(Circulation. 2000;102:e189.)
© 2000 American Heart Association, Inc.
Correspondence |
Relation of Contractile Reserve of Hibernating Myocardium to Myocardial Structure in Humans
Cardiothoracic Surgical Unit, Queen Elizabeth Hospital, Birmingham University, Birmingham, UK
MRC-Cyclotron Unit, Hammersmith Hospital, Imperial College School Of Medicine, London, UK
To the Editor:
Nagueh and colleagues1 investigated the
relationship between myocardial ultrastructure and the inotropic
contractile reserve of the hibernating myocardium. They suggested that
the amount of interstitial fibrosis in a dysfunctional myocardial
segment is an important determinant of both inotropic contractile
reserve during dobutamine stimulation and of the recovery of function
after revascularization. The authors showed that myocardium with 
30%
interstitial fibrosis does not respond to dobutamine and that its
function does not improve after revascularization. This is in agreement
with earlier reports, which also demonstrated that the presence of this
magnitude of interstitial fibrosis is associated with irreversible
myocardial
dysfunction.2 3 We
suggest, therefore, that myocardial segments with these characteristics
be removed from the analysis because they represent irreversibly
damaged scar tissue rather than hibernating myocardium.
Nagueh et al1 conclude that the contractile response to dobutamine inversely correlates with the extent of interstitial fibrosis. However, close analysis of their data does not support this conclusion. Two groups of hibernating segments are reported. Group 3 consisted of segments with near-normal ultrastructure and minimal fibrosis (1%) that exhibited inotropic contractile reserve and recovered function after revascularization; in group 2, despite the modest amount of fibrosis (9%), 50% of the segments that had improved function after revascularization (ie, hibernating) did not exhibit inotropic contractile reserve. No continuous relationship between fibrosis and inotropic contractile reserve can be demonstrated in these segments. Thus, in hibernating myocardium, which is defined by the occurrence of improved systolic function after revascularization, the amount of interstitial fibrosis is low and seems unlikely to impair the response to adrenergic stimulation.
A number of studies, including our own, have also reported
the lack of inotropic contractile reserve in a substantial number of
hibernating myocardial
segments,4 5
particularly in those from patients with severe left ventricular
dysfunction. Our work indicated that hibernating myocardial segments
(defined by contractile improvement after revascularization) without
inotropic contractile reserve have an amount of fibrosis (
14%)
similar to that in segments that exhibit a response to dobutamine but a
greater number of myocytes with marked myofibrillar loss (26% versus
11%).6 This known
ultrastructural "adaptation" of hibernating myocardium provides a
plausible explanation for the lack of response to adrenergic
stimulation. We suggest that the lack of inotropic contractile reserve
found in many hibernating myocardial segments, which can be identified
as viable by PET scanning and as hibernating by postoperative recovery
of function, is due to the abundance of myocytes depleted of
contractile units rather than the presence of fibrosis.
References
1.
Nagueh SF,
Mikati I, Weilbaecher D, et al. Relation of the contractile reserve of
hibernating myocardium to myocardial structure in humans.
Circulation. 1999;100:490–496.
2.
Shivalkar B, Maes
A, Borgers M, et al. Only hibernating myocardium invariably
shows early recovery after coronary revascularization.
Circulation. 1996;94:308–315.
3.
Depre’ C,
Vanoverschelde J, Melin J, et al. Structural and metabolic correlates
of the reversibility of chronic left ventricular ischemic dysfunction
in humans. Am J Physiol. 1995;268:H1265–H1275.
4.
Gerber B,
Vanovershelde J-L, Bol A, et al. Myocardial blood flow, glucose uptake,
and recruitment of inotropic reserve in chronic left ventricular
ischemic dysfunction: implications for the pathophysiology of chronic
myocardial hibernation.
Circulation. 1996;94:651–659.
5.
Pagano D, Bonser
R, Townend J, et al. Predictive value of dobutamine echocardiography
and positron emission tomography in identifying hibernating myocardium
in patients with postischaemic heart failure.
Heart. 1998;79:281–288.
6.
Pagano D, Townend
J, Parums DV, et al. Hibernating myocardium: morphological correlates
of inotropic stimulation and glucose uptake.
Heart. 2000;83:456–461.
Response
Department of Medicine, Cardiology Section, Baylor College of Medicine, Houston, Texas
Drs Pagano and Camici question the relation of
interstitial fibrosis to contractile reserve and systolic function
after revascularization in patients with dysfunctional myocardium. We
believe that our data strongly show that there is indeed a significant,
inverse relationship between fibrosis and segmental function in
response to dobutamine (see Figure 4 in our article) and postoperative
thickening (see Figure 5 of our
article).R1 They further
suggest excluding segments with 30% fibrosis from the analysis.
Although it is easy to exclude such segments after the biopsies have
been acquired, it was not possible to ascertain the extent of fibrosis
beforehand.
Segments were biopsied if they met all of the
following criteria: (1) abnormal function, (2) end-diastolic thickness
0.9 cm, and (3) lack of a bright, reflective appearance indicative of
scar tissue.R2 These
were all reasonable measures taken to avoid including predominantly
scar segments. Furthermore, these inclusion criteria assured the
inclusion of segments that resemble, to a great extent, the majority of
segments in which myocardial viability is to be determined. As such,
our "sampled segments" are very similar to the "general
population of segments" and, therefore, we believe that our results
are generalizable. We also disagree with the principle of changing
inclusion criteria after they have been determined and the study has
been conducted.
As stated clearly, our objective was to evaluate the relationship between the extent of viable myocardium by histopathology, resting perfusion as determined by rest-redistribution thallium-201, and the different contractile responses exhibited during dobutamine echocardiography. We determined our objectives a priori, and we reported what we set out to do. Excluding certain segments from the analysis to support a certain hypothesis and deviating from the purpose of the study is not appropriate.
Drs Pagano and Camini then examine data from <50% of the biopsied segments (16 of 37). They looked at the following 2 groups (see Figure 3). Group 2 included a total of 8 segments, of which 6 recovered and 3 had contractile reserve (fibrosis, 9%). Group 3 had a total of 8 segments, all of which recovered and had a contractile reserve during dobutamine (fibrosis, 1%). Even then and contrary to what is stated in their letter, it remained true that when the extent of fibrosis was higher (group 2 versus 3), both contractile reserve and recovery were less frequent. It is unclear to us where the assertion regarding the lack of a relationship between fibrosis and contractile reserve came from. In fact, when limiting the analysis to segments with <30% fibrosis, significant relationships were still present between interstitial fibrosis and thickening at low-dose dobutamine (r=–0.73; P<0.05) and with postoperative systolic function (r=–0.62; P<0.05). Finally, we believe that fibrosis alone accounted for the majority (69%) of the contractile reserve variance observed in our study but, as stated in our discussion, other parameters undoubtedly play a role; these include cellular function, coronary flow reserve, energy stores, and adrenergic receptors.R3
References
1. Nagueh SF, Mikati I, Weilbaecher D, et al. Relation of the contractile reserve of hibernating myocardium to myocardial structure in humans. Circulation. 1999;100:490–496.
2. Faletra F, Crivellaro W, Pirelli S, et al. Value of transthoracic two-dimensional echocardiography in predicting viability in patients with healed Q-wave anterior wall myocardial infarction. Am J Cardiol. 1995;76:1002–1006.[Medline] [Order article via Infotrieve]
3. Shan K, Bick R, Poindexter B, et al. Altered myocardial adrenergic receptor density: a possible mechanism of depressed myocardial function in patients with hibernating myocardium. Circulation. 1999;100(suppl I):I-24. Abstract.
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