TY - JOUR
AU1 - Wu, Eline
AU2 - Mårtensson, Jan
AU3 - Broström, Anders
AB - Abstract Background Refractory angina pectoris (AP) is a persistent, painful condition characterized by angina caused by coronary insufficiency in the presence of coronary artery disease. It has been emphasized that there are possible underlying neuropathophysiological mechanisms for refractory AP but chronic ischemia is still considered to be the main problem. These patients suffer from severe AP and cannot be controlled by a combination of pharmacological therapies, angioplasty or coronary bypass surgery. AP has a negative impact on quality of life and daily life. Enhanced external counterpulsation (EECP) is a therapeutic option for these patients. Aims The aim of this study was to evaluate EECP after six months regarding physical capacity and health-related quality of life (HRQoL) in patients with refractory AP. Methods This was a study with single case research experimental design involving 34 patients treated with EECP. Six minute walk test (6MWT), functional class with Canadian Cardiological Society (CCS) classification and self-reported HRQoL questionnaires as Short Form 36 (SF-36) were collected at baseline and after treatment. CCS class and SF-36 were repeated at six months follow-up. Results Patients enhanced walk distance on average by 29 m after EECP (p<0.01). CCS class also improved (p<0.001) and persisted at six months follow-up (p<0.001). HRQoL improved significantly and the effects were maintained at follow-up after the treatment. Conclusion Patients with refractory AP receive beneficial effects from EECP both in physical capacity and HRQoL. As other treatment options for this patient group are scarce, EECP should be offered to improve physical health and HRQoL in these patients. Refractory angina pectoris, enhanced external counterpulsation, physical capacity, health-related quality of life Introduction Improved pharmacological treatment and better accessibility to invasive therapies have led to an increased prevalence of angina pectoris (AP) in most European countries.1,2 An updated and recent definition describes refractory AP as a persistent, painful condition characterized by angina caused by coronary insufficiency in the presence of coronary artery disease which cannot be controlled by a combination of pharmacological therapies and revascularizations. It has been emphasized that there are possible underlying neuropathophysiological mechanisms for refractory AP but chronic ischemia is still considered as the main problem.3 Refractory AP is often associated with a more severe heart disease, higher mortality and an impaired quality of life.4 The current pharmacological treatment is based on a combination of beta-blockers, calcium channel blockers, long and short-acting nitrates and antiplatelet agents.5,6 According to European guidelines, the goal for the treatment is to improve quality of life by reducing the frequency of symptoms, but also to improve prognosis.2 Despite a combination of different drugs, invasive and surgical treatment, patients with refractory AP often continue to have symptoms.7,8 Further revascularization when disabling angina symptoms occur is often not an option because of the risk of complications during the intervention.1,9 The main focus may therefore be on alleviating symptoms with other treatment options.10 Enhanced external counterpulsation (EECP) is an additional treatment option for refractory AP that can be performed by a trained health professional (e.g. nurse) during cardiovascular monitoring.11 External pressure cuffs are wrapped around the patient’s calves, thighs and buttocks.6,12 The EECP provides an increased aortic diastolic pressure during diastole by a blast created by the external cuffs that are inflated sequentially at diastole and leads to an improved coronary perfusion. Inflation of the cuffs also creates an increased venous return which leads to an increased preload. During systole all the air in the cuffs is released suddenly and creates a suction-like effect leading to a reduced afterload.13 Randomized controlled trials from both Buschmann et al. and Gloekler et al.14,15 reported a significantly increased coronary collateral flow and collateral growth in patients with stable AP after being treated with EECP. Reduced AP may be due to improved myocardial perfusion since EECP was shown to promote the formation of new collaterals.15–17 Only a few clinical studies have investigated the effects of the treatment of anginal symptoms.18–20 The developments in pharmacological therapies and revascularization have led to an increased number of patients suffering from refractory AP.1 EECP is therefore an important complement to traditional therapy in patients with refractory AP.21 Physical training and activity is an important part in the non-pharmacological treatment of AP.22 The Canadian Cardiological Society (CCS) classification (i.e. classes I–VI) is a well known tool to classify symptoms in relation to different levels of physical activity.2 Patients in CCS class I can perform ordinary activities without suffering symptoms, and AP occurs only with strenuous or rapid or prolonged exertion. In CCS class II, patients have a slight limitation of ordinary activity. AP can occur when walking or climbing stairs rapidly, walking uphill, in cold weather and under emotional stresses.2 Patients in CCS class II can have a milder refractory AP.20 However, patients with refractory AP are typically in classes III or IV indicating a moderate to severe AP.6,10 This means that they have a marked limitation of ordinary physical activity and/or an inability to perform physical activity without discomfort, signs of myocardial ischemia and persistent symptoms.21 These patients often have a tendency to limit their physical activity for fear of further deterioration of their cardiac status. This protective attitude can contribute to a sedentary lifestyle23 that prevents positive cardiovascular effects of physical activity, and also to a negative impact on their quality of life. Health-related quality of life (HRQoL) relates primarily to function and well-being during illness and treatment.24 Refractory AP is associated with impaired HRQoL due to lack of energy, poor sleep, reduced exercise capacity, increased anxiety and depression25 as well as an increase in severity of AP.26,27 EECP may lead to reduced nitroglycerin consumption, improved well-being and increased physical activity9 which can improve HRQoL for patients suffering from refractory AP. The treatment has been used in clinical practice12 but few, if any, studies have investigated the long-term effects of a nurse-based intervention with EECP on both physical capacity and HRQoL. The aim of this study was therefore to evaluate the effects of EECP six months after completion of treatment regarding physical capacity and HRQoL in patients with refractory AP. Methods Design, context and sample A prospective and longitudinal pilot study using a single case research experimental design was carried out (Figure 1). Since late 2005, a university hospital in a large city in Sweden has had the opportunity to offer EECP treatment to patients with refractory AP. Suitable patients were, as in normal clinical practice, referred from other cardiology clinics both in and outside the area to undergo the treatment. Exclusion criteria for EECP were aortic valve insufficiency and leg ulcers. A total of 42 patients had been treated with EECP between the years 2005–2010. Those who had difficulty with the Swedish language (n=2) were not included because the evaluation of HRQoL was performed with self-reported questionnaires in Swedish. A total of 40 patients were asked to participate and 37 of them gave informed consent. Three patients were excluded as the questionnaires were incompletely answered. Hence, a total of 34 patients were included and 10 out of these did not have a scheduled follow-up at the study site, which led to incomplete assessments at six months follow-up. Complete assessments were therefore collected on 24 patients. For the treatment, predetermined clinical routines were used and EECP was provided during weekdays at an outpatient ward at the hospital, near the cardiology department, in the presence of a trained cardiac nurse. The treatment included 35 one-hour sessions over a period of seven to eight weeks. Relevant medical equipment (i.e. defibrillator and oxygen equipment) were installed in the treatment room and the responsible nurse could at anytime contact a physician if problems arose. After the treatment, referral to physical therapy was given if needed. Figure 1. Open in new tabDownload slide Study design CCS: Canadian Cardiological Society; EECP: enhanced external counterpulsation; SF-36: Short Form 36. Clinical, objective data and self-report questionnaires Data collection was conducted at baseline, after completion of EECP and at six months follow-up. Patient characteristics were collected from medical records by the first author. Due to the predetermined clinical routines either transthoracic echocardiogram and/or in some cases myocardinal perfusion scintigraphy were performed before EECP to exclude aortic valve insufficiency. Functional class was assessed with the CCS classification as recommended by the European Society of Cardiology Guidelines2 at baseline, post EECP and at six months follow-up. Physical capacity was assessed with the six minute walk test (6MWT) according to recommendations from the American Thoracic Society,28 at baseline and after completion of EECP (n=29). The dropouts were due to dizziness and balance problems (n=2), AP during walk test (n=2) and reduced strength (n=1). Estimation of intensity of exertion was done with the Borg scale rate of perceived exertion (RPE) after a 6MWT and intensity of pain with the Borg scale CR10. Borg scale RPE rate exertion on a scale from 6–20, where a higher score means higher intensity of symptoms, while the Borg scale CR10 rate pain on a scale 0–10 and follows a similar principle as Borg scale RPE.29 HRQoL was evaluated with the Short Form 36 (SF-36) at baseline, after completion of EECP and at six months follow-up. SF-36 is a validated and generic instrument30 that measures HRQoL on eight subscales: physical function, role disability due to physical health, role disability due to emotional health, social function, bodily pain, general health, vitality and mental health. Each subscale is presented with a value from 0–100, and a higher value indicates better HRQoL. Physical component summary and mental component summary are two summary measures which are also included in SF-36.24 Statistical analysis Statistical analysis was carried out using Predictive Analytics SoftWare (PASW Statistics) Version 18. Patient characteristics data were compiled with descriptive statistics. Walking distance was analyzed using the paired t-test. Non-parametric variables such as the perception of intensities of exertion and pain according to the Borg scales and the CCS classification were analyzed with the Wilcoxon rank sum test. HRQoL data were analyzed with the Friedman test. The statistical significance level was chosen at p<0.05. Ethics Information regarding the study was given both orally and in written documentation to the patients. Written consent was obtained from all participants in the study. Permission to conduct the study was obtained from the clinical board at the hospital where the study was conducted. The investigation conforms with the principles outlined in the Declaration of Helsinki. Results Population The majority of patients were men (91%) and mean age was 66 (range 52–81) years (Table 1). The patients had a history of significant coronary artery disease with 55% suffering from at least one previous acute myocardial infarction. Seventy-seven percent and 62% of patients had undergone a percutaneous coronary intervention or coronary artery by-pass grafting, respectively. Approximately one-third of the patients were treated for diabetes mellitus. Heart failure with varying degrees of impaired left ventricular function was detectable in 47% of the patients. More than half of the patients were treated for hypertension (68%) and some had previously been smokers (41%). Three patients were referred to physical therapy after EECP. Current pharmacological therapies are described in Table 1. Table 1. Patient characteristics data N=34 . n (%) unless otherwise stated . Sociodemographic data Gender Men 31 (91) Women 3 (9) Age mean (range) 66 (52–81) Smokers Yes 1 (3) No 19 (56) Quit smoking 14 (41) Clinical data BMI mean (range) 28 (23–35) Number of AMI median (range) 1 (0–8) Type of AMI NSTEMI 9 (26) STEMI 10 (29) No AMI 15 (44) PCI Yes, one time 8 (24) Yes >one time 18 (53) No, never 8 (24) Coronary artery by-pass grafting 21 (62) Hypertension 23 (68) Hyperlipidemia 21 (62) Stroke 4 (12) Diabetes mellitus Yes 11 (32) No 23 (68) Heart failure EF >55 % 18 (53) EF 45–54 % 9 (26) EF 30–44 % 6 (18) EF <30 % 1 (3) Pharmacological treatments Beta blockers 30 (88) Lipid-lowering agents 34 (100) Aspirin 27 (79) Calcium channel blockers 21 (62) Antiplatelet agents 11 (32) Warfarin 7 (21) ACE-inhibitors 12 (35) Angiotensin receptor blockers 13 (38) Nitrates Long-acting 4 (12) Short-acting 5 (15) Combination therapies 24 (71) N=34 . n (%) unless otherwise stated . Sociodemographic data Gender Men 31 (91) Women 3 (9) Age mean (range) 66 (52–81) Smokers Yes 1 (3) No 19 (56) Quit smoking 14 (41) Clinical data BMI mean (range) 28 (23–35) Number of AMI median (range) 1 (0–8) Type of AMI NSTEMI 9 (26) STEMI 10 (29) No AMI 15 (44) PCI Yes, one time 8 (24) Yes >one time 18 (53) No, never 8 (24) Coronary artery by-pass grafting 21 (62) Hypertension 23 (68) Hyperlipidemia 21 (62) Stroke 4 (12) Diabetes mellitus Yes 11 (32) No 23 (68) Heart failure EF >55 % 18 (53) EF 45–54 % 9 (26) EF 30–44 % 6 (18) EF <30 % 1 (3) Pharmacological treatments Beta blockers 30 (88) Lipid-lowering agents 34 (100) Aspirin 27 (79) Calcium channel blockers 21 (62) Antiplatelet agents 11 (32) Warfarin 7 (21) ACE-inhibitors 12 (35) Angiotensin receptor blockers 13 (38) Nitrates Long-acting 4 (12) Short-acting 5 (15) Combination therapies 24 (71) ACE: angiotensin-converting-enzyme; AMI: acute myocardial infarction; BMI: body mass index; EF: ejection fraction; NSTEMI: non-ST segment elevation myocardial infarction; PCI: percutaneous coronary intervention; STEMI: ST segment elevation myocardial infarction. Open in new tab Table 1. Patient characteristics data N=34 . n (%) unless otherwise stated . Sociodemographic data Gender Men 31 (91) Women 3 (9) Age mean (range) 66 (52–81) Smokers Yes 1 (3) No 19 (56) Quit smoking 14 (41) Clinical data BMI mean (range) 28 (23–35) Number of AMI median (range) 1 (0–8) Type of AMI NSTEMI 9 (26) STEMI 10 (29) No AMI 15 (44) PCI Yes, one time 8 (24) Yes >one time 18 (53) No, never 8 (24) Coronary artery by-pass grafting 21 (62) Hypertension 23 (68) Hyperlipidemia 21 (62) Stroke 4 (12) Diabetes mellitus Yes 11 (32) No 23 (68) Heart failure EF >55 % 18 (53) EF 45–54 % 9 (26) EF 30–44 % 6 (18) EF <30 % 1 (3) Pharmacological treatments Beta blockers 30 (88) Lipid-lowering agents 34 (100) Aspirin 27 (79) Calcium channel blockers 21 (62) Antiplatelet agents 11 (32) Warfarin 7 (21) ACE-inhibitors 12 (35) Angiotensin receptor blockers 13 (38) Nitrates Long-acting 4 (12) Short-acting 5 (15) Combination therapies 24 (71) N=34 . n (%) unless otherwise stated . Sociodemographic data Gender Men 31 (91) Women 3 (9) Age mean (range) 66 (52–81) Smokers Yes 1 (3) No 19 (56) Quit smoking 14 (41) Clinical data BMI mean (range) 28 (23–35) Number of AMI median (range) 1 (0–8) Type of AMI NSTEMI 9 (26) STEMI 10 (29) No AMI 15 (44) PCI Yes, one time 8 (24) Yes >one time 18 (53) No, never 8 (24) Coronary artery by-pass grafting 21 (62) Hypertension 23 (68) Hyperlipidemia 21 (62) Stroke 4 (12) Diabetes mellitus Yes 11 (32) No 23 (68) Heart failure EF >55 % 18 (53) EF 45–54 % 9 (26) EF 30–44 % 6 (18) EF <30 % 1 (3) Pharmacological treatments Beta blockers 30 (88) Lipid-lowering agents 34 (100) Aspirin 27 (79) Calcium channel blockers 21 (62) Antiplatelet agents 11 (32) Warfarin 7 (21) ACE-inhibitors 12 (35) Angiotensin receptor blockers 13 (38) Nitrates Long-acting 4 (12) Short-acting 5 (15) Combination therapies 24 (71) ACE: angiotensin-converting-enzyme; AMI: acute myocardial infarction; BMI: body mass index; EF: ejection fraction; NSTEMI: non-ST segment elevation myocardial infarction; PCI: percutaneous coronary intervention; STEMI: ST segment elevation myocardial infarction. Open in new tab Functional class At baseline four patients were in CCS class I–II or II and 22 patients were in CCS classes III or IV (Figure 2(A)). The outcome after completion of treatment showed that 75% of the patients (n=26) were in CCS class I or II and only one patient remained in CCS class III and no patient was in either CCS classes III-IV or IV (p<0.001). Figure 2(B) shows that CCS classes were improved and sustained at follow-up. Two out of 24 patients were in CCS class III after six months, significantly less (p<0.001) compared to baseline when 15 patients were either in CCS classes III, III–IV or IV. Figure 2. Open in new tabDownload slide Canadian Cardiological Society (CCS) classes at (A) baseline and post enhanced external counterpulsation (EECP) in patients with refractory angina pectoris (n= 34) and at (B) baseline and six months after EECP treatment in patients with refractory angina pectoris. Data in (B) are based on patients (n=24) where data were collected both at baseline and at six months follow-up Physical capacity The results from the 6MWT showed that the walking distance increased about 7% on average from 410 m to 439 m (p<0.01) (Table 2). Two out of 29 patients had the same outcome after treatment and four patients decreased it while the rest (n=23) increased their walking distance. The estimation of exertion and pain with the Borg scales showed that patients scored significantly lower pain levels in relation to the 6MWT after EECP compared to after the initial 6MWT (p<0.05). However, no significant difference was found regarding estimated levels of exertion. Table 2. Outcome of six minute walk test (6MWT) pre and post enhanced external counterpulsation (EECP) in patients with refractory angina pectoris (n=29) . pre EECP . post EECP . p value . Walking distance meters mean (SD) 410 (97) 439 (87) <0.01 Level of effort according to Borg scale RPE mean (SD) 12.8 (2.7) 12.0 (2.2) NS Level of pain according to Borg scale CR10 mean (SD) 2.7 (2.0) 1.7 (1.9) <0.05 . pre EECP . post EECP . p value . Walking distance meters mean (SD) 410 (97) 439 (87) <0.01 Level of effort according to Borg scale RPE mean (SD) 12.8 (2.7) 12.0 (2.2) NS Level of pain according to Borg scale CR10 mean (SD) 2.7 (2.0) 1.7 (1.9) <0.05 NS: not significant; SD: standard deviation. Open in new tab Table 2. Outcome of six minute walk test (6MWT) pre and post enhanced external counterpulsation (EECP) in patients with refractory angina pectoris (n=29) . pre EECP . post EECP . p value . Walking distance meters mean (SD) 410 (97) 439 (87) <0.01 Level of effort according to Borg scale RPE mean (SD) 12.8 (2.7) 12.0 (2.2) NS Level of pain according to Borg scale CR10 mean (SD) 2.7 (2.0) 1.7 (1.9) <0.05 . pre EECP . post EECP . p value . Walking distance meters mean (SD) 410 (97) 439 (87) <0.01 Level of effort according to Borg scale RPE mean (SD) 12.8 (2.7) 12.0 (2.2) NS Level of pain according to Borg scale CR10 mean (SD) 2.7 (2.0) 1.7 (1.9) <0.05 NS: not significant; SD: standard deviation. Open in new tab HRQoL Figure 3 shows a significant improvement (p<0.01 – p<0.001) in seven out of eight subscales on the SF-36 and the effects were maintained at follow-up. Emotional role function was the subscale that did not reach significant improvement. The summary measure for the physical component showed a statistical improvement (p<0.001). No significant improvement was identified for the summary measure for mental component. Figure 3. Open in new tabDownload slide Outcomes of the eight subscales and two summary measures from Short Form 36 (SF-36) ***p<0.001, **p<0.01, *p <0.05. BP: bodily pain; EECP: enhanced external counterpulsation; GH: general health; MCS: mental component summary; MH: mental health; NS: not significant; PCS: physical component summary; PF: physical function; RE: role disability due to emotional health; RP: role disability due to physical health; SF: social function; VT: vitality. Discussion The main findings demonstrate that EECP significantly improved functional class, physical capacity and HRQoL in patients with refractory AP. The effects on CCS class were sustained six months after treatment. The results of the 6MWT after completion of EECP showed that patients were able to perform, with an unchanged level of exertion, a longer walking distance with significant lower level of pain. Significant improvements were shown in all HRQoL subscales except for emotional role function and the effects were maintained at six months follow-up. In the present study patients with mild to moderate refractory AP were followed over time. Initially the majority of patients were in CCS class III and IV. After treatment the majority moved to CCS class II (p<0.001) and this functional class was maintained at six months follow-up (p<0.001). Other authors31,32 have also reported that patients in CCS classes III and IV seem to respond best to EECP and that the effects persist at long-term follow-up ranging from one to three years after treatment. We found that the patients improved their walking distance about 7%, on average by 29 m (p<0.01) and decreased pain scores on average from 2.7 (standard deviation (SD) 2.0) to 1.7 (SD 1.9) according to the Borg scale CR10 (p<0.05) after EECP. Effects of EECP have been similar to those observed with regular physical exercise, although the mechanisms may include more pronounced coronary shear stress, improved endothelial function in arteries, as well as a reduction in peripheral vascular resistance.33,34 Furthermore, improved physical tolerance after EECP may be due to reduced cardiac workload and the increased myocardial perfusion.35 Studies have showed that regular exercise is associated with several cardio-protective effects, including improved endothelial function, reduced myocardial ischemia and AP attacks and improved functional capacity.36 No specific information about physical activity was included in our study, but the patients were encouraged to continue with physical activity after EECP, with the hope of maintaining the effects that EECP had given and in some cases they were referred to physical therapy (n=3) due to a fear of doing physical activities by themselves. To pick up physical activities is an important aspect of self-care management in the treatment for cardiovascular diseases and one positive outcome after EECP would be that patients can be more physical active with less AP symptoms after treatment. Future interventional studies should include components of physical activity, as well as information about the positive effects of physical activity. The positive results in the present study for both CCS class and 6MWT showed that the patients improved their physical capacity after being treated with EECP. These results are in line with the subjective measurement of physical health (i.e. physical functioning, physical role functioning and bodily pain) on the SF-36. Clinical significance is essential and a five point difference represents a threshold for a clinically significant change in SF-36 scores.37 Seven of eight subscales in SF-36 showed improvement by eight or more points both after EECP and at follow-up. The outcome of the physical subscales showed a significant improvement both in physical function and role function by about 17 and 15 points, respectively, six months after completion of EECP as compared to baseline. Likewise, bodily pain improved by 11 points at six months follow-up (p<0.001). Peterson38 found in a recent study that AP can lead to depression and patients undergoing surgical treatment who subsequently suffer from AP are more likely to feel loneliness, depression, stress and anxiety. The subscale for emotional role function in the present study did not, despite the improvements in CCS classes, detect any statistical significance. These patients have undergone several treatments before EECP for their AP without lasting effects and therefore it is possible that EECP did not impact the dimension in this short amount of time due to fear to once again face failure in treatment. However, a clinical effect may have been achieved since a difference of nearly 10 points was seen at six months follow-up as compared to baseline. Also, any significant difference in the summary measure for mental health could not be ascertained, even if a significant improvement was seen in the subscale of mental health (p<0.01) which is strongly associated with the mental health dimension.24 A study found improvements in HRQoL 12 months after EECP which can lead to an increased ability to perform daily activities, a feeling of energy and stamina that leads to an increased engagement in social activities with family and friends.39 The improvements by EECP in HRQoL in the present study confirm what patient-registry studies have reported.32,40 Some earlier studies with long-term follow-up have shown that the effects can persist for years.20,30,41 The negative impact of refractory AP on daily life and HRQoL is obvious in many patients. Healthcare personnel should offer interventions/treatments based on the patient’s perspective. One way to achieve this is to frequently use quality of life measurements (i.e. a measure based on the patient’s own values of function and well-being) in clinical practice.24 HRQoL instruments are used more often as a measure of treatment outcomes in clinical trials42,43 and not as an integrated, natural part in clinical practice. Furthermore, knowledge of EECP, its validated efficient effects on improved coronary collateral flow and peripheral artery flow and its benefits are not widespread among healthcare personnel.14,15,44 Thus, there is a need to raise awareness since EECP is a safe treatment with good potential to improve HRQoL, especially for patients in CCS classes III and IV.11,31,45 The results from this study further support EECP being considered in patients with refractory AP to a greater extent than has been the case so far. Limitations This pilot study has some limitations that need to be considered. Limited referral of patients to treatment was a reason why we used a design with single case research experimental design (i.e. the patients acted as their own control). A randomized controlled trial is to be preferred but was not feasible. Since this is a relatively uncommon treatment a multicenter design may be needed in future studies. However, despite the small sample size for an interventional study, we were able to demonstrate significant therapeutic treatment results. The study sample was predominantly male which meant that gender differences in the outcome could not be analyzed. Another limitation is that the 6MWT was not repeated at six months follow-up. Furthermore CCS class could not be assessed in almost one-third of the patients at six months follow-up, since the follow-ups were in other clinics and primary care, which may have affected the outcome. Also the fact that the patients (n=3) were receiving physical therapy may have affected their outcome at follow-up because physical training may have impacted on endothelial function and functional capacity.36 A further limitation of the study was lack of control of dose changes on cardiovascular drugs and its impact on the outcomes of the study. Adjustments of drugs occurred only in few cases (n=7) due to hypotension (n=4) and hypertension (n=3) why this was not analyzed. Conclusions This study demonstrates that EECP has significant effects on both physical capacity and HRQoL for patients with refractory AP. As other treatment options for this patient group are scarce, EECP should be offered to improve physical health and HRQoL in patients with refractory AP. Acknowledgement The authors wish to thank Inger Hagerman, Margareta Berglund and Gunilla Förstedt, all from the Department of Cardiology Karolinska University Hospital, Stockholm, Sweden, for their contributions to the study. Special thanks to Christer Sylvén, from the Department of Medicine, Karolinska Institute, Stockholm, Sweden, for his valuable advice and suggestions on the manuscript. Finally, the authors also want to thank Alicja Korszunowa, in the Department of Cardiology M82, Karolinska University Hospital, Stockholm, Sweden, for her support and encouragement during this research. Declaration of conflicting interest None declared Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. References 1. Mannheimer C , Camici P, Chester R et al. . The problem of chronic refractory angina – Report from the ESC Joint Study Group on the Treatment of Refractory Angina . Eur Heart J 2002 ; 23 : 355 – 370 . Google Scholar Crossref Search ADS PubMed WorldCat 2. Fox K , Alonso M, Ardissino D et al. . 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TI - Enhanced external counterpulsation in patients with refractory angina pectoris: a pilot study with six months follow-up regarding physical capacity and health-related quality of life
JF - European Journal of Cardiovascular Nursing
DO - 10.1177/1474515112468067
DA - 2013-10-01
UR - https://www.deepdyve.com/lp/oxford-university-press/enhanced-external-counterpulsation-in-patients-with-refractory-angina-FG0x74JImV
SP - 437
EP - 445
VL - 12
IS - 5
DP - DeepDyve
ER -