Richard J. Kovacs

Management of Patients With Peripheral Artery Disease (Compilation of 2005 and 2011 ACCF/AHA Guideline Recommendations) A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines

Thom W. Rooke, MD, FACC, Chair [†][1] Alan T. Hirsch, MD, FACC, Vice Chair [⁎][2] Sanjay Misra, MD, FAHA, FSIR, Vice Chair [⁎][2],[‡][3] Anton N. Sidawy, MD, MPH, FACS, Vice Chair [§][4] Joshua A. Beckman, MD, FACC, FAHA[⁎][2][∥][5] Laura Findeiss, MD[‡][3] Jafar Golzarian, MD

Management of Patients With Atrial Fibrillation (Compilation of 2006 ACCF/AHA/ESC and 2011 ACCF/AHA/HRS Recommendations) A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines

This document is a compilation of the current American College of Cardiology Foundation/American Heart Association (ACCF/AHA) practice guideline recommendations for atrial fibrillation (AF) from the “ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation),”* the “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline)”† and the “2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Update on Dabigatran).”‡ Updated and new recommendations from 2011 are noted and outdated recommendations have been removed. No new evidence was reviewed, and no recommendations included herein are original to this document. The ACCF/AHA Task Force on Practice Guidelines chooses to republish the recommendations in this format to provide the complete set of practice guideline recommendations in a single resource. ### 1.1. Pharmacological and Nonpharmacological Therapeutic Options #### 1.1.1. Rate Control During AF Class I 1. Measurement of the heart rate at rest and control of the rate using …

Usefulness of Fragmented QRS on a 12-Lead Electrocardiogram in Acute Coronary Syndrome for Predicting Mortality

Electrocardiographic signs of a non-ST elevation myocardial infarction (NSTEMI) are nonspecific, and therefore the diagnosis of NSTEMI during acute coronary syndromes (ACS) depends mainly on cardiac biomarker levels. Fragmented QRS (fQRS) represents myocardial conduction abnormalities due to myocardial infarction (MI) scars in patients with coronary artery disease. However, the time of appearance of fQRS during ACS has not been investigated. It was postulated that in patients with ACS, fQRS on 12-lead electrocardiography occurs within 48 hours of presentation with NSTEMI as well as ST elevation MI and that fQRS predicts mortality. Serial electrocardiograms from 896 patients with ACS (mean age 62 +/- 11 years, 98% men) who underwent cardiac catheterization were studied. Four hundred forty-one patients had MIs, including 337 patients with NSTEMIs, and 455 patients had unstable angina (the control group). Serial electrocardiograms were obtained every 6 to 8 hours during the first 24 hours after the diagnosis of MI and the next day (<48 hours). Fragmented QRS on 12-lead electrocardiography was defined by the presence of single or multiple notches in the R or S wave, without a typical bundle branch block, in > or =2 contiguous leads in 1 of the major coronary artery territories. Fragmented QRS developed in 224 patients (51%) in the MI group and only 17 (3.7%) in the control group (p <0.001). New Q waves developed in 122 (28%), 76 (23%), and 2 (0.4%) patients in the MI, NSTEMI, and control groups, respectively. The sensitivity values of fQRS for ST elevation MI and NSTEMI were 55% and 50%, respectively. The specificity of fQRS was 96%. Kaplan-Meier survival analysis revealed that patients with fQRS had significantly decreased times to death compared to those without fQRS. Fragmented QRS, T-wave inversion, and ST depression were independent predictors of mortality during a mean follow-up period of 34 +/- 16 months. In conclusion, fQRS on 12-lead electrocardiography is a moderately sensitive but highly specific sign for ST elevation MI and NSTEMI. Fragmented QRS is an independent predictor of mortality in patients with ACS.

Docosahexaenoic acid induces apoptosis in Jurkat cells by a protein phosphatase-mediated process.

Docosahexaenoic acid (DHA) is an omega-3 fatty acid under intense investigation for its ability to modulate cancer cell growth and survival. This research was performed to study the cellular and molecular effects of DHA. Our experiments indicated that the treatment of Jurkat cells with DHA inhibited their survival, whereas similar concentrations (60 and 90 microM) of arachidonic acid and oleic acid had little effect. To explore the mechanism of inhibition, we used several measures of apoptosis to determine whether this process was involved in DHA-induced cell death in Jurkat cells. Caspase-3, an important cytosolic downstream regulator of apoptosis, is activated by death signals through proteolytic cleavage. Incubation of Jurkat cells with 60 and 90 microM DHA caused proteolysis of caspase-3 within 48 and 24 h, respectively. DHA treatment also caused the degradation of poly-ADP-ribose polymerase and DNA fragmentation as assayed by flow cytometric TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay. These results indicate that DHA induces apoptosis in Jurkat leukemic cells. DHA-induced apoptosis was effectively inhibited by tautomycin and cypermethrin at concentrations that affect protein phosphatase 1 (PP1) and protein phosphatase 2B (PP2B) activities, respectively, implying a role for these phosphatases in the apoptotic pathway. Okadaic acid, an inhibitor of protein phosphatase 2A, had no effect on DHA-induced apoptosis. These results suggest that one mechanism through which DHA may control cancer cell growth is through apoptosis involving PP1/PP2B protein phosphatase activities.

Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Preamble, Principles, and General Considerations : A Scientific Statement From the American Heart Association and American College of Cardiology

This document addresses medical issues related to trained athletes with cardiovascular abnormalities. The objective is to present, in a readily useable format, consensus recommendations and guidelines principally addressing criteria for eligibility and disqualification from organized competitive sports for the purpose of ensuring the health and safety of young athletes. Recognizing certain medical risks imposed on athletes with cardiovascular disease, it is our aspiration that the recommendations that constitute this document will serve as a useful guide to the practicing community for clinical decision making. The ultimate goal is prevention of sudden death in the young, although it is also important not to unfairly or unnecessarily remove people from a healthy athletic lifestyle or competitive sports (that may be physiologically and psychologically intertwined with good quality of life and medical well-being) because of fear of litigation. It is our goal that the recommendations in this document, together with sound clinical judgment, will lead to a healthier, safer playing field for young competitive athletes. There have been 3 prior documents, all sponsored by the American College of Cardiology (ACC),1–3 that addressed eligibility and disqualification criteria for competitive athletes with cardiovascular diseases: Bethesda Conferences 16 (1985), 26 (1994), and 36 (2005), published and used over a 30-year period. Each of the 3 initiatives (and the present American Heart Association (AHA)/ACC scientific statement) were driven by the tenet that young trained athletes with underlying cardiovascular abnormalities are likely at some increase in risk for sudden cardiac death (usually on the athletic field) compared to nonathletes or competitive athletes without cardiovascular disease.4–8 All 3 Bethesda Conferences and the present derived AHA/ACC document provide expert consensus recommendations. These insights use (1) the experience and expertise of the panelists (ie, individual and collective judgments, using the “art of medicine”) and (2) …

Eligibility and Disqualification Recommendations for Competitive Athletes with Cardiovascular Abnormalities: Task Force 1: Classification of Sports: Dynamic, Static, and Impact: A Scientific Statement from the American Heart Association and American College of Cardiology

*On behalf of the American Heart Association Ele Arrhythmias Committee of the Council on Clinical C Cardiovascular Disease in the Young, Council o Stroke Nursing, Council on Functional Genomi Biology, and the American College of Cardiology. The American Heart Association and the Amer ology make every effort to avoid any actual or interest that may arise as a result of an outs personal, professional, or business interest of a m panel. Specifically, all members of the writing g complete and submit a Disclosure Questionnaire lationships that might be perceived as real or interest. The Preamble and other Task Force r ceedings are available online at www.onlinejacc.o 2015;66:2343–9; 2356–61; 2362–71; 2372–84; 2385– 2406–11; 2412–23; 2424–8; 2429–33; 2434–8; 24 2447–50). This statement was approved by the Americ Science Advisory and Coordinating Committee o the American Heart Association Executive Commi and by the American College of Cardiology Bo Executive Committee on June 3, 2015. Aaron L. Baggish, MD, FACC* Richard J. Kovacs, MD, FAHA, FACC* Mark S. Link, MD, FACC*

Development and Validation of a Risk Score to Predict QT Interval Prolongation in Hospitalized Patients

Background—Identifying hospitalized patients at risk for QT interval prolongation could lead to interventions to reduce the risk of torsades de pointes. Our objective was to develop and validate a risk score for QT prolongation in hospitalized patients. Methods and Results—In this study, in a single tertiary care institution, consecutive patients (n=900) admitted to cardiac care units comprised the risk score development group. The score was then applied to 300 additional patients in a validation group. Corrected QT (QTc) interval prolongation (defined as QTc>500 ms or an increase of >60 ms from baseline) occurred in 274 (30.4%) and 90 (30.0%) patients in the development group and validation group, respectively. Independent predictors of QTc prolongation included the following: female (odds ratio, 1.5; 95% confidence interval, 1.1–2.0), diagnosis of myocardial infarction (2.4 [1.6–3.9]), sepsis (2.7 [1.5–4.8]), left ventricular dysfunction (2.7 [1.6–5.0]), administration of a QT-prolonging drug (2.8 [2.0–4.0]), ≥2 QT-prolonging drugs (2.6 [1.9–5.6]), or loop diuretic (1.4 [1.0–2.0]), age >68 years (1.3 [1.0–1.9]), serum K+ <3.5 mEq/L (2.1 [1.5–2.9]), and admitting QTc >450 ms (2.3; confidence interval [1.6–3.2]). Risk scores were developed by assigning points based on log odds ratios. Low-, moderate-, and high-risk ranges of 0 to 6, 7 to 10, and 11 to 21 points, respectively, best predicted QTc prolongation (C statistic=0.823). A high-risk score ≥11 was associated with sensitivity=0.74, specificity=0.77, positive predictive value=0.79, and negative predictive value=0.76. In the validation group, the incidences of QTc prolongation were 15% (low risk); 37% (moderate risk); and 73% (high risk). Conclusions—A risk score using easily obtainable clinical variables predicts patients at highest risk for QTc interval prolongation and may be useful in guiding monitoring and treatment decisions.

Prevalence of QT Interval Prolongation in Patients Admitted to Cardiac Care Units and Frequency of Subsequent Administration of QT Interval-Prolonging Drugs

BackgroundCardiac arrest due to torsades de pointes (TdP) is a rare but catastrophic event in hospitals. Patients admitted to cardiac units are at higher risk of drug-induced QT interval prolongation and TdP, due to a preponderance of risk factors. Few data exist regarding the prevalence of QT interval prolongation in patients admitted to cardiac units or the frequency of administering QT interval-prolonging drugs to patients presenting with QT interval prolongation.ObjectiveThe aim of this study was to determine the prevalence of Bazett’s-corrected QT (QTc) interval prolongation upon admission to cardiac units and the proportion of patients presenting with QTc interval prolongation who are subsequently administered QT interval-prolonging drugs during hospitalization.MethodsThis was a prospective, observational study conducted over a 1-year period (October 2008–October 2009) in 1159 consecutive patients admitted to two cardiac units in a large urban academic medical centre located in Indianapolis, IN, USA. Patients were enrolled into the study at the time of admission to the hospital and were followed daily during hospitalization. Exclusion criteria were age <18 years, ECG rhythm of complete ventricular pacing, and patient designation as ‘outpatient’ in a bed and/or duration of stay <24 hours. Data collected included demographic information, past medical history, daily progress notes, medication administration records, laboratory data, ECGs, telemetry monitoring strips and diagnostic reports. All patients underwent continuous cardiac telemetry monitoring and/or had a baseline 12-lead ECG obtained within 4 hours of admission. QT intervals were determined manually from lead II of 12-lead ECGs or from continuous lead II telemetry monitoring strips. QTc interval prolongation was defined as ≥470 ms for males and ≥480 ms for females. In both males and females, QTc interval >500 ms was considered abnormally high. A medication was classified as QT interval-prolonging if there were published data indicating that the drug causes QT interval prolongation and/or TdP. Study endpoints were (i) prevalence of QTc interval prolongation upon admission to the Cardiac Medical Critical Care Unit (CMCCU) or an Advanced Heart Care Unit (AHCU); (ii) proportion of patients admitted to the CMCCU/AHCU with QTc interval prolongation who subsequently were administered QT interval-prolonging drugs during hospitalization; (iii) the proportion of these higher-risk patients in whom TdP risk factor monitoring was performed; (iv) proportion of patients with QTc interval prolongation who subsequently received QT-prolonging drugs and who experienced further QTc interval prolongation.ResultsOf 1159 patients enrolled, 259 patients met exclusion criteria, resulting in a final sample size of 900 patients. Patient characteristics: mean (± SD) age, 65 ±15 years; female, 47%; Caucasian, 70%. Admitting diagnoses: heart failure (22%), myocardial infarction (16%), atrial fibrillation (9%), sudden cardiac arrest (3%). QTc interval prolongation was present in 27.9% of patients on admission; 18.2% had QTc interval >500ms. Of 251 patients admitted with QTc interval prolongation, 87 (34.7%) were subsequently administered QT interval-prolonging drugs. Of 166 patients admitted with QTc interval >500ms, 70 (42.2%) were subsequently administered QT interval-prolonging drugs; additional QTc interval prolongation ≥60 ms occurred in 57.1% of these patients.ConclusionsQTc interval prolongation is common among patients admitted to cardiac units. QT interval-prolonging drugs are commonly prescribed to patients presenting with QTc interval prolongation.

Cytochrome P450 3A5 Genotype is Associated with Verapamil Response in Healthy Subjects

We hypothesized that CYP3A5 genotype contributes to the interindividual variability in verapamil response. Healthy subjects (n=26) with predetermined CYP3A5 genotypes were categorized as expressers (at least one CYP3A5*1 allele) and nonexpressers (subjects without a CYP3A5*1 allele). Verapamil pharmacokinetics and pharmacodynamics were determined after 7 days of dosing with 240 mg daily. There was a significantly higher oral clearance of R‐verapamil (165.1±86.4 versus 91.2±36.5 l/h; P=0.009) and S‐verapamil (919.4±517.4 versus 460.2±239.7 l/h; P=0.01) in CYP3A5 expressers compared to nonexpressers. Consequently, CYP3A5 expressers had significantly less PR‐interval prolongation (19.5±12.3 versus 44.0±19.4 ms; P=0.0004), and had higher diastolic blood pressure (69.2±7.5 versus 61.6±5.1 mm Hg; P=0.036) than CYP3A5 nonexpressers after 7 days dosing with verapamil. CYP3A5 expressers display a greater steady‐state oral clearance of verapamil and may therefore experience diminished pharmacological effect of verapamil due to a greater steady state oral clearance.

Eligibility and Disqualification Recommendations for Competitive Athletes with Cardiovascular Abnormalities: Task Force 7: Aortic Diseases, Including Marfan Syndrome: A Scientific Statement from the American Heart Association and American College of Cardiology

*On behalf of the American Heart Association Electrocardiography and Arrhythmias Committee of the Council on Clinical Cardiology, Council on Cardiovascular Disease in the Young, Council on Cardiovascular and Stroke Nursing, Council on Functional Genomics and Translational Biology, and the American College of Cardiology. The American Heart Association and the American College of Cardiology make every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. The Preamble and other Task Force reports for these proceedings are available online at www.onlinejacc.org (J Am Coll Cardiol 2015;66:2343–9; 2350–5; 2356–61; 2362–71; 2372–84; 2385–92; 2393–7; 2406–11; 2412–23; 2424–8; 2429–33; 2434–8; 2439–43; 2444–6; and 2447–50). This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on June 24, 2015, and the American Heart Association Executive Committee on July 22, 2015, and by the American College of Cardiology Board of Trustees and Executive Committee on June 3, 2015. The online-only Data Supplement is available with this article at http:// jaccjacc.acc.org/Clinical_Document/TF_7_Aortic_Z-score_calculator_Task_ Force_7_Braverman.xlsx. Kevin M. Harris, MD, FACC* Richard J. Kovacs, MD, FAHA, FACC* Barry J. Maron, MD, FACC*