Clinical impact of preemptive pharmacogenomic testing on antiplatelet therapy in a real-world setting.

CYP2C19 genotyping to guide antiplatelet therapy after patients develop acute coronary syndromes (ACS) or require percutaneous coronary interventions (PCIs) reduces the likelihood of major adverse cardiovascular events (MACE). Evidence about the impact of preemptive testing, where genotyping occurs while patients are healthy, is lacking. In patients initiating antiplatelet therapy for ACS or PCI, we compared medical records data from 67 patients who received CYP2C19 genotyping preemptively (results >7 days before need), against medical records data from 67 propensity score-matched patients who received early genotyping (results within 7 days of need). We also examined data from 140 patients who received late genotyping (results >7 days after need). We compared the impact of genotyping approaches on medication selections, specialty visits, MACE and bleeding events over 1 year. Patients with CYP2C19 loss-of-function alleles were less likely to be initiated on clopidogrel if they received preemptive rather than early or late genotyping (18.2%, 66.7%, and 73.2% respectively, p = 0.001). No differences were observed by genotyping approach in the number of specialty visits or likelihood of MACE or bleeding events (all p > 0.21). Preemptive genotyping had a strong impact on initial antiplatelet selection and a comparable impact on patient outcomes and healthcare utilization, compared to genotyping ordered after a need for antiplatelet therapy had been identified.

CYP2C19 genotype-directed P2Y12 inhibitor antiplatelet therapy normalizes risk for major adverse cardiovascular events after percutaneous coronary intervention.

OBJECTIVE: To study the use of CYP2C19 genotyping to guide P2Y12 inhibitor selection to maximize efficacy, and attenuate risk in appropriate patients who underwent PCI for CAD. METHODS: We performed a retrospective analysis of 868 patients with CAD who received CYP2C19 genotyping after PCI and changed P2Y12 inhibitor based on the results. Patients were divided into two groups based on clopidogrel metabolizer status. Group I: Intermediate (IM) and poor metabolizers (PM). Group II: Ultra-rapid (UM), rapid (RM) and normal metabolizers (NM). Each group was then categorized to one of two treatment arms guided by CYP2C19 genotype. Category 1: IM/PM started on clopidogrel, switched to ticagrelor or prasugrel; 2:IM/PM started on ticagrelor/prasugrel, continued these medications; 3: UM/RM/NM started on ticagrelor/prasugrel, switched to clopidogrel; 4: UM/RM/NM started on clopidogrel, continued clopidogrel. Death due to cardiac causes, bleeding events, non-fatal MI, target vessel revascularization (TVR), and MACE in all four categories were considered at 1, 6 and 12 months. RESULTS: We did not observe significant difference between phenotypes for MACE at 1 (p = 0.274), 6 (p = 0.387), and 12 months (p = 0.083). Death due to cardiac causes, MI, and bleeding events were not significant at 1, 6, and 12 months. There was no significant difference in TVR at 6 (p = 0.491), and 12 months (p = 0.423) except at 1 month (p = 0.012). CONCLUSION: CYP2C19 genotype-based intervention can be implemented effectively and reliably to guide selection of P2Y12 inhibitor to optimize patient quality and safety when appropriate in post PCI patients.

Current Evidence and Rationale of Percutaneous Therapy for Chronic Total Coronary Occlusions.

The prevalence of chronic total occlusion (CTO) lesions in coronary arteries is notably high in patients with significant coronary artery disease. However, only a relatively small fraction of observed CTOs classically go for revascularization. Recent advances in techniques and equipment has greatly improved the success rates of CTO revascularization while reducing complications. There has also been an increasing body of evidence regarding clinical benefit of CTO revascularization. However, until recently majority of the evidence was observational and based on data from large multicenter registries. Recent randomized studies have reported on clinical benefits of CTO revascularization particularly with relief of angina. However, there is heterogeneity of results among different studies and the magnitude of benefit is not consistently seen in all studies. This article reviews the existing literature on the current evidence regarding clinical benefits and other rationale for CTO revascularization.

Outcomes and Safety of Transcatheter Aortic Valve Implantation With and Without Routine Use of Transesophageal Echocardiography.

Transesophageal echocardiography (TEE) has been extensively used historically for Transcatheter aortic valve implantation (TAVI) but focus is shifting from routine use of TEE and general anesthesia to "as needed" use. We evaluated patients who had TAVI in our institution from September 2012 to February 2017. Decision for implantation and use of TEE during procedure was made by the structural heart team on a case-to-case basis, based on FDA approved indications. Data including procedural details, length of stay and rehospitalizations were obtained from all patients. TAVI was performed on 178 patients during the study period of which 104 of 178 had TEE during TAVI. Baseline characteristics were fairly comparable in both groups. Similar proportion of self-expanding and balloon expanding valves were deployed. Patients in TEE group had longer overall procedure time (107 minute vs 83 minute, p = 0.0002) and longer length of stay (5.01days vs 2.49days, p < 0.0001). Echocardiographic study postprocedure showed similar incidence of paravalvular leak and similar gradients and velocities across aortic valve. Rates of 30-day readmissions were similar in both groups. In conclusion, in this single-center retrospective analysis-TAVI without the 'routine use' of TEE was comparable with those done with TEE guidance in terms of periprocedural complications and 30-day readmissions. Overall procedure length and length of stay was predictably higher in the TEE group.

Multisite Investigation of Outcomes With Implementation of CYP2C19 Genotype-Guided Antiplatelet Therapy After Percutaneous Coronary Intervention.

OBJECTIVES: This multicenter pragmatic investigation assessed outcomes following clinical implementation of CYP2C19 genotype-guided antiplatelet therapy after percutaneous coronary intervention (PCI). BACKGROUND: CYP2C19 loss-of-function alleles impair clopidogrel effectiveness after PCI. METHODS: After clinical genotyping, each institution recommended alternative antiplatelet therapy (prasugrel, ticagrelor) in PCI patients with a loss-of-function allele. Major adverse cardiovascular events (defined as myocardial infarction, stroke, or death) within 12 months of PCI were compared between patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy. Risk was also compared between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy. Cox regression was performed, adjusting for group differences with inverse probability of treatment weights. RESULTS: Among 1,815 patients, 572 (31.5%) had a loss-of-function allele. The risk for major adverse cardiovascular events was significantly higher in patients with a loss-of-function allele prescribed clopidogrel versus alternative therapy (23.4 vs. 8.7 per 100 patient-years; adjusted hazard ratio: 2.26; 95% confidence interval: 1.18 to 4.32; p = 0.013). Similar results were observed among 1,210 patients with acute coronary syndromes at the time of PCI (adjusted hazard ratio: 2.87; 95% confidence interval: 1.35 to 6.09; p = 0.013). There was no difference in major adverse cardiovascular events between patients without a loss-of-function allele and loss-of-function allele carriers prescribed alternative therapy (adjusted hazard ratio: 1.14; 95% confidence interval: 0.69 to 1.88; p = 0.60). CONCLUSIONS: These data from real-world observations demonstrate a higher risk for cardiovascular events in patients with a CYP2C19 loss-of-function allele if clopidogrel versus alternative therapy is prescribed. A future randomized study of genotype-guided antiplatelet therapy may be of value.

Reduction in Contrast Nephropathy From Coronary Angiography and Percutaneous Coronary Intervention With Ultra-Low Contrast Delivery Using an Automated Contrast Injector System.

OBJECTIVE: To evaluate the incidence of contrast-induced nephropathy (CIN) following coronary angiography and percutaneous coronary intervention (PCI) utilizing a novel ultra-low contrast delivery (ULCD) technique. BACKGROUND: Current techniques for reducing contrast volumes during angiographic and PCI procedures require the use of advanced coronary imaging methods, such as intravascular ultrasound and coronary flow wires. We propose the use of an automated contrast injector system (ACIS) with a novel programming technique that significantly reduces contrast volumes and CIN development. METHODS: From 2013 to 2014, a total of 123 patients with stage III or higher chronic kidney disease (CKD) underwent coronary angiography, PCI, or a combined procedure using the ULCD technique. A retrospective analysis was conducted to evaluate contrast volumes and rate of CIN development. Patients developing CIN were compared using tests of proportions. RESULTS: The median contrast volume was 17.9 mL (n = 123). The study cohorts comprised diagnostic (15.2 mL; n = 72), PCI (17.1 mL; n = 30), and PCI + diagnostic groups (27.9 mL; n = 21). The incidence of CIN observed in the entire cohort through day 7 was 3.3% (4/123). Seventy-five percent of the CIN cases occurred following diagnostic angiography alone. Longitudinal follow-up at 21 days identified an additional 5 cases of CIN. Compared to literature data, the ULCD technique delivers less contrast per case. CONCLUSION: The adaptation of the ULCD technique for coronary procedures significantly reduces contrast volume delivery when compared with conventional practice or previously described low-contrast techniques. The ULCD appears to be an efficacious method of limiting CIN development in a susceptible population with CKD.

18-year-old female with acute ST elevation myocardial infarction.

Acute coronary syndrome (ACS) is a rare disease entity among young female patients. Intra mural hematoma is a diagnostic consideration in a population at low risk for classic pathophysiologic mechanisms underlying acute coronary syndromes, namely plaque rupture or plaque erosion. We describe a case of a young female patient presenting with acute coronary syndrome attributed to intra mural hematoma.

Stenting of the unprotected left main coronary artery in a nonagenarian presenting with recurrent non-ST elevation myocardial infarction.

Coronary artery disease (CAD) involving the left main (LM) artery has traditionally been considered an indication for coronary artery bypass surgery (CABG). With recent advances in the field of percutaneous coronary interventions (PCI), angioplasty and stenting of the unprotected' LM has been performed in patients at high surgical risk. This is a challenging intervention as a large area of myocardium is at risk during the procedure. Features that make it especially high risk are distal stenosis of this vessel and presence of coronary disease in other territories. Left ventricular assist devices need to be considered in these situations so as to minimize the risk involved. We present a case of a 90-year-old female with myocardial infarction who underwent complex angioplasty involving the distal LM and proximal left anterior descending (LAD) coronary artery, without left ventricular assist device or balloon pump support.

Propafenone associated severe central nervous system and cardiovascular toxicity due to mirtazapine: a case of severe drug interaction.

We describe a rare case of severe drug-drug interaction between propafenone and mirtazapine leading to propafenone toxicity. A 69-year-old Caucasian male taking propafenone for atrial fibrillation was prescribed mirtazapine for insomnia. Subsequent to the first dose of mirtazapine the patient experienced seizures, bradycardia and prolonged QRS as well as QTc intervals on EKG. The patient was admitted to the ICU and recovered after supportive management. Propafenone is an established class IC antiarrhythmic drug commonly used in the treatment of atrial fibrillation. It is metabolized through the CYP4502D6 pathway. Five to 10 percent of Caucasians are poor metabolizers. Mirtazapine is a commonly prescribed antidepressant drug, which is also metabolized through and may modulate the CYP4502D6 pathway leading to altered metabolism of propafenone and possible adverse effects. In this case, toxicity was reversed once the offending drugs were discontinued. An extensive review of the literature revealed this to be the first described case of drug interaction between propafenone and mirtazapine.

Incidental finding of subclavian steal in a cardiac catheterization for acute coronary syndrome.

The subclavian steal syndrome (SSS) refers to neurological symptoms that develop from a proximal subclavian artery occlusion. We present a case of an asymptomatic patient found to have subclavian steal (SS) on angiography. A brief literature review follows.

A novel application of GuideLiner catheter for thrombectomy in acute myocardial infarction: a case series.

Angiographically visible thrombus and distal embolization are relatively common during percutaneous coronary intervention (PCI) in myocardial infarction (MI) and correspond to worse outcomes. Several aspiration and thrombectomy devices have been shown to be effective for prevention of distal embolization. We present a technique with successful use of the GuideLiner catheter (Vascular Solutions) for thrombus aspiration after dedicated manual aspiration thrombectomy devices have failed. Our case series includes large thrombus burden in clinical scenarios of ST-elevation MI in a native vessel, non-ST elevation MI in a vein graft, and ST-elevation MI due to native vessel in stent thrombosis.

Effects of enhanced external counterpulsation on stress radionuclide coronary perfusion and exercise capacity in chronic stable angina pectoris.

Enhanced external counterpulsation (EECP) is an effective noninvasive treatment for patients with coronary artery disease (CAD). EECP has been demonstrated to improve anginal class and time to ST-segment depression during exercise stress testing. This study assesses the efficacy of EECP in improving stress-induced myocardial ischemia using radionuclide perfusion treadmill stress tests (RPSTs). The international study group enrolled patients from 7 centers with chronic stable angina pectoris and a baseline ischemic pre-EECP RPST. Patients' demographic and clinical characteristics were recorded. A baseline pre-EECP maximal RPST was performed within 1 month before EECP treatment. The results were compared with a follow-up RPST performed within 6 months of completion of a 35-hour course of EECP. Four centers performed post-EECP RPST to the same level of exercise as pre-EECP, whereas 3 centers performed maximal RPST post-EECP. The study enrolled 175 patients (155 men and 20 women). Improvement in angina, defined by > or =1 Canadian Cardiovascular Society angina class change, was reported in 85% of patients. In the centers performing the same level of exercise, 81 of 97 patients (83%) had significant improvement in RPST perfusion images. Patients who underwent maximal RPST revealed improvement in exercise duration (6.61 +/- 1.88 pre-EECP vs 7.41 +/- 2.03 minutes post-EECP, p <0.0001); 42 of the 78 patients (54%) in this group showed significant improvement in RPST perfusion images. Thus, EECP was effective in improving stress myocardial perfusion in patients with chronic stable angina at both comparable (baseline) and at maximal exercise levels.