Raymond Y. Kwong

2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease: Executive Summary A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons

WRITING COMMITTEE MEMBERS* Stephan D. Fihn, MD, MPH, Chair†; Julius M. Gardin, MD, Vice Chair*‡; Jonathan Abrams, MD‡; Kathleen Berra, MSN, ANP*§; James C. Blankenship, MD*\; Apostolos P. Dallas, MD*†; Pamela S. Douglas, MD*‡; JoAnne M. Foody, MD*‡; Thomas C. Gerber, MD, PhD‡; Alan L. Hinderliter, MD‡; Spencer B. King III, MD*‡; Paul D. Kligfield, MD‡; Harlan M. Krumholz, MD‡; Raymond Y.K. Kwong, MD‡; Michael J. Lim, MD*\; Jane A. Linderbaum, MS, CNP-BC¶; Michael J. Mack, MD*#; Mark A. Munger, PharmD*‡; Richard L. Prager, MD#; Joseph F. Sabik, MD***; Leslee J. Shaw, PhD*‡; Joanna D. Sikkema, MSN, ANP-BC*§; Craig R. Smith, Jr, MD**; Sidney C. Smith, Jr, MD*††; John A. Spertus, MD, MPH*‡‡; Sankey V. Williams, MD*†

Characterization of the Peri-Infarct Zone by Contrast-Enhanced Cardiac Magnetic Resonance Imaging Is a Powerful Predictor of Post–Myocardial Infarction Mortality

Background— Accurate risk stratification is crucial for effective treatment planning after myocardial infarction (MI). Previous studies suggest that the peri-infarct border zone may be an important arrhythmogenic substrate. In this pilot study, we tested the hypothesis that the extent of the peri-infarct zone quantified by contrast-enhanced cardiac magnetic resonance (CMR) is an independent predictor of post-MI mortality. Methods and Results— We studied 144 patients with documented coronary artery disease and abnormal myocardial delayed enhancement (MDE) consistent with MI. A computer-assisted, semiautomatic algorithm quantified the total infarct size and divided it into the core and peri-infarct regions based on signal-intensity thresholds (>3 SDs and 2 to 3 SDs above remote normal myocardium, respectively). The peri-infarct zone was normalized as a percentage of the total infarct size (%MDEperiphery). After a median follow-up of 2.4 years, 29 (20%) patients died. Patients with an above-median %MDEperiphery were at higher risk for death compared with those with a below-median %MDEperiphery (28% versus 13%, log-rank P<0.01). Multivariable analysis showed that left ventricular systolic volume index and %MDEperiphery were the strongest predictors of all-cause mortality (adjusted hazard ratio [HR] for %MDEperiphery, 1.45 per 10% increase; P=0.002) and cardiovascular mortality (adjusted HR, 1.51 per 10% increase; P=0.009). Similarly, after adjusting for age and left ventricular ejection fraction, %MDEperiphery maintained strong and independent associations with all-cause mortality (adjusted HR, 1.42; P=0.005) and cardiovascular mortality (adjusted HR, 1.49; P=0.01). Conclusions— In patients with a prior MI, the extent of the peri-infarct zone characterized by CMR provides incremental prognostic value beyond left ventricular systolic volume index or ejection fraction. Infarct characteristics by CMR may prove to be a unique and valuable noninvasive predictor of post-MI mortality.

Impact of Unrecognized Myocardial Scar Detected by Cardiac Magnetic Resonance Imaging on Event-Free Survival in Patients Presenting With Signs or Symptoms of Coronary Artery Disease

Background— Contrast-enhanced cardiac magnetic resonance imaging (CMR) can determine the extent of myocardial scar from infarction (MI). However, the prognostic significance of unrecognized myocardial scar by CMR in patients without a history of MI is unknown. Methods and Results— One hundred ninety-five patients without a known prior MI underwent CMR for assessment of left ventricular (LV) function and late gadolinium enhancement (LGE). We assessed the prognostic value of LGE and other CMR variables beyond the strongest clinical predictors and built the best overall models for major adverse cardiac events (MACE) and cardiac mortality. During a median follow-up of 16 months, 31 patients (18%) experienced MACE, including 17 deaths. LGE demonstrated the strongest unadjusted associations with MACE and cardiac mortality (hazard ratios of 8.29 and 10.9, respectively; both P<0.0001). Patients in the lowest tertile of LGE-involved myocardium (mean LV mass, 1.4%) experienced a >7-fold increased risk for MACE. By multivariable analyses, LGE was independently associated with MACE beyond the clinical model (P<0.0001) or the clinical model combined with angiographically significant coronary stenosis (P=0.0007), LV ejection fraction (P=0.001), LV end-systolic volume index (P=0.0006), or segmental WMA (P=0.002). LGE remained the strongest predictor selected in the best overall models for MACE and cardiac mortality. Conclusions— Among patients with a clinical suspicion of coronary artery disease but without a history of MI, LGE involving a small amount of myocardium carries a high cardiac risk. In addition, LGE provides incremental prognostic value to MACE and cardiac mortality beyond common clinical, angiographic, and functional predictors.

ACCF/ASNC/ACR/AHA/ASE/SCCT/SCMR/SNM 2009 Appropriate Use Criteria for Cardiac Radionuclide Imaging

Peter Alagona, JR, MD, FACC* Timothy M. Bateman, MD, FACC† Manuel D. Cerqueira, MD, FACC, FAHA, FASNC† James R. Corbett, MD, FACC‡ Anthony J. Dean, MD, FACEP§ Gregory J. Dehmer, MD, FACC, FAHA* Peter Goldbach, MD, FACC Leonie Gordon, MB, CHB¶ Frederick G. Kushner, MD, FACC# Raymond Y. Kwong, MD, MPH, FACC** James Min, MD, FACC†† Miguel A. Quinones, MD, FACC‡‡ R. Parker Ward, MD, FACC† Michael J. Wolk, MD, MACC* Scott H. Yang, MD, PHD, FACC*

Sudden Cardiac Death Prediction and Prevention Report From a National Heart, Lung, and Blood Institute and Heart Rhythm Society Workshop

Despite the significant decline in coronary artery disease (CAD) mortality in the second half of the 20th century,1 sudden cardiac death (SCD) continues to claim 250 000 to 300 000 US lives annually.2 In North America and Europe the annual incidence of SCD ranges between 50 to 100 per 100 000 in the general population.3,–,6 Because of the absence of emergency medical response systems in most world regions, worldwide estimates are currently not available.7 However, even in the presence of advanced first responder systems for resuscitation of out-of-hospital cardiac arrest, the overall survival rate in a recent North American analysis was 4.6%.8 SCD can manifest as ventricular tachycardia (VT), ventricular fibrillation (VF), pulseless electric activity (PEA), or asystole. In a significant proportion of patients, SCD can present without warning or a recognized triggering mechanism. The mean age of those affected is in the mid 60s, and at least 40% of patients will suffer SCD before the age of 65.4 Consequently, enhancement of methodologies for prediction and prevention of SCD acquires a unique and critical importance for management of this significant public health issue. Prediction and prevention of SCD is an area of active investigation, but considerable challenges persist that limit the efficacy and cost-effectiveness of available methodologies.7,9,10 It was recognized early on that optimization of SCD risk stratification will require integration of multi-disciplinary efforts at the bench and bedside, with studies in the general population.11,–,13 This integration has yet to be effectively accomplished. There is also increasing awareness that more investigation needs to be directed toward identification of early predictors of SCD.14 Significant advancements have occurred for risk prediction in the inherited channelopathies15,–,17 and …

Myocardial Fibrosis as an Early Manifestation of Hypertrophic Cardiomyopathy

BACKGROUND Myocardial fibrosis is a hallmark of hypertrophic cardiomyopathy and a proposed substrate for arrhythmias and heart failure. In animal models, profibrotic genetic pathways are activated early, before hypertrophic remodeling. Data showing early profibrotic responses to sarcomere-gene mutations in patients with hypertrophic cardiomyopathy are lacking. METHODS We used echocardiography, cardiac magnetic resonance imaging (MRI), and serum biomarkers of collagen metabolism, hemodynamic stress, and myocardial injury to evaluate subjects with hypertrophic cardiomyopathy and a confirmed genotype. RESULTS The study involved 38 subjects with pathogenic sarcomere mutations and overt hypertrophic cardiomyopathy, 39 subjects with mutations but no left ventricular hypertrophy, and 30 controls who did not have mutations. Levels of serum C-terminal propeptide of type I procollagen (PICP) were significantly higher in mutation carriers without left ventricular hypertrophy and in subjects with overt hypertrophic cardiomyopathy than in controls (31% and 69% higher, respectively; P<0.001). The ratio of PICP to C-terminal telopeptide of type I collagen was increased only in subjects with overt hypertrophic cardiomyopathy, suggesting that collagen synthesis exceeds degradation. Cardiac MRI studies showed late gadolinium enhancement, indicating myocardial fibrosis, in 71% of subjects with overt hypertrophic cardiomyopathy but in none of the mutation carriers without left ventricular hypertrophy. CONCLUSIONS Elevated levels of serum PICP indicated increased myocardial collagen synthesis in sarcomere-mutation carriers without overt disease. This profibrotic state preceded the development of left ventricular hypertrophy or fibrosis visible on MRI. (Funded by the National Institutes of Health and others.)

Detecting Acute Coronary Syndrome in the Emergency Department With Cardiac Magnetic Resonance Imaging

Background—Managing chest pain in the emergency department remains a challenge with current diagnostic strategies. We hypothesized that cardiac MRI could accurately identify patients with possible or probable acute coronary syndrome. Methods and Results—The diagnostic performance of MRI was evaluated in a prospective study of 161 consecutive patients. Enrollment required 30 minutes of chest pain compatible with myocardial ischemia but an ECG not diagnostic of acute myocardial infarction. MRI was performed at rest within 12 hours of presentation and included perfusion, left ventricular function, and gadolinium-enhanced myocardial infarction detection. MRI was interpreted qualitatively but also analyzed quantitatively. The sensitivity and specificity, respectively, for detecting acute coronary syndrome were 84% and 85% by MRI, 80% and 61% by an abnormal ECG, 16% and 95% for strict ECG criteria for ischemia (ST depression or T-wave inversion), 40% and 97% for peak troponin-I, and 48% and 85% for a TIMI risk score ≥3. The MRI was more sensitive than strict ECG criteria for ischemia (P <0.001), peak troponin-I (P <0.001), and the TIMI risk score (P =0.004), and MRI was more specific than an abnormal ECG (P <0.001). Multivariate logistic regression analysis showed MRI was the strongest predictor of acute coronary syndrome and added diagnostic value over clinical parameters (P <0.001). Conclusions—Resting cardiac MRI exhibited diagnostic operating characteristics suitable for triage of patients with chest pain in the emergency department. Performed urgently to evaluate chest pain, MRI accurately detected a high fraction of patients with acute coronary syndrome, including patients with enzyme-negative unstable angina.

Interrelation of Coronary Calcification, Myocardial Ischemia, and Outcomes in Patients With Intermediate Likelihood of Coronary Artery Disease A Combined Positron Emission Tomography/Computed Tomography Study

Background— Although the value of coronary artery calcium (CAC) for atherosclerosis screening is gaining acceptance, its efficacy in predicting flow-limiting coronary artery disease remains controversial, and its incremental prognostic value over myocardial perfusion is not well established. Methods and Results— We evaluated 695 consecutive intermediate-risk patients undergoing combined rest-stress rubidium 82 positron emission tomography (PET) perfusion imaging and CAC scoring on a hybrid PET-computed tomography (CT) scanner. The frequency of abnormal scans among patients with a CAC score ≥400 was higher than that in patients with a CAC score of 1 to 399 (48.5% versus 21.7%, P<0.001). Multivariate logistic regression supported the concept of a threshold CAC score ≥400 governing this relationship (odds ratio 2.91, P<0.001); however, the frequency of ischemia among patients with no CAC was 16.0%, and its absence only afforded a negative predictive value of 84.0%. Risk-adjusted survival analysis demonstrated a stepwise increase in event rates (death and myocardial infarction) with increasing CAC scores in patients with and without ischemia on PET myocardial perfusion imaging. Among patients with normal PET myocardial perfusion imaging, the annualized event rate in patients with no CAC was lower than in those with a CAC score ≥1000 (2.6% versus 12.3%, respectively). Likewise, in patients with ischemia on PET myocardial perfusion imaging, the annualized event rate in those with no CAC was lower than among patients with a CAC score ≥1000 (8.2% versus 22.1%). Conclusions— Although increasing CAC content is generally predictive of a higher likelihood of ischemia, its absence does not completely eliminate the possibility of flow-limiting coronary artery disease. Importantly, a stepwise increase occurs in the risk of adverse events with increasing CAC scores in patients with and without ischemia on PET myocardial perfusion imaging.

Percutaneous Mitral Annuloplasty for Functional Mitral Regurgitation: Results of the CARILLON Mitral Annuloplasty Device European Union Study

Background— Functional mitral regurgitation (FMR), a well-recognized component of left ventricular remodeling, is associated with increased morbidity and mortality in heart failure patients. Percutaneous mitral annuloplasty has the potential to serve as a therapeutic adjunct to standard medical care. Methods and Results— Patients with dilated cardiomyopathy, moderate to severe FMR, an ejection fraction <40%, and a 6-minute walk distance between 150 and 450 m were enrolled in the CARILLON Mitral Annuloplasty Device European Union Study (AMADEUS). Percutaneous mitral annuloplasty was achieved through the coronary sinus with the CARILLON Mitral Contour System. Echocardiographic FMR grade, exercise tolerance, New York Heart Association class, and quality of life were assessed at baseline and 1 and 6 months. Of the 48 patients enrolled in the trial, 30 received the CARILLON device. Eighteen patients did not receive a device because of access issues, insufficient acute FMR reduction, or coronary artery compromise. The major adverse event rate was 13% at 30 days. At 6 months, the degree of FMR reduction among 5 different quantitative echocardiographic measures ranged from 22% to 32%. Six-minute walk distance improved from 307±87 m at baseline to 403±137 m at 6 months (P<0.001). Quality of life, measured by the Kansas City Cardiomyopathy Questionnaire, improved from 47±16 points at baseline to 69±15 points at 6 months (P<0.001). Conclusions— Percutaneous reduction in FMR with a novel coronary sinus-based mitral annuloplasty device is feasible in patients with heart failure, is associated with a low rate of major adverse events, and is associated with improvement in quality of life and exercise tolerance.

Incidence and Prognostic Implication of Unrecognized Myocardial Scar Characterized by Cardiac Magnetic Resonance in Diabetic Patients Without Clinical Evidence of Myocardial Infarction

Background— Silent myocardial infarctions (MIs) are prevalent among diabetic patients and inflict significant morbidity and mortality. Although late gadolinium enhancement (LGE) imaging by cardiac magnetic resonance (CMR) can provide sensitive characterization of myocardial scar, its prognostic significance in diabetic patients without any clinical evidence of MI is unknown. Methods and Results— We performed clinically indicated CMR imaging in 187 diabetic patients who were grouped by the absence (study group, n=109) or presence (control group, n=78) of clinical evidence of MI (clinical history of MI or Q waves on ECG). CMR imaging and follow-up were successful in 107 study patients (98%) and 74 control patients (95%). Cox regression analyses were performed to associate LGE with major adverse cardiovascular events (MACE), including death, acute MI, new congestive heart failure or unstable angina, stroke, and significant ventricular arrhythmias. LGE by CMR was present in 30 of 107 study patients (28%). At a median follow-up of 17 months, 38 of 107 patients (36%) experienced MACE, which included 18 deaths. Presence of LGE was associated with a >3-fold hazards increase for MACE and for death (hazard ratio, 3.71 and 3.61; P<0.001 and P=0.007, respectively). Adjusted to a model that combines patient age, sex, ST or T changes on ECG, and left ventricular end-systolic volume index, LGE maintained a >4-fold hazards increase for MACE (adjusted hazard ratio, 4.13; 95% confidence interval, 1.74 to 9.79; P=0.001). In addition, LGE provided significant prognostic value with MACE and with death adjusted to a diabetic-specific risk model for 5-year events. The presence of LGE was the strongest multivariable predictor of MACE and death by stepwise selection in the study patients. Conclusions— CMR imaging can characterize occult myocardial scar consistent with MI in diabetic patients without clinical evidence of MI. This imaging finding demonstrates strong association with MACE and mortality hazards that is incremental to clinical, ECG, and left ventricular function combined.