Inside This Issue STATE-OF-THE-ART PAPER STATE-OF-THE-ART PAPER Obstructive Sleep Apnea in Obesity and Metabolic Syndrome 569 Luciano F. Drager, Sônia M. Togeiro, Vsevolod Y. Polotsky, Geraldo Lorenzi-Filho Obstructive sleep apnea (OSA) is an under-diagnosed clinical condition with a significant projected increase in its prevalence tied to the obesity epidemic. In this state-of-the-art paper, Drager and colleagues review the anatomical and functional factor that predispose obese patients to OSA. They review the evidence that supports the concept that OSA exacerbates the cardiometabolic risk attributed to obesity and the metabolic syndrome. They provide evidence that treatment can improve several components of the metabolic syndrome. They conclude that recognition and treatment of OSA may decrease the cardiovascular risk in obese and metabolic syndrome patients. CLINICAL RESEARCH CORONARY ARTERY DISEASE Prasugrel 5 mg the Very Elderly Coronary Patients 577 David Erlinge, Paul A. Gurbel, Stefan James, Tomas L. Lindahl, Peter Svensson, Jurrien M. Ten Berg, David P. Foley, Henrik Wagner, Patricia B. Brown, Junxiang Luo, Chunmei Zhou, Brian A. Moser, Joseph A. Jakubowski, David S. Small, Kenneth J. Winters, Dominick J. Angiolillo This study assesses the pharmacodynamic (PD) response for reduced 5-mg maintenance dose of prasugrel in very elderly (VE) (75 years of age) patients. PD and active metabolite pharmacokinetics with prasugrel 5-mg and 10-mg and clopidogrel 75-mg in a 3-period study (12 days each) in VE (n ¼ 73) or non-elderly (NE) (45 and <65 years of age) (n ¼ 82) and stable coronary artery disease (CAD) patients with a background of aspirin were studied. The primary comparison was noninferiority of maximum platelet aggregation (MPA) comparing the median for prasugrel 5-mg in VE versus the 75th percentile for prasugrel 10-mg in NE. Prasugrel 5-mg in the VE met the pharmacodynamic noninferiority criteria versus prasugrel 10-mg in NE. MPA was significantly lower (57 14%) than clopidogrel (63 14%, p ¼ 0.001) in VE but higher than prasugrel 10-mg in NE (46 12%). The study shows that in aspirin-treated stable CAD patients, prasugrel 5-mg in the VE attenuates platelet inhibition and was noninferior to prasugrel 10-mg in the NE with significantly better PD response and fewer poor responders compared with clopidogrel 75-mg in VE. AUGUST 13, 2013 VOLUME 62, NO.7 JOURNAL of the AMERICAN COLLEGE of CARDIOLOGY (continued on page A-32)
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AUGUST 13, 2013VOLUME 62, NO. 7
JOURNAL of the AMERICAN COLLEGE of CARDIOLOGY
Inside This Issue
STATE-OF-THE-ART PAPER STATE-OF-THE-ART PAPER
Obstructive Sleep Apnea in Obesity and Metabolic Syndrome
569
Luciano F. Drager, Sônia M. Togeiro, Vsevolod Y. Polotsky, Geraldo Lorenzi-Filho
Obstructive sleep apnea (OSA) is an under-diagnosed clinical condition with a significantprojected increase in its prevalence tied to the obesity epidemic. In this state-of-the-art paper,Drager and colleagues review the anatomical and functional factor that predispose obesepatients to OSA. They review the evidence that supports the concept that OSA exacerbatesthe cardiometabolic risk attributed to obesity and the metabolic syndrome. They provideevidence that treatment can improve several components of the metabolic syndrome. Theyconclude that recognition and treatment of OSA may decrease the cardiovascular risk inobese and metabolic syndrome patients.
CLINICAL RESEARCH
CORONARY ARTERY DISEASE
Prasugrel 5 mg the Very Elderly Coronary Patients
577
David Erlinge, Paul A. Gurbel, Stefan James, Tomas L. Lindahl, Peter Svensson, Jurrien M. Ten Berg,
David P. Foley, Henrik Wagner, Patricia B. Brown, Junxiang Luo, Chunmei Zhou, Brian A. Moser,
Joseph A. Jakubowski, David S. Small, Kenneth J. Winters, Dominick J. Angiolillo
This study assesses the pharmacodynamic (PD) response for reduced 5-mg maintenance doseof prasugrel in very elderly (VE) (�75 years of age) patients. PD and active metabolitepharmacokinetics with prasugrel 5-mg and 10-mg and clopidogrel 75-mg in a 3-period study(12 days each) in VE (n ¼ 73) or non-elderly (NE) (�45 and <65 years of age) (n ¼ 82) andstable coronary artery disease (CAD) patients with a background of aspirin were studied. Theprimary comparison was noninferiority of maximum platelet aggregation (MPA) comparingthe median for prasugrel 5-mg in VE versus the 75th percentile for prasugrel 10-mg in NE.Prasugrel 5-mg in the VE met the pharmacodynamic noninferiority criteria versus prasugrel10-mg in NE. MPA was significantly lower (57 � 14%) than clopidogrel (63 � 14%,p ¼ 0.001) in VE but higher than prasugrel 10-mg in NE (46 � 12%). The study shows thatin aspirin-treated stable CAD patients, prasugrel 5-mg in the VE attenuates plateletinhibition and was noninferior to prasugrel 10-mg in the NE with significantly better PDresponse and fewer poor responders compared with clopidogrel 75-mg in VE.
Dalane W. Kitzman, Peter H. Brubaker, David M. Herrington, Timothy M. Morgan,
Kathryn P. Stewart, W. Gregory Hundley, Abdelhamed Abdelhamed, Mark J. Haykowsky
Elderly patients with heart failure with preserved ejection fraction (HFPEF) have severelyreduced peak exercise oxygen consumption (VO2) that improves with exercise training (ET).The mechanism of the improvement is unclear. Kitzman and colleagues evaluate the effectsof endurance exercise training (ET) on endothelial dependent flow-mediated arterial dilation(FMD) and coronary artery stiffness and their potential contribution to the training relatedincrease in peak exercise VO2. A total of 63 HFPEF patients were randomized to 16 weeks ofET. ET increased peak VO2 (ET: 15.8 � 3.3 ml/kg/min vs. controls: 13.8 � 3.1 ml/kg/min,p ¼ 0.0001) and quality of life. Brachial artery FMD, carotid artery distensibility, and restingleft ventricular systolic and diastolic function were unchanged by ET. Kitzman and colleaguesconclude that mechanisms (other than those studied), such as enhanced skeletal muscleperfusion and/or oxygen utilization, may be responsible for ET-mediated increase in peakVO2 in older HFPEF patients.
Editorial Comment: Steven J. Keteyian, p. 593
HEART RHYTHM DISORDERS
Prognostic of Nonsustained Ventricular Tachycardia in Asymptomatic Volunteers
595
Joseph E. Marine, Veena Shetty, Grant V. Chow, Jeanette G. Wright, Gary Gerstenblith, Samer S. Najjar,
Edward G. Lakatta, Jerome L. Fleg
Marine and colleagues investigated the clinical predictors and prognostic significance ofexercise induced non-sustained ventricular tachycardia (NSVT) in a large population ofasymptomatic volunteers. A total of 2,099 subjects (mean age 52 years, 52.2% male) from theBLSA study and free of known cardiovascular disease were included. A total of 79 (37%)subjects developed NSVT with exercise on at least 1 test with a mean duration of 3 beats(�5 beats in 84%) and median rate of 175 beats/min. Subjects with NSVT were older andmore likely to be male and have baseline electrocardiographic abnormalities or ischemicST-segment elevation changes with exercise. Over a mean follow-up of 13.5 � 7.7 years, 518deaths (24.6%) occurred, however, after multivariable adjustment, exercise-induced NSVTwas not significantly associated with total mortality. The study concludes that exercise-induced NSVT occurred in nearly 4% of asymptomatic adults and did not independentlyincrease risk of total mortality.
Standardizing Survival for Hospital Cardiac Arrest
601
Paul S. Chan, Robert A. Berg, John A. Spertus, Lee H. Schwamm, Deepak L. Bhatt,
Gregg C. Fonarow, Paul A. Heidenreich, Brahmajee K. Nallamothu, Fengming Tang,
Raina M. Merchant, for the AHA GWTG-Resuscitation Investigators
A foundation with which hospitals can improve quality is to be able to benchmark their risk-adjusted performance against other hospitals. A total of 48,841 patients from 272 hospitalswith at least 10 cardiac arrests admitted between 2007 and 2010 and with an in-hospitalcardiac arrest were included (Get With the Guidelines [GWTG]-Resuscitation Registry). Amodel for survival to hospital discharge and calculate risk-standardized survival rate (RSCRs)was derived (two-third of patients) and validated (one-third of patients). The final modelconsisted of 9 variables including age, initial cardiac arrest rhythm, hospital location of arrest,hypotension, septicemia, metastatic or hematologic malignancy, hepatic insufficiency, andrequirements for mechanical ventilation or intravenous vasopressor prior to cardiac arrest.The survival rate was 21.0% and 21.2% for the derivation and validations cohorts,respectively. After risk standardization, 143 (52.6%) of hospitals had at least a 10% positive ornegative absolute change in percentile rank and 50 (23.2%) had a �20% absolute change inpercentile rank. The authors derived and validated a model to risk-standardize hospital ratesof survival for in-hospital cardiac arrest and use of this model can allow for comparison ofhospital resuscitation outcomes as a foundation for quality assessment and improvement.
HEART RHYTHM DISORDERS
Sleep Apnea and Cardiac Death
610
Apoor S. Gami, Eric J. Olson, Win K. Shen, R. Scott Wright, Karla V. Ballman, Dave O. Hodge,
Regina M. Herges, Daniel E. Howard, Virend K. Somers
The authors investigate the risk of sudden cardiac death (SCD) associated with obstructivesleep apnea (OSA). A total of 10,701 consecutive adults undergoing first diagnosispolysomnogram between July 1987 and July 2003 were followed for up to 15 years. SCD wasbest predicted by age >60 years (HR: 5.53), apnea-hypopnea index 20 (HR: 2.93), andnocturnal O2sat 78% (HR: 2.60, all p < 0.0001). The authors concluded that in thispopulation referred for polysomnography, OSA predicted sudden death and magnitude ofrisk was predicted by multiple parameters characterizing OSA severely. Nocturnal hypoxiastrongly predicted SCD independent of well-established risk factors.
Myocardial Infarction on Post-Mortem Cardiac 3-T MRI
617
Christian Jackowski, Nicole Schwendener, Silke Grabherr, Anders Persson
The authors investigate if post-mortem magnetic resonance imaging (pmMRI) can detectmyocardial infarction and hypointensity in T2-weighted images as possible myocardialappearance for arrhythmic sudden cardiac death. A total of 136 human forensic corpseunderwent cardiac 3-T pmMR studies prior to forensic autopsy. In 76 cases, a total of 124myocardial lesions were detected by pmMRI (chronic 25, subacute 16, acute 30, and peracute53) with excellent correlation to autopsy findings. Peracute infarctions (age range: minutes toapproximately 1 h) were not visible at macroscopic autopsy and histology but verified bytargeted histological investigations in 62.3%. The authors conclude that 3-T pmMRIvisualizes chronic, subacute, and acute myocardial infarction in situ. In peracute infarctions(as a possible source of sudden cardiac death) it demonstrates affected myocardial areasinvisible at autopsy.
Elevation of cardiac troponin T (cTnT) is frequently observed in heart failure (HF) patientsfree of coronary artery disease although the mechanism remains unclear. Transcardiac high-sensitive cTnT and plasma B-type natriuretic peptide (BNP) release and coronary flowreserve (CRF) using intracoronary Doppler guidewire were measured. Transcardiacdifference was the difference between coronary sinus (CS) and aortic root (AO), and cTnTlevels (DcTnT [CS-AO]) and BNP levels (DBNP [CS-AO]), respectively. Regressionanalysis identified left ventricular end-diastolic pressure as an independent parameter thatcorrelated with DcTnT (CS-AO). Coronary microvascular dysfunction diagnosed by CFR<2.0 was observed in 18 of 58 HF patients. DcTnT (CS-AO) was highest in patients withcoronary microvascular dysfunction (4.8 [2.0 to 8.1] mg/l) than those without (2.0 [1.2 to4.6] mg/l; p ¼ 0.04). The authors conclude that cTnT release from failing myocardiumcorrelate with diastolic load and coronary microvascular dysfunction in nonischemic HFpatients.
