Leonardo Clavijo

Correlates and Long-Term Outcomes of Angiographically Proven Stent Thrombosis With Sirolimus- and Paclitaxel-Eluting Stents

Background— Stent thrombosis (ST) is a serious complication of drug-eluting stent (DES) implantation regardless of the timing (acute, subacute, or late). The correlates of ST with DES are not yet completely elucidated. Methods and Results— From a total cohort of 2974 consecutive patients treated with DES since April 2003, we identified 38 patients who presented with angiographic evidence of ST (1.27%). The ST occurred acutely in 5 patients, subacutely (≤30 days) in 25 patients, and late (>30 days) in 8 patients. The clinical, angiographic, and procedural variables of these patients were compared with the remaining 2936 consecutive patients who underwent DES implantation and did not experience ST during a follow-up of 12 months. Logistic regression analysis was conducted to determine the correlates of ST. Compared with patients without ST, patients with ST had a higher frequency of diabetes, acute postprocedural renal failure, and chronic renal failure. There were more bifurcation lesions, type C lesions, and a trend for smaller-diameter stents. Discontinuation of clopidogrel was higher in these patients (36.8% versus 10.7%; P<0.0001). The mean duration to ST from the stent implantation was 8.9±8.5 days in subacute and 152.7±100.4 days in late thrombosis cases. Mortality was significantly higher in patients with ST compared with those without ST at 6 months (31% versus 3%; P<0.001). Multivariate analysis detected cessation of clopidogrel therapy, renal failure, bifurcation lesions, and in-stent restenosis as significant correlates of ST (P<0.05). Conclusions— ST continues to be a serious complication of contemporary DES use. Careful management is warranted in patients with renal failure and in those undergoing treatment for in-stent restenosis and bifurcations. Special focus on clopidogrel compliance may minimize the incidence of ST after DES implantation.

Janus Phenomenon The Interrelated Tradeoffs Inherent in Therapies Designed to Enhance Collateral Formation and Those Designed to Inhibit Atherogenesis

normous advances have occurred in the understanding ofthe molecular and cellular mechanisms responsible forboth collateral development (collaterogenesis*) and athero-genesis. This advancement has been accompanied by paralleladvances in therapies designed to enhance collaterals and toinhibit the development and progression of atherosclerosis.Our laboratory has been interested in both areas, and duringour work, we noticed a consistent tradeoff: Whatever inter-vention enhanced collaterals increased atherogenesis and visaversa. We refer to this tradeoff as the Janus phenomenon.†This observation, if correct, is of more than passing interestgiven the many antiatherosclerotic interventions used inpatients and the proangiogenic interventions being tested thatmay soon be used therapeutically. Therefore, if the Janusphenomenon is real, its clinical implications would be ofcritical importance. Equally as important, the concept mightprovide mechanistic insights into both atherogenesis andcollaterogenesis.Consequently, we began to track phenomena compatiblewith the Janus concept. Table 1 lists a few molecules forwhich reasonable evidence exists relating to both their ath-erosclerotic and collaterogenic effects and the actions ofwhich are compatible with the Janus phenomenon.

Sirolimus-eluting stents and calcified coronary lesions: clinical outcomes of patients treated with and without rotational atherectomy.

This study examined the outcomes of patients who underwent sirolimus‐eluting stent (SES) implantation for the treatment of heavily calcified coronary lesions (HCCL) with and without the use of rotational atherectomy (rotablator). We investigated 150 consecutive patients with angiographic evidence of HCCL who underwent SES implantation. Sixty‐nine patients underwent SES implantation without the need of rotablator (SES), and 81 patients required rotational atherectomy to modify the plaque and facilitate the delivery of the stent (SES + rotational atherectomy). Clinical success was equivalent in both groups (>98%) and there were no in‐hospital outcome differences. At 6 months, the target lesion revascularization rate was 4.9% in SES vs. 4.2% in SES + rotational atherectomy groups, respectively (P = NS). Mortality at 6 months was 7.9% in the SES group vs. 6.8% in the SES + rotational atherectomy group (P = NS). SES performs well in patients with complex HCCL, with a relative low event rate. Lesions requiring rotational atherectomy to facilitate dilation and stenting had similar outcomes after SES implantation to those that could be stented without the need for rotablator.

Rapamycin attenuates atherosclerotic plaque progression in apolipoprotein E knockout mice : Inhibitory effect on monocyte chemotaxis

Rapamycin has been shown to reduce neointimal thickening in the setting of balloon angioplasty and chronic graft vessel disease. This study was designed to test the effect of oral rapamycin on atherosclerotic plaque progression and the possible mechanism involved. Apolipoprotein E (apoE) knockout mice were fed either a diet supplemented with cholesterol or with cholesterol and rapamycin. At 4 and 8 weeks, quantitative analyses of plaque area and macrophage numbers were determined. Plasma cholesterol, triglyceride, and whole-blood rapamycin levels were measured. Rapamycin could be detected in the blood of mice (117 ± 7 pg/mL). In mice fed with rapamycin, atherosclerotic lesions covered 22% of the aortic arch as compared with 41% in cholesterol-fed mice. The macrophage count was significantly lower in the rapamycin-fed mice as compared with cholesterol-fed mice. Rapamycin, in a dose-dependent manner, inhibited monocyte chemotaxis elicited by stromal cell-derived factor-1. Lesions in the cholesterol-fed mice had complex atherosclerotic plaque with acellular core, cholesterol clefts, and an abundant collection of monocytes/macrophages. Lesions in the rapamycin-fed mice were mainly composed of monocytes/macrophages. Oral rapamycin is effective in slowing the progression of atherosclerosis. Along with its multitude actions, attenuation of monocyte chemotaxis may be one more way by which rapamycin attenuates plaque progression.

Impact of overlapping drug-eluting stents in patients undergoing percutaneous coronary intervention

Background: Sirolimus‐eluting stent (SES) implantation for the treatment of single coronary lesions is proven to be effective and durable. However, the safety and efficacy of overlapping SES for the treatment of long lesions have not been well established. Objectives: We conducted a retrospective analysis to compare the clinical outcomes of overlapping versus nonoverlapping SES. Methods: Fifty‐five patients who received overlapping SES were compared with 39 patients who received nonoverlapping SES. Results: The baseline clinical and angiographic characteristics were balanced between the two study groups. The in‐hospital complications were similar between groups, except that non‐Q‐wave myocardial infarction was significantly higher in the Overlapping SES group when compared with the Nonoverlapping SES group (23.6% vs. 7.7%, P = 0.04). This higher rate of myonecrosis is due to periprocedural side branch compromises, including side branch narrowing, occlusion, and flow reduction. At 30 days and 6 months follow‐up, all clinical outcomes were similar between the study groups. In addition, the event‐free survival rate was similar between groups (P = 0.87). Conclusions: The implantation of overlapping SES for the treatment of long, native coronary lesions is feasible and effective but is associated with an increased rate of periprocedural myonecrosis. This phenomenon is caused primarily by side branch compromises, but does not have any adverse impact on late clinical events.

Use of regadenoson for measurement of fractional flow reserve

To compare the use of regadenoson to adenosine for measurement of fractional flow reserve (FFR).

Cerebral Vasospasm and Concurrent Left Ventricular Outflow Tract Obstruction: Requirement for Modification of Hyperdynamic Therapy Regimen

BackgroundMedical treatment of arterial vasospasm following aneurysmal subarachnoid hemorrhage (SAH) generally consists of triple H therapy, which frequently relies on inotropic agents in order to increase cardiac output (CO). Patients with concurrent left ventricular outflow tract (LVOT) obstruction may have paradoxical decreases in CO following administration of inotropic pressors, placing them at significant risk for cerebral ischemia and stroke.MethodsThe clinical courses of two patients with SAH-induced arterial vasospasm and underlying left ventricular outflow obstruction are reported. Both patients had hypotension and low cardiac output that were refractory to medical management with triple H therapy. Echocardiography in both patients demonstrated LVOT obstruction secondary to hypertrophic obstructive cardiomyopathy (HOCM).ResultsIntervention in both patients included discontinuation of inotropic agents and maintenance of hypervolemia to a target pulmonary capillary wedge pressure range, resulting in improved cardiac output and mean arterial pressure.ConclusionMedical treatment for cerebral vasospasm with inotropic pressor agents may result in paradoxical decreases in hemodynamic parameters and cerebral perfusion in patients with LVOT obstruction. While HOCM is the most likely structural abnormality to cause this phenomenon, it can be induced by several physiological conditions encountered in the neurocritical care setting. Modifications in triple H therapy regimens may be required in order to optimize cerebral perfusion and prevent cerebral ischemia and stroke in these patients.

Percutaneous left ventricular support for high-risk PCI and cardiogenic shock: who gets what?

BACKGROUND Temporary use of a percutaneous left ventricular assist device (PLVAD) may be beneficial in patients undergoing high-risk percutaneous coronary intervention (PCI) and those with cardiogenic shock (CS). METHODS Seventy-four consecutive patients undergoing high-risk PCI and those with CS receiving intraaortic balloon pump (IABP), TandemHeart (TH), or Impella device (IMP) were enrolled. Patient undergoing high-risk PCI (n=57) and those treated for CS (n=17) were analyzed as separate cohorts. Patients undergoing IABP-assisted PCI were compared to those undergoing PLVAD (TH and IMP)-assisted PCI. The primary end point was in-hospital major adverse cardiovascular events, and the secondary end point was in-hospital vascular complications. RESULTS For the high-risk PCI cohort (n=57), 22 received PLVAD and 35 received IABP. Patients receiving IABP were younger and less likely to have a prior myocardial infarction (MI) and less likely to be on dialysis compared to those receiving PLVAD support. Patients receiving PLVAD support had a higher baseline Syntax score, had a higher prevalence of unprotected left main disease, underwent treatment of more coronary lesions, received more coronary stents, and more likely received drug-eluting stents compared to those receiving IABP support. The primary and secondary end points were similar between both groups. For the CS cohort (n=17), 4 received PLVAD and 13 received IABP. Patients receiving PLVAD support were more likely to have a prior MI, had a lower ejection fraction, underwent treatment of more coronary lesions, and received more coronary stents compared to those receiving IABP support. The primary and secondary end points were similar between both groups. CONCLUSIONS IABP compared with PLVAD use for high-risk PCI and CS is associated with significantly different baseline patient, clinical, procedural, and angiographic characteristics. In-hospital clinical outcome was similar between both groups in both the high-risk PCI and the CS cohorts. When physicians have access to each of these devices, short-term clinical outcome appears to be similar.

Antiplatelet therapy for peripheral arterial disease and critical limb ischemia: guidelines abound, but where are the data?

Antiplatelet therapy is invariably prescribed for patients with peripheral arterial disease and critical limb ischemia, and numerous major society guidelines espouse their use, but high-quality data in this high-risk and challenging patient population are often lacking. This article summarizes the major guidelines for antiplatelet therapy, reviews the major studies of antiplatelet therapy in peripheral arterial disease (including data for aspirin, clopidogrel, dipyridamole, cilostazol, and prostanoids), and offers perspective on the potential benefits of ticagrelor, vorapaxar, and rivaroxaban. The review concludes with a discussion of the relative lack of efficacy that antiplatelet therapy has shown in regard to peripheral vascular outcomes.

Critical Limb Ischemia

Critical limb ischemia (CLI), the most advanced form of peripheral artery disease (PAD), carries grave implications with regard to morbidity and mortality. Within 1 year of CLI diagnosis, 40% to 50% of diabetics will experience an amputation, and 20% to 25% will die. Management is optimally directed at increasing blood flow to the affected extremity to relieve rest pain, heal ischemic ulcerations, avoid limb loss, and prevent cardiovascular events. This management is achieved by guideline-directed medical therapy and risk factor modification, whereas the mainstay of therapy remains revascularization by endovascular or surgical means for patients who are deemed potential candidates.