Case report

Professor F.C. Visser
Department of Cardiology, University Hospital, Vrije Universiteit, Amsterdam, 
The Netherlands

I saw a 74-year-old male patient for the first time at the outpatient clinic 6 weeks after discharge from hospital where he had stayed for 12 days for the treatment of heart failure. Since 1996 his GP had been treating him with aspirin and long-acting nitrates for mild angina, retrospectively estimated as New York Heart Association (NYHA) class II angina. In early 1999 he was admitted to hospital due to acute dyspnoea after a short period of increasing breathlessness during exercise. Prior to admission he had also been experiencing some increase in anginal symptoms on exercise.
On admission, the patient was tachypnoeic (blood pressure 180/90, pulse 92 regular, central venous pressure not elevated), his temperature was normal and there were no audible carotid bruits. Heart sounds were normal and at the apex a soft holosystolic murmur was audible, radiating to the axilla, compatible with mitral regurgitation. Rales were audible over the lungs up to the axilla. His liver was not enlarged and he had no signs of peripheral oedema.
The ECG on admission showed a sinus rhythm of 100/min, normal PQ times and a QRS duration of 0.09 s, q-waves in leads V4–V6 with positive T waves, compatible with a previous silent lateral infarction. There were mild repolarization abnormalities in the inferior leads. Chest x-ray revealed an enlarged heart and signs of interstitial oedema.
The echocardiogram, made several days after admission, showed a dilated, poorly contracting left ventricle with regional wall motion abnormalities and end-diastolic and end-systolic dimensions of 70 and 56 mm, respectively. There was moderate mitral and mild-to-moderate tricuspid regurgitation. Radionuclide angiography (RNA) was performed and the calculated ejection fraction (EF) was 23%.
The patient’s laboratory examination revealed no increase in cardiac enzymes, no anaemia, slightly increased creatine (114 mmol/l) and slightly elevated liver enzymes, which returned to normal during hospitalization.
He was treated with diuretics and angiotensin-converting enzyme inhibitors; the long-acting nitrates were continued and because of his poor left ventricular function, aspirin was replaced by warfarin. He recovered very quickly, and no rales were subsequently heard, no signs of congestion were seen on chest x-ray and his ECG remained essentially unchanged.
Six weeks after discharge the patient continued to complain of dyspnoea on exercise, but his exercise tolerance was increased in comparison with the weeks before submission. No signs of overt heart failure were present on physical examination. Because of the absence of heart failure, the patient was treated with the beta-blocker carvedilol, starting with a low dose of 3.125 mg twice daily and gradually increasing to 25 mg twice daily over a period of 4 months. Within the first week of beta-blocker treatment, RNA was repeated and showed an EF of 28%.
Additional diagnostic procedures were performed because of a suspected ischaemic aetiology of the heart failure. A dipyridamole and rest perfusion single photon emission computed tomographic (SPECT) scintigram was obtained. The vertical long-axis views (Figure 1) showed a perfusion defect at the apex and distal anterior, which was partly reversible. 

Figure 1. Vertical long-axis view of the dipyridamole and rest MIBI SPECT study. A partially reversible defect at the distal anterior segment and apex can be seen.

The rest perfusion image showed moderately decreased activity in the area of the infarction, suggesting the presence of viable tissue. The other areas showed no perfusion defects. The left ventricle was dilated.
Coronary angiography was performed 3 months after discharge from hospital. The ventriculogram showed moderately contracting left ventricle and slightly elevated end-diastolic pressures; the angiogram showed three-vessel disease with significant stenoses in the RCA, LAD and LCx.
Over time the patient reported less dyspnoea and his exercise tolerance increased substantially. His estimated functional class, 6 months after discharge, was NYHA II. He was also almost without anginal complaints. RNA repeated 7 months after discharge showed an EF of 49% (Figure 2). At present his symptoms remain unaltered.

Figure 2. Improved EF following treatment with beta-blockers.

Discussion
This patient with a history of (probably ischaemic) heart failure showed a remarkable improvement of left ventricular function after treatment with beta-blockers. Moreover, despite the fact that he had three-vessel disease, his perfusion scintigram showed only mild signs of ischaemia in the area of his previous silent infarction.

Beta-blockers in heart failure
The beneficial effects of beta-blockers have been discussed elsewhere in this issue. We have performed a pooled analysis of the effects of beta-blockers on left ventricular function (Figure 3).[1]

Figure 3. Mean increase and range in EF units of several beta-blockers.

Although the effects of beta-blockers are generally mild in patients with severe left ventricular dysfunction, with a mean increase in EF between 0 and 15%, a clinically significant improvement in individual patients may occur. In this patient the improvement in left ventricular function was at least 21 EF units.




Angiographic data versus perfusion data
In the recommendations of the American College of Cardiology/American Heart Association,[2] a class I indication for revascularization is the presence of three-vessel disease, independent of the severity of symptoms and the degree of left ventricular dysfunction.
However, it has long been recognized that there is a poor correlation between the angiographic and nuclear perfusion data. Patients with significant coronary artery disease on angiography may have normal perfusion in the area of the stenosed coronary arteries, indicating that the functional significance of the anatomic lesion is limited. Also nuclear stress-perfusion data have shown that the prognosis in patients with mild ischaemia on stress perfusion imaging is excellent. In a recent study of a large group of patients undergoing stress-rest perfusion imaging, Hachamovitch et al.[3] showed that survival of these patients is almost similar to that of patients without perfusion defects. Earlier studies have also shown that when adding angiographic data to perfusion imaging data, no significant increase in prognostic value can be expected.[4]

Viable tissue and improvement of left ventricular function after revascularization
One of the most important determinants of prognosis in patients with coronary artery disease is the degree of left ventricular dysfunction. Dr Roxy Senior, in this issue, clearly shows that dysfunctional but viable tissue improves its function after revascularization. Although patients in the viable tissue-revascularization studies may have used beta-blockers, the degree of improvement of left ventricular function in heart failure patients who favourably react to treatment with beta-blockers is unknown. The impact of revascularization in these patients is therefore unknown.

Summary
There are conflicting arguments surrounding the need for revascularization in this patient. On one hand, the argument in favour of revascularization is the presence of three-vessel disease and the history of heart failure, but on the other is the absence of extensive ischaemia and the improvement of left ventricular function and symptoms.
I decided to treat this patient conservatively. So far, 11 months after admission, the patient is stable and has no signs or symptoms of heart failure and almost no anginal complaints. 

If you have arguments for or against revascularization in this patient, please email me at fc.visser@azvu.nl with your opinion. Opinions will be published in a future issue of Heart and Metabolism.

REFERENCES
1. van Campen LCMC, Visser FC, Visser CA. Ejection fraction improvement by beta-blocker treatment in patients with heart failure: an analysis of studies published in the literature. J Cardiovasc Pharm 1998; 32 (suppl 1): S31–S35.
2. American College of Cardiology/American Heart Association Task Force on Practice Guidelines. ACC/AHA/ACP-ASIM guidelines for the management of patients with chronic stable angina: executive summary and recommendations. Circulation 1999; 99: 2829–2848.
3. Hachamovitch R, Berman DS, Shaw LJ et al. Incremental prognostic value of myocardial perfusion single photon emission computed tomography for the prediction of cardiac death: differential stratification for risk of cardiac death and myocardial infarction. Circulation 1998; 97: 535–543.
4. Iskandrian AS, Chae SC, Heo J et al. Independent and incremental prognostic value of exercise single-photon emission computed tomographic (SPECT) thallium imaging in coronary artery disease. J Am Coll Cardiol 1993; 22: 665–670.