Nainesh Gandhi

Frequency and risk of noncardiac surgery after drug-eluting stent implantation†

Background: Few studies have described the frequency and risk of surgery after drug‐eluting stent (DES) implantation. Methods: The medical records of 827 consecutive patients who received a DES at our institution between January 1, 2005 and July 1, 2008 were retrospectively reviewed to determine the outcomes of patients who subsequently underwent noncardiac surgery. Results: During a median follow‐up of 21 months, 135 patients underwent 191 noncardiac surgeries. The incidence of noncardiac surgery was 7% at 1 year, 18% at 2 years, and 22% at 3 years. Mean age was 62 years and 96% were men. A perioperative complication occurred in 19 surgeries (10%): excessive bleeding in 11 patients (6%), myocardial infarction in four patients (2%), acute renal failure in one patient (0.5%), hypotension and syncope in one patient (0.5%) and postoperative death in three patients (1.6%). Stent thrombosis occurred in one patient (0.5%). A complication occurred in six of 58 surgeries (10%) in which patients received perioperative clopidogrel vs. 13 of 133 surgeries (10%) in which patients did not receive perioperative clopidogrel (P = 0.90). Complications occurred in three of 25 surgeries performed within 6 months (16%), in four of 37 surgeries performed between 6 and 12 months (11%), and in 12 of 129 surgeries performed after >12 months (9%) from DES implantation (P = 0.90). Conclusion: Noncardiac surgery is frequently needed in the years after DES implantation and appears to carry a low risk of stent thrombosis and perioperative complications.

Systemic arterial hypertension but not IGF-1 treatment stimulates cardiomyocyte enlargement in neonatal lambs

Although cardiomyocyte terminal differentiation is nearly complete at birth in sheep, as in humans, very limited postnatal expansion of myocyte number may occur. The capacity of newborn cardiomyocytes to respond to growth stimulation by proliferation is poorly understood. Our objective was to test this growth response in newborn lambs with two stimuli shown to be potent inducers of cardiomyocyte growth in fetuses and adults: increased systolic load (Load) and insulin-like growth factor I (IGF-I). Vascular catheters and an inflatable aortic occluder were implanted in lambs. Hearts were collected for analysis at 18 days of age after a 7-day experiment and compared with control hearts. Load hearts, but not IGF-I hearts, were heavier ( P = 0.001) because of increased mass of the left ventricle (LV), septum, and left atrium (40-50%, P = 0.004). Terminal differentiation and cell cycle activity were not different between groups. Myocyte length was 7% greater in Load lamb hearts ( P < 0.05), and binucleated myocytes, which comprise ~90% of LV cells, were 25% larger in volume ( P = 0.03). Myocyte number per gram of myocardium was decreased in all ventricles of Load lambs ( P = 0.01). Cells from the IGF-I group were not different by any comparison. These results suggest that the newborn sheep LV responds to systolic stress with cardiomyocyte hypertrophy, not proliferation. Furthermore, IGF-I is ineffective at stimulating cardiomyocyte proliferation at this age (despite effectiveness when administered before birth). Thus, to expand cardiomyocyte number in the newborn heart, therapies other than systolic pressure load and IGF-I treatment need to be developed.Although cardiomyocyte terminal differentiation is nearly complete at birth in sheep, as in humans, very limited postnatal expansion of myocyte number may occur. The capacity of newborn cardiomyocytes to respond to growth stimulation by proliferation is poorly understood. Our objective was to test this growth response in newborn lambs with two stimuli shown to be potent inducers of cardiomyocyte growth in fetuses and adults: increased systolic load (Load) and insulin-like growth factor I (IGF-I). Vascular catheters and an inflatable aortic occluder were implanted in lambs. Hearts were collected for analysis at 18 days of age after a 7-day experiment and compared with control hearts. Load hearts, but not IGF-I hearts, were heavier ( P = 0.001) because of increased mass of the left ventricle (LV), septum, and left atrium (40-50%, P = 0.004). Terminal differentiation and cell cycle activity were not different between groups. Myocyte length was 7% greater in Load lamb hearts ( P < 0.05), and binucleated myocytes, which comprise ~90% of LV cells, were 25% larger in volume ( P = 0.03). Myocyte number per gram of myocardium was decreased in all ventricles of Load lambs ( P = 0.01). Cells from the IGF-I group were not different by any comparison. These results suggest that the newborn sheep LV responds to systolic stress with cardiomyocyte hypertrophy, not proliferation. Furthermore, IGF-I is ineffective at stimulating cardiomyocyte proliferation at this age (despite effectiveness when administered before birth). Thus, to expand cardiomyocyte number in the newborn heart, therapies other than systolic pressure load and IGF-I treatment need to be developed.

Rebuttal: What to do for patients who need noncardiac surgery post drug-eluting stent implantation?†

The best way to treat patients with drug-eluting stents (DES) who require noncardiac surgery, especially early post stent implantation, remains controversial [1]. Although the absolute risk appears to be low in most series, perioperative stent thrombosis is a catastrophic event with high mortality that may be very challenging to treat, given the risk of bleeding post surgery. Since many patients are currently receiving DES, novel approaches to minimize the perioperative stent thrombosis risk are needed. An ounce of prevention is worth a pound of cure. Accordingly, it is critical to avoid implanting DES in patients who are known to need subsequent noncardiac surgery. Moreover, surgery in patients who have received DES should be delayed for at least 12 months, if possible [1]. This strategy is not without limitations, however, as perioperative stent thrombosis has been reported even >5 years post stenting. Continuation of at least aspirin during the perioperative period appears to be safer than discontinuation of both the aspirin and the thienopyridine [2]. In DES patients who require surgery, especially early post implantation, preoperative prophylactic platelet transfusions guided by platelet function testing is a clever and innovative approach to perioperative stent thrombosis prevention. In the series of 37 patients presented in the letter to editor, there was no stent thrombosis, no excessive bleeding and no other perioperative complications when this strategy was utilized. However, important questions remain, such as the safety of a blood product administration, the duration of protection from bleeding and whether platelet infusion could actually trigger stent thrombosis. Another approach is preoperative ‘‘bridging’’ with a glycoprotein IIb/IIIa inhibitor that showed promising results in a 30-patient study [3] and is currently being evaluated prospectively in the ‘‘Bridging Therapy in Patients at High Risk for Stent Thrombosis Undergoing Surgery’’ (NCT00653601) study. However, preoperative bridging can be costly and exposes the patient to risks associated with prolonged hospitalization. Moreover, bridging can not prevent events occurring in the early postoperative period, during which the stent thrombosis risk is highest [4]. In the future, availability of short acting oral antiplatelet agents, such as ticagrelor, could facilitate antiplatelet agent discontinuation before surgery and obviate the need for prolonged hospitalization. Predicting the risk of perioperative stent-related events could significantly facilitate management decisions. In an ongoing study (NCT01288105) optical coherence tomography is used to determine whether preoperative bridging is needed (if there is incomplete stent strut coverage) or not (if there is near complete stent strut coverage). In patients at low risk of stent thrombosis it may be best to withhold antiplatelet therapy during the early postoperative period to minimize the risk of bleeding. Conversely for minor surgical procedures, the risk of bleeding is low and continuing dual antiplaletet therapy may be the best approach [5]. Studying an infrequent complication, such as perioperative stent thrombosis, is challenging and hence the controversy on the optimal prevention and treatment strategies is likely to continue. In the meantime it is prudent to operate on coronary stent patients at hospitals with experienced and continuously available cardiac catheterization laboratories that could treat perioperative stent thrombosis if it occurs [6].