Gharacholou, S. Michael

Ischemic symptoms may be explained by a multitude of coronary pathologies, including coronary artery tortuosity, atherosclerosis, fibromuscular dysplasia, vasculitis, coronary vasospasm, or microvascular disease. We present an unusual case of coronary kinking in a patient presenting with exertional jaw pain in the absence of atherosclerotic risk factors. Multimodality imaging, coronary imaging, and coronary physiology helped establish the diagnosis and guide management.

Abstract Introduction Cardiovascular disease has become the leading cause of mortality among breast cancer survivors. Patients with breast cancer who receive treatment with anthracycline and trastuzumab therapies are at risk for the development of non-ischemic cardiomyopathy. The development of heart failure during chemotherapy administration often results in interruption of these life saving therapies. Purpose We aim to investigate whether ACE Inhibitors/angiotensin receptor blockers (ACE-I/ARBs) and beta-blockers can be used as primary prophylaxis to prevent the development of chemotherapy induced cardiomyopathy. Methods This was a retrospective cohort study investigating women who were diagnosed with breast cancer at our medical center from January 2000 to December 2021. The primary endpoint was the development of cardiotoxicity after treatment with chemotherapy. Cardiotoxicity was defined as a decrease of LVEF by 5% or more to less than 55% in the presence of symptoms of heart failure or an asymptomatic decrease in LVEF by 10% or more to less than 55%. Cox-proportional hazard ratios were conducted to determine the impact of prophylactic ACE/ARBs and beta-blockers on the development of cardiotoxicity. Other baseline characteristics were also investigated for their potential impact on the primary endpoint. Results There were 459 patients included in the study of which 70 met criteria for chemotherapy induced cardiomyopathy. Median follow up time of included patients was 12 months and average age was 55 years. Among the included patients, 52% were treated with only trastuzumab, 34% were treated with only anthracycline, and 14% were treated with both therapies. Before chemotherapy was initiated, 15% of patients were taking only ACE-I/ARBs, 7% were taking only beta-blockers, and 5% of patients were taking a combination of ACE-I/ARBS and beta-blockers. There were no significant protective benefits noted for patients who were taking ACE-I/ARBs [HR: 0.49, 95% CI (0.17–1.4)], beta-blockers [HR: 0.50, 95% CI (0.16–1.6)], or both [HR: 1.30, 95% CI (0.44–3.9)]. Notably, there was an increased risk of cardiotoxicity noted for patients who were older [HR: 1.04, 95% CI (1.01–1.1)], smokers within the past 10 years [HR: 2.54, 95% CI (1.41–4.6)], or received a combination of both trastuzumab and anthracycline therapy [HR: 2.52, 95% CI (1.01–6.3)]. Conclusion Prophylactic use of ACE-I/ARBs and beta-blockers separately or in combination was not associated with beneficial reduction in the development of non-ischemic cardiomyopathy in patients receiving anthracycline or trastuzumab therapies. Older age, smoking within the past 10 years, and combination therapy with both anthracycline and trastuzumab were found to be associated with an increased risk. Further studies are needed to investigate the etiology of how smoking may augment the potential cardiotoxic effects in this population. Funding Acknowledgement Type of funding sources: None.

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.

Introduction: The efficacy and safety of novel oral anticoagulants (NOACs) has not been assessed in subjects with renal impairment. Methods: We performed a meta-analysis of RCTs comparing NOACs with warfarin in patients with atrial fibrillation (AF), in relation to renal function estimated by glomerular filtration rate (GFR): normal (GFR>80 ml/min/1.73m2), mild (50-80 mL/min/1.73m2), and moderate (<50 mL/min/1.73m2) impairment. MEDLINE, Embase, Web of Science and the Cochrane Library were searched to identify articles published up to the third week of January 2015. Data were supplemented with FDA data. Data on stroke or systemic embolism (S/SE) and major bleeding according to renal function were collected and extracted. We estimated the pooled relative risk (RR) of S/SE and major bleeding, for NOACs compared to warfarin. Results: We retrieved four randomized clinical trials (each randomizing dabigatran, rivaroxaban, apixaban, or endoxaban versus warfarin) enrolling a total of 58338 subjects, 29123 randomized to NOACs and 29123 randomized to warfarin; 21132 had normal renal function, 13126 had mild and 11027 had moderate renal impairment. In subjects with moderate renal impairment, compared to warfarin, NOACs reduced the risk of S/SE (RR 0.8; 95% CI 0.68-0.94) and major bleeding (RR 0.80; 95% CI 0.71-0.91). In subjects with mild renal impairment NOACs were associated with a reduced risk of S/SE (RR 0.75; 95% CI 0.66-0.85) and major bleeding (RR 0.87; 95% CI 0.79-0.95). In subjects with normal renal function no difference in the risk of S/SE was observed, while the risk of major bleeding was slightly less for subjects taking NOACs (RR 0.87; 95% CI 0.76-0.99). The test for interaction among groups of renal function was borderline significant for S/SE, but not for major bleeding. Conclusions: The use of NOACs was associated with a reduced risk of S/SE in subjects with mild or moderate renal impairment; while the risk of bleeding was reduced by NOACs compared to warfarin.

Introduction: Clinical predictive value of transient prolonged ventricular conduction and repolarization during right ventricular (RV) pacing have not been studied. Hypothesis: Ventricular conduction and repolarization prolongation during RV pacing predict risk of arrhythmic and mortality events. Methods: Electrophysiology studies in 501 patients with cardiomyopathy (CM) were reviewed. Duration changes of QRS and QT interval during pacing from the RV apex were measured. Subjects were followed up for a mean of 3.2 years for arrhythmic events and total mortality. Results: Participants had a mean age 65 yrs, 80% male, 74% funcional class II or III, and a mean EF of 33.1%. A paced QRS duration > 190 ms was associated with more severe CM and in multi-variable analysis it was associated with a 3.5 times higher risk of ventricular arrhythmias or appropriate defibrillator therapy (HR 3.5, 95% CI 2.3-5.4, p<0.01) and 2.6 times higher risk of total mortality or arrhythmic events (HR 2.6, 95% CI 2.3-3.4, p<0.01) compared to a paced QRS duration <190 ms, independent of baseline EF or baseline QRS duration, and after adjustment for electrophysiology study results, baseline functional class, type of cardiomyopathy and other relevant clinical factors. Similarly a QTc interval during RV pacing > 620 ms was associated with a 2.7 times higher risk of arrhythmic events compared to a QTc interval during RV pacing < 620 ms. Conclusions: Prolongation of ventricular conduction (QRS > 190 ms) and repolarization (QTc > 620 ms) observed during RV pacing in subjects with CM are associated with higher risk of arrhythmic events, defibrillator therapies and all-cause mortality.

Introduction: Relationship of QOL and frailty are poorly defined. Hypothesis: To study the prevalence and prognosis of poor QOL in frail patients. Methods: Predismissal standardized tests for frailty and QOL in 2 cohorts were administered. In cohort 1, 629 patients ≥ 65 years underwent percutaneous coronary intervention (PCI) from 2005-2008, frailty (Fried) and QOL [SF-36 and SAQ] were ascertained. Cohort 2 [921 patients, 535 PCI, ≥55 years] underwent cardiac catheterization from 2014-18, frailty (Rockwood) and QOL (Likert) were determined. Results: In cohort 1, 19%; and 20% in cohort 2 were frail. Lower median SAQ (58.9 vs. 82.2); physical (29.5 vs. 43.9) and mental (49.2 vs. 57.4) scores of SF-36 in cohort 1 higher rates of fair/poor health (56% vs 18%) in cohort 2 (all comparisons, p<0.001) was seen in frail patients. As compared to without, frail patients were 5 times more likely (59% vs. 11%, p<0.001) in cohort 1 and 7 times more likely (56% vs. 8%) in cohort 2 to have poor QOL. Adjusted three year all-cause death and death/myocardial infarction (MI) was significantly higher for patients undergoing PCI with frailty; [HR (95% CI) death, 4.20 (2.63, 6.68) and death or MI HR 2.72 (1.91, 3.87), p<0.001) and with poor QOL [HR death 2.47 (1.59, 3.84) 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) indicating their independent prognostic influence. Conclusions: Poor QOL is commonly seen with frailty. Both frailty and poor QOL had significant and independent association with long-term survival.

Background: Immunocompromised (IC) patients are at greater risk from cardiac surgery. Transcatheter aortic valve replacement (TAVR) may be more preferable for treating severe aortic stenosis (AS), though data regarding outcomes of IC patients are limited. Methods: We reviewed TAVR procedures performed at our institution from 1/2015-12/2019.We defined IC as either active malignancy receiving oncologic treatment or post organ transplant on immunosuppression, HIV, chronic steroid use (>5mg/day), or autoimmune disorder. Survival probability was estimated using the Kaplan-Meier (KM) method. Cox regression was used to evaluate the association of IC with survival. Results: Of 173 patients who underwent TAVR, 56 (32%) were IC: 30 (54%) had active malignancy undergoing active treatment, 19 (34%) were IC without malignancy, and 7 (13%) had both. Among the 19 IC patients without malignancy, 4 were post organ transplant, 3 were taking chronic steroids, 2 had autoimmune disorder, 1 had HIV, and 10 had ≥2 combination of the above. IC patients, as compared to non-IC patients, had similar baseline demographics and STS risk score (median 4.3 vs. 4.4), respectively. There were 37 deaths (16 IC and 21 non-IC) over a median follow up of 1.4 years (IQR 1.0-2.0 years). 1-year survival after TAVR was 84.5% for IC patients and 89.0% for non-IC patients (log rank p = 0.51). After adjusting for age and sex, an association between IC and survival was observed but not found to be statistically significant (adjusted HR, 1.55; 95% CI, 0.80-3.00). Conclusions: IC patients undergoing TAVR have similar baseline characteristics as non-IC patients with a trend towards worse survival. Longer term follow-up may help clarify the impact of IC status on survival after TAVR.

Abstract Background: Frailty assessment has often been performed only at baseline in cohort studies. Little is known regarding factors associated with changes in frailty indices over follow up in patients with coronary artery disease (CAD). Methods: Between 11/2008 - 8/2012, 142 community-dwelling adults ≥65 years of age with prior history of CAD (angina or revascularization) participated in a study of frailty assessment at Mayo Clinic Health System in La Crosse, WI. A sample of participants (n=45) were included for frailty re-assessment using the Fried frailty criteria approximately 5 years after their baseline measures. Frailty classification was based on absence of deficits (non-frail), 1-2 deficits (intermediately frail), or 3 or more deficits (frail). Factors associated with a change in frailty indices were studied. Results: There were 45 patients that had a second assessment of frailty indices. At baseline, 24 patients (60%) were not frail while 16 patients (40%) had at least 1 frail feature. At follow up, 20 patients (50%) were not frail while 20 patients (50%) had a frail feature. Those improving were more often being married, had prior revascularization, and were without angina. Interval development of slower gait speed (r = 0.46; p=0.004) and decreased grip strength (r = -0.39; p = 0.01) were associated with worsening frailty. Conclusions: Older adults with CAD are not often frail by standard criteria; however, incident deficits develop during long term follow-up. Spousal support, absence of angina, and change in functional indices are less often associated with frailty features.

Abstract Background Older adults with severe aortic stenosis (AS) are at high risk of mortality unless surgical or transcatheter aortic valve replacement (AVR) is performed. Risk stratification often becomes complicated in frail elders with multi-morbidity, and time constraints limit thorough evaluation of geriatric comorbidities in the outpatient clinic setting. Purpose Utilization of an automated administratively-derived electronic health record (EHR) tool may aid in risk stratification of AS patients undergoing AVR. Methods We reviewed patients with severe AS undergoing AVR at our hospital program and cross-referenced with the Elder Risk Assessment (ERA) score. The ERA score is an administratively abstracted score derived on adults &gt;60 years old followed by general medicine clinic. It contains the following variables: marital status, age, hospitalized days in preceding 2 years, diabetes, coronary disease, heart failure, stroke, pulmonary disease, cancer, and dementia; higher scores indicate greater risk for adverse outcomes. Kaplan-Meier method was used to estimate survival by ERA score tertile. Cox regression was used to test the association of ERA with survival. Results There were 97 patients with severe AS undergoing AVR with ERA scores. Mean age was 80.6 (±6.6) years, 37% were female, average Society of Thoracic Surgery (STS) score was 3.6% (± 2.6), and 7% had transcatheter AVR. Co-morbidities were prevalent and included atrial fibrillation (41%), chronic renal failure (16%), stroke (14%), and diabetes (35%). Over a mean follow-up of 68 months (± 37.9 months), there were 62 deaths. Elevated ERA score was associated with worse long term survival (p=0.016 by log-rank) (Figure 1), with only 49% surviving at 5 years in the highest ERA tertile vs 68% in the lowest ERA tertile. Cox regression demonstrated that the relative risk of death per 6 unit increase in ERA score was 1.54 (95% CI 1.21–1.96, P&lt;0.001) in single variable analysis and 1.43 (95% CI 1.11–1.84, P=0.006) after adjusting for STS score. Conclusions Patients undergoing AVR for severe AS are often co-morbid older adults. An automated EHR derived ERA score was independently associated with survival after accounting for STS score and may streamline and improve risk assessment in these patients. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Mayo Clinic