A 79-year-old male presents to the clinic with recurrent angina. He had undergone coronary artery bypass surgery 16 years ago and multiple percutaneous interventions since then. Past medical history includes hypertension, dyslipidemia, and mild chronic obstructive pulmonary disease. He reports limiting chest discomfort with simple daily activities over the past four months. His medications include carvedilol, lisinopril, isosorbide mononitrate, ranolazine, and amlodipine at maximum tolerated doses. In the clinic, his blood pressure is 101/58 mmHg. He is in sinus rhythm with a heart rate of 62 beats per minute. Patient is referred for selective coronary and bypass angiography which reveals patent internal mammary artery graft to the left anterior descending artery, patent vein grafts to distal right coronary artery and the first obtuse marginal branch. Stents in the first diagonal and second marginal branches are also patent. However, the distal segments of the left anterior descending, posterior descending, and marginal branches are small in caliber and exhibit severe diffuse disease. Left ventricular ejection fraction is 40%.
Which of the following is the least appropriate therapy for his refractory angina?
The correct answer is: E. Left ventricular assist device
Refractory angina is defined as multi-vessel CAD with ischemia and symptoms that cannot be controlled with medical therapy or surgical or percutaneous revascularization.1 Prior studies have suggested increase mortality in these patients in comparison to those who underwent complete revascularization.2 Alternative non-pharmacological therapies for relief of symptoms in patients with refractory angina include transmyocardial revascularization (TMR), enhanced external counterpulsation (EECP), and spinal cord stimulation.1 More recently, a randomized clinical trial demonstrated a potential role for a novel coronary sinus reducing device used in this patient population.3
Per 2014 ACCF/AHA guidelines for management of patients with stable ischemic heart disease, TMR, EECP, and spinal cord stimulation are considered Class IIb recommendations for relief of symptoms in patients with refractory angina.1 TMR involves creation of small, transmyocardial channels from the epicardium to endocardium through percutaneous or surgical approaches. Although the exact mechanism remains to be determined, this is thought to improve the perfusion of ischemic myocardium by stimulation of microcirculation, creation of myocardial scarring, and denervation of ischemic myocardium.4-5 In EECP, inflatable cuffs are wrapped around the lower extremities to increase venous return, augment diastolic blood pressure, and hence coronary perfusion.6 For spinal cord stimulation, a stimulation lead is inserted into the epidural space between C6 - T2 level and the mechanism for improvement in angina is thought to involve inhibition of pain transmission.7 Observational studies and limited randomized trials have suggested that these alternative therapies can lead to improvement in angina and quality of life, but with no effect on ventricular function or survival.4-7
The phase II Coronary Sinus Reducer for Treatment of Refractory Angina (COSIRA) trial was a double-blind, sham-controlled trial involving percutaneous implantation of a balloon-expandable device in the coronary sinus.3 Although the exact physiological effects are yet to be determined, the focal narrowing in the coronary sinus is thought to increase coronary sinus pressure, redistribute collateral flow, and alleviate symptoms in patients with refractory angina. The primary end point was the proportion of patients with improvement of at least two Canadian Cardiovascular Society (CCS) functional classes at 6 months. Improvement in at least two CCS angina grades were seen in 35% of the coronary sinus stent group versus 15% of the control group (p = 0.02). At least one CCS grade improvement occurred in 71% of the coronary sinus stent group versus 42% of the control group (p = 0.003). Although the trial was underpowered for secondary end points, quality of life as assessed by Seattle Angina Questionnaire was improved by 17.6 points in the treatment group, as compared with 7.6 points in the control group (p = 0.03), while exercise time and stress wall motion failed to show significant improvement. A larger phase III trial would be necessary to validate these findings and to examine the potential improvement in myocardial ischemia by objective means.
Left ventricular assist devices are used for end stage heart failure patients as a bridge for transplant therapy or as destination therapy. Left ventricular assist devices are not considered as an alternative therapy for refractory angina.
Fihn SD, Blankenship JC, Alexander KP et al. 2014 ACC/AHA/AATS/PCNA/SCAI/STS focused update of the guideline for the diagnosis and management of patients with stable ischemic heart disease: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines, and the American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2014;64:1929-49.
Williams B, Menon M, Satran D et al. Patients with coronary artery disease not amenable to traditional revascularization: prevalence and 3-year mortality. Catheter Cardiovasc Interv 2010;75:886-91.
Verheye S, Jolicoeur EM, Behan MW et al. Efficacy of a device to narrow the coronary sinus in refractory angina. N Engl J Med 2015;372:519-27.
Lange RA, Hillis LD. Transmyocardial laser revascularization. N Engl J Med 1999;341:1075-6.
Liao L, Sarria-Santamera A, Matchar DB et al. Meta-analysis of survival and relief of angina pectoris after transmyocardial revascularization. Am J Cardiol 2005;95:1243-5.
Arora RR, Chou TM, Jain D et al. The multicenter study of enhanced external counterpulsation (MUST-EECP): effect of EECP on exercise-induced myocardial ischemia and anginal episodes. J Am Coll Cardiol 1999;33:1833-40.
Di Pede F, Lanza GA, Zuin G et al. Immediate and long-term clinical outcome after spinal cord stimulation for refractory stable angina pectoris. Am J Cardiol 2003;91:951-5.