Alejandra Gutierrez

Oxidant and Inflammatory Mechanisms and Targeted Therapy in Atrial Fibrillation: An Update

Abstract: Atrial fibrillation (AF) is an important cause of stroke and risk factor for heart failure and death. Current pharmacologic treatments for AF have limited efficacy, and treatments that more directly target the underlying causes of AF are needed. Oxidant stress and inflammatory activation are interrelated pathways that promote atrial electrical and structural remodeling, leading to atrial ectopy, interstitial fibrosis, and increased stroke risk. This review evaluates the impact of common stressors on atrial oxidant stress and inflammatory activation and the contribution of these pathways to atrial remodeling. Recent studies suggest that integrated efforts to target the underlying risk factors, rather than the AF per se, may have a greater impact on health and outcomes than isolated efforts focused on the electrical abnormalities.

Genomics of Atrial Fibrillation

Atrial fibrillation (AF) is a common clinical arrhythmia that appears to be highly heritable, despite representing a complex interplay of several disease processes that generally do not manifest until later in life. In this manuscript, we will review the genetic basis of this complex trait established through studies of familial AF, linkage and candidate gene studies of common AF, genome wide association studies (GWAS) of common AF, and transcriptomic studies of AF. Since AF is associated with a five-fold increase in the risk of stroke, we also review the intersection of common genetic factors associated with both of these conditions. Similarly, we highlight the intersection of common genetic markers associated with some risk factors for AF, such as hypertension and obesity, and AF. Lastly, we describe a paradigm where genetic factors predispose to the risk of AF, but which may require additional stress and trigger factors in older age to allow for the clinical manifestation of AF.

Usefulness of CHADS2 and CHA2DS2-VASc Scores for Stroke Prediction in Patients With Cancer and Atrial Fibrillation

Stroke prediction scores have not been validated in patients with cancer and atrial fibrillation (AF). We aimed to identify unique risk factors and evaluate validity of CHADS2 and CHA2DS2-VASc scores to predict risk of stroke and mortality. A retrospective review of all patients with cancer with pre-existing AF presenting from 2008 to 2014 was performed. Outcomes included ischemic stroke and mortality. Prognostic factors were identified with Fine and Gray regression for stroke and Cox proportional hazards analysis for survival. After excluding patients with hemorrhagic strokes, 2,037 patients were analyzed. Genitourinary cancers were the most common (29%) followed by gastrointestinal cancers (18%). Overall, 52% had CHADS2 ≥2. At a median of 6.4 months, 74 patients (3.6%) developed an ischemic stroke. Increased CHADS2 score was associated with stroke (hazard ratio [HR] 1.41, 95% confidence interval [CI] 1.19 to 1.67; p <0.001).

Carotid stenting versus endarterectomy for the treatment of carotid artery stenosis: Contemporary results from a large single center study.

To compare the complication rates associated with carotid endarterectomy (CEA) versus carotid artery stenting (CAS).

Unresolved pulmonary embolism leading to a diagnosis of pulmonary artery sarcoma

Pulmonary artery sarcomas (PAS) are rare tumors with a poor prognosis. They are often misdiagnosed as pulmonary embolism (PE) leading to futile anticoagulation treatment and delay in proper diagnosis. We present a case of a patient who was initially misdiagnosed and anticoagulated for presumed pulmonary embolism. Progressive symptoms and additional imaging led to the diagnosis of intimal pulmonary artery sarcoma for which he underwent surgical resection. This case serves as a reminder to consider pulmonary artery sarcoma in the differential diagnosis of patients with dyspnea and filling defects on CT pulmonary angiogram offering the potential for resection prior to metastasis.

Identifying predictors for bleeding in hospitalized cancer patients: A cohort study

BACKGROUND Bleeding and thrombosis are both major complications of hospitalization in cancer patients. Concern regarding bleeding risk may reduce compliance with thromboprophylaxis. We assessed incidence of major and clinically relevant non-major bleeding (MCRNMB) and identified risk factors associated with in-hospital bleeding risk in hospitalized cancer patients. METHODS We conducted a retrospective cohort study of consecutive adults admitted to general oncology floor at Cleveland Clinic from 11/2012-12/2014 (n=3525). Patients were excluded for bleeding on admission (n=108), age<18 (n=1), non-malignant disease (n=2) and incomplete data (n=56). Data collected included demographics, body mass index (BMI), cancer type, length of stay (LOS), use of anticoagulants and baseline laboratory values (+48h). Univariate risk factors were identified with logistic regression analysis. Multivariable risk factors were identified with stepwise logistic regression and confirmed with bootstrap analysis. RESULTS The study population comprised 3358 patients of whom 69 (2.1%) developed MCRNMB. Median age was 62 (range, 19-98) years and 56% male. Median length of stay was 5 (range, 0-152) days. The majority of bleeding events were either gastrointestinal (GI) (N=23, 33%) or retroperitoneal (N=10, 14%). In multivariable analysis, anemia as the reason for admission (7.78, 95% CI 4.0-15.1, P<0.001), GI cancer site (2.96, 95% CI 1.7-5.2 P<0.001), BMI≥40 (3.08, 95% CI 1.3-2.9, P=0.008) and thrombocytopenia (1.7, 95% CI 1.0-2.9, P=0.05) were predictive. CONCLUSION The incidence of MCRNMB in a population of hospitalized cancer patients was 2.1%. Risk factors at admission included type of cancer and morbid obesity. Improved prediction of bleeding risk can assist physicians in optimizing selection of thromboprophylaxis in this population that is also at increased risk of VTE.

Practicing Communication Skills For Responding to Emotionally Charged Questions

Objective: To assess the impact of a 1-hour communication skills workshop highlighting the “ask more and summarize technique” (AMST) to teach residents an effective way to respond to emotionally charged questions. Methods: From December 2015 to January 2017, residents on an inpatient oncology or palliative medicine rotation attended a mandatory 1-hour workshop on AMST involving a short introduction to the technique followed by skills practice. A survey (S1) was administered to the residents during the first session to assess their self-reported attitudes and practices. A follow-up survey (S2) was e-mailed at the end of the rotation to assess the usefulness of AMST. Results: Twenty-one participants completed S1, and 12 participants completed S2. A total of 62% (13/21) reported the workshop was “very useful.” There was a reported increased frequency of “summarizing back” between surveys (P = .01). Addressing fear and anxiety (75%, 9/12) and responding to patients who were angry/upset (67%, 8/12) were the situations where AMST was found to be the most useful. Fifty-four percent of respondents (7/12) felt they could have used AMST more. Conclusion: A 1-hour communication skills workshop targeting residents on an inpatient oncology or palliative rotation increased the use of summary statements in challenging situations. Practice Implications: A short skills practice workshop can be incorporated into a busy clinical curriculum to achieve changes in trainee behaviors and attitudes.

Clevidipine as a therapeutic and cost-effective alternative to sodium nitroprusside in patients with acute aortic syndromes

Background: Sodium nitroprusside is the preferred agent for the treatment of high blood pressure during acute aortic syndrome if blood pressure remains elevated after heart rate control with beta-blockers. The increasing cost of sodium nitroprusside in the USA led us to assess the efficacy and safety of intravenous clevidipine, a calcium channel blocker with quick onset of action, short half-life and significantly lower costs than sodium nitroprusside, in patients presenting with acute aortic syndrome. Methods: We performed a retrospective chart review of consecutive patients admitted to the Cleveland Clinic Cardiac Intensive Care Unit from 2013–2016 with a diagnosis of acute aortic syndrome. Patients who received intravenous sodium nitroprusside were compared with those receiving intravenous clevidipine. The primary outcome was a significant difference in blood pressure at one, three and six hours. Secondary outcomes included time to achieving blood pressure target and in hospital mortality with rates of hypotension and bradycardia as safety endpoints. Results: A total of 85 patients with suspected acute aortic pathology received clevidipine and 50 received sodium nitroprusside. Clinical and demographic characteristics were similar in both groups, except for a higher incidence of abdominal aortic aneurysm in the clevidipine group and for a trend towards higher use of labetalol in the clevidipine group. There were no significant differences in blood pressure or heart rate at one, three and six hours after starting either infusion. The rates of hypotension, bradycardia and in-hospital mortality did not differ. Time to achieve blood pressure control were also similar between groups. Conclusion: Intravenous clevidipine appears to be a safe and effective alternative to sodium nitroprusside for the management of high blood pressure during acute aortic dissection. In the USA, clevidipine could represent a cost effective therapy providing similar outcomes than sodium nitroprusside.

VENO-ARTERIAL ECMO PROGRAM FOR REFRACTORY CARDIOGENIC SHOCK IN THE CARDIAC INTENSIVE CARE UNIT: FEASIBILITY AND OUTCOME DATA AT A LARGE TERTIARY ACADEMIC CENTER

Background: Veno-Arterial Extracorporeal Membrane Oxygenation (VA-ECMO) is a rescue tool for refractory cardiogenic shock (RCS) and it has traditionally been placed and managed by cardiothoracic surgeons (CTS). A cardiologist managed (CM) VA-ECMO program is an attractive option to optimize care,