Skip Navigation

European Journal of Heart Failure 2006 8(7):716-722; doi:10.1016/j.ejheart.2006.01.008
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 arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Piccirillo, G.
Right arrow Articles by Marigliano, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Piccirillo, G.
Right arrow Articles by Marigliano, V.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© 2006 European Society of Cardiology

Influence of cardiac-resynchronization therapy on heart rate and blood pressure variability: 1-year follow-up

Gianfranco Piccirilloa,*, Damiano Magría, Silvia di Carloa, Tiziana De Laurentisa, Alessia Torrinia, Sabrina Materaa, Marzia Magnantia, Leda Bernardib, Franco Barillàb, Raffaele Quaglioneb, Evaristo Ettorrea and Vincenzo Mariglianoa

a Dipartimento di Scienze dell'Invecchiamento, I Clinica Medica, Policlinico Umberto I, Università "La Sapienza", 00161 Rome, Italy
b Istituto del Cuore e dei Grossi Vasi "Attilio Reale", Policlinico Umberto I, Università "La Sapienza", Rome, Italy

* Corresponding author. Tel.: +39 064463301 2 3; fax: +39 064940594. E-mail address: gianfranco.piocirillo{at}uniromal.it (G.Piccirillo).


   Abstract
Top
 Abstract
1. Introduction
 2. Method
 3. Results
 4. Discussion
 5. Limitations of the...
 References
 
Background: Several studies have shown that cardiac-resynchronization therapy (CRT) improves haemodynamic function, cardiac symptoms, and heart rate variability (HRV) and reduces the risk of mortality and sudden death in subjects with chronic heart failure (CHF). In subjects with CHF, power spectral values for the low-frequency (LF) component of RR variability ≥13 ms2, are associated with an increased risk of sudden death.

Aims and methods: To assess whether spectral indexes obtained by power spectral analysis of HRV and systolic blood pressure (SBP) variability could predict malignant ventricular arrhythmias in patients with severe CHF treated with an implantable cardioverter–defibrillator (ICD) alone or with ICD+CRT. In addition, changes in non-invasive spectral indices using short-term power spectral analysis of HRV and SBP variability during controlled breathing in 15 patients with CHF treated with an ICD alone and 16 patients receiving ICD+CRT, were assessed pre-treatment and at 1 year.

Results: Arrhythmias necessitating an appropriate ICD shock were more frequent in subjects who had low LF power. CRT improved all spectral components, including LF power.

Conclusions: Low LF power values predict an increased risk of malignant ventricular arrhythmias; after 1 year of CRT most non-spectral and spectral data, including LF power, improved. Whether these improvements lead to better long-term survival in patients with CHF remains unclear.

Key Words: Chronic heart failure • Cardiac resynchronization therapy • Implantable cardioverter–defibrillator • Sudden death • Heart rate variability • Power spectral analysis

Received June 22, 2005; Revised November 14, 2005; Accepted January 18, 2006


   1. Introduction
Top
 Abstract
 1. Introduction
2. Method
 3. Results
 4. Discussion
 5. Limitations of the...
 References
 
A low ejection fraction in patients with non-ischemic and ischemic dilated cardiomyopathy is a risk factor for sudden cardiac death [1,2]. Power spectral analysis of heart rate variability (HRV) has been shown to provide information on the mode of death in chronic heart failure (CHF) [3]. Furthermore, decreased low-frequency (LF) values of HRV are sensitive predictors of sudden death [4]. A paradoxical reduction in LF power in a condition such as CHF could be linked to reduced responsiveness of the adrenergic beta-receptor in the sinus node and to a loss of oscillatory behaviour during chronic sympathetic over activity [4-6]. A recent study has shown that the haemodynamic and clinical improvement following cardiac resynchronization therapy (CRT) is also associated with increased HRV [7]. The CARE-HF study showed that CRT also reduces the risk of sudden death [8] and the effect is maintained over an increased follow-up period [9].

The aim of this study was to investigate whether spectral analysis of HRV, in particular of LF power oscillations, predicts the occurrence of malignant ventricular arrhythmias in CHF patients (with a low ejection fraction and prolonged QRS interval) undergoing prophylactic treatment with an implantable cardioverter-defibrillator (ICD) alone or in combination with CRT (using a biventricular pacemaker). We also compared the effect of 1-year treatment with an ICD alone or in combination with CRT on New York Heart Association (NYHA) class and on spectral measures of HRV.


   2. Method
Top
 Abstract
 1. Introduction
 2. Method
3. Results
 4. Discussion
 5. Limitations of the...
 References
 
2.1. Study subjects
We selected 31 outpatients (25 men and 6 women) who had stable CHF secondary to ischaemic dilated cardiomyopathy, and 12 healthy control subjects (9 men and 3 women).

Criteria for inclusion of patients with CHF were; an ejection fraction ≤35%, a QRS interval >120 ms and sinus rhythm. Criteria for exclusion of all subjects were malignancy, primary valve disease, frequent extrasystole (more than one extrasystole per minute), atrial fibrillation or other arrhythmias requiring a pacemaker (A-V disturbances) or defibrillator for secondary prevention owing to a history of malignant arrhythmias.

All patients with CHF had stable symptoms of heart failure: none of them had been hospitalised, had experienced worsening symptoms, had changed therapy during the past 3 months or had recently undergone revascularization procedures or coronary angioplasty.

Patients were randomly assigned in a 1:1 ratio to receive an ICD alone (ICD group) or in combination with CRT using a biventricular pacemaker (ICD+CRT group) (Guidant, St Paul, Minnesota, USA), and hospitalised. The final pacing setting was VDD with a lower rate well below the patient's lowest intrinsic heart rate, to maintain natural atrial tracking under resting conditions. This type of pacing setting was essential to allow power spectral analysis of HRV. All ICD shocks were assessed by three expert cardiologists to evaluate appropriateness.

All participants gave their informed consent to the procedures and the ethics committee of the Department of the Science of Ageing, University of Rome, "La Sapienza" approved the study. The study complied with the ethical rules for human experimentation stated in the Declaration of Helsinki.

2.2. Study protocol and data acquisition
All CHF patients underwent two short-term (5 min) spectral recordings of HRV and SBP variability: one recording was made before implantation of the ICD or ICD+CRT and the second recording was performed after 1 year. The two physicians who assessed the spectral recordings were blinded to the patients' treatment group assignment. The control subjects only underwent the baseline assessment.

In accordance with the testing protocol, at about 9:00 am, after a resting period of 30 min in the recumbent position, the subject underwent assessment of HRV. During the study all subjects were required to breathe at a rate of 15 breaths/min in time with a metronome. Each subject underwent a simultaneous recording of single lead ECG (Telemetria Mortara Rangoni), arterial pressure (Finometer) and respiratory rate (strain-gauge belt). Data were collected during controlled respiration to prevent the abnormal respiratory patterns, frequently observed in patients with CHF from interfering with the results of autonomic assessment and RR spectral analysis [4,10-12].

The three analogical signals (ECG, arterial pressure, and respiratory activity) were acquired simultaneously and digitally converted using a custom-designed card (Keithley Metrabyte—DAS 1200 Series) at a sampling frequency of 500 Hz per channel with 12-bit precision.

For recognition and measurement of RR intervals, blood pressure and respiratory rate we used software developed in our laboratory, which is based upon an automated derivative/threshold algorithm.

An autoregressive algorithm was used to analyze the three digitized signals from the electrocardiographic recordings of heart rate, blood pressure and respiratory activity [4,12,13]. For each of these variables we then determined the total power (TP) of RR intervals (RR) and SBP (from 0 to 0.42 Hz Eq). For RR and SBP we calculated the following spectral components: a high-frequency (HF) component (from 0.15 to 0.42 Hz Eq), a low-frequency (LF) component (from 0.03 to 0.15 Hz Eq) and a very-low frequency (VLF) component (below 0.03 Hz Eq) [4,13]. We calculated spontaneous baroreflex sensitivity with the alpha (P) index [14-16]. This method yields an P index: P LF(square root of RR LF/square root of SBP LF) [17]. Before calculating the P index, to check that BP and RR intervals correlated we estimated the coherence function of the various spectral components. Coherence expresses the fraction of power at a given frequency in either time series that can be explained as a linear transformation between the two signals. Recordings showing less than 0.5 coherence in LF and HF between the pressure signal and RR variability were excluded.

2.3. Data and statistical analysis
Linear data are expressed as means±S.D. and nonlinearly distributed data as median (interquartile range), calculated as 75th percentile-25th percentile. All data were evaluated using SPSS-PC+ (SPSS-PC+ Inc., Chicago, Illinois). First, spectral and non-spectral data were compared in the two CHF groups (ICD and ICD+CRT) before implantation and in the healthy control group (baseline). The data for each CHF group were then compared at baseline and at 1 year. Spectral and non-spectral data were then compared in the ICD and ICD+CRT groups at 1 year after implantation. Last, independently of the group of origin, spectral data obtained at baseline were compared between subjects in whom severe arrhythmias, related to sustained ventricular tachycardia (Sustained VT) or ventricular fibrillation (VF) which led to an ICD shock, during follow-up and those in whom no arrhythmias developed.

One-way analysis of variance (ANOVA) was used to compare the general characteristics and other linear data between the study groups. We used the Kruskal-Wallis test and Mann-Whitney test for non-normally distributed data. Repeated-measures ANOVA was used to evaluate the differences in normally distributed non-spectral data at baseline and after 1-year follow-up. The Wilcoxon test was used for variables with a nonlinear distribution.

To assess the association between LF power and the risk of malignant ventricular arrhythmias, we used a cut-off value of ≤13 ms2 which has been shown to provide significant information in a population with CHF [4]. Event-free survival functions were estimated using the Kaplan-Meier method and differences between the curves were tested for significance by the log-rank statistic; relative risks were computed by Cox proportional-hazards regression model. Also based on the LF value of ≤13 ms2, the population was subgrouped and Fisher's exact test was used to determine whether the population subdivided in this way had a greater incidence of events.


   3. Results
Top
 Abstract
 1. Introduction
 2. Method
 3. Results
4. Discussion
 5. Limitations of the...
 References
 
A total of 31 patients with CHF were randomly assigned 1:1 to receive an ICD alone (n=15) or ICD+CRT (n=16) (Table 1). There were no major complications following implantation.


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

  		Table 1 Baseline characteristics of study subjects

 
There was no significant difference in age, BMI, sex distribution, or blood pressures between the two CHF groups and the control group at baseline. However, heart rate, ejection fractions, end-systolic diameter, end-diastolic diameter and QRS duration in the control group were significantly different to those in the two CHF groups.

Patients with CHF were taking standard medications for heart failure, including ramipril (2.5 to 10 mg/day) or losartan (50 mg/day), furosemide (25 to 250 mg/day), spironolactone (25 mg/day to 50 mg/day), carvedilol (6.25 to 50 mg/day) or bisoprolol (2.5 to 5 mg/day), digoxin (0.125 or 0.250 mg/day) and acetylsalicylic acid (100 mg/day) (Table 1).

All spectral variables, including baroreflex sensitivity calculated with the P index, were significantly lower in patients with CHF at baseline than in control subjects (TPRR, p<0.001; VLFRR, p<0.001; LFRR, p<0.001; HFRR, p<0.001; LF/HF, p<0.001; LFSBP, p<0.05; HFSBP, p<0.05; P LF, p<0.001) (Table 2).


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

  		Table 2 Data for heart rate and blood pressure variability in patients with chronic heart failure before treatment with an implantable cardioverter-defibrillator (ICD) alone or with ICD+cardiac resynchronization therapy (CRT) and healthy controls

 
All patients completed the study. During the follow-up year, 6 patients received appropriate ICD shocks: 4 patients in the ICD group (3 Sustained VT and 1 VF) and 2 patients in the ICD+CRT group (1 Sustained VT and 1 VF). No deaths were reported in either group, but 2 patients in the ICD group were hospitalised due to worsening CHF, 6 patients in the ICD group had their diuretic medications increased whereas 5 patients in the ICD+CRT group had them reduced. In the ICD+CRT group the mean ejection fraction increased by about 5% (from 23±1% to 28±1%, p<0.05) after 1 year, but in the ICD group, EF was unchanged (from 22±2% to 22±1%, p: Ns) (Table 3). In the ICD+CRT group, 4 subjects improved from NYHA class IV to class II and 5 from class IV to class III, 3 from class III to class II and 1 from class III to class I. Three subjects were considered "non-responders" as their NYHA class did not change. In the ICD group, 3 patients had a worsening in NYHA class from class III to class IV, and 1 patient improved from class III to class II (Table 3).


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

  		Table 3 Characteristics of patients with chronic heart failure at baseline and after 1 year of treatment with an implantable cardioverter-defibrillator (ICD) alone or with ICD+cardiac resynchronization therapy (CRT)

 
The subjects in whom Sustained VT or VF led to an ICD shock had significantly lower TPRR, p<0.001; VLFRR, p<0.001; LFRR, p<0.001; HFRR, p<0.001; LFSBP, p<0.05 than those in whom severe arrhythmias did not develop (Table 4).


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

  		Table 4 Data for heart rate and blood pressure variability of patients with chronic heart failure before treatment with an implantable cardioverter-defibrillator (ICD) alone or with ICD+cardiac resynchronization therapy (CRT) who during 1 year of follow-up had, or did not have, sustained ventricular arrhythmias (Sustained VT) or ventricular fibrillation (VF)

 
Of the 31 patients with CHF randomised to the two treatments, 9 had LFRR≤13 ms2 and of these 6 had at least one episode of arrhythmia; conversely, none of the 22 subjects with LFRR>13 ms2 had an arrhythmic event (p<0.05) (Fig. 1).


Figure 1
View larger version (8K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 1 LFRR values in patients who during 1 year of follow-up had, or did not have, sustained ventricular tachycardia (Sustained VT) or ventricular fibrillation (VF). The continuous line indicates the mean LFRR in each group, the dashed line represents the LFRR value of 13 ms2, the cut-off risk level for sudden death [4].

 
The presence of LFRR≤13 ms2 was associated with a significant increase in the risk of arrhythmic episodes (Sustained VT or VF) (Fig. 2) that required appropriate ICD shocks (relative risk, 3.1; 95% confidence interval, 1.4 to 7.1, p<0.05). No other variable studied, including the P LF index was a significant predictor of arrhythmic episodes (SVT or VF).


Figure 2
View larger version (7K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 2 Kaplan-Meier estimates of the probability of remaining free of potentially fatal arrhythmias among subjects with LFRR ≤ or >13 ms2.

 
In all subjects in the ICD+CRT group, including the "non-responders" after 1 year, the following spectral indices increased significantly from baseline: TPRR, p<0.001; LFRR, p<0.001; LF/HF, p<0.001; LFSBP, p<0.05; and HFSBP, p<0.05. Baroreflex sensitivity calculated with the P index also improved significantly (P LF, p<0.05).

Conversely, in the ICD group, spectral data at 1 year after implantation was unchanged from baseline. Compared with the group randomised to receive an ICD alone, the ICD+CRT group at 1 year had higher LFRR, LF/HF, and P LF values (Table 5, Fig. 3).


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

  		Table 5 Data for heart rate and blood pressure variability in patients with chronic heart failure after 1 year of an implantable cardioverter-defibrillator (ICD) alone or with ICD+cardiac resynchronization therapy (CRT)

 


Figure 3
View larger version (19K):
[in this window]
[in a new window]
[Download PowerPoint slide]
  		Fig. 3 Individual LFRR values before and after 1 year of ICD alone and ICD+CRT. Black circles represent subjects in the ICD+CRT group considered "non-responders" but in whom LFRR power nevertheless increased.

 
None of the 3 subjects in the ICD+CRT group considered "non-responders" received ICD shocks during the follow-up.


   4. Discussion
Top
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
5. Limitations of the...
 References
 
This study yielded two major findings. It provided evidence that power spectral analysis of HRV, and most importantly LFRR power, can predict the development of malignant ventricular arrhythmias in patients with CHF with a low ejection fraction and prolonged QRS interval, treated with an ICD alone or an ICD combined with CRT (using a biventricular pacemaker). Subjects with low spectral indices of RR variability (TPRR, LFRR, HFRR) and SBP (LFSBP) [18] have a higher incidence of potentially fatal ventricular arrhythmias; furthermore an LFRR of ≤13 ms2 is a risk factor for malignant ventricular arrhythmias in subjects receiving ICD+CRT and those with an ICD alone.

The other major finding is that spectral indices improve more in subjects who have received ICD+CRT than in those treated with an ICD alone.

One of the main causes of malignant ventricular arrhythmias in patients with CHF, especially in those with a low ejection fraction, such as the patients we studied, is autonomic nervous system dysfunction characterised by sympathetic hyperactivity, reduced vagal control, and low baroreflex sensitivity. This autonomic pattern is associated with a reduction in all the spectral components of RR variability and with a low P index. This reduction could be mediated by a reduction in the oscillatory components of heart rate and partly by the mechanical effect of increased right atrial pressure on the sinus node [4,5,19]. Especially important is the paradoxical reduction in LFRR power [4,5,20-22].

Our finding that LFRR, after 1 year of therapy, increased only in the group randomised to ICD+CRT implies that this therapy reduced sympathetic hyperactivity and might therefore reduce the risk of potentially fatal ventricular arrhythmias [4]. Increased LFRR values in patients with severe CHF indicate reduced sympathetic activity [4,5]. This observation is supported by data from a previous study in patients with CHF, showing that after carvedilol therapy, haemodynamic variables improved, sympathetic hyperactivity diminished, and LFRR increased [6]. Some investigators consider that the LFRR component is not only a marker of sympathetic modulation but is also an index of baroreflex sensitivity [23,24]. If so, then an LFRR increase indicates improved baroreflex sensitivity.

Since clinical conditions worsened and spectral measures did not improve in the group receiving ICD alone we can reasonably attribute these improvements to CRT. The increase in power spectral components observed in subjects with ICD+CRT depends on the improvement in haemodynamic variables [7]. These benefits were shown in CARE-HF study [8] and were confirmed in a recent extension of this study [9]. This improvement is probably the most important cause of the reduced sympathetic hyperactivity and increased baroreflex sensitivity (P-index). In severe CHF, autonomic cardiovascular control can be worsened by the "diastolic ventricular interaction", namely reduced right ventricular filling caused by increased left ventricular end-diastolic pressure. This phenomenon also leads to poor reflex control of peripheral resistances [25] and to a reduction in spectral components [26]. Since CRT is able to reduce the diastolic ventricular interaction [27], we presume that the improvement in power spectral data obtained in the ICD+CRT group could be partially attributed to a reduction in diastolic ventricular interaction.

Another important point to underline is that in the CRT "non-responders", namely those who failed to improve NYHA class, spectral measures distinctly improved, we therefore presume that CRT merely slowed the progression of the disease in this group of subjects. Yet even this benefit is an achievement, especially given that none of the "non-responders" experienced malignant arrhythmias.

Finally, in the subjects with CHF we studied, the P index of baroreflex sensitivity does not seem to be a predictor of malignant arrhythmias. Conversely, baroreflex sensitivity calculated with the phenylephrine method seems to be a valid prognostic tool for stratifying the risk of malignant arrhythmias. Unfortunately, the two techniques do not yield perfectly overlapping results hence the data are hard to compare [15-17]. Data are therefore lacking on the validity of the P index for stratifying the potentially fatal arrhythmias. Our small study sample prevents us from providing an answer.

Even though our small study population requires a larger prospective study to confirm our findings, our data show that high LF spectral power levels reduce the risks of malignant ventricular arrhythmias. Notably, a relative risk of 3.1 indicates a 67% reduction in potentially fatal arrhythmic episodes among patients with LF power values of >13 ms2 compared with those with LF values of ≤13 ms2. What we need to find out now is whether the improvement in spectral data is accompanied by a better prognosis in the longer term.


   5. Limitations of the study
Top
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
 5. Limitations of the...
References
 
The first limitation of our study, from a single centre, is the small number of subjects enrolled, and the fact that we enrolled only patients with post-ischaemic dilated cardiomyopathy and none with primary dilated cardiomyopathy. This limitation arose because we wanted to choose the most homogeneous group possible, to avoid confounding factors. Some investigators maintain that mortality varies in the two types of dilated cardiomyopathy [28] and the general characteristics often differ in patients with these two forms of CHF.

A second possible limitation of our study is that because we used a short-term spectral analysis we cannot provide reliable data on changes in the VLF component of HRV. Nevertheless, as we stated in the introduction, we designed this study primarily to investigate whether LF≤13 ms2, a spectral marker that has already been shown to predict sudden death, will predict the occurrence of malignant ventricular arrhythmias in patients with CHF undergoing prophylactic treatment with an ICD alone or in combination with CRT.

Because all subjects were recruited and underwent implantation before the publication of the COMPANION trial [2] we have no definitive data on the CRT-induced reduction in mortality even if the CARE-HF extension study [9] seems to supply evidence in this sense.

These limitations notwithstanding we consider our findings of clinical importance because they document a clinical and spectral improvement and a reduction in potentially fatal arrhythmias in patients treated with an ICD+CRT. Furthermore, our study suggests that power spectral analysis of HRV could be a useful non-invasive tool to distinguish subjects who need ICD+CRT (subjects with LF≤13 ms2) from those who need only CRT (subjects with LF>13 ms2). Nevertheless, this hypothesis should now be tested in a larger study sample.


   References
Top
 Abstract
 1. Introduction
 2. Method
 3. Results
 4. Discussion
 5. Limitations of the...
 References
 

  1. Moss A.J., Zareba W., Hall W.J., et al. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N Engl J Med (2002) 346:877–883.[Abstract/Free Full Text]
  2. Bristow M.R., Saxon L.A., Boehmer J., et al. Cardiac resynchronization therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med (2004) 350:2140–2150.[Abstract/Free Full Text]
  3. Guzzetti S., La Rovere M.T., Pinna G.D., et al. Different spectral components of 24 h heart rate variability are related to different modes of death in chronic heart failure. Eur Heart J (2005) 26(4):357–362.[Abstract/Free Full Text]
  4. La Rovere M.T., Pinna G.D., Maestri R., et al. Short-term heart rate variability strongly predicts sudden cardiac death in chronic heart failure patients. Circulation (2003) 107:565–570.[Abstract/Free Full Text]
  5. 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]
  6. Piccirillo G., Leonetti Luparini R., Celli V., et al. Effects of Carvedilol on heart rate and blood pressure variability in subjects with chronic heart failure. Am J Cardiol (2000) 86:1392–1395.[CrossRef][Web of Science][Medline]
  7. Adamson P.B., Kleckner K.J., Van Hout W.L., Srinivasan S., Abraham W.T. Cardiac resynchronization therapy improves heart rate variability in patients with symptomatic heart failure. Circulation (2003) 108:266–269.[Abstract/Free Full Text]
  8. Cleland J.G., Coletta A.P., Lammiman M., et al. Clinical trials update from the European Society of Cardiology meeting 2005: CARE-HF extension study, ESSENTIAL, CIBIS III, S-ICD, ISSUE-2, STRIDE-2, SOFA, IMAGINE, PREAMI, SIRIUS-II and ACTIVE. Eur J Heart Fail (2005) 7(6):1070–1075.[Abstract/Free Full Text]
  9. Cleland J.G., Daubert J.C., Erdmann E., et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med (2005) 352(15):1539–1549.[Abstract/Free Full Text]
  10. 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 measures of heart rate variability. Circulation (1997) 96:246–252.[Abstract/Free Full Text]
  11. El-Omar M., Kardos A., Casadei B. Mechanism of respiratory sinus arrhythmia in patients with mild heart failure. Am J Physiol Heart Circ Physiol (2001) 280(1):H215–H231.
  12. Piccirillo G., Magrì D., Naso C., et al. Factor influencing HRV power spectral analysis during controlled breathing in patients with chronic heart failure or hypertension and in healthy normotensive subjects. Clin Sci (2004) 107:183–190.[CrossRef][Web of Science][Medline]
  13. Task force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. Heart rate variability. Standard of measurements, physiological interpretation and clinical use. Circulation (1996) 93:1043–1065.[Free Full Text]
  14. Pagani M., Somers V., Furlan R., et al. Changes in autonomic regulation induced by physical training in mild hypertension. Hypertension (1988) 12:600–610.[Abstract/Free Full Text]
  15. Piccirillo G., Di Giuseppe V., Nocco M., et al. Influence of aging and other cardiovascular risk factors on baroreflex sensitivity. J Am Geriatr Soc (2001) 49:1059–1065.[CrossRef][Web of Science][Medline]
  16. Piccirillo G., Cacciafesta M., Viola E., et al. Influence of aging on cardiac baroreflex sensitivity determined noninvasively by power spectral analysis. Clin Sci (2001) 100:267–274.[CrossRef][Web of Science][Medline]
  17. Pitzalis M.V., Mastropasqua F., Passantino A., et al. Comparison between noninvasive indices of baroreceptor sensitivity and the phenylephrine method in post myocardial infarction patients. Circulation (1998) 97:1362–1367.[Abstract/Free Full Text]
  18. La Rovere M.T., Bigger J.T. Jr., Marcus F.I., Mortara A., Schwartz P.J. Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction. ATRAMI (Autonomic Tone and Reflexes After Myocardial Infarction) Investigators. Lancet (1998) 351(9101):478–484.[CrossRef][Web of Science][Medline]
  19. Horner S.M., Murphy C.F., Coen B., et al. Contributions to heart rate variability by mechanoelectric feedback. Stretch of the sinoatrial node reduces heart rate variability. Circulation (1996) 94:1762–1767.[Abstract/Free Full Text]
  20. Mortara A., La Rovere M.T., Signorini M.G., et al. Can power spectral analysis of heart rate variability identify a high risk subgroup of congestive heart failure patients with excessive sympathetic activation? A pilot study before and after heart transplantation. Br Heart J (1994) 71:422–430.[Abstract/Free Full Text]
  21. Guzzetti S., Cogliati C., Turiel M., et al. Sympathetic predominance followed by functional denervation in progression of chronic heart failure. Eur Heart J (1995) 16:1100–1107.[Abstract/Free Full Text]
  22. Van de Borne P., Montano N., Pagani M., Oren R., Somers V.K. Absence of low-frequency variability of sympathetic nerve activity in severe heart failure. Circulation (1997) 95:1449–1454.[Abstract/Free Full Text]
  23. Parati G., Saul J.P., Di Rienzo M., Mancia G. Spectral analysis of blood pressure and heart rate variability in evaluating cardiovascular regulation. Hypertension (1995) 25:1276–1286.[Abstract/Free Full Text]
  24. Eckberg D.L. Sympathovagal balance. A critical appraisal. Circulation (1998) 96:3224–3232.
  25. Atherton J.J., Thomson H.L., Moore T.D., et al. Diastolic ventricular interaction: a possible mechanism for abnormal vascular responses during volume unloading in heart failure. Circulation (1997) 96(12):4273–4279.[Abstract/Free Full Text]
  26. Atherton J.J., Thomson H.L., Moore T.D., et al. Diastolic ventricular interaction in chronic heart failure: relation to heart rate variability and neurohumoral status. Heart Vessels (1998) 136(13(6):269–277.
  27. Bleasdale R.A., Turner M.S., Mumford C.E., et al. Left ventricular pacing minimizes diastolic ventricular interaction, allowing improved preload-dependent systolic performance. Circulation (2004) 110(16):2395–2400.[Abstract/Free Full Text]
  28. Alla F., Briancon S., Juilliere Y., et al. Differential clinical prognostic classifications in dilated and ischemic advanced heart failure: the EPICAL study. Am Heart J (2000) 139(5):895–904.[Web of Science][Medline]

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



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 arrow Search for citing articles in:
ISI Web of Science (1)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Piccirillo, G.
Right arrow Articles by Marigliano, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Piccirillo, G.
Right arrow Articles by Marigliano, V.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?