Skip Navigation

European Journal of Heart Failure 2002 4(2):159-166; doi:10.1016/S1388-9842(01)00221-5
This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Malfatto, G.
Right arrow Articles by Facchini, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Malfatto, G.
Right arrow Articles by Facchini, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2002 European Society of Cardiology

Recovery of cardiac autonomic responsiveness with low-intensity physical training in patients with chronic heart failure

Gabriella Malfattoa,*, Giovanna Branzia, Beatrice Rivaa, Luca Salaa, Gastone Leonettia,b and Mario Facchinia

a Divisione di Cardiologia, Istituto Scientifico Ospedale San Luca, Istituto Auxologico Italiano IRCCS via Spagnoletto, 3-20147 Milan, Italy
b Università degli Studi di Milano Milan, Italy

* Corresponding author. Tel.: +39-02-582161; fax: +39-02-5821-6712. E-mail address: malfi{at}auxologico.it


   Abstract
Top
 Abstract
1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 
Background: A gradual worsening of autonomic control of cardiovascular function accompanies the progression of heart failure. Exercise training modulates autonomic balance, and may affect the prognosis of the disease.

Aims: The sympathovagal balance was studied after 3 months of low-intensity rehabilitation compared with conventional therapy in 45 patients with heart failure (52% ischemic, 48% idiopathic), of whom 30 underwent rehabilitation and 15 did not. In 11 rehabilitated patients we also studied the effects on autonomic profile of 6 additional months of home-based training. Rehabilitated and non-rehabilitated patients had similar NYHA class, ejection fraction, exercise pVO2; 50% assumed carvedilol (39±5 mg/day).

Methods and results: Autoregressive power spectral density of RR intervals variability were assessed during 10 min of: (1) supine rest and free breathing; (2) supine rest and breathing at 20 acts/min (= vagal stimulus); (3) standing (= sympathetic stimulus). During each period, the ratio LF/HF of the individual autospectrum indicated the sympathovagal balance. After 3 months of rehabilitation, pVO2 increased (20%); LF/HF at rest was unchanged (8.7±1.2 vs. 9.2±1.2); it decreased with controlled breathing (–18%) and increased during standing (+79%) (P<0.05). These changes were more evident after 6 months of home-based training, when pVO2 was still high: LF/HF at rest was reduced (5.4±0.9 vs. 8.5±2.1), decreased during controlled breathing (–17%) and increased during standing (87%) (P < 0.05). No changes in any variable were seen in non-rehabilitated patients.

Conclusions: A low intensity rehabilitation program restores autonomic tone and reactivity to vagal and sympathetic stimuli. Some of these effects are already evident after the initial hospital-based phase.

Key Words: Heart failure • Cardiac rehabilitation • Autonomic nervous system • Power spectrum

Received March 14, 2001; Revised June 21, 2001; Accepted September 7, 2001


   1. Introduction
Top
 Abstract
 1. Introduction
2. Methods
 3. Results
 4. Discussion
 References
 
The therapeutic approach to heart failure has changed over time. Positive inotropic drugs, diuretics and vasodilators have been widely used in the past. Recently, other drugs, such as angiotensin-converting enzyme inhibitors (ACE-inhibitors), β-blockers, and spironolactone have appeared as the optimal treatment for this disease [1–3], probably having synergistic action [2,3]. Remarkably, all these latter drugs interfere with the neurohormonal axis in an antiadrenergic direction at various levels. The possibility thus exists that any intervention modulating the autonomic nervous system by blunting sympathetic activation could slow the progression of the disease [4]. Indeed, in patients with congestive heart failure, the worsening of myocardial function is accompanied by the appearance of a marked neurohormonal derangement [5–10], with signs of sympathetic activation [5], parasympathetic withdrawal [6,7], and peripheral organ unresponsiveness to autonomic activation [8–10]. An abnormal neurohormonal control may per se explain the mechanism of disease advancement in heart failure [4]: it is indeed well known that the amount of circulating catecholamines in patients relates to the prognosis [5,8]. More recently, studies of the pathophysiology of autonomic control in the failing heart utilizing the analysis of RR intervals variability demonstrated progressive abnormalities in the power spectral profile of patients [9,10]. The utility of the analysis of heart rate variability for risk stratification in patients with congestive heart failure has indeed been proposed [11–13]. Among non-pharmacological approaches to reduce sympathetic hyperactivity, exercise training could be of considerable importance. In the last decade, it has been reported that besides increasing functional capability and improving functional class, exercise does not have serious adverse effects, and may improve prognosis in selected populations of patients with heart failure [14–16]. In a pioneering study, Coats et al. [17] demonstrated a significant shift towards parasympathetic modulation of autonomic control after a 6 months period of training. According to the therapeutic guidelines of the time, patients in that study were under treatment with digitalis, vasodilators and diuretics; approximately 75% of them assumed ACE-inhibitors, and none was on β-blockers. Moreover, the level of training was of the endurance type. Nowadays, treatment with high doses of ACE-inhibitors and β-blocking drugs has become widespread, digitalis is not required in patients in low NYHA class and sinus rhythm [18], and physical exercise in heart failure patients is often suggested at a lower level of effort, that offers good clinical results without the potentially adverse side effects on ventricular wall stress [19,20]. Thus, the purpose of the present study was two-fold. First, to determine if in the current era of treatment, exercise training could still affect cardiovascular autonomic control. Second, to evaluate whether a period of low-intensity, non-endurance cardiac rehabilitation could influence the sympathovagal balance and reactivity in patients with heart failure. Preliminary data have been presented [21].


   2. Methods
Top
 Abstract
 1. Introduction
 2. Methods
3. Results
 4. Discussion
 References
 
2.1. Patient population
We studied 45 patients with clinically stable heart failure, not enlisted for heart transplantation, referred to our rehabilitation program. Exclusion criteria for the study were: diabetic neuropathy, atrial fibrillation, severe ventilatory impairment. The etiology of heart failure was ischemic cardiomyopathy in 23 patients and idiopathic dilated cardiomyopathy in 22. Thirty patients (group 1) underwent 3 months of hospital-based, ambulatory rehabilitation; of them, 11 also completed a further 6-month period of home-based training (see below). For logistic reasons (they lived too far from the institution and could not reach it daily), 15 patients did not adhere to the rehabilitation program: they were considered as an open control group (group 2), and agreed to come back after 3 months for the same clinical and autonomic evaluation as rehabilitated patients. Table 1 shows the clinical characteristics of the two groups. Patients had comparable NYHA class, left ventricular ejection fraction (EF), exercise pVO2, anaerobic threshold (AT), ventilatory response to exercise (VE/VCO2 ratio). Therapy with the β-blocker carvedilol (25–75 mg/day, mean dose 39±5 mg) was also equally distributed. During a preliminary, brief hospitalization, we investigated if periodic breathing and/or nocturnal arterial desaturation were present. It was important to exclude these two conditions, because an abnormal central respiratory pattern may account for most of the periodic oscillations in the heart period in patients with heart failure [22,23], and can therefore interfere with the analysis and interpretation of the heart rate variability data obtained with spectral techniques.


View this table:
[in this window]
[in a new window]

  		Table 1 Clinical characteristics of the two groups of patients

 
2.2. Autonomic evaluation
Variability of RR intervals in the frequency domain was assessed, as in a previous study [24] during: (1) 10 min of quiet supine resting and free breathing; (2) 10 min of regular breathing at a frequency of 20 acts/min (a constant breathing pattern activates the predominantly parasympathetic cardiopulmonary receptors [25,26]); and (3) 10 min of active standing (sympathetic orthostatic stimulation [25,27]). We used a custom-made acquisition package (Marazza Inc., Monza, Italy) that simultaneously recorded ECG and respiratory oscillations by pletismography. The ECG was digitized at 500 Hz; QRS complex was recognized by cross-correlation with a template. Premature beats and the subsequent interval were automatically discarded, and this detection was also visually checked. The autoregressive algorithm used DC filtering and an Akaike model between 20 and 24 to provide the best statistical estimate [26]. Boundaries of the low frequency oscillation (LF=0.03–0.15 Hz) and of the high frequency oscillation (HF=0.15–0.40 Hz) were chosen by the investigator: their area was calculated by the software, and converted in normalized units (n.u.) to better identify the individual spectral component [26,27]. The amount of LF and HF oscillation (in n.u.) and their ratio LF/HF were calculated. The short-time autospectra of this group of patients with a normal breathing pattern did not show the very low frequency component (VLF: 0.00–0.03 Hz) that is probably linked to abnormal respiration and cyclic arterial desaturation [23]. As discussed above, both phenomena were absent in the study patients. In fact, the spectral analysis of respiratory tracing showed a very clear predominant component that cross-correlated with the high frequency component of the RR intervals spectrum [26]: no low- and very-low frequency components were usually observed. The ratio LF/HF of each autoregressive power spectrum was used as an index of sympathovagal balance. We choose this index instead of the more popular and extensively applied time domain variables [27,28] because there is convincing evidence that this index represents a solid and reliable tool for pathophysiological investigations on autonomic cardiovascular regulation [9,26,29]. Concerning this methodological issue, recent experimental evidence indicates that time-domain variables, included total and individual variance of the low- and high- frequency components of the spectrum, have a strong dependence on heart rate [30,31]: as a consequence, results of time- domain analysis are difficult to compare in patients in whom heart rate differs, because of drug treatment such as β-blockers, and decreases as is the case after exercise training (see Section 3).

2.3. Rehabilitation program
Rehabilitation was performed on an outpatient basis, and was a low-intensity training, as described by Belardinelli and colleagues [19]. Patients exercised for 1 h, 5 days per week for 3 months. The intensity of the calisthenics, treadmill or bicycle exercise was initially titrated to the heart rate reached at 40–50% of peak oxygen consumption, and could be increased gradually according to heart rate and to the referred fatigue (Borg scale). Educational sessions and individual counseling, were performed by the medical and paramedical staff. After the initial hospital-based period, patients were invited to continue their training program at home, two to three times per week, and to maintain the lifestyle changes introduced in the acute phase. The compliance to drug therapy and lifestyle and exercise prescriptions was assessed with monthly visits to the heart failure clinic.

2.4. Statistical analysis
Results are expressed as mean value±1 S.D. Differences between patients regarding discrete variables (e.g. therapies) were assessed by the {chi}2-square test. Differences among continuous variables were analyzed by ANOVA for repeated measurements (within patients) or by ANOVA (among groups of patients). Post-hoc comparisons were analyzed by the t-test with Bonferroni's correction. P<0.05 was considered significant.


   3. Results
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
4. Discussion
 References
 
3.1. Baseline autonomic profile
The two groups of patients (i.e. those who underwent rehabilitation and the open control group) were similar when their autonomic profiles were compared at baseline. All showed signs of increased sympathetic activation at rest, with a shallow, non-significant response to regular breathing and to orthostatic sympathetic stimulation (Table 2). No relationship was found between LF/HF, and it shifts with the various stimuli, and other clinical parameters, such as ventilation, peak oxygen consumption, anaerobic threshold, ejection fraction. We confirmed our recent finding that patients with heart failure of ischemic origin showed a stronger baseline sympathetic activation [24].


View this table:
[in this window]
[in a new window]

  		Table 2 Baseline spectral density of RR intervals variability in patients

 
3.2. Effects of hospital based rehabilitation
After 3 months of rehabilitation, all 30 patients showed an improvement in functional class and in exercise tolerance, as shown in Table 3a: NYHA class was reduced, baseline heart rate was reduced, peak VO2 and aerobic threshold rose, the ventilatory response (VE/VCO2) was reduced. Moreover, we did not observe any deterioration in ventricular function after rehabilitation: if anything, left ventricular ejection fraction slightly increased (Table 3a). The autonomic tone at rest was not significantly changed from baseline (Table 3b and Figs. 1 and 2), but patients showed an increased responsiveness to parasympathetic stimulation with regular breathing (LF/HF was reduced) and to sympathetic stimulation with standing (LF/HF increased). There was no relationship between the amount of improvement in exercise capability (expressed as % change in pVO2) and the amount of change in autonomic responsiveness (expressed as changes in LF/HF during controlled respiration or during standing). In the 15 patients who did not undergo rehabilitation, no changes were observed in functional class, exercise variables, autonomic profile (Table 3, Fig. 2).


View this table:
[in this window]
[in a new window]

  		Table 3 Effects of hospital-based rehabilitation on (a) clinical variables and (b) autonomic tone and reactivity

 


Figure 1
View larger version (12K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 Example of the power spectrum of a patient with clinically stable heart failure of ischemic origin, being treated with enalapril, 40 mg/day, and isosorbide mononitrate, 60 mg/day. The autospectrum at baseline showed a predominant low frequency component at rest, and no significant changes of the spectral profile during regular breathing and standing (left panels). This pattern changed after 3 months of rehabilitation, when a high frequency component became evident at rest and increased during regular breathing, while the low frequency component prevailed during standing.

 


Figure 2
View larger version (8K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 Average results of 3 months of rehabilitation on the LF/HF index. The top panel represents 30 patients who underwent rehabilitation, the bottom panel represents 15 patients who did not. A significant modulation of autonomic reactivity to regular breathing and standing was observed only in the former group.

 
3.3. Long-term home-based training
Eleven of the 30 patients completed the long-term part of the rehabilitation program. When released from the outpatients clinic, they were instructed to follow an individualized exercise program based on their daily activities (e.g. a daily walk of a given distance for a certain duration, daily series of calisthenics, a cycling session twice per week, etc.). The compliance of each patient was assessed by weekly phone calls and monthly visits, and was judged satisfactory. At the end of this additional home based program, patients showed a stable, improved functional class, exercise tolerance and left ventricular ejection fraction, as shown in Table 4a. At this time, a clear blunting of sympathetic activation was evident at rest (Table 4b and Fig. 3). Moreover, patients maintained the previously observed responsiveness to parasympathetic stimulation with regular breathing (LF/HF was reduced by 17±6%, P<0.05) and to sympathetic stimulation with standing (LF/HF increased by 87±8%, P<0.05) (Table 4b and Fig. 3).


View this table:
[in this window]
[in a new window]

  		Table 4 Effects of home-based rehabilitation on (a) clinical variables (n=11) and (b) autonomic tone and reactivity

 


Figure 3
View larger version (12K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 Average results of 3 and 9 months of rehabilitation on the LF/HF index. The data on 10 patients who continued rehabilitation for an additional 6-month period are presented. A significant modulation of autonomic tone, and a more pronounced reactivity to regular breathing and standing was observed with a longer period of physical exercise.

 

   4. Discussion
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
References
 
In this paper we show that low-intensity physical exercise modulates the abnormal autonomic profile observed in patients with mild to moderate heart failure. This effect accompanies a significant improvement in the clinical status of patients, who reached a lower NYHA class, showed a better exercise performance and, last but not least, did not have any deterioration in left ventricular ejection fraction. In fact, left ventricular ejection fraction slightly improved after rehabilitation: this finding is in line with previous reports showing a favorable ventricular remodeling in patients with reduced ejection fraction after myocardial infarction [32].

Concerning the effects of rehabilitation on autonomic control, our data confirm the previous work of Coats et al. [17], although in a different therapeutic setting and with a different exercise protocol. Thus, light physical activity, well tolerated by patients, can be proposed as a further tool for the antiadrenergic approach in the treatment of heart failure. In partial contrast with previous observations on patients with symptomatic moderate heart failure [9], at baseline we found signs of sympathetic hyperactivity with a prominent LF component in all patients, despite the fact that many of them were in NYHA class III and 33% had a pVO2 between 10 and 15 ml/kg per min (Table 1). In none of our patients was a prominent VLF component observed, or the LF component of the autospectrum was small or absent: we actually observed this spectral pattern (whose negative prognostic value has been recently well defined [33]) only in patients in NYHA class IV, who were unable to exercise and could not undergo a rehabilitation program (Malfatto et al., unpublished). A likely explanation of this apparent discrepancy may be as follows: in previous studies the established therapy was the traditional association of digitalis and diuretics [9,17]. On the contrary, among our asymptomatic patients in NYHA class II–III no one was on digitalis, according to the international guidelines for subjects with heart failure in sinus rhythm [18]; moreover, they were all being treated with ACE inhibitors, and more than half were also on β-blockers. These drugs improve the clinical condition and survival in patients with heart failure, probably through an improvement in cardiovascular autonomic control [34,35] as in the case of patients after myocardial infarction [36–38]. Thus, therapy with ACE-inhibitors and β-blockers, may help the sinus node to recover its responsiveness to the central command most likely responsible for the low frequency oscillations perceived with the spectral analysis [29].

A relevant finding of our study is that the modulation of autonomic tone and responsiveness has a long time-course. At variance with what has been observed after a first uncomplicated myocardial infarction, when 2 months of regular training produced a significant shift in baseline sympatho-vagal balance [39], 9 months were necessary to obtain the same results in patients with heart failure. In fact, after the first 3 months of rehabilitation, the baseline high sympathetic tone was unmodified, and only the responsiveness of the autonomic nervous system to vagal and sympathetic stimulation were restored. On one side, this difference could be due to the fact that post-MI patients underwent an endurance type of training, while patients with heart failure exercised at a much lower level. However, this explanation is unlikely, because patients in the study of Coats et al. [17] also performed an endurance training and showed a slow time-course of recovery from the abnormal autonomic control. More realistically, the abnormality in autonomic control is much greater and severe in patients with heart failure than in those with a first uncomplicated MI, who do not have a long-lasting disease: thus, the ‘reverse autonomic remodeling’ of autonomic abnormalities may need a longer period to take place.

A similar modulation of the sympathovagal balance, shifting it toward a greater parasympathetic tone is offered in patients with heart failure, by β-adrenergic blocking drugs [34,35]. In a different population, we previously showed that this potentially favourable autonomic outcome interacted with that offered by β-blockers and could persist in the long term [37]. It is still unknown whether the same may be true in patients with heart failure: the present data are too scanty to allow any deduction.

In conclusion, a low intensity rehabilitation program is safe, feasible and restores autonomic tone and reactivity to vagal and sympathetic stimuli. It can thus be offered as an adjunctive treatment to full dose pharmacologic therapy in patients with mild to moderate heart failure.


   Acknowledgements
 
We are grateful to Ada Spiezia, RN, for her help in collecting the data and her accuracy in keeping the patients’ files at the Rehabilitation Clinic.


   References
Top
 Abstract
 1. Introduction
 2. Methods
 3. Results
 4. Discussion
 References
 

  1. CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure. Results of the north Scandinavian enalapril survival study. N Engl J Med (1987) 316:1429–1435.[Abstract]
  2. Packer M., Bristow M.R., Cohn J.N., et al. Carvedilol Heart Failure Study Group The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. N Engl J Med (1996) 334:1349–1355.[Abstract/Free Full Text]
  3. Pitt B., Zannad F., Remme W.J., et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized ALdactone Evaluation Study Investigators. N Engl J Med (1999) 341:709–717.[Abstract/Free Full Text]
  4. Packer M. The neurohormonal hypothesis: a theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol (1992) 20:248–254.[Abstract]
  5. Cohn J.N., Levine T.B., Olivari M.T., et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med (1984) 311:819–823.[Abstract]
  6. Eckberg D.L., Drabinsky M., Braunwald E. Defective cardiac parasympathetic control in patients with heart disease. N Engl J Med (1971) 285:877–883.[Web of Science][Medline]
  7. Binkley P.F., Nunziata E., Haas G.J., Nelson S.D., Cody R.J. Parasympathetic withdrawal is an integral component of autonomic imbalance in congestive heart failure: demonstration in human subjects and verification in a paced canine model. J Am Coll Cardiol (1991) 18:464–472.[Abstract]
  8. Grassi G., Seravalle G., Cattaneo B.M., et al. Sympathetic activation and loss of reflex sympathetic control in mild congestive heart failure. Circulation (1995) 92:3206–3211.[Abstract/Free Full Text]
  9. Guzzetti S., Cogliati C., Turiel M., Crema C., Lombardi F., Malliani A. Sympathetic predominance followed by functional denervation in the progression of chronic heart failure. Eur Heart J (1995) 16:1100–1107.[Abstract/Free Full Text]
  10. Ponikowsky P., Chua T.P., Amadi A.A., et al. Detection and significance of a discrete very low frequency rhythm in RR interval variability in chronic congestive heart failure. Am J Cardiol (1996) 77:1320–1326.[CrossRef][Web of Science][Medline]
  11. Ponikowsky P., Anker S.D., Chua T.P., et al. Depressed heart rate variability as an independent predictor of death in chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. Am J Cardiol (1997) 79:1645–1650.[CrossRef][Web of Science][Medline]
  12. Nolan J., Batin P.D., Andrews R., et al. Prospective study of heart rate variability and mortality in chronic heart failure: results of the united Kingdom heart failure evaluation and assessment of risk trial (UK-heart). Circulation (1998) 98:1510–1516.[Abstract/Free Full Text]
  13. Lucreziotti S., Gavazzi A., Scelsi L., et al. Five-minutes recording of heart rate variability in severe chronic heart failure: correlates with right ventricular function and prognostic implications. Am Heart J (2000) 139:1088–1095.[CrossRef][Web of Science][Medline]
  14. McKelvie R.S., Teo K.K., McCartney N., Humen D., Montague T., Yusuf S. Effects of exercise training in patients with congestive heart failure: a critical review. J Am Coll Cardiol (1995) 25:789–796.[Abstract]
  15. European Heart Failure Training Group. Experience from controlled trials of physical training in chronic heart failure. Eur Heart J (1998) 19:466–475.[Abstract/Free Full Text]
  16. Belardinelli R., Georgiou D., Cianci G., Purcaro A. Randomized, controlled trial of long-term moderate exercise training in chronic heart failure: effects on functional capacity, quality of life and clinical outcome. Circulation (1999) 99:1173–1182.[Abstract/Free Full Text]
  17. Coats A.J.S., Adamopoulos S., Radaelli A., et al. Controlled trials of physical training in chronic heart failure. Circulation (1992) 85:2119–2131.[Abstract/Free Full Text]
  18. Task Force of the Working Group on Heart Failure of the European Society of Cardiology. The treatment of heart failure. Eur Heart J (1997) 18:736–753.[Free Full Text]
  19. Belardinelli R., Georgiou D., Scocco V., Barstow T.J., Purcaro A. Low intensity exercise training in patients with chronic heart failure. J Am Coll Cardiol (1995) 26:975–982.[Abstract]
  20. Demopoulos L., Bijou R., Fergus I., Jones M., Strom J., LeJemthel T.H. Exercise training in patients with severe congestive heart failure: enhancing peak aerobic capacity while minimizing the increase in ventricular wall stress. J Am Coll Cardiol (1997) 29:597–603.[Abstract]
  21. Malfatto G., Gritti S., Sala L., et al. A short period of low intensity physical training restores cardiac autonomic responsiveness in patients with heart failure [Abstract]. Eur J Heart Failure (2000) 2:50.[Free Full Text]
  22. Pinna G., Maestri R., La Rovere M.T., Mortara A. An oscillation of the respiratory control system accounts for most of the heart period variability of chronic heart failure patients. Clin Sci (1996) 91(Suppl):89–91.[Medline]
  23. Mortara A., Sleight P., Pinna G.D., et al. Abnormal awake respiratory patterns are common in chronic heart failure and may prevent evaluation of autonomic tone by measurements of heart rate variability. Circulation (1997) 96:246–252.[Abstract/Free Full Text]
  24. Malfatto G., Gritti S., Sala L., et al. Different baseline sympathovagal balance and cardiac autonomic responsiveness in ischemic and non-ischemic congestive heart failure. Eur J Heart Failure (2001) 3:197–202.[Abstract/Free Full Text]
  25. Hayano J., Mukai S., Sakakibara M., Okada A., Takata K., Fujinami T. Effects of respiratory interval on vagal modulation of heart rate. Am J Physiol (1994) 267:H33–H40.[Web of Science][Medline]
  26. Pagani M., Lombardi F., Guzzetti S., et al. Power spectral analysis of heart rate and arterial pressure variabilities as a marker of sympathovagal interaction in man and conscious dog. Circ Res (1986) 59:178–193.[Abstract/Free Full Text]
  27. Task force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability. Standard of measurement, physiological interpretation and clinical use. Circulation (1996) 93:1043–1065.[Free Full Text]
  28. The Multicentre post-infarction Research Group. Kleiger R.E., Miller J.P., Bigger J.T., Moss A.J. Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. Am J Cardiol (1987) 59:256–262.[CrossRef][Web of Science][Medline]
  29. Cooley R.L., Montano N., Cogliati C., et al. Evidence for a central origin of the low-frequency oscillation in RR-interval variability. Circulation (1998) 98:556–561.[Abstract/Free Full Text]
  30. Rocchetti M., Malfatto G., Lombardi F., Zaza A. Role of the input/output relation of sinoatrial myocytes in cholinergic modulation of heart rate variability. J Cardiovasc Electrophys (2000) 11:522–530.[CrossRef][Web of Science][Medline]
  31. Zaza A., Lombardi F. Autonomic indexes based on the analysis of heart rate variability: a view from the sinus node. Cardiovasc Res (2001) 50:434–442.[Abstract/Free Full Text]
  32. Giannuzzi P., Tavazzi L., Temporelli P.L., et al. Attenuation of unfavorable remodeling by exercise training in postinfarction patients with left ventricular dysfunction. Circulation (1997) 96:1790–1797. for the ELVD study group.[Abstract/Free Full Text]
  33. Galinier M., Pathak A., Fourcade J., et al. Depressed low frequency power of heart rate variability as an independent predictor of sudden death in chronic heart failure. Eur Heart J (2000) 21:475–482.[Abstract/Free Full Text]
  34. Mortara A., la Rovere M.T., Pinna G.D., Maestri R., Capomolla S., Cobelli F. Nonselective beta-adrenergic blocking agent, carvedilol, improves arterial baroreflex gain and heart rate variability in patients with stable chronic heart failure. J Am Coll Cardiol (2000) 36:1612–1628.[Abstract/Free Full Text]
  35. Malfatto G, Branzi G, Riva B, et al. Carvedilol restores both autonomic tone and responsiveness in moderate heart failure [Abstract], Eur Heart J (in press).
  36. Sandrone G., Mortara A., Torzillo D., La Rovere M.T., Malliani A., Lombardi F. Effects of beta blockers (atenolol or metoprolol) on heart rate variability after acute myocardial infarction. Am J Cardiol (1994) 74:340–345.[CrossRef][Web of Science][Medline]
  37. Kontopoulos A.G., Athyros V.G., Papageorgiou A.A., Papadopoulos G.V., Avramidis M.J., Boudoulas H. Effect of quinapril or metoprolol on heart rate variability in post-myocardial infarction patients. Am J Cardiol (1996) 77:242–246.[CrossRef][Web of Science][Medline]
  38. Malfatto G., Facchini M., Sala L., Branzi G., Bragato R., Leonetti G. Effects of cardiac rehabilitation and beta blocker therapy on heart rate variability after first acute myocardial infarction. Am J Cardiol (1998) 81:834–840.[CrossRef][Web of Science][Medline]
  39. Malfatto G., Facchini M., Sala L., Branzi G., Bragato R., Leonetti G. Short and long term effects of exercise training on the tonic autonomic modulation of heart rate variability after myocardial infarction. Eur Heart J (1996) 17:532–538.[Abstract/Free Full Text]

Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Circ Heart FailHome page
G. Parati, G. Malfatto, S. Boarin, G. Branzi, G. Caldara, A. Giglio, G. Bilo, G. Ongaro, A. Alter, B. Gavish, et al.
Device-Guided Paced Breathing in the Home Setting: Effects on Exercise Capacity, Pulmonary and Ventricular Function in Patients With Chronic Heart Failure: A Pilot Study
Circ Heart Fail, September 1, 2008; 1(3): 178 - 183.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. Sports. Med.Home page
M Pagkalos, N Koutlianos, E Kouidi, E Pagkalos, K Mandroukas, and A Deligiannis
Heart rate variability modifications following exercise training in type 2 diabetic patients with definite cardiac autonomic neuropathy
Br. J. Sports Med., January 1, 2008; 42(1): 47 - 54.
[Abstract] [Full Text] [PDF]

Home page
 J. Appl. Physiol.Home page
R. U. Pliquett, K. G. Cornish, K. P. Patel, H. D. Schultz, J. D. Peuler, and I. H. Zucker
Amelioration of depressed cardiopulmonary reflex control of sympathetic nerve activity by short-term exercise training in male rabbits with heart failure
J Appl Physiol, November 1, 2003; 95(5): 1883 - 1888.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Malfatto, G.
Right arrow Articles by Facchini, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Malfatto, G.
Right arrow Articles by Facchini, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?