The effectiveness of enhanced external counterpulsation (EECP) in patients suffering from chronic refractory angina previously treated with transmyocardial laser revascularisation

IJCA-16376; No of Pages 3 International Journal of Cardiology xxx (2013) xxx–xxx

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Letter to the Editor

The effectiveness of enhanced external counterpulsation (EECP) in patients suffering from chronic refractory angina previously treated with transmyocardial laser revascularisation☆ Poay Huan Loh a, b,⁎, 1, Elizabeth Kennard c, 1, Christos V. Bourantas a, 1, Raj Chelliah b, 1, Paul Atkin a, 1, Jocelyn Cook a, 1, John G. Cleland a, b, 1, Andrew Michaels d, 1, John C.K. Hui e, 1for the International EECP Patient Registry (IEPR) a

Academic Cardiology Department, University of Hull, Castle Hill Hospital, Hull, UK Cardiology Department, Hull and East Yorkshire Hospitals NHS Trust, Hull, UK c Department of Epidemiology, University of Pittsburgh, USA d Cardiology, St. Joseph Hospital, Eureka, USA e Divison of Cardiology, State University of New York, USA b

a r t i c l e

i n f o

Article history: Received 27 April 2013 Accepted 4 May 2013 Available online xxxx Keywords: Enhanced external counterpulsation Refractory angina Angina pectoris Coronary artery disease Ischemic heart disease

Dear Editor, Despite advances in surgical and interventional cardiology, up to a third of the patients with symptomatic coronary artery disease are not suitable for or cannot be fully revascularised [1,2]. These patients have poor quality of life and high morbidity and mortality [1,3–5]. The management of these patients with chronic refractory angina is challenging, but there is no consensus in major guidelines to address their unmet needs [2]. Depending on local expertise and availability, many have resolved to alternative treatment methods, including enhanced exter-

☆ Disclosure: Dr. JCK Hui is the chief technology officer and the senior vice president of Vasomedical Inc. (NY, USA), manufacturer of EECP device. Dr. Hui also hold some stocks of the company. ⁎ Corresponding author at: Academic Cardiology Department, University of Hull, Castle Hill Hospital, Hull & East Yorkshire Hospitals NHS Trust, Hull, HU16 5JQ, UK. Tel.: +44 1482 875875; fax: +44 1482 461526. E-mail address: [email protected] (P.H. Loh). 1 Authors’ statement: All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed their discussed interpretation.

nal counterpulsation (EECP), myocardial laser revascularisation (TMR), spinal cord stimulation and others. However, when one method has failed, it is unclear whether the others would be effective. EECP is a repeatable, safe, effective and technically simple technique to improve angina control, exercise tolerance, myocardial perfusion and quality of life in patients with refractory angina with sustained long-term benefit [5,6]. We investigated the safety and effectiveness of EECP in treating patients who experienced refractory angina despite a prior TMR treatment enrolled in the International EECP Patient Registry (IEPR) Phase 1 and Phase 2. Every participating centre received local ethical or institutional review board approvals. All patients gave written informed consent and were treated using EECP© equipment (Vasomedical Inc., Westbury, New York, USA) [5]. A standard course of 35 one-hour treatment sessions was recommended. Of the 4,306 consecutive patients from centres that provided complete 1-year follow-up data, 91 patients (2.1%) had a prior laser revascularisation (TMR), 3,790 (88.0%) had a prior percutaneous coronary intervention or coronary artery bypass graft surgery (PCI/CABG) and 425 (9.9%) received medical treatment alone (Medical). Of the TMR patients, 88 had transmyocardial laser revascularisation and 3 had either percutaneous therapy or the mode of laser treatment was unknown. Compared to PCI/CABG and Medical patients, TMR patients were younger but had more extensive and longer duration of coronary disease and higher prevalence of a prior myocardial infarction and history of heart failure, and the majority had had a prior conventional coronary revascularisation and were considered unsuitable for further intervention (Table 1). TMR patients also suffered from more frequent and severe angina than the other patients despite taking more anti-anginal medications. Immediately post-EECP, CCS improved by at least one class in 66% of TMR, 76% of PCI/CABG and 79% of Medical patients, p b 0.05. CCS III/IV was reported in 45% of TMR, 26% of PCI/CABG and 21% of Medical patients, p b 0.001 (Fig. 1a). Nitroglycerine (GTN) usage was discontinued in 33% of TMR, 49% of PCI/CABG and 54% of Medical patients (p b 0.001), but the mean reduction in weekly GTN use was similar in all the three groups (TMR 9 ± 13, PCI/CABG 7 ± 11 and

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Please cite this article as: Loh PH, et al, The effectiveness of enhanced external counterpulsation (EECP) in patients suffering from chronic refractory angina previously treated with transmyocardial laser revascularisation, Int J Cardiol (2013), http://dx.doi.org/10.1016/j.ijcard.2013.05.050

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P.H. Loh et al. / International Journal of Cardiology xxx (2013) xxx–xxx

Table 1 Baseline characteristics of the patients in Medical, PCI/CABG and TMR groups.

Age (years) Man LVEF (%) CAD diagnosis (years) Multi-vessel CAD PCI CABG Previous EECP Unsuitable for PCI/CABG Myocardial infarction Heart failure Hypertension Diabetes Hypercholesterolaemia Smoking history Medications Anti-platelets Beta-blockers Lipid-lowering agents ACEIs Calcium channel blockers Long-acting nitrates GTN use CCS class I II III IV Angina (episodes/week) GTN use (times/week) EECP treatment Treatment course (hours) Treatment completed Treatment discontinued Patient's choice Clinical events Clinical events Skin breakdown Musculoskeletal Unstable angina Myocardial infarction Heart failure PCI CABG Death MACE

Medical (n = 425)

PCI/CABG (n = 3790)

TMR (n = 91)

P

68 ± 13 59.1 49 ± 16 7±9 62.0 – – – 81.6 51.8 26.8 74.7 44.2 76.6 62.9

67 ± 11 73.9 47 ± 14 11 ± 8 84.2 76.4 78.0 5.5 88.8 72.5 31.3 76.2 44.7 87.3 70.1

62 ± 12 79.1 46 ± 13 12 ± 9 91.7 94.3 94.5 4.5 91.2 81.1 40.9 76.7 44.0 92.3 69.9

b0.001 b0.001 b0.05 b0.001 b0.001 b0.001 b0.001 ns b0.001 b0.001 b0.01 ns ns b0.001 ns

68.3 73.6 63.0 41.2 38.6 68.0 59.0

78.3 81.0 78.3 44.0 43.4 78.6 73.7

80.2 93.3 86.8 42.9 62.6 91.2 88.9

ns b0.001 b0.001 ns b0.001 b0.001 b0.001

2.8 10.4 63.1 23.8 8 ± 11 8±8

1.1 7.0 64.5 27.4 12 ± 14 10 ± 13

0 2.2 63.7 34.1 18 ± 17 13 ± 14

b0.01

b0.001 b0.001

32.8 ± 9.2 85

33.0 ± 9.3 83

31.5 ± 11.1 75

ns ns

3.5 3.1

4.8 3.2

4.4 3.3

ns ns

3.6 1.9 1.9 1.0 2.4 0.5 0.5 1.2 2.6

2.3 1.5 3.6 0.9 1.9 1.1 0.3 0.5 2.4

3.5 1.1 11.2 4.5 3.4 2.2 0 1.1 5.5

ns ns b0.001 b0.01 ns ns ns ns ns

Data are in percentages unless otherwise stated. ACEIs, angiotensin converting enzyme inhibitors or angiotensin receptor blockers; CABG, coronary artery bypass graft operation; CAD, coronary artery disease; CCS, Canadian Cardiovascular Society Angina Class; GTN, nitroglycerine; LVEF, left ventricular ejection function; MACE, major adverse clinical events; ns, not significant; PCI, percutaneous coronary intervention.

Medical 6 ± 8 times/week, p = ns) (Fig. 1c and d). The reduction in angina frequency was the greatest in TMR group compared to the others (TMR 12 ± 18, PCI/CABG 9 ± 12 and Medical 6 ± 29 episodes/week, p b 0.001) (Fig. 1b). In all patients, there was no significant change in medication use during treatment period. After 12 months, 3 TMR, 201 PCI/CABG and 28 Medical patients had died. Of those who survived, fewer TMR patients had sustained improvement in CCS (68% TMR, 76% PCI/CABG and 87% Medical, p b 0.001) and weekly angina frequency (73% TMR, 76% PCI/CABG and 85% Medical, p b 0.001) (Fig. 1a). However, the mean weekly angina frequency and GTN use remained lower in all 3 groups compared to those of pre-EECP (Fig. 1b and d). Similar proportion of TMR, PCI/CABG and Medical patients completed their course of EECP (Table 1). Adverse events were uncommon during treatment period, although the incidence of acute

coronary syndrome was higher in the TMR patients (Table 1). During 1-year follow-up, TMR patients had a higher PCI and repeat EECP rates, while Medical patients had higher CABG and mortality rates (Table 2). Fewer TMR patients experienced a reduction in CCS with a higher treatment major adverse cardiovascular event (MACE) rate compared to the other patients may be partly explained by a more extensive coronary artery disease and higher prevalence of co-morbidities in these patients. Nevertheless, a large proportion of TMR patients experienced a reduction in CCS and, similar to the other patients, with a sustained reduction in the frequency of angina and GTN use during 1-year follow-up. An observational study has suggested that EECP may reduce angina to a greater extent than spinal cord stimulation [7]. EECP can also be repeated safely to improve symptom in a large proportion of the patients with refractory angina [8]. In the absence of randomised data comparing different treatment methods, EECP can be one of the first options to be considered especially when another treatment is ineffective. This study highlights the challenge faced in managing patients with chronic refractory angina. Many patients continued to experience severe angina despite a previous coronary intervention and TMR. These patients also had a high MACE rate. Indeed, the 1-year mortality in patients treated with TMR ranges from 5% to 15% with a low eventfree survival of 54% [9]. Consistent with previous study, a proportion of patients could only be managed medically as conventional revascularisation was not feasible and the prognosis of these patients was particularly poor [1]. However, some patients were treated with conventional revascularisation during follow-up suggestive that vigilance is needed in reassessing these patients as coronary lesions may progress or develop. Establishing regional specialised centres would encourage a more concerted effort in identifying the best treatment strategy and facilitating research in existing or novel therapies [10]. We should acknowledge some limitations to this study. It is an observational study and the number of TMR patients is small. However, it represents the actual clinical setting since consecutive patients received ≥1 hour of treatment were enrolled in the IEPR. The duration between EECP and TMR treatment was not available. In conclusion, patients who have a prior TMR suffer from more advanced coronary disease, and a large proportion of them will benefit from EECP. Patients with refractory angina have a high MACE rate and effort should be encouraged in order to identify the best treatment strategy to address their unmet needs.

References [1] Williams B, Menon M, Satran D, et al. Patients with coronary artery disease not amenable to traditional revascularization: prevalence and 3-year mortality. Catheter Cardiovasc Interv 2010;75(6):886–91. [2] Mannheimer C, Camici P, Chester MR, 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(5):355–70. [3] Mukherjee D, Comella K, Bhatt DL, Roe MT, Patel V, Ellis SG. Clinical outcome of a cohort of patients eligible for therapeutic angiogenesis or transmyocardial revascularization. Am Heart J 2001;142(1):72–4. [4] Moore RK, Groves D, Bateson S, et al. Health related quality of life of patients with refractory angina before and one year after enrolment onto a refractory angina program. Eur J Pain 2005;9(3):305–10. [5] Loh PH, Cleland JG, Louis AA, et al. Enhanced external counterpulsation in the treatment of chronic refractory angina: a long-term follow-up outcome from the International Enhanced External Counterpulsation Patient Registry. Clin Cardiol 2008;31(4): 159–64. [6] Arora RR, Chou TM, Jain D, et al. The multicenter study of enhanced external counterpulsation (MUST-EECP): effect of EECP on exercise-induced myocardial ischemia and anginal episodes. J Am Coll Cardiol 1999;33(7):1833–40. [7] Bondesson S, Pettersson T, Erdling A, Hallberg IR, Wackenfors A, Edvinsson L. Comparison of patients undergoing enhanced external counterpulsation and spinal cord stimulation for refractory angina pectoris. Coron Artery Dis 2008;19(8): 627–34. [8] Lawson WE, Barsness G, Michaels AD, et al. Effectiveness of repeat enhanced external counterpulsation for refractory angina in patients failing to complete an initial course of therapy. Cardiology 2007;108(3):170–5.

Please cite this article as: Loh PH, et al, The effectiveness of enhanced external counterpulsation (EECP) in patients suffering from chronic refractory angina previously treated with transmyocardial laser revascularisation, Int J Cardiol (2013), http://dx.doi.org/10.1016/j.ijcard.2013.05.050

P.H. Loh et al. / International Journal of Cardiology xxx (2013) xxx–xxx

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Fig. 1. shows (a) the CCS class distribution, (b) the mean weekly angina frequency, (c) the proportion of patients required GTN use and (d) the mean weekly GTN use in the Medical, PCI/CABG and TMR patients before their EECP treatment and immediately and 1 year after the treatment.

Table 2 Clinical events (Kaplan-Meier rate) during 1-year follow-up.

Repeat EECP PCI CABG MI Death MACE

Medical

PCI/CABG

TMR

p

4.8 3.3 5.4 5.1 6.6 17.0

10.1 7.9 2.5 4.6 5.3 17.0

13.7 14.6 1.2 8.1 3.5 24.7

b0.01 b0.001 b0.01 ns b0.05 ns

[9] Allen KB, Dowling RD, Fudge TL, et al. Comparison of transmyocardial revascularization with medical therapy in patients with refractory angina. N Engl J Med 1999;341(14):1029–36. [10] Jolicoeur EM, Ohman EM, Temple R, et al. Clinical and research issues regarding chronic advanced coronary artery disease part II: trial design, outcomes, and regulatory issues. Am Heart J 2008;155(3):435–44.

Data are presented in percentages. CABG, coronary artery bypass graft surgery; MI, myocardial infarction; ns, not significant; PCI, percutaneous coronary intervention; MACE, major adverse cardiovascular event (PCI/CABG/MI/Death).

Please cite this article as: Loh PH, et al, The effectiveness of enhanced external counterpulsation (EECP) in patients suffering from chronic refractory angina previously treated with transmyocardial laser revascularisation, Int J Cardiol (2013), http://dx.doi.org/10.1016/j.ijcard.2013.05.050