Michael P. Kelley

One-year clinical outcomes of protected and unprotected left main coronary artery stenting

Aims To evaluate outcomes for left main coronary artery (LMCA) stenting and compare results between protected (left coronary grafted) and unprotected LMCA stenting in the current bare-metal stent era. Methods We reviewed outcomes among 142 consecutive patients who underwent protected or unprotected LMCA stenting since 1997. All-cause mortality, myocardial infarction (MI), target-lesion revascularization (TLR), and the combined majoradverse clinical event (MACE) rates at one year were computed. Results Ninety-nine patients (70%) underwent protected and 43 patients (30%) underwent unprotected LMCA stenting. In the unprotected group, 86% were considered poor surgical candidates. Survival at one year was 88% for all patients, TLR 20%, and MACE 32%. At one year, survival was reduced in the unprotected group (72% vs. 95%, P <0.001) and MACE was increased in the unprotected patients (49% vs. 25%, P =0.005). Conclusions In the current era, stenting for both protected and unprotected LMCA disease is still associated with high long-term mortality and MACE rates. Stenting for unprotected LMCA disease in a high-risk population should only be considered in the absence of other revascularization options. Further studies are needed to evaluate the role of stenting for unprotected LMCA disease.

Angiographic methods to assess human coronary angiogenesis

It is unclear how agents designed to promote angiogenesis in the human heart affect the arteriographic appearance of the collateral circulation. Possible changes in collateral vessels include new collateral vessels arising from epicardial arteries, new branches emanating from existing collateral vessels, wider or longer collateral vessels, and higher dye transit rates that result in improved recipient vessel filling. Given the multiple mechanisms by which these new agents may improve myocardial perfusion, a rigorous, systematic, and comprehensive analysis of coronary arteriograms is required to discern the true mechanism of benefit. The method of analysis must account for potential changes in collateral blood flow, number, branching pattern, and length as well as changes in recipient vessel filling. The ability to detect differences between intricate networks of vessels in an angiographic study is dependent on maintaining consistency in cinefilming as well as the core laboratory methods between time points. In this report, we describe the methodology our angiographic core laboratory has found to be most effective to evaluate these very complex angiograms and attempt to capture all the possible modalities of angiogenesis.

Methodologic drift in the assessment of TIMI grade 3 flow and its implications with respect to the reporting of angiographic trial results

BACKGROUND The Thrombolysis in Myocardial Infarction (TIMI) Study Group originally defined TIMI grade 3 flow (complete perfusion) as antegrade flow into the bed distal to the obstruction that occurs as promptly as antegrade flow into the bed proximal to the obstruction. Recently, several groups have defined TIMI grade 3 flow as opacification of the coronary artery within 3 cardiac cycles. METHODS AND RESULTS On the basis of heart rate data at the time of the cardiac catheterization and the time for dye to go down the artery (TIMI frame count/30 = seconds), we estimated the number of patients who would meet the 3 cardiac cycle criterion and compared this with the number of patients with TIMI grade 3 flow by using the original definition in 1157 patients from 3 recent TIMI trials (10 A, 10B, and 14). In 74 patients without acute myocardial infarction and normal coronary arteries, the fraction of a cardiac cycle required for dye to traverse the artery was a mean of 0.93 +/- 0.34 cardiac cycles (n = 74) (median 0.80, minimum 0.44, maximum 2.1, none >3.0 cycles). The mean heart rate at 90 minutes after thrombolysis in the TIMI 14 trial was 79.6 +/- 16.8 beats/min (n = 194), and the duration of 3 cardiac cycles was a mean of 2.36 seconds, or a TIMI frame count of 70.8 frames. In all trials, the rate of TIMI grade 3 flow was 57.3% (n = 663/1157) with the original definition and 66.8% (n = 743/1113) with the <3 cardiac cycle definition (P <.001). CONCLUSIONS A duration of 3 cardiac cycles for dye to traverse the artery lies approximately 6 SD above that observed in normal coronary arteries. A 3 cardiac cycle definition of TIMI grade 3 flow results in rates of normal perfusion that are approximately 10% higher than if the original definition of TIMI grade 3 flow is applied. Application of this simple correction factor may help place data reported with the 3 cardiac cycle definition of TIMI grade 3 flow in context.

Early post-transplant lymphoproliferative disease following heart transplantation in the absence of lymphocytolytic induction therapy.

We report a case of post-transplant lymphoproliferative disease presenting as a disseminated polymorphous B-cell lymphoma involving the cardiac allograft 3 months following transplantation in a recipient who did not receive anti-lymphocyte induction immunosuppression. In situ hybridization for the lytic Epstein-Barr virus marker NOT I was positive within a lymphocytic infiltrate on endomyocardial biopsy. Our case is the third of early post-transplant lymphoproliferative disease (within 6 months of transplantation) involving the heart allograft in the absence of anti-lymphocyte induction immunosuppression. Post-transplant lymphoproliferative disease of the heart allograft should be considered in the presence of an atypical cardiac lymphocytic infiltrate, with possible differentiation from allograft rejection using in situ hybridization for Epstein-Barr virus.

Changes in lipoprotein(a) concentration after orthotopic heart transplantation

BACKGROUND Elevated concentrations of lipoprotein(a) have been considered an important risk factor in the development of premature cardiovascular disease and have been proposed as a risk factor in the development of accelerated cardiac allograft vasculopathy after orthotopic heart transplantation. METHODS We prospectively measured lipoprotein(a), fasting cholesterol, and triglyceride concentrations before (n = 38), 6 months (n = 38), and 1 year (n = 21) after orthotopic heart transplantation. The mean age of the patients was 52 +/- 2 years. Eighty-seven percent of the patients were men, 82% were white, and 61% had ischemic cardiomyopathy. RESULTS Mean lipoprotein(a) concentration was lower 6 months after transplantation than it was before the operation (23 +/- 3 mg/dL vs 17 +/- 3 mg/dL; P =.014) and remained low 1 year after transplantation (23 +/- 3 mg/dL vs 18 +/- 4 mg/dL; P = not significant). In contrast, mean cholesterol concentration was higher 6 months after transplantation (171 +/- 8 mg/dL vs 221 +/- 8 mg/dL; P <.001) and 1 year (171 +/- 8 mg/dL vs 205 +/- 10 mg/dL; P <.01) than it was before transplantation. Triglyceride concentration was higher 1 year after transplantation than it was before the operation (146 +/- 13 mg/dL vs 184 +/- 20 mg/dL; P =.017). CONCLUSIONS Lipoprotein(a) concentrations decrease during the 6 months after transplantation and stay low for at least 1 year after the operation. Additional studies are needed to ascertain the effect these changes in lipoprotein(a) concentration on the development of cardiac allograft vasculopathy.

Current Device Strategies in the Management of Acute Coronary Syndromes

Early head-to-head trials suggested no advantage of an early invasive approach to an early conservative approach in patients with acute coronary syndromes (ACS) (1–3). In part, the limitations to conventional percutaneous transluminal coronary intervention (PTCA) were due to dissection and attendant abrupt vessel closure, as well as frequent adverse clinical events: 5% incidence of myocardial infarction (MI), 2–3% risk of emergent coronary artery bypass graft (CABG) surgery, and 30–50% rate of late restenosis. Since these early trials, significant advances have been made in the understanding of the underlying pathologic processes that have historically limited PTCA. For example, a great deal of attention has focused on the development of new device strategies that diminish the degree of endothelial trauma and arterial wall inflammation. Major advances in adjuvant medications, including the judicious use of potent antiplatelet (thienopyridines and glycoprotein [Gp] IIb/IIIa antagonists) agents have dramatically decreased the rates of both early and late complications. Technological advances include stents (medicating and coated), directional coronary atherectomy, rotational atherectomy, laser atherectomy, cutting balloons, brachytherapy, and intravascular ultrasound. Together, the advances in medications and technology have greatly improved outcomes and have lead to the re-examination of the conclusion that medical therapy is preferred (4). The dramatic increase in available techniques has driven interventional cardiologists to take a lesion-specific approach to therapy, and in this context, the term percutaneous coronary intervention (PCI) has been adopted to reflect conventional PTCA and its alternatives. This chapter will summarize: (i) current techniques employed in PCI; (ii) coronary stents, including the techniques to treat in-stent restenosis; (iii) new pharmacologic approaches to ACS; and (iv) future directions in device strategies for the management of ACS.