Marker Of Left Ventricular Dysfunction Research Articles

New method of estimating myocardial infarct size using technetium-99m pyrophosphate and thallium-201 dual single photon emission computed tomography imaging.

A new method was devised to estimate infarct size using dual single photon emission computed tomography with thallium-201 and technetium-99m pyrophosphate. Designating the ratio of infarct area to whole myocardial volume as %MI, the correlation of %MI with other markers of left ventricular dysfunction was examined: peak creatine kinase, ejection fraction and left ventricular asynergy. As %MI correlated well with these markers, it is considered that %MI will be useful for estimating infarct size and predicting the severity of left ventricular dysfunction in the early stage of acute myocardial infarction.

Elevated B-type natriuretic peptide levels after anthracycline administration

Background Cardiotoxicity leading to congestive heart failure is a complication of the anthracyclines. Biochemical methods to diagnose and monitor cardiac function after anthracycline administration would be most useful. We examined the diagnostic role of B-type natriuretic peptide (BNP), a potent biochemical marker of left ventricular dysfunction, in patients administered anthracyclines.Methods Twenty-seven consecutive patients receiving anthracyclines were investigated by serial measurements of BNP levels and other cardiac neurohormones (A-type natriuretic peptide, renin, aldosterone, angiotensin II, norepinephrine, and epinephrine) and myocardial markers (creatine kinase-MB and myosin light chain). Echocardiography was done to assess systolic (ejection fraction) and diastolic (mitral inflow A/E ratio) functions.Results Of the examined cardiac biochemical markers, BNP levels alone showed marked elevations to abnormal levels after anthracycline administration. Most patients showed transient increases (peak at 3 to 7 days). Patients with persistent elevations showed a poor prognosis. A/E ratio also correlated with increases in BNP levels in selected patients, which may suggest that raised BNP levels are reflective of induced diastolic dysfunction.Conclusions Our studies suggest the possible use of BNP levels to assess the cardiac state after anthracycline administration. BNP levels most likely reflect cardiac tolerance to the cardiotoxic agent. Serial BNP profiles also suggest persistent elevations to be associated with potentially decompensatory states in contrast to tolerable transient increases. Diagnosis of degree of cardiac tolerance by response to drug administration may be analogous to use of stress testing (exercise) to help define underlying left ventricular dysfunction. (Am Heart J 1998;136:362-3.)

Relationship between rate-corrected QT interval and wall motion abnormalities in the setting of acute myocardial infarction

We studied 108 patients (73 men and 35 women, mean age of 63.1±11.2 years) with Q-wave acute myocardial infarction (anterior −52, inferior −41, and combined anteroinferior −15) 4 days after infarct onset to determine whether any correlation exists between rate-corrected QT interval (QTc) and functional infarct size, expressed as wall motion index. QTc was calculated by Hodges' linear algorithm [QT+(1.75×heart rate−60)]. Wall motion index was determined using a 16-segments model, as recommended by the American Society of Echocardiography. Wall motion index was significantly higher in anterior and in combined infarctions. QTc was shortest in inferior infarction. There was a statistically significant overall correlation between wall motion index and QTc (r=0.83, p<0.001). The relationship was weakest in inferior infarction. In conclusion, prolonged QTc may be implicated as an additional marker of left ventricular dysfunction in patients with acute anterior and combined anteroinferior myocardial infarction.

A metaanalysis of predischarge risk stratification after acute myocardial infarction with stress electrocardiographic, myocardial perfusion, and ventricular function imaging

We assessed the relation of abnormal predischarge noninvasive test results to outcomes in postmyocardial infarction patients. We included series published from 1980 to 1995 containing only myocardial infarction patients, enrolling most patients after 1980, testing within 6 weeks of infarction, having follow-up rates > 80%, and having 2 × 2 frequency outcome rates for test results, that were the latest of multiple reports. Sensitivity, specificity, and predictive values were calculated for test results for 1-year outcomes (cardiac death, cardiac death or reinfarction). Univariable and summary odds were calculated for test results. Reports (n = 54) included a total of 19,874 patients and were primarily retrospective (76%) and small series (35% of reports included < 5 deaths). One-year mortality ranged from 2.5% for pharmacologic stress echocardiography to 9.3% for exercise radionuclide angiography. Positive predictive values for most noninvasive risk markers were < 0.10 for cardiac death and 0.20 for death or reinfarction. Electrocardiographic, symptomatic, and scintigraphic risk markers of ischemia (ST-segment depression, angina, a reversible defect) were less sensitive (≤44%) for identifying morbid and fatal outcomes than markers of left ventricular dysfunction or heart failure (exercise duration, impaired systolic blood pressure response, and peak left ventricular ejection fraction). The positive predictive value of predischarge noninvasive testing is low. Markers of left ventricular dysfunction appear to be better predictors than markers of ischemia. Limitations of the literature—small samples and widely varying event rates—impede our ability to discern the accuracy of predischarge noninvasive testing. More rigorous, controlled trials are required to elucidate the relative value of these tests for risk stratification.

Plasma levels and molecular forms of proatrial natriuretic peptides in healthy subjects and in patients with congestive heart failure.

A specific and sensitive radioimmunoassay (RIA) for the N-terminal fragment of proatrial natriuretic peptide (NproANP) was developed. Antiserum raised in rabbits against a mixture enriched with prohormone was 100% cross-reactive with human proANP(1-30). Plasma concentrations of proANP(1-30) and ANP immunoreactivities (ir-) were simultaneously measured in healthy subjects and patients with congestive heart failure (CHF; 26 dilated cardiomyopathy and 5 ischemic heart disease). High plasma levels of both ir-proANP(1-30) and ir-ANP were detected in CHF patients. Circulating ir-ANP levels were elevated in New York Heart Association functional Classes II and III patients but not in Class I patients. However, plasma levels of ir-proANP(1-30) were higher in asymptomatic patients than in healthy subjects, and markedly increased in patients of Classes II and III. Analysis of ir-proANP(1-30) by gel filtration chromatography or reverse-phase high pressure liquid chromatography revealed a 10 kDa peptide circulating as a distinct entity. These findings indicate that: (i) the most probable form of NproANP in human plasma is a 10 kDa peptide and (ii) in CHF patients the rise in plasma ir-proANP(1-30) levels is more pronounced than the variation in plasma ir-ANP. Thus, NproANP plasma levels may prove to be a more sensitive marker of left ventricular dysfunction than ANP.

Markers of left ventricular dysfunction induced by exercise, dipyridamole or combined stress on ECG-gated myocardial perfusion scans.

An index of left ventricular contraction can be extracted from the cavitary time-activity curve of electrocardiographic (ECG)-gated myocardial perfusion scans. To assess the induction of stress-induced myocardial depression, we compared contraction indexes derived from immediate poststress and delayed 201Tl images with indexes of ventricular dilation and lung uptake in the prediction of severe coronary artery disease (defined as two or more 90% stenoses). Stress procedures were performed in 93 patients with symptom-limited supine bicycle exercise alone, and in 227 with intravenous dipyridamole, combined where possible with exercise. The immediate and delayed contraction indexes reflected left ventricular dysfunction on ventriculography (P < 0.0001), but additionally the immediate index was reduced (P < 0.0001) in severe coronary disease. Stress-induced hypokinesis was seen frequently after each of the test modes. The relationship with angiographic findings was better defined for indexes of contraction than for lung uptake or ventricular dilation (P < 0.01). The prediction of severe coronary disease was optimized by combining the poststress contraction index and lung uptake. These data support the use of ECG-gated myocardial scans in evaluating the functional consequences of stress/imaging procedures.

Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. The Adverse Experience Committee; and the Multicenter Diltiazem Postinfarction Research Group.

The Multicenter Diltiazem Postinfarction Trial (MDPIT) reported no consistent diltiazem effect on new or worsened congestive heart failure (CHF) during 12-52 months' follow-up after acute myocardial infarction. This was puzzling in light of the observation that patients with findings suggesting left ventricular dysfunction (LVD) at baseline on diltiazem had more cardiac events (cardiac mortality or recurrent nonfatal infarction) than such patients on placebo. We hypothesized that diltiazem increased the frequency of late CHF as well as of cardiac events, but only in patients predisposed by LVD. Using the same characterizing variables as the primary MDPIT analysis, we found that patients with pulmonary congestion, anterolateral Q wave infarction, or reduced ejection fraction (EF) at baseline were more likely to have CHF during follow-up than those without these markers of LVD. CHF was particularly frequent in the patients with LVD who were randomized to diltiazem. Among those with a baseline EF of less than 0.40, late CHF appeared in 12% (39/326) receiving placebo and 21% (61/297) receiving diltiazem (p = 0.004). Life table analysis in patients with an EF of less than 0.40 confirmed more frequent late CHF in those taking diltiazem (p = 0.0017). In addition, the diltiazem-associated rise in the frequency of late CHF was progressively greater with increasingly severe decrements in baseline EF. This diltiazem effect was absent in patients with pulmonary congestion at baseline but an EF of 0.40 or more, suggesting a unique association between diltiazem-related late CHF and systolic LVD.(ABSTRACT TRUNCATED AT 250 WORDS)

Evolution of the temporal contraction sequence after acute experimental myocardial infarction

The effect of infarct maturation on the temporal sequence of contraction within infarct zones has not previously been described. Accordingly, the time-varying pattern of contraction within ischemic/infarct zones was studied with use of cross-sectional echocardiography in 17 dogs at 10 min to 6 weeks after acute experimental myocardial infarction.Left ventricular short-axis images were digitized from end-diastole to end-systole and endocardial fractional radial change along 36 evenly spaced rays was calculated. The circumferential extent of dyskinesia and the number of rays that exhibited maximal dyskinesia were determined for each decile of the normalized contraction sequence. Between 10 min and 1 week after infarction, the greatest circumferential extent of dyskinesia occurred between the 3rd and 4th deciles of the normalized contraction sequence. However, as the infarct matured, the greatest spatial expanse of dyskinesia was noted to occur progressively earlier in the contraction sequence (second decile at 6 weeks), and the extent of mid- to late-systolic dyskinesia decreased markedly. Whereas end-systolic dyskinesia was present in 30% to 50% of ischemic/infarct zone rays from 10 min to 48 h, end-systolic dyskinesia was no longer observed at 6 weeks. Similarly, the maximal amplitude of dyskinesia was most commonly observed during midsystole from 10 min to 48 h, but occurred progressively earlier as the infarct matured, falling during the first decile at 6 weeks after infarction.These data suggest that maximal circumferential extent and amplitude of dyskinesia occur progressively earlier in the systolic contraction sequence as the infarct matures. An awareness of these temporal variations in the contraction pattern is important in the use of wall motion as a marker of left ventricular dysfunction after myocardial infarction.

Social fate and long-term survival of patients with a recent myocardial infarction, after cardiac rehabilitation.

The aim of this study was to assess the social fate (work resumption) and long-term (four years) survival in 141 patients who completed a cardiac rehabilitation programme after a recent myocardial infarction. Out of the 100 patients who had been working up to recently before the myocardial infarction, 58 resumed their work. Of the predischarge evaluation (clinical data, resting radionuclide ventriculography, bicycle ergometry and 24-h ambulatory ECG monitoring) and bicycle ergometry after the rehabilitation, the only significant predictor of work resumption was a better exercise tolerance at discharge (P less than 0.02). Work was resumed by 68% of white-collar workers and by 52% of blue-collar workers. The four-year cardiac mortality in patients who completed the rehabilitation was 8.5% (N = 12). Four patients died during the first year. Clinical, ventriculographic and ergometric variables collected at hospital discharge, which were related to left ventricular dysfunction, were predictive of survival, while ventricular arrhythmias and markers of myocardial ischaemia were less predictive. The exercise testing performed after the rehabilitation programme was not useful for risk assessment. It is concluded that markers of left-ventricular dysfunction are predictive of a poor outcome; however, due to the low risk of patients who were referred to our rehabilitation unit and completed the rehabilitation programme, it seems reasonable for return to work to be based primarily on clinical information, exercise tolerance, and on psychological and social grounds. An additional extensive cardiological evaluation should be individually tailored for patients with specific symptoms.

Factors determining programmed stimulation responses and long-term arrhythmic outcome in survivors of ventricular fibrillation with ischemic heart disease

The clinical and angiographic features of 38 patients with ischemic heart disease and nonacute infarction pre-hospital ventricular fibrillation (VF) were examined as a function of their drug-free programmed electrical stimulation (PES) responses. Twenty-two patients (58%) had inducible ventricular tachycardia (VT) at drug-free PES (group I) and 16 patients (42%) did not (group II). Group I had more patients with: (1) remote infarction (22 of 22 vs 2 of 16; p < 0.01; (2) history of congestive failure (16 of 22 vs 0 of 16; p < 0.01); (3) prior cardiac arrest (11 of 22 vs 0 of 16; p < 0.01); (4) left ventricular (LV) ejection fraction < 40% (19 of 22 vs 1 of 16; p < 0.01); and (5) akinetic or dyskinetic LV wall motion (22 of 22 vs 2 of 16; p < 0.001). Group II had more patients with: (1) LV segments at “ischemic jeopardy” (16 of 16 vs 14 of 22; p < 0.01) and (2) factors suggestive of ischemia at the onset of VF (13 of 16 vs 1 of 22; p < 0.001). Inducible VT (IVT) was suppressed in 16 of the 20 group I patients surviving hospitalization while four were discharged with persistence of IVT despite therapy. At 27 ± 15 months, all four with persistent IVT had a recurrence of their arrhythmia. In the 16 group II patients, therapy was limited to antilschemic measures: coronary bypass in 12, propranolol in 3, and angioplasty in one. At 38 ± 9 months, no group II patient has had a recurrence of his arrhythmia. In patients with coronary disease and nonacute infarction VF: (1) absence of IVT at drug-free PES is a common finding; (2) patients free of IVT typically have features that implicate acute ischemia in the pathogenesis of VF; and (3) the outcome of such patients is excellent when antilschemic therapy is empioyed. IVT at drug-free PES is typically limited to patients with markers of LV dysfunction. Arrhythmogenesis in the inducible patient appears to derive from a state of chronic electrical instability caused by prior myocardial infarction.

Prognostic importance of thallium uptake by the lungs during exercise in coronary artery disease.

We studied the value of thallium imaging as compared with clinical and exercise-test variables in predicting cardiac events occurring over five years in 525 consecutive patients referred for thallium-exercise testing in 1979. Follow-up was obtained on 467 patients (89 percent). There were 105 cardiac events--25 cardiac deaths, 33 myocardial infarctions, and 47 coronary bypass procedures. A Cox survival analysis identified increased thallium uptake by the lungs, a marker of left ventricular dysfunction during exercise, as the best predictor of a cardiac event (relative risk ratio = 3.5; 95 percent confidence interval, 2.2 to 5.4). The next most powerful predictors were a history of typical angina, a previous myocardial infarction, and ST-segment depression during exercise (relative risk ratios = 2.1, 1.8, and 1.7, respectively). No combination of variables made up for the loss in prognostic power when the variable of increased thallium uptake by the lungs was removed from the model. Cardiac events occurred over five years in 10 (5 percent) of 192 patients with a normal thallium scan, 41 (25 percent) of 163 patients with an abnormal thallium scan but normal thallium activity in the lungs, and 54 (67 percent) of 81 patients with increased thallium uptake by the lungs (P less than 0.0001). We conclude that increased uptake of thallium by the lungs during exercise predicts a high risk of subsequent cardiac events.

Submaximal predischarge exercise testing after myocardial infarction: prognostic value and limitations.

The prognostic value of abnormalities resulting from predischarge submaximal treadmill exercise testing was evaluated in 222 patients after myocardial infarction. The presence of the following variables--ST segment depression and elevation, an abnormal blood pressure response, limited exercise duration, angina pectoris, ventricular arrhythmias--were predictive of subsequent cardiac events (P less than 0.001) among the 154 patients with one or more of these abnormalities. When the presence or absence of specific variables was assessed, only an abnormal blood pressure response, limited exercise duration (P less than 0.001), and ST segment elevation and shift (P less than 0.05), were significantly associated with cardiac death. Exercise-induced angina was predictive only of the development of subsequent angina (P less than 0.05), and ST depression was associated only with future coronary surgery (P less than 0.01). Ventricular arrhythmias had no independent prognostic value. Markers of left ventricular dysfunction elicited by submaximal exercise testing are therefore valuable in identifying patients at high risk of death after infarction. Hallmarks of residual reversible myocardial ischaemia are of limited prognostic importance. The test result may be useful in selecting patients for coronary angiography.

Determinants of operative mortality and long-term survival in patients with unstable angina: The CASS experience

To identify the factors that determine operative mortality and long-term survival, we analyzed the data from 3,311 patients who underwent surgical therapy for unstable angina according to clinical presentation. Overall operative mortality was 3.9% and no differences in operative mortality were found between patients with coronary insufficiency, new-onset angina, rest angina, or changing patterns of angina. Logistic regression analysis indicated that age, left ventricular score, and presence of a left main stenosis in a left dominant circulation were related to operative mortality. The 7 year cumulative survival rate was 79%. Features predictive of long-term outcome by Cox analysis included left ventricular score, congestive heart failure score, other illness, extent of coronary disease, and cardiomegaly. Operative mortality of those patients who underwent coronary bypass during their initial hospitalization with unstable angina was similar to that of patients who were discharged and readmitted for operation at a later date. Thus, patients with unstable angina demonstrate a relatively low operative mortality, which is unrelated to the clinical presentation. Long-term survival is primarily determined by clinical and angiographic markers of left ventricular dysfunction, associated illness, and the extent of coronary disease.

The isovolumic index: A new noninvasive approach to the assessment of left ventricular function in man

Both a high ratio of preejection period (PEP) to left ventricular ejection time (LVET) and a prolonged isovolumic relaxation time are associated with left ventricular dysfunction. In pilot studies in instrumented dogs, we measured a combined isovolumic index, defined as (isovolumic contraction + isovolumic relaxation time)/LVET and found an inverse correlation with changes in fractional shortening. To test the utility of this index in human subjects, we used the electrocardiogram, mitral valve (MV) echogram, and indirect carotid arterial tracing to calculate isovolumic index as (time from R wave to MV opening — LVET)/LVET × 100%. Normal subjects had isovolumic index values that averaged 24 ± 7% (standard deviation), in contrast to patients with cardiomyopathy who averaged 5 ±14% ( p < 0.001 versus normal values) and patients with coronary artery disease who averaged 40 ±15% (p < 0.001 versus normal values and patients with cardiomyopathy). All normal subjects had an isovolumic index of < 32% and all patients with cardiomyopathy had values >32%. Of patients with coronary artery disease, 72% (21 of 29) had an isovolumic index >32%. An isovolumic index >32% identified 20 of 22 patients (91%) with a reduced ejection fraction and 12 of 14 (86% ) with a segmental wall motion abnormality, and it was a more sensitive marker of these abnormalities than abnormal E point-septal separation. In 6 patients with coronary artery disease who had simultaneous echocardiograms and measurements of left ventricular pressure by micromanometer tip catheter, the time constants of isovolumic pressure decrease were uniformly increased in association with an isovolumic index >32%. In contrast, all had normal PEP/LVET ratios. The isovolumic index is thus a sensitive, potentially useful noninvasive marker of left ventricular dysfunction that is easily obtained from the routine echocardiogram.