Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology.

We conducted a randomized trial involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian centers. Between 1999 and 2004, we assigned 1149 patients to undergo PCI with optimal medical therapy (PCI group) and 1138 to receive optimal medical therapy alone (medical-therapy group). The primary outcome was death from any cause and nonfatal myocardial infarction during a follow-up period of 2.5 to 7.0 years (median, 4.6). Results There were 211 primary events in the PCI group and 202 events in the medicaltherapy group. The 4.6-year cumulative primary-event rates were 19.0% in the PCI group and 18.5% in the medical-therapy group (hazard ratio for the PCI group, 1.05; 95% confidence interval [CI], 0.87 to 1.27; P = 0.62). There were no significant differences between the PCI group and the medical-therapy group in the composite of death, myocardial infarction, and stroke (20.0% vs. 19.5%; hazard ratio, 1.05; 95% CI, 0.87 to 1.27; P = 0.62); hospitalization for acute coronary syndrome (12.4% vs. 11.8%; hazard ratio, 1.07; 95% CI, 0.84 to 1.37; P = 0.56); or myocardial infarction (13.2% vs. 12.3%; hazard ratio, 1.13; 95% CI, 0.89 to 1.43; P = 0.33). Conclusions As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy. (ClinicalTrials.gov number, NCT00007657.)

https://www.medpagetoday.com/upload/2007/4/25/COURAGE1.pdf

Optimal Medical Therapy with or without PCI for Stable Coronary Disease

Coronary atherosclerosis is by far the most frequent cause of ischemic heart disease, and plaque disruption with superimposed thrombosis is the main cause of the acute coronary syndromes of unstable angina, myocardial infarction, and sudden death.1 2 3 4 5 Therefore, for event-free survival, the vital question is not why atherosclerosis develops but rather why, after years of indolent growth, it suddenly becomes complicated by life-threatening thrombosis. The composition and vulnerability of plaque rather than its volume or the consequent severity of stenosis produced have emerged as being the most important determinants for the development of the thrombus-mediated acute coronary syndromes; lipid-rich and soft plaques are more dangerous than collagen-rich and hard plaques because they are more unstable and rupture-prone and highly thrombogenic after disruption.6 This review will explore potential mechanisms responsible for the sudden conversion of a stable atherosclerotic plaque to an unstable and life-threatening atherothrombotic lesion—an event known as plaque fissuring, rupture, or disruption.7 8 

Atherosclerosis is the result of a complex interaction between blood elements, disturbed flow, and vessel wall abnormality, involving several pathological processes: inflammation, with increased endothelial permeability, endothelial activation, and monocyte recruitment9 10 11 12 13 14 ; growth, with smooth muscle cell (SMC) proliferation, migration, and matrix synthesis15 16 ; degeneration, with lipid accumulation17 18 ; necrosis, possibly related to the cytotoxic effect of oxidized lipid19 ; calcification/ossification, which may represent an active rather than a dystrophic process20 21 ; and thrombosis, with platelet recruitment and fibrin formation.1 22 23 Thrombotic factors may play a role early during atherogenesis, but a flow-limiting thrombus does not develop until mature plaques are present, which is why thrombosis often is classified as a complication rather than a genuine component of atherosclerosis. 

### Mature Plaques: Atherosis and Sclerosis 

As the name atherosclerosis implies, mature …

Coronary Plaque Disruption

The purpose of this report is to provide revised standards and guidelines for the exercise testing and training of individuals who are free from clinical manifestations of cardiovascular disease and those with known cardiovascular disease. These guidelines are intended for physicians, nurses, exercise physiologists, specialists, technologists, and other healthcare professionals involved in exercise testing and training of these populations. This report is in accord with the “Statement on Exercise” published by the American Heart Association (AHA).1

These guidelines are a revision of the 1995 standards of the AHA that addressed the issues of exercise testing and training.2 An update of background, scientific rationale, and selected references is provided, and current issues of practical importance in the clinical use of these standards are considered. These guidelines are in accord with the American College of Cardiology (ACC)/AHA Guidelines for Exercise Testing.3

### The Cardiovascular Response to Exercise

Exercise, a common physiological stress, can elicit cardiovascular abnormalities that are not present at rest, and it can be used to determine the adequacy of cardiac function. Because exercise is only one of many stresses to which humans can be exposed, it is more appropriate to call an exercise test exactly that and not a “stress test.” This is particularly relevant considering the increased use of nonexercise stress tests.

### Types of Exercise

Three types of muscular contraction or exercise can be applied as a stress to the cardiovascular system: isometric (static), isotonic (dynamic or locomotory), and resistance (a combination of isometric and isotonic).4,5 Isotonic exercise, which is defined as a muscular contraction resulting in movement, primarily provides a volume load to the left ventricle, and the response is proportional to the size of the working muscle mass and the intensity of exercise. Isometric exercise is defined as a muscular contraction without movement (eg, handgrip) and imposes greater pressure than volume …

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

Angina/Non-ST-Elevation Myocardial Infarction : ACC/AHA 2007 Guidelines for the Management of Patients With Unstable ISSN: 1524-4539 Copyright © 2007 American Heart Association. All rights reserved. Print ISSN: 0009-7322. Online 72514 Circulation is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX doi: 10.1161/CIRCULATIONAHA.107.18194

https://cdr.lib.unc.edu/downloads/vd66w2108

ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction)...

Of 22 randomized trials of rehabilitation with exercise after myocardial infarction (MI), one trial had results that achieved conventional statistical significance. To determine whether or not these studies, in the aggregate, show a significant benefit of rehabilitation after myocardial infarction, we performed an overview of all randomized trials, involving 4,554 patients; we evaluated total and cardiovascular mortality, sudden death, and fatal and nonfatal reinfarction. For each endpoint, we calculated an odds ratio (OR) and 95% confidence interval (95% CI) for the trials combined. After an average of 3 years of follow-up, the ORs were significantly lower in the rehabilitation than in the comparison group: specifically, total mortality (OR = 0.80 [0.66, 0.96]), cardiovascular mortality (OR = 0.78 [0.63, 0.96]), and fatal reinfarction (OR = 0.75 [0.59, 0.95]). The OR for sudden death was significantly lower in the rehabilitation than in the comparison group at 1 year (OR = 0.63 [0.41, 0.97]). The data were compatible with a benefit at 2 (OR = 0.76 [0.54, 1.06]) and 3 years (OR = 0.92 [0.69, 1.23]), but these findings were not statistically significant. For nonfatal reinfarction, there were no significant differences between the two groups after 1 (OR = 1.09 [0.76, 1.57]), 2 (OR = 1.10 [0.82, 1.47]), or 3 years (OR = 1.09 [0.88, 1.34]) of follow-up. The observed 20% reduction in overall mortality reflects a decreased risk of cardiovascular mortality and fatal reinfarction throughout at least 3 years and a reduction in sudden death during the 1st year after infarction and possibly for 2-3 years. With respect to the independent effects of the physical exercise component of cardiac rehabilitation, the relatively small number of "exercise only" trials, combined with the possibility that they may have had a formal or informal nonexercise component precludes the possibility of reaching any definitive conclusion. To do so would require a randomized trial of sufficient size to distinguish between no effect and the most plausible effect based on the results of this overview.

An overview of randomized trials of rehabilitation with exercise after myocardial infarction.

http://rd.springer.com/content/pdf/10.1007%2FBF02598088.pdf

Pilot Results for Unstable Angina in the Elderly

FVC as percent predicted (r, value range, 0.25 to 0.33). Statistical comparisons showed that the BDI score had significantly higher correlations than FVC (percent pre dicted), FEY1 (percent predicted), and Pimax values with physical functioning and role functioning. Multiple linear regression analysis showed that the BDI score was the only statistically significant predictor of role functioning, mental health, and health perceptions for general health status, whereas both the BDI score and FEV1 (percent predicted) were independent predictors of physical functioning and social functioning. Conclusion: Dyspnea ratings influence and predict general health status to a greater extent than do physiologic meas urements in symptomatic patients with COPD. A shift in focus from the pathophysiology of disease to assessment and relief of symptoms may provide more meaningful benefits for the individual patient in terms ofquality of life. This consideration requires that health-care providers use available measuring tools in clinical practice to quantify

Impactof Dyspneaand Physiologic Functionon GeneralHealthStatusin Patientswith ChronicObstructive PulmonaryDisease

OBJECTIVE A prospective regional study was conducted to determine if the observed differences in in-hospital mortality rates associated with coronary artery bypass grafting (CABG) are solely the result of differences in patient case mix. DESIGN-Regional prospective cohort study. Data including patient demographic and historical data, body surface area, cardiac catheterization results, priority of surgery, comorbidity, and status at hospital discharge were collected. This study presents data for 3055 CABG patients between July 1, 1987, and April 15, 1989. SETTING This study includes data from all surgeons performing cardiothoracic surgery in Maine, New Hampshire, and Vermont; the data were collected from five regional medical centers. PATIENTS Data were collected from all consecutive isolated CABG surgery patients during the study period. MAIN OUTCOME MEASURES Crude and adjusted in-hospital mortality rates associated with CABG. MAIN RESULTS The overall crude in-hospital mortality rate for isolated CABG was 4.3%. The rate varied among centers (range, 3.1% to 6.3%) and among surgeons (range, 1.9% to 9.2%). Predictors of in-hospital mortality included increased age, female gender, small body surface area, greater comorbidity, reoperation, poorer cardiac function as indicated by a lower ejection fraction, increased left ventricular end diastolic pressure and emergent or urgent surgery. After adjusting for the effects of potentially confounding variables, substantial and statistically significant variability was observed among medical centers (P = .021) and among surgeons (P = .025). CONCLUSION We conclude that the observed differences in in-hospital mortality rates among institutions and among surgeons in northern New England are not solely the result of differences in case mix as described by these variables and may reflect differences in currently unknown aspects of patient care. Understanding this variation requires a detailed understanding of the processes of care.

A Regional Prospective Study of In-Hospital Mortality Associated With Coronary Artery

Of22randomized trials ofrehabilitation withexercise after myocardial infarction (MI), one trial hadresults that achieved conventional statistical significance. Todetermine whether ornot these studies, intheaggregate, showa significant benefit ofrehabilitation after myocardial infarction, we performed an overview ofallrandomized trials, involving 4,554patients; we evaluated total andcardiovascular mortality, suddendeath, andfatal andnonfatal reinfarction. Foreachendpoint, we calculated anoddsratio (OR)and95%confidence interval (95%CI)for thetrials combined. After an averageof3yearsoffollow-up, theORswere significantly lower intherehabilitation thaninthecomparison group:specifically, total mortality (OR=0.80 [0.66, 0.96]), cardiovascular mortality (OR=0.78 [0.63, 0.96]), andfatal reinfarction (OR=0.75 [0.59, 0.95]). TheOR forsudden death was significantly lowerintherehabilitation thaninthe comparison groupat1year(OR=0.63 [0.41, 0.97]). Thedatawerecompatible witha benefit at2(OR=0.76 [0.54, 1.06]) and3years(OR=0.92 [0.69, 1.23]), butthesefindings were not statistically significant. Fornonfatal reinfarction, there were no significant differences between thetwogroupsafter 1(OR=1.09[0.76, 1.57]), 2(OR=1.10[0.82, 1.47]), or3years(OR=1.09 [0.88, 1.341) offollow-up. Theobserved 20%reduction inoverall mortality reflects adecreased riskofcardiovascular mortality andfatal reinfarction throughout atleast 3 yearsanda reduction insudden deathduring the1styearafter infarction andpossibly for2-3years.With respect totheindependent effects ofthephysical exercise component ofcardiac rehabilitation, therelatively small numberof"exercise only"trials, combined withthepossibility thatthey may havehadaformal orinformal nonexercise component precludes thepossibility ofreaching any definitive conclusion. Todoso wouldrequire a randomized trial ofsufficient size to distinguish between noeffect andthemostplausible effect based on theresults ofthis overview. (Circulation 1989;80:234-244)

Elaine M. Olmstead

Papers

An overview of randomized trials of rehabilitation with exercise after myocardial infarction.

Pilot Results for Unstable Angina in the Elderly

Impactof Dyspneaand Physiologic Functionon GeneralHealthStatusin Patientswith ChronicObstructive PulmonaryDisease

A Regional Prospective Study of In-Hospital Mortality Associated With Coronary Artery

AnOverview ofRandomized Trials of Rehabilitation WithExercise After Myocardial Infarction