Acute Heart Failure in Apical Ballooning Syndrome TakotsuboStress

Acute Heart Failure in Apical Ballooning Syndrome (Takotsubo/Stress Cardiomyopathy) Clinical Correlates and Mayo Clinic Risk Score Malini Madhavan, MBBS; Charanjit S. Rihal, MD, FACC; Amir Lerman MD, FACC; Abhiram Prasad, MD, FRCP, FACC Division of Cardiovascular Diseases Mayo Clinic, Rochester No relevant author disclosures J. Am. Coll. Cardiol. 2011; 57; 1400 -1401

Background • Apical ballooning syndrome (ABS) is characterized by transient regional systolic dysfunction of the left ventricle in the absence of obstructive coronary artery disease • Acute heart failure (HF) is the most common complication • Acute HF can cause significant morbidity in ABS

Aims • To examine the frequency and prognosis of patients with acute HF complicating ABS • To identify the risk factors for acute HF in ABS

Methods Study Population • Study cohort • 118 consecutive ABS patients identified between January 2002 and January 2008 • Validation cohort • 52 consecutive ABS patients identified between Feb 2008 and December 2009

Methods Mayo diagnostic criteria for ABS • Transient akinesis, hypokinesis or dyskinesis of the left ventricular mid segments with or without apical involvement. The regional wall motion abnormalities extend beyond a single epicardial vascular distribution • Absence of obstructive coronary disease or angiographic evidence of acute plaque rupture, • New ECG abnormalities (either ST-segment elevation and/or T wave inversion) or elevated cardiac troponin, • The absence of pheochromocytoma or myocarditis Prasad et al. Am Heart J 155(3): 408 -17

Methods: Definitions Acute heart failure • New onset symptoms such as dyspnea, and • At least 2 of the following physical signs - pulmonary rales, elevated central venous pressure, and the presence of a third heart sound Cardiogenic shock • Systolic blood pressure of <90 mm Hg for greater than 1 hour secondary to cardiac dysfunction associated with signs of hypoperfusion • Patients with systolic blood pressure increase to >90 mm Hg within 1 hour after administration of inotropic agents, who met other criteria for cardiogenic shock

Clinical Characteristics No Acute HF (N=65) Acute HF (N=53) p-value 67 (12) 73 (12) 0. 02 Female gender 63 (97%) 52 (98%) 0. 7 Presenting symptom Chest Pain Dyspnea 51 (78%) 26 (40%) 23 (43%) 35 (66%) <0. 0001 0. 005 Precipitating factor Emotional stress Physical stress 19 (30%) 23 (35%) 11 (21%) 37 (70%) Electrocardiogram ST-segment elevation Deep T wave inversion 23 (36%) 39 (60%) 31 (58%) 26 (49%) Variable Age (years) 0. 0003 0. 01 0. 2

Clinical Characteristics Variable Biomarkers Admission Troponin T (ng/ml) Peak Troponin T (ng/ml) BNP (pg/ml) (N=48) Angiography Ejection fraction (%) LVEDP (mm Hg) Grade 3 or 4 MR Admission Echocardiogram Ejection fraction (%) Wall motion score index No Acute HF (N=65) Acute HF (N=53) p-value 0. 37 (0. 42) 0. 55 (0. 56) 783 (753) 0. 71 (0. 85) 0. 93 (0. 90) 1161 (1010) 0. 009 0. 01 0. 1 46 (11) 23 (7) 5 (10%) 35 (13) 28 (7) 8 (21%) 0. 0001 0. 08 44 (13) 1. 74 (0. 41) 36 (13) 2. 05 (0. 47) 0. 004 0. 0006

Independent Predictors of Acute HF Multivariate Analysis Predictor Odds Ratio* 95% P value confidence interval 1. 02 - 1. 11 0. 001 Age (years) 1. 06 Physical stress trigger 4. 01 1. 64 – 10. 36 0. 002 Admission Troponin T 2. 43 1. 05 – 6. 59 0. 04 LV Ejection fraction 0. 96 0. 92 - 0. 99 0. 01 ST-segment elevation 1. 34 0. 5 – 3. 52 0. 7 *Per unit change in variable

Troponin T Stratified by Severity of HF

Mayo Clinic Risk Score for Acute HF in ABS • One point was assigned to each of the following independent risk factors: • Age > 70 years • Presence of physical stressor • Ejection fraction < 40% • Troponin T was not included due to heterogeneity in assay and cut-off value used at different institutions

Mayo Clinic Risk Score for Acute HF in ABS • Significant positive correlation between the frequency of acute HF and the risk score in the: • Development cohort – C statistic 0. 77, p<0. 001 • Validation cohort – C statistic 0. 77, p=0. 002

Acute HF Stratified by Mayo Risk Score Development cohort Validation cohort

Outcome in ABS Cardiogenic shock No acute HF (N=65) Acute HF (N=53) P value N/A 25 (47%) N/A Cardio respiratory support Inotrope use Intra-aortic balloon pump use Mechanical ventilation <0. 001 0 0 3 (5%) 20 (38%) 9 (17%) 15 (28%) Duration of hospitalization (days) 5. 4 (8. 7) 11. 2 (5. 4) 0. 0004 Outcome at discharge Residual HF Death in hospital N/A 0 (0%) 6 (11%) 3 (6%) N/A 0. 09 Discharge medications Beta blocking agent ACE inhibitor/ ARB Furosemide 49 (77%) 39 (61%) 6 (9%) 41 (82%) 37 (74%) 20 (40%) 0. 5 0. 1 0. 0001 Follow-up echocardiogram Time from presentation (days) Ejection fraction (%) Wall motion score index 74 (148) 62 (6) 1. 08 (0. 21) 78 (120) 60 (10) 1. 13 (0. 29) 0. 9 0. 3 0. 4

Conclusions • Heart Failure is a common complication of ABS • Approximately 50% developed HF • One in five developed cardiogenic shock • Patients who developed acute HF had, • Greater myocardial injury and stunning • Greater morbidity and longer hospitalization • Prognosis is good with resolution of HF with supportive management in the majority of patients • Mortality secondary to cardiogenic shock occurred in 3 patients

Conclusions • The Mayo Clinic risk score is predictive of acute HF in patients with ABS • Risk stratification using the Mayo Clinic risk score may: • Assist in triaging high risk patients to an intensive care unit for management • Allow physicians to identify patients in whom early initiation of beta-adrenergic blockers may be harmful