Equilibrium radionuclide angiography compared with tissue doppler imaging for detection of right ventricular dyssynchrony and prediction of acute response to cardiac resynchronization therapy.

OBJECTIVE: The aim of this study was to compare tissue doppler imaging (TDI) and equilibrium radionuclide angiography (ERNA) for detection of right ventricular (RV) dyssynchrony and prediction of the acute response to cardiac resynchronization therapy (CRT). METHODS: This study was approved by the local ethics committee of Huai'an First People's Hospital. Patient consent was not provided due to the use of completely anonymous images from which the individual could not be identified in this study. Thirty-three patients with nonischemic dilated cardiomyopathy underwent both TDI and ERNA before and within 48 hour after CRT implantation. RV dyssynchrony was measured with TDI using the difference in time to peak systolic velocity between the RV free wall and ventricular septum (RV-T). With ERNA, the standard of RV mean phase angle and RV phase standard deviation (RVmPA% and RVPSD%) were assessed. RESULTS: Moderate positive correlations were observed among baseline RVmPA%, RVPSD% and RV-T (r = 0.689 and 0.716, P < .001). Twenty patients (61%) with a reduction of at least 15% in LV end-systolic volume were categorized as acute responders after CRT. Responders showed significant reduction in RVmPA% and RVPSD% after CRT (53.60 ±â€Š4.15% to 43.95 ±â€Š6.88% and 14.00 ±â€Š2.41% to 10.40 ±â€Š1.67%, P < .05), whereas RV-T remained unchanged (50.10 ±â€Š10.28 ms to 49.25 ±â€Š13.64ms, NS). Receiver operating characteristic curve showed that the cut-off value of RV-T was 48.5ms, yielding 65% sensitivity and 77% specificity to predict acute respond to CRT. The cut-off value of RVmPA% was 49.5%, yielding 85% sensitivity and 85% specificity and the cut-off value of RVPSD% was 11.5%, yielding 85% sensitivity and 92% specificity. CONCLUSION: ERNA might be an appropriate alternative to TDI for assessment of RV dyssynchrony. Either RVmPA% or RVPSD% was highly predictive for acute response to CRT.

The prognostic value of mechanical left ventricular dyssynchrony defined by phase analysis from gated single-photon emission computed tomography myocardial perfusion imaging among patients with coronary heart disease.

BACKGROUND: The prognostic value of left ventricular dyssynchrony measured by gated single-photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI) and its relationship to electrical dyssynchrony measured by QRS duration are incompletely understood. The aim of this study was therefore to examine the independent and incremental prognostic value of dyssynchrony in yet the largest group of patients with coronary artery disease (CAD). METHODS AND RESULTS: Patients presenting for GSPECT- MPI between July 1993 and May 1999 in normal sinus rhythm were identified from the Duke Nuclear Cardiology Databank and the Duke Databank for Cardiovascular Disease (N = 1244). After a median of 4.2 years, 336 deaths occurred. At 8 years, the Kaplan-Meier estimates of the probability of death were 34.0% among patients with a phase bandwidth <100° and 56.8% among those with a bandwidth ≥100°. After adjustment for standard clinical variables, QRS dyssynchrony was independently associated with death (Hazard Ratio (HR), per 10°: 1.092, 95% Confidence Interval (CI) 1.048,1.139, P < .0001). Phase bandwidth was similarly associated with death after clinical adjustment (HR per 10°: 1.056, 95% CI 1.041,1.072, P < .0001). In clinically adjusted models examining QRS duration in addition to phase bandwidth, phase bandwidth had a stronger association with mortality. After accounting for left ventricular ejection fraction (LVEF), neither QRS duration nor phase bandwidth were statistically significant. Among patients with EF >35%, QRS duration and phase bandwidth together provided value above that provided by LVEF alone (P = 0.0181). When examining cardiovascular death, results were consistent with all-cause death. CONCLUSIONS: Among patients with CAD, mechanical left ventricular dyssynchrony measured by GSPECT MPI has a stronger relationship with outcomes than electrical dyssynchrony measured by QRS duration. After adjustment for baseline characteristics and LVEF, neither mechanical nor electrical dyssynchrony is independently associated with all-cause death or cardiac death. Among patients with EF >35%, mechanical and electrical dyssynchrony together provided prognostic value above that afforded by LVEF.

Yield of left ventricular dyssynchrony by gated SPECT MPI in patients with heart failure prior to implantable cardioverter-defibrillator or cardiac resynchronization therapy with a defibrillator: Characteristics and prediction of cardiac outcome.

BACKGROUND: Mechanical left ventricular dyssynchrony (MLVD) might contribute in the therapeutic decision-making in patients with heart failure (HF) prior to cardiac resynchronization therapy (CRT). Our aim was to assess MLVD in patients with HF prior to implantable cardioverter-defibrillator (ICD) compared to patients with CRT-D. METHODS: In a prospective study, patients with LVEF ≤ 35% who were scheduled for ICD or CRT-D, underwent gated SPECT myocardial perfusion imaging with technetium 99m sestamibi within 3 months prior procedure. MLVD was measured by phase analysis. RESULTS: The study cohort consisted of 143 patients, 71 with ICD and 72 with CRT-D. Age 68.3 ± 11 and LVEF 24 ± 6%. Phase standard deviation (SD) was 62.5 ± 18 and 59.7 ± 20 (P = NS), respectively. During follow-up of 23.7 ± 12.1 months, there were 10 vs 14 cardiac death in ICD and CRT-D, respectively (P = NS), hospitalization for HF, in 34 vs 53 (P < .001). In multivariate analysis, Phase SD was the independent predictor for cardiac death [HR 2.66 (95% CI 1.046-6.768), P = .04]. Kaplan-Meier curves of phase SD of 60° significantly identified ICD patients with and without cardiac deaths and hospitalization for HF exacerbation. CONCLUSIONS: MLVD by phase SD can identify patients with cardiac events and predict cardiac death in patients treated with ICD.

Qualitative and quantitative comparison of gated blood pool single photon emission computed tomography using low-energy high-resolution and SMARTZOOM collimation.

OBJECTIVE: The aim of this study was to assess the feasibility of IQ-SPECT gated blood pool (MUGA) under conditions of decreased scan time (ST). PATIENTS AND METHODS: Ten patients underwent routine 26-min, two-view planar, followed by LEHR and IQ-SPECT MUGA, on a Siemens dual-head Symbia scanner. Six 'back and forth' 4-min SPECT scans were summed into 4-, 8-, 12-, 16-, 20-, and 24-min equivalent scans, and reconstructed iteratively (IQ-SPECT and LEHR) and with FBP (LEHR). Uniformity, contrast, and wall motion were scored on a five-point scale. Linear regressions of left ventricular (LV) ejection fraction (EF) were performed between FBP, Flash 3D, and IQ-SPECT versus planar and Flash 3D and IQ-SPECT versus FBP. Agreement tables between Flash 3D and IQ-SPECT versus FBP LV EF were generated using a normal versus cardiotoxicity threshold of 50%. RESULTS: IQ-SPECT had the best scores for all STs, and 4, 8, and 16 min IQ-SPECT were judged to be similar to 24-min LEHR FBP, Flash 3D, and planar, respectively. The average LV EF correlation coefficients were 0.69, 0.71, and 0.63 between IQ-SPECT, Flash 3D, and FBP versus planar, respectively; 0.70 between IQ-SPECT and FBP; and 0.88 between Flash 3D and FBP, and all were statistically significant (P<0.05), except for 16-min FBP LEHR versus planar. Agreement tables showed diagnostic equivalence of IQ-SPECT, Flash 3D, and FBP. CONCLUSION: These preliminary results suggest that IQ-SPECT is equivalent to LEHR Flash 3D and FBP for MUGA SPECT, and better at reduced ST. A larger patient population study is necessary for a more definitive assessment.

Clinical values of left ventricular mechanical dyssynchrony assessment by gated myocardial perfusion SPECT in patients with acute myocardial infarction and multivessel disease.

PURPOSE: The aim of this study was to evaluate the prognostic value of additional evaluation of left ventricular mechanical dyssynchrony (LVMD) by gated myocardial perfusion single-photon emission computed tomography (GMPS) in patients with acute myocardial infarction (MI) and multivessel disease. METHODS: One hundred and nine acute MI patients with >50 % stenosis in at least one non-culprit artery who underwent GMPS within 2 weeks were enrolled. All patients underwent successful revascularization of the culprit arteries. Those with previous MI, atrial fibrillation, or frequent ventricular premature complexes, cardiac devices, significant patient motion, or procedure-related events were excluded. Phase standard deviation (PSD) and phase histogram bandwidth (PBW) were measured for assessment of LVMD. Patients were followed up for a median of 26 months after index MI, for composite major adverse cardiac events (MACE), which consisted with all-cause death, unplanned hospitalization due to heart failure and severe ventricular arrhythmias (sustained ventricular tachycardia or ventricular fibrillation). Independent predictors of MACE were evaluated. RESULTS: MACE occurred in 22 patients (20 %). Stress PSD (53.3 ± 17.3° vs. 35.3 ± 18.9°; p <0.001), stress PBW (147.6 ± 54.6° vs. 96.8 ± 59.2°; p = 0.001) and resting PBW (126.8 ± 37.5° vs. 96.6 ± 48.9°; p = 0.001) were significantly higher in patients with MACE compared to those without. Multivariate analysis revealed that stress PSD ≥45.5° and stress PBW ≥126.0° were predictive of MACE, as well as suboptimal non-culprit artery revascularization (SNR) and renin-angiotensin system (RAS) blockade medication. Higher stress PSD and stress PBW were associated with poorer prognosis both in patients with and without SNR, and those with RAS blockade medication, but not in those without RAS blockade medication. CONCLUSIONS: LVMD measured by GMPS showed added prognostic value in acute MI with multivessel disease. GMPS could serve as a comprehensive evaluation imaging tool in patients with acute MI and multivessel disease.

Predictors of high-risk coronary artery disease in subjects with normal SPECT myocardial perfusion imaging.

BACKGROUND: While uncommon, normal stress SPECT myocardial perfusion imaging (MPI) can be seen in patients with high-risk coronary artery disease (CAD) by invasive coronary angiography (ICA).The predictors of high-risk CAD in patients with normal SPECT-MPI have not been described. METHODS: We studied 580 patients (age 64 ± 12 years, 49% men) without known CAD who underwent stress-gated SPECT-MPI [exercise (41%) or vasodilator (59%)] <2 months before ICA and had summed stress score (SSS) <4. High-risk CAD was defined as 3 vessels with ≥70% stenosis, 2 vessels with ≥70% stenosis including proximal left anterior descending, or left main with ≥50% stenosis. Obstructive non-high-risk CAD was defined by the presence of a ≥70% stenosis but without having other high-risk criteria. Tenfold cross-validated receiver operating characteristic (ROC) estimates were obtained to assess the predictors of high-risk CAD. RESULTS: Forty-two subjects (7.2%) had high-risk CAD and 168 (29.0%) had obstructive non-high-risk CAD. Variables associated with high-risk CAD were pretest probability of CAD ≥66% (Odds ratio [OR] 3.63, 95% CI 1.6-8.3, P = .002), SSS > 0 (OR 7.46, 95% CI 2.6-21.1, P < 0.001), and abnormal TID (OR 2.16, 95% CI 1.0-4.5, P = 0.044). When substituted for TID, EF change was also predictive of high-risk CAD (OR 0.93, 95% CI 0.9-1.0, P = 0.023). The prevalence of high-risk CAD increased as the number of these predictors increased. In a sub-analysis of patients in whom quantitative total perfusion deficit (TPD) was available, TPD > 0 was also a predictor of high-risk CAD (OR 6.01, 95% CI 1.5-22.2, P = 0.011). CONCLUSION: Several clinical, stress, and SPECT-MPI findings are associated high-risk CAD among patients with normal SPECT-MPI. Consideration of these factors may improve the overall assessment of the likelihood of high-risk CAD in patients undergoing stress SPECT-MPI.

Variation in use of left ventriculography in the Veterans Affairs Health Care System.

BACKGROUND: Contrast left ventriculography is a method of measuring left ventricular function usually performed at the discretion of the invasive cardiologist during cardiac catheterization. We sought to determine variation in the use of left ventriculography in the Veterans Affairs (VA) Health Care System. METHODS AND RESULTS: We identified adult patients who underwent cardiac catheterization including coronary angiography between 2000 and 2009 in the VA Health Care System. We determined patient and hospital predictors of the use of left ventriculography as well as the variation in use across VA facilities. Results were validated using data from the VA's Clinical Assessment, Reporting, and Tracking (CART) program. Of 457 170 cardiac catheterization procedures among 336 853 patients, left ventriculography was performed on 263 695 (58%) patients. Use of left ventriculography decreased over time (64% in 2000 to 50% in 2009) and varied markedly across facilities (<1->95% of cardiac catheterizations). Patient factors explained little of the large variation in use between facilities. When the cohort was restricted to those with an echocardiogram in the prior 30 days and no intervening event, left ventriculography was still performed in 50% of cases. CONCLUSIONS: There is large variation in the use of left ventriculography across VA facilities that is not explained by patient characteristics.

Normality index of ventricular contraction based on a statistical model from FADS.

Radionuclide-based imaging is an alternative to evaluate ventricular function and synchrony and may be used as a tool for the identification of patients that could benefit from cardiac resynchronization therapy (CRT). In a previous work, we used Factor Analysis of Dynamic Structures (FADS) to analyze the contribution and spatial distribution of the 3 most significant factors (3-MSF) present in a dynamic series of equilibrium radionuclide angiography images. In this work, a probability density function model of the 3-MSF extracted from FADS for a control group is presented; also an index, based on the likelihood between the control group's contraction model and a sample of normal subjects is proposed. This normality index was compared with those computed for two cardiopathic populations, satisfying the clinical criteria to be considered as candidates for a CRT. The proposed normality index provides a measure, consistent with the phase analysis currently used in clinical environment, sensitive enough to show contraction differences between normal and abnormal groups, which suggests that it can be related to the degree of severity in the ventricular contraction dyssynchrony, and therefore shows promise as a follow-up procedure for patients under CRT.

Use and overuse of left ventriculography.

BACKGROUND: Left ventriculography provided the first imaging of left ventricular function and was historically performed as part of coronary angiography despite a small but significant risk of complications. Because modern noninvasive imaging techniques are more accurate and carry smaller risks, the routine use of left ventriculography is of questionable utility. We sought to analyze the frequency that left ventriculography was performed during coronary angiography in patients with and without a recent alternative assessment of left ventricular function. METHODS: We performed a retrospective analysis of insurance claims data from the Aetna health care benefits database including all adults who underwent coronary angiography in 2007. The primary outcome was the concomitant use of left ventriculography during coronary angiography. RESULTS: Of 96,235 patients who underwent coronary angiography, left ventriculography was performed in 78,705 (81.8%). Use of left ventriculography was high in all subgroups, with greatest use in younger patients, those with a diagnosis of coronary disease, and those in the Southern United States. In the population who had undergone a very recent ejection fraction assessment by another modality (within 30 days) and who had had no intervening diagnosis of new heart failure, myocardial infarction, hypotension, or shock (37,149 patients), left ventriculography was performed in 32,798 patients (88%)-a rate higher than in the overall cohort. CONCLUSIONS: Left ventriculography was performed in most coronary angiography cases and often when an alternative imaging modality had been recently completed. New clinical practice guidelines should be considered to decrease the overuse of this invasive test.

Positive spillover effects of prescribing requirements: increased cardiac testing in patients treated with trastuzumab for HER2+ metastatic breast cancer.

BACKGROUND: Cardiotoxicity is a concern in patients on trastuzumab therapy, and cardiac function assessment is a recommended practice. In 2006, trastuzumab was publically subsidised for human epidermal growth factor receptor-2 early stage breast cancer with a requirement for cardiac testing prior to and during treatment. AIM: To investigate the spillover effects of this requirement on testing rates in metastatic patients treated with trastuzumab where no monitoring requirements are applied. METHODS: We examined cardiac testing (echocardiography or multiple-gated acquisition scan) in 3779 women with metastatic breast cancer receiving trastuzumab between December 2001 and February 2010 and used interrupted time-series analyses to estimate changes in testing rates. The main outcome measures were the proportion of eligible patients, by quarter, receiving a cardiac function test pretreatment and during trastuzumab therapy. RESULTS: Only 21% of women had a cardiac function test pretreatment, and 47% were tested at some point during the first year of trastuzumab therapy. The introduction of mandatory cardiac testing for early breast cancer was associated with an immediate 8% increase (95% confidence interval, 2-14%) in pretreatment cardiac testing and an immediate 7% increase (95% confidence interval, 4-10%) in testing during therapy in metastatic patients. Testing rates during therapy increased steadily from early 2005, coinciding with the release of interim results from several trastuzumab trials reporting cardiac-safety outcomes. CONCLUSION: The introduction of mandatory cardiac testing for early stage disease spilled over to the metastatic setting. While deviation from guidelines may be warranted in some cases, this study suggests underutilisation of cardiac testing among patients treated with trastuzumab in the metastatic setting.

Results from an Australian and New Zealand audit of left ventricular ejection fraction from gated heart pool scan analysis.

AIM: A voluntary audit was undertaken to compare left ventricular ejection fraction (LVEF) calculations from gated heart pool studies using software packages currently available throughout Australia and New Zealand (ANZ). METHODS: A data set previously developed by a task group of the Institute of Physics and Engineering in Medicine (IPEM) consisting of 12 planar gated studies with LVEF ranging from 17 to 67% was provided to each site with worksheets to record individual technologist's results as well as information about individual department's equipment, software used for calculation of LVEF and experience of the analysers. Data analysis included calculation of an overall mean LVEF and standard deviation (SD) for all patients, which were compared with the mean IPEM LVEF. A comparison among software packages was done to examine differences in mean LVEF. RESULTS: Results were received from a total of 22 sites using six different software packages, with 187 processed studies included for analysis. Reproducibility of studies 4 and 8 showed good agreement, with an SD of 1.0 EF units (P=0.5290). Good correlation was found between the ANZ mean LVEF and the corresponding IPEM value per patient study, with R=0.98. The ANZ overall mean LVEF was 47%, which was higher that the IPEM mean by 4.9 EF units. The average difference among all software packages was +5.1 EF units. CONCLUSION: Differences were found between the IPEM mean and the ANZ mean LVEF. Variability in LVEF values between software packages was demonstrated, with an average of 5.1 EF units. The ANZ overall mean for LVEF was 47.2%, being 4.9 EF units higher than the IPEM value.

Assessing risk in acute chest pain: The value of stress myocardial perfusion imaging in patients admitted through the emergency department.

BACKGROUND: To prospectively assess the clinical value of stress-gated myocardial single photon emission computed tomography (SPECT) for triaging patients admitted through the emergency department (ED) with acute chest pain (ACP). METHODS: Prospective, observational cohort study in 1,576 consecutive patients who were evaluated for ACP over a 29-month period. Stress SPECT was performed within 24 hours of admission from the ED. Analysis included quantification of total and ischemic left ventricular perfusion defect size (PDS). Cardiac events were defined as an acute coronary syndrome during the index hospitalization or in follow-up over 7.3 ± 2.8 months. RESULTS: Eighty-five cardiac events occurred in 77 patients (4.9%). SPECT was abnormal in 135 patients (8.6%) of whom 83 (61.5%) had a reversible defect. Event rates were significantly higher in patients with an abnormal (40%) versus a normal (1.6%) SPECT (P < .0001); and in those with a (1) large (>15%) versus small (≤15%) PDS (50.0% vs 33.7%, P = .05) and (2) large (>10%) versus small (≤10%) ischemic PDS (87.5% vs 42.4%, P < .0001, respectively). SPECT best predicted cardiac events by multivariate analysis. The addition of SPECT to clinical variables significantly improved overall risk prediction (global χ(2) 103.6 vs 207.1, P < .001). CONCLUSIONS: Stress SPECT can accurately assess risk in a heterogeneous group of patients with ACP of unclear cardiac etiology, and beyond that provided by a clinical risk assessment alone. Our results support the use of stress SPECT for identifying very low-risk ACP patients with normal study results who can be safely discharged home.

Left ventricular dyssynchrony in patients with end-stage liver disease.

BACKGROUND: Limited published data suggested that patients with end-stage liver disease (ESLD) might have "cirrhotic cardiomyopathy," which could have an earlier stage manifested by mechanical dyssynchrony before left ventricular (LV) dysfunction. METHODS AND RESULTS: We studied consecutive patients with ESLD who had a stress-gated Tc-99m sestamibi myocardial perfusion imaging between 2008 and 2010 prior to liver transplant. Patients with LVEF < 50%, abnormal perfusion, or QRS ≥ 120 ms were excluded. Baseline demographics, co-morbidities, model for ESLD (MELD) score, LV volumes, mass, ejection fraction (EF), and dyssynchrony indices (standard deviation and bandwidth) were extracted. The phase indices were compared to a normal cohort. There were 179 patients with a mean age 53 ± 8 years, LVEF 72 ± 10%. Hepatitis C, non-alcoholic steatohepatitis, and alcohol abuse were the most common cause of liver cirrhosis (40%, 18%, and 14%, respectively). Patients with ESLD had similar standard deviation (14 ± 8° vs 15 ± 6°, P = NS) and bandwidth (41 ± 25° vs 42 ± 14°, P = NS) to the normal cohort. Only four patients (2%) had a standard deviation >27° (mean + 2 SD of the control group). The phase standard deviations and bandwidth similar in patients with MELD scores of ≤10, 11-18, 19-24, and ≥25 (P = NS for both). There was no correlation between the MELD score and standard deviation or bandwidth (r = -0.044 and -0.068, respectively, P = NS for both). Also, there was no correlation between the QTc and dyssynchrony indices. After 1-year follow-up, 22 patients died (12%). The dyssynchrony indices were similar among those who died and those who survived. CONCLUSION: Patients with ESLD and normal EF have no evidence for LV dyssynchrony.

Predictive value of myocardial and coronary imaging in the long-term outcome of potential renal transplant recipients.

BACKGROUND: Coronary artery disease is a major cause of morbidity and mortality in renal transplant recipients, but there is no agreed screening protocol. The value of myocardial perfusion imaging (MPI) and coronary angiography (CA) in predicting future cardiovascular events and mortality in unselected dialysis patients was studied. METHODS: Forty seven patients (mean age 51±14 years, 37 males), underwent both CA and MPI as part of pre-renal transplant assessment between 1995 and 1999. Follow-up period was 75±132 (range 3 to 143) months. RESULTS: Twenty-two (46.8%) patients had >50% stenosis of at least one major coronary artery (CAD), only 10 patients had abnormal MPI. Positive CA was found in all patients with angina and in 80% of diabetics. During follow-up 18 (38.3%) patients received a transplant and 28 (59.6%) patients died, of which 16 were proven or suspected cardiac deaths. Survival was significantly longer in patients with negative MPI or CA (92 and 96 versus 29 and 54 months for positive studies, respectively). CA had PPV of 95.7% and NPV of 54.2% for predicting the combined outcome of death and cardiovascular events whereas for MPI and MUGA, PPVs were 90.9% and 73.3% and NPVs 37.8% and 30%, respectively. CONCLUSIONS: Although MPI had a high specificity for CAD detection, its sensitivity appears limited in dialysis patients. The study suggests that those with angina and/or diabetes should undergo CA because of the high incidence of CAD in these groups, but MPI was at least as important as CA in overall mortality prediction over a long follow-up.

Blunted heart rate response as a predictor of cardiac death in patients undergoing vasodilator stress technetium-99m sestamibi gated SPECT myocardial perfusion imaging.

INTRODUCTION: The prognostic value of a blunted heart rate response (BHR) during ECG-gated vasodilator stress SPECT MPI in relation to ventricular function on long-term cardiovascular events is not well established. We performed this study to evaluate the incremental prognostic value of BHR during pharmacological stress SPECT MPI. METHODS: Consecutive patients who underwent dipyridamole stress Tc-99m sestamibi ECG-gated SPECT MPI (without exercise) were identified. The ratio of peak stress heart rate to baseline was noted. If the ratio was <1.20, it was considered blunted (BHR). The images were interpreted using the standard ASNC 17 segment model. Patients were followed up for a mean time period of 2.3 +/- 1.5 years. RESULTS: Sixty-four percent (2,890/4,484) of patients demonstrated BHR during dipyridamole stress testing. Cardiac death, the primary end point, occurred in 6.8% of patients. Patients with BHR had a significantly lower cardiac death-free survival as compared to NO BHR group in total population (83% vs 94%; P < .001) as well as in subgroup with normal ejection fraction (89% vs 96%; P < .001). BHR was an independent predictor of cardiac death after adjusting for multiple clinical, perfusion, and function-related gated SPECT variables. CONCLUSION: Blunted heart rate response during vasodilator stress SPECT MPI is an important prognostic marker for cardiac death.

Diagnostic characteristics of clozapine-induced myocarditis identified by an analysis of 38 cases and 47 controls.

OBJECTIVE: To analyze cases of clozapine-induced myocarditis for clinical and diagnostic trends. METHOD: A case definition was developed by a multidisciplinary group using reports of myocarditis with clozapine submitted to the Australian Therapeutic Goods Administration. The definition uses for diagnosis either histology or the combination of new signs of cardiac dysfunction combined with a cardiac-specific diagnostic parameter occurring within 45 days of starting clozapine. Potential cases of clozapine-related myocarditis occurring between January 1993 and September 2008 and a comparative group of long-term clozapine users were documented from the patients' medical records. RESULTS: Thirty-eight of 59 reviewed cases met the case definition. Three patients died, and the diagnosis for these was confirmed on cardiac histology. Nearly all of the remaining patients had persistent tachycardia and elevated troponin level. The time to onset was 14-22 days in all except 2 patients. Of the patients who survived, 66% (23 cases) had eosinophilia occurring 0-7 days (mean, 4.0) after the peak in troponin. C-reactive protein (CRP) level was elevated to above 100 mg/L (952 nmol/L) in 79% (23 cases), and some had elevated levels of CRP when troponin level was still normal. None of the control group (47 patients) met the case definition. CONCLUSIONS: Eosinophil counts should not be relied on for diagnosis of clozapine-related myocarditis, but elevated CRP may be an early indicator of developing myocarditis. Patients starting clozapine should be actively monitored for myocarditis during the first 4 weeks, with extra care taken during week 3.

Evaluation of left ventricular volumes and ejection fraction by gated SPECT and cardiac MRI in patients with dilated cardiomyopathy.

PURPOSE: The goal of this study was to evaluate the accuracy of gated single photon emission computed tomography (SPECT) in the assessment of left ventricular (LV) end-diastolic/end-systolic volumes (EDV, ESV) and ejection fraction (LVEF) in patients with dilated cardiomyopathy, using cardiac magnetic resonance imaging (MRI) as the reference method. Furthermore, software-specific characteristics of Quantitative Gated SPECT (QGS), Emory Cardiac Toolbox (ECTB) and 4D-MSPECT were analysed. METHODS: Thirty-six patients with dilated cardiomyopathy who underwent gated (99m)Tc-methoxyisobutylisonitrile SPECT and cardiac MRI were included. LV EDV, ESV and LVEF values of gated SPECT were calculated using QGS, ECTB and 4D-MSPECT. RESULTS: The correlation between the results of gated SPECT and cardiac MRI was excellent for EDV [R = 0.872 (QGS), R = 0.879 (ECTB), R = 0.869 (4D-MSPECT)], ESV [R = 0.908 (QGS), R = 0.897 (ECTB), R = 0.880 (4D-MSPECT)] and LVEF [R = 0.794 (QGS), R = 0.763 (ECTB), R = 0.710 (4D-MSPECT)]. EDV and ESV assessed by QGS did not differ significantly from those assessed by cardiac MRI (all p = NS), whereas EDV and ESV were overestimated by ECTB and 4D-MSPECT compared with cardiac MRI (all p < 0.05). LVEF was overestimated by QGS, ECTB and 4D-MSPECT compared with cardiac MRI (all p < 0.05). CONCLUSIONS: The correlation between gated SPECT and cardiac MRI is excellent for LV volume and LVEF values calculated by QGS, ECTB and 4D-MSPECT in patients with dilated cardiomyopathy. However, algorithm-varying over- or underestimation of LV volumes and LVEF should be accounted for in the clinical context.

Stress/Rest Myocardial Perfusion Abnormalities by Gated SPECT: Still the Best Predictor of Cardiac Events in Stable Ischemic Heart Disease.

UNLABELLED: The prognostic power of myocardial perfusion imaging in patients with ischemic heart disease (IHD) has been demonstrated since planar imaging. We aimed to investigate whether gated SPECT retains this value in current cardiology if compared with a complete diagnostic work-up and with more recent prognostic indicators. METHODS: We selected from our database a cohort of 676 consecutive inpatients who underwent a complete diagnostic work-up that included gated SPECT and coronary arteriography for known or suspected IHD. Patients with acute myocardial infarction (MI), previous coronary artery bypass surgery, or overt hyperthyroidism and patients who were undergoing dialysis treatment were excluded. During follow-up (median, 37 mo), 24 patients died from cardiac causes and 19 experienced a nonfatal MI. RESULTS: The following were determined to be independent predictors of event-free survival (cardiac death and nonfatal MI) in the different phases of diagnostic work-up using Cox proportional hazards regression analysis: among clinical variables, a previous MI; among laboratory examinations, serum creatinine and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) cholesterol levels; among electrocardiographic and echocardiographic variables, left ventricular ejection fraction; and among SPECT variables, summed rest score (SRS) and summed difference score (SDS). In addition, a score of coronary stenoses at angiography was an independent predictor. When the above predictors were tested together, SRS (P < 0.0001), SDS (P = 0.0108), and serum creatinine (P = 0.0186) and LDL and HDL cholesterol levels (P = 0.0222) were the final independent predictors of event-free survival. When gated SPECT was added to the clinical, laboratory, electrocardiographic, and echocardiographic variables, the prognostic stratification significantly improved (P < 0.05); when coronary arteriography was added to gated SPECT, prognostic stratification did not further improve (P > 0.25). If the information provided by gated SPECT was made available after clinical, laboratory, electrocardiographic, echocardiographic, and angiographic variables, the prognostic stratification still improved significantly (P < 0.05). In 492 of these patients with ascertained IHD, SRS and SDS were the final independent predictors of survival. Medical treatment and coronary revascularization did not affect the prognostic information of gated SPECT. CONCLUSION: Myocardial perfusion abnormalities at rest and after stress are still the best predictors of cardiac event-free survival in patients with known or suspected IHD, even when compared with an extensive diagnostic work-up.