Download End-systolic pressure-volume relation predicts cardiac events in

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