Mechanisms of heart failure with well preserved ejection fraction in dogs following limited coronary microembolization.
OBJECTIVE
It has been suggested that in some settings, heart failure (HF) may occur with normal ejection fraction (EF) as a consequence of undetected systolic dysfunction. However, others have argued that this can only occur in the presence of diastolic dysfunction. We therefore sought to determine the contribution of diastolic dysfunction in an animal model of HF with normal EF.


RESULTS
Limited myocardial injury was induced in 21 dogs chronically instrumented to measure hemodynamics and LV properties by daily coronary microembolization ( approximately 115 microm beads) until LV end diastolic pressure (LVEDP) was > or =16 mm Hg. Nine dogs developed HF within 16+/-6 days (LVEDP 12+/-2 vs. 21+/-2 mm Hg, p<0.001) with no significant change in dP/dt(max) (2999+/-97 vs. 2846+/-189 mm Hg/s), mean arterial pressure (103+/-4 vs. 100+/-4 mm Hg), EF (57+/-5% vs. 53+/-4%) or E(es) (end-systolic elastance, 3.1+/-0.9 vs. 2.9+/-0.8 mm Hg/ml) but with an approximately 10 ml increase in V(o) (14+/-12 vs. 25+/-16 ml; p<0.01). The EDPVR and time constant of relaxation (tau, 25+/-3 vs. 28+/-3 ms) did not change significantly. These animals were hemodynamically stable out to 3 1/2 months. Neurohormonal activation occurred (elevations of NE, AngII, BNP) and there was intravascular volume expansion by approximately 16% (p<0.05).


CONCLUSIONS
A small amount of myocardial injury can lead to neurohormonal activation with intravascular volume expansion and elevation of LVEDP in the absence of reductions in dP/dt(max) or EF and without diastolic dysfunction. Thus, HF with preserved EF does not a priori equate with diastolic heart failure.
He
Kun-Lun
KL
Department of Cardio-Nephrology, Chinese PLA General Hospital, 28 Fuxing Road, Beijing 100853, China. hekunlun2002@yahoo.com
Dickstein
Marc
M
Sabbah
Hani N
HN
Yi
Geng-Hua
GH
Gu
Anguo
A
Maurer
Mathew
M
Wei
Chi-Ming
CM
Wang
Jie
J
Burkhoff
Daniel
D
D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001810:Blood Volume; D004285:Dogs; D004452:Echocardiography; D006333:Heart Failure / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D006439:Hemodynamics; D008833:Microcirculation; D009203:Myocardial Infarction / Q000150:complications* / Q000503:physiopathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010751:Phosphopyruvate Hydratase / Q000097:blood; D013997:Time Factors; D016276:Ventricular Function / Q000502:physiology*
D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D010751:Phosphopyruvate Hydratase