Effects of Crushed Ticagrelor Versus Eptifibatide Bolus Plus Clopidogrel in Troponin-Negative Acute Coronary Syndrome Patients Undergoing Percutaneous Coronary Intervention: A Randomized Clinical Trial.

Background After a loading dose of ticagrelor, the rate of high on-treatment platelet reactivity remains elevated, which increases periprocedural myocardial infarction and injury. This indicates that faster platelet inhibition with crushed ticagrelor (CTIC) or eptifibatide is needed to reduce high on-treatment platelet reactivity. The efficacy of CTIC versus eptifibatide bolus plus clopidogrel is unknown. Methods and Results A total of 100 P2Y12 naïve, troponin-negative patients with acute coronary syndrome were randomized to CTIC (180 mg) versus eptifibatide bolus (180 µg/kg×2 intravenous boluses) plus clopidogrel (600 mg) at the time of percutaneous coronary intervention. High on-treatment platelet reactivity was markedly higher with CTIC versus eptifibatide bolus plus clopidogrel (42% versus 0%; P<0.001) at 30 minutes and persisted up to 2 hours (12% versus 0%; P=0.01, respectively). Platelet aggregation by adenosine diphosphate dropped faster from baseline with eptifibatide bolus plus clopidogrel versus CTIC (0.5 versus 2 hours, respectively) and was higher with CTIC versus eptifibatide bolus plus clopidogrel at 0.5, 2, and 4 hours after loading dose (53±12% versus 1.3±2%; 35±11% versus 0.34±1.0%; and 23±9% versus 3.5±2%, respectively; P<0.001). Eptifibatide bolus plus clopidogrel, but not CTIC, significantly inhibited platelet aggregation induced by thrombin-receptor activating peptide. Periprocedural myocardial infarction and injury was higher with CTIC versus eptifibatide bolus plus clopidogrel (48% versus 28%, respectively; P=0.035). Post-percutaneous coronary intervention hemoglobin levels were not different between groups. Conclusions Eptifibatide bolus plus clopidogrel led to faster and more potent platelet inhibition than CTIC and reduced periprocedural myocardial infarction and injury in troponin-negative acute coronary syndrome patients undergoing percutaneous coronary intervention, with no significant hemoglobin drop after percutaneous coronary intervention. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02925923.

Large-field intravascular ultrasound for annular sizing and predicting paravalvular regurgitation during TAVR: comparisons with multidetector computed tomography and transoesophageal echocardiography.

AIMS: The use of contrast media with multidetector computed tomography (MDCT) may induce acute kidney injury in patients with renal failure undergoing transcatheter aortic valve replacement (TAVR). We investigated the role of large-field intravascular ultrasound (IVUS) vs. MDCT and two-dimensional transoesophageal echocardiography (2D-TEE) for annular sizing and predicting paravalvular regurgitation (PVR) during TAVR. METHODS AND RESULTS: The aortic annulus was measured by large-field IVUS and 2D-TEE, and compared with MDCT in 50 patients undergoing TAVR. The IVUS and MDCT annular areas and diameters were not significantly different (446 ± 87 mm2 and 23.8 ± 84 mm vs. 466 ± 84 mm2 and 24 ± 2.1 mm, respectively; P > 0.05). IVUS and MDCT mean annular diameters were significantly greater than TEE diameter (23.8 ± 2.4 and 24 ± 2.1 vs. 22 ± 0.65 mm, respectively; P < 0.01). PVR ≥ Mild occurred in 13 patients (26%); 5 patients required post-dilation and 2 patients a second valve. Receiver operating characteristic analyses showed that transcatheter heart valve (THV) area - IVUS or MDCT areas equally predicted of ≥ mild PVR (areas under the curve [AUC] 0.79 and 0.81, respectively; P < 0.001), and were greater than THV diameter-TEE diameter (AUC 0.79 and 0.81 vs. 0.56, respectively; P < 0.05). CONCLUSIONS: The aortic annular measurements and predicting PVR by large field IVUS were not significantly different from those of MDCT, but were greater than those of TEE. Large filed IVUS can be reliably used in lieu of MDCT for annular sizing in patients with aortic stenosis and renal failure or suboptimal MDCT images.

Impact of Transcatheter Aortic Valve Replacement on Surgical Volumes and Outcomes in a Tertiary Academic Cardiac Surgical Practice.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) was FDA approved for the Sapien valve (Edwards Lifesciences) in the United States in November 2011. We sought to examine the impact of TAVR post-FDA approval on aortic valve surgery at our institution. STUDY DESIGN: Prospective data were collected on 573 consecutive patients that underwent surgical aortic valve replacement (SAVR) or TAVR with either the Sapien or Sapien XT from January 1, 2009 through December 31, 2014. RESULTS: Patients were divided into the following groups: SAVR before TAVR (n = 215), SAVR post TAVR (n = 163), and TAVR (n = 195). The 30-day mortality was not different among the 3 groups, but the mortality for the SAVR post TAVR group was better than the SAVR before TAVR group (p = 0.03). Postoperative hospital length of stay, ventilation hours, and atrial fibrillation were all decreased in the TAVR group. The number of isolated SAVRs increased after TAVR from 60 per year in group 1 to 67 per year in group 2. The total number of all isolated aortic valve procedures (SAVR + TAVR) increased from 60 per year to 177 per year. The TAVR group was divided into the following subgroups to examine the procedural learning curve: patients 1 to 50, patients 51 to 100, and patients 101 to 195. Mortality was higher in group 1 (8%) vs group 2 (0%) and group 3 (1%). CONCLUSIONS: Since initiation of the TAVR program at our institution, the total number of aortic valve procedures has increased. Transcatheter aortic valve replacement patients had more preoperative comorbidities, but no difference in postoperative morbidity or mortality and shorter length of stay. Transcatheter aortic valve replacement mortality has continued to improve since the inception of the program.

Transcatheter aortic valve replacement program in the post-food and drug administration approval era: early outcomes at an academic medical center.

OBJECTIVE: Transcatheter aortic valve replacement (TAVR) has recently become a suitable alternative for treatment of symptomatic aortic stenosis in patients who are at very high risk for morbidity and mortality with conventional corrective surgery. In the fall of 2011, the Food and Drug Administration approved the use of TAVR, allowing for reimbursement at institutions outside of investigative trials. We report the initiation of a TAVR-based program at an academic tertiary care facility that did not participate in the Placement of Aortic Transcatheter Valves (PARTNER) 1 or PARTNER II trials. METHODS: A total of 160 patients were evaluated for TAVR from May 2012 through June 2013. Transcatheter aortic valve replacement was found to be appropriate for 50 (31%). RESULTS: In this experience, morbidity and mortality were similar to those reported for the PARTNER trial (30-day hospital mortality was 8%). A single case of presumed cerebrovascular accident was observed. These results demonstrate that the real-world application can be done with comparable results. Implementation of lessons learned in the trials allowed a very short learning curve and excellent results after only a limited number of patients. Use of computed tomography reconstructed images for operative planning, including fluoroscopic angle, facilitated minimal use of contrast in each case. CONCLUSIONS: Transcatheter aortic valve replacement is a viable option for patients at very high risk for surgical intervention in the post-Food and Drug Administration approval era. Real-world results comparable with published outcomes from experienced centers involved in the PARTNER trial can be achieved.

Circulatory support for shock complicating myocardial infarction.

We discuss a patient with acute myocardial infarction complicated by cardiogenic shock (AMI-CS) who underwent percutaneous coronary intervention and hemodynamic support with a new short-term percutaneously inserted device, the Impella CP (Abiomed). We also review the evidence for mechanical circulatory support and management strategies in patients with AMI-CS.

Superoxide production and oxygen consumption in endothelium-intact and -denuded artery stimulated by angiotensin II.

Arteries stimulated by angiotensin II (AII) to contract do not display the expected augmentation of O2 consumption seen with other cardiovascular contractile agonists. We tested the hypothesis that superoxide (O2-) or other reactive oxidant species generated by AII played a role in the paradoxical O2 consumption response in porcine carotid artery, with or without an intact endothelium. Endothelium-denuded arteries were incubated with either 1 microM diphenylene iodonium (DPI), an inhibitor of NAD(P)H oxidase, 300 u/ml superoxide dismutase (SOD), a scavenger of O2-, or 20 U/ml catalase, an enzyme which promotes conversion of O2- (scavenged in the form of H2O2) to O2. DPI treatment resulted in the expected increase in O2 consumption upon contractile activation with AII challenge (1.05+/- 0.23 micromol/g/min; n = 6, p < .01), as did treatment with SOD (0.67+/- 0.20 micromol/g/min; n = 4, p < .05). Catalase incubation resulted in a burst of O2 generation upon AII challenge (1.30 +/- 0.21 micromol/g/min; n = 10, p < .001). In endothelium-intact arteries, O2 consumption was again not augmented with AII challenge; instead, a burst of O2 production was observed (0.66 +/- 0.22 micromol/g/min; n = 9, p < .05), which was not affected further by addition of catalase. Thus, the absence of apparent augmentation of O2 consumption during contractile activation of endothelium-denuded arteries was attributed to simultaneous NAD(P)H oxidase-dependent production of O2-, and attendant H2O2 and O2 generation which either and masked the detection of O2 consumed or suppressed mitochondrial uptake of O2, or both. An intact endothelium was required to manifest the burst of O2 generation with AII stimulation under normal conditions.

Effect of angiotensin II on energetics, glucose metabolism and cytosolic NADH/NAD and NADPH/NADP redox in vascular smooth muscle.

Angiotensin II (AII) is a neurohormone and contractile agonist of vascular smooth muscle that has been shown to be involved in the pathogenesis of vascular disease, which may be partially caused by its effect on oxidant stress. Energy metabolism was examined in pig carotid arteries treated with AII, because the activity of pathways of intermediary metabolism of glucose determines the status of cytosolic NADH/NAD and NADPH/NADP redox, factors which are involved in oxidant stress. Contractile responses to AII were characterized by an increase in isometric force followed by a gradual decline to near-basal levels. Despite contractile activation, no change in glycolysis, lactate production, glucose oxidation, fatty acid oxidation, O2 consumption, glycogen content or high-energy phosphates was detected when compared to resting unstimulated arteries. Paradoxically, total uptake of glucose was inhibited by AII. Treatment with diphenylene iodinium, an inhibitor of NAD(P)H oxidase and superoxide production, reversed the inhibition of glucose uptake and revealed the expected increase in glucose uptake and oxidation upon contractile activation of smooth muscle by AII. The intracellular [lactate]/[pyruvate] ratio was increased, reflecting an increase in cytosolic NADH/NAD redox, whereas NADPH/NADP redox was decreased by AII. No change in NADPH/NADP redox was observed when membrane depolarization with K+ was used as the contractile agent. It is concluded that the pattern of force generation, metabolism and energetics of AII-stimulated contraction are significantly different from that of other contractile agonists. Most notably AII inhibited glucose uptake. NAD(P)H oxidase and/or attendant superoxide may play a role in modulating glucose metabolism. AII induces opposite changes in NADH/NAD redox and NADPH/NADP redox, which may have important consequences for oxidant stress.