Nora Goldschlager

Treadmill Stress Tests as Indicators of Presence and Severity of Coronary Artery Disease

The configuration, time of onset, and duration of depressed ST segments during and after treadmill exercise testing were evaluated in 269 patients with angiographically proven coronary artery disease and 141 normal subjects. The test specificity was 93% and sensitivity 64%, the latter being influenced by the type of ST response; false-positive responses were rare with depressed, downsloping STs (1 of 123, 1%), occurred more frequently with horizontal ST depression (9 of 60, 15%), and occurred commonly with slowly upsloping STs (15 of 47, 32%). Depressed downsloping STs, ischemic changes appearing in the first 3 minutes of exercise, and those persisting past 8 minutes in recovery were associated with 91%, 86%, and 90% prevalences of two- to three-vessel or main left coronary disease, respectively. It is concluded that attention to configuration, time of onset, and duration of ischemic ST depression aids both in assessing the validity of exercise responses in diagnosing coronary artery disease and in delineating patients with advanced coronary obstruction.

Prevention of atrial fibrillation: report from a national heart, lung, and blood institute workshop.

The National Heart, Lung, and Blood Institute convened an expert panel April 28 to 29, 2008, to identify gaps and recommend research strategies to prevent atrial fibrillation (AF). The panel reviewed the existing basic scientific, epidemiological, and clinical literature about AF and identified opportunities to advance AF prevention research. After discussion, the panel proposed the following recommendations: (1) enhance understanding of the epidemiology of AF in the population by systematically and longitudinally investigating symptomatic and asymptomatic AF in cohort studies; (2) improve detection of AF by evaluating the ability of existing and emerging methods and technologies to detect AF; (3) improve noninvasive modalities for identifying key components of cardiovascular remodeling that promote AF, including genetic, fibrotic, autonomic, structural, and electrical remodeling markers; (4) develop additional animal models reflective of the pathophysiology of human AF; (5) conduct secondary analyses of already-completed clinical trials to enhance knowledge of potentially effective methods to prevent AF and routinely include AF as an outcome in ongoing and future cardiovascular studies; and (6) conduct clinical studies focused on secondary prevention of AF recurrence, which would inform future primary prevention investigations.The National Heart, Lung, and Blood Institute convened an expert panel April 28-29, 2008 to identify gaps and recommend research strategies to prevent atrial fibrillation (AF). The panel reviewed the existing basic scientific, epidemiologic and clinical literature about AF, and identified opportunities to advance AF prevention research. After discussion, the panel proposed the following recommendations: 1) Enhance understanding of the epidemiology of AF in the population by systematically and longitudinally investigating symptomatic and asymptomatic AF in cohort studies; 2) Improve detection of AF by evaluating the ability of existing and emerging methods and technologies to detect AF; 3) Improve noninvasive modalities for identifying key components of cardiovascular remodeling that promote AF, including genetic, fibrotic, autonomic, structural and electrical remodeling markers; 4) Develop additional animal models reflective of the pathophysiology of human AF; 5) Conduct secondary analyses of already-completed clinical trials to enhance knowledge of potentially effective methods to prevent AF and routinely include AF as an outcome in ongoing and future cardiovascular studies; and 6) Conduct clinical studies focused on secondary prevention of AF recurrence, which would inform future primary prevention investigations.

Exercise-induced ventricular arrhythmias in patients with coronary artery disease. Their relation to angiographic findings.

Abstract Ventricular extrasystoles occurring before, during or after graded exercise testing were related to extent of coronary artery disease and to ventricular motion disorders in 81 symptomatic patients undergoing selective coronary and left ventricular angiography; the results were compared with data in 89 similar age-matched patients without arrhythmias. Compared with arrhythmia-free patients, 67 patients with exercise-induced arrhythmias had a significantly greater incidence of prior myocardial infarction, double or triple vessel disease and overall abnormal ventricular contractile patterns. Exercise induced extrasystoles occurred in only 11 percent of patients with insignificant coronary disease. Abolition of resting extrasystoles by exercise was not associated with less extensive coronary disease. Our study suggests that exercise-precipitated arrhythmias may represent a form of subclinical ischemia, signify more advanced degrees of coronary and left ventricular disease, and serve as an aid in detecting potentially high-risk patients.

The natural history of aortic regurgitation: A clinical and hemodynamic study☆

Abstract A combined prospective and retrospective analysis of clinical and hemodynamic data in 150 patients with aortic regurgitation was undertaken to review the natural history of this lesion. One hundred twenty-six patients were classified as having chronic aortic regurgitation and 24 as having acute aortic regurgitation. Serial hemodynamic studies were performed one to eight years apart in 24 patients with chronic aortic regurgitation. Clinical symptoms included dyspnea and fatigability as a consequence of reduced cardiac reserve, and chest pain and palpitations, symptoms not directly related to deteriorating cardiac function. As a rule, patients in younger age groups were free of symptoms; disability usually appeared in the fourth and fifth decades of life. Disability was poorly related to the degree of aortic regurgitation and extent of ventricular hypertrophy or cardiac enlargement. Hemodynamic abnormalities almost always preceded the development of clinical disability, but normal or near normal performance was usual in younger asymptomatic subjects despite severe degrees of aortic regurgitation and pronounced left ventricular hypertrophy. In patients with acute aortic regurgitation, findings ranged from near normal to severe cardiac decompensation requiring emergency surgical treatment. In our study (1) the protracted clinical course of chronic aortic regurgitation is confirmed: the asymptomatic state is present for decades in patients with severe aortic regurgitation even though serious hemodynamic deterioration can be documented; (2) the late appearance of clinical disability at a stage when irreversible myocardial damage may be present imposes, at present, an insoluble therapeutic dilemma with regard to the timing of surgical treatment; (3) except for the most severe, intolerable acute aortic regurgitation, there is considerable similarity between chronic and acute forms of aortic regurgitation; (4) ischemic cardiac pain is rare in aortic regurgitation, and syncope does not occur as part of this disease.

Use of treadmill score to quantify ischemic response and predict extent of coronary disease.

In this study we assessed whether various responses to exercise testing could be quantified in order to derive the probabilities of presence of coronary disease, and if present, to assess its severity. A treadmill score based on the exercise response was determined in 405 patients who had both treadmill tests and coronary angiograms. The score was derived using discriminant function analysis, by weighting and combining depth and configuration of ST depression (downsloping, horizontal or slowly upsloping), timing onset and duration of ischemia, grading ventricular arrhythmias, heart rate and blood pressure change, coexistence of exercise-induced chest pain and sex. The treadmill score was effective in detecting coronary disease (lesions with an greater than or equal to 50% narrowing), with a predictive accuracy (PA) (probability that a subject manifesting a positive test has disease) of 87%, a true negative rate (TNR) (probability of a subject with a negative test having no disease) of 80%, and sensitivity of 94%. The treadmill score also detected severe disease (triple-vessel, main left and/or greater than 90% proximal occlusion of the left anterior descending artery), with a PA of 73%, TNR of 79% and sensitivity of 82%. We conclude that the exercise response, expressed numerically as a treadmill score, permits analysis of most of the relevant data from exercise testing, increases test accuracy by 10-15% compared with standard criteria for treatmill test interpretation, and enables the derivation of probability statements for presence and severity of coronary disease. The validity of any prediction on the basis of exercise performance may thus be quantitatively judged.

Left Atrial Size and Atrial Fibrillation in Mitral Stenosis: Factors Influencing Their Relationship

In a series of 135 patients with mitral valvular stenosis, three groups were identified: those in sinus rhythm, those with intermittent atrial fibrillation, and those with longstanding, established atrial fibrillation. Examination of the relationships between atrial fibrillation, hemodynamic findings and radiologic data in mitral stenosis was undertaken. Analysis of clinical and hemodynamic factors in the three groups revealed that: 1) age is an etiological factor in the production of atrial fibrillation, as suggested by the age distribution among the three groups; 2) left atrial enlargement may be the result, rather than the cause, of atrial fibrillation; and 3) severity of mitral stenosis is not invariably related to the incidence of atrial fibrillation. Hemodynamic measurements were not significantly different among the three groups, with the single exception of lower cardiac outputs found in patients with established atrial fibrillation. Since no single consequence of mitral stenosis always produces atrial fibrillation, it is suggested that several factors in different combinations can initiate the self-perpetuating process of atrial fibrillation and that the classic form of the arrhythmia may lead secondarily to left atrial enlargement.

Electrocardiographic changes during hyperventilation resembling myocardial ischemia in patients with normal coronary arteriograms

Abstract In a series of 238 patients having hyperventilation tests just prior to treadmill exercise and selective coronary arteriography during the same hospital admission, 15 per cent of 46 patients with normal coronary vessels had electrocardiographic changes during hyperventilation that were virtually identical to those of myocardial ischemia. The hyperventilatory ECG changes were the sole basis for “false-positive” interpretation of their stress tests. Patients with normal coronary angiograms who had no ECG alterations during hyperventilation all had negative treadmill tests. In contrast, only 3 per cent of 192 patients with angiographically demonstrable coronary disease had ischemic changes during hyperventilation. Awareness that not all RST alterations seen during hyperventilation are easily distinguishable from those due to myocardial ischemia is of the utmost importance in evaluating treadmill tests, as errors in interpretation may thus be minimized, resulting in fewer “false-positive” readings. Although the number of patients is small, we found that “ischemic” ECG changes seen during hyperventilation (as well as during exercise) in patients with suspicious histories indicate that very probably no coronary artery disease exists. The routine performance of adequate hyperventilation testing prior to exercise is strongly urged.

Torsade de pointes during administration of pentamidine isethionate

Pentamidine isethionate is a diamidine compound used in the treatment of a number of parasitic diseases, notably Pneumocystis carinii pneumonia. Although cases of sudden death have been reported during the administration of pentamidine, there have been no reported cases in the literature of pentamidine-associated arrhythmias. Reported in this study are two cases of torsade de pointes occurring during the prolonged administration of pentamidine. In addition, electrocardiographic changes of marked QT interval prolongation, pronounced precordial T wave abnormalities, and ST segment changes were shown in both patients. Mild hypomagnesemia coexisted in both cases, but torsade de pointes persisted in one patient and electrocardiographic changes remained in both cases despite magnesium replacement. QT interval prolongation and electrocardiographic abnormalities resolved slowly over several days to weeks, paralleling the known elimination kinetics of pentamidine. These data suggest a proarrhythmic effect of pentamidine isethionate.

Variability of hemodynamic responses to acute digitalization in chronic cardiac failure due to cardiomyopathy and coronary artery disease

Eight patients with chronic congestive heart failure (four with cardiomyopathy and four with ischemic heart disease) underwent hemodynamic studies during acute administration of digoxin, given intravenously in two 0-5 mg doses 2 hours apart. Observations were made before administration of digitalis (control period) and serially therafter for 4 hours after the first dose. Resting mean cardiac index and pulmonary arterial wedge pressure were as follows: 2.0 liters/min per m2 and 23 mm Hg (control period); 2.1 and 24 (at 1 hour); 2.0 and 23 (at 2 hours); 2.7 and 19 (at 3 hours); and 2.3 and 20 (at 4 hours). Exercise responses of mean cardiac index and pulmonary arterial wedge pressure in five patients were: 3.1 liters/min per m2 and 36 mm Hg (control period); 3.2 and 33 (at 1 hour); 3.2 and 28 (at 2 hours); 3.1 and 27 (at.3 hours); and 3.4 and 31 (at 4 hours). The pulmonary arterial wedge pressure remained elevated during exercise in all cases. Arrhythmias were seen in five patients after administration of 0.5 mg of digoxin. Hemodynamic improvement at 4 hours involving both reduced filling pressure and increased blood flow was observed in only two patients at rest and in one additional patient during exercise. Acute deterioration of cardiac function (elevated pulmonary arterial wedge pressure of decreased cardiac index) occurred 30 minutes after administration of digoxin in four patients, concomitantly with increased systemic resistance. In six patients, a peak hemodynamic effect appeared 1 to 1 1/2 hours after administration of digoxin, with partial or total loss of initial benefit by 2 and 4 hours. In previously performed studies observations have seldom exceeded 1 hour; the results of this 4 hour study suggest that, in patients with cardiomyopathy or coronary artery disease and chronic congestive heart failure, acute digitalization does not necessarily lead to consistent, marked or lasting hemodynamic improvement. Thus, current concepts of the use of digitalis is such patients may require revision.

Determinants of prognosis of patients with aortic regurgitation who undergo aortic valve replacement

Insidious and potentially irreversible left ventricular dysfunction may develop in patients with aortic regurgitation. To determine whether preoperative variables can predict postoperative outcome, 113 consecutive patients with aortic regurgitation who underwent surgical correction between 1962 and 1977 were studied and survivors were followed up for 4.6 +/- 3.3 years. Clinical and hemodynamic examinations were made in all patients before the operation. Echocardiograms were performed in 44 patients preoperatively and in 36 patients postoperatively. Perioperative or postoperative death due to congestive heart failure occurred in only eight patients (19%). No statistically significant predictors of total mortality or death due to cardiac failure were found based on preoperative clinical, hemodynamic or echocardiographic findings. Survivors of the operation showed significant functional improvement: preoperatively, 77% of all patients were in functional class III or IV; postoperatively, 84% of patients were in class I or II (p less than 0.0001). A weak statistical correlation of functional improvement was found with a preoperative presence of increased cardiac diameter on the chest radiograph (p less than 0.05) and the severity of left ventricular hypertrophy (p less than 0.05). Improvement of left ventricular function was also consistently found in survivors and correlated best with the degree of preoperative preservation of left ventricular function. Patients with an echocardiographic preoperative fractional shortening of the minor diameter greater than 26%, end-systolic dimension less than 55 mm and end-diastolic dimension less than 80 mm were most likely to have normal function after the operation. It is concluded that operative mortality and survival after surgical correction of aortic regurgitation cannot be accurately predicted from preoperative findings.(ABSTRACT TRUNCATED AT 250 WORDS)