Leanne Du

Leflunomide-Associated Pancytopenia With or Without Methotrexate

OBJECTIVE: To report 18 cases of pancytopenia associated with leflunomide use in Australia, 5 of which were treated at Princess Alexandra Hospital, Brisbane. CASE SUMMARIES: Leflunomide was used in the treatment of rheumatoid arthritis in 17 of 18 patients; the other patient was diagnosed with systemic lupus erythematosus. Median age was 65.5 years (range 18–79), and 15 of the patients were female. Fourteen patients were on combined treatment with methotrexate. Pancytopenia was typically severe, requiring hospital admission, withdrawal of the immunosuppressant(s), intensive supportive therapy, and treatment of neutropenic sepsis. Five patients died, 4 of whom were receiving concomitant methotrexate. Time to onset of pancytopenia ranged from 11 days to 4 years (median 4 mo). In one case in which the patient had been stable while receiving leflunomide, methotrexate, and hydroxychloroquine for 4 years, fatal pancytopenia was triggered by acute renal failure secondary to dehydration and use of nonsteroidal antiinflammatory drugs. The Naranjo probability scale suggested a probable causal association in 5 cases and possible association in the remainder. DISCUSSION: Leflunomide, indicated for treatment of active rheumatoid arthritis, inhibits pyrimidine synthesis in lymphocytes and other rapidly dividing cells and may rarely be associated with life-threatening pancytopenia. Combination therapy with methotrexate may increase the risk. Time to onset is variable, and clinicians should remain vigilant, particularly when there is a change in the patients baseline health status. CONCLUSIONS: The risk of pancytopenia during leflunomide therapy appears to be increased when the drug is combined with methotrexate and in older patients. Onset may be delayed, and ongoing monitoring of blood counts is essential.

Cardiac CT Assessment of Prosthetic Aortic Valve Dysfunction Secondary to Acute Thrombosis and Response to Thrombolysis

A 58-year-old woman presented with a 2-week history of acute dyspnea in the setting of subtherapeutic warfarin anticoagulation (international normalized ratio, 1.7 on admission) with a history of previous St. Jude bileaflet aortic valve replacement (AVR) 5 years previously. Transthoracic echocardiography revealed severe elevation of the prosthetic aortic transvalvular gradient (peak velocity, 5 m/s; peak gradient, 125 mm Hg) with severe eccentric aortic regurgitation. The morphology of the prosthetic aortic valve was not clearly visualized secondary to an acoustic shadow from the metallic prosthesis. The patient was referred to cardiac computed tomography (CT) for further evaluation of prosthetic dysfunction and to exclude coronary artery disease in case surgical intervention was required.

Comparison between real-time three-dimensional echocardiography, T1-201 single photon emission computed tomography and cardiac magnetic resonance imaging in the quantitative assessment of left ventricular volumes

We sought to determine the relative impact of myocardial scar and viability on post-infarct left ventricular (LV) remodeling in medically-treated patients with LV dysfunction. Forty patients with chronic ischemic heart disease (age 64±9, EF 40±11%) underwent rest-redistribution Tl201 SPECT (scar = 50% transmural extent), A global index of scarring for each patient (CMR scar score) was calculated as the sum of transmural extent scores in all segts. LV end diastolic volumes (LVEDV) and LV end systolic volumes (LVESV) were measured by real-time threedimensional echo at baseline and median of 12 months follow-up. There was a significant positive correlation between change in LVEDV with number of scar segts by all three imaging techniques (LVEDV: SPECT scar, r = 0.62, p 15%) was predicted bySPECTscars(AUC= 0.79),DbEscars(AUC= 0.76),CMR scars (AUC= 0.70), and CMR scar score (AUC 0.72). There were no significant differences between any of the ROC curves (Z score <0.74). Number of SPECT scars (p = 0.002), DbE scars (p = 0.01), CMR scars (p = 0.004), and CMR scar score (p = 0.03) were independent predictors of LVEDV. The extent of scar tissue can predict global LV remodeling irrespective of cardiac imaging technique but myocardial viability may not be protective against LV remodeling in medically-treated patients.Transmural extent of infarction (TME) may be an important determinant of functional recovery and remodeling. Recent animal data suggest that strain rate imaging (SRI) maybe able to identify subendocardial ischemia.We compared SRI and cyclic variation of integrated backscatter (CVIB) for predicting TME in the quantitative assessment of regional subepicardial function. Forty-nine (n = 49) postmyocardial infarct patients (61±10 years, EF 41±10%) underwent tissue Doppler echocardiography (TDE) and contrast enhanced magnetic resonance imaging (CMR). A15 mm×2mm sampling volume (tracked to wall motion) was placed over the long axis subepicardial region of each segment during TDE offline analysis to measure peak longitudinal systolic strain rate (SR), peak longitudinal systolic strain (PS), and CVIB. Findingswere compared with TME classified into two categories of scar thickness by CMR: Non-transmural (TME≤50%), and transmural (TME > 50%). Of 213 segments identified with resting wall motion abnormalities, 145 segments showed delayed hyperenhancement on CMR. SR, PS and CVIB were similar with no significant differences between transmural and non-transmural infarcts regardless of the echo modality.Revascularization (RVS) of scar segts does not lead to recovery of left ventricular (LV) function, but its effect on post-infarct remodeling is unclear. We examined the impact of RVS on regional remodeling in different transmural extents of scar (TME). Dobutamine echo (DbE) and contrast enhanced magnetic resonance imaging (ce- MRI) were performed in 72 pts post MI (age 63±10, EF 49±12%). Pts were selected for RVS (n = 31) or medical treatment (n = 41). Segts were classified as scar if there were no contractile reserve during lowdose DbE.TMEwas measured by ce-MRI; a cutoff of 75% was used to differentiate transmural (TM) from non-transmural (NT) scars. Regional end systolic (ESV) and end diastolic volumes (EDV) were measured at baseline and 12 months follow up.Of 218 segts identified as scar on DbE, 164wereNTand 54 were TM on ce-MRI. Revascularization was performed to 62 NT and 11 TM segts. In the RVS group, there was reverse remodeling with significant reduction in LV volumes in NT (ESV, 6.8±3.2 ml versus 5.8±3.7 ml, p = 0.002; EDV, 10.9±4.9 ml versus 9.8±5.6 ml, p = 0.02), but no significant change in volumes in TM (ESV, 6.9±3.7 ml versus 5.4±2.1 ml, p = 0.09; EDV, 10.2±4.4 ml versus 9.4±4.3 ml, p = 0.5). In the medically treated group, there were no changes in LV volumes in both NT (ESV, 12.0±11.9 ml versus 12.7±13.8 ml, p = 0.3; EDV, 12.5±7.8 ml versus 12.6±9.7 ml, p = 0.8) and TM (ESV, 8.0±3.8 ml versus 7.9±4.6 ml, p = 0.8; EDV, 10.3±4.8 ml versus 10.4±5.4 ml, p = 0.9). Despite absence of contractile reserve on DbE, NT benefit from coronary revascularization with regional reverse LV remodeling.Left ventricular (LV) volumes have important prognostic implications in patients with chronic ischemic heart disease. We sought to examine the accuracy and reproducibility of real-time 3D echo (RT-3DE) compared to TI-201 single photon emission computed tomography (SPECT) and cardiac magnetic resonance imaging (MRI). Thirty (n = 30) patients (age 62±9 years, 23 men) with chronic ischemic heart disease underwent LV volume assessment with RT-3DE, SPECT, and MRI. Ano vel semi-automated border detection algorithmwas used by RT-3DE. End diastolic volumes (EDV) and end systolic volumes (ESV) measured by RT3DE and SPECT were compared to MRI as the standard of reference. RT-3DE and SPECT volumes showed excellent correlation with MRI (Table). Both RT- 3DE and SPECT underestimated LV volumes compared to MRI (ESV, SPECT 74±58 ml versus RT-3DE 95±48 ml versus MRI 96±54 ml); (EDV, SPECT 121±61 ml versus RT-3DE 169±61 ml versus MRI 179±56 ml). The degree of ESV underestimation with RT-3DE was not significant.

Coronary revascularization can improve regional left ventricular volumes in non-transmural scars without contractile reserve

We sought to determine the relative impact of myocardial scar and viability on post-infarct left ventricular (LV) remodeling in medically-treated patients with LV dysfunction. Forty patients with chronic ischemic heart disease (age 64±9, EF 40±11%) underwent rest-redistribution Tl201 SPECT (scar = 50% transmural extent), A global index of scarring for each patient (CMR scar score) was calculated as the sum of transmural extent scores in all segts. LV end diastolic volumes (LVEDV) and LV end systolic volumes (LVESV) were measured by real-time threedimensional echo at baseline and median of 12 months follow-up. There was a significant positive correlation between change in LVEDV with number of scar segts by all three imaging techniques (LVEDV: SPECT scar, r = 0.62, p 15%) was predicted bySPECTscars(AUC= 0.79),DbEscars(AUC= 0.76),CMR scars (AUC= 0.70), and CMR scar score (AUC 0.72). There were no significant differences between any of the ROC curves (Z score <0.74). Number of SPECT scars (p = 0.002), DbE scars (p = 0.01), CMR scars (p = 0.004), and CMR scar score (p = 0.03) were independent predictors of LVEDV. The extent of scar tissue can predict global LV remodeling irrespective of cardiac imaging technique but myocardial viability may not be protective against LV remodeling in medically-treated patients.Transmural extent of infarction (TME) may be an important determinant of functional recovery and remodeling. Recent animal data suggest that strain rate imaging (SRI) maybe able to identify subendocardial ischemia.We compared SRI and cyclic variation of integrated backscatter (CVIB) for predicting TME in the quantitative assessment of regional subepicardial function. Forty-nine (n = 49) postmyocardial infarct patients (61±10 years, EF 41±10%) underwent tissue Doppler echocardiography (TDE) and contrast enhanced magnetic resonance imaging (CMR). A15 mm×2mm sampling volume (tracked to wall motion) was placed over the long axis subepicardial region of each segment during TDE offline analysis to measure peak longitudinal systolic strain rate (SR), peak longitudinal systolic strain (PS), and CVIB. Findingswere compared with TME classified into two categories of scar thickness by CMR: Non-transmural (TME≤50%), and transmural (TME > 50%). Of 213 segments identified with resting wall motion abnormalities, 145 segments showed delayed hyperenhancement on CMR. SR, PS and CVIB were similar with no significant differences between transmural and non-transmural infarcts regardless of the echo modality.Revascularization (RVS) of scar segts does not lead to recovery of left ventricular (LV) function, but its effect on post-infarct remodeling is unclear. We examined the impact of RVS on regional remodeling in different transmural extents of scar (TME). Dobutamine echo (DbE) and contrast enhanced magnetic resonance imaging (ce- MRI) were performed in 72 pts post MI (age 63±10, EF 49±12%). Pts were selected for RVS (n = 31) or medical treatment (n = 41). Segts were classified as scar if there were no contractile reserve during lowdose DbE.TMEwas measured by ce-MRI; a cutoff of 75% was used to differentiate transmural (TM) from non-transmural (NT) scars. Regional end systolic (ESV) and end diastolic volumes (EDV) were measured at baseline and 12 months follow up.Of 218 segts identified as scar on DbE, 164wereNTand 54 were TM on ce-MRI. Revascularization was performed to 62 NT and 11 TM segts. In the RVS group, there was reverse remodeling with significant reduction in LV volumes in NT (ESV, 6.8±3.2 ml versus 5.8±3.7 ml, p = 0.002; EDV, 10.9±4.9 ml versus 9.8±5.6 ml, p = 0.02), but no significant change in volumes in TM (ESV, 6.9±3.7 ml versus 5.4±2.1 ml, p = 0.09; EDV, 10.2±4.4 ml versus 9.4±4.3 ml, p = 0.5). In the medically treated group, there were no changes in LV volumes in both NT (ESV, 12.0±11.9 ml versus 12.7±13.8 ml, p = 0.3; EDV, 12.5±7.8 ml versus 12.6±9.7 ml, p = 0.8) and TM (ESV, 8.0±3.8 ml versus 7.9±4.6 ml, p = 0.8; EDV, 10.3±4.8 ml versus 10.4±5.4 ml, p = 0.9). Despite absence of contractile reserve on DbE, NT benefit from coronary revascularization with regional reverse LV remodeling.Left ventricular (LV) volumes have important prognostic implications in patients with chronic ischemic heart disease. We sought to examine the accuracy and reproducibility of real-time 3D echo (RT-3DE) compared to TI-201 single photon emission computed tomography (SPECT) and cardiac magnetic resonance imaging (MRI). Thirty (n = 30) patients (age 62±9 years, 23 men) with chronic ischemic heart disease underwent LV volume assessment with RT-3DE, SPECT, and MRI. Ano vel semi-automated border detection algorithmwas used by RT-3DE. End diastolic volumes (EDV) and end systolic volumes (ESV) measured by RT3DE and SPECT were compared to MRI as the standard of reference. RT-3DE and SPECT volumes showed excellent correlation with MRI (Table). Both RT- 3DE and SPECT underestimated LV volumes compared to MRI (ESV, SPECT 74±58 ml versus RT-3DE 95±48 ml versus MRI 96±54 ml); (EDV, SPECT 121±61 ml versus RT-3DE 169±61 ml versus MRI 179±56 ml). The degree of ESV underestimation with RT-3DE was not significant.

The relative impact of scar and viable tissue in predicting global left ventricular remodeling in medically treated patients

We sought to determine the relative impact of myocardial scar and viability on post-infarct left ventricular (LV) remodeling in medically-treated patients with LV dysfunction. Forty patients with chronic ischemic heart disease (age 64±9, EF 40±11%) underwent rest-redistribution Tl201 SPECT (scar = 50% transmural extent), A global index of scarring for each patient (CMR scar score) was calculated as the sum of transmural extent scores in all segts. LV end diastolic volumes (LVEDV) and LV end systolic volumes (LVESV) were measured by real-time threedimensional echo at baseline and median of 12 months follow-up. There was a significant positive correlation between change in LVEDV with number of scar segts by all three imaging techniques (LVEDV: SPECT scar, r = 0.62, p 15%) was predicted bySPECTscars(AUC= 0.79),DbEscars(AUC= 0.76),CMR scars (AUC= 0.70), and CMR scar score (AUC 0.72). There were no significant differences between any of the ROC curves (Z score <0.74). Number of SPECT scars (p = 0.002), DbE scars (p = 0.01), CMR scars (p = 0.004), and CMR scar score (p = 0.03) were independent predictors of LVEDV. The extent of scar tissue can predict global LV remodeling irrespective of cardiac imaging technique but myocardial viability may not be protective against LV remodeling in medically-treated patients.Transmural extent of infarction (TME) may be an important determinant of functional recovery and remodeling. Recent animal data suggest that strain rate imaging (SRI) maybe able to identify subendocardial ischemia.We compared SRI and cyclic variation of integrated backscatter (CVIB) for predicting TME in the quantitative assessment of regional subepicardial function. Forty-nine (n = 49) postmyocardial infarct patients (61±10 years, EF 41±10%) underwent tissue Doppler echocardiography (TDE) and contrast enhanced magnetic resonance imaging (CMR). A15 mm×2mm sampling volume (tracked to wall motion) was placed over the long axis subepicardial region of each segment during TDE offline analysis to measure peak longitudinal systolic strain rate (SR), peak longitudinal systolic strain (PS), and CVIB. Findingswere compared with TME classified into two categories of scar thickness by CMR: Non-transmural (TME≤50%), and transmural (TME > 50%). Of 213 segments identified with resting wall motion abnormalities, 145 segments showed delayed hyperenhancement on CMR. SR, PS and CVIB were similar with no significant differences between transmural and non-transmural infarcts regardless of the echo modality.Revascularization (RVS) of scar segts does not lead to recovery of left ventricular (LV) function, but its effect on post-infarct remodeling is unclear. We examined the impact of RVS on regional remodeling in different transmural extents of scar (TME). Dobutamine echo (DbE) and contrast enhanced magnetic resonance imaging (ce- MRI) were performed in 72 pts post MI (age 63±10, EF 49±12%). Pts were selected for RVS (n = 31) or medical treatment (n = 41). Segts were classified as scar if there were no contractile reserve during lowdose DbE.TMEwas measured by ce-MRI; a cutoff of 75% was used to differentiate transmural (TM) from non-transmural (NT) scars. Regional end systolic (ESV) and end diastolic volumes (EDV) were measured at baseline and 12 months follow up.Of 218 segts identified as scar on DbE, 164wereNTand 54 were TM on ce-MRI. Revascularization was performed to 62 NT and 11 TM segts. In the RVS group, there was reverse remodeling with significant reduction in LV volumes in NT (ESV, 6.8±3.2 ml versus 5.8±3.7 ml, p = 0.002; EDV, 10.9±4.9 ml versus 9.8±5.6 ml, p = 0.02), but no significant change in volumes in TM (ESV, 6.9±3.7 ml versus 5.4±2.1 ml, p = 0.09; EDV, 10.2±4.4 ml versus 9.4±4.3 ml, p = 0.5). In the medically treated group, there were no changes in LV volumes in both NT (ESV, 12.0±11.9 ml versus 12.7±13.8 ml, p = 0.3; EDV, 12.5±7.8 ml versus 12.6±9.7 ml, p = 0.8) and TM (ESV, 8.0±3.8 ml versus 7.9±4.6 ml, p = 0.8; EDV, 10.3±4.8 ml versus 10.4±5.4 ml, p = 0.9). Despite absence of contractile reserve on DbE, NT benefit from coronary revascularization with regional reverse LV remodeling.Left ventricular (LV) volumes have important prognostic implications in patients with chronic ischemic heart disease. We sought to examine the accuracy and reproducibility of real-time 3D echo (RT-3DE) compared to TI-201 single photon emission computed tomography (SPECT) and cardiac magnetic resonance imaging (MRI). Thirty (n = 30) patients (age 62±9 years, 23 men) with chronic ischemic heart disease underwent LV volume assessment with RT-3DE, SPECT, and MRI. Ano vel semi-automated border detection algorithmwas used by RT-3DE. End diastolic volumes (EDV) and end systolic volumes (ESV) measured by RT3DE and SPECT were compared to MRI as the standard of reference. RT-3DE and SPECT volumes showed excellent correlation with MRI (Table). Both RT- 3DE and SPECT underestimated LV volumes compared to MRI (ESV, SPECT 74±58 ml versus RT-3DE 95±48 ml versus MRI 96±54 ml); (EDV, SPECT 121±61 ml versus RT-3DE 169±61 ml versus MRI 179±56 ml). The degree of ESV underestimation with RT-3DE was not significant.

Local geometric changes in left ventricular remodeling post-infarction can lead to apparent reduction in scar thickness

We sought to determine the relative impact of myocardial scar and viability on post-infarct left ventricular (LV) remodeling in medically-treated patients with LV dysfunction. Forty patients with chronic ischemic heart disease (age 64±9, EF 40±11%) underwent rest-redistribution Tl201 SPECT (scar = 50% transmural extent), A global index of scarring for each patient (CMR scar score) was calculated as the sum of transmural extent scores in all segts. LV end diastolic volumes (LVEDV) and LV end systolic volumes (LVESV) were measured by real-time threedimensional echo at baseline and median of 12 months follow-up. There was a significant positive correlation between change in LVEDV with number of scar segts by all three imaging techniques (LVEDV: SPECT scar, r = 0.62, p 15%) was predicted bySPECTscars(AUC= 0.79),DbEscars(AUC= 0.76),CMR scars (AUC= 0.70), and CMR scar score (AUC 0.72). There were no significant differences between any of the ROC curves (Z score <0.74). Number of SPECT scars (p = 0.002), DbE scars (p = 0.01), CMR scars (p = 0.004), and CMR scar score (p = 0.03) were independent predictors of LVEDV. The extent of scar tissue can predict global LV remodeling irrespective of cardiac imaging technique but myocardial viability may not be protective against LV remodeling in medically-treated patients.Transmural extent of infarction (TME) may be an important determinant of functional recovery and remodeling. Recent animal data suggest that strain rate imaging (SRI) maybe able to identify subendocardial ischemia.We compared SRI and cyclic variation of integrated backscatter (CVIB) for predicting TME in the quantitative assessment of regional subepicardial function. Forty-nine (n = 49) postmyocardial infarct patients (61±10 years, EF 41±10%) underwent tissue Doppler echocardiography (TDE) and contrast enhanced magnetic resonance imaging (CMR). A15 mm×2mm sampling volume (tracked to wall motion) was placed over the long axis subepicardial region of each segment during TDE offline analysis to measure peak longitudinal systolic strain rate (SR), peak longitudinal systolic strain (PS), and CVIB. Findingswere compared with TME classified into two categories of scar thickness by CMR: Non-transmural (TME≤50%), and transmural (TME > 50%). Of 213 segments identified with resting wall motion abnormalities, 145 segments showed delayed hyperenhancement on CMR. SR, PS and CVIB were similar with no significant differences between transmural and non-transmural infarcts regardless of the echo modality.Revascularization (RVS) of scar segts does not lead to recovery of left ventricular (LV) function, but its effect on post-infarct remodeling is unclear. We examined the impact of RVS on regional remodeling in different transmural extents of scar (TME). Dobutamine echo (DbE) and contrast enhanced magnetic resonance imaging (ce- MRI) were performed in 72 pts post MI (age 63±10, EF 49±12%). Pts were selected for RVS (n = 31) or medical treatment (n = 41). Segts were classified as scar if there were no contractile reserve during lowdose DbE.TMEwas measured by ce-MRI; a cutoff of 75% was used to differentiate transmural (TM) from non-transmural (NT) scars. Regional end systolic (ESV) and end diastolic volumes (EDV) were measured at baseline and 12 months follow up.Of 218 segts identified as scar on DbE, 164wereNTand 54 were TM on ce-MRI. Revascularization was performed to 62 NT and 11 TM segts. In the RVS group, there was reverse remodeling with significant reduction in LV volumes in NT (ESV, 6.8±3.2 ml versus 5.8±3.7 ml, p = 0.002; EDV, 10.9±4.9 ml versus 9.8±5.6 ml, p = 0.02), but no significant change in volumes in TM (ESV, 6.9±3.7 ml versus 5.4±2.1 ml, p = 0.09; EDV, 10.2±4.4 ml versus 9.4±4.3 ml, p = 0.5). In the medically treated group, there were no changes in LV volumes in both NT (ESV, 12.0±11.9 ml versus 12.7±13.8 ml, p = 0.3; EDV, 12.5±7.8 ml versus 12.6±9.7 ml, p = 0.8) and TM (ESV, 8.0±3.8 ml versus 7.9±4.6 ml, p = 0.8; EDV, 10.3±4.8 ml versus 10.4±5.4 ml, p = 0.9). Despite absence of contractile reserve on DbE, NT benefit from coronary revascularization with regional reverse LV remodeling.Left ventricular (LV) volumes have important prognostic implications in patients with chronic ischemic heart disease. We sought to examine the accuracy and reproducibility of real-time 3D echo (RT-3DE) compared to TI-201 single photon emission computed tomography (SPECT) and cardiac magnetic resonance imaging (MRI). Thirty (n = 30) patients (age 62±9 years, 23 men) with chronic ischemic heart disease underwent LV volume assessment with RT-3DE, SPECT, and MRI. Ano vel semi-automated border detection algorithmwas used by RT-3DE. End diastolic volumes (EDV) and end systolic volumes (ESV) measured by RT3DE and SPECT were compared to MRI as the standard of reference. RT-3DE and SPECT volumes showed excellent correlation with MRI (Table). Both RT- 3DE and SPECT underestimated LV volumes compared to MRI (ESV, SPECT 74±58 ml versus RT-3DE 95±48 ml versus MRI 96±54 ml); (EDV, SPECT 121±61 ml versus RT-3DE 169±61 ml versus MRI 179±56 ml). The degree of ESV underestimation with RT-3DE was not significant.