ALTERNATIVE METHODS OF TREATMENT IN REFRACTORY ANGINA PECTORIS
Mihaela Rugina, Mihaela Salagean, S. Bubenek-Turconi, E. Apetrei, Maria Dorobantu
- Effort-induced angina refractory to treatment – Options of treatment
- Myocardial revascularization with extracorporeal cardiac shock wave therapy (ESWT). Physiology and mechanism of action of extracorporeal shock waves (ESW).
- Angiogenesis induced by ESWT.
- Indications of ESWT.
- Treatment protocol of myocardial revascularization therapy with ESWT
- 1. INTRODUCTION
Coronary artery disease (CAD) is recognized as a leading cause of morbidity and mortality worldwide.
Current therapies for the treatment of CAD include medical treatment, percutaneous coronary angioplasty (PCI), coronary artery bypass graft surgery (CABG), transmyocardial laser revascularization (RLM), sympathectomy, external counterpulsation, spinal cord stimulation and gene therapy. But these approaches are invasive and sometimes are not indicated for the treatment of advanced refractory angina (RA) and cardiovascular complications associated with these procedures are high.
The prognosis for patients with end stage CAD, without indications for CABG or PCI, is SEVERE. Using RLM demonstrated benefits in patients with diffuse coronary lesions.
However, RLM is used as an adjunctive therapy for CABG, if CABG fails to achieve a complete revascularization.
Alternative approaches such as gene therapy or stem cell transplantation are promising, but still in preclinical stages, and both methods are equally invasive.
It is important to note that exist a large number of patients with RA and these patiens continue to present arisk of sudden death (over 20% of patients in Courage Study and NHLBI Dynamic Registry) (1, 2). This was a reason to introduce a new technique, non- invasive treatment in RA -therapy with ESW- that can relieve angina by promoting angiogenesis and thus improve myocardial perfusion and quality of life of patients with RA.
Vasculogenesis, angiogenesis, and arteriogenesis are processes that are responsible for development and maintenance of the circulatory system. New vessel growth occurs in post-embryonic stage and it is called „angiogenesis.” Angiogenesis is very important, not only during normal growth, but also in pathological situations (3). Certain pathological conditions such as neoplastic diseases are aggravated by excessive vessel growth (excessive angiogenesis), while in others conditions such as CAD, lack of adequate blood supply contributes to increased morbidity and mortality.
- 2. EFFORT- INDUCED ANGINA REFRACTORY TO TREATMENT – OPTIONS OF TREATMENT
Despite significant advances in revascularization techniques and medical therapy, there remains a significant population of patients who continue to have intractable angina symptoms which is defined as angina pectoris refractory (RA) to maximal medical therapy and coronary revascularization procedures standard.
CAD with no therapy solution is defined „END STAGE” or ischemia unresponsive to „classic” treatment and can be characterized by several clinical entities: angina pectoris „refractory” to maximal treatment, dilated ischemic cardiomyopathy with systolic dysfunction (EF-LV <30% ) with multiple revascularization procedures ( PCI and / or CABG) or severe comorbidities limiting cardiac treatment. Thus, this group include elderly patients with an increased EUROSCORE without viable myocardium, with an anatomy which is not suitable for revascularization: distal lesions, diabetic patients with serious injuries, the presence of pulmonary hypertension > 60 mmHg or contraindications for heart transplantation – defines patients with no myocardial therapeutic solution.
Anatomical and functional definition of CAD „END STAGE” includes inducible myocardial ischemia, refractory multivessel CAD (> 2 vessels), and diffuse injury affecting mainly small vessels, closed grafts, coronary anatomy unfavorable for PCI or CABG.
The prevalence of CAD „END STAGE” in a descriptive Study estimated by the Cleveland Clinic revealed a rate of 11.6% (59 of 500 patients) with coronary anatomy which is not favorable for a repeat of revascularization procedures, functional angina pectoris class >2, inducible myocardial ischemia (26). In theU.S., 13.2 million patients have CAD and of these it is estimated that approximately 0.8-2.4 million patients with CAD are not eligible for CABG or PCI. Their number increases with the combination of obesity, palliative treatment failure and disease progression (27).
In Europe, the prevalence of angina pectoris is about 20 – 40%, meaning 20-40 000 angina cases per million inhabitants, more than in North and East. Refractory angina occurs in 5-10% of patients with stable angina, which is 3-7‰ of the population 45-75 years (28). Indirect 9.6% of patients with angina sent to CABG were rejected, despite severe symptoms (Sweden,1994) and 5-15% of patients had angina refractory angiography (Sweden 1998), concluding that about 30-50000 patients /year in Europehave RA. In Romania, the average incidence is about 20% higher than the U.S. in 2000, the estimated prevalence of RA in Romania is 40 – 80‰, with a tendency to decrease (29, 39).
Coronary revascularization reduces mortality only if there is viable myocardium (30).
Detection of myocardial viability can be determined by performing single-photon emission computed tomography imaging using thallium-201 chloride and/or technetium-99m labeled, PET (positron emission tomography using F18-fluorodeoxyglucose), resting cine MRI magnetic detection for myocardial scars (end-diastolic wall thickness <5 to 6 mm is a marker of transmural MI and excludes viability), electro-mechanical mapping, pharmacologic and echocardiography stress at rest and with dobutamine to detect regional contractile activity.
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