L. Howard Hartley

Ambient Pollution and Blood Pressure in Cardiac Rehabilitation Patients

Background—Multiple studies have demonstrated a consistent association between ambient particulate air pollution and increased risk of hospital admissions and deaths for cardiovascular causes. We investigated the associations between fine particulate pollution (PM2.5) and blood pressure during 631 repeated visits for cardiac rehabilitation in 62 Boston residents with cardiovascular disease. Methods and Results—Blood pressure, cardiac risk factor, and exercise data were abstracted from records of rehabilitation visits between 1999 and 2001. We applied mixed-effect models, controlling for body mass index, age, gender, number of visits, hour of day, and weather variables. For an increase from the 10th to the 90th percentile in mean PM2.5 level during the 5 days before the visit (10.5 &mgr;g/m3), there was a 2.8-mm Hg (95% CI, 0.1 to 5.5) increase in resting systolic, a 2.7-mm Hg (95% CI, 1.2 to 4.3) increase in resting diastolic, and a 2.7-mm Hg (95% CI, 1.0 to 4.5) increase in resting mean arterial blood pressure. The mean PM2.5 level during the 2 preceding days (13.9 &mgr;g/m3) was associated with a 7.0-mm Hg (95% CI, 2.3 to 12.1) increase in diastolic and a 4.7-mm Hg (95% CI, 0.5 to 9.1) increase in mean arterial blood pressure during exercise in persons with resting heart rate ≥70 bpm, but it was not associated with an increase in blood pressure during exercise in persons with heart rate <70 bpm. Conclusions—In patients with preexisting cardiac disease, particle pollution may contribute to increased risk of cardiac morbidity and mortality through short-term increases in systemic arterial vascular narrowing, as manifested by increased peripheral blood pressure.

A critical pathway for management of patients with acute chest pain who are at low risk for myocardial ischemia : Recommendations and potential impact

Acute chest pain is a common and costly problem [1, 2]. Various strategies have been evaluated to increase the efficiency of care for persons with acute chest pain, including reducing the number of inappropriate admissions, expediting transfer from intensive care units to intermediate-care units, or disseminating practice guidelines [1, 3-6]. Such interventions have achieved only modest success [5]. Many institutions are developing innovative strategies to address this problem [7, 8], including immediate exercise treadmill testing [9, 10], early noninvasive imaging [11, 12], use of new markers for myocardial injury [13], and creation of emergency departments for chest pain [6, 14, 15]. Although some of these strategies have been evaluated [6], few data describe the expected or actual effects of most strategies on clinical outcomes or resource use. Nevertheless, short observation protocols for patients with chest pain are being implemented throughout the United States [14, 15]. Previous studies [16-18] addressed whether a patient who presents to an emergency department has unstable angina or acute myocardial infarction. An emerging paradigm instead asks whether it is safe to discharge the patient or whether it is safe for the patient to undergo an exercise treadmill test. This paradigm focuses attention on the safety of the management strategy rather than on the diagnosis because diagnosis often cannot be conclusively determined in the time frame available [19, 20]. We developed a comprehensive, evidence-based approach to management of patients with acute chest pain in the emergency department. We used published investigations to define the strategy and resolved differences or gaps in the literature by consensus of local experts. Quality management techniques were incorporated by using critical pathways to reduce variation in patient care [21-23]. Critical pathways define and manage the timing and sequence of the rate-limiting steps in the process of providing health care [21]. Management of this process includes simultaneously monitoring and giving feedback to providers of information about achievement of expected and unexpected patient outcomes. Health care providers can then adjust patient management to prevent or modify unexpected outcomes. Critical pathways are distinct from clinical guidelines and algorithms [21]. Clinical guidelines define the appropriateness of care [21], and clinical algorithms define the step-by-step procedure for providing care, usually with conditional logic (if-then statements) [22]. Neither guidelines nor algorithms use simultaneous management of the process of care delivery to monitor compliance with recommended practice and identify opportunities for improvement. The specific goals of our critical pathway were to reduce admission rates and total days of hospitalization among patients who were at low risk for complications of ischemic disease and to limit adverse outcomes. To address these goals, we developed an explicit sequence of care and recommended the daily availability of early exercise treadmill testing in low-risk patients. We retrospectively applied the criteria of the critical pathway to data from a large cohort of patients with acute chest pain to assess the potential effects of implementation of the pathway on resource use and adverse outcomes. Methods The Critical Pathway Development We developed the critical pathway on the basis of scientific evidence and the experience of local opinion leaders and physician-investigators with long-standing interest in the topic. Relevant articles from the medical literature were identified by doing a MEDLINE search for English-language articles from 1990 to 1995 using the keywords chest pain, unstable angina, and myocardial infarction combined with randomized, controlled trial (PT) and cohort study. All identified papers were reviewed for relevance. Study quality was not explicitly evaluated because existing quality scales either have not been validated [24] or do not consider the value of Bayesian analyses [25]. Relevant articles were supplemented with a national clinical practice guideline for management of unstable angina [26]. Opinion leaders included staff emergency department physicians, staff cardiologists, and a cardiologist affiliated with a large health maintenance organization. An informal nominal group process was used to reach consensus [27]. The process consisted of a series of meetings and draft documents. Team members contributed recommendations based on the medical literature, and group discussion clarified and evaluated each recommendation. Team members independently reviewed the documents between meetings to comment on the work in progress. Consensus was achieved by unanimity. Content The flow of the critical pathway is shown in Figure 1. The pathway consisted of flowsheets with instructions and preprinted orders to facilitate use. Instructions provided suggestions to the end-user (usually an emergency department physician) about what information may facilitate decision making. The preprinted orders were designed to be selected by the physician in response to the instructions. Figure 1. Critical pathway for management of patients with acute chest pain who are at low risk for myocardial ischemia. Variance tracking was incorporated into the critical pathway to monitor the length of time that patients were present in the emergency department and the disposition and clinical outcomes of patients enrolled in the pathway [28, 29]. Time goals were suggested for the performance of key elements of the care process. Failure to meet these performance standards or occurrence of other explicit events were considered key variances, which may be reviewed later in aggregate to facilitate improvement of quality of care. We recommended recording the time interval between arrival in the emergency department and completion of the following tasks: 1) obtaining an electrocardiogram, 2) deciding to perform exercise treadmill testing, 3) obtaining the results of exercise treadmill testing, and 4) deciding to admit or discharge the patient. Eligibility Four clinical categories of patients were ineligible for enrollment in the critical pathway: patients with ongoing chest pain, patients with congestive heart failure present at initial clinical examination, patients with ischemia or injury present on the initial electrocardiogram (defined as ST-segment elevation, ST-segment depression, or T-wave inversion suggestive of ischemia or infarction and not known to be old), and patients judged by physicians to be at sufficiently low risk for myocardial ischemia to be discharged. At Brigham and Womens Hospital, Boston, Massachusetts, patients with active ischemia or infarction are treated by following other protocols [30]. Patients who clearly do not have ischemic chest pain are considered for direct discharge from the emergency department, as recommended by a national consensus panel [26]. Patients with left bundle-branch block and other electrocardiographic changes who might not be candidates for exercise electrocardiography were not explicitly excluded from eligibility for the pathway; patients could undergo alternative tests, such as exercise echocardiography or nuclear medicine studies, assuming that these technologies were available. Data Clinical, demographic, and outcome data were previously collected for a prospective cohort of consenting patients 30 years of age or older from the ongoing Chest Pain Study at Brigham and Womens Hospital [5, 31, 32]. These patients presented to the emergency department with chest pain and had no history of trauma or abnormal radiologic findings between 2 July 1990 and 18 February 1994. Inclusion criteria, definition of outcomes, and verification of outcomes for that cohort study are summarized below [5, 31, 32]. Clinical data were recorded by the emergency department physician at the time of presentation or by a research nurse before he or she had any knowledge of the patients outcome. These data were recorded on a standardized form that was part of the permanent medical record. A study nurse reviewed the charts of all admitted patients to determine subsequent outcome. Reviewers who were blinded to baseline clinical data classified patients into three categories on the basis of their final discharge diagnoses [5, 33]: acute myocardial infarction, unstable angina, or other. Acute myocardial infarction was diagnosed in admitted or discharged patients on the basis of characteristic evolution of serum enzyme levels, electrocardiographic changes, or sudden unexpected death within 72 hours of presentation [16]. Acute myocardial infarction was also diagnosed in 1) patients who did not meet these criteria but received acute reperfusion therapy with intravenous thrombolytic agents or primary percutaneous angioplasty and 2) patients who had new ST-segment elevation that evolved over the next day and had total occlusion of the infarction-related artery, an echocardiographic wall-motion abnormality that corresponded to the acute electrocardiographic changes, or an elevated total creatine kinase level and a creatine kinase-MB isoenzyme level greater than 2.5% of the total creatine kinase level, with characteristic evolution. Unstable angina was diagnosed if the original chest pain that led the patient to present to the emergency department was described by the patient as similar to or worse than previous symptoms of angina or myocardial infarction or if unstable angina was diagnosed by the senior clinician associated with the case. Other cardiac diagnoses, such as congestive heart failure or arrhythmias, and noncardiac diagnoses were made by the senior clinician involved with the case. Life-threatening complications were defined as nonfatal ventricular fibrillation, new type II second-degree atrioventricular block, new complete heart block, new atrioventricular dissociation, pulmonary edema, infarction extension, c

Cholesterol and recurrent events : a secondary prevention trial for normolipidemic patients

Although elevated plasma cholesterol levels represent a well-established and significant risk for developing atherosclerosis, there is a wide spectrum of cholesterol levels in patients with coronary artery disease (CAD). Most secondary prevention studies have generated convincing evidence that cholesterol reduction in patients with high cholesterol levels is associated with improved clinical outcome by reducing risk of further cardiovascular events. However, other risk factors may play a prominent role in the pathogenesis of coronary disease in the majority of patients with near-normal cholesterol values. The Cholesterol and Recurrent Events (CARE) study was designed to address whether the pharmacologic reduction of cholesterol levels with the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, pravastatin, would reduce the sum of fatal coronary artery disease (CAD) and nonfatal myocardial infarction (MI) in patients who have survived an MI yet have a total cholesterol value < 240 mg/dl (< 6.2 mmol/liter). The other inclusion criteria for this study were age 21-75 years, low density lipoprotein (LDL) cholesterol levels of 115-174 mg/dl (3.0-4.5 mmol/liter), and fasting serum triglyceride levels < 350 mg/dl (< 4.0 mmol/liter). A total of 4,159 eligible consenting patients without other study exclusions were then randomly assigned to receive either pravastatin 40 mg daily or matching placebo in addition to their individualized conventional therapy. The trial was designed to have a median follow-up of 5 years. Study endpoints will be evaluated with respect to predefined subgroups according to baseline lipid values, age, gender, prior cardiovascular risk factors, and history.(ABSTRACT TRUNCATED AT 250 WORDS)

Mechanism of the attenuated peak heart rate response to exercise after orthotopic cardiac transplantation.

The mechanism responsible for attenuation of the peak heart rate response to exercise in patients after cardiac transplantation was studied. Because the donor heart is believed to be surgically denervated, the peak heart rate response to exercise is dependent primarily on 1) an increase in the circulating levels of the catecholamines norepinephrine and epinephrine at peak exercise, and 2) the end-organ responsiveness of the sinoatrial (SA) node to beta-adrenergic stimulation. To assess the former mechanism, the levels of plasma nonepinephrine and epinephrine were measured at rest and at peak exercise on a cycle ergometer in 23 transplant recipients an average of 7 +/- 1 months after transplantation and in 23 normal subjects matched for age. To assess the latter mechanism, the heart rate response to a graded infusion of isoproterenol was determined in six normal subjects with and without atropine pretreatment and in eight transplant recipients. In transplant recipients, both the absolute plasma levels of nonepinephrine and epinephrine at peak exercise and the increments from baseline to peak exercise were comparable with or greater than those in normal subjects. In transplant recipients, the isoproterenol dose that increased heart rate by 25 beats/min over baseline was not different from that in atropine-treated normal subjects (normal subjects 9 +/- 2 ng/kg per min; transplant recipients 11 +/- 1 ng/kg per min; p = NS). These data show that after cardiac transplantation, there is a normal or slight elevation of circulating catecholamines at peak exercise, and that the responsiveness of the SA node to beta-adrenergic stimulation is normal.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Correlates and Prognostic Significance of Early Negative Exercise Tolerance Test in Patients With Acute Chest Pain Seen in the Hospital Emergency Department

An exercise tolerance test (ETT) is often performed to identify patients for early discharge after observation for acute chest pain, but the safety of this strategy is unproven. We prospectively studied 276 low-risk patients who underwent an ETT within 48 hours after presentation to the emergency department with acute chest pain. The ETT was considered negative if subjects achieved at least stage I of the Bruce protocol and the electrocardiogram showed no evidence of ischemia. There were no complications associated with ETT performance. The ETT was negative in 195 patients (71%); there was no identifiable subsets of patients at very low probability of an abnormal test. During the 6-month follow-up, patients with a negative ETT had fewer additional visits to the emergency department (17% vs 21%, respectively; p < 0.05) and fewer readmissions to the hospital (12% vs 17%; p < 0.01) than those with positive or inconclusive ETTs. No patient with a negative ETT died and only 4 patients with a negative ETT experienced a major cardiac event (myocardial infarction, coronary angioplasty, or bypass) within 6 months. Among these 4 patients, only 1 had an event within 4 months. In conclusion, our results suggest that ETT can be safely used to identify patients at low risk of subsequent events. Patients without a clearly negative test are at increased risk for readmission and cardiac events, and should be reevaluated either during the same admission or shortly after discharge.

The quiz electrocardiogram: a new diagnostic and research technique for evaluating the relation between emotional stress and ischemic heart disease.

To evaluate possible cardiovascular effects of emotional stress, a specially designed 12 minute tape-recorded stress quiz was administered to 43 subjects while blood pressure and the electrocardiogram were monitored. For the entire group, the heart rate and blood pressure rose from respective control levels of 76 beats/min and 136/87 mm Hg to a mean during the quiz of 87 beats/min and 158/94 mm Hg. This difference was highly significant. Of the 43 subjects, 33 were classified as executives and 10 as nonexecutives. There were three groups of executives: control and angina with and without a history of hypertension. Both groups of executives with angina responded with a significantly higher heart rate than that of the executive control group. Blood pressure response was significantly greater in executives with angina and hypertension than in the other groups. Heart rate and systolic blood pressure responses to the quiz were lower in nonexecutives with angina than in executives with angina. During the quiz, 10 of 14 executives with angina had S-T segment depression greater than 0.5 mm; of these, 7 evidenced greater than 1.0 mm depression, andin 3 of these the depression was greater than 1.5 mm and in 2 greater than or equal to 2.0 mm. None of the executive control subjects had S-T depression greater than 0.5 mm Among nonexecutives, 2 had S-T depression greater than 0.5 mm but none greater than 1.0 mm S-T depression. Seventeen of the patients also were given a bicycle exercise tolerance test. There was a significant correlation between S-T depression in response to exercise and to the quiz (r = 0.63; P less than 0.01). The quiz electrocardiogram is presented as a new research technique and diagnostic test for evaluating the relation of emotional stress to ischemic heart disease.

Recipient-to-donor atrioatrial conduction after orthotopic heart transplantation: surface electrocardiographic features and estimated prevalence☆

Recipient-to-donor atrioatrial conduction across a suture line has been rarely reported after orthotopic heart transplantation. The relation of such conduction to symptomatic arrhythmias and its prevalence are not known. Recipient-to-donor atrioatrial conduction was demonstrated in a 28-year-old woman with paroxysmal supraventricular tachycardia 7 years after orthotopic heart transplantation. Atrial tachycardia in the recipient atria conducted 2:1 to the donor atria and was eliminated by radiofrequency catheter ablation of a left-sided atrioatrial electrical connection. The electrocardiogram at rest and during exercise, recorded before ablation of the recipient-to-donor connection, showed frequent atrial premature complexes, with variable coupling to the preceding sinus beats, and a change in P-wave morphology during exercise, which reverted to normal during the recovery period. These findings were eliminated by ablation of the recipient-to-donor connection. To determine the prevalence of recipient-to-donor atrioatrial conduction late after transplantation, we evaluated the exercise electrocardiograms of 50 subjects > 5 years after heart transplantation for these features of recipient-to-donor conduction. At least 1 feature was present in 5 subjects, and both were present in 1 subject. Electrical conduction can occur across surgical suture lines in the atria. Recipient-to-donor atrioatrial conduction may occur in < or = 10% of patients late after heart transplantation. It is a potential cause of arrhythmias that can be effectively treated with radiofrequency catheter ablation.

Selectivity of Corticosteroid and Catecholamine Responses to Various Natural Stimuli

For about the past 15 years, we have been involved in an experimental approach to the study of the neuroendocrine motor system of the brain which views the many interdependent neuroendocrine systems on as broad a scope as possible. Figure 1 presents a schematic view of the assemblage of the principal neuroendocrine systems known at the present time. When we began our studies during the 1950’s, interest in neuroendocrine regulation was heavily concentrated on just two systems, the pituitary-adrenal cortical and sympathetic-adrenal medullary systems. The view was steadily emerging in endocrinology, however, that the hormones of the various glands are highly interdependent in their metabolic effects throughout the body, being variously aligned in patterns of antagonistic, synergistic, or additive relationships with each other. No single hormone acts entirely alone in isolation. Houssay, among others, has emphasized that there is always a balance between opposing and cooperating hormones acting on any particular metabolic process (Houssay, 1957). Our guiding working hypothesis has been, therefore, that if hormones are so closely interdependent in their actions at the metabolic level, then it seems logical that the integrative mechanisms controlling endocrine secretion are organized in a manner closely in keeping with such interdependencies and that the secretion of the many hormones probably is accordingly coordinated on an overall basis (Mason, 1968c).

Risk of All-Cause Mortality, Recurrent Myocardial Infarction, and Heart Failure Hospitalization Associated With Smoking Status Following Myocardial Infarction With Left Ventricular Dysfunction

Patients with left ventricular (LV) systolic dysfunction after myocardial infarction (MI) are at particularly high risk for recurrent adverse outcomes. The magnitude of the decrease in risk associated with smoking cessation after MI has not been well described in patients with LV dysfunction after MI. We aimed to quantify the risk decrease associated with smoking cessation in subjects with LV dysfunction after MI. The Survival and Ventricular Enlargement (SAVE) trial randomized 2,231 subjects with LV dysfunction 3 to 16 days after MI. Smoking status was assessed at randomization and at regular intervals during a median follow-up of 42 months. Propensity score-adjusted Cox proportional hazard models were used to quantify the decrease in risk of all-cause mortality, death or recurrent MI, and death or heart failure (HF) hospitalization associated with smoking cessation. In baseline smokers who survived to 6 months without interval events, smoking cessation at 6-month follow-up was associated with a significantly lower adjusted risk of all-cause mortality (hazard ratio [HR] 0.57, 95% confidence interval [CI] 0.31 to 0.91), death or recurrent MI (HR 0.68, 95% CI 0.47 to 0.99), and death or HF hospitalization (HR 0.65, 95% CI 0.46 to 0.92). In conclusion, in patients with LV dysfunction after MI, smoking cessation is associated with a 40% lower hazard of all-cause mortality and a 30% lower hazard of death or recurrent MI or death or HF hospitalization. These findings indicate that smoking cessation is beneficial after high-risk MI and highlight the importance of smoking cessation as a therapeutic target in patients with LV dysfunction after MI.

Decreased [Vdot]O2 Consumption during Exercise with Elicitation of the Relaxation Response

Oxygen consumption is usually considered to be predictable and unalterable at a fixed work intensity. The relaxation response is hypothesized to be an integrated hypothalamic response which results in generalized decreased sympathetic nervous system activity. One physiologic manifestation of the relaxation response is decreased oxygen consumption. The possibility that the elicitation of the relaxation response could decrease oxygen consumption at a fixed work intensity was investigated. Oxygen consumption was decreased 4 percent (p less than 0.05) in eight subjects working at a fixed intensity when the relaxation response was simultaneously elicited.