Left ventricular pressure-volume analysis by radionuclide angiography.
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Biomedical subjects
Publications and source records attributed to M V Green.
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Successful coronary artery bypass grafting (CABG) improves exercise-induced left ventricular (LV) dysfunction in patients with coronary artery disease (CAD), but its potential for improving resting LV function remains controversial. To assess the influence of CABG on LV function at rest, 31 CAD patients without previous myocardial infarction were studied before and 6 months after CABG by radionuclide angiography after all cardiac medicines were withdrawn. No patient had angina or ischemic electrocardiographic changes at rest. In 27 patients with patent bypass grafts, CABG significantly increased LV ejection fraction during exercise (47 +/- 11% before to 63 +/- 9% after operation, p less than 0.001), indicating reduction in exercise-induced LV ischemia. Moreover, LV ejection fraction at rest also increased (55 +/- 9 to 60 +/- 8%, p less than 0.001), with 20 of 27 patients manifesting an increase compared with preoperative values. Eleven of these 20 patients had apparently normal LV function at rest (ejection fraction and regional wall motion) before CABG. LV regional ejection fraction was computed by dividing the LV region of interest into 20 sectors. Regional analysis indicated that improved ejection fraction at rest after CABG occurred in regions developing ischemia during exercise before CABG. In 4 patients with occluded grafts, the ejection fraction at rest was unchanged by CABG globally (59 +/- 8 to 58 +/- 9%, difference not significant) and regionally. Thus, LV global and regional function at rest improved after successful CABG, even in patients with normal global LV ejection fraction and no visually detectable wall motion abnormality before surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
In many patients with coronary artery disease or hypertrophic cardiomyopathy, reduced left ventricular rapid diastolic filling is related to asynchronous left ventricular regional diastolic function. Because left ventricular filling also declines with aging in normal subjects, in this study the influence of regional ventricular diastolic asynchrony on global ventricular filling as a function of age was investigated in 66 normal volunteers aged 19 to 77 years (mean 42) by radionuclide angiography. No subject had systemic hypertension or left ventricular hypertrophy. Indexes of left ventricular systolic function at rest did not vary with age, but rapid diastolic filling significantly declined with age: peak filling rate decreased (r = 0.69), time to peak filling rate increased (r = 0.53) and magnitude of rapid filling (% of left ventricular end-diastolic volume) decreased (r = 0.76) with aging. Left ventricular synchrony was assessed from regional volume curves derived by dividing the global ventricular region of interest into four quadrants. Indexes of systolic synchrony were unaffected by age, but regional variation in time to peak filling rate, an index of diastolic asynchrony, increased with aging (r = 0.51, p less than 0.001). Moreover, variation in time to peak filling rate correlated with global peak filling rate and magnitude of rapid filling (r = 0.48 and 0.54, p less than 0.001 for both). Multivariate analysis indicated that these effects were independent of age-related changes in blood pressure. Thus, aging alters left ventricular diastolic function, with reduced rate and extent of the rapid filling phase related to increased regional diastolic asynchrony.(ABSTRACT TRUNCATED AT 250 WORDS)
A method is presented for obtaining accurate positron emission tomography transmission measurements after tracer injection. A transmission scan is performed using a rotating source immediately before or after a conventional emission scan. Sinogram windowing, which removes most scattered and random coincidences, also removes most of the emission counts contaminating the transmission measurement. Data from the emission scan can be used to subtract the remaining emission counts to produce accurate transmission measurements. For studies with moderate to low emission count rates (e.g., fluorodeoxyglucose) there is little increase in noise in the resulting attenuation correction factors. This method was tested in experiments with phantoms and a rotating source simulator and validated against conventional ring transmission measurements. Applications of the technique can significantly shorten the time between transmission and emission studies, and thereby reduce the likelihood of patient motion and increase scanning throughput.
ECG gated gamma-ray energy spectra from the left ventricle were created each 50 msec during the cardiac cycle. Nine of ten subjects were studied with a nonimaging Nal probe, and the tenth with a high-resolution Germanium detector. Placing multiple energy windows over the energy spectra, EF was found to vary with the energy window selected. Moving a 20% window across the photopeak produced a roughly linear increase in EF with energy (2.3 EF units per 10 keV increase in energy) in eight of the ten subjects. Dividing the photopeak into a low (126-140 keV) and high-energy (140-154 keV) portion gave significantly different EFs (high energy exceeding low energy by 17%). Increasing the width of a narrow window centered about the photopeak produced negligible change in EF. Examining the energy spectra showed that the small-angle scattered radiation (126-139 keV) was proportionately greater at end systole than at end diastole, after normalizing the spectra to the same photopeak area.
Patients with coronary artery disease (CAD) may undergo periods of reversible myocardial ischemia without experiencing angina. To study the prognostic implications of "silent" myocardial ischemia induced by exercise, exercise electrocardiography and radionuclide angiography were performed in 131 consecutive patients with CAD, preserved left ventricular (LV) function at rest and mild or no symptoms during medical therapy. All patients who died during medical therapy were in the subgroup of patients with 3-vessel CAD in whom exercise-induced ischemia developed, which was characterized by both a decrease in LV ejection fraction and ST-segment depression. Patients in whom angina pectoris developed during exercise (54% of all patients) had a greater prevalence of this combined ischemic response to exercise than patients without angina (61% vs 27%, p less than 0.001) and also a greater prevalence of left main or 3-vessel CAD (59% vs 25%, p less than 0.001). However, when inducible ischemia was demonstrated, risk stratification and prognosis were the same whether the ischemic episode was symptomatic or silent. Among patients having both a reduction in ejection fraction and a positive ST-segment response, the likelihood of significant left main narrowing (13% vs 26%), 3-vessel CAD (56% vs 51%) and death during subsequent medical therapy (16% vs 9%) was similar in patients with silent compared to those with symptomatic ischemia. These data indicate that patients in whom angina develops during exercise have a greater prevalence of high-risk coronary anatomy and of inducible ischemia than patients without angina. However, once inducible ischemia is documented, the symptomatic response to exercise appears irrelevant for prognostic or risk stratification considerations.
Left ventricular relaxation and filling are impaired in many patients with hypertrophic cardiomyopathy. To investigate the influence of regional heterogeneity on these global abnormalities, 48 patients with hypertrophic cardiomyopathy and sinus rhythm were studied by radionuclide angiography before and after 1 to 2 weeks of verapamil therapy (320 to 640 mg/day, median 480). Left ventricular regional function was assessed by subdividing the ventricular region of interest into 20 sectors and into four quadrants from which regional time-activity curves were derived. Diastolic asynchrony was measured as the regional variation in timing between minimal volume and peak filling rate, and heterogeneity in the magnitude of rapid diastolic filling was measured as the regional variation in percent contribution of atrial systole to end-diastolic volume. Compared with 28 normal subjects, the patients with hypertrophic cardiomyopathy had greater regional variation in both timing (35 +/- 24 versus 12 +/- 6 ms, p less than 0.001) and magnitude (10 +/- 6 versus 7 +/- 4%, p less than 0.02) of rapid filling. Verapamil reduced the regional variation in timing (to 21 +/- 16 ms, p less than 0.001) and magnitude (to 7 +/- 3%, p less than 0.001) of rapid filling. These regional changes, indicating more uniform regional diastolic performance after verapamil, were associated with improved global diastolic filling: global rapid filling increased in both rate and magnitude and time to peak filling rate decreased. These findings indicate that the beneficial effect of verapamil on left ventricular diastolic function in hypertrophic cardiomyopathy may be mediated by reduction in regional asynchrony.
The role of rest and exercise radionuclide angiography (RNA) in predicting the cardiotoxic effects of doxorubicin was assessed prospectively in 48 patients who received a mean total doxorubicin dose of 522 mg/m2 (range 480 to 600). Thirty-three of these patients also received cyclophosphamide (mean 5,220 mg/m2). Left ventricular (LV) ejection fraction (EF) at rest progressively decreased from the baseline value of 55 +/- 9% to 52 +/- 8% after 338 mg/m2 to 47 +/- 8% after completion of doxorubicin therapy (p less than 0.001). In 42 patients (88%) EF at rest decreased after doxorubicin administration. Although no patient had known prior heart disease, the EF response to exercise was abnormal in 11 patients before doxorubicin. EF at rest after doxorubicin was significantly lower (41 +/- 6% vs 49 +/- 8%, p less than 0.02) in these 11 patients than in the 29 patients in whom the pretreatment EF response to exercise was normal, and in 4 of the 11 patients congestive heart failure developed. While age was an independent risk factor, cyclophosphamide did not appear to enhance the cardiotoxicity of doxorubicin. By multivariate analysis, age (p = 0.01) and EF at the midcourse of doxorubicin therapy (p less than 0.001) were the most significant predictors of final EF after completion of doxorubicin therapy; neither rest nor exercise EF before doxorubicin appreciably improved the predictive value of age and EF at midcourse of therapy. Thus, some depression of LV function occurs in most patients receiving doxorubicin, and patients with abnormal baseline function appear to be at greater risk of clinical congestive heart failure after doxorubicin therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
Left ventricular isovolumic relaxation and the relation between relaxation and filling were studied in 90 patients with hypertrophic cardiomyopathy and 29 control subjects using radionuclide angiography. The isovolumic relaxation period was determined automatically on left ventricular time-activity curves as the interval between minimal volume and onset of rapid filling. In 17 patients, M-mode echocardiography performed simultaneously with radionuclide angiography demonstrated that onset of mitral valve opening correlated well with onset of rapid filling (r = 0.84, p less than 0.001). The isovolumic relaxation period was longer in patients with hypertrophic cardiomyopathy than in control subjects (95 +/- 44 versus 50 +/- 23 ms, p less than 0.01) and was longer in patients without an outflow tract gradient at rest than in patients with a gradient (109 +/- 37 versus 86 +/- 35 ms, p less than 0.05). In these patients without obstruction, a weak linear relation between duration of the isovolumic period and peak filling rate was found (r = 0.48, p less than 0.02). Filling was impaired in patients with hypertrophic cardiomyopathy, as assessed by lower peak filling rate (3.2 +/- 1.2 versus 3.5 +/- 0.5 end-diastolic volume/s, p less than 0.05) and prolonged time to peak filling rate (185 +/- 44 versus 145 +/- 20 ms, p less than 0.01) compared with values in control subjects. The delay in time to peak filling rate was caused primarily by the prolonged isovolumic period, because the interval from onset of rapid filling to peak filling rate was similar in patients with hypertrophic cardiomyopathy and control subjects (87 +/- 31 versus 95 +/- 25 ms, NS).(ABSTRACT TRUNCATED AT 250 WORDS)
Although alpha-adrenergic stimulation can increase coronary vascular resistance, it remains unknown whether the vasoconstriction can override intrinsic coronary regulatory influences to produce ischemia. Methoxamine, 2 to 4 mg, was infused into the circumflex coronary artery of 23 chloralose-anesthetized open chest dogs, and resulted in a 68% increase in coronary vascular resistance. The functional consequence of this increased coronary vascular resistance was assessed by gated radionuclide ventriculography and ST-T wave changes on the electrocardiogram. In six dogs (Group I), aortic pressure changed trivially (less than 5 mm Hg) to allow distinction between direct effects of the flow reduction and indirect effects of increased aortic pressure. In this group, coronary blood flow decreased 33% from a control value of 44 +/- 10 ml/min (p less than 0.001) and left ventricular ejection fraction decreased from 0.54 +/- 0.12 to 0.46 +/- 0.10 (p less than 0.025). In eight dogs (Group II) in which aortic pressure increased by more than 5 mm Hg, left ventricular ejection fraction decreased from 0.46 +/- 0.07 to 0.39 +/- 0.09 (p less than 0.002). Pressure gradients were measured between the aorta and a distal coronary artery branch to calculate small and large vessel resistances separately in four other dogs (Group III). The resistance of small coronary arteries accounted for 92% of the total increase in coronary vascular resistance produced by methoxamine. In five other dogs (Group IV), intracoronary methoxamine, 2 mg, produced ST-T wave changes suggestive of ischemia as it increased coronary vascular resistance by 33%.(ABSTRACT TRUNCATED AT 250 WORDS)
A new technique called the weighted integration method for the measurement of local CBF (LCBF) in humans with positron emission tomography (PET) is presented. LCBF is calculated from weighted time integrals of the blood and tissue radioactivity curves. This method is computationally efficient and achieves nearly optimal statistical estimation of LCBF. The predicted root mean squared error of the weighted integration method is verified by simulation studies and is only 1-2% larger than the minimum possible error that can be achieved by an ideal estimation algorithm. For LCBF of greater than 30 ml/min/100 g, the weighted integration method provides reduced noise compared with the integrated projection technique, the PET autoradiographic method, and the steady-state technique. In addition, an error analysis is performed to study the sensitivity of the weighted integration method to tissue mixtures, blood sample timing errors, and changes in LCBF during the data collection period.
Thirty-three patients with chest pain despite angiographically normal coronary arteries underwent both coronary flow studies during pacing and resting and exercise gated blood pool scintigraphy. During atrial pacing after administration of ergonovine, those patients developing their typical chest pain demonstrated significantly lower great cardiac vein flow (97 +/- 31 vs 150 +/- 33 ml/min, p less than .001), higher coronary resistance (1.27 +/- 0.43 vs 0.77 +/- 0.18 mm Hg/ml/min, p less than .005), and less lactate consumption (30.5 +/- 22.0 vs 69.7 +/- 41.1 mM . ml/min, p less than .005) and a higher left ventricular end-diastolic pressure after pacing (20 +/- 4 vs 12 +/- 1, p less than .001) compared with those without pain and in the absence of significant luminal narrowing of the epicardial coronary arteries. The 26 patients with abnormal vasodilator reserve demonstrated reduced left ventricular ejection fraction during exercise (58 +/- 8%) compared with the seven patients with appropriate vasodilator reserve (66 +/- 4%, p less than .05) and with a group of 52 control patients of similar age and sex distribution and free of known heart disease (66 +/- 10%, p less than .001). In addition, 12 of the 26 patients with abnormal vasodilator reserve demonstrated exercise-induced regional wall motion abnormalities. Many of these patients also manifested impaired left ventricular diastolic filling at rest compared with the control subjects (peak filling rate 2.6 +/- 0.7 vs 3.2 +/- 0.7 end-diastolic volume/sec, p less than .005). Thus, patients with chest pain resulting from abnormal vasodilator reserve demonstrate abnormalities of left ventricular systolic and diastolic function suggestive of myocardial ischemia.
Left ventricular diastolic filling is impaired in many patients with coronary artery disease and normal left ventricular systolic function, and is improved in many patients after coronary angioplasty (PTCA). To investigate the mechanisms for this improvement, we studied regional asynchrony by radionuclide angiography in 26 patients with single-vessel coronary artery disease before and after successful PTCA. Before PTCA, all patients had normal ejection fractions at rest and normal qualitative left ventricular regional wall motion, as determined by radionuclide and contrast angiography. Quantitative left ventricular regional function was assessed by dividing the left ventricular region of interest into 20 sectors. Phase analysis was performed on each sector's time-activity curve, and the average intersector phase difference was used as an index of left ventricular regional synchrony. Before PTCA, average intersector phase difference was increased compared with normal (6.0 +/- 2.2 vs 4.0 +/- 1.7 degrees, p less than .005), indicating asynchronous regional function. After PTCA, ejection fraction at rest was unchanged, but peak left ventricular filling rate at rest increased from 2.5 +/- 0.6 to 3.0 +/- 0.6 end-diastolic volume/sec (p less than .001) and was associated with a decrease in average intersector phase difference from 6.0 +/- 2.2 to 5.1 +/- 2.3 degrees (p less than .05). Average intersector phase difference decreased in 16 of 21 patients in whom peak filling rate increased after PTCA (p less than .005), compared with one of five patients in whom peak filling rate was unchanged or decreased. Hence, improved global left ventricular filling after PTCA was associated with more synchronous left ventricular regional behavior. To identify the cause of regional asynchrony before PTCA, we then generated time-activity curves from each of four left ventricular quadrants. These data indicated that the asynchrony was caused by regional variation in timing of diastolic rather than systolic events and that PTCA resulted in reduction in regional diastolic asynchrony. These data suggest that in many patients with coronary artery disease and normal left ventricular systolic function, impaired global diastolic filling may result from asynchronous left ventricular regional diastolic function, which is a reversible manifestation of myocardial ischemia or reduced coronary flow.
Verapamil improves exercise tolerance and decreases symptoms in many patients with hypertrophic cardiomyopathy. The mechanisms responsible for these effects are not completely understood, although previous studies indicate that verapamil enhances left ventricular relaxation and diastolic filling in such patients. To investigate the association between changes in left ventricular filling and exercise tolerance after verapamil, we studied 55 patients with hypertrophic cardiomyopathy by radionuclide angiography and graded treadmill testing before and after 1 to 4 weeks of therapy with orally administered verapamil, 320 to 640 mg/d. The verapamil-induced increase in peak left ventricular filling rate at rest (from 3.1 +/- 1.3 to 3.7 +/- 1.3 end-diastolic volumes/sec; p less than .001) was associated with an increase in exercise tolerance (from 5.9 +/- 3.6 to 8.7 +/- 4.7 min; p less than .001); exercise capacity increased in 34 of 43 patients (79%) manifesting an increase in peak filling rate but only one of 12 patients (8%) with unchanged or decreased peak filling rate (p less than .001). This initial trend persisted in 25 patients studied after 1 year of therapy; 11 of 16 patients (69%) with a persistent increase in peak filling rate had persistent improvement in exercise tolerance relative to preverapamil values, compared with only one of nine patients (11%) in whom peak filling rate was unchanged or decreased relative to preverapamil levels (p less than .02). Verapamil withdrawal after 1 to 2 years in 24 patients resulted in reduction in peak filling rate (p less than .001) and was associated with deterioration in exercise tolerance in 17 patients (71%). Hence, verapamil-induced changes in left ventricular peak filling rate were associated significantly with objective symptomatic improvement. These data support the concept that enhanced left ventricular diastolic filling is an important mechanism contributing to the clinical improvement experienced by many patients with hypertrophic cardiomyopathy during therapy with verapamil.
To demonstrate that the anorexia and depletion of cachexia reverses on tumor removal, F344 rats underwent sarcoma resection when their food intake fell to 0 g/day. In survivors of surgery, reversal in food intake was apparent within 3 days postoperatively, followed after 2 days by gain in host weight. To detect whether the transmission of anorexia/cachexia in these tumor-bearing (TB) rats was via the circulation, four groups were studied: single non-tumor bearing (NTB); single TB; parabiotic NTB; and parabiotic TB. The measured blood exchange rate between parabiotic halves was 1.2-1.5%/min. No cachectic effect was detected in either half of the NTB parabionts. There was no evidence of sarcoma metastases in the tumor-free half of the parabiotic TB pair. All the rats associated with the presence of tumor showed cachectic effects but the degree and timing of effect varied among the three conditions, single TB, parabiotic TB half, and parabiotic tumor-free half. In all variables examined (fall in food intake, time of first fall in food intake, host weight loss, elevation of blood urea nitrogen) the severities were always in the same sequence: single TB greater than parabiotic TB half greater than parabiotic tumor-free half greater than NTB. In addition, the TB parabiotic pair had a significantly longer survival time and grew a significantly larger tumor than did the single TB animal. The parabiotic tumor had a slower initial growth rate and a slower deceleration rate than the singlet tumor. These results provide evidence for the humoral mediation of cancer-associated cachexia.
To determine prospectively whether the severity of reversible left ventricular ischemia provides prognostic information in mildly symptomatic patients with coronary-artery disease and preserved left ventricular function at rest (ejection fraction greater than 40 per cent), we studied 117 patients by means of exercise electrocardiography and radionuclide angiography. No patient had stenosis of the left main coronary artery. Mortality during subsequent medical therapy was significantly associated (by univariate life-table analysis) with three-vessel coronary-artery disease and the magnitude of the ejection fraction during exercise. In patients with three-vessel disease who had both ST-segment depression of 1 mm or more and a decrease in ejection fraction during exercise, in association with an exercise tolerance of 120 W or less, the probability of survival at four years was only 71 +/- 11 per cent (S.E.). All deaths occurred in this subgroup. Thus, objective evidence of left ventricular ischemia during exercise and exercise capacity identify one subgroup of minimally symptomatic patients with three-vessel disease with an excellent prognosis and another subgroup at relatively high risk of dying during subsequent medical therapy.
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Asynchronous motion of left ventricular myocardium during the period of left ventricular isovolumic relaxation has often been observed in patients with coronary artery disease. Detection and quantitation of this abnormality with noninvasive nuclear tracer methods, however, have not yet been reported. Thus, functional images of regional left ventricular time to minimum counts (or volume), computed from gated blood pool image sequences, were analyzed to detect and quantitate myocardial asynchrony during this interval. The method was tested by comparing regional with global time to minimum counts before and after coronary artery occlusion in the awake dog. After occlusion, minimum counts in the ischemic region occurred later in the cardiac cycle than did global minimum counts (average difference 69 +/- 37 ms, p less than 0.001). Before occlusion, however, minimum counts in the same region occurred at the same moment as global minimum counts (average difference 4 +/- 12 ms, NS). Thus, acute ischemia in dogs produces a pronounced asynchrony in myocardial motion during the earliest moments of diastole. The magnitude of this asynchrony (69 ms) probably corresponds to the length of the global isovolumic relaxation period in these animals after occlusion. This method might be useful in detecting and quantitating isovolumic asynchrony in ischemia and changes in this asynchrony with therapy (verapamil therapy, for example).