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End-systolic pressure-volume relation predicts cardiac events in patients with abnormal ejection fraction and negative stress echocardiography T. Bombardini1, R. Sicari1, Q. Ciampi2, S. Gherardi3, L. Pratali1, S. Salvadori1, E. Picano1 (1) Institute of Clinical Physiology of CNR, Pisa, Italy (2) Fatebenefratelli Hospital, Division of Cardiology, Benevento, Italy (3) M. Bufalini Hospital, Department of Cardiology, Cesena, Italy no conflict of interest Background • A maximal negative stress echo identifies a low risk subset for coronary events • However, the potentially prognostically relevant information on cardiovascular hemodynamics for heart failure-related events is unsettled Aim • To assess the prognostic value of the stress-induced variation in the left ventricular end-systolic pressure-volumeratio (ESPVR) in patients with abnormal (< 50%) left ventricular ejection fraction (LVEF) and negative stress Echocardiography Methods • We enrolled 400 patients (dilated cardiomyopathy, n = 225; ischemic dilated cardiomyopathy, n = 139; suspected coronary artery disease, n = 36) • 306 males, mean age 63 ± 12 • ejection fraction 30 ± 9% • with negative (exercise 57, dipyridamole 165, dobutamine 160, non-invasive pacing 18) stress echocardiography result • the ESPVR was determined at rest and at peak stress • Main outcome measures: combined death and heart failure (HF) related hospitalization Results • During a median follow-up of 19 months (interquartile range 6-48), 53 deaths (49 cardiac, 4 non-cardiac), and 83 HF-related hospitalization occurred • Event-free survival was higher (p < 0.001) in patients with ΔESPVR (the difference between peak and rest ESPVR) ≥ 0.4 mmHg/mL/m2 • Multivariable indicators of event-free survival were rest EF (HR 0.955), ACE-inhibitor therapy (HR 0.543), Wall Motion Score Index stress improvement (HR 0.367), and ΔESPVR (HR 0.501) • At incremental analysis, ΔESPVR ≥ 0.4 mmHg/mL/m2 added prognostic information Conclusions • Patients with < 50% rest LVEF despite no inducible ischemia may still experience an adverse outcome related to abnormal contractile reserve • The abnormal contractile reserve can be identified by ΔESPVR < 0.4 mmHg/mL/m2 Prognostic predictors Left panel. The ROC curve for predicting combined death or heart failure (HF) hospitalization by left ventricular function stress changes, as reflected by the increase in LVEF: light line, and by the difference between peak and rest end-systolic pressure-volume relation, ΔESPVR: dark line Middle panel. Kaplan-Meier survival curves according to the presence of stress left ventricular ejection fraction-based contractile reserve Right panel. Kaplan-Meier survival curves in medically treated patients stratified according to the ΔESPVR ≥ 0.4 mmHg/mL/m2 vs rest as cut-off value Survival in patients according to the stress employed Kaplan-Meier survival curves according to the presence of stress end-systolic pressure-volume relation-based contractile reserve (ΔESPVR ≥ 0.4 mmHg/mL/m2 vs rest as cut-off value). Left panel, patients (n = 57) exercise stress echo. Middle panel, patients (n = 165) dipyridamole stress echo. Right panel, patients (n = 160) dobutamine stress echo Survival in patients and different rest LV dysfunction Kaplan-Meier survival curves in medically treated patients stratified according to the presence of stress end-systolic pressure-volume relation-based contractile reserve (ΔESPVR ≥ 0.4 mmHg/mL/m2 vs rest as cut-off value) in patients with moderate (left panel), severe (middle panel), or extreme (right panel) rest LV dysfunction “there is a clear overlap between contractility, which should be independent of load or heart rate, and the effects of load and heart rate on the cellular mechanism. …hence, the traditional separation of inotropic state from load or heart rate effects is no longer simple.” Lionel Opie, 2005 Force-frequency relation or Bowditch treppe in the isolated papillary muscle Measurements of twitch tension in isolated left-ventricular strips Force-frequency relationship in the cath lab Liu C. et al. Circulation 1993; 88:1893 Contractility in stress echo lab: simplify for success Systolic Blood Pressure + 1/ End-systolic volume = Contractility SP + ESV = Contractility SP + = ESV = Contractility + /= ESV = Contractility =/ SP Force-Frequency Relationship (upsloping normal) HF = 80 bmp HF = 115 bmp HF = 130 bmp HF = 140 bmp ESV = 30 ml ESV = 25 ml ESV = 23 ml ESV = 16 ml SBP = 140 mmHg SBP = 170 mmHg SBP = 190 mmHg SBP = 210 mmHg SBP/ESV = 4.6 SBP/ESV = 6.8 SBP/ESV = 8.2 SBP/ESV = 13 15 10 5 Delta SP/ESV (peak – rest) = 13 - 4.6 = 8.4 Force-Frequency Relationship (flat-biphasic abnormal) HF = 60 bmp HF = 80 bmp HF = 100 bmp HF = 120 bmp ESV = 120 ml ESV = 100 ml ESV = 81 ml ESV = 95 ml SBP = 110 mmHg SBP = 120 mmHg SBP = 130 mmHg SBP = 140 mmHg SBP/ESV = 0.9 SBP/ESV = 1.2 SBP/ESV = 1.6 SBP/ESV = 1.5 2 1.5 1 Delta SP/ESV (peak – rest) = 1.5 - 0.9 = 0.6 Inotropic reserve in the stress echo lab EXERCISE DOB DIP PACEMAKER Contractility + + + + Inotropic reserve + + + - Bowditch treppe + + =/+ ++ User-friendly + ++ ++ +++ Capability to exercise Intravenous line Intravenou s line Permanent pacemaker Requisites Bombardini et al JASE 2003 Int J Cardiol 2007 JNC 2008 Bombardini et al EHJ 2005 Bombardini et al J Heart Lung Transpl 2009 Bombardini et al Eur J Heart Failure 2004