Lennon, Ryan J.

Common genetic variation in CYP2C19 (cytochrome P450, family 2, subfamily C, polypeptide 19) *2 and *3 alleles leads to a loss of functional protein, and carriers of these loss-of-function alleles when treated with clopidogrel have significantly reduced clopidogrel active metabolite levels and high on-treatment platelet reactivity resulting in increased risk of major adverse cardiovascular events, especially after percutaneous coronary intervention. The Food and Drug Administration has issued a black box warning advising practitioners to consider alternative treatment in CYP2C19 poor metabolizers who might receive clopidogrel and to identify such patients by genotyping. However, routine clinical use of genotyping for CYP2C19 loss-of-function alleles in patients undergoing percutaneous coronary intervention is not recommended by clinical guidelines because of lack of prospective evidence. To address this critical gap, TAILOR-PCI (Tailored Antiplatelet Initiation to Lessen Outcomes due to Decreased Clopidogrel Response After Percutaneous Coronary Intervention) is a large, pragmatic, randomized trial comparing point-of-care genotype-guided antiplatelet therapy with routine care to determine whether identifying CYP2C19 loss-of-function allele patients prospectively and prescribing alternative antiplatelet therapy is beneficial.

Background: Serum uric acid may serve as a marker of cardiovascular events and outcomes in men, but further studies are required to determine its role in women. We aimed to determine differences in procedural characteristics and outcomes in women undergoing percutaneous coronary intervention(PCI). Methods: We retrospectively analyzed the Mayo Clinic Cardiovascular Catheterization Laboratory database, and included patients undergoing PCI from 1/1/2000 to 12/31/2007. There were 495 women who underwent PCI in this time period. Patients were divided into normal uric acid (n=240) and high uric acid (n=255) groups, and high uric acid was defined as >6.0 mg/dL. Patients were followed for adverse outcomes for a median of 47.1 (IQR 23.8, 62.8) months. Results: Mean age was 66.6 + 12.7 years in the normal group vs. 70.5 + 11.2 years in the elevated uric acid group(p=0.01). Hypertension and diabetes were more prevalent in the elevated uric acid group (p<0.01). BMI was significantly higher in the elevated uric acid group (p=0.001). There was a higher prevalence of calcified lesions among women with elevated uric acid when compared to those with normal uric acid levels (47% vs. 30% p<0.001). There was significantly lower TIMI=3 flow postprocedurally in those with elevated uric acid levels when compared to those with normal uric acid levels (91 % vs. 97%, p=0.003). After adjusting for potential confounders including age, hyperlipidemia, hypertension, BMI, diabetes, and chronic kidney disease, elevated uric acid was associated with increased likelihood of death (HR 1.8, p=0.01) and the composite endpoint of death or subsequent myocardial infarction (HR 1.5, p=0.03). Discussion: Uric acid may be an independent determinant of procedural characteristics and a predictor of outcomes after percutaneous intervention. Further studies are required to better understand the effect of uric acid on cardiovascular events in women.

Abstract Mental and physical stress is thought to play an important causative factor in apical ballooning syndrome (ABS) likely secondary to the vasomotor dysfunction. However, there are currently few data related to the impact of physical stress in this unique cardiomyopathy. A total 18 patients, including 8 females with history of ABS and 10 post-menopausal controls, underwent physical and mental tests. Assessments included the pain-induced peripheral artery tonometry scores (PIPATs) and mental stress peripheral artery tonometry scores (PATs). Compared with control group, PIPATs were significantly attenuated in patients with ABS in both baseline and post-mental stress (0.94 ± 0.08 vs1.30 ± 0.54, P <.05 and 0.87 ± 0.19 vs1.24 ± 0.21 P = .01, respectively); mental stress PATs were significantly lower in patients with ABS, both in Stroop test (0.79 ± 0.30 vs 1.24 ± 0.43, P = .01) and arithmetic test (0.91 ± 0.27 vs 1.36 ± 0.57, P = .01). PIPATs correlated significantly with mental stress PATs, both in arithmetic and Stroop test (P <.05). The PIPATs were attenuated in female with history of ABS and the vascular response to pain may provide a different pathogenesis mechanism on detecting patients with ABS.

Background Participation in cardiac rehabilitation ( CR ) is an essential component of care for patients with coronary artery disease. However, little is known about its benefit on cardiovascular outcomes in patients with diabetes mellitus ( DM ) who have undergone percutaneous coronary intervention. The aim of our study was to evaluate the impact of CR in this high‐risk group of patients. Methods and Results We performed a retrospective analysis of all patients with DM who underwent percutaneous coronary intervention in Olmsted County (Minnesota) between 1994 and 2010, assessing the impact of CR participation on clinical outcomes. CR participation was significantly lower in patients with DM (38%, 263/700) compared with those who did not have DM (45%, 1071/2379; P =0.004). Using propensity score adjustment, we found that in patients with DM , CR participation was associated with significantly reduced all‐cause mortality (hazard ratio, 0.56; 95% confidence interval, 0.39–0.80; P =0.002) and composite end point of mortality, myocardial infarction, or revascularization (hazard ratio, 0.77; 95% confidence interval, 0.60–0.98; P =0.037), during a median follow‐up of 8.1 years. In patients without DM , CR participation was associated with a significant reduction in all‐cause mortality (hazard ratio, 0.67; 95% confidence interval, 0.55–0.82; P <0.001) and cardiac mortality (hazard ratio, 0.67; 95% confidence interval, 0.47–0.95; P =0.024). Conclusions CR participation after percutaneous coronary intervention is associated with lower all‐cause mortality rates in patients with DM , to a similar degree as for those without DM . However, CR participation was lower in patients with DM , suggesting the need to identify and correct the barriers to CR participation for this higher‐risk group of patients.

ObjectivesThe purpose of this study was to compare the prevalence and impact of work‐related musculoskeletal pain in cardiac sonographers to a large control group of peer employees with similar demographics.BackgroundCardiac sonographers are known to have high levels of occupational musculoskeletal pain. Comparative studies with other employees within cardiology/radiology departments have never been performed.MethodsAn electronic survey was administered to Mayo Clinic employees at six major patient care facilities in four different states.ResultsThere were 2682 employees within the departments of cardiology and radiology who were contacted, and 1532 (57%) completed the survey. After excluding those who wore protective lead aprons, 517 employees comprised the control group and 66 cardiac sonographers made up the study group. Cardiac sonographers reported work‐related musculoskeletal pain more frequently than the control group (88% vs 40%; P<.001). This association persisted after multivariable adjustment for age, sex, body mass index, length of current employment, and history of preexisting musculoskeletal pain (OR 11.6; [95% CI 5.32, 25.5]; P<.001). Cardiac sonographers sought medical care for their work‐related pain more often (55% vs 21%; P<.001) and missed more work due to pain (35% vs 12%, P<.001). In a secondary analysis, cardiac sonographers also experienced more work‐related musculoskeletal pain than nurses, technicians, and physicians working in the interventional laboratory who regularly wear a protective lead apron (P<.001).ConclusionsIn this multisite cross‐sectional study, cardiac sonographers experienced significantly more work‐related pain and missed more work due to pain than peer employees within cardiology/radiology departments.

Introduction Apical ballooning syndrome (ABS) is typically associated with an antecedent stressful situation. Affected patients have been reported to have higher frequencies of premorbid affective disorders. We hypothesised that patients with ABS would have elevated levels of neuroticism (tendency to experience negative affect) and greater vulnerability to stress. Methods In this cross-sectional study, all active participants in the Mayo Clinic ABS prospective follow-up registry were invited to complete the third edition of the NEO Personality Inventory (NEO-PI-3). The NEO-PI-3 is the universally accepted measure of the ‘Five-Factor Model’ of personality. Inventory responses were scored using the NEO-PI-3 computer program and the data were compared with US normative sample used in standardisation of the inventory. Significance was set at 0.0014 to account for multiple comparisons. Results Of 106 registry participants approached, 53 completed the inventory. There was no difference in age, gender, time from ABS diagnosis, type of antecedent stressor (emotional, physical or none) or severity of initial illness between the responders and non-responders. Responders had mean Neuroticism T-scores of 48.0±10.6 (95% CI 45.1 to 50.9); p=0.18, when compared with the normal mean of 50. There was also no significant difference in the facet scale of Vulnerability: 46.9±8.4 (44.6 to 49.2), p=0.038, at α=0.0014. Conclusions Contrary to our hypothesis, patients with ABS do not manifest higher levels of neuroticism and do not have greater vulnerability to stress than the general population. These findings have implications for the clinicians’ perception of, and approach to, patients with ABS.

Background— Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic acute coronary syndrome for which optimal management remains undefined. Methods and Results— We performed a retrospective study of 189 patients presenting with a first SCAD episode. We evaluated outcomes according to initial management: (1) revascularization versus conservative therapy and (2) percutaneous coronary intervention (PCI) versus conservative therapy stratified by vessel flow at presentation. Demographics were similar in revascularization versus conservative (mean age, 44±9 years; women 92% both groups), but vessel occlusion was more frequent in revascularization (44/95 versus 18/94). There was 1 in-hospital death (revascularization) and 1 late death (conservative). Procedural failure rate was 53% in those managed with PCI. In the subgroup of patients presenting with preserved vessel flow, rates of PCI failure were similarly high (50%), and 6 (13%) required emergency coronary artery bypass grafting. In the conservative group, 85 of 94 (90%) had an uneventful in-hospital course, but 9 (10%) experienced early SCAD progression requiring revascularization. Kaplan–Meier estimated 5-year rates of target vessel revascularization and recurrent SCAD were no different in revascularization versus conservative therapy (30% versus 19%; P =0.06 and 23% versus 31%; P =0.7). Conclusions— PCI for SCAD is associated with high rates of technical failure even in those presenting with preserved vessel flow and does not protect against target vessel revascularization or recurrent SCAD. A strategy of conservative management with prolonged observation may be preferable.

Background— The impact of changing demographics on causes of long-term death after percutaneous coronary intervention (PCI) remains incompletely defined. Methods and Results— We evaluated trends in cause-specific long-term mortality after index PCI performed at a single center from 1991 to 2008. Deaths were ascertained by scheduled prospective surveillance. Cause was determined via telephone interviews, medical records, autopsy reports, and death certificates. Competing-risks analysis of cause-specific mortality was performed using 3 time periods of PCI (1991–1996, 1997–2002, and 2003–2008). Final follow-up was December 31, 2012. A total of 19 077 patients survived index PCI hospitalization, of whom 6988 subsequently died (37%, 4.48 per 100 person-years). Cause was determined in 6857 (98.1%). Across 3 time periods, there was a 33% decline in cardiac deaths at 5 years after PCI (incidence: 9.8%, 7.4%, and 6.6%) but a 57% increase in noncardiac deaths (7.1%, 8.5%, and 11.2%). Only 36.8% of deaths in the recent era were cardiac. Similar trends were observed regardless of age, extent of coronary disease, or PCI indication. After adjustment for baseline variables, there was a 50% temporal decline in cardiac mortality but no change in noncardiac mortality. The decline in cardiac mortality was driven by fewer deaths from myocardial infarction/sudden death ( P <0.001) but not heart failure ( P =0.85). The increase in noncardiac mortality was primarily attributable to cancer and chronic diseases ( P <0.001). Conclusions— This study found a marked temporal switch from predominantly cardiac to predominantly noncardiac causes of death after PCI over 2 decades. The decline in cardiac mortality was independent of changes in baseline clinical characteristics. These findings have implications for patient care and clinical trial design.