William A. Littler

Coronary artery bypass surgery as treatment for ischemic heart failure: the predictive value of viability assessment with quantitative positron emission tomography for symptomatic and functional outcome

OBJECTIVES To determine the predictive value of quantitative evaluation of myocardial viability on changes in left ventricular function, exercise capacity, and quality of life after coronary artery bypass grafting in patients with ischemic heart failure (congestive heart failure, New York Heart Association class > or = III) with and without angina. METHODS Thirty-five patients, 14 with congestive heart failure and angina (CHF-angina) and 21 with congestive heart failure without angina (CHF-no angina) were studied at baseline and 6 months after coronary bypass grafting. Left ventricular function was evaluated with transthoracic echocardiography and radionuclide ventriculography. Myocardial viability was assessed with [18F]-2-fluoro-2-deoxy-D-glucose using positron emission tomography. Peak aerobic capacity (peak oxygen consumption) and anaerobic threshold were assessed with treadmill exercise test and quality of life with a questionnaire. RESULTS A total of 286 of 336 dysfunctional left ventricular segments were viable. There were two perioperative deaths (5.7%) and three late deaths. Left ventricular ejection fraction increased from 23% +/- 7% to 32% +/- 9% (p < 0.0001), and a linear correlation was found between the number of viable segments and the changes in ejection fraction (r = 0.65; p = 0.0001). Receiver operating characteristics curve identified eight viable segments as the best predictor for increase of ejection fraction more than 5 percentage points. Peak oxygen consumption increased from 15 +/- 4 to 22 +/- 5 ml/kg per minute (p < 0.0001). Preoperatively, anaerobic threshold was identified in one patient from the CHF-angina group and in all from the CHF-no angina group and increased from 13 +/- 4 to 19 +/- 4 ml/kg per minute (p < 0.0001). Quality of life scores improved significantly in both groups. No correlation was found between the amount of viable dysfunctional myocardium and changes in exercise capacity or quality of life. CONCLUSIONS In patients with postischemic congestive heart failure the amount of viable myocardium dictates the degree of improvement in left ventricular function after revascularization.

Felodipine in patients with chronic heart failure: discrepant haemodynamic and clinical effects.

Previous open studies have suggested that felodipine, a selective calcium antagonist and vasodilator, may be useful in the treatment of heart failure. A double blind placebo controlled crossover trial was therefore conducted to investigate the clinical and haemodynamic effects of felodipine in 15 patients with chronic ischaemic heart failure in New York Heart Association symptom class III. Felodipine significantly increased resting and exercise (25W bicycle ergometry) cardiac output without producing concomitant changes in resting or exercise heart rate or right and left ventricular filling pressures. Felodipine did not significantly improve symptom scores or exercise capacity in the group as a whole. It also resulted in significant fluid retention as shown by a rise in ankle circumference, body weight, and a fall in haematocrit. Further research is required to elucidate the mechanism that is responsible for the discrepancy between the haemodynamic and clinical effects of felodipine in patients with moderately severe heart failure.

Immunoglobulin response to intravenous streptokinase in acute myocardial infarction.

OBJECTIVE--To devise assays to assess and follow the specific antibody response in patients treated with streptokinase for acute myocardial infarction. DESIGN--Venous blood samples were collected before treatment with streptokinase started and subsequently at regular intervals over one year. Specific IgG and subclass IgG1 were assessed by an enzyme linked immunosorbent assay. SETTING--Coronary care unit in a general hospital. PATIENTS--48 patients with acute myocardial infarction: 22 patients had venous blood samples taken at presentation only; serial blood samples were taken from 20 patients who then received thrombolytic therapy with streptokinase and six patients who were unsuitable for thrombolytic therapy. RESULTS--Titres of antibodies to streptokinase were low at presentation in 36 (75%) of the 48 patients. Serial measurements made in 20 patients showed the virtual disappearance of antibody within the first 24 hours. This was followed by a steady increase in the specific IgG1 titre, which peaked at day 14 before gradually declining. Values at one year remained significantly higher than baseline values. There was no evidence of an IgM response in the patients studied. CONCLUSION--Low titres of antibodies to streptokinase were widespread in the population. Antibody was consumed after treatment and the subsequent immunoglobulin rise suggested a secondary immune responses; the recently described neutralising capacity to streptokinase is probably related to this antibody.

Evaluation of PCR in the molecular diagnosis of endocarditis

OBJECTIVE Infective endocarditis (IE) is diagnosed by the Duke criteria, which can be inconclusive particularly when blood cultures are negative. This study investigated the application of polymerase chain reaction (PCR) to identify bacterial DNA in excised valvular tissue, and its role in establishing the diagnosis of IE. METHODS Ninety-eight patients undergoing valve replacement surgery were studied. Twenty-eight patients were confirmed as definite for endocarditis by the Duke criteria; nine were considered as possible and 61 had no known or previous microbial infection of the endocardium. A broad-range PCR technique was used to amplify prokaryotic 16S rRNA genes present within homogenised heart valve tissue. Subsequent DNA sequencing of the PCR amplicon allowed identification of the infecting microorganism. RESULTS PCR results demonstrated the presence of bacterial DNA in the heart valves obtained from 14 out of 20 (70%) definite IE patients with positive blood cultures preoperatively. The causative microorganism for one patient with definite culture negative endocarditis was identified by PCR. Two out of nine (22%) of the valves from possible endocarditis patients also had bacterial DNA present converting them into the definite criteria whereas in the valves of seven out of nine (78%) of these patients no bacterial DNA was detected. CONCLUSION The application of PCR to the explanted valves in patients with possible or confirmed diagnosis can augment the Duke criteria thereby improving post-surgical antimicrobial therapeutic options.

Beneficial haemodynamic effects of intravenous dopexamine in patients with low-output heart failure.

Summary: Dopexamine is a novel compound that has DArdopaminergic and β2-adrenergic agonist properties capable of producing beneficial systemic and renal vasodilation. The acute haemodynamic effects in 10 patients with low-output-state ischaemic cardiac failure (NYHA IV) were recorded before (control) and during graded incremental doses of dopexamine infusion from 0.5 to 6.0 μ.g/kg/min. Dopexamine produced a marked increase in cardiac index from 1.6 ± 0.2 (control) to a maximum of 2.8 ±0.4 L/min/m2 (p < 0.001) primarily by inducing vasodilation, with reduction in systemic vascular resistance from 1,720 <136 (control) to 1,116 ± 136 dynes s cm−5 (p < 0.05). Using a more sophisticated analytical technique which enables us to separate direct inotropic from vasodilatory effects, we were able to identify, in eight of the patients, a direct dopexamine-induced positive inotropism. These beneficial central haemodynamic effects of dopexamine, when coupled with its known DA1-dopaminergic agonist property, indicate that dopexamine may have a place in the management of patients in severe heart failure

Serum cortisol levels predict infarct size and patient mortality

We have investigated prospectively the serum cortisol response to acute myocardial infarction in 70 consecutive patients admitted to a coronary care unit and we have shown that the levels are significantly raised early in the course of the illness and prior to elevation of the cardiac specific enzyme fraction, creatine kinase MB. The magnitude of the cortisol response is related to the size of the ensuing infarction (rs = 0.54) as calculated from the total creatine kinase MB release (P < 0.001) and very high levels (> 2000 mumol/l) are predictive of mortality (P < 0.05). Serum cortisol levels may have a role in the early identification of myocardial infarction and in predicting those patients with a poor prognosis.

The microbial diagnosis of infective endocarditis

This review suggests an evidence-based algorithm for sequential testing in infective endocarditis. It discusses blood culture and the merits and drawbacks of serology in making the diagnosis. Newer techniques are briefly reviewed. The proposed algorithm will complement the Duke criteria in clinical practice.

Angiotensin II modulates cardiovascular autonomic control in the absence of baroreflex loading

Objective To investigate the effects of angiotensin II in the absence of baroreflex activation. Design Ten healthy male volunteers were studied in a single blind, randomised, crossover study of heart rate variability during intravenous angiotensin II infusion (5–20 ng/kg/min) compared with a control pressor infusion of phenylephrine (0.7–2.8 μg/kg/min). Each infusion was titrated to increase mean blood pressure by 20 mm Hg; sodium nitroprusside was then infused simultaneously to restore blood pressure to baseline values. Results During concomitant angiotensin II (AII) and sodium nitroprusside (SNP) infusion, the mean (SD) RR interval (864 (117) ms) was significantly shorter than during phenylephrine (PE) and sodium nitroprusside infusion (1057 (163) ms), and was significantly shorter than at baseline (999 (164) ms), despite comparable levels of blood pressure. Values of high frequency heart rate variability measured in the time and frequency domains were significantly lower during AII/SNP infusion than during PE/SNP: percentage of successive RR interval differences exceeding 50 ms, 30(16)% v 57(21)%; root mean square of successive RR interval differences, 63 (39)v 90 (40) ms; high frequency power 0.48 (0.19) v 0.66 (0.26) nu. Conclusions When the pressor response is controlled by sodium nitroprusside, angiotensin II infusion is associated with tachycardia. Analysis of heart rate variability suggests that this reflects inhibition of cardiac vagal activity.

Effects of perindopril on ambulatory intra-arterial blood pressure, cardiovascular reflexes and forearm blood flow in essential hypertension.

The effects of monotherapy with the angiotensin converting enzyme (ACE) inhibitor perindopril (8mg once daily) on 24-h ambulatory intra-arterial blood presure, forearm blood flow, left ventricular mass, vasoactive hormones and cardiovascular reflexes were determined in eight hypertensive patients using a randomized, double blind, placebo-controlled, cross-over protocol. Six weeks of perindopril treatment was associated with a significant reduction of ambulatory blood pressure and a significant increase in forearm blood flow. Whilst the haemodynamic responses to Valsalvas manoeuvre, tilt, isometric forearm exercise and cold pressor testing were unaffected by perindopril, significant augmentation of the bradycardia during facial immersion was seen after chronic therapy. Sino-aortic baroreceptor-heart rate reflex resetting was apparent within 2h of the first dose; this effect persisted throughout the active treatment period. Withdrawal of treatment was associated with a persisting hypotensive effect and an increase in heart rate which was not accompanied by an increase in plasma catecholamines. We conclude that perindopril, in a dose of 8mg once daily, was an effective antihypertensive agent. We postulate that chronic therapy was associated with a sustained increase in parasympathetic tone.

COMPARISON OF THE HAEMODYNAMIC EFFECTS OF DOPEXAMINE AND DOBUTAMINE IN PATIENTS WITH SEVERE CONGESTIVE HEART FAILURE

Dopexamine hydrochloride is a novel compound with properties of DA1-dopaminergic and beta 2-adrenergic receptor agonism and neuronal noradrenaline uptake inhibition. It has been shown to produce beneficial renal and haemodynamic effects in patients with severe heart failure. We compared the haemodynamic effects of dopexamine (0.5 to 6 micrograms/kg/min) with those of dobutamine (5 to 25 micrograms/kg/min) in 9 patients with severe congestive heart failure. The two drugs were similar in their effects at peak infusion rates: heart rate increased (dopexamine 87 +/- 17 to 100 +/- 14; dobutamine 91 +/- 18 to 103 +/- 17 min-1), cardiac index increased (dopexamine 1.7 +/- 0.5 to 2.8 +/- 1.1; dobutamine 1.8 +/- 0.5 to 3.0 +/- 1.1 l.min-1.m-2) and systemic vascular resistance decreased (dopexamine 1553 +/- 221 to 1117 +/- 432; dobutamine 1721 +/- 347 to 1280 +/- 433 dyne.s.cm-5). Neither drug affected pulmonary artery wedge pressure (dopexamine 24 +/- 6 to 22 +/- 6; dobutamine 25 +/- 9 to 24 +/- 10 mm Hg). Dopexamine had significantly lower peak effects on left ventricular stroke work index (dopexamine 20 +/- 9, dobutamine 27 +/- 15 g.m.m-2, P less than 0.05) and cardiac power output (dopexamine 0.71 +/- 0.36, dobutamine 0.93 +/- 0.46 W, P less than 0.05). These haemodynamic effects, due largely to vasodilatation but with some contributory positive inotropy, indicate that dopexamine will be useful in the acute treatment of congestive heart failure.