Difference in the mortality of the CABRI diabetic and nondiabetic populations and its relation to coronary artery disease and the revascularization mode.

In diabetics with coronary artery disease (CAD), there remains uncertainty as to whether revascularization by percutaneous transluminal coronary angioplasty (PTCA) or coronary artery bypass surgery (CABG) is preferable. To address this, 4-year mortality and level of pre- and postrevascularization angiographic CAD (measured by a series of coronary scores) were compared between both diabetics and nondiabetics and between revascularization modes in the Coronary Angioplasty versus Bypass Revascularization Investigation population as a whole, and then substratified by diabetic status and then by procedure to which they were randomized. The 1,054 randomized subjects contained 125 diabetics (11.9%) who had significantly greater mortality than nondiabetics (RR 2.19, p = 0.001). Among diabetics or nondiabetics, there was no significant mortality difference between those randomized to PTCA versus those to CABG. Diabetics randomized to PTCA and those to CABG had higher mortalities than respective nondiabetics; the association reached significance only in the former (RR 2.41, p = 0.002). All subgroups had similar prerevascularization CAD. Postrevascularization residual CAD was consistently significantly greater in PTCA than in respective CABG subgroups. Most measurements of CAD were greater in diabetic than in nondiabetic subgroups, but none was significant. In the Coronary Angioplasty versus Bypass Revascularization Investigation, diabetics had double the mortality of nondiabetics; this difference was statistically significant both for the entire population and for those randomized to PTCA, but not for those randomized to CABG. Among diabetics or nondiabetics, there was no significant mortality difference between PTCA and CABG. The higher diabetic mortality was more likely related to more rapid disease progression than to greater postrevascularization disease.

The effect of adjusting for baseline risk factors and post revascularisation coronary disease on comparisons between coronary angioplasty and bypass surgery.

BACKGROUND: In CABRI at 1 year PTCA was associated with greater repeat revascularisation and angina (but not myocardial infarction or death). We determined whether adjusting for baseline risk factors and post revascularisation coronary disease offsets this disadvantage of PTCA. METHODS: In the CABRI population the crude association of revascularisation mode (i.e. PTCA or CABG) with four clinical outcome (i.e. mortality, myocardial infarction, repeat revascularisation and angina) was adjusted for the baseline risk factors using a logistic regression model for each clinical outcome. A number of measures of angiographic coronary disease were used to assess post revascularisation coronary disease. One at a time, each of these measures was added to each of the four outcome models, to adjust for post revascularisation coronary disease. RESULTS: Comparing adjusted and crude unadjusted association of PTCA with repeat revascularisation there was an increase from 12.8 (P<0.0005) (crude relative risk) to 16.7 (P<0.0005) (adjusted odds ratio), with angina, from 1.89 (P=0.001) to 1.98 (P<0.0019), and with mortality from 1.84 (P=0.092) to 2.15 (P=0.060). PTCA was not significantly associated with myocardial infarction, either crudely or after adjustment. CONCLUSION: Adjusting for baseline risk factors and post revascularisation coronary disease tended to strengthen rather than weaken associations between PTCA and 1 year mortality, repeat revascularisation and angina at 1 year.

Influence of clinical and angiographic factors on development of collateral channels.

BACKGROUND: The degree of coronary collateralization is believed to be related to several clinical and angiographic factors. The duration and frequency of angina may be important factors in determining development of collateral channels. OBJECTIVE: To assess these factors for a consecutive series of patients suspected to have coronary artery disease. METHODS: Patients without at least one stenosis of < 50% and patients who had previously undergone bypass surgery were excluded from our study. Severity of stenosis was quantified by digital analysis, antegrade flow in terms of TIMI grade, and collaterals using the Rentrop classification. RESULTS: We reviewed 106 patients [mean age 61 years (range 35-84), 77.6% men]. Of these, 22 (21%) had presented with an acute coronary syndrome on this admission, whilst 46 patients (43%) had previously had an acute coronary syndrome. Collaterals were more likely in patients with stenoses of > 90% (Spearman correlation 0.65, P < 0.001) in patients with lower than normal TIMI flow grade (Spearman correlation 0.86, P < 0.01) and were related to regions of hypokinesis (Spearman correlation 0.35, P < 0.01). Significant collaterals were present in 14 patients (13%) despite their having TIMI grade II/III flow. Two of these patients had grade 2/3 collaterals with TIMI grade II/III antegrade flow. Degree of collateralization was not related to chronicity and frequency of symptoms, age, risk factors for atherosclerosis and nature of presentation (i.e. acute or stable symptoms). CONCLUSION: The likelihood of coronary collateralization cannot be prospectively predicted from clinical history alone, but appears to be largely a function of severity of stenosis and level of antegrade flow. A few patients develop high-grade collateral channels despite the presence of good antegrade flow.

Relation between coronary artery disease, baseline clinical variables, revascularization mode, and mortality. CABRI Participants. Coronary Angioplasty vs. Bypass Revascularisation Investigation.

The Coronary Angioplasty vs. Bypass Revascularisation Investigation (CABRI) trial comparing percutaneous transluminal coronary angioplasty (PTCA) with coronary artery bypass grafting did not show a difference in mortality with either procedure. Nonrandomized studies suggest that coronary artery disease (CAD) severity and distribution influences outcome. In the present study we explored the effect of prerevascularization CAD on 1-year mortality in the CABRI population, while adjusting for other baseline variables. Of the 1,054 patients recruited, there were sufficient angiographic results to derive the CAD scores in 974 (92.4%). Of these 974, there were 32 deaths. A number of CAD scores, both weighted for proximal disease (Duke and Leaman) and nonweighted, were used. These scores were then cross-tabulated against mortality. Demographic and clinical variables were also cross-tabulated against mortality and used to derive an initial logistic regression model to predict mortality. The effect of adding each of the CAD scores to this initial model was then assessed. After inclusion of the CAD scores, the best model was: (1) presence of peripheral vascular disease (odds ratio [OR] 3.89, p = 0.0025), (2) previous cerebrovascular accident (OR 2.86, p = 0.043), (3) older age (OR 1.05, p = 0.039), (4) a higher Duke score (OR 2.84, p = 0.0061), and (5) having undergone PTCA (OR 2.12, p = 0.047). In the CABRI population, adjustment for baseline variables, including prerevascularization CAD, revealed significantly higher mortality in those who underwent PTCA than in those who underwent coronary artery bypass grafting.

Stabilisation of medically refractory ventricular arrhythmia by intra-aortic balloon counterpulsation.

OBJECTIVE: To review the efficacy of intra-aortic balloon counterpulsation (IABCP) in medically refractory ventricular arrhythmia. DESIGN: Retrospective analysis of the outcome of patients with ventricular arrhythmia treated with IABCP after transfer between 1992 and 1997. SETTING: Tertiary cardiac referral centre. PATIENTS: 21 patients (mean age 58 years) who underwent IABCP for control of ventricular arrhythmia. All had significant left ventricular impairment (mean ejection fraction 28.6%); 18 had coronary artery disease. RESULTS: Before IABCP, 10 patients had incessant monomorphic ventricular tachycardia and 11 had paroxysmal ventricular tachycardia and/or ventricular fibrillation (VT/VF). IABCP resulted in suppression of ventricular arrhythmia in 18 patients, of whom 13 were weaned from IABCP. After stabilisation of ventricular arrhythmia, 10 patients were maintained on medical treatment alone and one underwent endocardial resection. IABCP was maintained until cardiac transplantation in five patients. One patient had a fatal arrest before discharge and one died from progressive heart failure. IABCP failed to control ventricular arrhythmia in three patients and was subsequently discontinued. A cardiac assist device was employed in one of these until cardiac transplantation; the other two were eventually stabilised on medical treatment. Nineteen patients were discharged from hospital. Overall survival was 95% at mean follow up of 25.7 months. CONCLUSIONS: IABCP can be an effective means of controlling refractory ventricular arrhythmia, allowing time for the institution of more definitive treatment.

Impact of postangioplasty restenosis on comparisons of outcome between angioplasty and bypass grafting. Coronary Angioplasty versus Bypass Revascularisation Investigation (CABRI) Investigators.

Restenosis is a major limitation of percutaneous transluminal coronary angioplasty (PTCA). In this study, we assessed the impact of restenosis on PTCA with reference to coronary angioplasty bypass grafting (CABG). In the Coronary Angioplasty versus Bypass Revascularisation Investigation (CABRI) PTCA population, those who had restenosis were defined as those needing a second revascularization at a site revascularized at the initial procedure. The 1-year clinical outcome of the nonrestenotic group (n=437) was compared with those who underwent CABG (n=453). There was no difference in deaths. In the nonrestenotic PTCA group, the incidence of more infarctions was insignificant (relative risk [RR] 1.9, 95% confidence intervals [CI] 0.96 to 3.75, p=0.064), there was a much greater need for repeat revascularization (RR 8.6, CI 5.14 to 14.41, p <0.0005), and patients had a poorer angina status (RR 1.46, CI 1.01 to 2.13, p=0.046). Using 2 measures of coronary disease, the degree of pre- and postrevascularization disease was compared between groups. There were no differences in prerevascularization disease. However, using either measure, residual postrevascularization disease was more frequent in the nonrestenotic PTCA group. Restenosis only partially accounts for the greater morbidity seen after PTCA, compared with CABG, in multivessel disease. The greater likelihood of residual disease post-PTCA may contribute to this greater morbidity.

Simplified method for compression of femoral false aneurysms.

False aneurysm formation is a not uncommon complication of cardiac catheterization. Until recently, surgical repair was the only therapeutic option available when conservative management failed. However, Doppler-guided compression of the aneurysm has been advocated in recent years; the method requires prolonged indirect manual compression of the femoral artery aneurysm and is uncomfortable for both the patient and operator. In ten consecutive patients the use of Doppler-guided clamp placement and aneurysm compression for 60 min resulted in complete thrombosis of the aneurysm in eight, and only one patient required surgical repair. The procedure was well tolerated by all patients (analgesia was administered liberally). Eight patients were discharged within 24 h, one after 2 days and the single surgical patient remained an inpatient for 6 days. Doppler-guided clamp compression of false aneurysms is a safe, effective and cost effective method of managing these patients.

Late endothelial function of free and pedicled internal mammary artery grafts.

The internal mammary artery has greater long-term patency than the saphenous vein when used for coronary bypass grafting. Therefore, bilateral use of the internal mammary artery for grafting with the right internal mammary artery used as a "free" graft may result in improved graft survival. The study objectives were to compare the endothelial-dependent and -independent vasodilatory response in free and pedicled internal mammary artery grafts in patients who had previously undergone coronary surgery. Free (group 1, n = 8) and pedicled (group 2, n = 7) internal mammary artery grafts were studied by comparing the response to selective infusion of the endothelial-dependent vasodilator substance P (1.4 up to 22.4 pmol/min in doubling dose increments) followed by isosorbide dinitrate (2 mg over 2 minutes), in patients undergoing coronary angiography, 1 month to 6 years after coronary surgery. Maximal dilatory response to substance P was 8.7% +/- 1.8% in pedicled grafts compared with 8.8% +/- 2.3% in free grafts (p = not significant), with the dose response for both groups being similar. Infusion of isosorbide dinitrate produced only minimal further dilatation in both groups. No significant difference was found in endothelium-dependent and -independent vasodilatory response between free and pedicled internal mammary artery grafts, suggesting that the use of the free right internal mammary artery and other arterial grafts may enhance graft survival.

Direct relationship between ischaemic burden and myocardial release of products of lipid peroxidation in patients undergoing percutaneous transluminal coronary angioplasty.

BACKGROUND: Recent studies have shown that free radical activity is increased in humans during percutaneous transluminal coronary angioplasty. These studies, however, have failed to localize the site of free radical activity or to demonstrate a relationship between ischaemic burden and free radical production. METHODS: The relationship between ischaemic burden and subsequent lipid peroxidation was studied during 16 inflations in eight patients undergoing angioplasty to anterior descending artery lesions. Two inflations 15 min apart were studied in each patient, one using a conventional (occlusive) balloon and one using the ACS Rx 'perfusion' balloon. The severity of the ischaemic insult associated with each inflation was assessed by contrast ventriculography, change in left ventricular end-diastolic pressure and myocardial lactate release 30 s after balloon deflation. Plasma levels of lipid peroxidation products were assessed by analysis of thiobarbituric-acid-reactive substances. RESULTS: A direct relationship was observed between the ischaemic burden and the myocardial release of lipid peroxidation products over the first 4 min after balloon deflation (F = 5.6; P < 0.006). In each patient, one of the inflations was associated with a greater degree of ischaemia. Left ventricular ejection fraction was lower (P < 0.001) and left ventricular end-diastolic pressure was higher (P < 0.002) during the 'ischaemic' inflations. Myocardial release of lipid peroxidation products was significantly higher after the 'ischaemic' balloon inflation (F = 7.65; P < 0.009). CONCLUSION: Brief periods of human myocardial ischaemia result in myocardial release of lipid peroxidation products in direct proportion to the severity of the preceding ischaemic insult.

Haemodynamic deterioration after treatment with adenosine.

A 26 year old woman presented with a narrow complex tachycardia with a rate of 210 beats/min. Adenosine converted this to atrial fibrillation with a rate of 280 beats/min with associated haemodynamic deterioration that needed electrical cardioversion.

Allopurinol pretreatment improves postoperative recovery and reduces lipid peroxidation in patients undergoing coronary artery bypass grafting.

In this prospective, randomized, double-blind, placebo-controlled study, the clinical, biochemical, and hemodynamic effects of xanthine oxidase inhibition in patients undergoing coronary artery bypass grafting were assessed. Allopurinol pretreatment significantly reduced the use of inotropic support after the operation (5 of 25 patients versus 13 of 25 patients, p < 0.01) and increased the rate of peripheral warming (11.4 +/- 0.85 hours versus 14.4 +/- 1 hours, p < 0.02). Twenty patients (9 in the allopurinol group and 11 in the placebo group) underwent invasive hemodynamic monitoring and intraoperative coronary sinus cannulation. The cardiac indexes of both groups were similar before the operation and for the first postoperative hour; thereafter, the cardiac index increased significantly in only the active treatment group (F = 3.33 and df = 5.90, p < 0.004). Products of lipid peroxidation (thiobarbituric acid reactive substances) increased significantly in only the placebo group, with increases being evident both in the systemic circulation (9.5 +/- 3.2 nmol/gm albumin, p < 0.007, and 24 +/- 5 nmol/gm albumin, p < 0.001, at 30 seconds and 2 minutes of reperfusion, respectively) and the coronary sinus (19.4 +/- 5.8 nmol/gm albumin, p < 0.004, and 28 +/- 4 nmol/gm albumin, p < 0.001, at 2 and 5 minutes of reperfusion, respectively. No significant difference was evident between the groups with respect to cardiac enzyme or vitamin E release. It is proposed that xanthine oxidase inhibition exerts its beneficial effects by reducing the level of free radical activity associated with reperfusion during coronary artery bypass grafting.

Lipid peroxidation and changes in vitamin E levels during coronary artery bypass grafting.

The effects of ischemia and reperfusion on arterial and coronary sinus vitamin E and thiobarbituric acid reactive substance levels were investigated in 10 patients undergoing routine coronary artery bypass grafting. Serial sampling was performed during bypass operations, before the initial period of crossclamping and at 30 seconds and 2, 5, and 10 minutes after final crossclamp removal. A net myocardial loss of vitamin E occurred in the first 5 minutes of myocardial reperfusion (0.84 +/- 0.21 mumol/mmol cholesterol; p < 0.01). Myocardial vitamin E loss correlated positively with the total crossclamp time (rho = -0.695; p < 0.05) but was independent of cardiac enzyme release and duration of cardiopulmonary bypass. The concentration of thiobarbituric acid reactive substance rose significantly in the systemic circulation (+14 nmol/gm albumin; F > 17; p < 0.002) at 2 and 5 minutes after crossclamp removal. A significant increase of thiobarbituric acid reactive substance levels was also found in the coronary sinus blood 10 minutes after crossclamp removal (+8 nmol/gm albumin; F > 14; p < 0.004). However, there was no net arterial-coronary sinus difference in thiobarbituric acid reactive substance levels. The change in arterial thiobarbituric acid reactive substance levels in each patient was inversely correlated with their control vitamin E level (F = 9.53; p < 0.01). Our findings suggest that systemic lipid peroxidation occurs during bypass and that vitamin E may play a protective role during routine bypass grafting by attenuating the degree of peroxidative damage.

The use of intra-aortic balloon counterpulsation in malignant ventricular arrhythmias.

We describe a patient with recurrent ventricular arrhythmias post anterior myocardial infarction who stabilised following intra-aortic balloon counterpulsation. Antiarrhythmic drugs and continuous ventricular pacing were ineffective. The possible mechanisms of the improvement with counterpulsation and other treatment options are discussed.

Doppler examination of superior vena caval flow for the detection of acute cardiac rejection.

BACKGROUND: Doppler echocardiographic studies have previously documented abnormalities of mitral flow during acute rejection similar to those seen in patients with "restrictive" physiology. As central venous flow is known to be abnormal in such patients, it was proposed that examination of superior vena caval flow with Doppler echocardiography might be useful for the detection of acute cardiac rejection. METHODS AND RESULTS: Thirty orthotopic cardiac transplant patients, 15 of whom had acute cardiac rejection diagnosed by endomyocardial biopsy, were studied within 36 hours of biopsy. Superior vena caval Doppler flow velocities as well as mitral and tricuspid flow velocities were recorded using a Hewlett-Packard Sonos 500/1000 echocardiograph system. Examinations were performed blinded to the biopsy result. Mitral and tricuspid peak early flow velocities in the nonrejector group were similar to those seen in normal subjects (mitral, 70 +/- 5 cm/sec; tricuspid midexpiratory apnea, 50 +/- 11 cm/sec). Superior vena caval flow was abnormal with 13 of 15 patients demonstrating a biphasic pattern of forward flow with dominant diastolic flow. In the 15 patients with acute cardiac rejection, both mitral and tricuspid flow velocities developed a "restrictive"-type pattern with increased peak early flow velocities (mitral, 89 +/- 24 cm/sec; tricuspid midexpiratory apnea, 63 +/- 19 cm/sec; p < or = 0.05 versus nonrejectors) and decreased mitral early flow-velocity deceleration times (rejectors, 97 +/- 26 msec; nonrejectors, 144 +/- 41 msec; p < or = 0.05). The pattern of superior vena caval flow became markedly abnormal with a virtually complete loss of forward systolic flow (rejectors, 4.4 +/- 6.6 cm/sec; nonrejectors, 26.1 +/- 8.8 cm/sec at midexpiratory apnea; p < or = 0.0001). In 10 of 15 patients, systolic forward flow was absent. If acute rejection was defined as forward systolic flow < or = 17 cm/sec, then sensitivity was 100%, specificity was 80%, and predictive accuracy was 90%. CONCLUSIONS: During acute cardiac rejection, forward systolic superior vena caval flow is markedly diminished compared with nonrejectors. This is accompanied by other Doppler echocardiographic features consistent with the development of "restrictive" physiology. It is postulated that the loss of forward systolic flow in the superior vena cava is due to diminished long-axis shortening of the right ventricle associated with acute cardiac rejection.

Paradoxical early lengthening and subsequent linear shortening of the QT interval in response to exercise.

The QT responses to exercise during ventricular pacing were evaluated in 12 patients in whom permanent pacemakers were implanted for complete heart block. The initial response of the QT to exercise was a paradoxical lengthening during the first minute of exercise (mean 4.8 ms P < 0.01). Thereafter, the QT was found to shorten in a linear fashion in response to increasing exercise, both in terms of exercise duration (r = 0.787; P < 0.001) and atrial rate (r = 0.712; P < 0.001). The total QT shortening with exercise was small (20 ms for a mean increase in atrial rate of 60 beats.min-1) and displayed substantial inter-individual variability (9-31 ms). These results explain some of the limitations of the QT pacemaker, and provide insights in to the dynamics of the QT response, which may help tailor the programming of these systems to the individual patient.

Oral treatment with enoximone in patients referred for cardiac transplantation.

A prospective, uncontrolled, open ended study was performed to assess the effect of treatment with oral enoximone therapy in patients with end stage cardiac failure unresponsive to conventional treatment. The primary objective of treatment, hospital discharge, was achieved in 27 of 35 patients studied. Baseline haemodynamics were obtained in 21 patients. The mean cardiac index of patients who improved by one or more grades (New York Heart Association) was 2.1 litres/min while, in those who had less improvement, the mean cardiac index was 1.5 l/min (P less than 0.01). The average duration of treatment was 13 weeks, treatment being discontinued in 25 patients within twelve weeks. The main reasons for discontinuation were side effects (n = 11), and progressive cardiac failure (n = 7). The prognosis of patients in whom therapy was discontinued was very poor, only 5 of 28 being discharged from hospital without cardiac transplantation. Sudden death was uncommon (1/13), and Holter monitoring in 17 showed no aggravation of ventricular arrhythmias. Oral treatment with enoximone is a useful adjunct in the treatment of end stage cardiac failure.