Paul Kligfield

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*†

Standardization of M-mode echocardiographic left ventricular anatomic measurements

To improve standardization of echocardiographic left ventricular anatomic measurements, echographic left ventricular dimensions and mass were related to body size indexes, sex, age and blood pressure. Independent normal populations comprised 92 hospital-based subjects (64 women, 28 men) and 133 subjects from a population sample (55 women, 78 men). All measurements of chamber size, wall thickness and mass differed between men and women in both series (p less than 0.01 to p less than 0.001). Left ventricular mass was related most closely to body surface area among measurements of body size (r = 0.37, p less than 0.01 to r = 0.57, p less than 0.001) in all four groups. Indexation by body surface area eliminated sex differences in wall thicknesses and internal dimension, but a significant sex difference in left ventricular mass index persisted (89 +/- 21 g/m2 in men versus 69 + 19 g/m2 in women in the entire series, p less than 0.0001). The 97th percentile of left ventricular mass index was identical in both groups of men (136 and 132 g/m2) and women (112 and 109 g/m2). A highly significant difference in lean body mass, estimated from 24 hour urine creatine excretion, was observed between men and women (58 +/- 15 versus 40 +/- 13 kg, p less than 0.001) and no sex difference existed in left ventricular mass indexed by lean body mass (3.4 +/- 1.3 versus 3.5 +/- 1.5 g/kg). Weak correlations were observed between left ventricular mass/lean body mass and systolic or diastolic blood pressure (r = 0.25, p less than 0.05 and r = 0.28, p less than 0.01, respectively) but not age (18 to 72 years).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiogenesis Gene Therapy Phase I Assessment of Direct Intramyocardial Administration of an Adenovirus Vector Expressing VEGF121 cDNA to Individuals With Clinically Significant Severe Coronary Artery Disease

BACKGROUND Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

Exercise Standards for Testing and Training A Scientific Statement From the American Heart Association

The 2001 version of the exercise standards statement1 has served effectively to reflect the basic fundamentals of ECG–monitored exercise testing and training of both healthy subjects and patients with cardiovascular disease (CVD) and other disease states. These exercise standards are intended for use by physicians, nurses, exercise physiologists and specialists, technologists, and other healthcare professionals involved in exercise testing and training of these populations. Because of an abundance of new research in recent years, a revision of these exercise standards is appropriate. The revision deals with basic fundamentals of testing and training, with no attempt to duplicate or replace current clinical practice guidelines issued by the American Heart Association (AHA), the American College of Cardiology Foundation (ACCF), and other professional societies. It is acknowledged that the published evidence for some recommendations made herein is limited, but the depth of knowledge and experience of the writing group is believed to provide justification for certain …

Assessment of Functional Capacity in Clinical and Research Settings A Scientific Statement From the American Heart Association Committee on Exercise, Rehabilitation, and Prevention of the Council on Clinical Cardiology and the Council on Cardiovascular Nursing

The assessment of functional capacity reflects the ability to perform activities of daily living that require sustained aerobic metabolism. The integrated efforts and health of the pulmonary, cardiovascular, and skeletal muscle systems dictate an individual’s functional capacity. Numerous investigations have demonstrated that the assessment of functional capacity provides important diagnostic and prognostic information in a wide variety of clinical and research settings. This scientific statement, an update of the previously published American Heart Association (AHA) document,1 highlights the major clinical and research applications of functional capacity assessment. For a comprehensive review of exercise testing, the reader is referred to the American College of Cardiology (ACC)/AHA Guidelines for Exercise Testing.2,3 Functional capacity is the ability of an individual to perform aerobic work as defined by the maximal oxygen uptake (Vo2max), that is, the product of cardiac output and arteriovenous oxygen (a−Vo2) difference at physical exhaustion, as shown in the following equation: ![Formula][1] Where HR indicates heart rate and SV indicates stroke volume. Because Vo2max typically is achieved by exercise that involves only about half of the total body musculature, it is generally believed that Vo2max is limited by maximal cardiac output rather than peripheral factors.4 Although Vo2max is measured in liters of oxygen per minute, it usually is expressed in milliliters of oxygen per kilogram of body weight per minute to facilitate intersubject comparisons. In addition, functional capacity, particularly when estimated from the work rate achieved rather than directly measured Vo, is frequently expressed in metabolic equivalents (METs), with 1 MET representing the resting energy expenditure (≈3.5 mL O2 · kg−1 · min−1). In this instance, functional capacity is commonly expressed clinically as a multiple of the resting metabolic rate. Vo2max … [1]: /embed/graphic-1.gif

Improved sex-specific criteria of left ventricular hypertrophy for clinical and computer interpretation of electrocardiograms: validation with autopsy findings.

In a previous study of 543 patients we developed, using echocardiographic left ventricular mass as the reference standard, two new sets of criteria that improve the electrocardiographic diagnosis of left ventricular hypertrophy (LVH). One set of criteria, which is suitable for routine clinical use, detects LVH when the sum of voltage in RaVL + SV3 (Cornell voltage) exceeds 2.8 mV in men and 2.0 mV in women. The second set of criteria, suitable for use in interpretation of the computerized electrocardiogram, uses logistic regression models based on electrocardiographic and demographic variables with independent predictive value for LVH, with separate equations for patients in sinus rhythm and atrial fibrillation. To test these criteria prospectively with use of a different reference standard, antemortem electrocardiograms were compared with left ventricular muscle mass measured at autopsy in 135 patients. Sensitivity of standard Sokolow-Lyon voltage (SLV) criteria (SV1 + RV5 or RV6 greater than 3.5 mV) for LVH was only 22%, but specificity was 100%. The Cornell voltage criteria improved sensitivity to 42%, while maintaining high specificity at 96%. Higher sensitivity (62%) was achieved by use of the new regression criteria, with a specificity of 92%. Overall test accuracy was 60% for SLV criteria, 68% for the Cornell voltage criteria, and 77% for the new regression criteria (p less than .005 vs SLV). We conclude that the Cornell voltage criteria improve the sensitivity of the electrocardiogram for detection of LVH and are easily applicable in clinical practice.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrocardiographic identification of increased left ventricular mass by simple voltage-duration products☆

OBJECTIVES This study was conducted to validate the hypothesis that the product of QRS voltage and duration, as an approximation of the time-voltage area of the QRS complex, can improve the electrocardiographic (ECG) detection of echocardiographically determined left ventricular hypertrophy and to further assess the relative contribution of QRS duration to the ECG detection of hypertrophy. BACKGROUND The ECG identification of left ventricular hypertrophy has been limited by the poor sensitivity of standard voltage criteria alone. However, increases in left ventricular mass can be more accurately related to increases in the time-voltage area of the QRS complex than to changes in QRS voltage or duration alone. METHODS Standard 12-lead ECGs and echocardiograms were obtained for 389 patients, including 116 patients with left ventricular hypertrophy. Simple voltage-duration products were calculated by multiplying Cornell voltage by QRS duration (Cornell product) and the 12-lead sum of voltage by QRS duration (12-lead product). RESULTS In a stepwise logistic regression model that also included Cornell voltage, Sokolow-Lyon voltage, age and gender, QRS duration remained a highly significant predictor of the presence of left ventricular hypertrophy (chi-square 26.9, p < 0.0001). At a matched specificity of 96%, each voltage-duration product significantly improved sensitivity for the detection of left ventricular hypertrophy compared with simple voltage criteria alone (Cornell product 37% vs. Cornell voltage 28%, p < 0.02, and 12-lead product 50% vs. 12-lead voltage 43%, p < 0.005). Sensitivities of both the Cornell product and the 12-lead product were significantly greater than the 27% sensitivity of QRS duration alone (p < 0.01 vs. p < 0.001), the 20% sensitivity of a Romhilt-Estes point score > 4 (p < 0.001) and the 33% sensitivity of the best-fit logistic regression model in this cohort (p < 0.05 vs. p < 0.001). CONCLUSIONS QRS duration is an independent ECG predictor of the presence of left ventricular hypertrophy, and the simple product of either Cornell voltage or 12-lead voltage and QRS duration significantly improves identification of left ventricular hypertrophy relative to other ECG criteria that use QRS duration and voltages in linear combinations.

Electrocardiographic Detection of Left Ventricular Hypertrophy by the Simple QRS Voltage-Duration Product

OBJECTIVES The object of this study was to assess the hypothesis that the product of QRS voltage and duration, as an approximation of the time-voltage integral of the QRS complex, can improve the electrocardiographic (ECG) identification of left ventricular hypertrophy. BACKGROUND Electrocardiographic identification of left ventricular hypertrophy has been limited by the poor sensitivity of standard voltage criteria. However, increases in left ventricular mass can be more closely related to increases in the time-voltage integral of the summed left ventricular dipole than to changes in voltage or QRS duration alone. METHODS Antemortem ECGs were compared with left ventricular mass at autopsy in 220 patients. There were 95 patients with left ventricular hypertrophy, defined by left ventricular mass index > 118 g/m2 in men and > 104 g/m2 in women. The voltage-duration product was calculated as the product of QRS duration and Cornell voltage (Cornell product) and the 12-lead sum of QRS voltage (12-lead product). RESULTS At partitions with a matched specificity of 95%, each voltage-duration product significantly improved sensitivity for the detection of left ventricular hypertrophy when compared with simple voltage criteria alone (Cornell product 51% [48 of 95] vs. Cornell voltage 36% [34 of 95], p < 0.005 and 12-lead product 45% [43 of 95] vs. 12-lead voltage 31% [30 of 95], p < 0.001). Sensitivity of both the Cornell product and 12-lead product was significantly greater than that found for QRS duration alone (28%, 27 of 95, p < 0.005) and the Romhilt-Estes point score (27%, 26 of 95, p < 0.005), and compared favorably with the sensitivity of the complex Cornell multivariate score (44%, 42 of 95, p = NS). Comparison of receiver operating characteristic curves demonstrated that improved performance of the voltage-duration products for the detection of left ventricular hypertrophy was independent of test partition selection. In addition, test performance of the voltage-duration products was not significantly affected by the presence or absence of a bundle branch block. CONCLUSIONS These data suggest that the simple product of either Cornell or 12-lead voltage and QRS duration can identify left ventricular hypertrophy more accurately than can voltage or QRS duration criteria alone and may approach or exceed the performance of more complex multiple regression analyses.

Prevention of Torsade de Pointes in Hospital Settings A Scientific Statement From the American Heart Association and the American College of Cardiology Foundation

Cardiac arrest due to torsade de pointes (TdP) in the acquired form of drug-induced long-QT syndrome (LQTS) is a rare but potentially catastrophic event in hospital settings. Administration of a QT-prolonging drug to a hospitalized population may be more likely to cause TdP than administration of the same drug to an outpatient population, because hospitalized patients often have other risk factors for a proarrhythmic response. For example, hospitalized patients are often elderly people with underlying heart disease who may also have renal or hepatic dysfunction, electrolyte abnormalities, or bradycardia and to whom drugs may be administered rapidly via the intravenous route. In hospital units where patients’ electrocardiograms (ECGs) are monitored continuously, the possibility of TdP may be anticipated by the detection of an increasing QT interval and other premonitory ECG signs of impending arrhythmia. If these ECG harbingers of TdP are recognized, it then becomes possible to discontinue the culprit drug and manage concomitant provocative conditions (eg, hypokalemia, bradyarrhythmias) to reduce the occurrence of cardiac arrest. The purpose of this scientific statement is to raise awareness among those who care for patients in hospital units about the risk, ECG monitoring, and management of drug-induced LQTS. Topics reviewed include the ECG characteristics of TdP and signs of impending arrhythmia, cellular mechanisms of acquired LQTS and current thinking about genetic susceptibility, drugs and drug combinations most likely to cause TdP, risk factors and exacerbating conditions, methods to monitor QT intervals in hospital settings, and immediate management of marked QT prolongation and TdP. The term torsade de pointes was coined by Dessertenne in 1966 as a polymorphic ventricular tachycardia characterized by a pattern of twisting points.1 Several ECG features are characteristic of TdP and are illustrated in Figure 1. First, a change in the amplitude and morphology (twisting) of the QRS …

Arrhythmias in ischemic and nonischemic dilated cardiomyopathy: Prediction of mortality by ambulatory electrocardiography

To test the hypothesis that ventricular arrhythmias detected by ambulatory electrocardiography can stratify mortality risk in patients with ischemic and those with nonischemic dilated cardiomyopathy, clinical, hemodynamic and neurohumoral findings were evaluated in 31 patients. By Kaplan-Meier analysis, the total population had 51% survival at 12 months and 19% survival at 25 months. Subgroups based on peak complexity of ventricular arrhythmias included 9 patients with simple ventricular arrhythmias (peak Lown grades 1 to 3) and 22 patients with complex ventricular arrhythmias (peak Lown grades 4 or 5). Clinical variables and baseline catecholamine levels and renin-angiotensin system activity were similar in the simple and complex arrhythmia subgroups. Patients with simple and those with complex arrhythmias were comparable by all hemodynamic indexes except for a higher mean pulmonary capillary wedge pressure in the complex arrhythmia subgroup. Survival was strikingly related to arrhythmias: mortality was 11% (1 of 9) in the simple ventricular arrhythmia subgroup and 59% (13 of 22) in the complex ventricular arrhythmia subgroup (p less than 0.025 by log-rank test). Twelve patients died suddenly and 2 patients died in circulatory failure, and the risk of death was not affected by the etiology of cardiomyopathy. The higher mortality among the patients with complex arrhythmia could not be explained by the presence of elevated filling pressures alone. Thus, ambulatory electrocardiography can stratify mortality risk among patients with severe ischemic and nonischemic dilated cardiomyopathy.(ABSTRACT TRUNCATED AT 250 WORDS)