Safety of Percutaneous Coronary Intervention Alone in Symptomatic Patients with Moderate and Severe Valvular Aortic Stenosis and

Aortic stenosis (AS) is prevalent in 2–7% of the population over 65 years of age.¹ Atherosclerotic coronary artery disease (CAD) coexists in 27–43% of patients with AS.² Management of CAD in patients with AS poses special problems since timing of surgery for AS depends on the development of symptoms, and treatment of CAD is often by concomitant coronary artery bypass graft (CABG) surgery. Surgical aortic valve replacement (AVR) is recommended in patients with moderate AS undergoing CABG, and in all patients with symptomatic severe AS.³ Whether PCI can be undertaken to fix coronary disease and defer AVR in these patients is an intriguing question. Ours is a retrospective study which evaluated the outcomes of PCI alone in surgically inoperable patients with moderate AS and compared them to patients who had AVR earlier and developed CAD over the following years. Patients with severe AS who are deemed unfit for surgical AVR are managed with balloon aortic volvotomy and if this is not possible, with medical therapy. Coexisting CAD in these patients is treated with drug therapy. Whether PCI is safe in these patients is also addressed in this study. Methods A retrospective analysis of the medical records of patients with aortic valve stenosis who underwent PCI (n = 416) at our institution between 1994 and 2002 was conducted. Among them, patients with AVR (n = 55) and without (n = 361) were identified by chart review. Those without AVR were categorized as mild (n = 305), moderate (n = 28), and severe (n = 28) AS, respectively (Figure 1). Patients with mild AS were excluded and moderate and severe AS patients (all inoperable) were compared with AVR patients. The procedural complications, in-hospital course, and 1-year clinical outcomes of these three groups were compared. Study definitions. Severe AS was defined on the basis of 2D and Doppler echocardiography by using a continuous equation as aortic valve area (AVA) 4 m/sec or peak instantaneous gradient (PIG) of > 75 mm Hg; and moderate aortic stenosis as AVA between 0.75 cm2 and 1.1cm2, V max 3.5–4 m/sec or PIG of 36–50 mm Hg.^3,4 Patients were classified as having severe or moderate AS if they had >= 1 of the above criterion. Coronary artery stenosis was considered significant if > 70% diameter stenosis was observed on coronary angiography. Statistics. Continuous variables are presented as mean ± 1 standard deviation and compared using a Student’s t-test. Categorical data are presented as frequencies and percentages and are compared using Chi-square statistics or a Fisher’s exact test when appropriate. Multivariate analysis conducted using age, hypertension, diabetes mellitus, renal insufficiency, post procedural creatine phosphokinase (CPK)-MB elevation twice or more than normal and aortic stenosis as variables revealed severe AS as the only predictor of death or myocardial infarction (MI) at 1 year. Results Clinical characteristics were comparable except that patients with AVR were younger and had more prior percutaneous transluminal coronary angioplasty (PTCA). The mean duration between AVR and PCI was 7.1 ± 5.3 years. These patients had fewer incidences of hypertension and renal insufficiency compared to those patients with moderate and severe AS (Table 1). The mean AVA, V max, PIG, and left ventricular ejection fraction (LVEF) of patients with moderate and severe AS are shown in Table 2. Procedural characteristics and post-procedure complications were similar between the groups. The total number of lesions dilated was 97 in moderate and severe AS patients and 78 in AVR patients (average 1.7 vs. 1.4 per patient, p = ns). More than one lesion was treated in 48.3% of patients with moderate and severe AS, and in 35.3% of AVR patients. The distribution of lesions (%) in left main, left anterior descending, left circumflex, right coronary artery, and saphenous vein graft were 6.2, 28.9, 20.6, 28.9, 15.5 in the moderate and severe AS group and 2.6, 34.6, 21.8, 15.4, 25.7 in the AVR group (p = 0.11), respectively. Peri-procedural CPK-MB elevation was significantly higher in patients with moderate and severe AS compared to patients with AVR (Table 3). Analysis of 6-month and 1-year follow-up events including MI, non-Q-wave MI, death and out-of-hospital death were similar between patients with AVR and moderate AS, whereas all of these events were significantly high in patients with severe AS (Tables 4 and 5). Survival curves at 1 year showed freedom from death or MI were lowest in patients with severe AS compared to moderate AS and AVR groups (Figure 2). Discussion The main findings of our study show that patients with moderate and severe AS undergoing PCI had higher post-procedure CPK-MB elevations compared to patients with AVR. Six-month and 1-year outcomes of PCI were similar in patients with moderate AS when compared to the AVR group, but were significantly worse in patients with severe AS. Peri-procedural release of CPK-MB after conventional PCI predicts early and late cardiac events.^5–7 Elevation of CPK-MB following PCI is reported to occur in 5–30% of patients⁸ and is associated with peri-procedural angiographic complications and reduced long-term survival rates.^9,10 Possible factors for elevated cardiac enzymes in patients with AS compared to AVR patients may be related to impaired microvascular perfusion secondary to older age, diffuse atherosclerosis and left ventricular hypertrophy. In our study, significantly elevated CPK-MB levels in patients with moderate and severe AS are likely due to increased muscle mass secondary to hypertrophic left ventricle as compared to patients with AVR. As shown in previous studies, the poor outcomes in these patients could be related to elevated peri-procedural enzymes. In patients with moderate AS (AVA between 0.75 cm2 and 1.1 cm2), management decisions are difficult because the key issue is evaluation of symptoms which include angina, dyspnea, and syncope; and establishing valvular etiology for these symptoms. Timing of AVR in them is based on the development of symptoms and is complicated by the fact that few patients rapidly progress from the asymptomatic to the symptomatic stage and then to sudden death.¹¹ The issue is further complicated by the lack of specificity of these symptoms and by the inability of the non invasive tests to identify the ischemic component due to CAD.³ Thus, some patients are referred to AVR prematurely when the symptoms are equivocal, thus exposing them to the risk of surgery and prosthetic valve-related complications. Among patients with moderate AS, disease progression is little or none over a 3- to 9-year period. Recent reports suggest the use of statins to retard the progression of aortic stenosis severity.¹² Our findings are encouraging in that the 6-month and 1-year clinical outcomes of patients with moderate AS and AVR are similar. It may be possible to defer surgery in moderate AS patients by treating CAD with PCI and continuing statin therapy. Further prospective studies are warranted to test this strategy. The second question addressed by our study is that of the influence of PCI in patients with severe AS and CAD who could not undergo AVR. Currently, patients with severe AS and clear symptoms are referred to AVR and CABG if significant CAD co-exists. Medical management is suggested for inoperable patients. Although CAD is known to produce symptoms, there is no data as to whether PCI can be undertaken safely in these patients. Our findings suggest that at 6 months and 1 year, clinical outcomes are worse in these patients — with higher incidences of non-Q-wave MI and out-of-hospital deaths. The out-of-hospital deaths are probably of arrhythmic origin attributed to AS in these patients. Thus, it is clear that treatment of AS should be the priority in these patients, which may be accomplished by balloon aortic volvotomy if possible. If this is successful, treatment of CAD can be undertaken in a staged manner. With the potential for percutaneous AVR in the future,^13,14 the possibility of total percutaneous treatment including valve replacement and coronary intervention for these inoperable patients seems feasible. Limitations. The left ventricular mass in patients with AS in this study could not be calculated because of the retrospective nature of the data. A definite relationship to elevated cardiac enzymes and purported left ventricular hypertrophy could not be established. Patients with AVR did not have echocardiographic evaluation before PCI, and therefore, this data is not represented. Similarly, follow-up is only available up to 1 year in the database, and longer follow-up, at least in patients with moderate AS, will give us more insight into the feasibility of deferring AVR. It was also difficult to identify the exact cause of out-of-hospital death in patients with severe AS, yet, we presume it could be due to sudden cardiac death attributable to valvular stenosis.

1. Stewart BF, Siscovick D, Lind BK, et al. Clinical factors associated with calcific aortic valve disease. Cardiovascular Health Study. J Am Coll Cardiol 1997;29:630–634. 2. Rapp AH, Hillis LD, Lange RA, Cigarroa JE. Prevalence of coronary artery disease in patients with aortic stenosis with and without angina pectoris. Am J Cardiol 2001;87:1216–1217. 3. Bonow RO. ACC/AHA Guidelines for the Management of Patients With Valvular Heart Disease A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Management of Patients With Valvular Heart Disease). J Am Coll Cardiol 1998;32:1486–1588. 4. Reynolds T. In: The Echocardiographer's Pocket Reference Book, Arizona, School of Cardiac Ultrasound, Arizona Heart Institute Foundation, 1993, pp.13–19. 5. Kong TQ, Davidson CJ, Meyers SN, et al. Prognostic implication of creatine kinase elevation following elective coronary artery interventions. J Am Med Assoc 1997;277:461–466. 6. Harrington RA, Lincoff AM, Califf RM, et al. Characteristics and consequences of myocardial infarction after percutaneous coronary intervention: Insights from the Coronary Angioplasty Versus Excisional Atherectomy Trial (CAVEAT). J Am Coll Cardiol 1995;25:1693–1699. 7. Stone GW, Mehran R, Dangas G, et al. Differential impact on survival of electrocardiographic Q-wave versus enzymatic myocardial infarction after percutaneous intervention: A device-specific analysis of 7147 patients. Circulation 2001;104:642–647. 8. Califf RM, Abdelmeguid AE, Kuntz RE, et al. Myonecrosis after revascularization procedures. J Am Coll Cardiol 1998;31:241–251. 9. Ghazzal Z, Ashfaq S, Morris DC, et al. Prognostic implication of creatine kinase release after elective percutaneous coronary intervention in the pre-IIb/IIIa antagonist era. Am Heart J 2003;145:1006–1012. 10. Brener SJ, Ellis SG, Schneider J, Topol EJ. Frequency and long-term impact of myonecrosis after coronary stenting. Eur Heart J 2002;23:869–876. 11. Carabello BA. Evaluation and management of patients with aortic stenosis. Circulation 2002;105:1746–1750. 12. Novaro GM, Tiong IY, Pearce GL, et al. Effect of hydroxymethylglutaryl coenzyme A reductase inhibitors on the progression of calcific aortic stenosis. Circulation 2001;104:2205–2209. 13. Cribier A, Eltchaninoff H, Bash A, et al. Percutaneous Transcatheter implantation of an aortic valve prosthesis for calcific aortic stenosis — First human case description. Circulation 2002;106:3006–3008. 14. Eltchaninoff H, Tron C, Bauer F, et al. Early clinical experience with percutaneous trans-catheter implantation of aortic valve prosthesis for calcific stenosis in non-operable patients. Circulation 2003;108:IV–492.