CLINICAL RESEARCH: CORONARY ARTERY DISEASE
Patients With Hibernating Myocardium Show Altered Left Ventricular Volumes and Shape, Which Revert After Revascularization
Evidence That Dyssynergy Might Directly Induce Cardiac Remodeling
Erberto Carluccio, MD*,
Paolo Biagioli, MD*,
Gianfranco Alunni, MD*,
Adriano Murrone, MD*,
Claudio Giombolini, MD*,
Temistocle Ragni, MD ,
Paolo N. Marino, MD ,
Gianpaolo Reboldi, MD, PhD, MSc and
Giuseppe Ambrosio, MD, PhD, FACC*,*
* Department of Cardiology, University of Perugia School of Medicine, Perugia, Italy
Department of Cardiac Surgery, University of Perugia School of Medicine, Perugia, Italy
Department of Internal Medicine, University of Perugia School of Medicine, Perugia, Italy
Division of Cardiology, University of Piemonte Orientale, Novara, Italy
Manuscript received March 25, 2005;
revised manuscript received September 8, 2005,
accepted September 19, 2005.
* Reprint requests and correspondence: Dr. Giuseppe Ambrosio, Cardiologia Ospedale Silvestrini, Via S. Andrea delle Fratte, 06156 Perugia, Italy (Email: giuseppe.ambrosio{at}ospedale.perugia.it).
Presented at the 54th Annual Scientific Sessions of the American College of Cardiology, Orlando, Florida, March 6–9, 2005.
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Abstract
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OBJECTIVES: The purpose of this study was to investigate whether post-ischemic left ventricular (LV) remodeling might be induced by regional contractile dysfunction per se (i.e., in the absence of transmural necrosis) and whether this phenomenon is potentially reversible after contractile recovery.
BACKGROUND: Formation of extensive scar tissue is thought to be chiefly responsible for post-infarction LV remodeling; however, myocardial necrosis also causes loss of contractility. We investigated LV geometry and shape in a setting in which contractile dysfunction occurs in the presence of preserved myocyte viability, and thus it is potentially reversible.
METHODS: In 42 patients with chronically dysfunctional myocardium, we evaluated (by two-dimensional echocardiography) LV global and regional function, volumes, and sphericity index (SI), at baseline and 8 ± 3 months after coronary revascularization. Myocardial viability before revascularization was evaluated by dobutamine echocardiography.
RESULTS: At baseline, regional and global function were depressed and LV dilation was present. Revascularization was followed by recovery of ejection fraction (from 33 ± 6% to 45 ± 10%, p < 0.0001) and wall motion score index (from 2.29 ± 0.31 to 1.74 ± 0.42, p < 0.0001). After revascularization, significant improvement of end-systolic volume index (from 78 ± 23 ml/m2 to 56 ± 23 ml/m2, p < 0.0001), end-diastolic volume index (from 118 ± 26 ml/m2 to 99 ± 26 ml/m2, p < 0.0001), and SI (from 0.69 ± 0.14 to 0.52 ± 0.11, p < 0.0001) was also observed. Improvement in LV volumes and SI were significantly correlated to the number of segments recovering function after revascularization.
CONCLUSIONS: Hibernating myocardium is associated with major alterations in LV volumes and shape, which significantly revert after revascularization. Thus, chronic dyssynergy per se is sufficient to induce ischemic LV remodeling in patients.
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Abbreviations and Acronyms
| | EDVI = end-diastolic volume index | | ESVI = end-systolic volume index | | LV = left ventricle | | SI = sphericity index | | WMSI = wall motion score index |
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Occurrence of large transmural infarction is followed by a series of events (collectively referred to as "post-infarction ventricular remodeling") characterized by replacement of necrotic myocardium with scar tissue, increased size of myocytes and interstitial fibrosis in remote areas, and alteration in shape and dilation of the whole left ventricle (LV). Typically, remodeling develops after large transmural infarcts, particularly of the anterior wall (1–5).
Regarding the mechanisms through which myocardial infarction might alter LV geometry, emphasis is currently concentrated on the structural and inflammatory consequences of the healing process that follows transmural necrosis. In the few years since 2000, over 70 studies have been published dealing with experimental models of post-ischemic LV remodeling secondary to transmural infarction (see the Appendix); within this setting, research almost exclusively focused on remodeling as influenced either by scar formation/extracellular collagen deposition (e.g., through metallo-proteinase activity) or by the inflammatory response (for review, see references [6–9]; also see the Appendix). Those mechanisms, however, are unlikely to entirely explain the complex pathophysiology of ischemic remodeling. Indeed, the only clinical data available do not support inhibition of metallo-proteinases as a means of preventing post-infarction remodeling (10).
Necrosis obviously implies replacement of normal myocardium with non-contracting tissue. Thus, in addition to the specific process of tissue repair, the infarcted area is also characterized by lack of contribution to cardiac contraction. Yet, whether such a "mechanical" factor contributes to post-infarction remodeling is largely unknown, in part because of the obvious difficulty of separating the effects of necrosis on contractility from those on scar formation. This would be important to understand, because it is expected that regional dysfunction might augment LV load and wall stress, which in turn might trigger remodeling (7,11).
We investigated whether regional contractile dysfunction per se is sufficient to promote LV remodeling. Toward this goal, we exploited the peculiar clinical condition of patients in whom chronic regional contractile dysfunction occurs in the absence of necrosis, distal to severe coronary artery stenosis. Furthermore, because this dyssynergic myocardium retains viability, it is amenable to functional recovery after revascularization; this would allow an assessment of whether LV remodeling might also revert after regain of contractile function, which in turn would offer additional insight toward establishing a link between chronic dyssynergy and ischemic remodeling.
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Methods
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Patient selection.
We enrolled consecutive patients scheduled to undergo elective coronary artery revascularization. Inclusion criteria were: 1)  70% stenosis in at least one major coronary artery at angiography, suitable for surgical or percutaneous revascularization; 2) LV dysfunction (ejection fraction <40%); 3) adequate echocardiographic evaluation of function in all LV segments; and 4) no evidence of transmural infarction (i.e., no deep Q waves in inferior leads and preserved R waves in anterior leads; absence of hyperechogenic, thinned segments at echocardiography; absence of scar upon direct inspection at surgery). Patients were excluded if they had acute coronary syndrome  3 months preceding the study, significant valvular heart disease, left bundle branch block, or previous surgical revascularization.
Study protocol.
After signing the informed consent, LV global and regional function was evaluated by baseline two-dimensional echocardiography; viability of dyssynergic segments was then assessed by contractile response to dobutamine (see "Dobutamine stress echocardiography" section to follow). Therapy was maintained, except for beta-blockers, which were discontinued 48 h before dobutamine echocardiography. Patients were then referred to undergo revascularization within one month. Follow-up evaluation, performed 4 months after coronary revascularization, included repeat assessment of LV global and regional function and of LV volumes and shape.
Baseline echocardiography.
Two-dimensional echocardiography was performed with a SONOS 4500 machine (Philips Technologies, Andover, Massachusetts), equipped with a 2.5-MHz transducer. Patients were studied in left lateral decubitus, in parasternal short- and long-axis and apical four- and two-chamber views. The endocardial border at end-diastole and end-systole was planimetered including papillary muscles in the blood volume. End-diastole was defined as the frame with the largest cavity immediately before the onset of QRS complex and end-systole as the frame with the smallest cavity area. The LV volumes and ejection fraction were calculated according to the modified Simpson’s rule (12). Three cardiac cycles were averaged for each measurement. Volume indexes were obtained dividing LV volumes by body surface area. The LV sphericity index (SI) was calculated as: end-diastolic volume/([long-axis diameter3 x  ]/6) (13). Long-axis diameter was measured in the apical four-chamber view from the distance in diastole between apical endocardium and mitral annulus; the higher the SI, the more spherical the left ventricle (13). Meridional and circumferential end-systolic wall stress were calculated by standard formulas (14,15). Systolic thickening of septum and posterior wall was calculated from M-mode tracings obtained by two-dimensional images of short-axis views at the papillary muscle level. Regional wall motion was assessed with a 16-segment model of the LV on a four-point grade scale, according to the American Society of Echocardiography (12). Wall motion score index (WMSI) was calculated as the sum of the score of each segment divided by the number of segments scored. Severity of mitral regurgitation was estimated by the area of color-Doppler flow velocity in the left atrium, as suggested by the Doppler Quantification Task Force Committee of the American Society of Echocardiography (16).
Echocardiograms were recorded with a Super-VHS videotape recorder or digitally stored on optical disk. Subsequent off-line analysis was performed by two investigators without knowledge of clinical and angiographic data. Disagreements in interpretation were resolved by consensus.
Reproducibility of LV volume measurements was assessed in 15 randomly-chosen baseline echocardiograms. By Bland-Altman method (17), mean ± SD difference between two observers for end-diastolic volume was –0.57 ± 12 ml (r = 0.96), and –4.3 ± 12 ml for end-systolic volume (r = 0.96).
Dobutamine stress echocardiography.
To assess LV contractile reserve, dobutamine was infused intravenously via a syringe pump at the dose of 5 µg/kg/min for 5 min and increased to 10 µg/kg/min for an additional 5 min; in case of no contractile response, an additional 15 µg/kg/min were infused for further 5 min. Parasternal long-axis and short-axis and apical four- and two-chamber views were monitored during the study. Electrocardiogram, heart rate, and blood pressure were recorded at rest, every 2 min during the test, and up to 10 min after the end of drug infusion. Criteria for stopping dobutamine infusion included hypotension, angina, worsening of wall motion, and significant ventricular arrhythmias. The WMSI was calculated at baseline and at the end of dobutamine infusion. Improvement of contractile function of 1 grade from baseline in at least two adjacent dysfunctional segments was considered as a sign of viability. The number of viable segments in response to dobutamine was also considered; viability index (VI) was calculated as the number of viable segments divided by the number of total dysfunctional segments at baseline (18). Intraobserver and interobserver reproducibility of stress-echo readings in our laboratory is >90% (19).
Statistical analysis.
Continuous data are presented as mean ± SD. Categorical variables were compared by chi-square test; in case of 2 x 2 tables, when the df = 1, Yates correction was applied. Comparison of continuous variables at baseline between groups was performed by unpaired t test; Mann-Whitney U test was used for non-parametric data such as WMSI. Resting and peak values, as well as baseline and follow-up data, were compared using paired t test; Wilcoxon rank sum test was used for non-parametric data such as WMSI. Comparison between groups (viability+ vs. viability–) from baseline to follow-up was performed with analysis of variance for repeated measures corrected for unbalanced design. Pearson’s correlation coefficient was used to determine relation between variables. Univariate and multiple regression analyses were performed to evaluate the association between clinical and echocardiographic variables and changes in end-diastolic volume index (EDVI), end-systolic volume index (ESVI), and SI at follow-up. Inter-observer variability of EDVI and ESVI was analyzed by linear regression analysis and Bland-Altman method (17). A p value < 0.05 was considered significant. The SPSS statistical package version 10 was used for analysis (SPSS Inc., Chicago, Illinois).
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Results
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Patients.
Fifty-five patients met the inclusion criteria and were enrolled. Two patients subsequently refused to undergo revascularization. After 20 ± 9 days, patients were readmitted; echocardiography confirmed the persistence of LV dysfunction; on the subsequent morning, patients were revascularized by percutaneous transluminal coronary angioplasty (n = 16), or coronary artery by-pass graft (n = 37). The choice of modality of revascularization was made by the attending physicians independent of the study, on the basis of coronary anatomy and clinical status. There were no periprocedural myocardial infarctions. Of 53 revascularized patients, 3 died before follow-up and 6 were lost at follow-up. Two patients were excluded because of acute coronary syndrome before follow-up. Thus, 42 patients constitute the final population. Baseline clinical, demographic, and echocardiographic features of study patients are summarized in Table 1 and presented for each patient as in the Appendix.
Baseline echocardiography.
At baseline, all patients showed enlarged LV and depressed global function (Table 2). Extensive regional contractile dysfunction was also present. Of a total 516 dysfunctional segments, 182 were hypokinetic and 323 akinetic. Only 11 segments were dyskinetic and always localized in the inferior region.
Low-dose dobutamine echocardiography unmasked substantial contractile reserve in an average of 6 ± 3 segments per patient. The WMSI averaged 2.29 ± 0.31 at baseline, and it largely improved to 1.79 ± 0.32 (p < 0.0001) at the end of dobutamine infusion, with a mean viability index of 0.49 ± 0.21.
Revascularization and LV function and volumes.
Patients were reevaluated 7.6 ± 3.3 months after revascularization. Revascularization significantly improved global and regional LV function (Table 2). In the whole population, ejection fraction increased from 33 ± 6% to 45 ± 10% (p < 0.0001) and WMSI from 2.29 ± 0.31 to 1.74 ± 0.42 (p < 0.0001). Of the 6 ± 3 segments per patient identified as viable at baseline, 88 ± 32% exhibited substantial recovery of function at follow-up, with an average 5 ± 3 segments per patient showing 1 grade of improvement. The number of segments that recovered function at follow-up was significantly related to the number of viable segments identified by dobutamine echocardiography at baseline (r = 0.68, p < 0.0001) and to viability index (r = 0.65, p < 0.0001).
In addition to wall motion analysis, regional contractile function was also directly assessed by measuring systolic thickening of dysfunctional and remote regions. Systolic thickening of interventricular septum was depressed at baseline, compared with that of the posterior wall (23 ± 20% vs. 43 ± 23%, p < 0.01). At follow-up, systolic thickening of the interventricular septum significantly increased to 33 ± 23% (p < 0.01); thickening of the posterior wall also showed an increase (to 49 ± 21%), which did not reach statistical significance.
Improvement of function after revascularization was also accompanied by major improvement of LV volumes and geometry, as shown by significant reduction of ESVI (p < 0.0001), EDVI (p < 0.0001), and SI (p < 0.0001) (Table 2). Figure 1 shows the changes in ESVI, EDVI, and SI, from baseline to follow-up in each patient. A reduction of ESVI was observed in all but 5 patients, and in 29 (69%) it decreased by 20%, which is considered an index of significant positive reverse remodeling (20).
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Figure 1 Individual changes in end-systolic volume index (ESVI), end-diastolic volume index (EDVI), and sphericity index (SI) from baseline to follow-up after revascularization. Bars = mean ± SD.
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Determinants of remodeling.
We observed a strong dependence of LV dilation upon the mass of dysfunctional but viable myocardium. Patients having the largest amount of dyssynergic myocardium at baseline were also those in whom the largest decrease in ESVI and EDVI was observed after revascularization (Figs. 2A and 2B). Furthermore, Figure 2C shows a direct relationship when changes in ESVI or EDVI are plotted as a function of the number of myocardial segments that recovered contractility at follow-up. Interestingly, our data indicate that the relationship between severity of contractile deficit and LV dilation is actually maintained also in the post-revascularization condition. Figure 3 shows the significant correlation between WMSI and absolute values of ESVI at baseline (left panel). When the plot was repeated, analyzing follow-up data (right panel), although there was an expected improvement in regional function and volumes as a consequence of revascularization, ESVI continued to be linearly correlated to WMSI. This observation suggests that degree of contractile function influences systolic volumes, regardless of revascularization status. Together, these various findings demonstrate that the greater the degree of dysfunction, the greater the impact on LV remodeling.
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Figure 2 Correlations between echocardiographic indices of viability and changes in ESVI (upper panels) or EDVI (bottom panels), from baseline to follow-up. (Upper panels) (A) DeltaESVI = 5.576 + (–5.472 x no. of viable segments); standard error of estimate (SEE) = 6.6; (B) DeltaESVI = 3.601 + (–62.13 x viability index); SEE = 6.9; (C) DeltaESVI = 0.9636 + (–5.183 x no. of recovered segments); SEE = 4.3. (Bottom panels) (A) DeltaEDVI = 4.3256 + (–3.3366 x no. of viable segments); SEE = 5.6; (B) DeltaEDVI = 4.9007 + (–41.6070 x viability index); SEE = 5.61; (C) DeltaEDVI = 0.2879 + (–2.9370 x no. of recovered segments); SEE = 4.11. Abbreviations as in Figure 1.
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Figure 3 Correlations between absolute values of end-systolic volume index (ESVI) and wall motion score index (WMSI), at baseline (left; r = 0.39, p < 0.05) and at follow-up (right; r = 0.66, p < 0.0001).
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Among patients studied, seven (17%) actually had no or negligible evidence of myocardial viability by dobutamine challenge at baseline. They still underwent revascularization on the basis of clinical considerations made by attending physicians and predictably showed no appreciable recovery of regional function after revascularization (0.9 ± 1 segment per patient). We retrospectively reanalyzed data from these patients separately, as they afford the opportunity to evaluate whether LV dilation might improve at follow-up independently of recovery of function, but because of other possible effects of revascularization. Baseline characteristics of patients according to the response to dobutamine are shown in Table 3. At baseline, patients with and without viability had very similar values of global and regional function and of LV volumes. At follow-up, ESVI decreased in 29 of 35 patients (83%) in whom viability was present, whereas ESVI did not change or even increased in all patients without viable myocardium (Table 4). Similarly, NYHA functional status significantly improved at follow-up in patients with myocardial viability (p < 0.0001), whereas it remained unchanged in patients without myocardial viability (Table 3). Figure 4 shows changes in ESVI, EDVI, and SI, brought about by revascularization when data are analyzed according to the initial response to dobutamine. A striking difference is present, because viability at baseline predicted marked and directionally opposite changes in LV volumes at follow-up. Two illustrative cases are shown in Figure 5.
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Table 3. Clinical Characteristics of Patients Divided According to Presence or Absence of Viable Myocardium by Low-Dose Dobutamine Echocardiography
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Table 4. Echocardiographic Parameters at Baseline and at Follow-Up After Revascularization in Patients Divided According to Presence of Viability at Entry
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Figure 4 Percent changes in left ventricular volumes and geometry at follow-up according to presence of viability (Viab+) or absence of viability (Viab–) during dobutamine echocardiography before revascularization. EDVI = end-diastolic volume index; ESVI = end-systolic volume index; SI = sphericity index.
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Figure 5 Two-dimensional apical four-chamber view of left ventricular (LV) end-diastolic and end-systolic cavity silhouettes at baseline (left) and >4 months after revascularization (right). (A) In a patient with no viable myocardium (viability index = 0.13), no recovery of function and no reverse remodeling at follow-up. (B) In a patient with substantial myocardial viability (viability index = 0.56) and eight segments that recovered function after revascularization. Marked reduction of LV end-diastolic and end-systolic volumes is appreciable at follow-up examination.
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To further characterize the independent contribution of reversible dysfunction to remodeling, multiple regression analysis was performed. Variables used were: age, diabetes, hypertension, hypercholesterolemia, previous myocardial infarction, medication, baseline ejection fraction, type of revascularization (coronary artery by-pass graft vs. percutaneous transluminal coronary angioplasty), number of stenosed vessels, baseline EDVI and ESVI, VI, and number of segments recovering function after revascularization. For multiple regression analysis, factors showing a value of p < 0.1 in univariate analysis were selected. Number of segments with recovery of function after revascularization (p < 0.0001) and VI (p < 0.01) were the only independent predictors of a change in ESVI 20% at follow-up.
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Discussion
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The present study shows that in patients with coronary artery disease, presence of a substantial amount of dysfunctional but otherwise viable myocardium is associated with major alterations of LV volumes and shape. Those alterations largely reverted when contractility of dyssynergic areas was restored by revascularization. Together, these data demonstrate that impairment of contractile function per se might play a major role for development of ischemic LV remodeling and that extensive scar formation is not an obligatory prerequisite in this process.
Because of the relevance of the phenomenon, understanding the mechanisms through which ischemic remodeling occurs has spurred much interest. This has resulted in many experimental studies, which have mostly focused, however, on processes involved with local reparative changes, the emphasis being on biochemical and cellular aspects of the healing process, such as changes in collagen metabolism (7,8) and inflammation (6,9,21) (also see the Appendix). Yet, occurrence of necrosis implies more than a series of inflammatory/reparatory events, however important, because loss of contractile function is the first and foremost consequence of myocardial infarction. This issue is particularly relevant, because impaired function of the infarcted area increases LV wall stress and stretching of remote myocardium, factors potentially capable of triggering remodeling (7,10,22). In spite of this, information about a specific role of contractile dysfunction in remodeling is scarce; this conceivably comes from the difficulty in separating the effects of dyssynergy from those of necrosis. The only clue comes from a swine model of chronic (two months) coronary stenosis (23) in which persistent coronary flow reduction was associated with regional dysfunction but no infarct; these changes were accompanied by LV remodeling with increased cavity size and mass (23).
Rahimtoola (24) was the first to attract attention to the peculiar condition in which areas of LV are non-contracting yet retain viability. He also suggested that revascularizing these hearts would improve LV function and volumes. This clinical condition has been popularized as myocardial "hibernation." Actually, it is becoming progressively evident that, in addition to true hibernation, the pathophysiology of chronically dysfunctional yet viable myocardium might be more complex, encompassing also "repetitive stunning" and passive tethering (25,26). These entities might be difficult to distinguish clinically and might even coexist (25,27–30); however, regardless of the precise initiating mechanism, they are all characterized by presence of dyssynergic but viable myocardium, which is amenable to recovery upon revascularization. In the present study we took advantage of this condition, as it offers two distinct advantages: first, it allows direct investigation of the effects of regional dyssynergy on LV geometry and shape in the absence of changes secondary to the healing process; second, since this "dormant" myocardium might recover its function after revascularization, it offers the opportunity to "double-check" the hypothesis that impaired contractility might contribute to remodeling, by investigating whether recovery of function also results in reversal of LV remodeling.
Several lines of evidence concur to indicate that in our patients LV remodeling was directly linked to the presence of large areas of hibernating myocardium. First, we made efforts to select patients without transmural scars; although it is possible that additional investigation (e.g., by magnetic resonance imaging) could have revealed focal areas of necrosis, the combination of electrocardiogram and echocardiography criteria, the absence of visible scar at surgery, and the presence of inotropic reserve indicate that extensive necrosis was unlikely. Second, regional function did improve after revascularization: importantly, this was accompanied by reversal of LV remodeling, the extent of which was strictly related to the extent of functional recovery (Figs. 2 and 3), indicating that the larger the dyssynergic area, the greater the impact on LV geometry and volumes, which might nonetheless revert upon restoration of contractility. Finally, in patients with altered LV volumes and geometry—in whom, however, no viability was present—revascularization did not improve regional function (Figs. 4 and 5, Table 4). Consistent with our hypothesis, these patients showed no reversal of remodeling at follow-up; this finding also rules out other effects of revascularization as an explanation for our observations. Together, these data demonstrate that regional dysfunction per se might play a direct role in ischemic LV remodeling in patients.
The mechanisms by which regional dyssynergy might induce and maintain LV remodeling can only be postulated. Severe LV dysfunction with reduced cardiac output stimulates compensatory mechanisms that might promote remodeling, such as adrenergic and renin-angiotensin system activation (7,22). Furthermore, increased LV radial length might increase regional wall stress (Table 2), which in turn induces an increase in oxygen consumption of inner subendocardial layers. Because hibernating myocardium is characterized by reduced coronary flow reserve, an increase in oxygen demand might induce ischemia (27–29). We (31) and others (32) have shown in patients that transient episodes of increased oxygen demand might induce prolonged contractile impairment (i.e., "stunning"), which might be cumulative (32). Evidence is accumulating to indicate that there might be a temporal progression from repetitive episodes of ischemia-reperfusion to hibernation (25,27–29,33), whereas viability might be maintained because hibernating myocardium is relatively tolerant toward ischemia (28,33,34). This sequence might be interrupted upon revascularization, which might reverse ischemia (if resting blood flow is low) and/or prevent repetitive stunning. Interestingly, even in the absence of extensive necrosis, there might still be a role for inflammation in the pathophysiology of remodeling. Hibernating myocardium shows signs of chronic inflammation, akin to what is found after experimental microembolization (27,35). Furthermore, if "loss of contractile units" (due to necrosis) is actually the initial trigger of an array of molecular events leading to remodeling at the cellular level (36), then it might be speculated that a "functional loss" of contractile units might similarly occur in the presence of large areas of hibernating myocardium.
Study limitations.
In our series, typical of investigations on patients with hibernation, the precise condition of the LV before initiating the whole process is unknown; however, recovery after revascularization is an indication of the reversibility of the phenomenon and hence a clue to the initial status. Another limitation lies with patient population; on the one hand, we cannot rule out a role for subendocardial necrosis, because no specific magnetic resonance imaging assessment was performed. On the other hand, by study design we excluded patients with clear evidence of transmural scar: thus, our data might not be applicable to patients with chronic cardiomyopathy secondary to large transmural infarction. Finally, because of the lack of regional myocardial blood flow measurements, we cannot establish the role of repeated stunning as the main mechanism of dyssynergy.
Implications.
The finding that dyssynergy , in itself, might promote remodeling might have potentially important implications. First, because of expanding use of reperfusion therapy, less frequently do patients with acute myocardial infarction develop large areas of transmural necrosis; yet, our data suggest that they might not be spared from remodeling if myocardium salvaged from necrosis remains dysfunctional. Second, recognition that a sizable portion of LV is actually hibernating in many patients with ischemic cardiomyopathy (37,38) suggests that LV function and size might improve in these patients as an effect of revascularization. Finally, if what matters is contractile reserve, regardless of the specific pathophysiology underlying dyssynergy, our data suggest that dobutamine echo might be the preferred test to predict reversal of remodeling.
In conclusion, our data show that, in patients with chronic ischemic heart disease, the alterations of LV volumes and geometry, which are a hallmark of post-infarction remodeling, can be directly induced by impaired function of hibernating myocardium.
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Appendix
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For a list of publications linking left ventricular remodeling to inflammation/scar formation after transmural necrosis and the baseline clinical characteristics of individual patients, please see the online version of this article.
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Footnotes
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Supported by grants PRIN 2003, 2003064224_008, and FIRB 2001, RBNE01HLAK_005, from the MIUR, Rome, Italy.
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References
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