Percutaneous Coronary Intervention of Complex Calcific Coronary Lesions Utilizing Orbital Atherectomy Prior to Transcatheter Aortic Valve Replacement.

BACKGROUND: Coronary artery disease (CAD), often with severe calcification, is present in up to 75% of patients with severe aortic stenosis (AS) referred for transcatheter aortic valve replacement (TAVR). Management of CAD in such patients is challenging. Orbital atherectomy (OA) is an effective treatment of severely calcified coronary lesions prior to stent implantation. However, there is limited data on the use of OA for percutaneous coronary intervention (PCI) to treat calcific CAD patients prior to TAVR (OA PCI + TAVR). METHODS: Retrospective analysis of patients with moderate/severe calcific CAD and moderate/severe AS who underwent staged OA PCI + TAVR at one high-volume institution. Data were analyzed to assess the 1-year major adverse cardiac events after index OA PCI [MACE: death, target lesion revascularization (TLR), and myocardial infarction (MI)]. RESULTS: There were 18 patients (mean age of 82) treated with staged OA PCI + TAVR, and of those, 10 (56%) were male, 7 (39%) Caucasian, and 11 (61%) Hispanic/Latino. The average left ventricular ejection fraction was 49% and congestive heart failure was present in 12 patients (67%). There were no angiographic complications (0%), stent thrombosis (0%), or stroke events (0%). The 30-day and 1-year MACE rates were 5.6% (0% death, 0% TLR, 5.6% MI) and 17% (0% death, 11% TLR, and 17% MI [all non-Q-wave MI]), respectively. CONCLUSIONS: In this single-center observational cohort series, patients with heavily calcified coronary lesions treated with OA prior to TAVR had low rates of MACE at 30 days and 1 year. The results demonstrate the feasibility and safety of OA for the treatment of complex calcific coronary lesions prior to TAVR. An up-to-date literature review of atherectomy before, during, or after TAVR in patients with concomitant severe AS and calcific CAD is also provided. TABLE OF CONTENTS SUMMARY: There is limited data on the use of orbital atherectomy (OA) for percutaneous coronary intervention (PCI) to treat calcific coronary artery disease (CAD) patients prior to transcatheter aortic valve replacement (TAVR). Our primary aim was to evaluate the feasibility, safety, and 1-year outcome of OA PCI pre-TAVR in patients with complex CAD and severe aortic stenosis (AS). We also aimed to provide a brief up-to-date literature review of atherectomy before, during, or after TAVR in patients with concomitant severe AS and calcific CAD. This retrospective cohort study found that OA is feasible and safe for the treatment of severely calcified coronary lesions before TAVR, resulting in acceptable 30-day and 1-year outcomes.

Determination of non-Vitamin K oral anticoagulant (NOAC) effects using a new-generation thrombelastography TEG 6s system.

Non vitamin K oral anticoagulants (NOACs) do not require regular monitoring but information about their pharmacodynamic effect may be importantin situations like trauma, stroke oremergent surgery. Currently, no standardized point-of-care test is available to evaluate the anticoagulant effects of NOACs. We evaluated the anticoagulant effect of NOACs with the next generation point-of-care TEG assay (TEG® 6S) based on a fully-automated thrombelastography system. We used two TEG® 6S assays, the DTI assay and Anti-Factor Xa (AFXa) assay, to detect anticoagulant effects and classify NOACs. Blood from healthy volunteers (n = 26) was used to obtain a baseline reference range. Data derived from patients on factor Xa inhibitors (FXi) (rivaroxaban and apixaban) (n = 39), and direct thrombin inhibitors (DTIs) (dabigatran) (n = 25) were compared against the reference range for detection of drug effect and drug classification. TEG®6s R-time highly correlated to each NOAC. Presence of NOACs caused elongation of R-time on the AFXa assay compared to the reference range (4.3 ± 1.7 vs. 1.3 ± 0.3 min. for FXi, p < 0.001 and 3.5 ± 1.2 vs. 1.3 ± 0.3 min. for DTI, p < 0.001). R-time on the DTI assay was elongated only in presence of a DTI (3.4 ± 1.0 vs. 1.5 ± 0.2 min, p < 0.001). The cutoff for detection of a DTI effect was an R time of 1.9 min and for anti-Xa effect was 1.95 min. For detection of NOAC therapy, there was ≥92% sensitivity and ≥95% specificity. The automated TEG®6s NOAC assay may be an effective tool to identify an anticoagulant effect from NOAC therapy and facilitate care of patients with bleeding or at risk of bleeding in the event of needing emergency surgery.

Statin therapy and inflammation in patients with diabetes treated with high dose aspirin.

BACKGROUND: Statin and aspirin form the therapeutic cornerstone in patients with coronary artery disease (CAD) and diabetes. Little is known about relationship of statins with blood thrombogenicity and inflammation in these patients. METHODS: Two hundred nine consecutive patients with diabetes and suspected CAD undergoing elective cardiac catheterization were divided in groups based on statin treatment in the Multi-Analyte, Thrombogenic, and Genetic Markers Atherosclerosis study. Urinary 11-dehydrothromboxane B2 (11-dh-TxB2), lipid profile and oxLDL/ß2GPI were measured by AspirinWorks™ ELISA assay, vertical density gradient ultracentrifugation and immunoassay respectively. Thrombelastography, and ADP- and collagen-induced light transmittance aggregometry assessed thrombogenicity. CAD was classified as none/minor [<20% diameter stenosis (DS)], moderate (20-75% DS), or severe (>75% DS). RESULTS: Severe, moderate, and no CAD was observed in 66, 19, and 15% of patients respectively. Patients on statins had significantly lower 11-dh-TxB2, collagen-induced aggregation, total cholesterol, total LDL, LDL3, oxidized-LDL, Apo B100, and ApoB100/A1 ratio (p<0.01 for all). Statin therapy demonstrated a lower proportion of patients with high urinary 11-dh-TxB2 (>1500pg 11-dh-TxB2/mg creatinine) (25 vs. 57%, p=0.01). CONCLUSION: Statins along with aspirin, confers additional anti-inflammatory and antithrombotic effect in diabetics with CAD. Urinary 11-dh-TxB2 may be a useful biomarker for personalizing statin therapy.

Association of weight gain with coronary artery disease, inflammation and thrombogenicity.

Obese individuals, despite having increased cardiovascular (CV) risk factors experience adverse CV outcomes less frequently than non-obese. Little is known about association of long-term weight gain to development of coronary artery disease (CAD), inflammation and thrombogenicity. 418 consecutive patients with suspected CAD undergoing elective cardiac catheterization were included in a sub-analysis of the multi analyte, thrombogenic, and genetic markers of atherosclerosis study. Maximum weight gain (MWG) was defined as percentage increase in weight since age 17 years to year of heaviest weight and categorized as: minor (<30 %), moderate (30-47 %), severe (>47-69 %), and extreme (>69 %). Lipid profiling was determined by vertical density gradient ultracentrifugation, thrombin-induced platelet fibrin clot strength (TIP-FCS) by thrombelastography, and urinary 11-dehydrothromboxane B2 (11-dhTxB2) by ELISA. CAD severity was defined as minimal (<20 %), moderate (20-75 %), and severe (>75 %) luminal diameter obstruction of any major coronary vessel. The mean MWG was 53 ± 33 %. Extreme MWG group had a higher incidence of diabetes mellitus (48 %), hypertension (81 %), depression (25 %), and were most often female (60 %) (p < 0.05 for all). In women, CAD severity was inversely associated to MWG (p = 0.05), whereas in men no such association was observed (p = 0.18). TIP-FCS increased in a stepwise fashion with MWG (p = 0.001). 11-dTxB2 levels were higher in the extreme MWG group, regardless of lipid lowering therapy (p < 0.05). Our data suggest that maximal weight gain since age 17 years is associated with heightened thrombogenicity, inflammation and a poorer lipid profile but not an increased risk for severe CAD development.