Radionuclide Angiography Research Articles

Ventricular performance during exercise in patients with chronic obstructive pulmonary disease (COPD)

We assessed ventricular performance during exercise in 16 COPD patients and 8 normal control subjects by means of radionuclide equilibrium angiography using technetium-99m as a tracer. Supine exercise on a bicycle ergometer was performed until symptom-limited exhaustion. Data were accumulated for 300 heart beats at rest and 150 heart beats during exercise. We used the standard voxel count method to calculate the ventricular volumes. Age, FEV1.0%, %VC, PaO2 and PaCO2 of the COPD patients were 63 +/- 8 yr, 46 +/- 11%, 69 +/- 18%, 68 +/- 11 Torr and 44 +/- 7 Torr (mean +/- SD), respectively. Systolic dysfunction of both the left and right ventricles was well confirmed in the present study. In 12 patients who also underwent hemodynamic studies, resting total pulmonary vascular resistance index (TPVRI) and mean pulmonary artery pressure (Ppa) significantly correlated with right ventricular end-systolic volume index (RVESVI) obtained by RI angiography; gamma = 0.769 (p less than 0.01) and gamma = 0.631 (p less than 0.05), respectively. A significant relationship was also observed between left ventricular dysfunction and the degree of hypercapnia. In response to exercise testing, 10 of 16 patients exhibited insufficient augmentation of stroke volume, and both left and right end-diastolic volumes decreased in half of 10 patients. It is suggested that cardiac function may be disturbed by mechanical factors such as pulmonary hyperinflation in COPD patients.

Cardiac resynchronization therapy; the importance of evaluating cardiac metabolism

Cardiac resynchronization therapy; the importance of evaluating cardiac metabolism

Gated blood-pool SPECT versus cardiac magnetic resonance imaging for the assessment of left ventricular volumes and ejection fraction

BackgroundWe evaluated the accuracy of planar radionuclide angiography and different count-based and space-based electrocardiogram (ECG)-gated blood-pool single-photon emission computed tomography (GBPS) algorithms for assessment of left ventricular end-diastolic volume (LVEDV), end-systolic volume (LVESV), and ejection fraction (LVEF) compared with the gold standard of cardiac magnetic resonance imaging (cMRI). The goal is to assess the accuracy of a recently developed GBPS algorithm. Methods and ResultsSubjects had planar, GBPS, and cMRI sequentially. Datasets were processed by QBS software (Cedar-Sinai) and by MHI software (Montreal Heart Institute). Space-based approaches were used to compute LVEDV, LVESV, and LVEF. Count-based techniques were also used to assess LVEF. All results were compared to cMRI. Fifty-five patients (85% male; mean age 63 ± 9 years) completed the study. LVEFs and their correlations to cMRI values were 43 ± 12% (r = .82), 39 ± 14% (r = .82), and 39 ± 13% for MHIspace, QBSspace, and cMRI methodologies, respectively. LVEF by count-based methods also demonstrated good correlation to LVEF provided by cMRI (42 ± 13%, r = .88 for MHIcount and 46 ± 15%, r = .84 for QBScount). Strong correlations were obtained for LVEDV (r = .96 for MHI and r = .92 for QBS) and for LVESV (.97 for MHI and r = .94 for QBS). ConclusionsAll Gated blood-pool SPECT algorithms had significant variation in estimating LVEF. Nevertheless our software provides good estimates of LV volumes and LVEF. Such software may, therefore, be applied to assess LV morphology and function.

Evaluation of Ventricular Synchrony with Equilibrium Radionuclide Angiography: Assessment of Variability and Accuracy

Equilibrium radionuclide angiography (ERNA) has become an established method for assessing cardiac function. However, limited data are available to evaluate ventricular synchrony with ERNA. The aim of this study was to assess the variability and accuracy of ERNA to evaluate ventricular synchrony by means of phase images in healthy individuals and to compare them with a group of subjects with left bundle-branch block (interventricular dyssynchrony, LBBB) and with a group of patients with nonischemic, dilated cardiomyopathy (DCM) (inter- and intraventricular dyssynchrony). The population was divided into groups as follows: group 1 included 22 healthy subjects, group 2 included 11 patients with LBBB and normal left ventricular ejection fraction (LVEF), and group 3 included 14 DCM patients with LVEF <35% and LBBB. Interventricular synchrony was measured as the difference between LV mean phase angle (mPA) and RV mPA (LV-RV mPA). Intraventricular synchrony for each ventricle was measured as the standard deviation (SD) of the RV mPA and LA mPA blood pools. Intra- and interobserver correlation coefficients were high for both inter- and intraventricular synchrony parameters. Area under the curve (AUC) was 0.98 for LV-RV mPA (p <0.001; 95% CI: 0.947-1.0). A cutoff value of 10 degrees yielded 96% sensitivity and 99% specificity to identify interventricular dyssynchrony. AUC was high for SD RV mPA and SD LV mPA (AUC = 1.0, p <0.001; 95% CI: 1.0-1.0 and AUC = 0.99, p <0.001; 95% CI: 0.979-1.0). A cutoff value of 22 degrees for SD LV mPA yielded 100% sensitivity and 100% specificity to identify LV intraventricular dyssynchrony. A cutoff value of 20 degrees for SD RV mPA yielded 100% sensitivity and 99% specificity to identify RV intraventricular dyssynchrony. ERNA is an accurate and highly reproducible technique for evaluation of ventricular function and synchrony.

192 Assessment of a relationship between functional and structural abnormalities in Brugada syndrome

Although Brugada syndrome (BrS) is a primarily electrical disease leading to conduction slowing, it is now acknowledged that structural alterations of the myocardium are frequently associated. Those two factors, may result in both contraction heterogeneity and remodeling of the right ventricle (RV). Radionuclide angiocardiography (RNA) with phase analysis is able to quantify contraction delays and to evaluate volumes and systolic function of ventricles. The aim of this study was to assess both functional and structural alterations of the RV in patients with BS and to investigate a relationship between them. Multiharmonic Fourier phase analysis of planar RNA was used to quantify contraction heterogeneity, and gated bloodpool SPECT to assess ventricular volumes and function in 71 patients with proven BrS [classified according to their spontaneous ECG pattern recorded just prior to ERNA as: concealed (n=26), type 2/3 (n=28), type 1 (n=17)] and 18 controls. RV contraction heterogeneity was greater in patients with BrS compared to controls (17.2±0.4° vs 15.1±0.7° respectively, p=0.007), and increased according to the repolarisation pattern from concealed forms to type 1 (ANOVA p=0.02). The increase of RV contraction heterogeneity was associated with an increased apex to RVOT contraction delay (r=0.4, p=0.006). RV end-diastolic and end-systolic volumes were greater in patients with BrS compared to controls (156±6 vs 134±7 ml, and 88±4 vs 73±4 ml respectively, p=0.02), to a similar proportion so as the ejection fraction was not significantly impaired (44±1% vs 45±2% respectively, p=0.4). Finally, there was no relationship between the magnitude of contraction heterogeneity and RV remodeling. The left ventricle was free of abnormality. In patients with BrS, RV contraction heterogeneity increases with the magnitude of repolarisation abnormalities, contrary to RV remodeling which is present to a mild extent whatever the repolarisation pattern.

Cardiac resynchronization therapy; evaluation by advanced imaging techniques

Cardiac resynchronization therapy; evaluation by advanced imaging techniques

Dose-Dense (dd) Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel (P) with Trastuzumab (T) and Lapatinib (L) in Early Breast Cancer (EBC); Troponin I and C-Reactive Protein as Biomarkers of Cardiotoxicity.

Abstract BackgroundThe early detection of cardiotoxicity and congestive heart failure (CHF) from anthracyclines and anti-HER2 agents is currently limited to measuring changes in left ventricular ejection fraction (LVEF) at arbitrary time points. This approach has limited sensitivity and specificity and has led to the investigation of putative biomarkers such as cardiac Troponin I (TnI), a highly specific marker of myocardial damage and C-reactive protein (CRP), a sensitive inflammatory marker. In a pre-planned analysis we investigated these as biomarkers of cardiotoxicity within a prospective study testing the feasibility of ddAC- followed by weekly P with T and L.Materials and MethodsPatients (pts) with HER2+ EBC enrolled at MSKCC and DF/HCC and received ddAC (A 60mg/m2 + C 600mg/m2) x 4 → weekly P (80mg/m2) x 12 + T + L (1000mg/day). T+L continued for a total of 1yr. At baseline pts had LVEF ≥50%. Pts with unstable angina, CHF, recent MI, uncontrolled arrhythmia, grade 3 QT prolongation were excluded. LVEF was assessed by MUGA scan at mths 0, 2, 6, 9 and 18. TnI and CRP were measured every 2 wks right before treatment (Rx) during ddAC-PTL, then at mths 6, 9 and 18. TnI was categorized as “undetectable” (&amp;lt; 0.06 ng/ml; MSKCC, &amp;lt;0.04 ng/ml; DF/HCC), “minimally elevated” (&amp;lt;0.31 ng/ml) and “elevated” (&amp;gt;0.31ng/ml). Elevated CRP was defined as (&amp;gt;0.8mg/dl; MSKCC, &amp;gt;0.3mg/dl; DF/HCC). Investigators were blinded to these results until pts completed 18mth follow-up (F/U).ResultsFrom Apr 07- Apr 08, 95 pts were enrolled; 39/95 (41%) withdrew due to PTL toxicities (incl. 3 with asymptomatic LVEF (aLVEF) declines and 3 with CHF). Final biomarker results were available in 84 pts (88%) and 11 pts (12%) continue on study. During Rx, minimal elevations in TnI occurred in 55 pts (65%). One pt had ↑TnI above normal range with AC#4; MUGA 1 wk later was unchanged (LVEF 75%), but she died from sepsis during subsequent Rx without evidence of CHF. Elevations in TnI occurred only during chemoRx and no pt had a ↑TnI during TL or at 18mth F/U. Of 55pts with elevated TnI, 25 (45%) had aLVEF declines (3 ↓ ≥16%, 10 ↓ 10-15%, 12 ↓ 5&amp;lt;10%). Of 29 pts with undetectable TnI, 7 (24%) had aLVEF declines (1 ↓ ≥16%, 4 ↓ 10-15%, 2↓ 5&amp;lt;10%). Elevations in CRP occurred in 61/84 (73%) pts during chemoRx but only in 22 (26%) during TL or at 18mth F/U. Three pts discontinued Rx for aLVEF ↓ at mths 4, 5 and 7 respectively; 2 (66%) had rises in CRP and 2 had minimal elevation in TnI. Three pts developed CHF at mths 3, 6, and 12 respectively, all had rises in CRP; 1 pt had a single ↑TnI of 0.08 ng/ml during chemoRx, and 2pts had no ↑TnIs.ConclusionsIn pts receiving ddAC-PTL fluctuations in TnI and CRP are common but do not persist after chemoRx (during TL). These biomarkers do not appear to predict for CHF. One possibility is that the timing of the drawing of these biomarkers (immediately preceding the specified treatment cycle and after Rx completion) may have been suboptimal. We plan to assess for potential biomarkers by assessing both immediately preceding and following therapy in a planned trial. Updated results will be presented. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3088.

Phase II Trial of Neoadjuvant Pegylated Liposomal Doxorubicin with Paclitaxel and Trastuzumab in Patients with Operable Her2-Positive Breast Cancer.

Abstract Background: Doxorubicin, paclitaxel and trastuzumab are among the most active agents used in the treatment of Her2-positive invasive breast cancer. However, trastuzumab is associated with cardiotoxicity that is significantly amplified in the presence of doxorubicin. Pegylated liposomal doxorubicin (PLD) has been reported to have greatly reduced cardiotoxicity when compared to native doxorubicin. This pilot study was designed to assess safety and efficacy of concurrent PLD, paclitaxel (TAX), and trastuzumab in the preoperative setting.Methods: Eligible patients included women with T1c-T4, N0-1, M0, Her2-positive invasive breast cancer who had received no prior treatment. The treatment regimen consisted of concomitant PLD 24 mg/m2 or 20 mg/m2 (14pts/10pts) q 3 weeks, TAX 80 mg/m2 weekly, and trastuzumab 2mg/m2 weekly after an initial 4 mg/m2 loading dose, for a total of 18 weeks. MUGA scans were obtained at baseline, after 9 weeks, and after 18 weeks prior to surgery. The primary endpoint was pathologic complete response (pCR).Results: Twenty-four patients were entered on study. The median age was 55 (range 30-72). One subject had AJCC Stage I disease, 14 subjects had Stage II disease, 9 subjects had Stage III disease, and the median pre-treatment tumor size was 4.5 cm (1.2 cm-10.0 cm). Twelve subjects required dose reductions of PLD, 9 required dose reduction of TAX, and 5 discontinued therapy early. One subject withdrew during the 1st cycle, and 1 patient died due to an event unrelated to the investigational treatment. Thirteen of the 22 evaluable subjects had pCR (59%), 9 subjects had PR (41%). The principal treatment-related toxicity was Grade II or III skin toxicity in 18 of 24 subjects (75%). No overt cardiotoxicity was noted, with the mean change between pre-treatment and pre-surgical MUGA of -.25% (range -12-7%).Discussion: The combination of PLD, TAX, and trastuzumab given every 3 weeks, appears to be a highly effective regimen, without evidence of increased cardiotoxicity. However skin toxicity is prominent and may be exacerbated by a previously reported effect of TAX on PLD pharmacokinetics. Further investigation of this highly effective regimen should focus on reducing skin toxicity, while maintaining efficacy. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 1098.

Right ventricular systolic function and cardiac resynchronization therapy

The effect of cardiac resynchronization therapy (CRT) on right ventricular ejection fraction (RVEF) has not been well studied. Furthermore, it is unclear whether baseline RVEF influences response to CRT. To evaluate the acute and chronic effects of CRT on right ventricular systolic function, and to investigate whether baseline RVEF impacts response to CRT. Forty-four patients with a standard indication for CRT underwent radionuclide angiography at baseline and after at least 6 months' follow-up for measuring RVEF, right ventricular synchrony (using phase analysis), and left ventricular ejection fraction (LVEF). In addition, NYHA functional class and 6-min walking distance (6MWD) were evaluated. There were no significant acute changes in RVEF with CRT. After a mean follow-up of 9 +/- 5 months, RVEF was slightly improved (by 1.9 +/- 5.0% in absolute terms, P = 0.016), and to a lesser extent than LVEF (5.1 +/- 9.0%, P = 0.009 compared with RVEF). Right ventricular dyssynchrony was significantly improved at follow-up (P = 0.016). Patients with a baseline RVEF < or = 0.35 (n = 19) were less likely to improve in NYHA class (P = 0.016), and also tended to improve less in 6MWD and LVEF (P < 0.06). Cardiac resynchronization therapy has no acute effect on RVEF, and only slightly improves RVEF at follow-up. Patients with reduced RVEF at baseline were less likely to respond to CRT, indicating that right ventricular systolic dysfunction may play a role in patient selection.

Assessment of poststress left ventricular ejection fraction by gated SPECT: comparison with equilibrium radionuclide angiocardiography

We compared left ventricular (LV) ejection fraction obtained by gated SPECT with that obtained by equilibrium radionuclide angiocardiography in a large cohort of patients. Within 1 week, 514 subjects with suspected or known coronary artery disease underwent same-day stress-rest (99m)Tc-sestamibi gated SPECT and radionuclide angiocardiography. For both studies, data were acquired 30 min after completion of exercise and after 3 h rest. In the overall study population, a good correlation between ejection fraction measured by gated SPECT and by radionuclide angiocardiography was observed at rest (r=0.82, p<0.0001) and after stress (r=0.83, p<0.0001). In Bland-Altman analysis, the mean differences in ejection fraction (radionuclide angiocardiography minus gated SPECT) were -0.6% at rest and 1.7% after stress. In subjects with normal perfusion (n=362), a good correlation between ejection fraction measured by gated SPECT and by radionuclide angiocardiography was observed at rest (r=0.72, p<0.0001) and after stress (r=0.70, p<0.0001) and the mean differences in ejection fraction were -0.9% at rest and 1.4% after stress. Also in patients with abnormal perfusion (n=152), a good correlation between the two techniques was observed both at rest (r=0.89, p<0.0001) and after stress (r=0.90, p<0.0001) and the mean differences in ejection fraction were 0.1% at rest and 2.5% after stress. In a large study population, a good agreement was observed in the evaluation of LV ejection fraction between gated SPECT and radionuclide angiocardiography. However, in patients with perfusion abnormalities, a slight underestimation in poststress LV ejection fraction was observed using gated SPECT as compared to equilibrium radionuclide angiocardiography.

Feasibility of Outpatient Consolidation Chemotherapy and Toxicity in Elderly Patients with AML.

Abstract 1036Poster Board I-58 Introduction:Consolidation chemotherapy is frequently administered on an outpatient basis in younger AML patients. However, the safety of this maneuver in older patients is unclear owing to increased co-morbidities and declines in performance status (PS) in these patients. Methods:215 newly diagnosed AML patients aged >60 years were referred to Princess Margaret Hospital between 2002 and 2005. Of these, 108 received non-protocol treatments (32 non-intensive experimental therapy, 12 intensive chemotherapy on a study protocol, and 64 palliative therapy). The remaining 107 (50%) received standard induction chemotherapy with curative intent, consisting of cytarabine 100 mg/m2/day CIVI x 7 days and dauorubicin 60 mg/m2 IV daily x 3 (3+7). Patients achieving CR were eligible to receive two consolidations, with 3+7 (C#1) followed by mitoxantrone 10 mg/m2 daily x 5 plus etoposide 100 mg/m2 IV daily x 5 (C#2). All patients underwent cardiac assessment prior to each cycle with MUGA scan. If the ejection fraction (EF) dropped to < 50% or had fallen by >10%, amsacrine (100 mg/m2 IV daily x 5) was substituted for the anthracycline. Consolidation was administered on an inpatient or outpatient basis according to physician discretion. Inpatient consolidations were administered to patients judged to have significant co-morbidities and poor PS post-induction, while the remaining patients were given consolidation on an outpatient basis, with twice weekly monitoring until hematologic recovery. Oral antibiotic and antifungal prophylaxis was used. Febrile neutropenia (FN) was treated with inpatient IV broad-spectrum antibiotics. Results:The median age of patients was 68 years (range, 60-84). 59 of 107 pts (55%) achieved a CR and a further 5 patients a leukemia free state with induction chemotherapy. 55 patients achieving CR proceeded to consolidation therapy on protocol. 38/55 pts. (69%) received C#1 as outpatient; the rate of admission for FN in these patients was 45%. 39/55 pts (71%) went on to receive a second consolidation cycle. Reasons for attrition post-C#1 included medically unfit (6 pts), persistent aplasia (3) and relapse (4). 32/39 (82%) pts received C#2 as outpatient; the rate of admission for FN was 59%. There were no treatment related deaths during consolidation therapy. Among patients proceeding to consolidation, 35/55 (63%) had a significant decline in LVEF during, or at completion of, treatment: >10% drop in LVEF in 31 pts. and LVEF <50% in 17 pts (7 of these to <40%); 24/35 pts received a change in consolidation chemotherapy as a result. At a median follow-up of 11.0 months, 80/107 (75%) have died; the median overall survival (OS) was 11.4 months, 3 year OS for all patients was 20%. For those patients obtaining CR, the median relapse-free survival (RFS) was 8.4 months. There was no significant difference in RFS and OS between patients switched to amsacrine versus those receiving standard protocol (p=0.15 and 0.31 respectively). Discussion:We have demonstrated that post-remission consolidation chemotherapy can be safely administered on an outpatient basis in the majority of otherwise medically fit elderly AML patients in CR-1 using this regimen. Approximately one half will require admission for febrile neutropenia, but treatment related mortality is low. Cardiac toxicity with this anthracycline-intensive regimen is significant, and close monitoring of LV function is required. Switching anthracycline drug to amsacrine during post-remission therapy does not appear to adversely affect outcome. Disclosures:No relevant conflicts of interest to declare.

Dose-dense adjuvant Doxorubicin and cyclophosphamide is not associated with frequent short-term changes in left ventricular ejection fraction.

Doxorubicin and cyclophosphamide (AC) every 3 weeks has been associated with frequent asymptomatic declines in left ventricular ejection fraction (LVEF). Dose-dense (dd) AC followed by paclitaxel (P) is superior to the same regimen given every third week. Herein, we report the early cardiac safety of three sequential studies of ddAC alone or with bevacizumab (B). Patients with HER2-positive breast cancer were treated on two trials: ddAC followed by P and trastuzumab (T) and ddAC followed by PT and lapatinib. Patients with HER2-normal breast cancer were treated with B and ddAC followed by B and nanoparticle albumin-bound P. Prospective LVEF measurement by multigated radionuclide angiography scan before and after every 2 week AC for 4 cycles and at month 6 from all three trials were aggregated to determine the early risks of cardiac dysfunction. From January 2005 to May 2008, 245 patients were enrolled. The median age was 47 years (range, 27 to 75 years). Median LVEF pre-ddAC was 68% (range, 52% to 82%). LVEF post-ddAC was available in 241 patients (98%) and the median was unchanged at 68% (range, 47% to 81%). Per protocol no patients were ineligible for subsequent targeted biologic therapy based on LVEF decline post-ddAC. In addition, LVEF was available in 222 patients (92%) at 6 months, at which time the median LVEF was similar at 65% (range, 24% to 80%). Within 6 months of initiating chemotherapy, three patients (1.2%; 95% CI, 0.25% to 3.54%) developed CHF, all of whom received T. Dose-dense AC with or without concurrent bevacizumab is not associated with frequent acute or short-term declines in LVEF.

Close cardiac surveillance of patients treated with anthracyclines, also necessary after chemotherapy?

In women, breast cancer is the second most common form of cancer and the leading cause of death caused by malignancy. Anthracyclines are well known chemotherapeutics for treatment of these tumors, other solid tumors and hematologic malignancies. As adjuvant treatment in breast cancer it improves survival and reduces recurrence [1]. Unfortunately, their clinical use is currently limited by the development of a progressive dose-dependent cardiomyopathy that irreversibly evolves toward congestive heart failure, which is usually refractory to conventional therapy [2]. Studies have reported that 10–26% of patients administered cumulative anthracycline doses above those, develop congestive heart failure, and that more than 50% of patients administered these doses will experience measurable functional impairment months to years after the end of therapy [3]. The pathophysiology of this cardiomyopathy is incompletely understood. Anthracyclines decrease b-andrenoceptor density in the cell membrane, increase the permeability of myocytes and alter the ultrastructure of myofibrils and actin networks [4]. Risk factors for anthracycline-induced cardiotoxicity include high cumulative anthracycline doses, high anthracycline dose intensity, and radiotherapy. Radiotherapy in patients with cancer treated with anthracyclines can exacerbate cardiac tissue damage. Cardiovascular complications of treatment may be observed during administration of the drugs, days to months following administration, or years to decades following exposure. Several strategies have been developed to decrease the risk of cardiotoxicity while maintaining efficacy. These strategies include altered schedules of drug administration and adjunctive treatment with dexrazoxane. Unfortunately, none of these approaches have been successful, and patients remain at risk for the development of anthracycline cardiomyopathy, particularly with higher cumulative doses. Therefore careful serial monitoring is required for optimal medical management. Cardiomyopathy disease progression can be delayed in adults by using carvedilol or angiotensin-converting enzyme inhibitors [5, 6]. The permanent risk of cardiomyopathy by anthracyclines has made monitoring for the earliest evidence of cardiotoxicity necessary. In clinical practice monitoring is mostly performed using echocardiography or radionuclide angiography. The study of Appel et al. in the current issue of the International Journal of Cardiac Imaging shows that development of anthracycline toxicity is difficult to predict [7]. Although all patient in this study had a normal left ventricular function before receiving chemotherapy, 33% of the patients developed heart failure within a time period Editorial comment on the article of Appel et al. (doi:10.1007/ s10554-009-9518-2).

Measurement of Left Ventricular Ejection Fraction by Real Time 3D Echocardiography in Patients with Severe Systolic Dysfunction: Comparison with Radionuclide Angiography

Measurement of left ventricular ejection fraction (LVEF) using real time 3D echocardiography (3DE) has been performed in subjects with preserved or modestly reduced systolic function. Our aim was to evaluate this technique in the subset of patients with severe systolic dysfunction. Consecutive patients with LVEF less than 0.35 at two-dimensional echocardiography were included. LVEF obtained by 3DE was compared to the value measured by radionuclide angiography (RNA). Real time full-volume 3DE was performed, with offline semiautomated measurement of LVEF using dedicated software (Cardioview RT, Tomtec) by a single observer blinded to the results of RNA. A total of 50 patients were evaluated, of whom 38 (76%, 27 males, age 69 +/- 13 years) had a 3DE of sufficient quality for analysis. LVEF for this group was 0.21 +/- 0.07 using 3DE and 0.27 +/- 0.08 using RNA. The agreement between the two techniques was rather poor (r = 0.49; P < 0.001; 95% limits of agreements of -0.20 to 0.09). Truncation of the apex was observed in 6 of 38 (16%) patients. In patients with severe systolic dysfunction, 3DE shows poor agreement for measurement of LVEF as compared to RNA. There may be underestimation of up to 20% in absolute terms by 3DE. Accordingly, the two methods are not interchangeable for the follow-up of LV function. A limitation of 3DE may, at least in part, be related to the incomplete incorporation of the apical region into the pyramidal image sector in patients with dilated hearts.

The variable functional effects of the pacing site in normal and scarred ventricles

BackgroundThe pacing site has been shown to influence functional improvement with cardiac resynchronization therapy. We evaluated the effects of the pacing site on left ventricular (LV) function in an animal model. Methods and ResultsEquilibrium radionuclide angiography was acquired in sinus rhythm (NSR) and with ventricular pacing, from three pacing sites in seven normal and eight infarcted dogs. QRS duration, electrical activation pattern, wall motion, LV ejection fraction (EF), synchrony of ventricular contraction, and mean arterial pressure (MAP), were related to the pacing site and infarct size, during each of 120 episodes. Little changed during pacing in normals. In infarcted dogs, LV wall motion, and synchrony worsened, LVEF and MAP often fell. These changes related to altered activation patterns which were influenced by the pacing site but were not related to infarct size. ConclusionsHemodynamic and functional LV changes after infarction were found to vary with the pacing site and associated conduction and synchrony.

Equilibrium radionuclide angiography for evaluating the effect of percutaneous coronary intervention on ventricular aneurysm formation and systolic synchrony in patients with acute myocardial infarction

Left ventricular aneurysm (LVA) after myocardial infarction often results in serious complications. So far, when the LVA happened is unclear. Furthermore, it is a question whether percutaneous coronary intervention (PCI) can change or reverse the formation of LVA? And the report about the long term follow-up was rare. So this study was to evaluate the time sequence of the formation of LVA through left ventriculography in large scale of consecutive acute myocardial infarction (AMI) patients and evaluate the influence of PCI at different time after AMI on the change of systolic synchrony through phase analysis of equilibrium radionuclide angiography. The change of serum brain natriuretic peptide (BNP) was also measured to investigate its association with LVA. And follow up to 3 years to record the major adverse cardiac events. Total of 326 consecutive patients of anterior AMI with LVA were enrolled into this study. All patients were divided into four groups according to the time 'onset to balloon': group A (<3 h), group B (> or =3 and < or =6 h), group C (>6 and < or =12 h) and group D (>1 week). The paradox volume image as well as the parameters of left ventricular function and systolic synchrony were measured by equilibrium radionuclide angiography at 1 week and 6th month after AMI. Plasma BNP was measured in different time after AMI. The major adverse cardiac events were recorded up to 3 years. At the 6th month after AMI, left ventricular ejection fraction, peak ejection rate and peak filling rate in group A, B and C were significantly increased than those in group D while phase shift and peak phase standard deviation were decreased significantly (P < 0.05, respectively). At 6th month after AMI, the paradox volume index in group A was lowered than that in group B, C, and D (P < 0.05, respectively). In 18th hour, 5th day and 24th week after AMI, the values of BNP in group D were higher than those in group A, B and C (P < 0.05, respectively). There was not significantly different between group B and group C. Within the 3rd year follow-up, the incidences of angina post-AMI and mortality in group A, B, and C were significantly lowered than those in group D (P < 0.05, respectively). The LVA can formate shortly after the AMI. The early, fully and permanently patency of infraction related artery can effectively inhibit the left ventricular remodeling process, prevent LVA formation, improve its function and prognosis.

The relationship of myocardial contraction and electrical excitation—the correlation between scintigraphic phase image analysis and electrophysiologic mapping

BackgroundPhase imaging derived from equilibrium radionuclide angiography presents the ventricular contraction sequence. It has been widely but only indirectly correlated with the sequence of electrical myocardial activation. ObjectivesWe sought to determine the specific relationship between the sequence of phase progression and the sequence of myocardial activation, contraction and conduction, in order to document a noninvasive method that could monitor both. MethodsIn 7 normal and 9 infarcted dogs, the sequence of phase angle was correlated with the epicardial activation map in 126 episodes of sinus rhythm and pacing from three ventricular sites. ResultsIn each episode, the site of earliest phase angle was identical to the focus of initial epicardial activation. Similarly, the serial contraction pattern by phase image analysis matched the electrical epicardial activation sequence completely or demonstrated good agreement in approximately 85% of pacing episodes, without differences between normal or infarct groups. ConclusionsA noninvasive method to accurately determine the sequence of contraction may serve as a surrogate for the associated electrical activation sequence or be applied to identify their differences.

Evaluating the use of cardiac biomarkers for early detection of chemotherapy induced cardiotoxicity: A pilot study in a minority population

e20546 Background: Doxorubicin and trastuzumab are associated with characteristic Type I and Type II cardiomyopathy. As breast cancer survival improves and concern about long-term cardiotoxicity grows, we will need appropriate markers to detect cardiotoxicity before measurable myocardial systolic dysfuntion. Recent data and several guidelines suggest that Troponin-I and B-type natriuretic peptide (BNP) may serve as cardiac biomarkers for early detection of cardiotoxicity. This study seeks to evaluate feasibility and utility of these markers in an outpatient oncology clinic setting. Methods: As a quality care initiative in a high risk minority patient population for cardiac disease, 55 consecutive patients who received doxorubicin and/or trastuzumab for the treatment of breast cancer had serum Troponin-I and BNP measured prior to each dose of doxorubicin, and every three months on trastuzumab. All patients also had normal baseline left ventricular ejection fraction (≥ 50%) measured by MUGA scan. IRB approval was obtained and medical records were reviewed independently by two authors. Results: Of the 55 patients, two did not have adequate data; 58% of patients received dose dense doxorubicin; 15% of patients received trastuzumab. Significantly more number of patients had troponin-I rise as compared to BNP. Total 7 (13%) patients had abnormal LVEF by MUGA scan following chemotherapy. Five (71%) of these patients had rise in Troponin-I/BNP. Negative predictive value of biomarkers was 91%, with sensitivity of 71% and specificity of 44%. Conclusions: Use of standard cardiac biomarkers to detect early cardiotoxicity is feasible with a high negative predictive value for Troponin I and BNP in the first 90 days following chemotherapy with doxorubicin and/or trastuzumab. Patients with normal markers may not need intense cardiac monitoring. [Table: see text] [Table: see text]

Pegylated liposomal doxorubicin (PLD) with bevacizumab (B) in second-line treatment of ovarian cancer (OC): Pharmacokinetics (PK), safety, and preliminary outcome results

5548 Background: PLD activity in platinum-resistant OC is modest. B, with its activity in platinum(Plat)-sensitive and Plat-resistant patients (pts), has not been combined with PLD. PLD intratumoral concentrations, if affected by B, might be reflected in PLD PK. This phase II study of PLD + B was started in 2007 to accrue 48 pts, unless 4 serious (&gt; grade 3) adverse events (AEs) supervened. Methods: Improvement in progression-free survival (PFS) at 6 m from 25 to 40% at 6 m in Plat-resistant OC is primary endpoint. PK of PLD alone at 1h, d 7 and d 21 (cycle 1) vs with B (cycle 2), safety, and response rates (RECIST and CA125 criteria) were secondary endpoints. Dosing: PLD 30 mg/m2 followed by B 15 mg/kg on cycles 2–7 (with option to continue) d 1 every 3 w. Pts recurring within 6 m of platinum-based treatment for OC after &lt; 3 prior regimens (but no PLD or B) were eligible. Exclusions: bowel obstruction, prior perforation, uncontrolled hypertension, or vascular disease. Hematologic, mucocutaneous and renal toxicities were evaluated prior to each cycle, MUGA scans every third cycle; disease status by CA125 and/or RECIST every third cycle. Results: 21 of 24 pts enrolled to date are evaluable. Median age is 65, range 52–83; most had 2 prior chemotherapy regimens. Median 6 (range 3–12) cycles were given with 6 off study with progression at 3–7 cycles. RECIST and CA125 responses are under review; in 11 pts with baseline CA125 of &gt; 40 IU/mL, median increase was 31% by cycle 2; later falling to -57%. AEs did not exceed grade 3; hand-foot syndrome led to PLD dose reduction in 8 pts (33%); asymptomatic decreases in left ventricular ejection fraction (LVEF) &gt;10% in 3 pts were noted, with treatment discontinuation in 1. The mean (±SEM) secondary PK parameter estimates for Cmax, AUC, and elimination half life were 4.5 ± 0.5 ug/mL, 651.7 ± 61 ug/mL x h, and 93.3 ± 19.7 h, respectively. Conclusions: Cycles 1 and 2 PLD PK do not differ. PLD + B is tolerable with PLD dose modifications. Declines in LVEF in 1 institution have uncertain causality. Midway into the trial, safety and time on study encourage completion for study primary endpoint. [Table: see text]

Trastuzumab-mediated cardiotoxicity in the nontrial setting: Evaluation of patients receiving adjuvant trastuzumab at an academic centre

e11550 Background: Trastuzumab is effective in the treatment of HER-2 positive breast cancer. Although clinical trials have shown an increased risk of cardiotoxicity associated with trastuzumab, this risk has not been well studied in the non-trial setting. This study aims to examine (1) the incidence of cardiotoxicity associated with trastuzumab in the clinical setting (2) the relationship, if any, between risk factors and incidence of cardiotoxicity and (3) cardiac monitoring practices. Methods: A retrospective chart review was conducted of all patients receiving adjuvant trastuzumab therapy between August 2005 and May 2008, at a Canadian academic centre. The incidence of cardiotoxicity, defined as a significant reduction in left ventricular ejection fraction (drop of &gt;10% leading to an ejection fraction of &lt;50%) and/or New York Heart Association class III-IV CHF symptoms requiring trastuzumab delay or discontinuation was evaluated. Medical charts and patient surveys provided demographics, risk factors and cardiac toxicity for each patient. Results: 183 patients were included in the study. The average age of participating patients was 54.8 years and 51% of participants had node positive cancer. 72% were treated sequentially with Trastuzumab and 88% received anthracyclines. The incidence of cardiotoxicity was 6.0% (n=11). Upon univariate analysis, patient age was found to be the only variable significantly associated with the occurrence of cardiotoxicity (OR: 3.55, 95% CI 1.76–90.0). Left ventricular function was monitored by serial MUGA scan every 3.35 ±1.89 months as compared to the 3 month gold standard in clinical trials. Conclusions: In this study the incidence of cardiotoxicity was 6.0%. Patient age was the only significant variable associated with cardiotoxicity, as expected from previous studies. Clinically, this suggests that older patients may need more frequent monitoring for cardiac dysfunction via MUGA and/or ECHO scans. Future research needs to address the relationship between treatment regimens and the incidence of cardiotoxicity. Furthermore, we need to better define cardiotoxicity and the clinical significance of cardiac related symptoms. No significant financial relationships to disclose.