well-compensated heart failure, or to more protracted resistance training.     

Airflow limitation and control of end-expiratory lung volume during exercise

To test the hypothesis that the presence of airflow limitation (AFL) influences the control of end-expiratory lung volume (EELV) during exercise, 11 subjects with normal lung function, performed submaximal exercise (SM) on a cycle ergometer, with and without AFL. AFL was achieved during exercise by increasing the density of the air via a hyperbaric chamber, compressed to a depth of 3 atm (3 ATA; with AFL). Five subjects achieved AFL during SM exercise at 3 ATA while the remaining six subjects did not achieve AFL. SM exercise was performed with the same apparatus in the hyperbaric chamber at sea level pressure with none of the subjects achieving AFL (SL; no-AFL). EELV (% of TLC, BTPS), was significantly larger during exercise at 3 ATA than during exercise at SL for the AFL group (SL = 44 +/- 6%; 3 ATA-AFL = 51 +/- 9%, P < 0.05; but, was not for the no-AFL group (SL = 46 +/- 6%; 3 ATA-no AFL = 46 +/- 7%). End inspiratory lung volume was significantly elevated during exercise at 3 ATA compared with SL in the AFL group (SL = 80 +/- 6%; 3 ATA-AFL = 86 +/- 6%; P = 0.01) but not in the no-AFL group (SL = 82 +/- 4%; 3 ATA-no AFL = 84 +/- 4%). Tidal volume and ventilation were not different for any condition. These data suggest that the occurrence of AFL influences the control of EELV.     

Cardiopulmonary exercise testing in congestive heart failure

Cardiopulmonary exercise testing includes the monitoring of respiratory gases and airflow to determine oxygen uptake, carbon dioxide (CO2) production, respiratory rate, tidal volume, and minute ventilation during a graded maximal exercise test. A plateau in oxygen uptake, which occurs despite an increase in work load, and which is termed maximal oxygen uptake (VO2 max), correlates with the maximal exercise cardiac output and can therefore be used to grade the severity of heart failure. The anaerobic threshold occurs at 60 to 70% of VO2 max and is another indicator of the severity of heart failure and, when attained, indicates that the patient is close to performing a maximal test. We have found VO2 max and anaerobic threshold to be objective measures of efficacy of both investigational and noninvestigational therapy in patients with heart failure. A pulmonary limitation to exercise can be identified by the failure to attain anaerobic threshold or VO2 max, as well as exhaustion of the ventilatory reserve, as estimated by maximal voluntary ventilation. Thus, cardiopulmonary exercise testing can be used to (1) grade the severity of heart failure, (2) objectively follow the response to therapy, and (3) differentiate a cardiac from a pulmonary limitation to exercise.     

The resistive and elastic work of breathing during exercise in patients with chronic heart failure

Patients with heart failure (HF) display numerous derangements in ventilatory function, which together serve to increase the work of breathing (W(b)) during exercise. However, the extent to which the resistive and elastic properties of the respiratory system contribute to the higher W(b) in these patients is unknown. We quantified the resistive and elastic W(b) in patients with stable HF (n = 9; New York Heart Association functional class I-II) and healthy control subjects (n = 9) at standardised levels of minute ventilation (V'(E)) during graded exercise. Dynamic lung compliance was systematically lower for a given level of V'(E) in HF patients than controls (p<0.05). HF patients displayed slightly higher levels of inspiratory elastic W(b) with greater amounts of ventilatory constraint and resistive W(b) than control subjects during exercise (p<0.05). Our data indicates that the higher W(b) in HF patients is primarily due to a greater resistive, rather than elastic, load to breathing. The greater resistive W(b) in these patients probably reflects an increased hysteresivity of the airways and lung tissues. The marginally higher inspiratory elastic W(b) observed in HF patients appears related to a combined decrease in the compliances of the lungs and chest wall. The clinical and physiological implications of our findings are discussed.     

Symptom burden of sleep-disordered breathing in mild-to-moderate congestive heart failure patients.

The symptom burden resulting from sleep-disordered breathing (SDB) in patients with mild-to-moderate congestive heart failure (CHF) is unclear. The current authors monitored 24-h activity levels and compared subjective and objective measures of daytime sleepiness in 39 CHF patients, New York Heart Association class 2-3, on optimal medication. A total of 22 patients were classified as SDB (apnoea/hypopnoea index (AHI) median (range) 22.3 (16.6-100) events.h-1), and 17 as no SDB (NoSDB; AHI 3.7 (0-12.3) events.h-1). SDB was defined as AHI>or=15 events.h-1. Patients were assessed by 24-h activity monitoring (actigraphy) for a period of up to 14 days, a single objective sleepiness test (Oxford Sleep Resistance test) and Epworth Sleepiness Scale. The duration of daytime activity was significantly shorter in the SDB group compared with the NoSDB group. The SDB group also had increased time in bed and poorer sleep quality, as shown by the fragmentation index. Objectively the SDB group when compared with the NoSDB group were significantly sleepier, subjectively the groups did not differ. The amount of napping was similar for both groups. Despite the lack of subjective symptoms of daytime sleepiness, congestive heart failure patients with sleep-disordered breathing were objectively sleepier during the day and had reduced daytime activity with longer periods in bed and poorer sleep quality when compared with those without sleep-disordered breathing.     

Diaphragmatic function after intense exercise in congestive heart failure patients.

Respiratory muscle strength and endurance is reduced in patients with congestive heart failure, making these patients susceptible to diaphragmatic fatigue during exercise. In order to determine whether or not contractile fatigue of the diaphragm occurs in patients with congestive heart failure following intense exercise, twitch transdiaphragmatic pressures (twitch Ptdi) were measured during unpotentiated and potentiated cervical magnetic stimulation (CMS) of the phrenic nerves before and at intervals after cycle endurance exercise. Ten patients aged 65.7+/-6.0 yrs (mean+/-SD) with an ejection fraction of 31.2+/-9.8% performed a constant-load symptom-limited exercise test at 60% of their peak work capacity. Twitch Ptdi at baseline were 15.9+/-6.3 cmH2O (unpotentiated CMS) and 28.8+/-10.7 cmH2O (potentiated CMS) and at 10 min postexercise were 16.4+/-4.7 cmH2O (unpotentiated CMS) and 27.6+/-10.1 cmH2O (potentiated CMS). One patient demonstrated a sustained fall in twitch Ptdi of > or = 15%, considered potentially indicative of diaphragmatic fatigue. Contractile diaphragmatic fatigue is uncommon in untrained patients with congestive heart failure following high-intensity constant-workload cycle exercise. Therefore, diaphragmatic fatigue is an unlikely cause of exercise-limitation during activities of daily living in heart failure patients.     

Treatment of sleep disordered breathing in congestive heart failure

In patients with congestive heart failure, sleep disordered breathing occurs commonly and is associated with an increased mortality. In addition to central sleep apnea (Cheyne–Stokes respiration), obstructive sleep apnea is more prevalent in patients with congestive heart failure than in the general population. As a result, a number of treatments have been investigated, with varying results. While many therapies may improve the severity of sleep disordered breathing, only positive pressure ventilation has been shown to improve cardiac function. Newer forms of positive pressure ventilation, such as adaptive servo-ventilation, appear to be even more effective at correcting central sleep apnea. Whether any of these treatments have an effect on transplant-free survival is presently unknown and awaits further study.     

Sleep disordered breathing and its treatment in congestive heart failure

Sleep disordered breathing (SDB) is a common problem with adverse cardiorespiratory, endocrinological, and endothelial effects. Recent studies demonstrate an even higher prevalence of SDB in congestive heart failure (CHF) than in a randomly selected population, with up to 40% and 11% having Cheyne Stokes respiration-central sleep apnoea and obstructive sleep apnoea-hypopnoea syndromes, respectively. Randomised controlled trials of nocturnal respiratory support for SDB associated with CHF for up to three months demonstrate significant benefits in terms of improvements in left ventricular ejection fraction, markers of sympathetic system activity, and quality of life. Further randomised controlled trials of larger scale and longer duration are required to establish the role and benefit of this intervention for the treatment of this debilitating condition. The evidence for the higher prevalence of SDB in CHF, its pathogenesis, its pathophysiological consequences, and the emerging benefits of respiratory support are reviewed.