P2Y12 Inhibition in Patients Requiring Oral Anticoagulation After Percutaneous Coronary Intervention: The SWAP-AC-2 Study.

BACKGROUND: Among patients treated with a novel oral anticoagulant (NOAC) undergoing percutaneous coronary intervention (PCI), combination therapy with clopidogrel (ie, known as dual antithrombotic therapy [DAT]) is the treatment of choice. However, there are concerns for individuals with impaired response to clopidogrel. OBJECTIVES: The authors sought to assess the pharmacodynamic (PD) effects of clopidogrel vs low-dose ticagrelor in patients with impaired clopidogrel response assessed by the ABCD-GENE score. METHODS: This was a prospective, randomized PD study of NOAC-treated patients undergoing PCI. Patients with an ABCD-GENE score ≥10 (n = 39), defined as having impaired clopidogrel response, were randomized to low-dose ticagrelor (n = 20; 60 mg twice a day) or clopidogrel (n = 19; 75 mg once a day). Patients with an ABCD-GENE score <10 (n = 42) were treated with clopidogrel (75 mg once a day; control cohort). PD assessments at baseline and 30 days post-randomization (trough and peak) were performed to assess P2Y12 signaling (VerifyNow P2Y12 reaction units [PRU], light transmittance aggregometry, and vasodilator-stimulated phosphoprotein); makers of thrombosis not specific to P2Y12 signaling were also assessed. The primary endpoint was PRU (trough levels) at 30 days. RESULTS: At 30 days, PRU levels were reduced with ticagrelor-based DAT compared with clopidogrel-based DAT at trough (23.0 [Q1-Q3: 3.0-46.0] vs 154.5 [Q1-Q3: 77.5-183.0]; P < 0.001) and peak (6.0 [Q1-Q3: 4.0-14.0] vs 129.0 [Q1-Q3: 66.0-171.0]; P < 0.001). Trough PRU levels in the control arm (104.0 [Q1-Q3: 35.0-167.0]) were higher than ticagrelor-based DAT (P = 0.005) and numerically lower than clopidogrel-based DAT (P = 0.234). Results were consistent by light transmittance aggregometry and vasodilator-stimulated phosphoprotein. Markers measuring other pathways leading to thrombus formation were largely unaffected. CONCLUSIONS: In NOAC-treated patients undergoing PCI with an ABCD-GENE score ≥10, ticagrelor-based DAT using a 60-mg, twice-a-day regimen reduced platelet P2Y12 reactivity compared with clopidogrel-based DAT. (Tailoring P2Y12 Inhibiting Therapy in Patients Requiring Oral Anticoagulation After PCI [SWAP-AC-2]; NCT04483583).

Outcome and Cost Comparisons Between Surgical and Transcatheter Aortic Valve Replacements.

OBJECTIVE: Surgical aortic valve replacement (SAVR) has been the standard of care for severe aortic stenosis. In 2019, annual transcatheter aortic valve replacement (TAVR) implantations surpassed SAVR. We compared in-hospital costs and outcomes between these two procedures. METHODS: A single-center retrospective review was performed of patients who underwent isolated SAVR or TAVR from October 2013 to December 2019. Baseline patient characteristics, operating room (OR) time, intensive care unit (ICU) length of stay (LOS), total LOS, cumulative cost, and complication rates were collected. Propensity matching was performed to identify differences in costs and outcomes between comparable groups. RESULTS: There were 515 patients who met inclusion criteria. TAVR was performed in 402 patients, while SAVR was performed in 113. Propensity matching resulted in 82 matched pairs. The SAVR cohort more frequently spent >1 day in the ICU, had longer total hospital LOS, longer OR time, and higher hospitalization cost. However, TAVR was associated with higher mean OR cost and higher valve cost. The cumulative index admission costs were not significantly different between groups. TAVR patients had less postoperative atrial fibrillation but more frequent pacemaker placement. One-year mortality was similar between SAVR (2.4%) and TAVR (3.8%), but 3-year (5.8% vs 19.2%) and 5-year (5.8% vs 37.2%) mortality favored SAVR. CONCLUSIONS: In propensity-matched groups, TAVR was associated with shorter ICU and hospital LOS and OR times but increased permanent pacemaker rates. In addition, while 1-year survival was similar between groups, SAVR had significantly improved 3-year and 5-year survival.

Monitored Anesthesia Care Versus General Anesthesia for Transcatheter Aortic Valve Replacement.

OBJECTIVE: Monitored anesthesia care (MAC) has been increasingly used in lieu of general anesthesia (GA) for transcatheter aortic valve replacement (TAVR). We sought to compare outcomes and in-hospital costs between MAC and GA for TAVR at a Veterans Affairs Medical Center. METHODS: A single-center retrospective review was performed of 349 patients who underwent transfemoral TAVR (MAC, n = 244 vs GA, n = 105) from January 2014 to December 2019. Baseline patient characteristics, operating room (OR) time, intensive care unit (ICU) length of stay (LOS), and cost, total LOS, hospital cost, total cost, and complication rates were collected. Propensity matching was performed and resulted in 83 matched pairs. RESULTS: In the unmatched TAVR cohort, MAC TAVR was associated with reduced OR time (146 vs 198 min, P < 0.001), ICU LOS (1.4 vs 1.8 days, P < 0.001), total hospital LOS (3.4 vs 5.4 days, P < 0.001), and lower index total cost ($81,300 vs $85,400, P = 0.010). After propensity matching, MAC TAVR patients had reduced OR time (146 vs 196 min, P < 0.05), ICU LOS (1.2 vs 1.7 days, P = 0.006), total LOS (3.5 vs 5.1 days, P = 0.001), and 180-day mortality (2.4% vs 12%, P < 0.03). There was no difference in total hospitalization cost or total cost. CONCLUSIONS: In propensity-matched groups, TAVR utilizing MAC is associated with improved OR time efficiency, decreased LOS, and a reduction in 180-day mortality but no significant difference in cost.

Relationship between Invasive and Echocardiographic Transvalvular Gradients after Transcatheter Aortic Valve Replacement.

INTRODUCTION: Lower transcatheter aortic valve replacement (TAVR) pressure gradients have been reported after implantation of self-expanding valves compared with balloon-expandable valves; however, there is a paucity of data on the relationship between invasively measured transvalvular pressure gradients and Doppler-derived measurements. METHODS: From September 2013 to September 2018, patients with native aortic valve stenosis who had both intraoperative invasive and postoperative echocardiography transvalvular pressure gradients were included for analysis. We used parametric and nonparametric statistics to compare aortic gradients within and between groups. RESULTS: Of 171 patients, 152 (88.9%) patients had TAVR with a balloon-expandable valve and 19 (11.1%) with a self-expanding valve. Among all patients, the invasive aortic gradient was 7.8 ± 3.2 mmHg and the Doppler-derived aortic gradient was 11.0 ± 4.5 mmHg (p < 0.001). Among those who received a balloon-expandable valve, the invasive aortic gradient was 7.5 ± 3 mmHg and the Doppler aortic gradient was 11.4 ± 4.5 mmHg (p < 0.001). In contrast, among patients who received a self-expanding valve, the invasive aortic gradient was 10.3 ± 3.4 mmHg and the Doppler aortic gradient was 8.5 ± 4.6 mmHg (p = 0.18). CONCLUSIONS: Balloon-expandable valves were associated with lower invasive measurements versus post-TAVR Doppler gradients, while results were inconclusive regarding self-expanding valves.

Trend and Outcomes of Direct Transcatheter Aortic Valve Replacement from a Single-Center Experience.

INTRODUCTION: When transcatheter aortic valve replacement (TAVR) was introduced, pre-implantation balloon aortic valvuloplasty (BAV) was a routine part of the procedure. Smaller device profiles have resulted in selective use of BAV; however, there is a paucity of data about the trend in use of direct TAVR and the safety of this strategy. METHODS: All patients who underwent TAVR at a Veterans Affairs Medical Center from September 2013 to November 2016 were included in this retrospective analysis. We reviewed angiography films and verified with procedure reports to assess if direct TAVR was performed. Troponin T was assessed within 72 h after the TAVR. Multivariate analysis examined the association between direct TAVR and periprocedural myocardial infarction (MI) or 1-year mortality. RESULTS: Overall, 207 patients were available for analysis. The mean follow-up was 13.3 months. A balloon-expandable valve was used 93.2% of the time, and 35.3% of patients were treated with conscious sedation. Periprocedural MI or 1-year mortality occurred in 12.5% of the direct TAVR group versus 18.3% of the pre-implantation BAV group (p = 0.30). After controlling for potential confounding variables, direct TAVR was not associated with periprocedural MI or 1-year mortality. CONCLUSIONS: Direct TAVR appears to be safe and is not associated with periprocedural MI or 1-year mortality. With current generation devices, this strategy can be considered for most patients undergoing TAVR.

Comparison of Different Invasive Hemodynamic Measurements as a Prediction Tool for Mortality after Transcatheter Aortic Valve Replacement in Men: A Retrospective Observational Study.

INTRODUCTION: Hemodynamic measurements can assess for paravalvular aortic regurgitation after transcatheter aortic valve replacement (TAVR). This study compared the utility of different invasive hemodynamic measures in providing prognostic information. METHODS: This retrospective observational study of TAVR patients at a Veterans Hospital assessed aortic regurgitation index, diastolic delta, pulse pressure, and heart rate adjusted diastolic delta obtained at valve implantation. The primary outcome was total mortality. RESULTS: Overall, 151 patients underwent TAVR. Immediately after implantation, mean aortic regurgitation index was 31 ± 8.6, mean diastolic delta was 38 ± 9.8 mmHg, mean pulse pressure was 67 ± 18 mmHg, and mean heart rate adjusted diastolic delta was 47 ± 14.3 mmHg/beats per minute. Two percent of patients had ≥ moderate paravalvular aortic regurgitation by postoperative transthoracic echocardiography. Total mortality was 15.2% at a mean follow-up of 12.7 ± 9.2 months. Aortic regurgitation index <25 vs. ≥25, diastolic delta <19 vs. ≥19 mmHg, and pulse pressure >60 vs. ≤60 mmHg were not associated with total mortality. However, total mortality was 50% for heart rate adjusted diastolic delta <25 mmHg/beats per minute vs. 12.6% for heart rate adjusted diastolic delta ≥25 mmHg/beats per minute (p = 0.017). In a multivariate Cox regression analysis, heart rate adjusted diastolic delta <25 mmHg/beats per minute vs. heart rate adjusted diastolic delta ≥25 mmHg/beats per minute was associated with total mortality (hazard ratio 9.4, 95% confidence interval 2.0-44, p = 0.004). CONCLUSIONS: Among a cohort of TAVR patients, the only invasive hemodynamic test independently associated with total mortality was heart rate adjusted diastolic delta.

Improvement of Subjective Well-Being by Ranolazine in Patients with Chronic Angina and Known Myocardial Ischemia (IMWELL Study).

INTRODUCTION: We aimed to assess if ranolazine would improve angina symptoms among patients with documented myocardial ischemia. METHODS: Eligible subjects had chronic stable angina and at least one coronary stenosis with fractional flow reserve (FFR) ≤0.80 or at least one chronic total occlusion (CTO) without attempted revascularization. Subjects were randomized to oral ranolazine 500 mg twice daily for 1 week, then ranolazine 1000 mg twice daily for 15 weeks versus matching placebo. The primary end point was change in angina at 16 weeks as assessed by the Seattle Angina Questionnaire (SAQ). RESULTS: Between September 2014 and January 2016, 25 subjects were randomized to ranolazine versus 25 to placebo. The most common reason for eligibility was CTO (72%), while the remainder had myocardial ischemia documented by low FFR. The mean FFR was 0.57 ± 0.12. Sixty-eight percent of subjects were on two or more anti-angina medications at baseline. Study medication was discontinued in 32% (eight of 25) of the ranolazine group versus 36% (nine of 25) of the placebo group. By intention-to-treat, 46 subjects had baseline and follow-up SAQ data completed. Ranolazine was not associated with an improvement in angina compared with placebo at 16 weeks. The results were similar among 33 subjects that completed study medication. The incidence of ischemia-driven hospitalization or catheterization was 12% (three of 25) of the ranolazine group versus 20% (five of 25) in the placebo group (p > 0.05). CONCLUSIONS: In subjects with chronic stable angina and documented myocardial ischemia, ranolazine did not improve angina symptoms at 16 weeks. FUNDING: Gilead. CLINICAL TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT02265796).

Late Paravalvular Aortic Regurgitation: Migration of the Valve or Late Recoil?

A 79-year-old man underwent trans-catheter aortic valve replacement for symptomatic severe aortic stenosis with a 26-mm Edwards SAPIEN XT valve. Immediately after valve deployment there was moderate amount of paravalvular leak. Post-dilation was performed with an additional 2 cc of volume, and the paravalvular leak was reduced to trace. Nine months later, trans-thoracic echocardiography revealed moderate to severe paravalvular leak and possible aortic migration of the valve. The patient was brought back for the treatment of the paravalvular leak which was suspected to be due to valve migration. However, fluoroscopy and trans-esophageal echocardiography showed good valve position. Measurement of late valve recoil in the Coplanar view using cine-angiographic analysis software showed that the lower third of the valve had the greatest late recoil (-1.74 mm, 6.55%), which presumably accounted for the progression of the paravalvular leak. Valve-in-valve trans-catheter aortic valve replacement was performed with a 26-mm SAPIEN 3 valve and the paravalvular leak was reduced to trace. This case displays late recoil as a likely mechanism for development of paravalvular leak after SAPIEN XT valve implantation. Our case illustrates that late recoil needs to be systematically evaluated in future studies, especially when trans-catheter aortic valve replacement is being expanded to lower risk and younger patients for whom the longevity and long-term performance of these valves is of critical importance.

Postgraduate Education in Quality Improvement Methods: Initial Results of the Fellows' Applied Quality Training (FAQT) Curriculum.

OBJECTIVE: Training in quality improvement (QI) is a pillar of the next accreditation system of the Accreditation Committee on Graduate Medical Education and a growing expectation of physicians for maintenance of certification. Despite this, many postgraduate medical trainees are not receiving training in QI methods. We created the Fellows Applied Quality Training (FAQT) curriculum for cardiology fellows using both didactic and applied components with the goal of increasing confidence to participate in future QI projects. METHODS AND RESULTS: Fellows completed didactic training from the Institute for Healthcare Improvement's Open School and then designed and completed a project to improve quality of care or patient safety. Self-assessments were completed by the fellows before, during, and after the first year of the curriculum. The primary outcome for our curriculum was the median score reported by the fellows regarding their self-confidence to complete QI activities. Self-assessments were completed by 23 fellows. The majority of fellows (15 of 23, 65.2%) reported no prior formal QI training. Median score on baseline self-assessment was 3.0 (range, 1.85-4), which was significantly increased to 3.27 (range, 2.23-4; P = 0.004) on the final assessment. The distribution of scores reported by the fellows indicates that 30% were slightly confident at conducting QI activities on their own, which was reduced to 5% after completing the FAQT curriculum. An interim assessment was conducted after the fellows completed didactic training only; median scores were not different from the baseline (mean, 3.0; P = 0.51). CONCLUSION: After completion of the FAQT, cardiology fellows reported higher self-confidence to complete QI activities. The increase in self-confidence seemed to be limited to the applied component of the curriculum, with no significant change after the didactic component.

Risk of Bleeding in End-Stage Liver Disease Patients Undergoing Cardiac Catheterization.

Patients with end-stage liver disease frequently have baseline coagulopathies. The international normalized ratio is in common use for the estimation of bleeding tendency in such patients, especially those undergoing an invasive procedure like cardiac catheterization. The practice of international normalized ratio measurement-followed by pharmacologic (for example, vitamin K or fresh frozen plasma) or nonpharmacologic intervention-is still debatable. The results of multiple randomized trials have shown the superiority of the radial approach over femoral access in reducing catheterization bleeding. This reduction in bleeding in turn decreases the risk and cost of blood-product transfusion. However, there is little evidence regarding the use of the radial approach in the end-stage liver disease patient population specifically. In this review, we summarize the studies that have dealt with cardiac catheterization in patients who have end-stage liver disease. We also discuss the role of the current measurements that are used to reduce the risk of bleeding in these same patients.

Effects of enhanced external counterpulsation on arterial stiffness and myocardial oxygen demand in patients with chronic angina pectoris.

Enhanced external counterpulsation (EECP) is a noninvasive technique for treatment of symptomatic coronary artery disease in patients not amenable to revascularization procedures. However, the mechanisms underlying the benefits of EECP remain unknown. We hypothesized that decreases in arterial stiffness and aortic wave reflection are a therapeutic target for EECP. Patients with coronary artery disease and chronic angina pectoris were randomized (2:1 ratio) to 35 1-hour sessions of EECP (n = 28) or sham EECP (n = 14). Central and peripheral arterial pulse-wave velocity and aortic wave reflection (augmentation index) were measured using applanation tonometry before, and after 17 and 35 1-hour treatment sessions. Wasted left ventricular pressure energy and aortic systolic tension-time index, markers of left-ventricular myocardial oxygen demand, were derived from the synthesized aortic pressure wave. Exercise duration, anginal threshold, and peak oxygen consumption were measured using a graded treadmill test. Central arterial stiffness and augmentation index were decreased after 17 and 35 sessions in the treatment group. Measurements of peripheral arterial stiffness were decreased after 35 sessions in the treatment group. Changes in aortic pressure wave reflection resulted in decreased measurements of myocardial oxygen demand and wasted left ventricular energy. No changes in central or peripheral arterial stiffness were observed in the sham group. Furthermore, measurements of exercise capacity were improved in the EECP group but unchanged in the sham group. In conclusion, EECP therapy decreases central and peripheral arterial stiffness, which may explain improvements in myocardial oxygen demand in patients with chronic angina pectoris after treatment.

Enhanced external counterpulsation improves peripheral artery flow-mediated dilation in patients with chronic angina: a randomized sham-controlled study.

BACKGROUND: Mechanisms responsible for anti-ischemic benefits of enhanced external counterpulsation (EECP) remain unknown. This was the first randomized sham-controlled study to investigate the extracardiac effects of EECP on peripheral artery flow-mediated dilation. METHODS AND RESULTS: Forty-two symptomatic patients with coronary artery disease were randomized (2:1 ratio) to thirty-five 1-hour sessions of either EECP (n=28) or sham EECP (n=14). Flow-mediated dilation of the brachial and femoral arteries was performed with the use of ultrasound. Plasma levels of nitrate and nitrite, 6-keto-prostaglandin F(1α), endothelin-1, asymmetrical dimethylarginine, tumor necrosis factor-α, monocyte chemoattractant protein-1, soluble vascular cell adhesion molecule, high-sensitivity C-reactive protein, and 8-isoprostane were measured. EECP increased brachial (+51% versus +2%) and femoral (+30% versus +3%) artery flow-mediated dilation, the nitric oxide turnover/production markers nitrate and nitrite (+36% versus +2%), and 6-keto-prostaglandin F(1α) (+71% versus +1%), whereas it decreased endothelin-1 (-25% versus +5%) and the nitric oxide synthase inhibitor asymmetrical dimethylarginine (-28% versus +0.2%) in treatment versus sham groups, respectively (all P<0.05). EECP decreased the proinflammatory cytokines tumor necrosis factor-α (-16% versus +12%), monocyte chemoattractant protein-1 (-13% versus +0.2%), soluble vascular cell adhesion molecule-1 (-6% versus +1%), high-sensitivity C-reactive protein (-32% versus +5%), and the lipid peroxidation marker 8-isoprostane (-21% versus +1.3%) in treatment versus sham groups, respectively (all P<0.05). EECP reduced angina classification (-62% versus 0%; P<0.001) in treatment versus sham groups, respectively. CONCLUSIONS: Our findings provide novel mechanistic evidence that EECP has a beneficial effect on peripheral artery flow-mediated dilation and endothelial-derived vasoactive agents in patients with symptomatic coronary artery disease.

Effect of enhanced external counterpulsation on inflammatory cytokines and adhesion molecules in patients with angina pectoris and angiographic coronary artery disease.

Cardiovascular disease is associated with chronic low-level inflammation, as evidenced by elevated circulating proinflammatory cytokines. Experimental evidence suggests that inflammation can be suppressed under conditions of high shear stress. This study was conducted to examine the effects of enhanced external counterpulsation (EECP), a noninvasive therapy that increases endothelial shear stress, on circulating levels of inflammatory biomarkers and adhesion molecules in patients with angina pectoris. Twenty-one patients were randomly assigned to either 35 1-hour treatments at cuff pressures of 300 mm Hg (EECP; n=12) or 75 mm Hg (sham; n=9). Plasma tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and soluble vascular cell adhesion molecule-1 were measured before and after 35 1-hour sessions of treatment or sham. Patients in the EECP group demonstrated reductions in tumor necrosis factor-alpha (6.9+/-2.7 vs 4.9+/-2.5 pg/ml, p<0.01; -29%) and monocyte chemoattractant protein-1 (254.9+/-55.9 vs 190.4+/-47.6 pg/ml, p<0.01; -19%) after treatment, whereas there was no change in the sham group. Changes in soluble vascular cell adhesion molecule-1 were not observed in either group. In conclusion, 35 sessions of EECP decreased circulating levels of proinflammatory biomarkers in patients with symptomatic coronary artery disease.