Spinal cord stimulation for refractory angina: 100 case-experience from the National Refractory Angina Service

July 2016Br J Cardiol 2016;23:106–9doi:10.5837/bjc.2016.025 Leave a comment

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Authors: Blandina Gomes, Kamen Valchanov, William Davies, Adam Brown, Peter Schofield

First published online July 13, 2016

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Refractory angina represents an important clinical problem. Spinal cord stimulation (SCS) for refractory angina has been used for over two decades to improve pain and, thus, quality of life. This case series reports the clinical efficacy and safety profile of SCS.

We included patients who had a SCS device implanted between 2001 and 2015 following a rigorous selection process. Patients were prospectively followed. We performed a descriptive analysis and used paired t-test to evaluate the difference in Canadian Cardiovascular Society angina (CCS) class before and after SCS implant.

Of the 100 patients included, 89% were male, the mean age was 65.1 years and mean follow-up time was 53.6 months. The CCS class after SCS implant was statistically improved from before (p<0.05) and 88% of patients who gave feedback were very satisfied. Thirty-two patients died, 58% of those who had a documented cause of death, died from a non-cardiac cause.

This study shows the outcome of 14 years’ experience of SCS implantation. The anginal symptoms had a statistically significant improvement and the satisfaction rate was higher than 90%. The complication rate is within the range reported in the literature. SCS seems to be an effective and safe treatment option for refractory angina.

Introduction

Spinal cord stimulation (SCS) therapy has been used for more than four decades in a variety of chronic pain conditions. The introduction of neurostimulation was a logical consequence of the ‘gate-control’ theory published in 1965.¹ According to this model, the activation of large afferent nerve fibres inhibits pain input mediated by small fibres into the dorsal horn of the spinal cord. The goal of SCS is to attenuate discomfort by provoking paraesthesia in the same area.

The European Society of Cardiology defines refractory angina as a chronic condition characterised by the presence of angina caused by coronary insufficiency in the presence of coronary artery disease, which cannot be controlled by a combination of medical therapy, angioplasty and coronary bypass surgery.² This condition represents an important clinical problem with an incidence of 100,000 new cases per year in Europe.³ The presence of reversible myocardial ischaemia should be clinically established to be the cause of the symptoms. Chronic is defined as duration of more than three months.⁴ Many of these patients have already had coronary surgery and percutaneous coronary interventions. These patients have reversible ischaemia yet the coronary vessels are not amenable to surgery or stenting. SCS for refractory angina has been used for over two decades. This treatment does not improve disease progression, but is used in a palliative mode, by improving the pain symptoms and quality of life. The detailed mechanisms of action of SCS for refractory angina are complex, as it may improve coronary perfusion, in addition to attenuating pain signals. Interestingly, the majority of the refractory angina patients have been diagnosed with this condition, but cannot be offered a good estimate of survival, as the prognosis is very variable.

The increasing success of traditional treatment methods to treat coronary events has led to an improvement in survival rate of these patients and, as a consequence, to an increase in the number of patients presenting with refractory angina.

Randomised-controlled trials^5-10 have shown an improvement in symptoms (daily angina attacks or Canadian Cardiovascular Society angina class) after the use of SCS. Most trials have also shown a statistically significant improvement in quality of life,^5,6,8,9 as pointed out by Tsigaridas et al. in their recent systematic review.¹¹

The aim of this study was to assess the clinical improvement of our patients, as well as to evaluate the safety of SCS by analysing the complications, long-term survival, cause of death and satisfaction with treatment, in our centre.

Methods

This study included all patients who had an SCS device implanted for refractory angina, from January 2001 to September 2015, and were prospectively followed-up in the pain clinic of a tertiary referral centre for cardiovascular disease. The treatment is offered as part of a refractory angina national programme. All patients were assessed by a multi-disciplinary team to ensure that there were no further opportunities for revascularisation, either surgically or percutaneously. All patients were on optimal medical therapy, as tolerated. Some of the referred patients are offered further surgical or percutaneous revascularisation, some are offered cardiac surgery, and some are optimised with medical therapy. Patients not suitable for any of these options were then assessed with an extensive psychological questionnaire, prior to being considered for SCS implantation.

Patients

At the time of implantation, Canadian Cardiology Society (CCS) class III/IV symptoms were present despite maximal medical therapy in all patients. All patients had documented obstructive coronary artery disease, reversible myocardial ischaemia, and were not suitable for further surgical or percutaneous coronary artery revascularisation.

Procedure

After informed consent, the implantation of a SCS system was undertaken in an operating theatre under fluoroscopic guidance. All procedures from 2001 to 2011 were undertaken by two operators (one cardiologist and one anaesthetist). All procedures from 2011 to 2015 were undertaken by a single operator (anaesthetist). All operators were trained in the technique at Gottenburg, a recognised leading centre for SCS implantation. All patients received Medtronic SCS systems with a quad lead, connecting lead and IPG (implantable pulse generator – ITREL III, followed by Synergy, followed by ITREL IV, in time). The epidural space was located at the level of T4–T6 using a right paramedian approach, and a single electrode lead was advanced up to C5–C6, slightly to the left of midline, under fluoroscopic guidance. The final location was adjusted up to the level where the activation of the stimulator evoked paraesthesiae, which covered the area of the anginal pain. The leads were then connected through extension cables tunnelled subcutaneously to the pulse generator, implanted in the subcostal area. The programming of the SCS was done by one of two experienced cardiac pacing technicians, who also performed all follow-up checks and reprogramming sessions. The implantation was always completed in a single sitting. Patients were observed overnight as inpatients and discharged home on the following day, with post-operative instructions to wear a soft neck collar, and to take five days of antibiotic prophylaxis. Patients were advised to continue the same anti-anginal medication to allow accumulative prognostic benefit. As the success rate is very high in this patient group, all patients received a short trial of electrical stimulation on the operating table, and had the permanent system implanted at the same sitting.

The patients were instructed to use the SCS for one hour three times per day, in addition to stimulation during angina attacks and before physical activities that would otherwise cause angina pain.

Surgery for mechanical lead problems and IPG replacements took place in the same style, under local anaesthesia and in an operating theatre.

Post-operative assessment

These patients were routinely reviewed in a follow-up clinic at one month after implantation and every year thereafter. If there were problems with the device or programming, the outpatient reviews were more frequent. If there were low energy readings of the IPG, the reviews were reduced to six monthly.

We reviewed the patients’ files to obtain the following data: time of implant, previous cardiac surgery, symptom severity before and after the SCS, failure or complications, time of follow-up, satisfaction with SCS treatment, and cause of death, when applicable. When the data were incomplete, we conducted a telephone consultation with the patient to assess symptom severity after the SCS and degree of satisfaction with the treatment (‘very dissatisfied’, ‘dissatisfied’, ‘unsure’, ‘satisfied’, ‘very satisfied’). Telephone calls were also made to general practitioners to determine cause of death when it was not clear from patients’ files.

Ethics and statistical analysis

Local Ethics Committee approval was sought and the study approved.

Numerical variables were tested for normality, and results are shown as mean and standard deviation (SD).

Data from CCS class was recorded before SCS implant and at the most recent follow-up. To test if the difference between CCS classes before and after SCS implant was significant, we used a paired t-test with a significance level of p<0.05.

Results

Patients

One hundred patients were identified, of whom 89 (89%) were male and the mean age at the time of SCS implant was 65.1 years (SD 8.34 and range 44.4–86.5). In this group of patients, 89% had previous cardiac surgery for ischaemic heart disease.

Mean follow-up time was 53.6 months. In our sample, 32 patients died during the follow-up period and one patient was lost from follow-up.

Effect on symptoms

Data regarding the effect on symptoms was obtained from 68 patients (68%), seven of these are from patients who have subsequently died. From the patients that are still alive, we lack data from six (9%) of them because their devices were explanted, and from one other patient that was lost to follow-up. The majority of these patients received SCS early in the programme (five patients had explants 2001–2007, and one patient in 2013).

Before SCS implantation, the mean value for CCS class was 3.1 (0.8) and, at the latest follow-up, it was 2.0 (0.7). The mean difference between these two was 1.0 (0.97) and it was statistically significant at p<0.05 (p=0.00001).

From the 68 patients alive, 67 gave feedback regarding satisfaction, 59 (88%) were very satisfied, two (3%) were satisfied, and six (9%) were dissatisfied (those whose devices were explanted). Of all IPGs used (ITREL III, Synergy, ITREL IV) during the study period 14 needed replacement. The mean time, in years, that the batteries lasted was 8.4 (2.2).

Complications

Procedures and complications are listed in table 1.

The two cases of SCS replacement were due to failure and infection. Of the three lead replacements, two were done because of casing breakage (8–10 years after implantation), and one because of surgical damage during IPG replacement. Of the two lead revisions, one was done for poor initial position and the other for infection. The case of infection in IPG pocket resolved after one week of antibiotics and later on, the patient was implanted with a new SCS.

The only case of epidural lead infection was in a female patient in whom the brassiere catch had eroded the skin in the area of T5/T6 within a month after implantation. This was treated with antibiotics, and the wound revised. The patient changed the brassiere type and there were no further problems.

Explants were due to inadequate pain control or patient discomfort. In one patient the implantation of SCS up to C5 produced constant nausea, even after switching the device off. The symptoms of angina had completely disappeared. A large renal tumour was diagnosed and removed, but the patient progressed to stage 3 renal failure. After one year of use, the device was explanted and the patient followed-up for a further year.

Fourteen patients had IPG replacement during this period (IPGs used were not rechargeable).

Cause of death

Considering the 32 patients who died during follow-up, 12 (37.5%) have a documented cause of death in either the GP’s records or ours. Seven (58%) of these patients died from a non-cardiac cause, for example cancer, accident, stroke or infection. The other five (42%) died of myocardial infarction, congestive heart failure or sudden collapse.

Prior to death, the mean duration of SCS use for this group of patients was 44 months.

Discussion

This study shows the outcome from 14 years of experience implanting SCS for refractory angina. We present data from a single cardiothoracic centre with refractory angina patients assessed by a multi-disciplinary team. Only selected patients, not suitable for revascularisation and with documented reversible ischaemia, were considered for SCS. Over the last 14 years, 100 SCS were implanted.

Our results show that SCS implantation produces a statistically significant improvement in angina symptoms. The effect of SCS on pain control was previously reported,^5-10 using number of angina attacks and CCS class with different types of stimulation. However, the number of randomised-controlled trials (RCTs) is small, as is the number of patients included in each of them. This may be due to the strict inclusion criteria for RCTs. Additionally, given the invasive nature of the procedure for SCS implantation and the effect of paraesthesia produced by the stimulation, it is difficult to have patients blinded in these studies.

Even though we did not have a comparison group, we were able to compare the severity of the angina at two different time-points. Each subject acted as their own control. Additionally, our sample was bigger than each of the studies analysed in the recent systematic review,¹¹ when taken separately.

More than 90% of the patients were satisfied or very satisfied with the SCS treatment.

Our rate of complications is within the range reported in different studies.^7,9,10,12,13 Reprogramming solved the unsatisfactory coverage. However, there were six patients who requested removal of SCS for inadequate pain control or discomfort. These were the patients who were dissatisfied with the treatment.

Of our patients, 32% died during follow-up, none of these deaths were related to the SCS implant and less than half of them died from a cardiac cause, where the cause of death was known. Although we aimed to find out the cause of death and, hence, whether the patients died from non-cardiac pathology, this task proved to be particularly difficult and we could not draw any conclusions.

The death rate of patients with SCS implantation in our centre is higher than previously reported,^6,7,12,13 which might be due to a highly selected sample in our centre that is referred to the pain clinic by cardiologists, only when all other treatment options have been utilised.

Although this study has the advantage of reporting the experience from a single centre with a good sample size, it also has some limitations. Among them are:

There are incomplete records from a few patients, namely regarding pain severity after SCS in the deceased and their cause of death.
Lack of information regarding additional therapy.
Patients who requested removal of SCS were not considered for the analysis of pain severity after SCS implant, which might overestimate the effect of SCS.

In conclusion, SCS appears to be an effective and safe treatment option with a low complication rate in the management of refractory angina patients. This treatment is recommended by the European Society of Cardiology (ESC),² American Heart Association (AHA), and six more associations,¹⁴ as a class IIb recommendation with a level of evidence B and C, respectively. Detailed patient assessment for suitability for SCS and post-implant follow-up by an experienced team offer good patient satisfaction rates.

Conflict of interest

None declared.

Key messages

Spinal cord stimulation (SCS) is used for refractory angina and improves pain symptoms and quality of life
There is a statistically significant decrease in angina pain class with SCS
SCS appears to be an effective and safe treatment option with a low complication rate in the management of refractory angina patients
Detailed patient assessment for suitability for SCS and post-implant follow-up by an experienced team offer good patient satisfaction rates

References

1. Melzack, R, Wall PD. Pain mechanisms: a new theory. Science 1965;150:971–9. http://dx.doi.org/10.1126/science.150.3699.971

2. Montalescot G, Sechtem U, Achenbach S et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J 2013;34:2949–3003. http://dx.doi.org/10.1093/eurheartj/eht296

3. Mukherjee D, Bhatt DL, Roe MT et al. Direct myocardial revascularization and angiogenesis – how many patients might be eligible? Am J Cardiol 1999;84:598–60. http://dx.doi.org/10.1016/S0002-9149(99)00387-2

4. 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;23:355–70. http://dx.doi.org/10.1053/euhj.2001.2706

5. Eddicks S, Maier-Hauff K, Schenk M et al. Thoracic spinal cord stimulation improves functional status and relieves symptoms in patients with refractory angina pectoris: the first placebo controlled randomized study. Heart 2007;93:585–90. http://dx.doi.org/10.1136/hrt.2006.100784

6. Lanza G, Grimaldi R, Greco S et al. Spinal cord stimulation for the treatment of refractory angina pectoris: a multicenter randomized single-blind study (the SCS-ITA trial). Pain 2011;152:45–52. http://dx.doi.org/10.1016/j.pain.2010.08.044

7. Zipes D, Svorkdal N, Berman D et al. C. Spinal cord stimulation therapy for patients with refractory angina who are not candidates for revascularization. Neuromodulation 2012;15:550–8. http://dx.doi.org/10.1111/j.1525-1403.2012.00452.x

8. Di Pede F, Zuin G, Giada F et al. A. Long-term effects of spinal cord stimulation on myocardial ischemia and heart rate variability: results of a 48-hour ambulatory electrocardiographic monitoring. Ital Heart J 2001;2:690–5.

9. de Jongste MJ, Hautvast RW, Hillege HL, Lie KI. Efficacy of spinal cord stimulation as adjuvant therapy for intractable angina pectoris: a prospective, randomized clinical study. Working Group on Neurocardiology. J Am Coll Cardiol 1994;23:1592–7. http://dx.doi.org/10.1016/0735-1097(94)90661-0

10. Hautvast RW, DeJongste MJ, Staal MJ, Gilst WH, Lie KI. Spinal cord stimulation in chronic intractable angina pectoris: a randomized, controlled efficacy study. Am Heart J 1998;136:1114–20. http://dx.doi.org/10.1016/S0002-8703(98)70171-1

11. Tsigaridas N, Naka K, Tsapogas P et al. Spinal cord stimulation in refractory angina. A systematic review of randomized controlled trials. Acta Cardiol 2015;70:233–43. http://dx.doi.org/10.2143/AC.70.2.3073516

12. Mannheimer C, Eliasson T, Augustinsson LE et al. Electrical stimulation versus coronary artery bypass surgery in severe angina pectoris: the ESBY study. Circulation 1998;97:157–63. http://dx.doi.org/10.1161/01.CIR.97.12.1157

13. McNab D, Khan SN, Sharples LD et al. An open label, single-centre, randomized trial of spinal cord stimulation vs. percutaneous myocardial laser revascularization in patients with refractory angina pectoris: the SPiRiT trial. Eur Heart J 2006;27:1048–53. http://dx.doi.org/10.1093/eurheartj/ehi827

14. Fihn SD, Gardin JM, Abrams J et al. American College of Cardiology Foundation/American Heart Association Task Force. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation 2012;126:354–471. http://dx.doi.org/10.1161/CIR.0b013e318277d6a0

Highlights from international meetings: ACC, EAS and ADA

July 2016Br J Cardiol 2016;23:93 Leave a comment

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Authors: BJCardio Staff

First published online July 13, 2016

News highlights from the American College of Cardiology, European Atherosclerosis Society and American Diabetes Association.

American College of Cardiology

The Annual Scientific Session of American College of Cardiology (ACC) took place in Chicago, USA, from April 2nd–4th 2016.

FIRE AND ICE: to freeze or fry the atrium?

Cryoballoon atrial ablation was found to be non-inferior to radiofrequency (RF) ablation with respect to efficacy for the treatment of patients with drug-refractory paroxysmal atrial fibrillation (AF). There was also no significant difference between the two procedures in regard to patient safety, according to late-breaking clinical trial research presented at ACC and simultaneously published in the New England Journal of Medicine (doi: 10.1056/NEJMoa160201).

The FIRE AND ICE trial, conducted by Dr Karl-Heinz Kuck (Department of Cardiology, Asklepios Klinik, St Georg, Hamburg, Germany) and co-investigators, is the largest randomised trial of its kind, and included participants from 16 centres in eight European countries. “The FIRE AND ICE trial demonstrated that the cryoballoon, a newer, easier-to-use ablation catheter, worked as well as the established technology, which ultimately means that more patients can be treated for AF without having [to go to a] specialised cardiac centre,” said Dr Kuck. “In addition there was, in general, a low risk of procedural complications in both groups, demonstrating that catheter ablation has become much safer over the years.”

The authors compared the effectiveness of point-by-point mode applied RF ablation to that of cryoballoon ablation applied in a single step mode, a newer and less complex technique. The primary efficacy end point of the trial was time to first documented recurrence of AF/atrial tachycardia/atrial flutter, prescription of antiarrhythmic drugs, or repeat ablation.

The multi-centre, randomised, non-inferior open-label trial analysed data gathered from patients ranging from 18 to 75 years old, with symptomatic paroxysmal AF and prior antiarrhythmic drug failure. After exclusions for previous left atrial (LA) ablation, percutaneous coronary intervention (PCI) or myocardial infarction within three months of enrollment, and other clinical issues, 693 patients undergoing pulmonary vein isolation were randomly assigned in a 1:1 ratio: 352 underwent RF ablation and 341 underwent cryoballoon ablation.

In-office visits were scheduled at three, six, and 12 months and every six months after. The primary efficacy end point occurred in 138 patients in the cryoballoon group and in 143 patients in the RF group. A pre-specified superiority test performed for the primary efficacy end point did not indicate a significant difference between the treatment groups. The most common treatment-related serious adverse events were groin site complication and atrial flutter or atrial tachycardia.

The authors observed significant procedural differences between the two groups. RF ablation required less fluoroscopy time (17 vs. 22 minutes). Procedure time was shorter in the cryoballoon group (124 minutes vs. 141 minutes). LA dwell time in the cryoballoon group was shorter as well (92 vs. 109 minutes). A favourable safety profile was observed in both groups.

One limitation of the study is that it did not investigate ablation for treating patients with more advanced stages of AF. A separate trial would be needed to assess the ablation technique’s effectiveness and safety for that patient population, he said.

Deferred stenting shows no clinical benefit

Delayed or deferred stent implantation in patients experiencing ST-segment elevation myocardial infarction (STEMI) failed to reduce death from any cause, hospitalisation for heart failure, subsequent heart attacks or the need for a repeat procedure to restore blood flow to the heart, according to findings from DANAMI 3-DEFER (Third Danish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction: DEFERred stent implantation in connection with primary PCI).

“The take-home message from this study is that deferred stent implantation cannot be recommended as a routine procedure for STEMI patients treated with primary PCI,” said Dr Henning Kelbaek (Roskilde Hospital, University of Copenhagen, Denmark), lead author of the study. “Our results completely rebut the promising findings of preliminary studies that suggested deferred stenting should translate to clinical benefit.”

Contradicting findings of promising preliminary studies, DANAMI-3-DEFER was the largest trial yet conducted to evaluate whether delaying stent implantation would improve patients’ survival and reduce their risk of heart failure or another heart attack.

In the study, 1,234 patients (average age 61 years; 75 % male) with acute STEMI symptoms of less than 12 hours’ duration were randomly assigned to receive standard angioplasty with immediate stent implantation or angioplasty followed by deferred stent implantation after a re-examination 24 to 48 hours later.

After an average follow-up time of 43 months, 109 (18 %) in the standard treatment group and 105 patients (17%) in the deferred group met the primary end point, a composite of death from any cause, hospitalisation for heart failure, a second heart attack, and unplanned repeat angioplasty – a non-significant difference.

Although the trial was the largest so far to address the issue of deferred stent implantation, it may not have been large enough to detect a difference between the two treatment groups, Dr Kelbaek said. Another limitation is that the trial did not select patients who were at the highest risk for developing another arterial blockage, such as those over age 65 years, those who have had more than one heart attack or those known to have a large number of blood clots.

“We cannot rule out that a fraction of our patients who met these criteria might have benefitted from delayed stent placement, especially because we found a small improvement in heart-muscle function 18 months after treatment among patients who underwent deferred stenting,” Dr Kelbaek said.

The study was not powered to detect this improvement, but Dr Kelbaek said he and his team would now look carefully for possible “hypothesis-generating” findings in subsets of patients – both those who might have benefitted from the deferred-treatment strategy and, equally important, those in whom this strategy might have worsened their condition.

The study was published in The Lancet (doi: 10.1016/S0140-6736(16)30072-1) with an accompanying editorial by van’t Hof and Ottervanger (doi: 10.1016/S0140-6736(16)30123-4).

Stem cell therapy improves outcomes in severe heart failure

A new therapy using stem cells significantly improved long-term health outcomes in patients with severe and end-stage heart failure, who normally have few other treatment options.

The regenerative therapy study, a phase 2 clinical trial for a new stem cell therapy known as ixmyelocel-T, enrolled 109 ischaemic cardiomyopathy patients, who were randomised to receive ixmyelocel-T, which involved extracting stem cells from a patient’s own bone marrow, or placebo (n=58 and n=51, respectively). The composite primary end point (a composite of deaths, cardiovascular hospitalisations and clinic visits for sudden worsening of heart failure symptoms over a 12-month period) was reached by 38% of patients in the stem cell therapy group and 49% of patients in the placebo group, a reduction of 37%.

“To date, this is the largest double-blind, placebo-controlled stem cell trial for treatment of heart failure to be presented,” said Dr Timothy Henry (Cedars-Sinai Heart Institute, Los Angeles, USA), one of the study’s lead authors. “Based on these positive results, we are encouraged that this is an attractive potential therapy for patients with class III and class III and IV heart failure…who currently have limited options.”

The trial builds upon lessons learned from previous smaller-scale stem cell studies, which have mostly shown modest improvements in outcomes for heart failure. Past trials with ixmyelocel-T have shown better results in patients with ischaemic cardiomyopathy than in those with non-ischaemic cardiomyopathy. In addition, previous studies have shown greater success with procedures in which the stem cells are injected percutaneously via the groin compared with open-heart surgery, so the new trial used a percutaneous approach.

A key limitation of the new trial is its modest size. Dr Henry said the next step is to expand the investigation of percutaneous, intramyocardial ixmyelocel-T treatment in a larger sample of heart failure patients with ischemic cardiomyopathy.

This study was published online in The Lancet at the time of presentation (doi: 10.1016/S0140-6736(16)30137-4).

European Atherosclerosis Society

The 84th Congress of the European Atherosclerosis Society (EAS) took place in Innsbruck, Austria from 29th May–1st June 2016.

New guidelines on CVD prevention

The recently published Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice was reviewed by EAS President, Professor Alberico Catapano (University of Milan, Italy) in a special Congress session. He focused on key areas including risk assessment, goals and targets for important cardiovascular risk factors, recommendations for imaging, and lipid control, as well as intervention strategies.

Risk assessment

Risk assessment is recommended in individuals at increased risk i.e. with a family history of premature cardiovascular disease (CVD) or major risk factors, and this should be repeated at least every five years, and more often in those with risk factors at levels close to targets for management. Systematic risk assessment may be considered in men aged >40 years or women >50 years or post-menopausal women with no known cardiovascular risk factors. Global risk estimation is based on the SCORE approach, with charts providing the 10-year risk of fatal CVD, according to age, sex, smoking, systolic blood pressure and total cholesterol. In addition, relative risk charts, adapted from SCORE, may offer additional value in young individuals with risk factors.

Risk factors

Much of the focus of discussion was on lipids. While low-density lipoprotein cholesterol (LDL-C) goals remain unchanged across the spectrum of cardiovascular risk, the alternative goal of at least 50% reduction from baseline LDL-C levels for high-risk and very high-risk patients has been refined. This can be considered in very high-risk patients with baseline LDL-C levels between 1.8 and 3.5 mmol/L (70 and 135 mg/dL), and high-risk patients with baseline LDL-C levels between 2.6 and 5.1 mmol/L (100 and 200 mg/dL).

While the Societies have recognised emerging evidence for high fasting triglycerides (>1.7 mmol/L or >~150 mg/dL) as a CVD risk factor, there is still no support for targets. Similarly, beyond recognition of low high-density lipoprotein cholesterol (HDL-C) being a CVD risk factor (i.e. <1.0 mmol/L or 40 mg/dL in men and <1.2 mmol/L or <45 mg/dL in women), there is no good evidence for targets for HDL-C.

Imaging and treatment

The guidelines consider coronary artery calcium scoring, atherosclerotic plaque detection by carotid artery scanning, and ankle brachial index as risk modifiers in cardiovascular risk assessment. Carotid intima-media thickness screening is not recommended for cardiovascular risk assessment.

As with all guidelines, the Sixth Joint Task Force guidelines place diet at the heart of prevention of CVD. Lifestyle advice is recommended even for people at very low risk (SCORE <1%), with LDL-C levels <2.6 mmol/L or 100 mg/dL.

For lipid control, statins remain the first choice for treating elevated LDL-C. In patients at high or very high-risk of cardiovascular events, who require further LDL-C lowering to reach goal, ezetimibe is the treatment of choice for combination with a statin. With respect to new therapies, the guidelines recognise that there is consistent support from clinical trials for up to 60% lowering of LDL-C with the new proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

Results of ongoing outcomes studies are needed before any definitive recommendations on their use can be made. Overall, these Sixth Joint Task Force guidelines have provided alignment with the 2011 Joint European Society of Cardiology/European Atherosclerosis Society guidelines; updates to these guidelines are expected at this year’s European Society of Cardiology Congress in Rome, Italy.

The guidelines have highlighted the importance of adherence, and have provided specific recommendations for attaining and improving adherence. These include simplifying the treatment regimen, assessment of medication adherence, as well as reasons for non-adherence by clinicians, and considering combination therapies strategies – a polypill – to improve adherence.

The guidelines are published in the European Heart Journal (doi: 10.1093/eurheartj/ehw106).

American Diabetes Association

The 76th Scientific Sessions of the American Diabetes Association (ADA 2016) took place in New Orleans, 10th–14th June 2016.

Diabetes drug, liraglutide shows CV benefits in LEADER trial

The main results of the LEADER (Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results—A Long Term Evaluation) trial were presented at the ADA meeting and also published in the New England Journal of Medicine (doi: 10.1056/NEJMoa1603827). The diabetes drug, liraglutide significantly reduced the risk of the composite primary end point of cardiovascular (CV) death, non-fatal myocardial infarction or non-fatal stroke by 13% versus placebo (95% confidence interval [CI]: 0.78; 0.97, p=0.01), when added to standard of care in 9,340 adults with type 2 diabetes at high CV risk.

Liraglutide is the only approved glucagon-like peptide-1 (GLP-1) receptor agonist to demonstrate a superior reduction of major CV events versus placebo, both on top of standard of care, in a cardiovascular outcomes trial.

There was a significant 22% reduction in CV death with liraglutide treatment versus placebo (95% CI: 0.66; 0.93, p=0.007) and non-significant reductions in non-fatal myocardial infarction (HR=0.88, 95% CI: 0.75; 1.03, p=0.11) and non-fatal stroke (HR=0.89, 95% CI: 0.72; 1.11, p=0.30).

“These findings are exciting, as it demonstrates that Victoza® (liraglutide) can improve outcomes beyond glucose reduction and weight loss by helping to avoid cardiovascular complications and death in people with type 2 diabetes,” said Dr John Buse, (Director of the Diabetes Care Centre at the University of North Carolina School of Medicine, Chapel Hill, USA) chairman of the LEADER Steering Committee.

All-cause death was significantly reduced by 15% with liraglutide compared to placebo (95% CI: 0.74; 0.97, p=0.02). The expanded CV end point (which included the three components of the primary end point in addition to unstable angina leading to hospitalisation, coronary revascularisation and hospitalisation for heart failure) was significantly reduced by 12% with this treatment compared to placebo (95% CI: 0.81; 0.96, p=0.005).

From a mean baseline of 8.7% (both groups), there was a greater reduction in HbA1c with liraglutide versus placebo, both on top of standard of care, at three years (estimated treatment difference [ETD]: -0.40%, 95% CI: -0.45; -0.34). Weight loss was also sustained over three years with the drug treatment versus placebo (ETD: -2.3 kg, 95% CI: -2.5; -2.0). Mean baseline weight was 91.9 kg and 91.6 kg, respectively.

Systolic blood pressure was 1.2 mmHg lower and diastolic pressure 0.6 mmHg lower with liraglutide versus placebo although heart rate was 3 beats per minute higher with liraglutide treatment. The proportion of adults experiencing adverse events was similar between the treatment and placebo groups (62.3% versus 60.8%, respectively). The most common adverse events leading to the discontinuation of liraglutide were gastrointestinal events. The incidence of pancreatitis was non-significantly lower in the treatment group than in the placebo group.

Cardiovascular applications:
apps – a beginner’s guide

July 2016Br J Cardiol 2016;23:100 Leave a comment

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Authors: Jonathan Bennett

First published online July 13, 2016

Junior doctor Jonathan Bennett reviews cardiovascular apps and makes recommendations to fellow juniors of those he found most useful.

Introduction

In less than a decade since the first iPhone, smartphone technology has become more powerful and portable. The opportunity to become more connected to friends, family and information has been nearly universally embraced.

The ability of the smartphone has not been underestimated, and the development of the mobile health (mHealth) industry has been rapid.¹ The approval of iECG² for mobile patient-lead telemetry, the Dexcom cutaneous blood glucose monitoring³ and most recently the Proteus Digital ingestible sensor to promote medication adherence⁴ prove, not only how powerful the technology is, but also that people are willing to incorporate it into their lifestyles.

Having signed the contract for my first iPhone in 2013, it has been incorporated into the final years of medical education and been in my pocket for my foundation year training. The app store has on offer >160,000 medical apps,¹ which is over 50 being released every day since its inception. A quick glance at this section and you’ll notice that most of these are aimed at the public with the top paid app being one to listen to your baby’s heartbeat.

While I doubt the validity of this claim (and haven’t had the chance to try the app on any pregnant women) there have also been concerns raised of other apps available. Multiple apps promise to measure your blood pressure,⁵ but in the fine print assert that they are just for fun. This has led to discussions on whether apps promote health or harm,⁶ and the Royal College of Physicians have advised that if it doesn’t have a CE stamp, health professionals shouldn’t be using apps.⁷

However, over the years I have built up a small collection of apps that I find myself using at least a few times a week, I’m not alone in this with over 50% of clinicians having apps on their smartphone.⁸ There have also been many more that have fallen by the wayside for numerous reasons. I’ve found that radiology apps don’t translate well to the small screen of my smartphone and use up far too much storage space. However, the ability (for ~£140 per month) to attach a portable ultrasound probe to your phone and ditch the stethoscope, in possibly the not too distant future, is an exciting prospect (unless you run out of battery).⁹

But as we aren’t quite there yet, I’d like to share with you the apps that have seen me through medical school and the foundation year programme. Endeavouring to pursue a cardiovascular career they tend to lean towards that field, however, they cover many other bases as well. The perceived efficacy of apps is highly variable,¹⁰ therefore, what works for me may not for you. However, if you are coming up to starting foundation year 1 and are mildly apprehensive about your first on-call shift, these apps really did help me through.

ECG Guide by QxMD

Available: iOS, Android

Price: £0.79 (iOS), £3.01 (Android)

QxMD are consistently creating excellent apps aimed squarely at the health professional and have made a few apps that appear in this article. The ECG Guide describes itself as a “critical companion,” and is listed as a core medical app by Georgetown Medical School.

There are over 200 high-quality examples of most conceivable electrocardiograms (ECGs) that fulfil the 2009 American Heart Association (AHA)/American College of Cardiology Foundation (ACCF)/Heart Rhythm Society (HRS) recommendations for the standardisation and interpretation of the ECG. The bulk of the content is focused bullet-pointed lists with a zoomable accompanying ECG. There is usually a brief description and differential attached, however, in-depth explanations will need to be found elsewhere.

ECG Source is another good app covering the same content, however, ECG Guide has very slick formatting that is easy to navigate. This is probably my most used app, I consistently use it a few times a week, especially on-call and in the emergency department. It’s been particularly useful at minimising those head scratching moments that I’m sure we’ve all had while reading an ECG.

ESC Pocket Guidelines

Available: iOS, Android

Price: Free (with email registration)

Societies are increasingly making apps so that their guidelines are more accessible (and hopefully more consulted). The European Society of Cardiology’s (ESC) does just that with the ability to hold the pocket version of their guidelines on your phone.

The app allows you to choose which guidelines you’d like to download and has an automatic update feature for when new ones are released, this saves space and keeps you up-to-date.

The app isn’t perfect, only the pocket guidelines are available along with a few primitive decision tools. When first released it would frequently crash, however, this seems to be largely dealt with. The formatting of some of the tables is poor, making them difficult for those with less delicate fingers.

As a method of keeping you up-to-date with their latest guidelines the app does admirably, however, a few tweaks to their formatting would improve it further.

Calculate by QxMD

Available: iOs, Android

Price: Free (iOS, Android)

Another excellent offering from QxMD is their extensive and regularly updated collection of different scoring systems. Nowadays there appears to be a score for everything, with multiple algorithms overlapping, and this simple app covers >150 of them, of which a significant proportion cover cardiovascular care.

Like the ECG Guide app, it is slickly designed and foolproof to use, with the ability for a favourites list. Much like the ECG app, this gets used most weeks.

Oxford Handbook of Acute Medicine, 3^rd Edition

Available: iOS, Android

Price: £39.99 (iOS), £34.99 (Android)

While not strictly an app, but having lost my physical copy two weeks into foundation year 1, I invested, as it seemed more convenient and less likely to get lost/borrowed. Like the ESC Guidelines app formatting from print to digital is an issue and not as readable as the physical copy. However, as I’ve not lost it yet, I’m willing to put up with it.

It feels that a new edition would be welcome (having been published in 2010) but most of the information is still relevant. I’m using it less and less, but glad I had it for the foundation programme.

British National Formulary

Available: iOs, Android

Price: Free (with NHS Athens login)

With 8.9% of medication orders by foundation year doctors containing an error,¹¹ carrying the BNF is probably more essential than any of the rest of the apps here. While other apps (such as Epocrates) has more interactivity for potential interaction checking, the BNF is the UK prescribing standard and the first port of call for prescribing.

Read by QxMD

Available: iOS, Android

Price: Free (requires subscription to specific journal or institutional login for access)

Another offering from QxMD allows you to make a virtual bookshelf of your favourite journals, and also do a basic PubMed search, all within a single app. You can enable notifications for when new editions are released and download them as a PDF to your phone for printing, emailing or reading without signal.

When I first downloaded this, I was mildly aspirational of the amount of journals that I placed on my list, and the majority went unread. Also, in those rarer moments when you do get some reading time, the Annals of Internal Medicine isn’t always top of the list, however, since being installed, I’ve read more than when I didn’t have the app, so it’s remained on my phone.

Heart Risk by JBS

Available: iOS, Android

Price: Free

The app version of the Joint British Societies’ cardiovascular risk calculator is mildly stripped back from the online version, however, the essential functions remain. While I do have this installed, the times that I’ve been estimating risk, I’ve used the online calculator, as I’ve been at a desktop. Also, I feel the strengths of the JBS3 lie in its interactivity, and this translates better onto a larger screen, rather than you and your patient huddling round your phone. However, for anyone regularly estimating risk this is certainly an option.

iResus

Available: iOS, Android

Price: Free

The UK Resuscitation Council have done very well in turning their guidelines into an app. While simulation training has, hopefully, done most of the work for those real-life crash calls, having this at your fingertips, just in case, is comforting.

Jonathan Bennett
FY2 Doctor, London
([email protected])

References

1. Bhavnani SP, Narula J, Sengupta PP. Mobile technology and the digitization of healthcare. Eur Heart J 2016;37:1428–38. http://dx.doi.org/10.1093/eurheartj/ehv770

2. Saxon LA, Smith A, Doshi S, Dinsdale J, Albert D. iPhone Rhythm Strip – the implications of wireless and ubiquitous heart rate monitoring. J Am Coll Cardiol 2012;59(13s1):E726–E726. http://dx.doi.org/10.1016/S0735-1097(12)60727-X

3. Del Favero S, Facchinetti A, Sparacino G, Cobelli C, AP@home consortium. Retrofitting of continuous glucose monitoring traces allows more accurate assessment of glucose control in outpatient studies. Diabetes Technol Ther 2015;17:355–63. http://dx.doi.org/10.1089/dia.2014.0230

4. Au-Yeung KY, Moon GD, Robertson TL et al. Early clinical experience with networked system for promoting patient self-management. Am J Managed Care 2011;17:e277–e287. Available from: http://www.ajmc.com/journals/issue/2011/2011-7-vol17-n7/AJMC_11jul__Au_Yeung_e277to287/

5. Misra S. Blood pressure app study shows that top health app was highly inaccurate. Available from: http://www.imedicalapps.com/2016/03/instant-blood-pressure-app-study/ [accessed 15 May 2016].

6. Husain I, Spence D. Can healthy people benefit from health apps? BMJ 2015;350:h1887. http://dx.doi.org/10.1136/bmj.h1887

7. Royal College of Physicians. Using apps in clinical practice guidance. Available from: https://www.rcplondon.ac.uk/guidelines-policy/using-apps-clinical-practice-guidance [accessed 15 May 2016].

8. Franko OI, Tirrell TF. Smartphone app use among medical providers in ACGME training programs. J Med Sys 2012;36:3135–9. http://dx.doi.org/10.1007/s10916-011-9798-7

9. Philips. Philips Lumify – Portable Ultrasound Machine. Available from: https://www.lumify.philips.com/web/ [accessed 15 May 2016].

10. Powell CA, Torous J, Chan S et al. Interrater reliability of mHealth app rating measures: analysis of top depression and smoking cessation apps. JMIR mHealth uHealth 2016;4:e15. http://dx.doi.org/10.2196/mhealth.5176

11. Dornan T, Ashcroft D, Heathfield H et al. An in-depth investigation into causes of prescribing errors by foundation trainees in relation to their medical education: EQUIP study. London: General Medical Council, 2009;1–215. Available from: http://www.gmc-uk.org/FINAL_Report_prevalence_and_causes_of_prescribing_errors.pdf_28935150.pdf

Management of refractory angina: the importance of winning over both hearts and minds

June 2016Br J Cardiol 2016;23:45–6doi:10.5837/bjc.2016.018 Leave a comment

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Authors: Christine Wright, Ranil de Silva

You can earn CPD credits while reviewing this subject in-depth, with our updated and revised angina learning programme (available here)

Refractory angina (RA) is an increasingly common, chronic, debilitating condition, which severely reduces quality of life. It can severely impact on physical, social and psychological wellbeing. RA should be considered in patients with known coronary artery disease, who continue to experience frequent angina-like symptoms, despite surgical or percutaneous revascularisation and optimal medical therapy. Objective evidence of reversible ischaemia should also be demonstrated. Treatment is challenging and often not delivered adequately. Management should ideally be provided by a specialist multi-disciplinary team, but national provision of such services is extremely limited. As a result, patients with RA commonly enter a downward spiral of long-term local review, cycling between the outpatient department and Accident and Emergency (A&E). Consequently, a disproportionately high proportion of healthcare resource is consumed in the management of these patients due to high attendance rates in primary and secondary care, unscheduled hospitalisation, prolonged hospital stays, investigations and polypharmacy. This may be improved by the implementation of more appropriate models of care delivery.

Continue reading Management of refractory angina: the importance of winning over both hearts and minds →

The short- and long-term impact of psychotherapy in patients with chronic, refractory angina

June 2016Br J Cardiol 2016;23:57–60doi:10.5837/bjc.2016.019 Leave a comment

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Authors: Peysh A Patel, Murad Khan, Chia Yau, Simerjit Thapar, Sarah Taylor, Paul A Sainsbury

You can earn CPD credits while reviewing this subject in-depth, with our updated and revised angina learning programme (available here)

Refractory angina (RA) describes those patients with persistence of symptoms despite optimal conventional strategies. It is often associated with a maladaptive psychological response, resulting in significant burden on hospital services. This observational study sought to assess the short- and long-term impact of psychotherapy on quality of life, mood and symptoms.

Between 2011 and 2012, consecutive attendees to a specialised RA service were recruited. Intervention consisted of a course of cognitive-behavioural therapy allied with an education programme. Outcome measures were collated pre-intervention, one month and two years post-intervention. Validated questionnaires were utilised for scoring assessments: SF-36 (Short-Form 36) for quality of life, HADS (Hospital Anxiety and Depression Scale) for anxiety/depression, and SAQ (Seattle Angina Questionnaire) for functional assessment.

There were 33 patients included. Median SF-36 scores increased and this effect remained in the long term. Levels of depression reduced, and improved further at subsequent review. Frequency of angina was comparable, both short and long term. Usage of glyceryl trinitrate (GTN) spray was similar at one-month follow-up and at two years.

In conclusion, a short course of psychotherapy appears to improve quality of life and mood in patients with RA, and is achieved independent of symptom control. Further research is warranted so that the debilitating morbidity associated with this disorder can be abrogated.

Introduction

Angina results from myocardial ischaemia as a consequence of mismatch between supply and demand.¹ Most cases are secondary to atherosclerotic disease of coronary arteries.² Conventional therapy to manage such patients has relied on pharmacotherapy and revascularisation strategies. Pharmacological options routinely include aspirin, statin, rate-limiting therapy, such as beta blocker or calcium-channel antagonist, and vasodilators, such as isosorbide mononitrate and nicorandil. Revascularisation may be through percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG).³

Chronic, refractory angina constitutes a particular subset of patients that have persistence of symptoms, despite targeting of modifiable risk factors, optimal pharmacotherapy as tolerated and revascularisation when anatomically feasible.⁴ The condition affects in excess of 5% of patients with angina, and results in significant public health burden.⁵ The most contemporary data on prognosis in these cohorts estimate a mortality rate of approximately 30% after nine years.⁶ Symptoms are typified by chronic, disabling chest pain secondary to myocardial ischaemia. This is commonly aligned with a maladaptive psychological response to their disorder. As a consequence, there is greater utilisation of medical services including frequent hospital admissions with recurrent and sustained pain.⁷ This results in predictable compromise on health-related quality of life, co-existent with a high incidence of anxiety and depression.⁸ Its economic burden has been found to be comparable with other prevalent conditions such as chronic, non-cancerous pain.⁹

Management options for such patients are rather limited. Focus of care has traditionally centred on dose optimisation of established pharmacotherapy and use of adjunct therapy such as ranolazine and/or ivabradine.¹⁰ Further therapeutic strategies offered in specialised centres include enhanced external counter-pulsation (EECP), coronary sinus reducer, transcutaneous electrical nerve stimulation (TENS) and stellate ganglion block.¹¹ However, a structured pathway of care to address the maladaptive psychological responses in these cohorts appears to be lacking and is often neglected.

Bradford Royal Infirmary provides a focused service to manage patients with refractory angina (BRAS). A component of this involves a short psychological intervention composed of a course of pragmatic rehabilitation based on a combination of cognitive-behavioural therapy (CBT) and an education programme.¹² It is delivered over four weekly sessions, with each lasting two hours. These are delivered by a Clinical Nurse Specialist and Clinical Psychologist working in partnership. This study aimed to investigate its short-term and long-term impact on quality of life, mood and symptoms.

Method

Recruitment of patients for the initial study was obtained from consecutive attendees to BRAS between September 2011 and November 2012. Verbal, informed consent was obtained in all cases. Outcome measures of interest included quality of life, levels of anxiety/depression, angina frequency and use of glyceryl trinitrate (GTN) spray. Well-established and validated survey questionnaires were used for quantitative scoring assessments.

The Short-Form Health Survey (SF-36) provides a measure of health status and quality of life.¹³ It consists of eight scale scores, each carrying equal weight. Areas covered include vitality, physical functioning, bodily pain, general health perceptions, physical, emotional and social role functioning, and mental health. A score of 0 constitutes maximum disability, with 100 equivalent to no disability. The Hospital Anxiety and Depression Scale (HADS) was utilised to assess for levels of anxiety and depression.¹⁴ It incorporates a seven-item scale for each, with scoring from 0–3. Therefore, a person can score between 0 and 21 for both, and a cut-off of 8/21 is generally utilised for diagnostic purposes.¹⁵ The Seattle Angina Questionnaire (SAQ) is utilised commonly as a functional status measure of coronary artery disease.¹⁶ Two specific questions were adapted to assess for frequency of angina (Question 3) and usage of GTN spray (Question 4). Questionnaires were completed immediately pre- and one-month post-intervention via phone consultation with a co-author, who had no direct involvement with delivery of the CBT programme. In November 2014, after a two-year duration, the same questionnaires were utilised on the cohort by a different co-author to assess long-term effects on the outcome measures. Collation and analysis of data were performed in an identical fashion to the earlier study.

Data analysis was conducted by a different co-author to enhance internal validity. Information was collated using Microsoft Excel 2012. Statistical analyses were performed using Minitab 16. Non-parametric data were compared using Wilcoxon signed-rank testing and presented as medians. Statistical significance was defined by p<0.05.

Results

There were 33 patients recruited for the initial study: 76% (25/33) were male with 24% (8/33) female. Median age was 63 years (inter-quartile range of 9 years).

Results are summarised in table 1. During short-term follow-up, median SF-36 scores for quality of life increased (30 vs. 44; p=0.0001). Levels of anxiety (8 vs. 8; p=0.115) were similar but depression (9.5 vs. 8; p=0.015) decreased. Question 3 of the SAQ was adapted to explore frequency of angina symptoms (“over the past four weeks, on average, how many times per day have you had chest pain, chest tightness, or angina?”). Values showed no statistically significant difference (5 vs. 4; p=0.883). Question 4 of the SAQ was adapted to assess frequency of GTN spray usage (“over the past four weeks, on average, how many times per day have you had to take GTN [nitroglycerin tablets or spray] for your chest pain, chest tightness or angina?”). No change was noted pre- and post-intervention (4 vs. 5; p=0.098).

Table 1. Short-term and long-term effects of psychotherapy on response to survey questionnaires in patients with chronic, refractory angina — Table 1. Short-term and long-term effects of psychotherapy on response to survey
questionnaires in patients with chronic, refractory angina

Over the course of a two-year duration, three patients in the cohort underwent revascularisation and were, therefore, excluded from follow-up evaluation. Therefore, 30 patients were eligible (83% male [25/30] and 17% female [5/30]). Responses from questionnaires were directly compared with those obtained from short-term follow-up. SF-36 scores for quality of life appeared similar (45 vs. 44; p=0.126). Levels of anxiety (4 vs. 8; p=0.26) and depression (4 vs. 8; p=0.004) were improved. There appeared to be no statistically significant difference in frequency of angina (5 vs. 4; p=0.085) or usage of GTN spray (5 vs. 5; p=0.114).

Discussion

Refractory angina is a chronic disease with significant associated morbidity. Traditional management strategies have relied upon pharmacological therapy to try and alleviate ischaemic symptoms. However, the condition has strong associations with a maladaptive psychological response predominantly driven by fear, with frequent utilisation of hospital services. A structured approach that targets the psychological burden of this disorder is commonly not available across the UK.

Bradford Royal Infirmary offers a specialised service (BRAS) to address these deficiencies. The four foundation sessions are run sequentially on a weekly basis. The focus of these sessions are to help patients develop more effective coping strategies, primarily based on a greater understanding of what angina is, and by dealing with the many misconceptions that patients have developed. Furthermore, patients engage with the concept that management is not solely limited to pharmacotherapy and revascularisation, but also involves a fundamental alteration in thought processes involved with symptom recognition and interpretation. Particular emphasis is placed on lifestyle alterations including pacing, setting of realistic goals, relaxation exercises, energy conservation and sleep quality enhancement. A rigorous underpinning in social, cognitive and behavioural theories is critical to achieve success. Sessions are run in small groups, providing an informal forum to share and engage with experiences of others to achieve a collective goal of more effective self-management of this chronic condition.

Previous studies assessing the benefits of psychotherapy have been largely positive. A meta-analysis by McGillion et al. pooled the results of seven randomised-controlled trials of self-management programmes for chronic angina, including refractory angina.¹⁷ Results from 949 participants suggested that intervention resulted in approximately three fewer episodes of angina per week, accompanied by a reduction in usage of GTN spray. Of note, there was heterogeneity in methodology and sampling, which limited external validity. In a cohort of 271 patients, Moore et al. demonstrated a statistically significant reduction in frequency of hospital admissions (2.40 to 1.78 per annum) and duration of admission (15.4 to 10.3 days), with an effect that was immediate and sustained.¹⁸

Results from our study largely corroborate these findings. Short-term follow-up data suggest that psychotherapy is effective in improving patients’ quality of life and mood with comparable levels of anxiety and reduced severity of depression. Interestingly, however, this appears to be achieved independent of improvement in angina frequency or GTN spray usage. Long-term follow-up after a two-year duration demonstrates that improvement in quality of life and mood is sustained, and again, this is not correlated with alterations in symptoms. One may hypothesise from this that education and psychotherapy has beneficial effects in altering a patient’s perception of their chronic disease, with subsequent positive impact on quality of life and mood.

Limitations

Our study does have intrinsic limitations. The relatively small sample size in our study limits extrapolation of findings, and may account for the non-statistically significant differences with some comparisons. Information on background medical therapy, left ventricular function and ischaemic burden was not consistently available and, therefore, could not be included in our analysis, albeit of clear relevance in enhancing external generalisability. Additionally, we were unable to access data relating to adjunct non-pharmacological therapy during the period of study (TENS or EECP, for example), which could clearly act as a potential confounder. The rationale behind correlating responses to survey questionnaires via telephone was to ensure that answers were not processed, with the hope that this would reflect their true perceptions at that given time. However, one could legitimately argue that patients may have experienced indirect coercion through such means, and this would result in manipulation of attained responses.

Conclusion

In conclusion, this study provides an impression that education and psychotherapy, in the context of patients with chronic, refractory angina, may be of use in alleviating perception of symptoms, with resultant impact on quality of life and mood. Despite its intrinsic limitations, results provide an impetus to explore this area of management further using larger-scale, multi-centre trials. This would be of pertinence in enabling a focused, systematic strategy to manage patients with refractory angina and improve the chronic, debilitating morbidity that is associated with the disorder.

Contributions

PAP, PAS and MK were involved with initial study design. ST and ST conducted the CBT sessions. MK collated data for short-term follow-up. YC collected the data for long-term follow-up. PAP wrote the manuscript as primary author and performed statistical analysis. PAS supervised the study and revised the article. All authors have approved the final version prior to formal submission.

Conflict of interest

None declared.

Funding

There are no external or internal sources of funding to declare.

Editors’ note

See also the editorial by Wright and De Silva on pages 45–6 of this issue. Also of interest, Tinson et al. on pages 61–4 of this issue.

Key messages

Refractory angina is often associated with a maladaptive psychological response to symptoms, resulting in a significant burden on hospital services
A short course of psychotherapy appears to improve quality of life, levels of anxiety and depression and this benefit is preserved long-term. Frequency of symptoms appears unchanged
Further research in this field appears to be warranted so that the significant morbidity associated with this chronic disorder can be negated

References

1. Mukherjee D, Bhatt D, Roe MT. Direct myocardial revascularization and angiogenesis. How many patients might be eligible? Am J Cardiol 1999;84:598–600. http://dx.doi.org/10.1016/S0002-9149(99)00387-2

2. Farb A, Tang AL, Burke AP et al. Sudden coronary death. Frequency of active coronary lesions, inactive coronary lesions, and myocardial infarction. Circulation 1995;92:1701–09. http://dx.doi.org/10.1161/01.CIR.92.7.1701

3. Mehta SR, Yusuf S, Peters RJ et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001;358:527–33. http://dx.doi.org/10.1016/S0140-6736(01)05701-4

4. Kim M, Kini A, Sharma SK. Refractory angina pectoris: mechanism and therapeutic options. J Am Coll Cardiol 2002;39:923–34. http://dx.doi.org/10.1016/S0735-1097(02)01716-3

5. Banai S, Ben Muvhar S, Parikh KH et al. Coronary sinus reducer stent for the treatment of chronic refractory angina pectoris. J Am Coll Cardiol 2007;49:1783–9. http://dx.doi.org/10.1016/j.jacc.2007.01.061

6. Henry TD, Satran D, Hodges S et al. Long-term survival in patients with refractory angina. Eur Heart J 2013;34:2683–8. http://dx.doi.org/10.1093/eurheartj/eht165

7. Moore RKG, Groves DG, Bridson JD et al. A brief cognitive-behavioural intervention reduces hospital admissions in refractory angina patients. J Pain Symptom Manage 2007;33:310–16. http://dx.doi.org/10.1016/j.jpainsymman.2006.10.009

8. Furze G, Lewin R, Murberg T et al. Does it matter what patients think? The relationship between changes in patients’ beliefs about angina and their psychological and functional status. J Psychosom Res 2005;59:323–9. http://dx.doi.org/10.1016/j.jpsychores.2005.06.071

9. McGillion M, Croxford R, Watt-Watson J et al. Cost of illness for chronic stable angina patients enrolled in a self-management education trial. Can J Cardiol 2008;24:759–64. http://dx.doi.org/10.1016/S0828-282X(08)70680-9

10. Kim M, Kini A, Sharma SK. Refractory angina pectoris: mechanism and therapeutic options. J Am Coll Cardiol 2002;39:923–34. http://dx.doi.org/10.1016/S0735-1097(02)01716-3

11. Mannheimer C, Carlsson CA, Emanuelson H. The effects of transcutaneous electrical stimulation in patients with severe angina pectoris. Circulation 1985;71:308–16.

12. Wright C, Towlerton G, Fox K. Optimal treatment for complex coronary artery disease and refractory angina. Br J Cardiol 2006;13:306–08.

13. RAND Health. 36-Item Short Form Survey from the RAND Medical Outcomes Study. Available from: https://www.rand.org/health/surveys_tools/mos/mos_core_36item.html [accessed on 6 May 2015].

14. Zigmond AS, Snaith RP. The hospital anxiety and depression scale. Acta Psychiatr Scand 1983;67:361–70. http://dx.doi.org/10.1111/j.1600-0447.1983.tb09716.x

15. Bjelland I, Dahl AA, Haug TT, Neckelmann D. The validity of the Hospital Anxiety and Depression Scale. An updated literature review. J Psychosom Res 2002;52:69–77. http://dx.doi.org/10.1016/S0022-3999(01)00296-3

16. Spertus JA, Winder JA, Dewhurst TA et al. Development and evaluation of the Seattle Angina Questionnaire: a new functional status measure for coronary artery disease. J Am Coll Cardiol 1995;25:333–41. http://dx.doi.org/10.1016/0735-1097(94)00397-9

17. McGillion M, Arthur H, Victor JC et al. Effectiveness of psychoeducational interventions for improving symptoms, health-related quality of life, and psychological well being in patients with stable angina. Curr Cardiol Rev 2008;4:1–11. http://dx.doi.org/10.2174/157340308783565393

18. Moore RK, Groves DG, Bridson JD et al. A brief cognitive-behavioral intervention reduces hospital admissions in refractory angina patients. Pain Symptom Manage 2007;33:310–16. http://dx.doi.org/10.1016/j.jpainsymman.2006.10.009

Clinical and psychological outcomes of an angina management programme

June 2016Br J Cardiol 2016;23:61–4doi:10.5837/bjc.2016.020 Leave a comment

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Authors: Deborah Tinson, Samantha Swartzman, Kate Lang, Sheena Spense, Iain Todd

You can earn CPD credits while reviewing this subject in-depth, with our updated and revised angina learning programme (available here)

Chronic refractory angina results in significant NHS costs due to chronic high use of resources. This audit evaluated the clinical effectiveness of a cognitive-behavioural (CBT) programme in reducing angina symptoms after maximal medical and surgical intervention. The primary outcome was self-reported angina. Additional questionnaire data comprised perceived quality of life/disability, angina misconceptions, self-efficacy and mood. Data from the electronic patient administration system was used to compare use of cardiology hospital resources in the two years before and two years after attendance. Patients completing questionnaires reported significant improvements in all areas post-group and at two months. Resource use was lower in the two years post-programme than the two years prior. A CBT-based approach to symptom management could offer additional clinical benefits in the cardiac rehabilitation menu.

Introduction

Chronic refractory angina is defined as coronary insufficiency in the presence of coronary artery disease with clinically established reversible myocardial ischaemia that cannot be controlled by a combination of medical therapy, angioplasty and coronary bypass surgery (CABG).¹ Symptom duration should exceed three months. It carries a small increased risk of mortality,² a significant risk of morbidity³ and accounts for more than 1% of the UK’s total health service budget.⁴

Triggers for angina include behavioural factors, such as activity and stress. Common misconceptions (e.g. that angina may precipitate myocardial infarction) may cause patients to avoid these triggers, which could lead to de-conditioning, worsening angina and low mood.⁵ Of patients in cardiac rehabilitation (CR), 27% have angina as a comorbidity,⁶ and yet, traditional programmes have not generally measured their impact on symptoms. Small UK studies have suggested that cognitive-behavioural therapy (CBT)-based CR may benefit symptoms, quality of life^7-9 and use of hospital resources.¹⁰ This audit looks at the outcomes of a programme, evolved from the angina management programme (AMP),⁷ for refractory angina patients considered by their cardiologists to be on optimal treatment and unsuitable for further intervention at that time (e.g. intervention not technically feasible or carrying unjustifiable risk).

Methods

Patients

Participants were referred between 2006 and 2013 by cardiologists and, occasionally, by GPs.

Recruitment procedure

Initial medical assessment:

Acknowledged the benefits and limits of current medical/surgical therapy and introduced the benefits of a self-management approach.
Assessed behavioural risk factors for coronary heart disease (CHD).
Explored possible mechanisms for non-ischaemic chest pain, where this co-existed with angina.
Risk stratified for exercise.

Pre-group therapist assessment explored:

Current strategies for coping with angina and readiness to change.
Valued areas of life, where change would impact on quality of life.
Factors requiring programme modification (e.g. physical/cognitive limitations).
Barriers/aids to change (e.g. low assertiveness, family support).
Whether low mood was associated with health, i.e. amenable to change through this intervention.

Individual CBT formulations underpinned treatment. By linking thoughts, behaviours and emotional reactions to symptoms, areas where change could reduce symptoms are highlighted. Background and social issues were considered in a case formulation.¹¹

Exclusion criteria

Unable to follow programme due to limitations in language or cognition, immediate life-threatening comorbidity or active psychosis, angina due to untreated valvular disease or hypertrophic cardiomyopathy. Previous attendance at CR was not an exclusion criterion.

AMP intervention

The AMP intervention is shown in table 1.

Table 1. The angina management programme

Measures

Self-report questionnaires were sent/given out in advance, to be completed independently by the patient and returned to staff at first assessment, final session and at two-month follow-up. In order to minimise missing data, an assistant looked through questionnaires as they came in and, if items were missed, he/she explained the item to the patient at their next attendance.

Angina symptoms diary – self-reported over a week: number and duration of episodes, severity rated on a scale from 0 to 100. Number of times glyceryl trinitrate (GTN) spray used.
Hospital Anxiety and Depression Scale (HADS)¹² is widely used and well validated. It can be used as a total measure of general distress or as separate anxiety and depression subscales. The latter range from 0–21, with 8 or more on each subscale indicating potential clinical significance.
The Roland Morris Disability Questionnaire¹³ assesses impact of disability upon everyday life. Higher scores indicate greater interference, with a maximum score of 24. It has good reliability and external validity.¹⁴ This was devised for back pain, but modified, by us, for angina.
The Pain Self-Efficacy Questionnaire¹⁵ assesses confidence in performing activities while in pain. It has 10 items with a maximum score of 60. Internal consistency and re-test reliability are high. The word ‘pain’ was changed, by us, to ‘angina’.
The York Angina Misconceptions Questionnaire¹⁶ assesses common mistaken beliefs about angina. Reliability and validity are good. Higher scores indicate more misconceptions. The original four-point scale was modified to scores of one for ‘yes’ and zero for ‘no’, with a total of 14.
Use of cardiology resources – for all patients starting a programme, data were collated (retrospectively and by a trained administrator) from the electronic patient administration system, for the two years before they started the programme and two years from the last session (excluding time on the programme).

Three categories of data were collected:

Number of inpatient appointments – including angioplasty, CABG and other infrequent cardiac surgery.
New outpatient appointments – including first visit to consultant, rapid access chest pain clinic, electrocardiography, pacemaker clinic, exercise treadmill test and transthoracic echo.
Cardiology outpatient review – all visits (except heart failure service).

Additional post hoc analyses examined whether reduction in angina frequency differed in those with clinically low mood compared with normal mood, and, also, whether demographic and clinical variables were associated with dropout.

Statistical analysis

Statistical analysis used SPSS version 16.0. Self-report variables were not normally distributed and non-parametric statistics were used for these. Wilcoxon signed-rank tests compared before and after measures. Cohen’s d quantified effect size. McNemar’s test compared percentage reaching clinical anxiety and depression before and after. Friedman’s test compared before, after and two-month follow-up. Chi-square tests or t-tests compared dropouts and completers on clinical and demographic data. Cardiology resource use data were normally distributed and were compared using paired t-tests.

Results

There were 148 patients referred and considered suitable for the AMP: 13 did not start due to illness, holiday or change of mind, i.e. 135 started. There were 23 groups run, with an average of 5.9 patients per group.

Numbers completing at least one questionnaire were: 124 pre-group, 87 post-group and 69 at follow-up. Due to missing data items, some questionnaire numbers in table 2 are lower for each time point. Of 135 patients beginning the AMP, 105 attended six sessions or more and were deemed to have completed the intervention (77%). The data from ‘dropouts’ are included in this analysis.

Table 2. Changes in clinical outcome measures and corresponding effect size

Mean age of participants was 70.2 (46–92) years with 73.4% male. Overall, 81% had at least one comorbidity (excluding the cardiac risk factors diabetes and hypertension), such as obesity, arthritis, other chronic pain, Parkinson’s disease, asthma, chronic obstructive airways disease, alcohol dependence, cancer, irritable bowel syndrome, renal problems and cardiomyopathy. Previous myocardial infarction was documented in 41.6%, coronary artery bypass surgery in 23%, percutaneous coronary intervention in 56% and previous cerebrovascular accident or transient ischaemic attack in 11%.

Significant improvement was found pre- to post-programme on all variables except severity of angina. Effect sizes were generally moderate (number of episodes 0.54, GTN 0.45, HADS 0.51, self-efficacy –0.46) though larger for misconceptions (0.66) and smaller for duration of episodes (0.23) and disability (0.33). Table 2 gives median variable values, interquartile range and significance of change, comparing before and after the AMP and follow-up.

Percentage of patients reaching clinical significance on the HADS depression subscale reduced from 45.1% before to 26.8% after the programme, which was significant (p=0.003). A reduction in anxiety from 58.5% to 42.7% was also significant (p=0.002).

Of participants, 69 attended follow-up groups and completed follow-up measures. Those who did had maintained benefits.

Cardiology resources use for all 135 patients starting the programme (including dropouts), reduced significantly. Mean admissions decreased from 1.6 prior to 0.5 post, t(149)=9.3, p<0.001. Mean new outpatient appointments decreased from 0.5 to 0.3, t(149)=2.3, p=0.02; and mean return outpatient appointments from 1.9 to 1.3, t(149)=3.8, p<0.001.

Post hoc analyses showed no difference in the decrease in angina frequency between people who initially had clinical levels of either anxiety or depression compared with people who reported no mood problems, t(59)=0.52, p=0.61. Dropout rate (attending five sessions or fewer) was 23%. This was not related to gender, χ²(df1, n=135)=0.13, p=0.72; number of comorbidities, t(116)=0.67, p=0.51; or initial total scores on HADS, t(112)=0.59, p=0.56; self-efficacy, t(27.8)=–1.1, p=0.3; or angina episodes, t(95)=1.88, p=0.06. Dropouts scored higher on initial misconceptions than completers, t(109)=3.3, p=0.001.

Discussion

The AMP was effective in its primary aim of reducing reported angina frequency and duration, though not angina severity. GTN use was reduced. There were significant improvements in perceived quality of life/disability, angina misconceptions, self-efficacy and mood, including clinical levels of anxiety and depression. These remained at two-month follow-up. Use of cardiology resources was significantly reduced two years post-programme.

What accounts for the reduction in angina? A randomised-controlled trial (RCT)¹⁷ of conventional exercise-based CR for angina patients, found improvements in functional ability, health anxiety and perceived angina threat but no difference in angina frequency and severity, suggesting that exercise alone is not sufficient to reduce symptom frequency. Our finding of reduced angina frequency is consistent with Lewin et al.⁸ The finding of no change in severity may suggest that the benefits of the AMP are not through altered pain perception. A recent meta-analysis of psycho-educational and CBT approaches for angina, found clear evidence of reduced symptom frequency.¹⁸ We would argue that improvements are attributable to the behavioural and home-focused nature of this programme.

This audit included patients who had other chronic illnesses or psychiatric history, who might be excluded from clinical trials. Improvements in self-reported symptoms, mental health and NHS resource use are important outcomes for patients with a long-term condition with multi-morbidities.^19,20

It is a significant concern that the groups have not been running at full capacity. The dropout rate of 23% is comparable with recent UK studies,²¹ but, over the seven-year period studied, the referral rate has remained low and is falling. We are, therefore, considering how to integrate the symptom management approach into our general CR programmes, and use it with patients with other symptoms, such as fatigue and breathlessness.

This is a clinical audit and patients who completed the post-group and follow-up questionnaires are likely to be those who had made most gains. Assessment could not be ‘blind’ as the questionnaires were returned to programme staff. The reduction in use of cardiology resources needs to be interpreted with caution, as patients are most likely to be referred to CR at a time of high attendance in cardiology, and the latter might reduce naturally over time. The strength of a clinical audit lies in it being representative of the kinds of patients with chronic cardiac conditions and multi-morbidities who are being referred to CR in the UK.

Acknowledgement

The authors would like to thank the CTR data team Lothian.

Conflict of interest

None declared.

Funding

No external financial support was sought for this study.

Editors’ note

See also the article by Patel et al. on pages 57–60 and the editorial by Wright and de Silva on pages 45–6 of this issue.

Key messages

The management of chronic refractory symptoms in long-term cardiac conditions is an important issue for the National Health Service (NHS)
An approach that integrates cognitive-behavioural strategies into cardiac rehabilitation is acceptable and effective for patients with refractory angina, many of whom have multiple comorbidities
Clinical trials are merited to evaluate rehabilitation approaches for this population

References

1. 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;23:355–70. http://dx.doi.org/10.1053/euhj.2001.2706

2. Henry TD, Satran D, Hodges JS et al. Long-term survival in patients with refractory angina. Eur Heart J 2013;34:2683–8. http://dx.doi.org/10.1093/eurheartj/eht165

3. 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 programme. Eur J Pain 2005;9:305–10. http://dx.doi.org/10.1016/j.ejpain.2004.07.013

4. Stewart S, Murphy NF, Walker A et al. The current cost of angina pectoris to the National Health Service in the UK. Heart 2003;89:848–53. http://dx.doi.org/10.1136/heart.89.8.848

5. Gravely-Witte S, De Gucht V, Heiser W et al. The impact of angina and cardiac history on health-related quality of life and depression in coronary heart disease patients. Chronic Illn 2007;3:66–76. http://dx.doi.org/10.1177/1742395307079192

6. British Heart Foundation. The National Audit of Cardiac Rehabilitation annual statistical report 2015. London: British Heart Foundation, 2015. Available from: http://www.cardiacrehabilitation.org.uk

7. Lewin B, Cay EL, Todd I. The angina management programme: a rehabilitation treatment. Br J Cardiol 1995;2:219–26.

8. Lewin RJP, Furze G, Griffith K et al. A randomized controlled trial of a self-management plan for patients with newly diagnosed angina. Br J Gen Pract 2002;52:194–201. Available from: http://bjgp.org/content/52/476/194.long

9. Zetta S, Smith K, Jones M et al. Evaluating the angina plan in patients admitted to hospital with angina: a randomized controlled trial. Cardiovasc Ther 2011;29:112–24. http://dx.doi.org/10.1111/j.1755-5922.2009.00109.x

10. Moore RK, Groves DG, Bridson JD et al. A brief cognitive-behavioural intervention reduces hospital admissions in refractory angina patients. J Pain Symptom Manage 2007;33:310–16. http://dx.doi.org/10.1016/j.jpainsymman.2006.10.009

11. Halford J, Brown T. Cognitive behavioural therapy as an adjunctive treatment in chronic physical illness. Adv Psychiatr Treat 2009;15:306–17. http://dx.doi.org/10.1192/apt.bp.107.003731

12. Zigmond AS, Snaith RP. The Hospital Anxiety and Depression Scale. Acta Psychiatr Scand 1983;67:361–70. http://dx.doi.org/10.1111/j.1600-0447.1983.tb09716.x

13. Roland MO, Morris RW. A study of the natural history of back pain. Part 1: Development of a reliable and sensitive measure of disability in low back pain. Spine 1983;8:141–4. http://dx.doi.org/10.1097/00007632-198303000-00004

14. Davies C, Nitz A. Psychometric properties of the Roland-Morris Disability Questionnaire compared to the Oswestry Disability Index a systematic review. Phys Ther Rev 2009;14:399–408. http://dx.doi.org/10.1179/108331909X12540993898134

15. Nicholas MK. The pain self-efficacy questionnaire: taking pain into account. Eur J Pain 2007;11:153–63. http://dx.doi.org/10.1016/j.ejpain.2005.12.008

16. Furze G, Bull P, Lewin RJ, Thompson DR. The York Angina Misconceptions Questionnaire. J Health Psychol 2003;8:307–15. http://dx.doi.org/10.1177/13591053030083002

17. Ashbury EA, Webb CM, Probert H et al. Cardiac rehabilitation to improve physical functioning in refractory angina: a pilot study. Cardiology 2012;122:170–7. http://dx.doi.org/10.1159/000339224

18. McGillion M, O’Keefe-McCarthy S, Carroll SL et al. Impact of self-management interventions on stable angina symptoms and health-related quality of life: a meta-analysis. BMC Cardiovasc Disord 2014;14:14. http://dx.doi.org/10.1186/1471-2261-14-14

19. British Association for Cardiovascular Prevention and Rehabilitation. The BACPR standards and core components for cardiovascular disease prevention and rehabilitation 2012. London: BACPR, 2012. Available from: http://www.bacpr.com/resources/46c_bacpr_standards_and_core_components_2012.pdf

20. Naylar C, Parsonage M, McDaid D, Knapp M, Fossey M, Galea A. Long-term conditions and mental health – the cost of co-morbidities. London: The Kings Fund and Centre for Mental Health, 2012. Available from: http://www.kingsfund.org.uk/sites/files/kf/field/field_publication_file/long-term-conditions-mental-health-cost-comorbidities-naylor-feb12.pdf

21. Sharp J, Freeman C. Patterns and predictors of uptake and adherence to cardiac rehabilitation. J Cardiopulm Rehabil Prev 2009;29:241–7. http://dx.doi.org/10.1097/HCR.0b013e3181adcf0f

Midodrine is safe and effective in the treatment of reflex syncope

June 2016Br J Cardiol 2016;23:73–7doi:10.5837/bjc.2016.021 Leave a comment

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Authors: Amir S Anwar, Yawer Saeed, Aly Zaki, Sanjiv Petkar, Sarah Collitt, Nicola Rice, Pam Iddon, Adam P Fitzpatrick

Reflex syncope is the most common cause of transient loss of consciousness. Practical manoeuvres may help, but additional measures are often required. In our experience, midodrine gives consistently good results in patients with reflex syncope. This study also provides reassurance that the effect on blood pressure is measureable, but small, and side effects are infrequent. UK prescribing may have been limited when midodrine was unlicensed, but midodrine is now licensed.

We treated 195 patients, age 40 ± 18 years, 72 (37%) aged under 30 years, 151 female (78%), who attended a Rapid Access Blackouts Triage Clinic and gave a clear history of reflex syncope. The median duration of symptoms was 28 months. A misdiagnosis of epilepsy had occurred in 39 patients and 42 had significantly low blood pressure.

Follow-up was 50 ± 42 months in 184 patients (93%), with 11 patients lost to follow-up. Twenty-eight patients had minor electrocardiogram (ECG) changes but had a normal echocardiogram. Overall, 143 (73%) patients improved on a mean dose of 10 mg a day of midodrine. Syncopal events fell from 16 ± 16 to 2.6 ± 5 per six months (p<0.05), and in 69 (35%) patients, syncope was eradicated. Nineteen (10%) patients were able to stop midodrine after 52 ± 42 months due to symptom resolution. Fifteen patients (7%) stopped midodrine because of side effects, while 17 (8%) patients failed to respond. Mean supine systolic blood pressure rose from 114 mmHg to 121 mmHg at final midodrine dose (p<0.05).

In conclusion, in patients with reflex syncope, midodrine shows clinical benefit in greater than 70%, with 24% having complete symptom resolution. Side effects are rare, and there is little evidence of a hypertensive effect.

Continue reading Midodrine is safe and effective in the treatment of reflex syncope →

Anomalous origin of the left coronary artery from the pulmonary artery: case report and review

June 2016Br J Cardiol 2016;23:79–81doi:10.5837/bjc.2016.022 Leave a comment

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Authors: Kully Sandhu, David Barron, Hefin Jones, Paul Clift, Sara Thorne, Rob Butler

Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital condition that proves to be fatal in most individuals during childhood due to significant left ventricular ischaemia. However, there are case reports of individuals surviving into adulthood that have varying presenting symptoms. We report a case of a young male, who presented to our cardiology clinic with typical ischaemic cardiac pain, with no established risk factors, and was found to have anomalous origin of the left coronary artery from the pulmonary artery that was subsequently surgically corrected.

Introduction

Figure 1. Diagnostic coronary angiogram via right femoral artery illustrating the presence of a large tortuous right coronary artery (RCA) with collaterals filling the left coronary arterial system (LCA) and retrograde flow of contrast within the main pulmonary artery (PA)

Anomalous origin of the left coronary artery from the pulmonary artery is a rare congenital condition that often proves fatal in infants. However, we present a case of a young patient presenting with angina-like chest pains since childhood, who subsequently underwent successful surgical correction resulting in alleviation of symptoms.

Case report

A 25-year-old normotensive, non-diabetic, non-smoker with no family history of ischaemic cardiac disease was referred to the cardiology clinic, by his general practitioner, for progressive exertional chest pains since childhood. Since the clinical scenario did not correlate with a low-risk cardiovascular profile, an exercise treadmill test was performed revealing non-specific ST changes within the anterior leads after nine minutes, with accompanying chest pain. A subsequent stress echocardiogram found a dilated left ventricle (LV) of 6.1 cm at end diastole, normal global systolic function at rest, with hypokinesia of mid and apical anterior wall during peak stress. The evidence of reversible ischaemia led to a coronary angiogram being performed via right femoral artery, revealing a dominant large tortuous right coronary artery (RCA) and, via collaterals, to the left coronary artery (LCA) system, with subsequent retrograde flow into the pulmonary artery (figure 1). An aortogram demonstrated no appreciable LCA origin. This led to a coronary computed tomography (CT) being performed that confirmed the diagnosis of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA). The large tortuous RCA originated from the aortic root, with the LCA attached to the main pulmonary artery (MPA) (figure 2). A curved planar reformatted CT image confirms the origin of the LCA from the MPA (figure 3).

Figure 2. Computed tomographic scan illustrating a large tortuous right coronary artery (RCA) arising from the aorta (Ao) and the left anterior descending coronary artery (LAD) attaches to the main pulmonary artery (MPA) — Figure 2. Computed tomographic scan illustrating a large tortuous right coronary artery (RCA) arising from
the aorta (Ao) and the left anterior descending coronary artery (LAD) attaches to the main pulmonary artery (MPA)

Our patient was referred to and seen at the regional adult congenital heart disease centre. The patient, consequently, underwent a translocated ALCAPA repair with bovine patch and MPA reconstruction in May 2014. The operative findings noted a large dominant RCA with left main stem originating within the lateral aspect of main pulmonary artery 3–5 mm above the post-pulmonary cusp leaflet. The mitral valve was structurally normal. Mild LV systolic impairment with mitral valve insufficiency improved post-operatively. Post-operative recovery was uneventful, with no reported symptoms, and greatly improved exercise tolerance at subsequent outpatient follow-up.

Discussion

ALCAPA is a rare congenital cardiovascular defect with an estimated incidence of one in 300,000 live births, however, this may be an underestimate considering patients may die prior to diagnosis.¹ The true incidence of older patients is not known, with only case reports of patients older than 50 years of age.^2,3

Figure 3. Computed tomographic reformatted curved planar image showing origin of the left anterior descending coronary artery (LAD) from the main pulmonary artery (MPA). White arrows identify cross-sections of larger tortuous right coronary artery (RCA)

Krause⁴ and Brooks⁵ first described anomalous arteries from the pulmonary artery in 1865 and 1885, respectively, from post-mortem examinations. Brooks⁵ went on to propose that the LCA had retrograde direction of blood flow to the pulmonary artery. ALCAPA may also be known as Bland, White and Garland syndrome after a published report of the constellation of symptoms, electrocardiographic (ECG) changes, and confirmation of ALCAPA on post-mortem examination of an infant.⁶

Symptoms are secondary to LV ischaemia due to retrograde flow of blood from the RCA, then via collaterals to LCA with draining into the pulmonary artery (PA). Therefore, the foetus is protected from LV ischaemia, as systemic and pulmonary arterial pressures are equal intra-uterine allowing anterograde flow down both left and right coronary arteries. However, during the neonatal period, pulmonary pressures decrease, and together with ductus arteriosus closure, result in an increase in systemic arterial pressure reversing the blood flow within the LCA retrograde into the PA. The severity of symptoms reflects the degree of myocardial ischaemia and is dependent on the extent of the collateralisation between RCA and LCA, with greater collateralisation leading to less myocardial ischaemia, resulting in fewer symptoms and increased survival. Therefore, explaining the spectrum of symptoms from death during infancy to survival into adulthood.⁷

Clinical presentation is often non-specific, ranging from angina, syncope, arrhythmias and exertional fatigue to nocturnal dyspnoea. A review found 66% of patients had symptoms of angina, dyspnoea, palpitations or fatigue: 17% presented with ventricular arrhythmia, syncope, or sudden death and 14% of patients were asymptomatic.¹

ECGs often show lateral ischaemia or evidence of previous anterior myocardial infarction with presence of Q waves in as many as 50% of patients, and left ventricular hypertrophy is seen in up to 28%, with 4% of patients having a normal ECG.¹ A dilated RCA with retrograde Doppler flow from LCA to PA with visualisation of septal flow due to collaterals have been described as diagnostic echocardiographic criteria for ALCAPA.⁸ However, normal echocardiograms may be seen in 10% of patients, and the presence of ischaemia in stress ECG or imaging, such as in our patient, is well documented.¹

Coronary angiography alludes to the diagnosis, with the presence of a large tortuous RCA with collaterals filling the LCA system, as seen with our patient (figure 1). Non-invasive imaging modalities, such as cardiac CT and/or magnetic resonance imaging (MRI), allow visualisation of the origin of the LCA from the PA, dilated tortuous RCA and collateral arteries, with cardiac magnetic resonance (CMR) having the advantage of being able to assess myocardial viability and ischaemia.⁹ Figures 2 and 3 show CT images of our patient confirming the diagnosis of ALCAPA.

Surgical correction is the treatment of choice in suitable patients and has been shown to improve chronic cardiac ischaemia, with encouraging post-operative long-term survival in infants undergoing surgical ALCAPA correction of 94.8%¹⁰ and 92%,¹¹ with only a handful of case reports reporting survival after ALCAPA surgical repair in adults. On both three- and six-month follow-up, our patient reported no symptoms with greatly improved exercise tolerance.

Conclusion

ALCAPA is a rare condition. A high index of suspicion is required. Coronary angiography may allude to the diagnosis, however, cardiac CT or MRI is a requisite for diagnostic confirmation. Surgical correction is the treatment of choice, with a frank discussion of risk and benefits being considered on an individual-patient basis. Long-term studies are limited but suggest good outcome.

Conflicts of interest

None declared.

References

1. Yau JM, Singh R, Halpem EJ, Fischman D. Anomalous origin of the left coronary artery from the pulmonary artery in adults: a comprehensive review of 151 adult cases and a new diagnosis in a 53-year-old woman. Clin Cardiol 2011;34:204–10. http://dx.doi.org/10.1002/clc.20848

2. Separham A, Aliakbarzadeh P. Anomalous left coronary artery from the pulmonary artery presenting with aborted sudden death in an octogenarian: a case report. J Med Case Rep 2012;6:12. http://dx.doi.org/10.1186/1752-1947-6-12

3. Fierens C, Budts W, Denef B, Van De Werf F. A 72 year old woman with ALCAPA. Heart 2000;831:e2. http://dx.doi.org/10.1136/heart.83.1.e2

4. Krause W. Uber den Ursprung einer akzessorischen A. coronaria aus der A. pulmonalis. Z Rat Med 1865;24:225–9.

5. Brooks HS. Two cases of an abnormal coronary artery of the heart arising from the pulmonary artery: with some remarks upon the effect of this anomaly in producing cirsoid dilatation of the vessels. J Anat Physiol 1885;20:26–9.

6. Bland EF, White PD, Garland J. Congenital anomalies of the coronary arteries: report of an unusual case associated with cardiac hypertrophy. Am Heart J 1933;8:787–801. http://dx.doi.org/10.1016/S0002-8703(33)90140-4

7. Shivalkar B, Borgers M, Daenen W, Gewillig M, Flameng W. ALCAPA syndrome: an example of chronic myocardial hypoperfusion? J Am Coll Cardiol 1994;23:772–8. http://dx.doi.org/10.1016/0735-1097(94)90767-6

8. Yang YL, Nanda NC, Wang XF et al. Echocardiographic diagnosis of anomalous origin of the left coronary artery from the pulmonary artery. Echocardiography 2007;24:405–11. http://dx.doi.org/10.1111/j.1540-8175.2006.00406.x

9. Pena E, Nguyen ET, Merchant N, Dennis G. ALCAPA syndrome: not just a pediatric disease. Radiographics 2009;29:553–65. http://dx.doi.org/10.1148/rg.292085059

10. Lange R, Vogt M, Horer J et al. Long-term results of repair of anomalous origin of the left coronary artery from the pulmonary artery. Ann Thorac Surg 2007;83:1463–71. http://dx.doi.org/10.1016/j.athoracsur.2006.11.005

11. Azakie A, Russell JL, McCrindle BW et al. Anatomic repair of anomalous left coronary artery from the pulmonary artery by aortic reimplantation: early survival, patterns of ventricular recovery and late outcome. Ann Thorac Surg 2003;75:1535–41. http://dx.doi.org/10.1016/S0003-4975(02)04822-1

New ESC heart failure guidelines

June 2016Br J Cardiol 2016;23:51 Leave a comment

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Authors: BJCardio Staff

Updated European Society of Cardiology (ESC) Guidelines for the diagnosis and treatment of acute and chronic heart failure have been published.¹

The 2016 guidelines include for the first time the new drug sacubitril/valsartan (previously known as LCZ696). This is the first drug in the class of angiotensin receptor neprilysin inhibitors (ARNIs) and was shown in the PARADIGM-HF trial to be superior to the angiotensin-converting enzyme (ACE) inhibitor enalapril for reducing the risk of death and hospitalisation in patients with heart failure with reduced ejection fraction (HFREF) who met strict inclusion and exclusion criteria.

Professor Piotr Ponikowski (Chairperson of the ESC Guidelines Task Force), said: “The issue of how to include LCZ696 in the treatment algorithm generated a lot of discussion. We recommend that the drug should replace ACE inhibitors in patients who fit the PARADIGM-HF criteria. The Task Force agreed that more data is needed before it can be recommended in a broader group of patients”.

New heart failure category

The guidelines also include a new category of heart failure with mid-range ejection fraction (HFMREF), added for patients with a left ventricular ejection fraction (LVEF) ranging from 40–49%. This category sits between HFREF, defined as LVEF <40%, and heart failure with preserved ejection fraction (HFPEF), defined as LVEF >50%. Explaining the new category, Professor Ponikowski said there were currently no evidence-based treatments for patients with a LVEF of 40% or above. “Many patients fall into the mid-range category and this should stimulate research into novel therapies,” he added.

Other changes in the new guidelines include:

Cardiac resynchronisation therapy (CRT) is now contraindicated in patients with a QRS duration of <130 msec after the EchoCRT study found it may increase mortality in
this group. This is a change from the 120 msec cut-off in the 2012 guidelines. The indications for CRT vary according to the presence or absence of left bundle branch block and QRS duration.
The concept of ‘time is muscle’ in acute heart failure is included for the first time and demands urgent diagnosis and treatment.
A new algorithm for the diagnosis of heart failure in the non-acute setting based on the evaluation of heart failure probability. “This algorithm will be more useful in clinical practice for general practitioners and other non-cardiologists faced with patients who may have heart failure,” said Professor Ponikowski. “It clearly defines when heart failure can be ruled out and when further tests are needed.”
Adaptive servo-ventilation (ASV) is not recommended in patients with HFREF and central sleep apnoea after mortality increased in the SERVE-HF trial. “We took for granted that ASV benefitted these patients. The trial was a big surprise and ASV is now contraindicated in this situation,” said Professor Ponikowski.
Novel recommendations to prevent or delay the onset of heart failure and prolong life. These include: treatment of hypertension, statins for patients with or at high risk of coronary artery disease, and empagliflozin (a sodium-glucose cotransporter 2 [SGLT2] inhibitor) for patients with type 2 diabetes. Professor Adriaan A Voors, Task Force Co-Chairperson explained: “Several drugs for diabetes were associated with a higher risk of deterioration of heart failure but now we have an SGLT2 inhibitor that reduces the risk of heart failure hospitalisations in high risk patients, although studies with SGLT2 inhibitors in patients with established heart failure are still lacking.”

Speaking at the launch, Professor Ponikowski concluded: “Heart failure is becoming a preventable and treatable disease. Implementing the guidelines published today will give patients the best chance of a positive outcome”.

Reference

1. Ponikowski P, Voors AA, Anker SD, et al. on behalf of authors/task force members. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2016 published online 20 May 2016. http://dx.doi.org/10.1093/eurheartj/ehw128

NICE go-ahead for sacubitril/valsartan

June 2016Br J Cardiol 2016;23:51 Leave a comment

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Authors: BJCardio Staff

The National Institute for Health and Care Excellence (NICE) has issued Technical Appraisal Guidance for sacubitril/valsartan (Entresto™, Novartis Pharmaceuticals). The drug has been approved for use within the NHS for the treatment of adults with symptomatic chronic heart failure with New York Heart Association class II to IV symptoms, a left ventricular ejection fraction of 35% or less, and who are also taking a stable dose of angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers.

Sacubitril/valsartan is the first of a new kind of drug called angiotensin receptor neprilysin inhibitors. NICE recognised sacubitril/valsartan as an innovative treatment, which it says “offers the potential to prevent deaths and reduce the more than 30,000 hospital admissions for this condition each year in England”.

It is the first non-cancer drug to be fast-tracked through the Medicines and Healthcare Products Regulatory Agency’s Early Access to Medicines Scheme. The scheme aims to give patients with life threatening or seriously debilitating conditions access to medicines before they are licensed where there is a clear, unmet medical need.

The guidance is available at http://www.nice.org.uk/guidance/indevelopment/gid-tag516

First published online July 13, 2016

Introduction

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Procedure

Post-operative assessment

Ethics and statistical analysis

Results

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Effect on symptoms

Cause of death

Discussion

Conflict of interest

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References

First published online July 13, 2016

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First published online July 13, 2016

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