D E Jewitt

Coronary artery perforation during percutaneous intervention: incidence and outcome

Objective: To examine the clinical outcome of percutaneous coronary intervention where the procedure was complicated by vessel perforation. Setting: Tertiary referral centre. Methods: The procedural records of 6245 patients undergoing coronary intervention were reviewed. In 52 patients (0.8%) the procedure was complicated by vessel perforation, ranging from wire exit to free flow of contrast into the pericardial space. The majority of lesions treated were complex (37% type B, 59% type C) and 9 of 52 (17%) were chronic occlusions. Ten patients (19%) received abciximab. Four underwent rotational atherectomy (8%). Results: In 28 of 52 patients (54%) the perforation was benign and managed conservatively without the development of haemodynamically significant sequelae. In 24 of 52 (46%) a significant pericardial effusion ensued requiring drainage. Of these 24 procedures 6 had involved the treatment of a chronic occlusion (25%). Eight of the 24 patients were referred for emergency bypass surgery (33%), 3 of whom died. Of the remaining 16 not referred for surgery, 3 died. Of the 10 procedures complicated by vessel perforation where abciximab had been administered, 9 (90%) led to pericardial tamponade. Latterly 2 vessel perforations were successfully treated by the deployment of a covered stent. Conclusions: Coronary artery perforation with sequelae during intervention is rare—26 of 6245 (0.4%). This complication was seen in the treatment of chronic occlusions, which are therefore not risk-free procedures. The development of pericardial tamponade carries a high mortality. While prompt surgical intervention may be life saving, expertise in the use of covered stents may provide a valuable rescue option for this serious complication. Caution should be exercised where coronary perforation occurs and abciximab has been used.

β-Adrenergic Receptor Blocking Drugs in Cardiac Arrhythmias

Summaryβ-Adrenergic receptor blocking (β-blocking) drugs now have an established place in the elective and prophylactic treatment of many cardiac arrhythmias. In isolated preparations of heart muscle, these drugs inhibit spontaneous diastolic depolarisation and in high concentrations which are unlikely to have clinical relevance, they exhibit membrane-depressant properties. In intact animals and man they slow the rate of discharge of the sinus and ectopic cardiac pacemakers and increase the functional refractory period of the AV node. They also retard conduction, both anterograde as well as retrograde, in anomalous pathways of the heart.Sinus tachycardia responds well to β-blocking drugs but they are particularly useful in atrial fibrillation in which their effect in reducing the ventricular rate by producing AV block is additive to that of digitalis. They do not, however, alter the atrial rate and sinus rhythm is restored in only a small number of cases. In atrial flutter, sinus rhythm is produced more frequently, but the usual response in this arrhythmia is an increase in AV block which may be useful as a diagnostic test in a complicated tachycardia.Reversion of paroxysmal supraventricular tachycardias is frequently produced by β-adrenergic receptor antagonists which are also effective in reducing the frequency of recurrences especially in the Wolff-Parkinson-White syndrome. They are the drugs of choice in this situation. Digitalis-induced tachyarrhythmias respond well to β-blocking drugs as do arrhythmias provoked by exercise or by paroxysmal release of catecholamines in phaeochromocytoma. Resistant arrhythmias after acute myocardial infarction, cardiac surgery, or from other causes, may respond to β-blocking drugs especially when they are combined with other antiarrhythmic drugs or electrical pacing. Supraventricular and ventricular arrhythmias following acute myocardial infarction respond well to elective treatment with intravenous β-blocking drugs, but when these drugs are given orally for prophylaxis there is no reduction in acute mortality.Pre-treatment with β-blocking drugs of patients having atrial fibrillation does not improve the conversion rate following DC countershock. Similarly, when they are given prophylactically to patients following successful cardioversion, relapse rate is not reduced except in combination with quinidine. β-Blocking drugs have been found useful in the treatment of arrhythmias occurring during anaesthesia and in the elimination of extrasystoles in patients during artificial cardiac pacemaking.Clinical and experimental evidence tends to support the view that β-blockade is the main determinant of the antiarrhythmic action of β-adrenergic receptor blocking drugs. Their membrane-depressant properties appear to be irrelevant in most clinical situations. Thus, propranolol, oxprenolol, alprenolol, pindolol and practolol are all likely to have comparable antiarrhythmic potencies in adequate doses, and the therapeutic superiority of one agent over another is likely to be related essentially to the frequency of side-effects with the different drugs. Aggravation of heart failure and the development of atrioventricular block or airways obstruction, are the most frequent unwanted side-effects of β-blocking drugs used in antiarrhythmic therapy. Practolol, at present, is the only cardio selective compound and is less likely than other β-blocking drugs to cause airways obstruction. It also seems the least likely to cause severe haemodynamic depression and in situations where airways obstruction or cardiac decompensation are present, it is preferred to the conventional agents such as propranolol, oxprenolol, alprenolol and pindolol.

Prostacyclin: haemodynamic and metabolic effects in patients with coronary artery disease.

The therapeutic potential of prostacyclin was evaluated in 10 patients with angina pectoris and angiographically proved coronary artery disease. Platelet aggregation and coronary and systemic haemodynamic effects were examined before and after intravenous infusions of 2, 4, 6, and 8 ng/kg/min of prostacyclin and were dose related. At 8 ng/kg/min the ADP concentration required to induce 50% of maximum platelet aggregation increased from 1.8 to 4.5 mumol/l (p less than 0.001). Heart rate and cardiac index rose from 77 to 93 beats/min and 2.47 to 3.48 l/min/m2, respectively (p less than 0.01). Mean blood pressure and systemic and pulmonary resistances fell from 107 to 92 mm Hg and 1704 to 1048 and 80 to 45 dyn s cm-5, respectively (p less than 0.01). Coronary vascular resistance also fell from 0.95 to 0.73 units (p less than 0.01). Mean atrial pacing time to angina rose from 142 to 241 s (p less than 0.05), while lactate production during rapid atrial pacing was decreased, lactate extraction ratio rising from -25 to -9% (p less than 0.05). These coronary and systemic vasodilator effects and the prolongation of pacing time to angina indicate an acute beneficial effect of prostacyclin on angina. Since prostacyclin has been shown to prevent platelet accumulation and progression to total occlusion in animals with experimental coronary stenoses, the observed inhibition of platelet aggregation suggests that prostacyclin should be further evaluated in unstable angina.

Evaluation of myocardial, hepatic, and renal perfusion in a variety of clinical conditions using an intravenous ultrasound contrast agent (Optison) and second harmonic imaging

OBJECTIVE To assess the potential of intravenous Optison, a second generation ultrasound contrast agent, and various ultrasound imaging modes to determine myocardial, kidney, and liver perfusion in normal subjects and patients with left ventricular dysfunction or chronic pulmonary disease together with renal or hepatic dysfunction. METHODS Five normal subjects and 20 patients underwent grey scale echocardiographic imaging of myocardium, kidney, and liver during 505 intravenous injections of Optison. Images were assessed qualitatively by two independent observers and quantitatively using video densitometry to determine the peak contrast enhancement effect. RESULTS Qualitative analysis showed that intermittent harmonic imaging was superior to either conventional fundamental or continuous harmonic imaging for all organs. Quantitative analysis showed that the peak change in echocardiographic intensity v baseline during continuous harmonic imaging was 11 units for myocardium (p < 0.03), 7 units for kidney (NS), and 14 units for liver (p < 0.05). During intermittent harmonic imaging the peak change was significantly greater, being 33 units for myocardium (p < 0.0001), 24 units for kidney (p < 0.0002), and 16 units for liver (p < 0.001). CONCLUSIONS Organ tissue perfusion can be demonstrated following intravenous injection of Optison, particularly when used in combination with intermittent harmonic imaging techniques. This contrast agent is effective in a variety of clinical conditions.

Effects of vasodilator treatment with felodipine on haemodynamic responses to treadmill exercise in congestive heart failure.

Treatment with vasodilators in heart failure has not always produced a useful improvement in the haemodynamic responses to exercise, and in many cases early drug tolerance has further limited the potential of this type of treatment. In a study to evaluate the efficacy of felodipine, a new calcium antagonist with selective vasodilator properties, in the management of congestive heart failure 10 patients with congestive heart failure underwent treadmill exercise testing before and during oral treatment with felodipine 30 mg daily. At every level of exercise felodipine lowered the pulmonary capillary wedge pressure, whereas cardiac index and stroke index increased considerably. The haemodynamic improvement was associated with an increase in the duration of exercise to exhaustion. Importantly, these beneficial effects were sustained throughout four weeks of treatment without evidence of drug tolerance. These observations suggest a useful role for felodipine in the long term management of congestive heart failure.

Acute haemodynamic and metabolic effects of felodipine in congestive heart failure.

Felodipine is a new calcium antagonist with a high degree of vascular selectivity. To examine its potential value as an afterload reducing agent in congestive heart failure 11 patients were studied. Substantial increments in cardiac index were associated with a fall in systemic vascular resistance. Left ventricular end diastolic pressure was also significantly reduced. Although left ventricular maximum dP/dt remained unchanged, maximum dP/dt/P increased. Left ventricular unloading was reflected by a reduction in cavity dimensions and a shift in the relation between end systolic pressure and dimension downwards and to the left. The myocardial oxygen supply to demand ratio was also improved: coronary sinus flow increased significantly despite a decline in myocardial oxygen consumption. These beneficial haemodynamic and metabolic effects suggest that felodipine may extend the clinical application of calcium antagonists to include the treatment of congestive heart failure.

Randomised trial of elective stenting after successful percutaneous transluminal coronary angioplasty of occluded coronary arteries

Background The value of angioplasty in occluded coronary arteries is limited by a restenosis/reocclusion rate of 50–70%. In patients with subtotal occlusion, stent implantation has been shown to reduce clinical and angiographic restenosis. Retrospective observational studies have suggested that stenting could reduce restenosis in total occlusions. The value of sustained coronary patency on global and regional left ventricular function in this clinical setting has not been defined clearly. Objectives To assess the medium term effect of elective intracoronary stent deployment after successful percutaneous transluminal coronary angioplasty (PTCA) of an occluded coronary artery. Methods Sixty patients with a total coronary occlusion successfully treated by PTCA were randomised to receive an intracoronary stent or no stent. Patients underwent clinical and angiographic follow up at six months. Results Thirty patients received a stent (group A) and 30 were treated by angioplasty alone (group B), all with initial success. One patient in group B required repeat angioplasty with stenting at 24 hours and one patient died after 10 days. Angiographic follow up was available for 57 patients. This showed a significantly reduced reocclusion rate in group A compared with group B (7% v 29%, p < 0.01) and a tendency to a reduced restenosis rate (22% v 40%, p = 0.105) in patients with no reocclusion. Left ventricular function, both global and regional, improved in group A. Only the regional left ventricular function in the area supplied by the target coronary artery improved in group B. Recurrence of symptoms and clinical events such as repeat angioplasty, coronary artery bypass grafting, death or myocardial infarction tended to be reduced in group A (4 (13%) v 9 (30%)). Conclusions Intracoronary stent insertion is effective in reducing the rate of reocclusion and shows a trend towards reduced restenosis after opening of a total coronary occlusion by balloon angioplasty. Sustained patency of the target coronary artery is associated with improvement in global and regional left ventricular function.

Hemodynamic effects of newer antiarrhythmic drugs

The aim of antiarrhythmic drug therapy is to terminate or suppress specific arrhythmias and improve cardiovascular function. Short-term studies of the new Class I drugs encainide, mexilitine, and tocainide have demonstrated only minor falls in cardiac index with modest rises in mean aortic pressure. In contrast, disopyramide has been shown to depress myocardial function in both animals and patient studies. Heart failure may be precipitated by therapy with disopyramide and electromechanical dissociation has been reported. Class II agents with beta-adrenergic blocking actions all produce a degree of myocardial depression. Atenolol resembles propranolol in patients with coronary artery disease in its hemodyanmic effects, whereas acebutolol is less of a depressant, resembling practolol. The Class III agent amiodarone has only a mild depressant effect associated with a reduction in afterload and an increase in coronary blood flow. The Class IV agent verapamil, which is a calcium channel blocker, has potent myocardial depressant actions and causes peripheral vasodilatation. Hypotension, heart failure, and shock have been precipitated particularly in patients receiving beta-blocking drugs concurrently. While all the new antiarrhythmic drugs currently studied will cause some degree of hemodyanmic depression in an appropriately high concentration, present investigations suggest that particular caution needs to be taken when disopyramide, aprindine, atenolol, and verampamil are administered either acutely by the intravenous route or chronically by the oral route.

Beneficial effects of diltiazem and propranolol, alone and in combination, in patients with stable angina pectoris.

The antianginal effects of diltiazem 180 mg/day and propranolol 240 mg/day, alone and in combination, were investigated in 15 patients with effort related angina in a double blind placebo controlled crossover trial, with each period of treatment lasting four weeks. Patients performed a symptom limited treadmill exercise test at the end of each period of treatment. Mean (SEM) time to onset of angina was increased from 293(32) s when receiving placebo to 347(38) s when receiving diltiazem alone, to 350(30) s when receiving propranolol alone, and further to 421(34) s when receiving diltiazem and propranolol combined. Similar changes occurred in the duration of exercise testing and time to 1 mm ST segment depression. The sum of ST segment depression at peak exercise was reduced by both diltiazem and propranolol alone compared with placebo, and combination treatment produced a further significant improvement. Rate pressure product was significantly reduced at rest and at peak exercise after propranolol alone and combination treatment. The study clearly showed the superior value of diltiazem and propranolol combined in effort related angina when compared with either drug used alone.

Relation between alcohol intake, myocardial enzyme activity, and myocardial function in dilated cardiomyopathy. Evidence for the concept of alcohol induced heart muscle disease.

Detailed drinking histories were taken in 38 patients in whom dilated cardiomyopathy was diagnosed by cardiac catheterisation and left ventricular biopsy. On the basis of the drinking history twenty patients were classified as being in an abstinent or light drinking group and eighteen patients as being in a heavy drinking group (daily alcohol intake in excess of 80 g or cumulative lifetime intake exceeding 250 kg). Activities of myocardial creatine kinase, lactate dehydrogenase, alpha hydroxybutyric dehydrogenase, malic dehydrogenase, and aspartate amino-transferase were all higher in the heavy drinkers and myocardial enzyme activity correlated with cumulative lifetime alcohol intake, maximum daily intake, and recent daily intake. Activities of creatine kinase, alpha hydroxybutyric dehydrogenase, and malic dehydrogenase correlated with ejection fraction, irrespective of the alcohol intake of the patient. These findings were not altered by exclusion of patients with hypertension. The results indicate that among patients with dilated cardiomyopathy there is a group characterised by a high alcohol intake and raised myocardial tissue enzymes which supports the concept of alcoholic heart muscle disease as a distinct entity.