Lennon, Ryan J.

Abstract Aims We hypothesize that poor quality of life (QOL) is highly prevalent in frail older adults and is associated with worse prognosis. Methods and results Predismissal standardized tests for frailty and QOL were prospectively administered to patients included in two cohorts. In Cohort 1, 629 patients ≥65 years who underwent percutaneous coronary intervention (PCI) from 2005 to 2008, frailty (Fried criteria), and QOL [SF-36 and Seattle Angina Questionnaires (SAQ)] were ascertained. Cohort 2 included 921 patients ≥55 years who underwent cardiac catheterization (535 had PCI) from 2014 to 2018 and frailty was determined by Rockwood criteria and QOL by single-item, self-reported health questionnaire. In Cohort 1, 19% were frail and 20% patients in Cohort 2 were frail with a frailty index >0.30. The median SAQ for physical limitation (58.9 vs. 82.2, P < 0.001), physical (29.5 vs. 43.9, P < 0.001), and mental (49.2 vs. 57.4, P < 0.001) component scores of SF-36 in Cohort 1 were lower and self-rating of fair/poor health (56% vs 18%, P < 0.001) in Cohort 2 was significantly higher in frail patients. As compared to patients without frailty, frail patients were five times more likely (59% vs. 11%, P < 0.001) in Cohort 1 and seven times more likely (56% vs. 8%) in Cohort 2 to be classified with poor QOL. Age- and gender-adjusted 3-year all-cause death and death or myocardial infarction (MI) was significantly higher for patients undergoing PCI with frailty; [hazard ratio (95% confidence interval) death, 4.20 (2.63–6.68, P < 0.001) and death or MI hazard ratio (HR) 2.72 (1.91–3.87, P < 0.001)] and with poor QOL [HR death 2.47 (1.59–3.84, P < 0.001)] and death or MI 1.61 (1.16–2.24, P < 0.001). There was no significant interaction between frailty and QOL (P = 0.64) and only modest attenuation was observed when considered together indicating their independent prognostic influence. Conclusion In elderly patients undergoing cardiac catheterization or PCI, poor QOL is seen more frequently in frail patients. Both frailty and poor QOL had significant and independent association with long-term survival.

AbstractBackgroundCurrent approaches in tracking Clostridioides difficile infection (CDI) and individualizing patient management are incompletely defined.MethodsWe recruited 468 subjects with CDI at Mayo Clinic Rochester between May and December 2016 and performed whole-genome sequencing (WGS) on C. difficile isolates from 397. WGS was also performed on isolates from a subset of the subjects at the time of a recurrence of infection. The sequence data were analyzed by determining core genome multilocus sequence type (cgMLST), with isolates grouped by allelic differences and the predicted ribotype.ResultsThere were no correlations between C. difficile isolates based either on cgMLST or ribotype groupings and CDI outcome. An epidemiologic assessment of hospitalized subjects harboring C. difficile isolates with ≤2 allelic differences, based on standard infection prevention and control assessment, revealed no evidence of person-to-person transmission. Interestingly, community-acquired CDI subjects in 40% of groups with ≤2 allelic differences resided within the same zip code. Among 18 subjects clinically classified as having recurrent CDI, WGS revealed 14 with initial and subsequent isolates differing by ≤2 allelic differences, suggesting a relapse of infection with the same initial strain, and 4 with isolates differing by >50 allelic differences, suggesting reinfection. Among the 5 subjects classified as having a reinfection based on the timing of recurrence, 3 had isolates with ≤2 allelic differences between them, suggesting a relapse, and 2 had isolates differing by >50 allelic differences, suggesting reinfection.ConclusionsOur findings point to potential transmission of C. difficile in the community. WGS better differentiates relapse from reinfection than do definitions based on the timing of recurrence.

Background: Type 2 myocardial infarction (T2MI) occurs because of an acute imbalance in myocardial oxygen supply and demand in the absence of atherothrombosis. Despite being frequently encountered in clinical practice, the population-based incidence and trends remain unknown, and the long-term outcomes are incompletely characterized. Methods: We prospectively recruited residents of Olmsted County, Minnesota, who experienced an event associated with a cardiac troponin T >99th percentile of a normal reference population (≥0.01 ng/mL) between January 1, 2003, and December 31, 2012. Events were retrospectively classified into type 1 myocardial infarction (T1MI, atherothombotic event), T2MI, or myocardial injury (troponin rise not meeting criteria for myocardial infarction [MI]) using the universal definition. Outcomes were long-term all-cause and cardiovascular mortality and recurrent MI. T2MI was further subclassified by the inciting event for supply/demand mismatch. Results: A total of 5460 patients had at least one cardiac troponin T ≥0.01 ng/mL; 1365 of these patients were classified as index T1MI (age, 68.5±14.8 years; 63% male) and 1054 were classified as T2MI (age, 73.7±15.8 years; 46% male). The annual incidence of T1MI decreased markedly from 202 to 84 per 100 000 persons between 2003 and 2012 ( P <0.001), whereas the incidence of T2MI declined from 130 to 78 per 100 000 persons ( P =0.02). In comparison with patients with T1MI, patients with T2MI had higher long-term all-cause mortality after adjustment for age and sex, driven by early and noncardiovascular death. Rates of cardiovascular death were similar after either type of MI (hazard ratio, 0.8 [95% CI, 0.7–1.0], P =0.11). Subclassification of T2MI by cause demonstrated a more favorable prognosis when the principal provoking mechanism was arrhythmia, in comparison with postoperative status, hypotension, anemia, and hypoxia. After index T2MI, the most common MI during follow-up was a recurrent T2MI, whereas the occurrence of a new T1MI was relatively rare (estimated rates at 5 years, 9.7% and 1.7%). Conclusions: There has been an evolution in the type of MI occurring in the community over a decade, with the incidence of T2MI now being similar to T1MI. Mortality after T2MI is higher and driven by early and noncardiovascular death. The provoking mechanism of supply/demand mismatch affects long-term survival. These findings underscore the healthcare burden of T2MI and provide benchmarks for clinical trial design.

INTRODUCTION: Microscopic colitis (MC) is a common cause of chronic watery diarrhea. Cross-sectional studies have suggested that patients with MC have a lower incidence of colon polyps compared to those without MC. However, existing literature is limited by a lack of longitudinal follow-up and the use of average-risk patients, rather than those with chronic diarrhea as controls. We aimed to further explore the association between MC and colon adenomas. METHODS: This retrospective cohort study included patients that underwent colonoscopy at Mayo Clinic (Rochester, MN) or Columbia University Medical Center (New York, NY) between 7/1/2006 and 12/31/2016. Consecutive cases with MC were identified using pathology databases at each center. Controls had chronic diarrhea, underwent colonoscopy, and did not have MC on biopsy. Cases and controls were matched 1:2 by age (±3 years), sex, and date of index colonoscopy (±6 months). Data was collected on demographics, tobacco and alcohol use, personal and family history of colon neoplasia, and presence of adenomas at the index or follow-up colonoscopies. RESULTS: The study included 376 patients with MC and 752 non-MC patients with chronic diarrhea. The median (range) age of patients was 64 (21, 88) years and 72% were female. Duration of follow-up was not significantly different between the 2 groups (total person years: cases 577, controls 972; P = 0.99) and 51 subjects had a new adenoma on follow-up. There were no significant differences in age, sex, alcohol use, family history of colon neoplasia, and personal history of inflammatory bowel disease between cases and controls. Patients with MC were more likely to be current tobacco users (10% vs. 6%, P = 0.02) and less likely to have a history of prior colon neoplasia (9% vs. 17%, P < 0.001). Patients with MC were significantly less likely to have colon adenomas at the time of their index colonoscopy (5% vs. 12%; odds ratio 0.36; 95% CI 0.21, 0.60; P < 0.001) after adjusting for tobacco use and history of prior lesions. However, when followed over time, there was no significant association between MC and risk of colon adenomas (Figure 1, P = 0.45) after adjusting for tobacco use, history of prior lesions, and presence of adenoma at index colonoscopy. CONCLUSION: Patients with MC are less likely to have colon adenomas at their index colonoscopy compared to those with chronic diarrhea without MC. However, when followed longitudinally, there appears to be no significant association between MC and risk of colon adenomas.

Background: We aim to study the incidence of major complications related to procedure defined as in-hospital death, myocardial infarction, stroke, pericardial effusion or tamponade, percutaneous coronary intervention due to iatrogenic coronary dissection, or unplanned bypass surgery within 72 hours after diagnostic left heart catheterization (LHC; primary end point). Furthermore, all causes of in-hospital death after LHC were adjudicated and reported (secondary end point). Methods and Results: Diagnostic LHC procedures (aortic angiography; coronary, including graft, angiography; and left ventricular angiography) from January 1, 2002, through December 31, 2013, were identified using the clinical scheduling system at Mayo Clinic, Rochester, and complications were identified through electronic records. International Classification of Diseases, Ninth Revision billing codes were used. Registration was queried to identify all-cause mortality. All events were reviewed and adjudicated. There were 43 786 diagnostic LHC procedures; 97.3% were coronary angiograms. The mean age of patients was 64.5 years (13.6), and the majority were male (61.5%). Primary end point was seen in 36 (0.082%) procedures or 8.2 of 10 000 LHCs. Combined right sided procedures with LHC did not increase the risk of major complications. Cardiogenic and septic shock, cardiac arrhythmia, and postsurgical complication were the most common causes of in-hospital death after LHC. Conclusions: The overall rates of major complications related to diagnostic cardiac catheterization procedures are extremely rare. The majority of the deaths occurring post-diagnostic LHC procedures were secondary to acute illness rather than directly related to diagnostic procedure.

Background Women with non‐obstructive coronary artery disease have increased cardiovascular morbidity. The role of risk factors in this population has yet to be established. We aimed to study the predictive effect of triglycerides and the triglyceride/high‐density lipoprotein ratio on major adverse cardiovascular events (MACE) in patients with non‐obstructive coronary artery disease, and to explore the role of lipid lowering therapy in modifying this risk. Methods and Results This is a prospective cohort study enrolling patients with anginal symptoms referred to the cardiac catheterization laboratory for suspected ischemia, who were subsequently diagnosed with non‐obstructive coronary artery disease, defined as no stenosis >20% on angiography. All patients had baseline laboratory testing and were followed for 7.8±4.3 years for the development of major adverse cardiovascular events. We performed Cox proportional hazard testing to determine the effect of triglycerides on risk of major adverse cardiovascular events among men and women by baseline statin use. A total of 462 patients were included. Median age was 53 (Q1, Q3: 45, 62) years. In a Cox proportional hazard model stratified by statin use adjusting for confounders, among those not on baseline statins, triglycerides were independently predictive of major adverse cardiovascular events in women (per 50 mg/dL risk ratio: hazard ratio 1.25 [95% CI : 1.06, 1.47]; P =0.01). This was not true among men. The interaction between triglycerides and sex, and triglycerides and statin was statistically significant. Conclusions Triglyceride levels may play a key role in predicting cardiovascular‐specific risk in women, and statin use may be protective. Further investigation is necessary to better delineate the role of statin use in preventing cardiovascular risk.

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.

Aim Angina pectoris in the absence of obstructive coronary artery disease (CAD) is common and is associated with poor quality of life (QOL). Coronary microvascular endothelial dysfunction is associated with myocardial ischaemia and is a common cause of angina. We hypothesise that evaluation of coronary endothelial function, its diagnosis and treatment will favourably impact QOL in patients with angina symptoms and non-obstructive CAD. Methods and results Follow-up was done on 457 patients with chest pain and non-obstructive coronary arteries who had undergone coronary vascular reactivity evaluation by administration of intracoronary acetylcholine at the time of diagnostic study. After a mean follow-up of 8.4±4.7 years, QOL was assessed by administration of the SF-36 QOL survey. Patients diagnosed and treated for microvascular endothelial dysfunction had a higher (better) overall mental composite score (44.8 vs 40.9, p=0.036) and mental health score (44.2 vs 40.7, p=0.047), and a trend towards higher vitality scores (39.1 vs 35.9, p=0.053) and role emotional scores (43.6 vs 40.4, p=0.073), compared with patients with normal endothelial function. Conclusion Among patients with chest pain and normal coronaries, diagnosis and treatment of coronary microvascular endothelial dysfunction in those with angina pectoris and non-obstructive CAD are associated with better QOL compared with patients with normal endothelial function.