Pathological Findings in Lower-Extremity Arteries Shed Light on Progression of PAD to CLI

Thrombotic luminal occlusion associated with insignificant atherosclerosis is commonly observed in critical limb ischemia (CLI) and suggests the possibility of thromboembolic disease, based on a study aimed at characterizing the pathology of peripheral artery disease (PAD) in below- and above-knee amputation specimens from CLI patients. The findings were presented at ESC Congress 2018 and published in the Journal of the American College of Cardiology.

Researchers examined 299 peripheral arteries in 121 amputations specimens from 95 patients, 75 of whom presented with CLI and 20 who had amputations for other reasons. The pathological characteristics were separately recorded for femoral and popliteal arteries (FEM-POP) and infrapopliteal arteries (INFRA-POP).

Atherosclerotic plaques were more frequent in FEM-POP (23 of 34; 67.6 percent) vs. INFRA-POP (79 of 205; 38.5 percent) arteries from CLI patients. Additionally, 69 percent of the arteries from CLI patients showed ≥70 percent stenosis; in 27.3 percent this was due to significant pathological intimal thickening, fibroatheroma, fibrocalcific lesions or restenosis, luminal thrombi in 23.6 percent and in 49.1 percent there were no significant atherosclerotic lesions.

The presence of chronic luminal thrombi was more frequently observed in arteries with insignificant atherosclerosis, especially INFRA-POP. Acute thrombotic occlusion was less frequently encountered in INFRA-POP than FEM-POP arteries. Medial calcification was also present in 71.1 percent of large arteries.

"The pathological findings in lower-extremity arteries suggest possible mechanisms of progression of PAD to CLI, and may support the preventive role of antithrombotic agents," researchers said.

Narula N, Dannenberg AJ, Olin JW, et al. J Am Coll Cardiol 2018;Aug 27:[Epub ahead of print].

Study Assesses Impact of On-Clopidogrel PR on HALT

Findings from a study assessing the impact of on-clopidogrel platelet reactivity (PR) on hypo-attenuated leaflet thickening (HALT) do not support dual antiplatelet therapy as standard of care following TAVR, researchers say. The study was presented at ESC Congress 2018 and simultaneously published in JACC: Cardiovascular Interventions.

Researchers prospectively tested whether patients with below-median on-clopidogrel PR have a lower incidence of HALT vs. patients with above-median on-clopidogrel PR. Patients were assigned either chronic dual antiplatelet therapy with clopidogrel and aspirin, or were given bolus doses of both drugs the day before undergoing TAVR. Prior to TAVR, ADP-induced multielectrode impedance aggregometry was performed before TAVR. Clopidogrel was continued in all patients following TAVR and computed tomography angiography (CTA) was performed to detect HALT.

Results showed 16 patients with below-median ADP-induced PR (<180 AU*min) were diagnosed with HALT vs. 20 patients with above-median PR. Among patients with high on-clopidogrel PR (>468 AU*min), seven displayed HALT vs. 19 with ADP-induced PR ≤468 AU*min. Researchers consistently noted that ADP-induced PR as continuous variable was not significantly associated with HALT (p=0.75). However, oral anticoagulation was associated with reduced rates of HALT.

"The level of residual ADP-induced platelet reactivity is not associated with the risk of early HALT as a sensitive marker of emerging valve thrombosis," researchers said. "The current findings question whether P2Y12 inhibition is sufficiently effective in preventing valve thrombosis to justify the increased risk of bleeding associated with it."

Nührenberg TG, Hromek J, Kille A, et al. JACC Cardiovasc Interv; Aug 27:[Epub ahead of print].

New Research Suggests Need For Better DAPT Assessment Tools

Better tools are needed to identify patients most likely to benefit from extending dual antiplatelet therapy (DAPT) beyond 12 months following coronary stenting, said researchers presenting findings from a nationwide study showing the DAPT score did not adequately discriminate ischemic and bleeding risk. The study was presented at ESC Congress 2018 and published in the Journal of the American College of Cardiology.

Researchers followed 41,101 patients from Sweden who had undergone 12 months of event-free DAPT post stenting for an additional 18 months. They compared risk of myocardial infarction (MI) or stent thrombosis, major adverse cardiovascular and cerebrovascular events (MACCE), and fatal or major bleeding using the DAPT score.

The DAPT score had a discrimination of 0.58 for MI or stent thrombosis, 0.54 for MACCE and 0.49 for fatal or major bleeding. Additionally, risk of MI or stent thrombosis was significantly greater in patients with DAPT scores of ≥3. Researchers noted MACCE risk "followed a J-shaped pattern" and increased at DAPT scores of ≥4. Absolute differences in fatal or major bleeding risk were small between scores and event rates of ischemic outcomes were comparable. However, "fatal or major bleeding rates were approximately half of those in the placebo-arm of the DAPT Study, from which the score was derived," researchers said.

Overall, the findings indicate the relationship between the score and ischemic risk do not correspond to the suggested decision rule for extended DAPT in patients with scores of 2 or higher. While the score may still help identify patients at high ischemic risk, researchers suggest that "the score and its decision rule may not be generalizable to real-world populations" and additional tools are needed.

"The DAPT score joins a plethora of statistical models that have uncertain utility," writes John A. Bittl, MD, FACC, in a related editorial comment. "Ueda et al., are commended for their exemplary analysis, which is a reminder that clinical decision rules must be held to a high standard. Doctors should rest assured that even the best mathematical models and prediction rules cannot replace clinical judgment."

Ueda P, Jernberg T, James S, et al. J Am Coll Cardiol 2018;Aug 26:[Epub ahead of print].

Studies Shed New Light On Complexity of Coronary Physiology in Severe AS Patients

Systolic coronary flow and hyperemic coronary flow are significantly reduced in severe aortic stenosis (AS) and change significantly post TAVR, based on findings presented during ESC Congress 2018 and published in JACC: Cardiovascular Interventions.

The study analyzed the phasic intracoronary pressure and flow velocity in 28 patients with severe AS and coronary artery disease (CAD) at rest and during hyperemia immediately before and after undergoing TAVR. Results found that flow during the wave-free period of diastole (iFR-flow) did not change post TAVR, while whole cycle hyperemic flow (FFR flow) increased significantly. Researchers noted this was secondary to significant increases in systolic hyperemic flow post TAVR. Additionally, instantaneous wave-free ratio (iFR) values did not change post TAVR, but fractional flow reserve (FFR) decreased significantly. Read More >>>

Risk Similar in TAVR vs. SAVR for AS Patients with Prior Cardiac Surgery

In patients with severe aortic stenosis (AS) with prior cardiac surgery, the risk for adverse clinical outcomes after two years was similar following TAVR and SAVR, according to research presented at ESC Congress 2018 and published in JACC: Cardiovascular Interventions.

In the PARTNER 2A trial, 2,032 patients with severe AS at intermediate surgical risk were randomized to TAVR with the SAPIEN XT valve or SAVR: 509 (25.1 percent) had prior cardiac surgery, mostly (98.2 percent) CABG.

At 30 days or two years, there were no significant differences between TAVR and SAVR patients regardless of whether they did or did not have prior cardiac surgery. However, while patients without prior cardiac surgery treated with TAVR had higher rates of 30-day major vascular complications vs. those treated with SAVR, the opposite was observed in patients with prior cardiac surgery. A similar interaction was observed for life-threatening or disabling bleeding.

According to the authors, these findings support the long-term efficacy of both TAVR and SAVR in patients with prior cardiac surgery, with a possible early safety advantage for TAVR vs. SAVR.

Chen S, Redfors B, Ben-Yehuda O, et al. JACC Cardiovasc Interv 2018;Aug 28:[Epub ahead of print].

Debris Captured by Dual-Filter Cerebral Embolic Protection Device Varies by Type

Debris captured by the dual-filter cerebral embolic protection device during TAVR varied by TAVR device, according to new findings presented at ESC Congress 2018 and published in JACC: Cardiovascular Interventions.

Researchers analyzed captured debris from the Claret Sentinel cerebral embolic dual-filter protection device in 100 consecutive patients implanted with three different valve types: 1) Edwards Sapien 3 balloon-expandable device (n=42); 2) Medtronic Evolut R self-expandable device (n=35); and 3) the Boston Scientific Lotus mechanically implantable device (n=23). There was no difference in baseline data including STS score for mortality, calcification or predilation between the three groups. Read More >>>