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The challenge of refractory angina

A symposium in the ESC 2011 Congress was dedicated to the challenging issue of the treatment of patients with refractory angina (RA). RA is usually defined as: 1) the occurrence of frequent attacks of angina pectoris that significantly limit the activities of the patient and may also occur at rest (Canadian Cardiovacular Society angina class III-IV); 2) inefficacy of optimal anti-ischaemic medical treatment in improving the angina pattern; 3) obstructive coronary artery disease (CAD) judged unsuitable for both percutaneous and surgical coronary revascularization. The prevalence and incidence of RA are poorly known at present, but they are expected to increase in the near future due to the prolongation of survival of patients with severe forms of CAD.

  • New options for medical treatment, presented by C Rapezzi (Bologna, IT) - Slides
  • Stem cell therapy, presented by D W Losordo (Chicago, US)
  • External counterpulsation, presented by O Soran (Pittsburgh, US) - Slides
  • Neuromodulation, presented by M J L DeJongste (Groningen, NL) - Slides
Chronic Ischaemic Heart Disease (IHD)

In the first presentation of the session, Prof. Claudio Rapezzi, from Bologna (IT), has illustrated the potential beneficial effects that some new anti-ischaemic drugs may have in RA patients. He has in particular focused his intervention on the effects of ranolazine (which reduces myocardial ischaemia through the improvement of diastolic function) and of ivabradine (which acts through a selective reduction of heart rate). These drugs have both been demonstrated to improve symptoms, in association with standard anti-ischaemic therapy, in patients with stable angina, and are therefore expected to improve symptoms also in the specific group of RA patients. Prof. Rapezzi, has particularly stressed the concept that the addition of ivabradine should be recommended to achieve a heart rate lower than 60 bpm in angina patients, which is not often achieved with tolerated doses of beta-blockers. In the second presentation, Dr. Douglas W. Losordo, from Chicago (USA), illustrated the effects of angiogenic stem cell therapy in patients with RA, by exposing the results of his recently published multicentre placebo-controlled study (Circulation 2011;109:428-36) of the intramyocardial injection of CD34+ cells through a percutaneous approach.

The study has shown, for the first time, after the disappointing results of some previous studies, that angiogenic therapy may improve symptoms and exercise capacity, although some perplexities can be raised by the fact that the higher dose of CD34+ cells used in the study did not achieve statistically significant results. Dr. Losordo has also shown some data demonstrating significant clinical benefits of stem cell therapy in peripheral chronic limb ischaemia, with a dramatic reduction of amputations compared to controls.

Dr. Ozlam Soran, from Pittsburgh (USA), reviewed the effects, in RA patients, of enhanced external counterpulsation (EECP), which consists in a series of inflation (in diastole) and deflation (in systole), in a distal-to-proximal sequence, of three sets of cuffs wrapped around the legs.
She showed that EECP has significantly improved symptoms and exercise capacity in large registry studies, as well as in some controlled clinical trials, in patients with RA, with a rate of success ranging from 70% to 80%, which persists over long-term follow-up.
She also discussed the potential mechanisms of this form of therapy, which can be multiple and may include improvement of endothelial function, development of new coronary collateral vessels, improvement in myocardial oxygen consumption and a peripheral "training effects" similar to that induced by exercise. EECP, she said, is also safe, although it has been associated with some major cardiac events, suggesting caution in some kinds of patients, as those with severe left ventricular dysfunction.

Finally, Dr. Mike J.L. DeJongste, from Groningen (NL), reviewed the data about the use of neuromodulatory techniques for the treatment of RA patients. He has underscored how neuromodulation has been used for more than 25 years to treat RA, with the application, specifically, of spinal cord stimulation (SCS), which consists in the stimulation of the spinal dorsal horns through a quadripolar wire catheter introduced in the epidural space of the spinal column through an intervertebral puncture.
DeJongste has underscored that these stimulation results in both modulation of pain signals and modulation of autonomic nerve function, resulting in improvement of myocardial ischaemia. He showed how SCS has been assessed in several studies, including registries and controlled studies, resulting in significant improvement in angina episodes and quality of life in about 75% of patients. He also showed that other neuromodulatory techniques are available, including transthoracic electrical neurostimulation (TENS), left stellate gangliectomy and the most recently proposed subcutenous electrical stimulation, but there are poor or no data in medical literature, at present, about their application.


In summary, this session showed that we have several possible therapeutic options for critical patients with RA. Besides the use of new anti-ischaemic drugs, it remains to establish which of the proposed treatments should be considered as that of first choice for RA patients. At present, in the absence of comparative studies, the choice should be individualized, taking into account a series of factors, including availability, experience of the Centres, costs and, in particular, risks of the treatment.




The challenge of refractory angina

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.