Gulati, Rajiv

Background: There are good data to support using a single high-sensitivity cardiac troponin T (hs-cTnT) below the limit of detection of 5 ng/L to exclude acute myocardial infarction. Per the US Food and Drug Administration, hs-cTnT can only report to the limit of quantitation of 6 ng/L, a threshold for which there are limited data. Our goal was to determine whether a single hs-cTnT below the limit of quantitation of 6 ng/L is a safe strategy to identify patients at low risk for acute myocardial injury and infarction. Methods: The efficacy (proportion identified as low risk based on baseline hs-cTnT<6 ng/L) of identifying low-risk patients was examined in a multicenter (n=22 sites) US cohort study of emergency department patients undergoing at least 1 hs-cTnT (CV Data Mart Biomarker cohort). We then determined the performance of a single hs-cTnT<6 ng/L (biomarker alone) to exclude acute myocardial injury (subsequent hs-cTnT >99th percentile in those with an initial hs-cTnT<6 ng/L). The clinically intended rule-out strategy combining a nonischemic ECG with a baseline hs-cTnT<6 ng/L was subsequently tested in an adjudicated cohort in which the diagnostic performance for ruling out acute myocardial infarction and safety (myocardial infarction or death at 30 days) were evaluated. Results: A total of 85 610 patients were evaluated in the CV Data Mart Biomarker cohort, among which 24 646 (29%) had a baseline hs-cTnT<6 ng/L. Women were more likely than men to have hs-cTnT<6 ng/L (38% versus 20%, P <0.0001). Among 11 962 patients with baseline hs-cTnT<6 ng/L and serial measurements, only 1.2% developed acute myocardial injury, resulting in a negative predictive value of 98.8% (95% CI, 98.6–99.0) and sensitivity of 99.6% (95% CI, 99.5–99.6). In the adjudicated cohort, a nonischemic ECG with hs-cTnT<6 ng/L identified 33% of patients (610/1849) as low risk and resulted in a negative predictive value and sensitivity of 100% and a 30-day rate of 0.2% for myocardial infarction or death. Conclusions: A single hs-cTnT below the limit of quantitation of 6 ng/L is a safe and rapid method to identify a substantial number of patients at very low risk for acute myocardial injury and infarction.

Background: Ischemic event rates are low after percutaneous coronary intervention (PCI), conversely second generation P2Y12 inhibitors increase bleeding therefore identifying patients at risk to enable precision in prescribing dual anti-platelet therapy (DAPT) is of clinical interest. Prior machine-learning predictive analyses have been limited by use of older generation stents and lack of genetic data. We utilized clinical and genetic data of patients with new generation stents enrolled in TAILOR-PCI, a 40-center international trial to predict ischemic events after PCI. Methods: There were 4398 eligible post PCI patients with acute coronary syndromes or stable coronary artery disease who were randomly split into training (n=3299) and validation (n=1099) cohorts. The primary endpoint comprising of cardiovascular death, myocardial infarction, stroke, or stent thrombosis within 12 months of PCI was predicted with patient characteristics prior to hospital discharge. First, random forests were used for feature selection with 1,000 bootstraps comprising equal numbers of those with and without ischemic events to minimize the bias of sample imbalance. Features were selected by a consensus on variable-importance over bootstraps. Second, using these features in the training cohort, support vector machines (SVM) with a polynomial kernel was trained with repeated 5-fold cross validation to choose a model with highest area under the receiver operating characteristic curve (AUC) which was then used to predict ischemic events in the validation cohort. Results: The primary endpoint occurred in 2.4% of patients. Using 89 clinical and genetic variables in the random-forest feature selection step, variable importance-based consensus identified 50 top predictors. These 50 predictors achieved AUC=0.703 in the SVM training cohort and AUC=0.744 (specificity=0.84; sensitivity =0.43) in the SVM validation cohort. Conclusions: Machine learning methods using baseline clinical and genetic data enables prediction of infrequent ischemic events in post PCI patients receiving new generation stents. The role of such artificial intelligence algorithms in individualization of DAPT by identifying high or low risk patients needs to be explored.

Introduction: Peripheral arterial disease (PAD) is a strong predictor of systemic atherosclerosis with substantial morbidity and mortality. Medical management in PAD and coronary artery disease (CAD) has changed in recent eras with the use of high intensity statin and dual antiplatelet therapies. Hypothesis: Test whether mortality and major adverse cardiovascular events (MACE) (death and MI) has decreased over eras among PAD patients undergoning revascularization with percutaneous coronary intervention (PCI). Methods: Longitudinal cohort study of 549 patients who underwent PCI and non-invasive lower arterial study between 1997 and 2008 as identified in the Mayo Clinic PCI registry were stratified into 2 time eras: 1997-2003 (era1), and 2004-2008 (era2). PAD was assessed using the highest resting ABI and stratified according to established categories; < 0.90 (definite PAD); 1.00-1.39 (normal); and ≥ 1.40 defined a non-compressible artery. Kaplan-Meier methods were used to analyze follow-up survival. Results: Stratified by ABI over both time eras, 225 patients had PAD, 94 were non-compressible, and 142 were normal. Overall mortality rates were higher in era2 non-compressible and PAD patients than in non-PAD patients when compared to era1 (58%, 33%, 26%, vs 49% 32%, 19%, p<0.001 for all within-era comparisons) (Figure 1). MACE-free survival were higher in era2 non-compressible and PAD patients than in non-PAD patients when compared to the era1 (64%, 41%, 29% vs 59% 39%, 25%, p≤0.005 for all within-era comparisons). There were significant differences in medical therapy between era2 vs. era1 with higher discharge use of aspirin (98%; 94%), beta-blockers (88%; 66%), any lipid lowering drugs (86%; 76%), ACE inhibitors (67%; 56%), and diuretics (52%; 40%). Conclusions: Over the past two eras, the overall mortality has increased among patients with PAD and non-compressible vessels in era2 vs. era1 despite higher utilization of statin and antiplatelet therapies.

Background: Spontaneous coronary artery dissection (SCAD) is a nonatherosclerotic cause of myocardial infarction (MI) occurring most often in young women without cardiovascular disease (CVD) risk factors. SCAD is associated with fibromuscular dysplasia (FMD), pregnant/postpartum state, and extreme mental stress or physical exertion. Migraine headaches have been reported common in SCAD and may increase CVD risk. The objective was to assess differences in presentation, clinical factors, and outcomes in SCAD patients with migraines (M-SCAD) compared to those without, and determine M-SCAD prevalence. Methods: A retrospective cross-sectional observation study of patients with angiographically confirmed SCAD was conducted using the Mayo Clinic SCAD Registry. Participant-provided data and records were reviewed for migraine history, CVD risk factors, SCAD details, CVD and migraine therapies, and outcomes. Ordinal and nominal variables were compared using Pearson's chi squared test, and continuous variables were compared using Student's t-test. Statistical significance was set at p < 0.05. Results: Among 586 patients with complete questionnaires, 236 had a history of migraines; the lifetime and 1-year prevalence of migraines were 40% and 27% respectively. Migraines are more common in SCAD survivors than a comparable population (40% vs 33%, p=0.0002). M-SCAD patients were more likely to be female (99.6% vs 94%, p=0.001), have SCAD at a younger age (45.3 yrs. vs 47.6 yrs., p=0.004), and report a history of aneurysms (7.6% vs 1.7%, p=0.0004), 46% of which occurred in head or neck vessels. There was a trend toward increased head and neck FMD in M-SCAD (32% vs 23%, p=0.095). Prevalence of depression (27% vs 17%, p=0.005), anxiety (32% vs 24%, p=0.038), recurrent angina (62% vs 44%, p=<0.001) and concern for recurrent SCAD (46% vs 37%, p=0.034) were higher in M-SCAD. Triptans were stopped in 39% of migraineurs at the time of MI. Conclusion: As compared to SCAD survivors without migraines, those with M-SCAD are younger, more often report a history of depression, anxiety, and aneurysms, and have more chest pain after SCAD. Further investigation into this association and development of safe, effective treatments of both headache and angina after SCAD is needed.

Background: Transcatheter aortic valve replacement (TAVR) is often complicated by AV block requiring pacing, but whether patients recover AV conduction and whether the need for pacing affects outcomes is unknown. Methods: We retrospectively studied 534 patients who underwent TAVR at Mayo Clinic in Rochester, Minnesota between November 2008 and January 2015. Of these, 115 patients had implantable cardiac devices. Data was collected from subsequent device follow-ups to determine pacemaker dependency and percentage pacing. Results: 44 patients (8.2%) had devices implanted in the immediate post procedural period. The most common indications for implantation were high grade AV block (18 patients) and complete heart block (14 patients). 17/44 (38.6%) patients were pacemaker-dependent at implant and only 4 of these patients were no longer pacemaker-dependent during subsequent followup. The indication for pacing among these four patients was high grade atrio-ventricular block (2 patients), asystole (1 patient) and complete heart block (1). Among non-pacemaker-dependent patients, no significant change in the ventricular pacing percentages was noted over time. Survival was similar between patients who required device implantation post TAVR and those who did not after adjustment for age and gender (HR 0.73 [0.39-1.36], p=ns; figure) Conclusion: Patients requiring pacing after TAVR are often pacemaker-dependent at the time of implant. It is uncommon for patients who are dependent at the time of implant to regain AV conduction, but the need for cardiac pacing is not associated with increased mortality.

Background A growing body of evidence links coronary artery atherosclerosis and calcification to osteoporosis in women. Coronary endothelial dysfunction (CED) is associated with adverse cardiovascular events. We aimed to study the association of CED and development of osteoporosis. Methods Coronary vascular reactivity was evaluated in 225 women, greater than age 50, with non-obstructive coronary arteries, by administration of intracoronary acetylcholine during diagnostic angiography. CED was defined as <50% increase in coronary blood flow (CBF) from baseline in response to maximal dose. After a median follow-up of 7 years, patients were assessed by a questionnaire for development of osteoporosis. Results The average age of the cohort was 60 years. Of 225 women, 60% (135) had CED. 18.2% (41 of 225 women) developed osteoporosis during follow-up. Women with CED were twice more likely to develop osteoporosis vs. women without CED (23% vs. 11.1%, p=0.024). Women who developed osteoporosis compared to those who did not had a markedly lower response (% change) in CBF: median (IQR)-4.3 (-28.3, 51.7) vs. 39.9 (-8.2, 106.0), p=0.007. In univariate analysis, CED was significantly associated with development of osteoporosis (p=0.024, relative risk 2.07, 95% CI: 1.07, 4.00). Multivariate analysis indicated CED as an independent predictor of osteoporosis (p=0.04). Discussion Endothelial dysfunction may account for or share similar mechanisms with development of osteoporosis in cardiac patients.

Background: Coronary endothelial dysfunction (CED) causes angina/ischemia in patients with nonobstructive coronary artery disease (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary autologous CD34+ cell therapy for CED. Methods: Twenty NOCAD patients with invasively diagnosed CED and persistent angina despite maximally tolerated medical therapy underwent baseline exercise stress test, GCSF (granulocyte colony stimulating factor)-mediated CD34+ cell mobilization, leukapheresis, and selective 1×10 5 CD34+ cells/kg infusion into left anterior descending. Invasive CED evaluation and exercise stress test were repeated 6 months after cell infusion. Primary end points were safety and effect of intracoronary autologous CD34+ cell therapy on CED at 6 months of follow-up. Secondary end points were change in Canadian Cardiovascular Society angina class, as-needed sublingual nitroglycerin use/day, Seattle Angina Questionnaire scores, and exercise time at 6 months. Change in CED was compared with that of 51 historic control NOCAD patients treated with maximally tolerated medical therapy alone. Results: Mean age was 52±13 years; 75% were women. No death, myocardial infarction, or stroke occurred. Intracoronary CD34+ cell infusion improved microvascular CED (%acetylcholine-mediated coronary blood flow increased from 7.2 [−18.0 to 32.4] to 57.6 [16.3–98.3]%; P =0.014), decreased Canadian Cardiovascular Society angina class (3.7±0.5 to 1.7±0.9, Wilcoxon signed-rank test, P =0.00018), and sublingual nitroglycerin use/day (1 [0.4–3.5] to 0 [0–1], Wilcoxon signed-rank test, P =0.00047), and improved all Seattle Angina Questionnaire scores with no significant change in exercise time at 6 months of follow-up. Historic control patients had no significant change in CED. Conclusions: A single intracoronary autologous CD34+ cell infusion was safe and may potentially be an effective disease-modifying therapy for microvascular CED in humans. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03471611.

AbstractObjectivesThe aim of this study was to determine the safety of eliminating the pre‐discharge transthoracic echocardiogram (TTE) on 30‐day outcomes in patients undergoing transcatheter aortic valve replacement (TAVR).BackgroundTTE is utilized before, during, and after TAVR. Post‐procedural, pre‐discharge TTE assists in assessment of prosthesis function and detection of clinically significant paravalvular leak (PVL) after TAVR.MethodsPatients who underwent TAVR at Mayo Clinic from July 2018 to July 2019 were included in a prospective institutional registry. Patients undergoing TAVR prior to February 2019 received a pre‐discharge TTE, while those undergoing TAVR after February 2019 did not. Both cohorts were evaluated with TTE at 30 days post‐TAVR.ResultsA total of 330 consecutive patients were included. Of these, 160 patients (age 81.1 ± 7.6) had routine pre‐discharge TTE, while 170 patients (age 78.9 ± 7.5) were dismissed without routine pre‐discharge TTE. Mortality at 30 days was similar between the two groups (0% and 1.2%, respectively). One episode of PVL requiring intervention (0.6%) occurred in the pre‐discharge TTE group and none in the group without pre‐discharge TTE at 30‐day follow‐up. There was a similar incidence of total composite primary and secondary adverse events between the cohort receiving a pre‐discharge TTE and those without (28.1% vs. 25.3%, P = 0.56) at 30 days. The most common event was need for permanent pacemaker or ICD implantation in both groups (13.1% vs. 11.8%, P = 0.71).ConclusionsElimination of the pre‐discharge TTE is safe and associated with comparable 30‐day outcomes to routine pre‐discharge TTE. These findings have implication for TAVR practice cost‐efficiency and health care utilization.

Background: Randomized controlled trials and meta-analyses have demonstrated the benefits of cardiac rehabilitation (CR) in patients with acute myocardial infarction (AMI). Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of AMI. However, the benefit of CR has not been well studied in patients with SCAD. Purpose: Our objective was to compare the psychosocial and physiological characteristics and outcomes of CR in SCAD patients who participated in CR compared to those who did not. Methods: We performed a retrospective descriptive analysis of patients with angiographically confirmed SCAD enrolled in the Mayo Clinic SCAD Registry from January 2010 through December 2014 who had completed questionnaires (n=354). Demographics, clinical characteristics, Generalized Anxiety Disorder 7-Item Scale (GAD-7), Patient Health Questionnaire-9 (depression measure; PHQ-9), and details about participants’ CR participation and experience were collected via medical record review and questionnaires. Univariate analyses were performed to determine the differences between baseline characteristics and outcomes according to CR participation status. Results: Mean age of participants at time of SCAD was 46 ± 10 years; 95% were female. Seventy-six percent of participants participated in at least one CR session, and those users averaged 18 ± 12 sessions. A majority of CR participants reported physical and emotional benefits (82% and 75%, respectively). Of those who did not participate in CR, the primary reason was because their healthcare provider did not recommend CR (67%). Other reasons included inadequate transportation (12%), no insurance coverage (8%), cost (2%), no energy (2%), and being too ill (2%). On comparative analyses, CR participants had higher mean GAD-7 scores (4.9 vs. 3.9; p=0.03) and were more likely to increase their amount of exercise (p<0.01). Conclusions: Despite the well-known benefits of CR, in this international registry, only 76% of SCAD patients participated. Lack of recommendation for CR by a health care provider was the primary reason patients did not participate. The majority of patients reported benefits from CR. Higher GAD-7 scores were associated with CR participation, an interesting result requiring further evaluation in a larger or prospective cohort.