Patients with ischaemic cardiomyopathy represent a subgroup at high risk of further cardiac events when treated medically.1^–3 Several studies have shown that coronary revascularisation may improve left ventricular ejection fraction (LVEF), symptoms and prognosis if a substantial amount of viable myocardium is present.4^–12 A meta-analysis,13 including 24 studies with 3088 patients, demonstrated that the cardiac death rate was 3% in patients with viable myocardium who underwent revascularisation as compared with 16% in patients with viable myocardium who were treated medically. The presence of myocardial viability has been shown to be predictive of LVEF improvement and better prognosis after coronary revascularisation.4^–12 However, the proportion of patients with viable myocardium showing a significant improvement of LVEF after revascularisation is extremely variable in the different studies. It has ranged from 36%4 to 88%.7 Hence, not all patients with viable myocardium show an improvement of LVEF postoperatively. Whether the prognosis of viable patients whose LVEF does not improve is different from the prognosis of viable patients whose LVEF does improve after revascularisation is unclear. Therefore, this study was performed to clarify whether viable patients without improvement in LVEF after revascularisation have a different prognosis than viable patients whose LVEF does improve. To this aim a large group of patients with ischaemic cardiomyopathy who had undergone coronary revascularisation were included in a long-term follow-up study.

PATIENTS AND METHODS

Study group and study protocol

Ninety-seven consecutive patients with ischaemic cardiomyopathy were initially included in the study. Patients were already scheduled for coronary revascularisation according to clinical criteria of reduced LVEF (<40%), symptoms of heart failure and/or angina, presence/absence of ischaemia and presence of critical coronary disease at angiography. The decision to revascularise was independent from the results of the viability studies. Only patients who had undergone coronary revascularisation alone were included in the study, whereas patients who had undergone mitral valvuloplasty or aneurismectomy in association with revascularisation were excluded.

The study protocol was designed as follows: before revascularisation radionuclide ventriculography (RNV) and resting two-dimensional echocardiography were performed to assess LVEF and regional wall motion abnormalities, respectively. Also left ventricular (LV) volumes were measured from the resting echocardiographic images. Subsequently, dobutamine stress echocardiography (DSE) was performed to assess myocardial viability in dysfunctional segments. Nine to 12 months after revascularisation, RNV was repeated to evaluate improvement in LVEF. Seven patients (7%) died in the postoperative period (within 30 days) and were not included in the analysis.

The study group, therefore, comprised 90 patients who survived the postoperative period and underwent RNV 9–12 months after revascularisation to assess change in LVEF. Patients were divided into three groups according to the presence of myocardial viability and LVEF improvement at 9–12 months after revascularisation: group 1, viable patients with LVEF improvement; group 2, viable patients without LVEF improvement, group 3, non-viable patients. Functional status (New York Heart Association (NYHA) and Canadian Cardiovascular Society (CCS) class) was evaluated in the three groups before and after revascularisation and cardiac events were recorded during a long-term follow-up (mean (SD) 4.6 (1.8) years). The local ethics committee approved the protocol and all patients gave informed consent before the study.

Two-dimensional echocardiography at rest

All echocardiograms were performed using a Sonos-5500 imaging system (Hewlett-Packard, Philips Medical Systems, Eindhoven, The Netherlands) equipped with a second harmonic 1.8–3.6 MHz transducer to optimise endocardial border visualisation. Standard parasternal and apical views of the LV were obtained.14 Regional wall motion and thickening were scored using the 16-segment model with a five-point grading scale: 1, normal; 2, mildly hypokinetic; 3, severely hypokinetic; 4, akinetic; 5, dyskinetic.4 The wall motion score index was calculated by dividing the summed wall motion score by the number of segments. From the apical two- and four-chamber views also LV end-diastolic and end-systolic volumes were measured using the biplane Simpson rule.14 Measurements were performed offline in separate reading sessions and in random order by two independent experienced readers blinded to patient data.

Assessment of myocardial viability: dobutamine stress echocardiography

Only severely dysfunctional segments (score 3–5) were evaluated for myocardial viability. Low–high dose DSE (up to 40 μg/kg/min with addition of 2 mg atropine, if necessary) was performed, as described previously.4 Four patterns of wall motion response were observed during DSE: 1, sustained improvement; 2, worsening; 3, biphasic response; 4, no change.15 Segments with biphasic response, sustained improvement or worsening of the wall motion during DSE were considered viable, with the exception of akinesia becoming dyskinesia.15 Segments with unchanged wall motion were considered non-viable (scar) tissue.15 Patients were defined as viable in the presence of a substantial amount of viable myocardium (⩾4 viable segments: ⩾25% of the left ventricle), whereas patients with <4 viable segments were defined as non-viable.4 Interpretation of the studies was performed offline from cineloops, displayed side by side in a quad-screen format, by two experienced observers in consensus, blinded to the clinical data. Agreement between the two readers was required for scoring each segments. In the event of disagreement, a third investigator resolved the dispute.

Inter- and intraobserver agreement for analysis of DSE studies was reported previously (92% and 94% respectively).16 All segments could be scored in all studies and no contrast agents were used to improve endocardial border visualisation.

Assessment of left ventricular ejection fraction

Before and 9–12 months after revascularisation the LVEF was assessed by RNV at rest. A small field-of-view gamma camera system (Orbiter, Siemens, Erlangen, Germany) was used, oriented in a 45° left anterior oblique position with a 5–10° caudal tilt. After injection of ^99mTc (740 MBq), RNV was performed at rest with the patient in a supine position. The LVEF was calculated by standard methods (Odyssey VP, Picker, Cleveland, Ohio, USA). An improvement in LVEF ⩾5% after revascularisation was considered clinically significant.4

Assessment of functional status and long-term follow-up

Before and after revascularisation, structured clinical interviews were performed, by an independent doctor blinded to all data, to assess the functional status according to the NYHA (for symptoms of heart failure) and the CCS criteria (for angina pectoris). The long-term follow-up was obtained by chart review and telephone contact and was complete in all 90 patients. Events included cardiac death, new myocardial infarction, admission to hospital for heart failure. Cardiac death was defined, based on chart review, as sudden death, death within 1 h of new symptoms of myocardial ischaemia or death due to heart failure. Myocardial infarction was defined according to classical criteria (symptoms, electrocardiographic changes and raised cardiac enzymes). Hospitalisation for heart failure was defined according to the hospital discharge diagnosis.

Statistical analysis

Continuous data are expressed as mean (SD) and dichotomous data as proportions. Continuous data were compared using the Student t test for paired and unpaired samples and analysis of variance analysis as indicated. Comparison of proportions was performed by χ² analysis. Cardiac event rate during the long-term follow-up was evaluated using the Kaplan–Meier method. Differences between curves were tested with the log-rank χ² statistics. For all tests, a p value <0.05 was considered significant.

RESULTS

Study group

Before revascularisation, all patients had heart failure symptoms (mean (SD) NYHA class 2.9 (0.9)). Angina pectoris was also present in 82 patients (CCS class 2.7 (0.6)). Previous myocardial infarction (⩾6 months) had occurred in the majority of the population (97%). Baseline LVEF was on average 33 (9)%. In 49 patients (54%) a severe reduction of LVEF (<30%) was present. Coronary revascularisation was performed by coronary artery bypass grafting in 75 patients (83%), using the left internal mammary artery in 97% of the patients. In the remaining 15 patients (17%), coronary revascularisation was performed by coronary angioplasty. Nine to 12 months after revascularisation, LVEF improved significantly in the entire population (from 33 (9)% to 35 (10)%, p = 0.01). However, an improvement of LVEF ⩾5% was seen in 33 patients (37%).

Myocardial viability

Analysis of resting echocardiographic images showed that 808/1440 segments (56%) were severely dysfunctional (wall motion score 3–5). Patients had on average 9 (4) severely dysfunctional segments. The mean (SD) wall motion score index was 2.8 (0.7). During DSE, 356/808 (44%) severely dysfunctional segments were considered as viable, whereas 452 segments were non-viable. A substantial amount of viable myocardium (⩾4 segments) was present in 42 patients (47%), who were defined as viable patients. Limited or no viable myocardium was present in the remaining 48 patients who were considered as non-viable patients. An analysis of the viability studies of the seven patients who died postoperatively showed that these patients had a large amount of scar (10.8 (3.0) segments) and only scarce viable myocardium (1.5 (3.0) segments). Accordingly, these patients had also a very low LVEF before revascularisation (23 (7)%).

Myocardial viability and LVEF improvement after revascularisation

After revascularisation, 27/42 viable patients (64%) showed a significant improvement in LVEF (group 1), whereas 15 viable patients (36%) did not improve in LVEF after revascularisation (group 2). An improvement in LVEF ⩾5% was observed infrequently (12%, p<0.001 vs viable patients) in the non-viable patients (group 3). After revascularisation, the LVEF was 42 (10)% in group 1, 32 (9)% in group 2 and 32 (10)% in group 3 (p<0.001).

Comparison between viable patients with and without LVEF improvement and non-viable patients

Preoperative clinical characteristics were comparable in the three groups (table 1). In particular, the three groups were similar with respect to number of stenotic vessels, angina pectoris and heart failure scores. Also the frequency of previous myocardial infarction and of the preoperative LVEF was similar in the three groups (table 1). An analysis of resting wall motion showed that the wall motion score index was 2.7 (0.8), 2.9 (0.6) and 2.7 (0.5) in groups 1, 2 and 3, respectively (p =  NS). However, both the end-diastolic volume and end-systolic volume of the left ventricle were significantly larger in groups 2 and 3 than in group 1 (table 2).

Functional class after revascularisation and clinical follow-up

Improvement of heart failure symptoms after revascularisation was seen in both groups 1 and 2, whereas in group 3 the heart failure score did not improve significantly. The NYHA class after revascularisation was 1.7 (0.7) in group 1, 1.7 (0.9) in group 2 and 2.7 (0.5) in group 3 (p<0.001). The angina pectoris score decreased in the entire group. The CCS class was 1.2 (0.7) in group 1, 1.2 (0.6) in group 2 and 1.2 (0.5) in group 3 (p =  NS). On long-term follow-up (up to 4 years after revascularisation), only one patient died in group 1 and none had myocardial infarction or hospitalisation for heart failure. In group 2, one patient died and two patients were hospitalised for heart failure. In group 3, six patients died, two patients had acute myocardial infarction and eight were admitted to hospital for heart failure. Overall, the cardiac event rate was low (4%) in group 1, intermediate (21%) in group 2 and high (33%) in group 3 (p = 0.01, fig 1).

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Figure 1

Kaplan–Meier curves showing the cardiac event rate in the three groups of patients. The event rate was high in non-viable patients (group 3), low in viable patients with LVEF improvement (⩾5%) after revascularisation (group 1) and intermediate in viable patients without improvement in LVEF after revascularisation (group 2).

DISCUSSION

In the past two decades, a large body of evidence has emerged demonstrating that in patients with ischaemic cardiomyopathy, the presence of a substantial amount of myocardial viability is associated with an increase in LVEF and improvement in prognosis after coronary revascularisation. The findings in this study demonstrated that after revascularisation a very good prognosis is present only in viable patients with improvement in LVEF. Conversely, patients without viable myocardium had a relatively poor prognosis and, of interest, an intermediate prognosis was found in viable patients without improvement in LVEF.

Coronary revascularisation of viable myocardium versus improvement in LVEF

The presence of myocardial viability has been associated with improvement of global LV function after revascularisation.17 In this study, significant improvement of LVEF (⩾5%) after revascularisation was seen in 64% of viable patients. Previous studies reported postoperative improvement of LVEF in variable proportions of viable patients. In the study by Cuocolo et al, 36% of patients with evidence of viable myocardium on thallium-201 imaging showed improvement in LVEF after revascularisation.5 Whereas Cornel et al used a comparable DSE protocol to assess viability and demonstrated an improvement in LVEF in 68% of patients, in line with the current findings.11 In addition, the various studies suggested that at least 25–30% of the left ventricle needed to be viable to allow improvement in global LV function.4^–12 However, not all patients with this extent of viable myocardium exhibit improvement in LVEF after revascularisation. There may be various reasons for this. First, extensive remodelling may prohibit improvement in LVEF despite the presence of viable myocardium.18^–20 Second, it has been shown that besides viable myocardium, the extent of scar tissue is also an important predictor of improvement in LVEF.21 22 Accordingly, in this study, LV dilatation and the extent of scar tissue were larger in the patients whose LVEF did not improve (table 2). Also, delayed revascularisation and graft closure or restenosis may inhibit functional recovery of viable myocardium.23

However, besides improvement in LVEF, improvement of symptoms after coronary revascularisation is also an important clinical end point. It has been shown that heart failure symptoms may significantly improve after revascularisation in the presence of substantial amount of viable myocardium.4 24^–27 Accordingly, in this study, the NYHA functional class significantly improved in all viable patients (both groups 1 and 2), but did not change significantly in patients with limited or non-viable myocardium (group 3). Improvement in contractile reserve may be responsible for improvement in heart failure symptoms in patients with viable myocardium and lack of improvement in LVEF.28

Coronary revascularisation of viable myocardium versus improvement of prognosis

Previous studies have shown that coronary revascularisation may improve prognosis in patients with ischaemic cardiomyopathy and viable myocardium,13 whereas in patients without viable myocardium revascularisation might not affect prognosis. Indeed, in our study, patients who died postoperatively showed an extensive amount of scar and only scarce viable myocardium. Allman et al demonstrated a high event rate in patients with viable myocardium who were treated medically, whereas a favourable prognosis was present in patients with viability who underwent revascularisation.13 In this study, only patients who underwent coronary revascularisation were included. During the 4 years’ follow-up, a low event rate (4%) was seen only in those viable patients whose LVEF improved after revascularisation (group 1). In contrast, viable patients without improvement in LVEF (group 2) had a considerable event rate (21%); the highest event rate (33%) was seen in non-viable patients (fig 1). It appears that, although all viable patients after revascularisation have a better prognosis than non-viable patients, the best prognosis is found in viable patients in whom coronary revascularisation resulted in improvement in LVEF. In a previous study by Cuocolo et al event-free survival did not differ between patients with viable myocardium with (36 patients) or without (14 patients) improvement in LVEF after revascularisation. Although, in our study the difference in event rate was not statistically significant between groups 1 and 2 (probably owing to the small number of patients), our results suggest that the prognosis in those viable patients whose LVEF does not improve might be worse than in patients with functional improvement. Samady et al showed that lack of improvement in LVEF after revascularisation in patients with ischaemic cardiomyopathy was not associated with worse outcome.29 It should be noticed, however, that viability data were not available in that study.29 More importantly, assessment of LVEF was performed on average 16 (33) days after revascularisation, which may be too early to demonstrate improvement in LV function.18 30 31

Study limitations

Coronary angiography was not performed after revascularisation. Therefore, graft occlusion may have prohibited LVEF improvement and affected long-term prognosis.

Moreover, recent studies have suggested that in addition to revascularisation, surgical remodelling of the left ventricle (resections of LV aneurysms, or akinetic regions) may improve long-term prognosis.32 Recently, cardiac magnetic resonance has been introduced to assess myocardial viability.33 In particular, contrast-enhanced magnetic resonance imaging showed a very high sensitivity (96%) and specificity (84%) for detection of viable myocardium,34 even in the presence of more severe contractile dysfunction.35 In addition, compared with DSE, contrast-enhanced magnetic resonance has the advantage that it does not require pharmacological stress, and thus involves less risk and less patient monitoring. Furthermore, the quality of images of contrast-enhanced magnetic resonance is nearly always excellent and its interpretation is less observer dependent than DSE. Nevertheless, contrast-enhanced magnetic resonance is still not widely available, it is expensive and only few data support the prognostic value of this technique in patients with ischaemic cardiomyopathy.

CONCLUSION

In patients with ischaemic cardiomyopathy, coronary revascularisation is associated with a favourable outcome if a substantial amount of viable myocardium is present. In this study, it has been shown that after revascularisation of viable myocardium the best prognosis is observed in viable patients who exhibited improvement in LVEF after revascularisation. Conversely, viable patients without improvement in LVEF had an intermediate prognosis, and non-viable patients had the worst prognosis.