IJCA-17070; No of Pages 3 International Journal of Cardiology xxx (2013) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letters to the Editor
Heart rate control in chronic heart failure: Resting versus mean heart rate with prolonged ambulatory ECG recording☆ Francisco J. Pastor-Pérez a,⁎,1, Sergio Manzano-Fernández a,1, Rebeca Goya-Esteban b,1, Domingo A. Pascual-Figal a,1, Iris P. Garrido Bravo a,1, Oscar Barquero-Pérez b,1, Jose Luis Rojo-Álvarez b,1, James L. Januzzi c,1, Mariano Valdés Chavarri a,1, Arcadio García-Alberola a,1 a b c
Department of Cardiology, Virgen de la Arrixaca University Hospital, Murcia, Spain Department of Signal Theory and Communications, University Rey Juan Carlos, Madrid, Spain Cardiology Division, Massachusetts General Hospital, Boston, MA, USA
a r t i c l e
i n f o
Article history: Received 7 September 2013 Accepted 20 October 2013 Available online xxxx Keywords: Heart failure Heart rate Holter monitoring
Although heart rate (HR) must be considered as a continuous variable in terms of prognosis in heart failure (HF), a threshold for increased risk appears to exist among those patients above 70 beats per minute (bpm) [1]. As effective HR control is an increasingly important goal of HF treatment, confident knowledge of pulse rate during treatment is relevant. Accordingly, the purpose of this study is to compare resting HR measurement with averaged values obtained with prolonged ambulatory electrocardiography recording. The study was carried out following the principles of the Helsinki Declaration. It was approved by the Local Ethics Committee, and a written informed consent was obtained from each patient. Patients were recruited during scheduled outpatient visits to the HF outpatient clinic in our centre. From June 2007 to May 2011, 75 patients in sinus rhythm with an established diagnosis of stable chronic HF according to contemporary guidelines [2] were included. All subjects had a 7-day (7D)
☆ Funding: This work was supported by Research Project from Medtronic Ibérica S.A. and by Research Grants TEC2010-19263 and URJC-CM-2010-CET-4882 from Spanish Government. ⁎ Corresponding author at: Department of Cardiology, University Hospital Virgen de la Arrixaca, Ctra. Madrid-Cartagena s/n, 30120 Murcia, Spain. Tel.: +34 968 369445; fax: +34 968 369662. E-mail address: [email protected] (F.J. Pastor-Pérez). 1 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
continuous electrocardiography monitoring performed at enrollment. We analyzed resting HR, mean HR both during the first day (1D) and at the end of the monitoring period. We assessed HR during waking (from 8:00 am to 12:00 pm) and sleep hours (from 12:00 pm to 8:00 am) and the amount of time spent at HR ≥ 70 bpm during the monitoring period. Seventy-five patients were included (age 53.0 ± 14.3 years; left ventricular ejection fraction 37 ± 9.9%). Table 1 shows clinical and demographics characteristics as a function of resting HR. Mean resting HR was 74 ± 13 bpm. During the day mean HR was 74 ± 11 bpm at 1D and 75 ± 11 bpm at 7D. Mean HR during the night was 65 ± 12 bpm and 65 ± 11 bpm at 1D and 7D respectively. Sixty-four percent of
Table 1 Clinical and demographics characteristics as a function of resting heart rate. Heart rate ≥ 70 (n = 49)
Heart rate b70 (n = 26)
p-value
Age, years Male Diabetes mellitus Hypertension Hypercholesterolemia Non-ischemic aethiology New York Heart Association class I or II Left ventricular ejection fraction, % Albumin, mg/dL Creatinine, mg/dL Haemoglobin, g/dL Sodium, mg/dL NT-proBNP, pg/mL
49 ± 14 41 (84) 15 (30) 8 (33) 7 (14) 36 (73) 45 (92) 36 ± 10 4.3 ± 1.4 0.9 [0.8–1.2] 14.0 [13.0–15.2] 140 [138–141] 321 [139–796]
60 ± 11 23 (88) 7 (27) 5 (19) 5 (19) 20 (77) 22 (85) 38 ± 9 4.1 ± 2.0 1.1 [0.8–1.3] 13.0 [12.0–14.1] 140 [138–142] 452 [118–1342]
0.02 0.30 0.90 0.75 0.58 0.74 0.33 0.90 0.60 0.27 0.09 0.65 0.39
Current treatment at inclusion Beta-blockers Bisoprolol, mg Carvedilol, mg ACE inhibitors/ARB Aldosterone antagonist Loop diuretics Amiodarone Digoxin
47 (96) 5.1 ± 2.2 27.5 ± 17.1 45 (92) 36 (73) 32 (65) 10 (20) 16 (32)
25 (96) 4.5 ± 1.4 34 ± 16.0 24 (92) 17 (65) 19 (73) 5 (19) 5 (19)
0.96 0.33 0.32 0.94 0.46 0.49 0.90 0.22
0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.10.071
Please cite this article as: Pastor-Pérez FJ, et al, Heart rate control in chronic heart failure: Resting versus mean heart rate with prolonged ambulatory ECG recording, Int J Cardiol (2013), http://dx.doi.org/10.1016/j.ijcard.2013.10.071
e2
F.J. Pastor-Pérez et al. / International Journal of Cardiology xxx (2013) xxx–xxx Table 2 Patients with resting heart rate b70 bpm but mean 1-day heart rate ≥70 bpm. Patient
Resting HR, bpm
Mean 1-day HR, bpm
Age years
Ejection fraction, %
NYHA functional class
NT-proBNP, pg/mL
1 2 3 4 5 6
61.5 69.5 68.4 67.8 63.0 68.4
75.7 72.0 74.5 76.9 71.0 71.1
69 42 48 53 44 45
35 48 38 44 45 37
II I II I II II
2659 118 1021 29 470 187
HR: Heart rate.
Fig. 1. Relationship between resting and mean 7-day heart rate.
patients had ≥70 bpm at rest; such patients were more likely to be older, but no other significant differences were found between groups. The intraclass correlation coefficient between days was 0.90 (95%CI 0.87–0.93, p b 0.001). Resting HR showed a positive correlation with both mean 1D and 7D HR (r = 0.76, p b 0.001 and r = 0.73, p b 0.001 respectively). Considering absolute values, resting HR (73 ± 11 bpm) was similar to both mean 1D (71 ± 11 bpm) and 7D HR (72 ± 10 bpm). The absolute differences for both 1D and 7D mean HR versus resting HR were: 45 patients (60%) between 0 and 5 bpm, 14 patients (19%) between 5 and 10 bpm and 16 patients (21%) more than 10 bpm. With regard to this last group almost all patients had resting HR ≥ 70 bpm (15 of 16 patients). Fig. 1 shows the agreement between resting and mean HR over the whole monitoring period. Forty-nine study participants (64%) had a resting HR ≥ 70 bpm (mean value 81 ± 10 bpm). Notably, 11 (23%) had mean HR b70 both at 1D (mean HR 64 ± 2 bpm) and 7D (mean HR 65 ± 1 bpm), p b 0.001. These patients spent less time at HR ≥ 70 than patients with concordant values (both resting and mean values ≥ 70) during either the whole, day or even the night monitoring period, as shown in Fig. 2A. In contrast, among the 26 study participants (36%) with resting HR b 70 (mean HR 60 ± 7 bpm), 6 (23%) had mean 1D and 7D HR ≥ 70 (73 ± 1 and 74 ± 1.0 bpm respectively), p b 0.05. These discordant patients are listed in Table 2. As shown in Fig. 2B they
also spent more time at HR ≥ 70 than patients with concordant values during the whole monitoring period, and also during the sleep time. The major findings of the present study are: 1) as an absolute value, resting HR is a good estimate of mean HR across multiple days of measurement; 2) When categorizing patients as a function of a target HR of 70 bpm, however, the concordance between resting and HR over the days was suboptimal in a quarter of them; In recent years, control of HR has become the focus of drug development in HF, as HR is a strong predictor of morbidity and mortality in cardiovascular disease including patients with chronic HF [3,4]. McAlister et al. [5] concluded that the extent to which HR reduction is achieved by beta blockade is significantly associated with the survival benefit obtained. The recent SHIFT trial [6] reduced morbidity and mortality in HF in relation to the HR achieved with ivabradine, supporting the notion that HR is not only a risk marker, but also a target of treatment. Given the findings of these and other prior studies, an articulated HR goal of b 70 bpm has been established [7]. We found resting HR accurately reflects more complex measurement of HR across an extended monitoring period in the majority of our HF patients. Important nuances to our results include the fact that a quarter of patients showed discordant results relative to resting HR. Importantly in one group, the resting HR was b70 bpm but mean HR was ≥70 bpm. According to current guidelines based on resting measures [7] these patients might not have been recognized as being candidates for improving treatment; such patients also spent more time at HR ≥ 70 bpm compared to patients with concordant values (both resting and mean HR b70 bpm) even during sleep hours indicating that the physical activity is not the only determinant of the discrepancy. The importance of our findings is that inadequate HR control over the days could exist despite resting HR b 70 bpm; prolonged HR monitoring can identify these patients, allowing for more assiduous care.
Fig. 2. Time spent above 70 bpm as a function of resting heart rate (≥70 in A and b70 in B) and mean heart rate over 1-day monitoring.
Please cite this article as: Pastor-Pérez FJ, et al, Heart rate control in chronic heart failure: Resting versus mean heart rate with prolonged ambulatory ECG recording, Int J Cardiol (2013), http://dx.doi.org/10.1016/j.ijcard.2013.10.071
F.J. Pastor-Pérez et al. / International Journal of Cardiology xxx (2013) xxx–xxx
Our study shows that resting HR is a generally adequate estimator of mean HR across the days. The use of prolonged HR monitoring showed that the concordance was suboptimal in a quarter of patients when categorizing patients as a function of a target HR of 70 bpm. Some of them would have been detected as being eligible for intensification of HR reducing agents.
[3] [4]
[5]
References [6] [1] Fox K, Ford I, Steg PG, et al. Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet 2008;372(9641):817–21. [2] Dickstein K, Cohen-Solal A, Filippatos G. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiol-
[7]
e3
ogy. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur J Heart Fail 2008;10(10):933–89. Kannel WB, Kannel C, Paffenbarger Jr RS, Cupples LA. Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J 1987;113(6):1489–94. Kolloch R, Legler UF, Champion A, et al. Impact of resting heart rate on outcomes in hypertensive patients with coronary artery disease: findings from the INternational VErapamil-SR/trandolapril STudy (INVEST). Eur Heart J 2008;29(10):1327–34. McAlister FA, Wiebe N, Ezekowitz JA, Leung AA, Armstrong PW. Meta-analysis: betablocker dose, heart rate reduction, and death in patients with heart failure. Ann Intern Med 2009;150(11):784–94. Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 2010;376(9744):875–85. McMurray JJ, Adamopoulos S, Anker SD. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012;33(14):1787–847.
Please cite this article as: Pastor-Pérez FJ, et al, Heart rate control in chronic heart failure: Resting versus mean heart rate with prolonged ambulatory ECG recording, Int J Cardiol (2013), http://dx.doi.org/10.1016/j.ijcard.2013.10.071
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letters to the Editor
Heart rate control in chronic heart failure: Resting versus mean heart rate with prolonged ambulatory ECG recording☆ Francisco J. Pastor-Pérez a,⁎,1, Sergio Manzano-Fernández a,1, Rebeca Goya-Esteban b,1, Domingo A. Pascual-Figal a,1, Iris P. Garrido Bravo a,1, Oscar Barquero-Pérez b,1, Jose Luis Rojo-Álvarez b,1, James L. Januzzi c,1, Mariano Valdés Chavarri a,1, Arcadio García-Alberola a,1 a b c
Department of Cardiology, Virgen de la Arrixaca University Hospital, Murcia, Spain Department of Signal Theory and Communications, University Rey Juan Carlos, Madrid, Spain Cardiology Division, Massachusetts General Hospital, Boston, MA, USA
a r t i c l e
i n f o
Article history: Received 7 September 2013 Accepted 20 October 2013 Available online xxxx Keywords: Heart failure Heart rate Holter monitoring
Although heart rate (HR) must be considered as a continuous variable in terms of prognosis in heart failure (HF), a threshold for increased risk appears to exist among those patients above 70 beats per minute (bpm) [1]. As effective HR control is an increasingly important goal of HF treatment, confident knowledge of pulse rate during treatment is relevant. Accordingly, the purpose of this study is to compare resting HR measurement with averaged values obtained with prolonged ambulatory electrocardiography recording. The study was carried out following the principles of the Helsinki Declaration. It was approved by the Local Ethics Committee, and a written informed consent was obtained from each patient. Patients were recruited during scheduled outpatient visits to the HF outpatient clinic in our centre. From June 2007 to May 2011, 75 patients in sinus rhythm with an established diagnosis of stable chronic HF according to contemporary guidelines [2] were included. All subjects had a 7-day (7D)
☆ Funding: This work was supported by Research Project from Medtronic Ibérica S.A. and by Research Grants TEC2010-19263 and URJC-CM-2010-CET-4882 from Spanish Government. ⁎ Corresponding author at: Department of Cardiology, University Hospital Virgen de la Arrixaca, Ctra. Madrid-Cartagena s/n, 30120 Murcia, Spain. Tel.: +34 968 369445; fax: +34 968 369662. E-mail address: [email protected] (F.J. Pastor-Pérez). 1 This author takes responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
continuous electrocardiography monitoring performed at enrollment. We analyzed resting HR, mean HR both during the first day (1D) and at the end of the monitoring period. We assessed HR during waking (from 8:00 am to 12:00 pm) and sleep hours (from 12:00 pm to 8:00 am) and the amount of time spent at HR ≥ 70 bpm during the monitoring period. Seventy-five patients were included (age 53.0 ± 14.3 years; left ventricular ejection fraction 37 ± 9.9%). Table 1 shows clinical and demographics characteristics as a function of resting HR. Mean resting HR was 74 ± 13 bpm. During the day mean HR was 74 ± 11 bpm at 1D and 75 ± 11 bpm at 7D. Mean HR during the night was 65 ± 12 bpm and 65 ± 11 bpm at 1D and 7D respectively. Sixty-four percent of
Table 1 Clinical and demographics characteristics as a function of resting heart rate. Heart rate ≥ 70 (n = 49)
Heart rate b70 (n = 26)
p-value
Age, years Male Diabetes mellitus Hypertension Hypercholesterolemia Non-ischemic aethiology New York Heart Association class I or II Left ventricular ejection fraction, % Albumin, mg/dL Creatinine, mg/dL Haemoglobin, g/dL Sodium, mg/dL NT-proBNP, pg/mL
49 ± 14 41 (84) 15 (30) 8 (33) 7 (14) 36 (73) 45 (92) 36 ± 10 4.3 ± 1.4 0.9 [0.8–1.2] 14.0 [13.0–15.2] 140 [138–141] 321 [139–796]
60 ± 11 23 (88) 7 (27) 5 (19) 5 (19) 20 (77) 22 (85) 38 ± 9 4.1 ± 2.0 1.1 [0.8–1.3] 13.0 [12.0–14.1] 140 [138–142] 452 [118–1342]
0.02 0.30 0.90 0.75 0.58 0.74 0.33 0.90 0.60 0.27 0.09 0.65 0.39
Current treatment at inclusion Beta-blockers Bisoprolol, mg Carvedilol, mg ACE inhibitors/ARB Aldosterone antagonist Loop diuretics Amiodarone Digoxin
47 (96) 5.1 ± 2.2 27.5 ± 17.1 45 (92) 36 (73) 32 (65) 10 (20) 16 (32)
25 (96) 4.5 ± 1.4 34 ± 16.0 24 (92) 17 (65) 19 (73) 5 (19) 5 (19)
0.96 0.33 0.32 0.94 0.46 0.49 0.90 0.22
0167-5273/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ijcard.2013.10.071
Please cite this article as: Pastor-Pérez FJ, et al, Heart rate control in chronic heart failure: Resting versus mean heart rate with prolonged ambulatory ECG recording, Int J Cardiol (2013), http://dx.doi.org/10.1016/j.ijcard.2013.10.071
e2
F.J. Pastor-Pérez et al. / International Journal of Cardiology xxx (2013) xxx–xxx Table 2 Patients with resting heart rate b70 bpm but mean 1-day heart rate ≥70 bpm. Patient
Resting HR, bpm
Mean 1-day HR, bpm
Age years
Ejection fraction, %
NYHA functional class
NT-proBNP, pg/mL
1 2 3 4 5 6
61.5 69.5 68.4 67.8 63.0 68.4
75.7 72.0 74.5 76.9 71.0 71.1
69 42 48 53 44 45
35 48 38 44 45 37
II I II I II II
2659 118 1021 29 470 187
HR: Heart rate.
Fig. 1. Relationship between resting and mean 7-day heart rate.
patients had ≥70 bpm at rest; such patients were more likely to be older, but no other significant differences were found between groups. The intraclass correlation coefficient between days was 0.90 (95%CI 0.87–0.93, p b 0.001). Resting HR showed a positive correlation with both mean 1D and 7D HR (r = 0.76, p b 0.001 and r = 0.73, p b 0.001 respectively). Considering absolute values, resting HR (73 ± 11 bpm) was similar to both mean 1D (71 ± 11 bpm) and 7D HR (72 ± 10 bpm). The absolute differences for both 1D and 7D mean HR versus resting HR were: 45 patients (60%) between 0 and 5 bpm, 14 patients (19%) between 5 and 10 bpm and 16 patients (21%) more than 10 bpm. With regard to this last group almost all patients had resting HR ≥ 70 bpm (15 of 16 patients). Fig. 1 shows the agreement between resting and mean HR over the whole monitoring period. Forty-nine study participants (64%) had a resting HR ≥ 70 bpm (mean value 81 ± 10 bpm). Notably, 11 (23%) had mean HR b70 both at 1D (mean HR 64 ± 2 bpm) and 7D (mean HR 65 ± 1 bpm), p b 0.001. These patients spent less time at HR ≥ 70 than patients with concordant values (both resting and mean values ≥ 70) during either the whole, day or even the night monitoring period, as shown in Fig. 2A. In contrast, among the 26 study participants (36%) with resting HR b 70 (mean HR 60 ± 7 bpm), 6 (23%) had mean 1D and 7D HR ≥ 70 (73 ± 1 and 74 ± 1.0 bpm respectively), p b 0.05. These discordant patients are listed in Table 2. As shown in Fig. 2B they
also spent more time at HR ≥ 70 than patients with concordant values during the whole monitoring period, and also during the sleep time. The major findings of the present study are: 1) as an absolute value, resting HR is a good estimate of mean HR across multiple days of measurement; 2) When categorizing patients as a function of a target HR of 70 bpm, however, the concordance between resting and HR over the days was suboptimal in a quarter of them; In recent years, control of HR has become the focus of drug development in HF, as HR is a strong predictor of morbidity and mortality in cardiovascular disease including patients with chronic HF [3,4]. McAlister et al. [5] concluded that the extent to which HR reduction is achieved by beta blockade is significantly associated with the survival benefit obtained. The recent SHIFT trial [6] reduced morbidity and mortality in HF in relation to the HR achieved with ivabradine, supporting the notion that HR is not only a risk marker, but also a target of treatment. Given the findings of these and other prior studies, an articulated HR goal of b 70 bpm has been established [7]. We found resting HR accurately reflects more complex measurement of HR across an extended monitoring period in the majority of our HF patients. Important nuances to our results include the fact that a quarter of patients showed discordant results relative to resting HR. Importantly in one group, the resting HR was b70 bpm but mean HR was ≥70 bpm. According to current guidelines based on resting measures [7] these patients might not have been recognized as being candidates for improving treatment; such patients also spent more time at HR ≥ 70 bpm compared to patients with concordant values (both resting and mean HR b70 bpm) even during sleep hours indicating that the physical activity is not the only determinant of the discrepancy. The importance of our findings is that inadequate HR control over the days could exist despite resting HR b 70 bpm; prolonged HR monitoring can identify these patients, allowing for more assiduous care.
Fig. 2. Time spent above 70 bpm as a function of resting heart rate (≥70 in A and b70 in B) and mean heart rate over 1-day monitoring.
Please cite this article as: Pastor-Pérez FJ, et al, Heart rate control in chronic heart failure: Resting versus mean heart rate with prolonged ambulatory ECG recording, Int J Cardiol (2013), http://dx.doi.org/10.1016/j.ijcard.2013.10.071
F.J. Pastor-Pérez et al. / International Journal of Cardiology xxx (2013) xxx–xxx
Our study shows that resting HR is a generally adequate estimator of mean HR across the days. The use of prolonged HR monitoring showed that the concordance was suboptimal in a quarter of patients when categorizing patients as a function of a target HR of 70 bpm. Some of them would have been detected as being eligible for intensification of HR reducing agents.
[3] [4]
[5]
References [6] [1] Fox K, Ford I, Steg PG, et al. Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial. Lancet 2008;372(9641):817–21. [2] Dickstein K, Cohen-Solal A, Filippatos G. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiol-
[7]
e3
ogy. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Eur J Heart Fail 2008;10(10):933–89. Kannel WB, Kannel C, Paffenbarger Jr RS, Cupples LA. Heart rate and cardiovascular mortality: the Framingham Study. Am Heart J 1987;113(6):1489–94. Kolloch R, Legler UF, Champion A, et al. Impact of resting heart rate on outcomes in hypertensive patients with coronary artery disease: findings from the INternational VErapamil-SR/trandolapril STudy (INVEST). Eur Heart J 2008;29(10):1327–34. McAlister FA, Wiebe N, Ezekowitz JA, Leung AA, Armstrong PW. Meta-analysis: betablocker dose, heart rate reduction, and death in patients with heart failure. Ann Intern Med 2009;150(11):784–94. Swedberg K, Komajda M, Bohm M, et al. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet 2010;376(9744):875–85. McMurray JJ, Adamopoulos S, Anker SD. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association (HFA) of the ESC. Eur Heart J 2012;33(14):1787–847.
Please cite this article as: Pastor-Pérez FJ, et al, Heart rate control in chronic heart failure: Resting versus mean heart rate with prolonged ambulatory ECG recording, Int J Cardiol (2013), http://dx.doi.org/10.1016/j.ijcard.2013.10.071
