- Email: [email protected]
DATA-DRIVEN TIMING OF OPTIMAL LV EJECTION FRACTION ASSESSMENT IN BREAST CANCER PATIENTS EXPOSED TO TRASTUZUMAB
Abstracts METHODS:
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A total of 470 patients referred for cardiac PET between May 2010 and September 2013 with normal ejection fraction (EF>40%), no documented CAD and no regional perfusion defects (summed stress score <4) were included in the analysis. Data was obtained from the Rubidium PET-Alternative Radiopharmaceutical for Myocardial Imaging (Rb-ARMI) database at the University of Ottawa Heart Institute. Patients with a confirmed diagnosis of HF (adjudicated via chart review examining clinical documents, discharge summaries, emergency department visits and echocardiographic data available through electronic medical records at the Ottawa Hospital; n¼120) were compared to patients with no evidence of dyspnea or known HF (n¼350). The primary outcome analyzed was global LV and regional (left anterior descending artery, LAD; left circumflex, LCx; right coronary artery, RCA) MFR measured as stress/rest myocardial blood flow. Secondary variables including age, gender, body mass index, smoking history, hyperlipidemia, hypertension, anemia (on the basis of haemoglobin, HgB), renal dysfunction (represented by creatinine level, Cr) and diabetes were also examined. RESULTS: The average age of this cohort was 63, with 57% females. Patients with HFpEF were more likely to be older, female and have comorbid hypertension, diabetes and anemia. HFpEF was associated with a significant reduction in global (2.70 in Controls vs 2.20 in HFpEF, p<0.001) and regional MFR (LAD, 2.73 vs 2.22; LCx, 2.63 vs 2.15; RCA, 2.70 vs 2.20; all p<0.001). HFpEF remained a significant predictor of reduced global MFR after adjustment for age, gender, diabetes, Cr, HgB, BMI, smoking history, hypertension and hyperlipidemia (p<0.001). CONCLUSION: HFpEF is associated with reduced MFR independent of other risk factors and epicardial CAD. Whether this has prognostic value or may be a therapeutic target requires further study.
heart rate was 82 bpm (IQR: 70-102), QRS duration was 104 msec (IQR: 90-136), and QTc was 471 msec (IQR: 444-499). A completely normal ECG was rare (7.7%); the most common abnormalities were left ventricular hypertrophy (LVH; 24%), bundle branch block (LBBB: 13%; RBBB: 8%), Q-waves (12%) and ST-segment deviation 1 mm not associated with LVH or BBB (26%). Death within 90 days was recorded in 13.6% of patients. After adjustment for key clinical variables (age, sex, creatinine, ejection fraction, and medical history), none of the ECG findings were associated with 90-day mortality. In patients with sinus rhythm, only the presence of Qwaves remained a significant predictor of 90-day mortality after adjustment (OR 2.58 [1.34 - 5.00], p¼0.005). CONCLUSION: ECG abnormalities are common in AHF; however, other clinical factors appear to be associated with mortality. Further exploration of the role of the ECG in prognostication and management for patients in sinus rhythm and AHF is needed.
274 INSIGHTS INTO THE IMPORTANCE OF THE ECG IN PATIENTS WITH ACUTE HEART FAILURE
CB Johnson, P Andrew, J Sulpher, H Majeed, N Graham, M Turek, D Susan
P Gouda, BH Rowe, F McAlister, PW Armstrong, M Podder, JA Ezekowitz Edmonton, Alberta BACKGROUND:
Although acute Heart Failure (AHF) is commonly associated with electrocardiographic (ECG) abnormalities, their prognostic relationship is unclear. METHODS: We used data from AHF patients prospectively enrolled in the Acute Heart Failure - Emergency Management (AHF-EM) cohort at 3 Canadian hospitals. First available emergency department ECGs were reviewed blinded to clinical outcomes and coded according to international definitions. The association between patient variables, ECG characteristics and 90-day outcomes were assessed; a multi-variable logistic regression was performed. RESULTS: 922 (97%) of 952 enrolled AHF patients had an ECG in the ED. Median age was 77 years, 54% were male, 53% had a history of atrial fibrillation and the median ejection fraction was 45% (IQR: 30-55). Overall, 54% were in sinus rhythm, 35% in atrial fibrillation and 11% paced. Median
CIHR 275 DATA-DRIVEN TIMING OF OPTIMAL LV EJECTION FRACTION ASSESSMENT IN BREAST CANCER PATIENTS EXPOSED TO TRASTUZUMAB
Ottawa, Ontario BACKGROUND:
Adjuvant trastuzumab has improved outcomes in HER2/neu positive breast cancer. However, this treatment has been associated with decreased left ventricular ejection fraction (LVEF). There is no data-driven schedule to inform clinicians of the optimal timing for serial LVEF monitoring during trastuzumab therapy. We conducted a hypothesis-generating pooled trend analysis to identify a timeline for monitoring LVEF changes secondary to trastuzumab therapy in patients with breast cancer. METHODS: An English language search of Medline, Cochrane, ASCO Library, and an extensive bibliography search from January, 1999 to April 2014 was performed. Inclusion and exclusion criteria were met by 35 clinical trials (n¼9936). Primary outcome was interval reduction in LVEF following trastuzumab versus baseline (baseline LVEF post-anthracycline, pre-trastuzumab). RESULTS: A quadratic trend was identified between LVEF and trastuzumab across time. Decline in LVEF with trastuzumab occurred significantly early at 2 months, peaked at 7-15 months, and recovered post 30 months (Friedman ANOVA:
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Canadian Journal of Cardiology Volume 30 2014
F ¼ 19.9, p<0.05). Sensitivity analysis revealed robustness of analysis to concurrent non-anthracycline chemotherapy. CONCLUSION: This pooled trend analysis reveals that LVEF drops early after trastuzumab therapy which supports current clinical trial and real world monitoring strategies in which LVEF monitoring occurs early after starting Trastuzumab. This data suggests that access to prompt cardiology consultation should be available to patients early after starting trastuzumab therapy. Further research is needed to define optimal LVEF monitoring once trastuzumab therapy is complete.
(5.531.45 vs 3.651.67, p¼0.06). Patients treated with endothelin receptor antagonists (ERA) had significantly lower FDG SUV in the RV than that in patients without ERA (3.711.72 vs 8.534.78, p¼0.01), however there was no relationship between RV metabolism and other PAH therapy. CONCLUSION: Clinical right HF is associated with changes in both glucose and fatty acid substrate utilization in the RV. Metabolic changes in the RV may provide incremental prognostic information and could potentially be a treatment target for right HF associated with PAH.
276 EVALUATION OF RIGHT VENTRICULAR METABOLISM IN RIGHT HEART FAILURE ASSOCIATED WITH PULMONARY ARTERIAL HYPERTENSION
277 PREVALENCE OF VITAMIN D DEFICIENCY IN CANADIAN HEART FAILURE PATIENTS AND INSIGHTS IN TO THE ROLE OF VITAMIN D DEFICIENCY IN THE PATHOPHYSIOLOGY OF HEART FAILURE
H Ohira, B Mc Ardle, R Klein, R Davies, R deKemp, E Pena, J DaSilva, D Stewart, G Chandy, V Contreras-Dominguez, R Dunne, R Beanlands, L Mielniczuk
A Pourdjabbar, G Dwivedi, L Mielniczuk, R Haddad, E Stadnick, RA Davies, M Ruzicka, PP Liu, H Haddad
Ottawa, Ontario BACKGROUND:
Pulmonary arterial hypertension (PAH) results in premature death as a result of right ventricular (RV) dysfunction. However, there are substantial differences among patients in their tendency to develop RV failure. RV metabolic changes may be able to predict the development of right heart failure (HF) in patients with PAH. The aim of the study was to assess the relationship between right ventricular cardiac metabolism using positron emission scanning (PET) and established parameters related to RV failure including the six minute walk test (6MWT), brain natriuretic peptide (BNP), cardiac index (CI), mean pulmonary artery pressure (mPAP), mean right atrial pressure (mRAP), clinical evidence of RV failure and RVEF. The relationship between PAH specific therapy and cardiac metabolism was also evaluated. METHODS: Fourteen consecutive patients with PAH underwent right heart catheterizationfor assessment of pulmonary hemodynamics. A total of 86% of patients were on PAH therapy at the time of enrollment and 43% had a diagnosis of right HF. RV glucose and fatty acid metabolism were assessed with FDG and FTHA PET imaging. Substrate utilization was reported as a maximum standard uptake value (SUV). Relative RV FDG and FTHA uptake were determined as the ratio of RV/LV SUV. RVEF was determined by cardiac magnetic resonance (CMR). The clinical diagnosis of right HF was adjudicated by PH experts blinded to the imaging results. RESULTS: There was a negative correlation between RVEF and RV/LV ratio of FTHA SUV (r¼-0.81, p¼0.0048) however no correlation was observed between RVEF and that of FDG SUV (r¼-0.41, p¼0.19). There was a positive correlation between mPAP and RV/LV ratio of FDG SUV (r¼0.74, p¼0.003), and a trend toward an increase in that of FTHA SUV (r¼0.56, p¼0.06). No significant correlation was shown between both metabolic parameters and 6MWT, BNP, mRAP or CI. Patients with right HF had a significant increase in RV FDG uptake (6.633.80 vs 3.331.73, p<0.05) with a trend towards increased uptake of FTHA
Ottawa, Ontario AIMS: Vitamin D has been implicated in the pathophysiology of congestive heart failure (CHF) and vitamin D status has been shown to be inversely associated with increased hospitalization and mortality. The aim of this study was to investigate the prevalence of vitamin D deficiency in a North American heart failure patient population and to investigate potential mechanisms through which Vitamin D deficiency can lead to worse clinical outcomes in patients with CHF. METHODS AND RESULTS: Patients seen in consultation in our heart function clinic were enrolled in this observational study and were randomized to 1 of 3 groups based on their vitamin D levels. The following results are the baseline results of the first 86 patients enrolled. 68.6% (59/86) of patients screened and enrolled, demonstrated Vitamin D insufficiency (<75nmol/L), with 15% (13/86) having severe insufficiency (<35nmol/L). There was no difference in the baseline mean NYHA class, left ventricular ejection fraction (LVEF), brain natureitic peptide (BNP), renal function or inflammatory status, irrespective of the baseline vitamin D status (TABLE).
S195
A total of 470 patients referred for cardiac PET between May 2010 and September 2013 with normal ejection fraction (EF>40%), no documented CAD and no regional perfusion defects (summed stress score <4) were included in the analysis. Data was obtained from the Rubidium PET-Alternative Radiopharmaceutical for Myocardial Imaging (Rb-ARMI) database at the University of Ottawa Heart Institute. Patients with a confirmed diagnosis of HF (adjudicated via chart review examining clinical documents, discharge summaries, emergency department visits and echocardiographic data available through electronic medical records at the Ottawa Hospital; n¼120) were compared to patients with no evidence of dyspnea or known HF (n¼350). The primary outcome analyzed was global LV and regional (left anterior descending artery, LAD; left circumflex, LCx; right coronary artery, RCA) MFR measured as stress/rest myocardial blood flow. Secondary variables including age, gender, body mass index, smoking history, hyperlipidemia, hypertension, anemia (on the basis of haemoglobin, HgB), renal dysfunction (represented by creatinine level, Cr) and diabetes were also examined. RESULTS: The average age of this cohort was 63, with 57% females. Patients with HFpEF were more likely to be older, female and have comorbid hypertension, diabetes and anemia. HFpEF was associated with a significant reduction in global (2.70 in Controls vs 2.20 in HFpEF, p<0.001) and regional MFR (LAD, 2.73 vs 2.22; LCx, 2.63 vs 2.15; RCA, 2.70 vs 2.20; all p<0.001). HFpEF remained a significant predictor of reduced global MFR after adjustment for age, gender, diabetes, Cr, HgB, BMI, smoking history, hypertension and hyperlipidemia (p<0.001). CONCLUSION: HFpEF is associated with reduced MFR independent of other risk factors and epicardial CAD. Whether this has prognostic value or may be a therapeutic target requires further study.
heart rate was 82 bpm (IQR: 70-102), QRS duration was 104 msec (IQR: 90-136), and QTc was 471 msec (IQR: 444-499). A completely normal ECG was rare (7.7%); the most common abnormalities were left ventricular hypertrophy (LVH; 24%), bundle branch block (LBBB: 13%; RBBB: 8%), Q-waves (12%) and ST-segment deviation 1 mm not associated with LVH or BBB (26%). Death within 90 days was recorded in 13.6% of patients. After adjustment for key clinical variables (age, sex, creatinine, ejection fraction, and medical history), none of the ECG findings were associated with 90-day mortality. In patients with sinus rhythm, only the presence of Qwaves remained a significant predictor of 90-day mortality after adjustment (OR 2.58 [1.34 - 5.00], p¼0.005). CONCLUSION: ECG abnormalities are common in AHF; however, other clinical factors appear to be associated with mortality. Further exploration of the role of the ECG in prognostication and management for patients in sinus rhythm and AHF is needed.
274 INSIGHTS INTO THE IMPORTANCE OF THE ECG IN PATIENTS WITH ACUTE HEART FAILURE
CB Johnson, P Andrew, J Sulpher, H Majeed, N Graham, M Turek, D Susan
P Gouda, BH Rowe, F McAlister, PW Armstrong, M Podder, JA Ezekowitz Edmonton, Alberta BACKGROUND:
Although acute Heart Failure (AHF) is commonly associated with electrocardiographic (ECG) abnormalities, their prognostic relationship is unclear. METHODS: We used data from AHF patients prospectively enrolled in the Acute Heart Failure - Emergency Management (AHF-EM) cohort at 3 Canadian hospitals. First available emergency department ECGs were reviewed blinded to clinical outcomes and coded according to international definitions. The association between patient variables, ECG characteristics and 90-day outcomes were assessed; a multi-variable logistic regression was performed. RESULTS: 922 (97%) of 952 enrolled AHF patients had an ECG in the ED. Median age was 77 years, 54% were male, 53% had a history of atrial fibrillation and the median ejection fraction was 45% (IQR: 30-55). Overall, 54% were in sinus rhythm, 35% in atrial fibrillation and 11% paced. Median
CIHR 275 DATA-DRIVEN TIMING OF OPTIMAL LV EJECTION FRACTION ASSESSMENT IN BREAST CANCER PATIENTS EXPOSED TO TRASTUZUMAB
Ottawa, Ontario BACKGROUND:
Adjuvant trastuzumab has improved outcomes in HER2/neu positive breast cancer. However, this treatment has been associated with decreased left ventricular ejection fraction (LVEF). There is no data-driven schedule to inform clinicians of the optimal timing for serial LVEF monitoring during trastuzumab therapy. We conducted a hypothesis-generating pooled trend analysis to identify a timeline for monitoring LVEF changes secondary to trastuzumab therapy in patients with breast cancer. METHODS: An English language search of Medline, Cochrane, ASCO Library, and an extensive bibliography search from January, 1999 to April 2014 was performed. Inclusion and exclusion criteria were met by 35 clinical trials (n¼9936). Primary outcome was interval reduction in LVEF following trastuzumab versus baseline (baseline LVEF post-anthracycline, pre-trastuzumab). RESULTS: A quadratic trend was identified between LVEF and trastuzumab across time. Decline in LVEF with trastuzumab occurred significantly early at 2 months, peaked at 7-15 months, and recovered post 30 months (Friedman ANOVA:
S196
Canadian Journal of Cardiology Volume 30 2014
F ¼ 19.9, p<0.05). Sensitivity analysis revealed robustness of analysis to concurrent non-anthracycline chemotherapy. CONCLUSION: This pooled trend analysis reveals that LVEF drops early after trastuzumab therapy which supports current clinical trial and real world monitoring strategies in which LVEF monitoring occurs early after starting Trastuzumab. This data suggests that access to prompt cardiology consultation should be available to patients early after starting trastuzumab therapy. Further research is needed to define optimal LVEF monitoring once trastuzumab therapy is complete.
(5.531.45 vs 3.651.67, p¼0.06). Patients treated with endothelin receptor antagonists (ERA) had significantly lower FDG SUV in the RV than that in patients without ERA (3.711.72 vs 8.534.78, p¼0.01), however there was no relationship between RV metabolism and other PAH therapy. CONCLUSION: Clinical right HF is associated with changes in both glucose and fatty acid substrate utilization in the RV. Metabolic changes in the RV may provide incremental prognostic information and could potentially be a treatment target for right HF associated with PAH.
276 EVALUATION OF RIGHT VENTRICULAR METABOLISM IN RIGHT HEART FAILURE ASSOCIATED WITH PULMONARY ARTERIAL HYPERTENSION
277 PREVALENCE OF VITAMIN D DEFICIENCY IN CANADIAN HEART FAILURE PATIENTS AND INSIGHTS IN TO THE ROLE OF VITAMIN D DEFICIENCY IN THE PATHOPHYSIOLOGY OF HEART FAILURE
H Ohira, B Mc Ardle, R Klein, R Davies, R deKemp, E Pena, J DaSilva, D Stewart, G Chandy, V Contreras-Dominguez, R Dunne, R Beanlands, L Mielniczuk
A Pourdjabbar, G Dwivedi, L Mielniczuk, R Haddad, E Stadnick, RA Davies, M Ruzicka, PP Liu, H Haddad
Ottawa, Ontario BACKGROUND:
Pulmonary arterial hypertension (PAH) results in premature death as a result of right ventricular (RV) dysfunction. However, there are substantial differences among patients in their tendency to develop RV failure. RV metabolic changes may be able to predict the development of right heart failure (HF) in patients with PAH. The aim of the study was to assess the relationship between right ventricular cardiac metabolism using positron emission scanning (PET) and established parameters related to RV failure including the six minute walk test (6MWT), brain natriuretic peptide (BNP), cardiac index (CI), mean pulmonary artery pressure (mPAP), mean right atrial pressure (mRAP), clinical evidence of RV failure and RVEF. The relationship between PAH specific therapy and cardiac metabolism was also evaluated. METHODS: Fourteen consecutive patients with PAH underwent right heart catheterizationfor assessment of pulmonary hemodynamics. A total of 86% of patients were on PAH therapy at the time of enrollment and 43% had a diagnosis of right HF. RV glucose and fatty acid metabolism were assessed with FDG and FTHA PET imaging. Substrate utilization was reported as a maximum standard uptake value (SUV). Relative RV FDG and FTHA uptake were determined as the ratio of RV/LV SUV. RVEF was determined by cardiac magnetic resonance (CMR). The clinical diagnosis of right HF was adjudicated by PH experts blinded to the imaging results. RESULTS: There was a negative correlation between RVEF and RV/LV ratio of FTHA SUV (r¼-0.81, p¼0.0048) however no correlation was observed between RVEF and that of FDG SUV (r¼-0.41, p¼0.19). There was a positive correlation between mPAP and RV/LV ratio of FDG SUV (r¼0.74, p¼0.003), and a trend toward an increase in that of FTHA SUV (r¼0.56, p¼0.06). No significant correlation was shown between both metabolic parameters and 6MWT, BNP, mRAP or CI. Patients with right HF had a significant increase in RV FDG uptake (6.633.80 vs 3.331.73, p<0.05) with a trend towards increased uptake of FTHA
Ottawa, Ontario AIMS: Vitamin D has been implicated in the pathophysiology of congestive heart failure (CHF) and vitamin D status has been shown to be inversely associated with increased hospitalization and mortality. The aim of this study was to investigate the prevalence of vitamin D deficiency in a North American heart failure patient population and to investigate potential mechanisms through which Vitamin D deficiency can lead to worse clinical outcomes in patients with CHF. METHODS AND RESULTS: Patients seen in consultation in our heart function clinic were enrolled in this observational study and were randomized to 1 of 3 groups based on their vitamin D levels. The following results are the baseline results of the first 86 patients enrolled. 68.6% (59/86) of patients screened and enrolled, demonstrated Vitamin D insufficiency (<75nmol/L), with 15% (13/86) having severe insufficiency (<35nmol/L). There was no difference in the baseline mean NYHA class, left ventricular ejection fraction (LVEF), brain natureitic peptide (BNP), renal function or inflammatory status, irrespective of the baseline vitamin D status (TABLE).