Enhanced evaluation of treadmill tests by means of scoring based on multivariate analysis and its clinical application: a study of 608 patients.

Six hundred eight patients being evaluated for chest pain who did not have valvular disease, cardiomyopathy, left ventricular hypertrophy or bundle branch block, and were not receiving digitalis, had treadmill tests and coronary angiograms. In 351, various exercise variables were correlated by multivariate analysis to coronary artery disease (CAD). In men, significant variables were: (1) maximal heart rate achieved less than 80% of maximal predicted heart rate (Mx PHR), (2) ST-T change greater than or equal to 1 mm, (3) age greater than or equal to 55 years and (4) treadmill time (TT) less than 8 minutes. These variables rated diagnostic scores of 9, 6, 5, and 3, respectively. A score of greater than or equal to 7 was considered diagnostic of CAD. In a test group of 192 men in which ST-T change was compared with treadmill score, sensitivity was 65 versus 85%, specificity 79 versus 74% and accuracy 69 versus 83%. In women, maximal heart rate less than 90% of Mx PHR and TT of less than 6 minutes were significant, with an accuracy of 75%. Moreover, 89% of incomplete tests and 70% of tests in patients with previous myocardial infarction were also correctly diagnosed. This method allows convenient use of significant exercise variables for clinical purposes with improved results.

Paradoxical septal motion in a patient with pulmonic stenosis.

This case will demonstrate abnormal (paradoxical) septal motion in a 31-year-old woman with an isolated pulmonary valvular stenosis. The right ventricular volume overload was exluded by the shunt series, special angiographic studies and at surgery. The echocardiographic abnormality persisted during a restudy three months after surgery.

Ischemic myocardial injury following aorto-coronary bypass surgery.

To assess the incidence of acute myocardial injury following aorto-coronary bypass surgery 151 patients (136 men and 15 women) were evaluated by studying serial preoperative and postoperative ECGs and SGOT, LDH and CPK levels. The mean age of men was 49.1 and of women, 53.1 years. Following surgery 15 patients (group I, 9.9 percent) developed new myocardial infarction as judged by Q wave criteria, 33 patients (group II, 22.5 percent) developed significant ST-T changes, and 103 patients (group III, 68 percent) had no significant ECG change. Mean postoperative SGOT values were: group I,126.2; group II, 100.6; and group III, 72.8. Only the difference in SGOT values between group I and III was significant (P less than 0.01). There was no correlation between type and site of surgery and the incidence of myocardial infarction. There were five deaths (3.3 percent). The combination of death and diagnosed myocardial infarction amounted to 12.6 percent of patients for this widely used elective procedure.

'Relative' chemotherapy sensitivity: the impact of number of salvage regimens prior to autologous stem cell transplant for relapsed and refractory aggressive non-Hodgkin's lymphoma.

The purpose of the study was to assess the impact of number of salvage regimens needed to demonstrate chemotherapy sensitivity on relapse rates, survival, and toxicity following high-dose therapy and autologous bone marrow transplantation (ABMT) in relapsed or refractory non-Hodgkin's lymphoma. We retrospectively reviewed 136 patients with intermediate-grade lymphoma who underwent ABMT. All patients were treated with salvage therapy to maximum tumor reduction. Three quarters (102/136) of the patients received one salvage regimen, while 31 (23%) patients received two or more regimens. When compared to patients requiring >or= two regimens, patients requiring only one salvage regimen to demonstrate chemosensitivity were more likely to have a longer previous CR from initial therapy (CR >or=12 months in 47% vs 26%; P = 0.04) and to have attained CR with salvage (54% vs 16%; P = 0.001). Both median relapse-free survival (RFS) and overall survival (OS) have not yet been reached in patients receiving one salvage regimen (median follow-up 50.6 months). This is superior to the median RFS of 9.1 months (P = 0.004) and OS of 11.1 months in patients requiring >or=two regimens to demonstrate chemosensitivity (P = 0.002). Time to engraftment, toxic deaths and incidence of myelodysplasia were similar in the groups. The survival rate observed in patients requiring >or=two salvage regimens, although inferior to that of patients receiving a single salvage regimen, are still generally superior to results in the literature for patients treated with chemotherapy alone without ABMT. We conclude that high-dose therapy with ABMT is appropriate for lymphoma patients even when disease reduction requires repeated numbers of salvage regimens.

Randomized trial of peripheral blood progenitor cell vs bone marrow as hematopoietic support for high-dose chemotherapy in patients with non-Hodgkin's lymphoma and Hodgkin's disease: a clinical and molecular analysis.

Filgrastim (r-metHuG-CSF)-mobilized peripheral blood progenitor cells (PBPC) and unstimulated bone marrow (BM) were evaluated and compared for reconstitution after high-dose chemotherapy in patients with relapsed Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) with respect to engraftment, overall and relapse-free survival, and contamination by lymphoma cells using molecular analysis of immunoglobulin gene rearrangements. Forty-four patients with either NHL or HD underwent autologous transplantation after high-dose chemotherapy. Patients were randomized to receive either Filgrastim-mobilized PBPC (n = 15) or unstimulated BM (n = 14). An additional 15 patients received PBPC without randomization because of a recent history of marrow involvement by lymphoma. Use of PBPC was associated with faster neutrophil engraftment than BM (11 vs 14 days to an absolute neutrophil count >0.5 x 10(9)/l, P = 0.04), but without any difference in platelet engraftment, infectious complications, or overall or event-free survival. Both BM (65%) and PBPC (73%) were frequently contaminated by tumor cells as assessed by CDR3 analysis. Patients with negative polymerase chain reaction analysis of a BM sample during the study had a trend towards an improved survival; however, BM involvement by disease had no impact on the ability to mobilize or collect PBPC. We conclude that PBPC are as effective as BM in reconstituting hematopoiesis after high-dose chemotherapy and that both products are frequently contaminated by sequences marking the malignant clone.

A quantitative relationship of electrocardiographic criteria of left ventricular hypertrophy with echocardiographic left ventricular mass: a multivariate approach.

The purpose of this study was to evaluate the sensitivity of various electrocardiographic (EKG) criteria of left ventricular hypertrophy (LVH) in relation to echocardiographic left ventricular mass (LVME) and to assess the relative strength of various EKG variables used in the diagnosis of LVH by multivariate analysis. An attempt was also made to determine if a new combination of precordial and T-wave voltage could improve the sensitivity of EKG. In 89 patients, M-mode echocardiograms and standard EKGs were studied. Correlation of Romhilt-Estes point-score system with LVME was r = 0.621, sensitivity and specificity was 57 and 81%, respectively. Other voltage criteria had lower sensitivity. Various combinations of precordial and T-wave voltage were not superior. The quantitative relationship of individual EKG variable, QRS duration, S V1-3, R V4-6, strain T wave, left atrial abnormality, intrinsicoid deflection and axis, with LVM was, r = 0.661, 0.595, 0.429, 0.42, 0.347, and 0.225, respectively. By multivariate analysis, QRS duration, S V1-3, T-wave and R V4-6 voltage had F-value (relative strength) of 27.95, 27.15, 22.02, and 4.03, respectively, other variables were statistically insignificant. In conclusion, the most important EKG variables predictive of LVH are QRS duration, S V1-3, strain T-wave and lateral voltage in decreasing value. Rescoring these variables in accordance to their correlation to LVM may improve EKG sensitivity for the diagnosis of LVH.

Interventricular septal thickness and left ventricular hypertrophy. An echocardiographic study.

Septal and left ventricular posterior wall (LVPW) thicknesses and their ratios were studied at the left ventricular outflow tract and left ventricular cavity in 66 patients with echocardiographically diagnosed left ventricular concentric hypertrophy, 20 with idiopathic hypertrophic subaortic stenosis (IHSS), and 34 normal subjects. Concentric hypertrophy was due to hypertension in 41 subjects and to valvular disease in 15 subjects. Septal thickness in normal subjects was related to body surface area (p less than 0.02). In 12% of normal subjects, 39% of patients with concentric hypertrophy and 95% with IHSS, the septal/LVPW ratio was greater than or equal to 1.3. Thirty-two percent of patients with hypertension, 78% with aortic stenosis, and 60% with aortic insufficiency had septal/LVPW ratios greater than or equal to 1.3 at left ventricular midcavity level. In conclusion, a septal/LVPW thickness ratio of greater than or equal to 1.3 is common in patients with concentric left ventricular hypertrophy and may also occur in normal subjects. A ratio greater than or equal to 1.5 may be more specific for genetically determined asymmetric septal hypertrophy.

Interesting approaches to the diagnosis of angina pectoris.

Twelve different approaches to laboratory diagnosis of angina pectoris are reviewed here. They employ no fewer than seven different means of intentionally provoking a disparity between myocardial requirement and supply: dynamic exercise, hypoxia, prandial stress, raised systemic vascular resistance, paced tachycardia, mental stress, and exposure to normal environment. Of these, only dynamic exercise and the diverse combinations of stresses in the normal environment are capable of altering the heart's oxygen requirement-supply ratio threefold or more, accounting for the successful results from tests using these means of stress. The reviewed tests use three different means of detecting myocardial ischemia provoked by stress: electrocardiography to indicate impaired ventricular repolarization, indirect graphic records sensitive to impairment of mechanical ventricular function, and detection of insufficient myocardial perfusion patterns by radioactive tracer. The latter approach is particularly appealing because it directly reflects the pathophysiologic anomaly of interest. It should be remembered, however, that the basic differences in these methods of detecting ischemia make them complementary to each other and encourage their use in combination for improved diagnostic sensitivity.

A quantitative technical quality assay method for electrocardiograms.

A method is presented for quantitative assessment of ECG technical quality to permit sensitive detection of performance trends of individual technicians or entire ECG laboratories. The common flaws in ECG recording technic are those which introduce ultra-low frequency artifact or baseline shift, powerline artifact, myographic and intermediate frequency artifact, clipping of waveforms, disconnection or reversal of electrodes and general faults of protocol adherence. Procedures for quantitating these attributes are presented and explained in order to arrive at a mean figure of merit for each ECG recording. Use of such a method can aid ECG technicians' understanding of the important features of tracing quality and provide an objective basis for the recognition of outstanding performance, on one hand, or the need for remedial training, on the other.

A controlled study of a new ECG electrode system.

A newly marketed resting ECG electrode system was compared with conventional metal suction and plate electrodes, electrode cream and patient cable. Two experienced technicians were given special training in the use of the new electrode, electrolyte and patient cable system and alternated daily in using new and conventional equipment. Nearly equal numbers of perfect-scoring ECGs were recorded with each system, attesting to the impartiality of the technicians. A total of 1,062 ECGs were evaluated, 554 with the new system and 508 with the conventional one. ECG tracings were evaluated by electrocardiographers unaware of which system was used for each. A quantitative scoring system was used to measure the technical quality of each tracing in terms of baseline drift, powerline artifact and myographic plus miscellaneous artifacts. The new system received mean scores of 2.33, 3.08, and 2.72, respectively, while the conventional electrodes received scores of 2.56, 3.03 and 2.79. We concluded that the two types of electrodes produced ECGs of essentially equal quality.

Stress testing with ST-segment depression at rest. An angiographic correlation.

Near maximal graded exercise tests and coronary angiograms were compared in 37 patients with a history of chest pain and with ST segment depression at rest, who were free of obvious nonischemic causes of ST depression. Additional ST depression of 0.1 mV or more occurred with exercise in 26 patients and 23 of these had obstruction of one or more coronary arteries (sensitivity = 0.92). Eleven patients showed no additional ST-segment depression with exercise, and nine of these had normal coronary angiograms (specificity = 0.75). Patients with no increase in ST depression on exercise developed the highest heart rates; those with asymptomatic additional ST depression achieved intermediate rates; and those with anginal attacks during testing demonstrated the least heart rate acceleration. Those with less coronary obstruction exercised longer on the treadmill than those with more obstruction. Those showing added ST depression were predominantly men (18 of 26) and were older (mean 54 years) than those who did not (mean 44 years). No test complications were encountered. This study suggests that safe and effective stress testing may be accomplished not only in persons with normal resting ECGs but also in selected patients who have abnormal ST segments at rest.

Repolarization current in embryonic chick atrial heart cells.

1. We have measured the delayed rectifier potassium current, IK, with the whole-cell patch-clamp technique from single cultured cells from the atria of 6- to 11-day-old chick embryonic hearts. 2. The IK component was activated with depolarizing voltage-clamp steps positive to -30 mV (holding potential in the -60 to -40 mV range). Maximum activation of the IK conductance occurred at +25 mV, based on deactivation, or tail current amplitudes upon return to the holding potential. Activation and tail current kinetics could both be described by single-exponential functions of time. 3. The IK kinetics were voltage dependent, with a maximum time constant, tau n, of approximately 2 s at V = -20 mV. 4. The IK reversal potential measurements suggest that this current is carried predominantly by potassium ions. 5. The IK results from single cells, or clusters of two or three cells, were comparable to our recent measurements of IK (IX2) in heart cell aggregates (Shrier & Clay, 1986). However, we did not obtain clear evidence in single cells for the IX1 repolarization current, in contrast to the aggregate results. 6. Computer simulations based on our IK measurements demonstrate that this component is sufficient to initiate repolarization of the action potential in single cells. However, it is not sufficient to reproduce the latter phase of repolarization for potentials negative to -30 mV. Addition of a relatively small IX1 component (2% in absolute terms compared to the aggregate work) is sufficient to account for this part of the action potential.

The echocardiogram after pericardiectomy.

Many factors may affect the interventricular septal motion. This study measures the effect of pericardiectomy on septal motion in 9 patients who were evaluated 1 week to 58 months after pericardiectomy. Echocardiography was performed with the patient in recumbent position with the special care to record motion of the muscular septum and not that of the aorta. No patient had left bundle branch block, angina, myocardial infarction, pericardial effusion or right ventricular volume overload. Septal motion was paradoxical in 7, normal in 1 and could not be evaluated 1 patient. The mean value of the right ventricular internal dimension was normal. Two of 9 patients had technically satisfactory echocardiograms preoperatively. Septal motion was normal in both, and both developed paradoxical septal motion postoperatively. We conclude that paradoxical septal motion pericardiectomy, but in contrast with other causes of this finding right ventricular internal dimension remains normal.

Maximal heart rate and treadmill performance of healthy women in relation to age.

Maximal treadmill exercise heart rate, work capacity and electrocardiographic response were studied in 95 asymptomatic, predominantly sedentary women between the ages of 19 and 69 years. Average maximal heart rate (MHR) was found inversely related to age, such that MHR = 216 -0.88 (years of age) +/- 10 beats/min (X +/- 1 SD). Treadmill exercise endurance was 7.64 min +/- 1.99. The reduction of treadmill endurance with advancing age was not statistically significant. Asymptomatic ST-segment depression occurred in 6% of subjects. In 5% the ST segment sloped upward, and in 1% it was flat. Mean age of women with ST depression was 52 years, compared with 39 years mean age of all subjects. Premature beats during exercise were found in 20 of 95 subjects, and were not related to age. Graded exercise testing of women employing target heart rates should use heart rate tablets developed especially for women. These tables do not require correction for athletically trained for sedentary life-style.

Direct measurement of left ventricular ejection time from echocardiographic posterior wall excursion time: validation of technique.

Echocardiography has proven useful in determining systolic time intervals. Left ventricular mean velocity of circumferential fiber shortening has been calculated utilizing the left ventricular ejection time measured in several manners, usually from the echocardiographic aortic valve opening time or indirect carotid pulse tracing. Left ventricular ejection time is related to the time of posterior wall excursion in patients without conduction defects or segmental wall motion abnormalities. Thus, a single echocardiographic view can measure ventricular diameters and approximate ejection time simultaneously without other echocardiographic or phonocardiographic measurements which may be cumbersome to obtain, particularly during dynamic echocardiographic studies.