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PubMed2004

Effects of trimetazidine on left ventricular function in patients with type 2 diabetes and heart failure.

UNLABELLED: Congestive heart failure and type 2 diabetes have a deleterious prognosis when combined. Trimetazidine, a metabolic agent with anti-ischemic properties, reduces fatty acid beta-oxidation via decreased 3-ketoacyl-coenzyme-A thiolase activity thereby facilitating energy production via the glycolytic pathway. OBJECTIVES: To assess myocardial function by Tissue Doppler Imaging (TDI) after one month of trimetazidine (Vastarel) added-on conventional treatment in patients with type 2 diabetes and heart failure. METHODS: Twenty diabetic patients with ischemic heart failure (mean age 66 years; NYHA class II-III) were randomized to trimetazidine (60 mg daily) or placebo in a double-blind crossover design. Exercise tolerance, 2-dimensional echocardiograms, and TDI (rest and exercise) were studied before and during treatment. RESULTS: Changes in exercise tolerance did not differ in the two groups. Ejection fraction at rest and moderate exercise only improved significantly with trimetazidine when analyzed for the first treatment period. TDI velocities did not change significantly during treatment periods. CONCLUSION: In this early pilot investigation of the effects of trimetazidine in patients with diabetes and heart failure there were only weak signs of improved systolic myocardial function at rest and exercise. The present observations indicate the need of further research to explore the effect of trimetazidine during longer treatment period or with more selected patient population.

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PubMed1999

Transmyocardial laser revascularisation compared with continued medical therapy for treatment of refractory angina pectoris: a prospective randomised trial. ATLANTIC Investigators. Angina Treatments-Lasers and Normal Therapies in Comparison.

BACKGROUND: Transmyocardial revascularisation (TMR) is an operative treatment for refractory angina pectoris when bypass surgery or percutaneous transluminal angioplasty is not indicated. We did a prospective randomised trial to compare TMR with continued medication. METHODS: We recruited 182 patients from 16 US centres with Canadian Cardiovascular Society Angina (CCSA) score III (38%) or IV (62%), reversible ischaemia, and incomplete response to other therapies. Patients were randomly assigned TMR and continued medication (n=92) or continued medication alone (n=90). Baseline assessments were angina class, exercise tolerance, Seattle angina questionnaire for quality of life, and dipyridamole thallium stress test. We reassessed patients at 3 months, 6 months, and 12 months, with independent masked angina assessment at 12 months. FINDINGS: At 12 months, total exercise tolerance increased by a median of 65 s in the TMR group compared with a 46 s decrease in the medication-only group (p<0.0001, median difference 111 s). Independent CCSA score was II or lower in 47.8% in the TMR group compared with 14.3% in the medication-only group (p<0.001). Each Seattle angina questionnaire index increased in the TMR group significantly more than in the medication-only group (p<0.001). INTERPRETATION: TMR lowered angina scores, increased exercise tolerance time, and improved patients' perceptions of quality of life. This operative treatment provided clinical benefits in patients with no other therapeutic options.

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PubMed2004

Chronic administration of an endothelin-A receptor antagonist improves exercise capacity in rats with myocardial infarction-induced congestive heart failure.

The effects of long-term administration of YM598, a selective endothelin-A antagonist, on improving the exercise tolerance of chronic heart failure model rats were examined using a treadmill exercise loading test. Rats were acclimatized to the treadmill apparatus and the coronary artery was ligated to prepare a myocardial infarction-induced congestive heart failure (CHF) model. Starting 10 days postoperatively, when the acute phase of infarction was over, YM598 was administered orally once daily for approximately 25 weeks at a dose of 1 mg/kg. At weeks 20 and 24 the treadmill test was performed. YM598 prolonged running time, which had been shortened as a result of heart failure. The weights, relative to the body weight, of the left and right ventricles and lungs of surviving rats with CHF were significantly greater than those of sham-operated rats, suggesting hypertrophy of the ventricles and congestion of the lungs. Administration of YM598 markedly reduced ventricular hypertrophy and pulmonary congestion. Examination of cardiac function revealed that, in surviving CHF rats, the peak positive first derivative of left ventricular pressure was significantly lower, and left ventricular end-diastolic pressure, right ventricular systolic pressure and central venous pressure were significantly higher in comparison to sham-operated rats. These data demonstrate that, in rats with CHF, the contractile and diastolic capacity of the left ventricle decreased and pulmonary hypertension and systemic congestion occurred. Long-term administration of YM598 improved left ventricular function of CHF rats to the level of sham-operated rats, and reduced the workload placed on the right side of the heart. Histological examination revealed that long-term treatment with YM598 prevented fibrosis of the surviving left ventricular myocardium. In conclusion, long-term administration of YM598 to rats with CHF improved exercise tolerance and inhibited remodeling of cardiac muscles, leading to marked improvement of cardiac function.

Administration, Oral↗

PubMed1986

Chronic exercise produces tolerance to muscarinic antagonists in rats.

Previous work has shown that exercise can modify behavioral sensitivity to antimuscarinic compounds. The present study examined the effect of 10 weeks of endurance exercise on atropine and scopolamine potency. The behaviorally disruptive effects of these compounds were evaluated in rats trained to respond under a MULT TO FR30 schedule of reinforcement for food reward. Following 10 weeks of endurance exercise, atropine and scopolamine dose response curves were significantly altered. The ED50 values were increased 10 and 40-fold, respectively. Tolerance to atropine or scopolamine has been reported previously only in response to chronic drug administration. The present data demonstrate that non-drug factors can significantly influence behavioral response to muscarinic antagonists.

Animals↗

PubMed1991

Effects on quality of life with comprehensive rehabilitation after acute myocardial infarction.

This investigation was designed to determine the impact of a brief period of cardiac rehabilitation, initiated within 6 weeks of acute myocardial infarction (AMI), on both disease-specific and generic health-related quality of life, exercise tolerance and return to work after AMI. With a stratified, parallel group design, 201 low-risk patients with evidence of depression or anxiety, or both, after AMI, were randomized to either an 8-week program of exercise conditioning and behavioral counseling or to conventional care. Although the differences were small, significantly greater improvement was seen in rehabilitation group patients at 8 weeks in the emotions dimension of a new disease-specific, health-related Quality of Life Questionnaire, in their state of anxiety and in exercise tolerance. All measures of health-related quality of life in both groups improved significantly over the 12-month follow-up period. However, the 95% confidence intervals around differences between groups at the 12-month follow-up effectively excluded sustained, clinically important benefits of rehabilitation in disease-specific (limitations, -2.70, 1.40; emotions, -4.86, 1.10, where negative values favor conventional care and positive values favor rehabilitation) and generic health-related quality of life (time trade-off, -0.062, 0.052; quality of well-being, -0.042, 0.035) or in exercise tolerance (-38.5, 52.1 kpm/min); also, return to work was similar in the 2 groups (relative risk, 0.93; confidence interval, 0.71, 1.64).(ABSTRACT TRUNCATED AT 250 WORDS)

Anxiety↗

PubMed1997

[Factors limiting exertion in respiratory diseases].

Factors limiting exercise capacity in patients with respiratory disease are determined in part by their response to an exercise test. Exercise tests evaluate the overall oxygen transport chain, i.e. exercise tolerance. The basic parameter is maximal oxygen consumption, VO2max which is very low in respiratory diseases. Decreased exercise tolerance results first from limited ventilatory capacity at maximal exercise: ventilatory reserve in these patients is low. At submaximal exercise, ventilation is on the contrary increased for a given exercise load. This relative hyperventilation is the consequence of the patient's general poor physical condition. In these patients the cardiovascular response to exercise is impaired because of decreased systolic ejection fraction related to bronchial obstruction. Finally, whatever investigation method is used, the metabolic response in patients with respiratory disease, i.e. peripheral muscle response, is greatly impaired. The aerobic is deficient and the anaerobic pathway predominates, sign that the sedentary status of these patients has altered their metabolic response.

Exercise Test↗

PubMed2002

Survival in primary pulmonary hypertension: the impact of epoprostenol therapy.

BACKGROUND: Primary pulmonary hypertension (PPH) is a severe and progressive disease. Without treatment, the median survival is 2.8 years, with survival rates of 68%, 48%, and 34% at 1, 3, and 5 years, respectively. Intravenous epoprostenol was the first Food and Drug Administration-approved therapy for PPH. The long-term impact that epoprostenol has made on PPH remains to be defined. METHODS AND RESULTS: One hundred sixty-two consecutive patients diagnosed with PPH and treated with epoprostenol were followed for a mean of 36.3 months (median, 31 months). Data including functional class, exercise tolerance, and hemodynamics were recorded in a customized database. Vital status was verified in each patient. Observed survival with epoprostenol therapy at 1, 2, and 3 years was 87.8%, 76.3%, and 62.8% and was significantly greater than the expected survival of 58.9%, 46.3%, and 35.4% based on historical data. Baseline predictors of survival included exercise tolerance, functional class, right atrial pressure, and vasodilator response to adenosine. Predictors of survival after the first year of therapy included functional class and improvement in exercise tolerance, cardiac index, and mean pulmonary artery pressure. CONCLUSIONS: Intravenous epoprostenol improves long-term survival in PPH.

Adult↗

PubMed1993

[Use of a rate responsive pacemaker in sick sinus syndrome].

In this study of 10 patients with sick sinus syndrome, we examined the benefits of a single-chamber ventricular pacing system that utilizes a sensor to detect the QT interval and then adjusts the heart rate. Changes in exercise tolerance capacity and cardiac function were evaluated when the pacing mode was changed from rate-variable mode (VVIR) to fixed-rate mode (VVI). Anaerobic threshold (AT), peak VO2 and cardiac output were measured in VVIR, during short-term VVI(VVI-S), which occurred two hours after the pacing mode was changed, and during long-term VVI (VVI-L), which occurred one month after the pacing mode was changed. 8 of 10 cases (80%) had their own beats during exercise. The AT and peak VO2 during VVI-S were not different from those during VVIR. However, AT and peak VO2 during VVI-L were significantly lower than those during VVIR pacing. (Respectively, 11.7 +/- 2.4 vs. 16.4 +/- 3.3, p < 0.01; 21.5 +/- 5.9 vs. 24.6 +/- 6.2, p < 0.01). At AT and peak VO2, there were no differences in cardiac output between VVIR and VVI-S, or between VVIR and VVI-L(NS). Physiologic changes in heart rate and cardiac output after exercise during VVIR were greater than those during VVI pacing. The present study suggests the above-mentioned changes after exercise effect, oxygen consumption in the peripheral circulation, which might lower exercise tolerance capacity in the chronic phase. The rate-variable pacing mode might improve exercise tolerance capacity and may be of benefit for patients with sick sinus syndrome.

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PubMed1983

Persistent improvement after coronary bypass surgery: ergometric and angiographic correlations at 5 years.

One hundred patients with angina pectoris who fulfilled specific entry criteria were randomly assigned to either medical therapy or bypass surgery. These groups were subjected to annual exercise testing during a 5-year follow-up period. The degree of revascularization was assessed by graft and native vessel angiography at 3 weeks, 1 year and 5 years after the operation. The exercise tolerance of the medical group remained largely unchanged during the follow-up. Eighty-five to 95% of the patients were using beta-blocking compounds at the successive testing situations. The surgical group exhibited a sustained improvement in exercise tolerance: Total work increased by 39-66% (p less than 0.02-0.001) and maximal ergometric load by 23-35% (p less than 0.01-0.001), and maximal ST depression decreased by 39-61% (p less than 0.05-0.001). The use of beta-blocking compounds in the surgical group steadily increased, from 44% at 6 months after operation to 63% of patients at 5 years. Division of the surgical group into subsets of complete and incomplete revascularization revealed that the improvement was confined to complete revascularization. Thus, the improved exercise tolerance after bypass surgery was a result of successful reestablishment of effective coronary perfusion; despite graft attrition (15% in 5 years) and new lesions in the native arteries, this improvement persisted for 5 years with appropriate medical therapy.

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PubMed1998

Mibefradil, a T-type channel-selective calcium antagonist: clinical trials in chronic stable angina pectoris.

Pharmacotherapy with nitrates, beta-blockers, and calcium antagonists is the cornerstone of management of patients with chronic stable angina pectoris. While these agents are all effective, their use may be limited by pharmacologic tolerance, side effects, and drug interactions. Mibefradil is a recently developed calcium antagonist with a unique chemical structure, pharmacologic profile, and mode of action. Unlike all previously available calcium antagonists, mibefradil acts primarily by selective blockade of T-type calcium channels, rather than L-type channels, at clinically relevant concentrations. It has been evaluated as a treatment for angina in placebo-controlled and active-controlled clinical trials. Treatment with 50 mg mibefradil resulted in a significant improvement in exercise tolerance test duration in three of the five placebo-controlled trials, and a significant improvement in time to onset of angina in two of the five trials. Time to onset of ischemia as evaluated by 0.1 mV ST-segment depression was increased in all five placebo-controlled trials. Treatment with 100 mg mibefradil resulted in significant improvement in all three exercise tolerance test parameters in all studies. Mibefradil further improved exercise tolerance test duration and other efficacy parameters when administered concomitantly to patients on background beta-blocker or nitrate therapy. In addition, treatment with mibefradil was associated with a dose-dependent decrease in heart rate, double product, frequency of anginal attacks, nitroglycerin consumption, and both frequency and duration of silent ischemic episodes. In comparative trials, 100 mg mibefradil once daily was superior in efficacy to 10 mg amlodipine once daily and was at least equivalent to diltiazem in both efficacy and tolerability. Mibefradil was safe and well tolerated in all studies.

Amlodipine↗

PubMed1990

Digoxin, converting-enzyme inhibition (quinapril), and the combination in patients with congestive heart failure functional class II and sinus rhythm.

In a randomized single-blind cross-over trial, the efficacy of digoxin, angiotensin-converting enzyme (ACE) inhibition by quinapril, and their combination on exercise tolerance, heart size (echocardiography), and neurohumoral systems was investigated in 19 outpatients with congestive heart failure (CHF) New York Heart Association functional class II and sinus rhythm. Baseline therapy consisted of 25 mg hydrochlorothiazide and remained unchanged. After treatment with quinapril, exercise tolerance significantly increased (606 vs. 644 s, 2 p less than 0.03) and left ventricular end-diastolic dimension (63 vs. 58 mm, 2 p less than 0.03), mean arterial blood pressure (MABP, 100 vs. 92 mm Hg, 2 p less than 0.03) and plasma norepinephrine (NE) levels (378 vs. 323 pg/ml, 2 p less than 0.03) were significantly reduced. Digoxin increased resting systolic blood pressure (SBP 133 vs. 142 mm Hg, 2 p less than 0.03). Combined administration of both drugs significantly increased fractional shortening (24 vs. 28%, 2 p less than 0.03), reflecting the positive inotropic action of digoxin in combination with afterload reduction. However, there was no further increase in exercise tolerance. Our data suggest that early administration of ACE inhibitors may be beneficial in patients with mild CHF and sinus rhythm, although the magnitude of improvement was less substantial than that reported for patients with more severe CHF.

Adult↗

PubMed2001

Efficacy of pulmonary rehabilitation in an Irish population.

This study evaluated the results after 8 and 52 weeks of a comprehensive pulmonary rehabilitation programme for patients with chronic obstructive pulmonary disease (COPD) in Ireland. 170 patients with clinical and physiological evidence of COPD (mean FEV1 43.1 +/- 17.0%pred.) were recruited into an 8 week programme. At the time of final evaluation 15 patients had died, 25 patients had not been compliant with required attendances and 1 patient had transferred to another programme. To date assessments of 106 of the remaining 129 patients were made after eight weeks and of 78 patients after 1 year. Assessment consisted of pulmonary function testing; exercise tolerance as measured by a progressive maximal walking test (shuttle walk test) and an endurance test (treadmill test); quality of life (QoL) as measured by the Chronic Respiratory Disease Questionnaire (CRDQ), the St. George's Hospital Questionnaire (SGHQ) and the Breathing Problems Questionnaire (BPQ); and perceived dyspnoea on the Borg scale. Significant improvements in exercise tolerance, (shuttle p<.001, treadmill p<.001), QoL, (BPQ p<.001, CRDQ p<.001, SGHQ p<.001) and dyspnoea (p<.001) were demonstrated after 8 weeks. These improvements were maintained at 1 year. These results suggest that pulmonary rehabilitation can increase exercise tolerance and improve QoL in patients with COPD.

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PubMed2003

Oxygen supplementation before or after submaximal exercise in patients with chronic obstructive pulmonary disease.

BACKGROUND: Evidence for improved exercise tolerance or relief of breathlessness by short term use of oxygen before or after exercise in patients with chronic obstructive pulmonary disease (COPD) is scant, and guidelines for this treatment are lacking despite widespread provision in the UK. METHODS: The effect of oxygenation either before or after exercise on perception of breathlessness and walk distance was studied in a group of patients with moderate to severe COPD (mean forced expiratory volume in 1 second (FEV(1)) 34% of predicted, mean 6 minute walk distance on air 283 m), all of whom desaturated by at least 4% on submaximal exercise. Oxygen (28%) or air was delivered double blind and in random order, either for 5 minutes before a standard 6 minute walk test (n=34) or for 5 minutes following the end of the test (n=18). Exercise tolerance was measured as the distance achieved and breathlessness was assessed using visual analogue scales (VAS) which were scored before and after exercise and during recovery. RESULTS: No increase in mean walk distance after oxygen (288 v 283 m) and no improvement in mean breathlessness scores (58 v 54 mm) or recovery times occurred with oxygen taken either before (177 v 184 seconds) or after exercise (182 v 151 seconds). CONCLUSIONS: This group of patients with COPD derived no physiological or symptomatic benefit from oxygen breathed for short periods before or after submaximal exercise. Domiciliary oxygen should only be prescribed for such patients if they have shown objective evidence of benefit on exercise testing.

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PubMed2004

Mechanisms of exercise intolerance: insights from tissue Doppler imaging.

BACKGROUND: A decreased ratio of early to late diastolic mitral inflow velocities (E/A <1.0) reflects slowing of left ventricular (LV) relaxation. This finding is widely believed to indicate significant diastolic dysfunction. However, E/A <1.0 is common during normal aging and often is not associated with symptoms of heart failure. We asked (1) whether slowed LV relaxation is associated with exercise intolerance and (2) whether tissue Doppler imaging of the early diastolic mitral annular velocity (Ea) is helpful in understanding mechanisms of exercise intolerance. METHODS AND RESULTS: Patients (n=121) underwent echocardiography before maximal exercise testing. Fifty-nine subjects had E/A <1.0, and 36 subjects had E/Ea > or =10. Exercise capacity was similar in the population with a normal mitral inflow pattern and those with a slow relaxation pattern when E/Ea was <10. In contrast, the subjects with slow relaxation and E/Ea > or =10 had reduced exercise tolerance. Of all the echo and clinical parameters assessed, E/Ea had the best correlation with exercise capacity (r=-0.684, P<0.001) and was the strongest independent predictor of exercise capacity < or =7 METs by multivariate analysis (prevalence-corrected odds ratio=12.6, P<0.001). E/Ea continued to be strongly associated with exercise capacity in all age groups and in those with preserved or reduced systolic function. CONCLUSIONS: Of the subjects with slow LV relaxation, only those with E/Ea > or =10 have objective evidence of reduced exercise tolerance. These data suggest that elevated LV filling pressures rather than slow relaxation per se reduce exercise capacity.

Adult↗

PubMed1984

Failure of resistive breathing training to improve pulmonary function tests in patients with chronic obstructive pulmonary disease.

The effects on pulmonary function tests and exercise tolerance of resistive breathing training (RBT) were assessed in 16 subjects with stable chronic obstructive pulmonary disease (COPD) who had received no benefit from previous programs of breathing retraining (BR) and medical therapy (MT). 16 male patients with mild degree stable COPD underwent detailed evaluation of pulmonary function tests, blood gas analysis and exercise tolerance test before and after a monthly program of RBT. The patients had received no physiological effects from previous monthly programs of BR and MT. No change in pulmonary function tests, blood gas analysis and exercise tolerance test was observed after RBT. Only maximal static expiratory pressure increased significantly after RBT. We conclude that RBT does not improve pulmonary function tests in subjects who received no physiological benefit from BR.

Abdominal Muscles↗

PubMed2006

Exercise testing and chronic lung diseases in children.

Exercise activity is an important part of daily life for both healthy children and children with respiratory diseases. Overall fitness level and responses to exercise can be assessed through cardiopulmonary exercise tests (using a treadmill or a cycloergometer). In asthmatic children exercise tests are useful to diagnose exercise-induced bronchoconstriction, which may affect up to 80% of asthmatic subjects. In cystic fibrosis patient, as the disease progresses, lung function deteriorates and exercise tolerance likewise diminishes. This reduced tolerance may not be predicted on the base of a standard spirometry while an exercise test can offer useful information. Eventually, exercise testing is useful in children with bronchopulmonary dysplasia to determine any presence and extent of gas exchange and ventilation dysfunction during exercise. Exercise challenges are a valuable tool to assess exercise tolerance that may be not adequately reflected by resting lung function tests.

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PubMed1999

Effect of long-term exercise training on regional myocardial perfusion changes in patients with coronary artery disease.

The cardiac rehabilitation of patients with coronary artery disease (CAD) promotes exercise tolerance, improves left ventricular function, and decreases the heart rate and systolic blood pressure at the same load intensity. Several studies have shown that cardiac rehabilitation improves myocardial perfusion in CAD patients. However, the long-term (> or = 1 year) effect of cardiac rehabilitation on myocardial perfusion is still controversial. The effect of long-term exercise training on myocardial perfusion in CAD patients was assessed using thallium-201 (201Tl) exercise studies at a baseline (4 months after the onset of CAD) and at a 1-year or more follow-up in 58 patients with stable CAD. The subjects had been divided into a training group (n=35) participating in supervised exercise 2 times per week for the follow-up period, and the control group (n=23). There was an improvement in the myocardial perfusion on stress 201Tl scintigraphy in 20 of the 35 (57.1%) trained patients and in 3 of the 23 (13.0%) of the control patients (p<0.001). The number of 201Tl stress myocardial perfusion defect segments was significantly decreased after the cardiac rehabilitation training (231 to 153 segments), but showed no change in the control group (158 to 156 segments) (p<0.01). In spite of no significant differences in the number of involved coronary arteries, it improved (12/17 patients: 70.6%) more in the patients who had trained for more than 2 years compared to the patients who had trained for less than 2 years. The exercise tolerance increased in 25 of the 35 training group patients (71.4%), and in only 3 of the 23 control group patients (13.0%). The peak double products increased from 20,131+/-6,010 to 28,370+/-5,600 (p<0.01) in the training group, and showed no change in the control group (20,567+/-5,112 to 20,964+/-7,728 (NS)). The results indicated that the long-term physical training increased exercise tolerance and the double products of CAD patients. In addition, the training resulted in improved cardiac perfusion as evidenced by 201Tl scintigraphy. The findings suggest that exercise training is an advisable and effective treatment for patients with CAD.

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PubMed2005

The prospective clinical and scintigraphic assessment of patients with preserved left ventricular systolic function after transmyocardial laser revascularisation.

AIM: To analyse the clinical outcome and myocardial perfusion and function after transmyocardial revascularisation (TMR) in patients with normal left ventricular function and multivessel coronary artery disease non-amenable for standard revascularisation. METHOD AND RESULTS: Twenty three severely symptomatic patients (CCS score median 4) with normal left ventricular systolic function but coronaries non-amenable for either PTCA or CABG were subjected to TMR. The angina score, left ventricular systolic and diastolic function in radionuclide ventriculography at rest, exercise tolerance and myocardial perfusion--Thallium-201 SPECT (adenosine stress 74 and 37 MBq under nitrate cover) were evaluated before and 3, 6, 12 months post-operatively. After an average of 40 +/- 12 (range 14-56) TMR channels angina score decreased significantly (p< 0.0001) and the exercise tolerance increased (from 6.0 +/- 4.5 to 9.1 +/- 4.6 after 6 months, p< 0.05) in 21 patients. During the follow up period two patients had a myocardial infarction and one committed suicide after 6 months. Ejection fraction dropped significantly only after 1 year post-TMR from 70 +/- 13 to 63 +/- 0.13%, p < 0.05. The overall perfusion improved initially in 14 patients with subsequent deterioration in time. The changes in segmental perfusion were not associated with the symptomatic improvement. CONCLUSION: Transmyocardial revascularisation in patients with normal ejection fraction may improve the angina class, exercise tolerance and overall but not segmental perfusion and does not show any immediate effect on left ventricular function.

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