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Since atrial fibrillation (AF) impacts the measurement and interpretation of left ventricular ejection fraction (LVEF), we hypothesized that the outcome in heart failure (HF) with AF and LVEF ≤ 35% would be more strongly associated with neurohormonal measures than LVEF. Cardiac adverse events [CAE; HF progression (HFP), life-threatening arrhythmia (ARR), and cardiac death (CD)] and all-cause mortality (ACM) were recorded prospectively in 954 patients with HF and LVEF ≤ 35%: 852 in sinus rhythm (SR) and 102 in AF. Cox proportional hazard models found that the univariate hazard ratios (HR) for LVEF and the first CAE (primary outcome), HFP, ARR, CD, and ACM were significant in SR (0.933, P

We previously developed an operator-interactive method for the measurement of left ventricular (LV) and right ventricular (RV) ejection fraction (EF) and end-systolic volume (ESV) and end-diastolic volume (EDV) using single-photon emission tomographic equilibrium radionuclide angiocardiography (SPECT ERNA). We aimed to compare our SPECT ERNA method with cardiac MRI (CMRI) for the determination of ventricular measures.Paired measurements of LV and RV EFs and ESV and EDV were carried out by SPECT ERNA and CMRI in a group of patients who had myocardial infarction due to left anterior descending coronary artery thrombosis.SPECT ERNA and CMRI provided similar estimations of the mean (SD) LV ESV [61 (23) vs. 61 (32) ml; P=0.99] and LV EDV [134 (29) vs. 141 (44) ml; P=0.28]. The mean (SD) LV EF by SPECT ERNA was slightly but significantly smaller than that by CMRI [0.55 (0.10) vs. 0.58 (0.11) ml; P=0.03]. SPECT ERNA, compared with CMRI, produced similar mean (SD) values of RV ESV [62 (17) vs. 67 (17) ml; P=0.10] and RV EDV [153 (28) vs. 149 (29) ml; P=0.51] and somewhat larger mean (SD) RV EF [0.60 (0.06) vs. 0.55 (0.06) ml; P0.001]. Excellent correlations were found between SPECT ERNA and CMRI for combined LV ESV and EDV (R=0.85, P0.001) and combined RV ESV and EDV (R=0.85, P0.001).This study further validates SPECT ERNA as a method to measure LV and RV EF, ESV, and EDV.

Background In patients with heart failure and reduced left ventricular ejection fraction (LVEF), the effect of upgrading from right ventricular (RV) apical to biventricular pacing on RV and left ventricular (LV) volumes and ejection fraction (EF) is unknown. Also, the relationship of symptom improvement after biventricular upgrade to RV and LV volumes and EF has not been clarified.

Successful thromboendarterectomy for chronic thromboembolic pulmonary hypertension promptly improves right ventricular (RV) function by decreasing RV volume and increasing ejection fraction (EF). Single photon emission computed tomography (SPECT) equilibrium radionuclide angiocardiography (ERNA) has been validated as a measure of RV and left ventricular (LV) volume and EF.Nine patients with chronic thromboembolic pulmonary hypertension underwent electron beam computed tomography (EBCT) and SPECT ERNA cardiac studies before and after thromboendarterectomy. EBCT and SPECT ERNA measures of RV and LV volume and EF were compared. Before thromboendarterectomy, EBCT and SPECT ERNA RV and LV volumes and RV EF were similar. LV EF was within the normal range with both methods but was slightly greater (P = .004) when measured by EBCT (mean +/- SD, 0.61 +/- 0.08) compared with SPECT ERNA (0.54 +/- 0.10). Thromboendarterectomy measured by EBCT and SPECT ERNA produced marked similar and significant decreases in RV end-systolic (-72 +/- 59 mL vs -58 +/- 25 mL) and end-diastolic (-75 +/- 85 mL vs -76 +/- 32 mL) volumes and similar slight increases in RV EF (0.12 +/- 0.07 vs 0.05 +/- 0.06). Slight decreases in mean LV end-systolic (-19 +/- 23 mL vs -5 +/- 13 mL, P = .05) and end-diastolic (-32 +/- 53 mL vs -9 +/- 31 mL, P = .21) volumes occurred, with little change in mean LV EF (0.05 +/- 0.07 vs 0.00 +/- 0.10).SPECT ERNA is an accurate method for measuring RV and LV volume and EF before and after thromboendarterectomy.

The frequency and determinants of early rapid diastolic filling abnormalities in the community and in cardiac patients are poorly understood.Early left ventricular (LV) rapid filling was assessed via equilibrium radionuclide angiocardiography in 70 community volunteers (LV ejection fraction [EF]or = 0.50) and 778 cardiac patients, all aged at least 45 years. The frequency of early rapid filling and the independent clinical, therapeutic, and hemodynamic variables predictive of early rapid filling abnormality were determined. Depending on the parameter assessed, early rapid filling was abnormal in 27% to 54% of the community volunteers, 34% to 53% of cardiac patients with an LVEF of 0.50 or greater, and 42% to 67% of cardiac patients with an LVEF lower than 0.50. On the basis of multivariate analysis, models of clinical, therapeutic, and hemodynamic variables were modestly predictive of early rapid filling abnormality. Age, sex, valvular insufficiency, hypertension, digoxin use, and heart rate were independent determinants of early rapid filling.In participants aged older than 44 years, early rapid filling was frequently abnormal in the community volunteers and in patients with an LVEF of 0.50 or greater and was most common in patients with an LVEF lower than 0.50. Clinical, therapeutic, and hemodynamic variables had modest independent predictive value for early rapid filling abnormality.

Background Heart failure with preserved left ventricular ejection fraction (LVEF) suggests isolated diastolic dysfunction. Aim The purpose of this study was to determine if systolic and diastolic dysfunction occurred with preserved LVEF. Methods Equilibrium resting radionuclide ventriculograms from 439 patients with an LVEF ≥0.50 were used to determine LV peak filling rate (PFR) and peak ejection rate (PER) in end-diastolic volumes per second and LV end-systolic volume (ml). Patients with low-normal (n=147; range, 0.50−0.58; mean±S.D., 0.53±0.02), intermediate-normal (161, 0.59−0.64, 0.61±0.02), and high-normal (131, 0.65−0.94, 0.72±0.06) LVEF were compared. Results From low-normal to intermediate-normal to high-normal LVEF, LV end-systolic volume decreased (93±36, 71±33, 43±26, respectively, P

To further characterize the effects of heart rate on systolic and diastolic function in patients with idiopathic dilated cardiomyopathy (IDCM), it was hypothesized that the relationship between heart rate and left ventricular systolic and diastolic function would be unaltered by beta-blockade and exercise.Eighteen patients with IDCM were randomized in a double-blind manner to receive either metoprolol or placebo for 3 months. Before and after 3 months of therapy, resting and exercise radionuclide left ventriculograms were obtained for assessment of left ventricular systolic and diastolic function.At rest, metoprolol treatment compared with placebo was associated with decreased heart rate (61 +/- 11 vs 99 +/- 10 beats/min, P.0001) and an increased left ventricular ejection fraction (0.32% +/- 0.10% vs 0.17% +/- 0.08%, P =.01). With exercise, metoprolol compared with placebo caused a decreased heart rate (86 +/- 18 vs 126 +/- 43 beats/min, P =.056), an increase in left ventricular ejection fraction (0.32% +/- 0.14% vs 0.19% +/- 0.07%, P =.052), a longer time to peak filling rate (164 +/- 21 vs 127 +/- 17 ms, P =.005), and a decreased peak filling rate (5.41 +/- 1.71 vs 8.40 +/- 1.85 stroke volumes/s, P =.012). Before beta-blockade, heart rate at rest was negatively correlated to left ventricular ejection fraction and positively correlated to peak filling rate; with exercise, the relationships of heart rate to left ventricular ejection fraction and peak filling rate were similar. After metoprolol treatment, the heart rate continued to have a similar positive correlation with the peak filling rate at rest and with exercise.In patients with IDCM, systolic and diastolic cardiac function, at rest and with exercise, was related to heart rate. After beta-blockade, at rest and with exercise, diastolic function continued to be related to heart rate.

Left ventricular function is modified by respiration and pericardial constraint. The aim of this study was to compare left ventricular systolic and diastolic function during inspiration and expiration in four patient groups: patients (1) without cardiac disease, (2) with severe pulmonary disease, (3) with cardiac amyloid and (4) with pericardial constriction (before and after pericardiectomy). Using blood-pool left ventriculography with modified gating, we obtained time-activity curves at the onset of inspiration and expiration. On inspiration and expiration, patients with pericardial constriction and patients with cardiac amyloid were significantly different from those without cardiac disease and those with severe pulmonary disease, in that left ventricular ejection fraction (LVEF) was less, peak filling rate was greater, time to peak filling rate was shorter, and rapid filling fraction was increased. When inspiration and expiration were compared, time to left ventricular peak filling rate was shorter (P = 0.05) on inspiration (118 +/- 48 ms) than on expiration (168 +/- 35 ms) in patients with pericardial constriction. No other measures differed between inspiration and expiration in pericardial constriction, and left ventricular function was unaffected by respiration in the other groups. Time to left ventricular peak filling rate was 49 +/- 69 ms less on inspiration than on expiration in pericardial constriction and this difference was significantly different (P = 0.04) from that in patients with cardiac amyloid (34 +/- 58 ms greater), patients without cardiac disease (2 +/- 69 ms greater) and patients with severe pulmonary disease (19 +/- 63 ms less). In pericardial constriction, pericardial resection caused an increase in LVEF without a change in left ventricular diastolic filling but abolished the differences present between inspiration and expiration in time to left ventricular peak filling rate. This respiratory response in time to left ventricular peak filling rate may be valuable in the diagnosis of pericardial constriction.

Background— Patients with diabetes mellitus have accelerated progression of heart failure and often have impaired cardiac sympathetic innervation. The present study examines the implications for heart failure progression of cardiac sympathetic denervation, assessed by I-123 metaiodobenzylguanidine imaging, in diabetic compared with nondiabetic subjects. Methods and Results— We evaluated 343 diabetic and 618 nondiabetic subjects with New York Heart Association class II or III heart failure and a left ventricular ejection fraction ≤35% over a median follow-up of 17 months. A multivariable Cox proportional hazards model was used to examine the influence of clinical variables, b-type natriuretic peptide, plasma norepinephrine, left ventricular ejection fraction, and I-123 metaiodobenzylguanidine imaging parameters on time to a heart failure event. The late heart-to-mediastinum (H/M) ratio and the interaction term of diabetes mellitus with the prospectively selected late H/M ratio Conclusions— The combination of diabetes mellitus and I-123 metaiodobenzylguanidine H/M ratio is an independent predictor of heart failure progression, confirming the high risk of diabetic subjects with impaired cardiac sympathetic nerve function. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00126438 and NCT00126425.

Background A method that uses single photon emission computed tomography (SPECT) equilibrium radionuclide angiocardiography (ERNA) to measure right ventricular (RV) and left ventricular (LV) volumes (in milliliters) and ejection fraction (EF) is described. Methods and Results We recorded 35 paired SPECT ERNA and electron beam computed tomography (EBCT) cardiac studies in 27 patients; for comparison with EBCT, a method for measurement of RV and LV volumes and EF with SPECT ERNA was developed in 18 paired studies and was validated and assessed for reproducibility in 17. Validation indicated that SPECT ERNA and EBCT were similar for measurement of RV volume (end-systolic and end-diastolic volumes in a combined analysis) and EF (180 ± 74 mL vs 182 ± 80 mL and 0.44 ± 0.11 vs 0.43 ± 0.11, respectively) and for measurement of LV volume and EF (88 ± 36 mL vs 84 ± 43 mL and 0.53 ± 0.081 vs 0.59 ± 0.07, respectively). The SPECT ERNA method was quite reproducible. Conclusions RV and LV volumes and EF can be measured readily via SPECT ERNA.

The Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT) risk score was derived from the PURSUIT trial population for 30-day mortality prediction.The PURSUIT risk score was calculated for 337 consecutive Olmsted County residents with non-ST-elevation acute myocardial infarction admitted to the coronary care unit of our institution from 1988 through 1998. Predischarge ejection fraction (EF) measurement was available for 246 patients (73%). After excluding patients with prior coronary artery bypass graft surgery (n = 42), 219 patients (65%) had coronary angiography within 30 days of admission. Mortality at 30 days was 8.9%. Among 30-day survivors, mortality at 1 year was 7.9%.Mean age was 70 +/- 13 years, and 37% of patients were women. Mean predischarge EF was 52% +/- 16%. Patients with higher PURSUIT risk score had lower EF (P.001). Three-vessel (or =70% stenosis in all 3 coronary arteries) or left main (or =50% stenosis) coronary artery disease was present in 60 of 219 patients (27%) who had coronary angiography. Higher PURSUIT risk score was associated with greater likelihood of 3-vessel or left main disease (P.001). The PURSUIT risk score had very good predictive accuracy for both early (30-day, C-statistic = 0.78) and late (30-day to 1-year, C-statistic = 0.77) mortality.The PURSUIT risk score correlates with EF, angiographic severity of coronary artery disease, and short- and long-term mortality of nonselected patients with non-ST-elevation acute myocardial infarction.

Diastolic and systolic left ventricular (LV) function may be affected early after the initiation of doxorubicin therapy. However, the role of mediastinal radiation and other cytotoxic agents in the production of these early cardiac effects is unclear. In this study LV diastolic and systolic function were assessed before and after doxorubicin (223+/-122 mg.m-2; range, 40-618) in 33 patients. After doxorubicin, LV ejection fraction declined (0.61+/-0.08 to 0.56+/-0.08, P=0.0008), peak filling rate decreased (3.38+/-1.10 to 2.82+/-0.62 end diastolic volumes/s, P=0.006), and time to peak filling rate increased (162+/-39 to 182+/-45 ms, P=0.04). The changes in LV systolic and diastolic function were not related to doxorubicin dose and the use of other cytotoxic agents; the decrease in LV ejection fraction with doxorubicin was more notable in men and in patients who received mediastinal irradiation concurrently with doxorubicin. It is concluded that the use of doxorubicin was associated with the simultaneous early development of LV systolic and diastolic dysfunction. Male gender and concurrent mediastinal irradiation were independent influences, but doxorubicin dose and the use of other cytotoxic agents were not associated with worse cardiac dysfunction.

To determine whether an increased QRS duration in the absence of bundle branch block (BBB) on the presenting electrocardiogram of patients with acute myocardial infarction (AMI) is associated with decreased survival, we retrospectively reviewed 781 consecutive patients admitted to the coronary care unit of our institution with AMI without BBB between 1988 and 1998. In patients with ST elevation AMI (n = 412), the groups with QRS durationor =100 ms and100 ms had similar survival. Conversely, in patients with non-ST elevation AMI (n = 369), in-hospital, 1-, 3-, and 5-year survival was 84.4%, 75.6%, 66.7%, and 52.2%, respectively, in the group with QRSor =100 ms compared with 95.4%, 89.2%, 83.8%, and 74.3%, respectively, in the group with QRS100 ms (p0.01, log-rank test). In patients with non-ST elevation AMI, those with QRS durationor =100 ms were more likely to be men, to have had a prior AMI that healed, to be in Killip class II, III, or IV, and to have lower ejection fraction than patients with QRS duration100 ms. After adjusting for age, sex, prior AMI or stroke, heart rate, and Killip class on admission, QRS durationor =100 ms was independently associated with in-hospital and overall mortality in patients with non-ST elevation AMI. QRS durationor =100 ms in the absence of BBB is an independent predictor of increased mortality in patients with non-ST elevation AMI.

The role of reverse remodelling of the right and left ventricle and symptom improvement after biventricular upgrade {#article-title-2} Background and objectives The role of right (R) and left (L) ventricular (V) reverse remodelling in symptom improvement after biventricular upgrade is unclear. Methods Tomographic radionuclide angiocardiographic RV and LV end-diastolic (EDV, mL) and end-systolic (ESV, mL) and New York Heart Association heart failure class (NYHA) were determined before and 3–6 months after upgrading from persistent RV pacing to persistent biventricular pacing in 19 patients. Results Symptoms improved (a decline in at least one NYHA class) in 9 patients (2.89 ± 0.33 to 1.67 ± 0.5) with no improvement in 10 (2.6 ± 0.52 to 2.6 ± 0.52). During chronic RV pacing and before biventricular upgrade, patients with symptom compared with those without symptom improvement had significantly larger LV EDV (221 ± 75 vs. 160 ± 42, P = 0.04). After biventricular upgrade, in patients with symptom improvement, significant declines in LV EDV (221 ± 75 to 180 ± 54, P = 0.04) and ESV (147 ± 58 to 109 ± 46, P = 0.01) occurred; no significant changes occurred in RV EDV (256 ± 64 vs. 220 ± 33) and ESV (157 ± 74 vs. 122 ± 43). After biventricular upgrade, patients without symptomatic improvement showed no significant changes in LV and RV volumes. Conclusions Symptomatic improvement after upgrading from chronic RV to biventricular pacing was associated with a larger baseline LV EDV and subsequent significant reduction in LV EDV and ESV. Reverse remodelling of the LV but not the RV after biventricular pacing upgrade was associated with symptom improvement. # CRT response score predicts the effects of cardiac resynchronization therapy {#article-title-3} Background and objectives The effectiveness of cardiac resynchronization therapy (CRT) has been verified by large multi-centre studies, but non-response phenomenon occurs in ∼30% of patients according to the indications of CRT recently. This study was designed to evaluate the factors that affect the effects of CRT, summarize CRT response score to predict clinical effects. Methods From December 2001 to August 2009, 110 patients with chronical heart failure were enrolled in this study. The patients underwent a clinical examination, 12-lead electrocardiography, echocardiographic evaluations before implantation. Patients were divided into control and response group which was defined as a decrease in left ventricular end-diastolic diameter of ≥15% at 6 months after operation. The follow-up duration was 12 months. The clinical endpoint considered was cardiovascular death and hospitalization due to heart failure. Results CRT-P/D devices were successfully implanted in 107 patients. Of the patients, 61.3% showed a response to CRT. Multiple logistic regression identified an independent association between duration of heart failure, ischaemic cardiomyopathy, ΔQRS, septal-to-posterior wall motion delay (SPWMD), and effects of CRT. Four score was assigned to duration of heart failure ≥5.0 years, ischaemic cardiomyopathy, ΔQRS 150 ms: what are the LV conduction delays in RBBB vs. LBBB? {#article-title-4} Rationale Surface QRS duration (QRSd) exceeding 150 ms predicts greater likelihood of CRT response in patients with LV dysfunction (HF). The reason may be greater delay of LV activation time (LVAT) since the premise of CRT requires late LV activation. However, the relation of QRSd and configuration to LVAT is unknown. This was assessed. Methods In HF patients (LV ejection fraction 23 ± 8%, n = 85) with QRS >120 ms left bundle branch block (LBBBHF, n = 54) and right bundle branch block (RBBBHF, n = 31), LVAT was estimated by interval from QRS onset to basal inferolateral LV depolarization during intrinsic conduction. Results QRSd in LBBBHF did not differ to RBBBHF (161 ± 29 vs. 165 ± 18 ms, P = NS), but LVAT was greater (136 ± 33 vs. 100 ± 24 ms, P 150/ < 150 ms (see figure). LVAT correlations with QRS duration were RBBBHF: P = 0.1; LBBBHF: P < 0.001. ![Figure][1] Conclusion LV activation delay in patients with LV dysfunction is greater when QRSd >150 ms. However, QRSd >150 ms with RBBBHF is less likely to contain prolonged LVAT. The probability distribution of LVAT according to QRS duration and configuration may determine the likelihood of response if CRT is applied universally to HF patients with QRS >150 ms. # Relationship between dyssynchrony improvement and reverse remodelling {#article-title-5} We aimed to investigate reverse remodelling (RR) according to a decrease in left ventricular end-systolic volume (LVESV) and an increase in left ventricular ejection fraction (LVEF) and their relationship between dyssynchrony improvements. Thirty patients with severe heart failure, scheduled for implantation of a CRT device, were identified as echocardiographic responders by 10% decrease in LVESV and/or 25% increase in LVEF. Intraventricular dyssynchrony was measured with TDI. Patients were divided in RR developed and non-developed groups. RR according to LVESV was developed in 18, 22, and 22 patients at 1st, 3rd, and 6th months, respectively. RR according to LVEF was developed in 10, 14, and 18 patients at 1st, 3rd, and 6th months, respectively. Ventricular dyssynchony improvement was significant at the end of the first month in both of RR developed and non-developed groups according to LVESV. Dyssynchrony improvement was continued in the RR developed group. However, it does not improve regularly in the RR non-developed group. Dyssynchrony improvement was significant at the end of the first month in the RR developed and non-developed patient groups according to LVEF and there was not any difference at the end of the 6th month. Ventricular dyssynchrony improvement plays an important role in RR according to LVESV. Synchronized contraction of the interventricular non-contracting chamber areas with CRT may be one of the reasons. However, there was not any difference in dyssynchrony improvement in RR developed and non-developed groups according to LVEF. RR in these groups may develop with a different mechanism. # Cardiac resynchronization therapy in heart failure patients with narrow QRS {#article-title-6} Background Cardiac resynchronization therapy (CRT) is an established therapy for severe symptomatic heart failure with depressed left ventricle (LV) systolic function and a wide QRS >120 ms. However, only 30% heart failure patients will fulfil these criteria. Studies have demonstrated benefits of CRT with narrow QRS

We hypothesized that, within the normal range of resting heart rate, heart rate and left ventricular ejection fraction would be inversely correlated and heart rate and left ventricular filling would be correlated in patients with dilated cardiomyopathy and not correlated in patients with normal cardiac function. At rest, heart rate, left ventricular ejection fraction, and three measures of diastolic filling (time to peak filling rate, peak filling rate, and first half filling fraction) were recorded using radionuclide ventriculography in subjects with no cardiac disease, patients with idiopathic dilated cardiomyopathy, and patients with dilated cardiomyopathy associated with ischemic heart disease. Heart rate had significant inverse correlations with left ventricular ejection fraction (r=-0.55, P=0.0007) and time to peak filling rate (r=-0.47, P=0.005) and a positive correlation with peak filling rate (r=0.73, P

The relation between left ventricular (LV) filling variables measured by gated blood pool radionuclide ventriculography and clinical symptoms and survival was examined in 93 patients who had decreased LV systolic function. The diastolic data were not significantly associated with clinical symptoms. Time to peak filling rate, peak filling rate and ejection fraction were associated independently with survival free of cardiac death (chi-square = 7.74, S.91 and 3.92, respectively, by stepwise Cox regression analysis). A short time to peak filling rate or increased peak filling rate was associated with decreased survival, whereas the opposite indicated a good prognosis. One-year Kaplan-Meier survival was 73 and 98% when time to peak filling rate was below or above the median value of 167 ms, respectively, 82 and 90% when peak filling rate was above or below the median value of 1.67 end-diastolic volumes per second, respectively, and 76 and 95% when LV ejection fraction was below or above the median value of 0.35, respectively. Thus, filling variables (time to peak filling rate and peak filling rate) measured by radionuclide ventriculography may be valuable in predicting survival in patients with decreased LV systolic function.

To examine the sequential changes in left ventricular volume after thrombolytic therapy for acute myocardial infarction, gated radionuclide ventriculography was performed within 12 hours of thrombolysis and at 1 and 6 weeks in 34 consecutive patients who received intravenous thrombolytic therapy in the Thrombolysis in Myocardial Infarction Trial. Angiographic confirmation of immediate reperfusion (mean 5.6 hours after onset of symptoms) that persisted at 24 hours was noted in 24 patients; 10 patients were not reperfused. A small (9.5%), but significant (p = 0.05), increase in end-diastolic volume index was noted in the reperfused group between 1 and 6 weeks; however, a marked degree of dilatation (35%) was noted in the nonreperfused group (p = 0.01). The change in left ventricular volume between 1 and 6 weeks differed in the 2 groups for both end-diastolic volume index and end-systolic volume index (p = 0.01 and p = 0.02, respectively). By 6 weeks, both end-diastolic volume index and end-systolic volume index were greater in the nonreperfused group (p < 0.05). Between the acute and 6-week studies, definite increases in end-diastolic volume index (p < 0.05) and end-systolic volume index (p < 0.01) occurred commonly in the nonreperfused group but rarely in the reperfused group. Compared to the nonreperfused group, the reperfused group also had significantly higher ejection fractions at both 1 and 6 weeks (p < 0.05). The change in end-diastolic volume index between 1 and 6 weeks correlated significantly and inversely with the ejection fraction at 1 week (r = -0.60, p < 0.001). These results indicate that ventricular dilatation occurs between 1 and 6 weeks after myocardial infarction, is proportional to systolic dysfunction and may be largely prevented by successful thrombolytic reperfusion.

Supine exercise radionuclide angiography was performed in 367 men to assess left ventricular (LV) systolic response to exercise; 58 had systemic hypertension without LV hypertrophy on a resting electrocardiogram and 309 were normotensive. All patients met the following criteria defining a low pretest likelihood of coronary artery disease: age less than 50 years; normal electrocardiographic response to exercise; absence of typical or atypical chest pain; and exercise heart rate greater than 120 beats/min. Patients taking beta-receptor blockers were excluded. There were no significant differences between hypertensive and normotensive groups in peak exercise heart rate, workload or exercise duration. However, hypertensive patients had significantly higher peak exercise systolic blood pressures and peak exercise rate-pressure products. There were no differences between patients with and without hypertension in resting ejection fraction, peak exercise ejection fraction (hypertensive patients 0.71 +/- 0.01, normotensive patients 0.70 +/- 0.05) or change in ejection fraction at peak exercise (hypertensive patients 0.07 +/- 0.01, normotensive patients 0.07 +/- 0.04). Diastolic and systolic ventricular volumes tended to be smaller in the hypertensive patients, but the difference was not statistically significant. The change in systolic volume with exercise was similar in the 2 groups (hypertensive -10 +/- 3 ml/m2, normotensive -10 +/- 1 ml/m2). In the absence of electrocardiographic evidence of LV hypertrophy, systemic hypertension does not influence LV systolic response to exercise.

Radionuclide angiography was used to study the effects of supine and upright bicycle exercise and handgrip exercise in 17 (12 well-trained) normal subjects before (control) and immediately after the administration of propranolol (160 mg/day for 4 days). Cardiac hemodynamic values were related to position in that control left ventricular volumes and the cardiac index were greater in the supine position than in the upright at rest but resting left ventricular ejection fraction was similar in both positions. The pressure volume index was greater in the upright position than in the supine. At maximal exercise before treatment, however, similar cardiovascular hemodynamic measurements were recorded in both positions. Propranolol increased left ventricular end-diastolic volume at rest and at maximal exercise. Left ventricular end-systolic volume, however, was substantially greater only in the upright position both at rest and at maximal exercise when compared with control values. Heart rate, systolic arterial pressure, cardiac index, and pressure volume index were decreased at rest and maximal exercise after treatment with propranolol. Ejection fraction was decreased in the upright position after propranolol administration but was unchanged in the supine position. Handgrip exercise primarily increased heart rate and arterial pressure and did not affect cardiac volume, and this response was unaffected by propranolol.

This study examines the recently reported gender differences in cardiac responses to exercise. The study group consisted of 192 men and 67 women with a low probability of coronary artery disease who underwent supine exercise radionuclide angiography.Men had a lower rest ejection fraction than that of women (0.63 versus 0.66, p = 0.02) and greater increases in ejection fraction with exercise (0.08 versus 0.02, p = 0.0001). The slope relating ejection fraction to metabolic equivalents of exercise (METs) was greater (p = 0.004) for men, even after adjustment for differences in rest ejection fraction and end-diastolic volume index. Compared with men, women had a smaller rest end-diastolic volume index (87 versus 97 ml/m2, p = 0.003) and a greater increase in end-diastolic volume index with exercise (6 versus −2 ml/m2, p = 0.002).The slope relating end-diastolic volume to METs was greater for women, even after adjustment for differences in rest end-diastolic volume index and peak work load. There are clear gender differences in the supine exercise response of ejection fraction and end-diastolic volume that are not explained by differences in exercise capacity.

Left ventricular (LV) filling at rest was studied by radionuclide ventriculography using alternate R-wave gating in 42 patients (29 men, 13 women) who had a low likelihood of cardiac disease. LV filling measurements differed little between men and women. Age was correlated positively with atrial filling duration (r = 0.55), atrial filling duration fraction (r = 0.52) and atrial filling fraction (r = 0.56) and negatively with rapid filling fraction (r = -0.58). Age was not correlated with peak filling rate, time to peak filling rate and first-half filling fraction. The heart rate at rest was significantly negatively correlated with rapid (r = -0.62), slow (r = -0.81) and atrial (r = -0.72) filling durations, but not with isovolumic duration. The heart rate at rest was weakly positively correlated with peak filling rate in end-diastolic volume per second (r = 0.36) and negatively correlated with first-half filling fraction (r = -0.35). Systolic pressure at rest influenced atrial filling duration. LV ejection fraction and end-diastolic volume index were not correlated significantly with LV filling in relatively normal subjects.

In 622 patients with known coronary artery anatomy, heart rate (HR).blood pressure (BP) product and left ventricular (LV) ejection fraction (EF) at maximal supine exercise measured by radionuclide ventriculography were used to estimate, by logistic regression analysis, the probabilities of absence of significant coronary artery disease (CAD), presence of significant CAD, presence of multivessel CAD and presence of 3-vessel CAD. Thus, for example, estimated probabilities of each of the aforementioned 4 categories of CAD are 0.39, 0.61, 0.32 and 0.12, respectively, for HR.BP product of 26,000 beats.mm Hg/min and LVEF of 0.6 at maximal exercise and 0.08, 0.92, 0.77 and 0.48, respectively, for HR.BP of 15,000 and LVEF of 0.4. The graphic presentations of these estimated probabilities form useful guidelines for interpreting the results of exercise radionuclide ventriculography. In addition, specific cutoff values at maximal exercise defined 2 groups: (HR.BP product greater than or equal to 21,000 beats.mm Hg/min and LVEF greater than or equal to 0.55) with a high (70%) likelihood of absence of significant CAD or 1-vessel CAD and a low (7%) likelihood of 3-vessel CAD, and (HR.BP product less than 21,000 and LVEF less than 0.55) with a high (72%) likelihood of multivessel CAD and a low (8%) likelihood of absence of CAD.

In 84 consecutive patients with resting T-wave inversion, radionuclide angiography revealed significant new wall motion abnormalities in 13 (28 percent) of the 47 patients with persistent T-wave inversion and in 23 (62 percent) of the 37 patients with T-wave pseudonormalization during exercise (p less than 0.01). The response of the ejection fraction to exercise was better in patients with persistent T-wave inversion than in those with pseudonormalization (p less than 0.04). Mechanical evidence of ischemia was seen in 14 (61 percent) of the 23 patients with T-wave pseudonormalization but without ST-segment depression. In patients with resting T-wave inversion, pseudonormalization was slightly more sensitive but less specific than a positive exercise test for predicting significant new wall motion abnormalities or decreases in the ejection fraction with exercise. Although pseudonormalization is not extremely useful alone, the presence or absence of this finding can increase the diagnostic accuracy of exercise electrocardiography in patients with resting T-wave inversion and suspected ischemic heart disease.

The significance of a decline in systolic blood pressure (BP) during supine exercise was examined in 820 patients who underwent both supine exercise gated equilibrium radionuclide ventriculography and coronary angiography. Twenty-seven patients, 3% of the study population, had a decrease in systolic BP at peak exercise of more than 10 mm Hg from the systolic BP at rest. Other indicators of ischemia--angina, ST-segment depression, a decrease in ejection fraction and wall motion abnormality during exercise--were present frequently but not uniformly in these patients. Although most patients had a decline in ejection fraction and a new wall motion abnormality with exercise, 4 patients had an increase in ejection fraction with exercise without any regional wall motion abnormalities. Coronary angiography in the 27 patients with systolic hypotension demonstrated severe coronary artery disease (CAD). Twenty-two patients (81%) had 3-vessel or left main CAD. Twenty of these 22 patients with 3-vessel CAD had at least 2 arteries with 90% or more diameter stenoses. Systolic hypotension during supine exercise radionuclide angiography is infrequent, usually associated with evidence of global and regional left ventricular dysfunction, and a marker of very severe CAD.

The exercise response of the ratio of systolic blood pressure to end-systolic volume was studied in 243 patients with chest pain and coronary artery disease who underwent supine rest and exercise equilibrium radionuclide angiography. There was a wide variation in both rest and exercise variables in this group. The exercise response of the systolic pressure/volume ratio also varied greatly, ranging from a decrease of 59% to an increase of 136%. Twenty-one clinical, catheterization and radionuclide angiographic variables were examined to determine their relation to the exercise response of the systolic pressure/volume ratio; nine variables were individually correlated with this ratio. Multiple regression analysis identified the change in end-diastolic volume index with exercise, rest systolic blood pressure, coronary artery Gensini score and peak work load as significant independent predictors of the exercise response of the systolic pressure/volume ratio; the latter correlated significantly with the change in ejection fraction with exercise (r = 0.73, p less than 0.0001). Its sensitivity for the detection of coronary artery disease in the study group (84%) and its "normalcy rate" in a group of 120 patients with a low likelihood of coronary artery disease (81%) were similar to those of the peak exercise ejection fraction (75 and 82%, respectively). These results demonstrate that the exercise response of the systolic pressure/end-systolic volume ratio is a complex response that is influenced by several pathophysiologic variables in the presence of coronary artery disease. It does not offer any advantage over ejection fraction measurements for the detection of exercise-induced ischemia.

The ability of exercise radionuclide angiography to predict the risk of having significant left main or three vessel coronary artery disease was examined in 681 patients who underwent both radionuclide and coronary angiography. There were significant differences in multiple variables between patients with or without such disease. Logistic regression analysis identified seven variables as independently predictive of the presence of left main or three vessel disease. Using these variables, low, intermediate and high probability groups could be identified. The four most important variables—the magnitude of exercise ST segment depression, peak exercise ejection fraction, peak exercise rate-pressure product and sex of the patient—can provide practical estimates of the risk of having ten main or three vessel disease. Exercise radionuclide angiography can provide a clinically useful uoninvasive estimate of the risk of having significant left main or three vessel disease.

We investigated whether exercise radionuclide angiography provides prognostic information in addition to that identified by resting left ventricular function and coronary anatomy in patients with medically treated coronary artery disease. Clinical follow-up (median, 21.7 months) was obtained in 424 medically treated patients who underwent exercise radionuclide angiography and coronary angiography. The mean age of the study population was 58 years, and 67% were men. Cardiac death occurred in 16 patients, nonfatal myocardial infarction in 16, and nonfatal out-of-hospital cardiac arrest in 1. Univariate analysis showed that multiple variables were associated with future cardiac events, including number of diseased vessels, exercise and rest radionuclide ejection fraction, history of myocardial infarction, exercise and rest left ventricular end-systolic and end-diastolic volume indices, peak exercise workload, age, abnormal resting electrocardiogram, and peak exercise ST-segment depression. Only three variables were independently associated with cardiac events on follow-up: number of diseased vessels, radionuclide ejection fraction at rest, and age. In patients with three-vessel disease and a resting radionuclide ejection fraction of more than 40%, a subgroup with higher risk could not be identified on the basis of exercise radionuclide response.