Acute changes in atrial natriuretic peptide, insulin-like growth factor-1, and lactate levels during left anterior descending coronary artery angioplasty.

This study examines acute changes in circulating levels of atrial natriuretic peptide (ANP) and insulin-like growth factor (IGF-1) during short periods of myocardial ischemia experienced at coronary angioplasty. Ten patients (mean age 55.7 +/- 3.9 years, nine men) undergoing angioplasty to the left anterior descending coronary artery were studied. Angioplasty of the left anterior descending coronary artery was performed with the balloon inflations maintained at 6 to 10 atm for 20 to 90 seconds. Blood was sampled from the coronary sinus for ANP, IGF-1 (both total and free), and lactate levels at (1) after catheterization of the coronary sinus, (2) after the initial left coronary angiography, (3) immediately after balloon deflation, and (4) 5 minutes after deflation. ANP levels (pmol/L +/- SEM) rose significantly at the end of balloon deflation (13.4 +/- 2.8; p < 0.01) compared with baseline levels (8.8 +/- 1.9). This rise was sustained for at least 5 minutes after balloon deflation (13.7 +/- 3.1; p < 0.01). ANP levels were not affected by the injections of angiographic contrast media. Free IGF-1 levels rose after injections of radiographic contrast but not after balloon inflation or deflation. Total IGF-1 levels did not change significantly at any of the sampling times. Lactic acid (mmol/L) levels rose at the end of balloon inflation (2.66 +/- 0.6) compared with baseline (2.13 +/- 0.7; p < 0.05) but returned to normal within 5 minutes of balloon deflation. Neither lactic acid levels nor release of ANP or IGF-1 correlated with the initial left ventricular end-diastolic pressure or the degree of electrocardiographic ST depression during the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular manifestations of Marfan's syndrome: improved evaluation by transoesophageal echocardiography.

OBJECTIVES: To assess the value of transoesophageal echocardiography in patients with Marfan syndrome particularly those with suspected aortic pathology or where conventional transthoracic imaging was suboptimal. DESIGN AND PATIENTS: Eleven patients with Marfan syndrome. Seven patients were studied because of suspected aortic dissection and four because of inadequate transthoracic imaging. INTERVENTION: Transoesophageal echocardiography and colour Doppler flow mapping by a 5 MHz single plane transoesophageal probe. RESULTS: Aortic dissection was identified in six patients with subsequent diagnostic confirmation in all six. No dissection was found in one patient in whom the diagnosis had been suspected clinically. Estimates of aortic root dimensions and assessment of aortic and mitral valve pathology were made in four other patients with inadequate transthoracic imaging. CONCLUSIONS: Transoesophageal echocardiography provides rapid diagnostic information in patients with Marfan syndrome with suspected aortic dissection and enhances the assessment of cardiovascular manifestations of this condition.

Transoesophageal echocardiography in the diagnosis of paradoxical embolism.

Two patients with systemic embolism were studied with transoesophageal contrast echocardiography which demonstrated its probable paradoxical nature. In both cases paradoxical embolism was associated with pulmonary embolism. Precordial contrast echocardiography demonstrated a right-to-left shunt in one patient but was unable to demonstrate a shunt in the second. Transoesophageal echocardiography suggested that the shunt was across a patent foramen oval in both cases and revealed large thrombi in the pulmonary arteries in one. When precordial contrast echocardiography reveals a right-to-left shunt or when it is technically inadequate in patients suspected of having one, transoesophageal contrast echocardiography can demonstrate the nature of the shunt and is an alternative to cardiac catheterisation techniques. In addition, it can reveal large thrombi in the pulmonary arteries.

Major complications of coronary arteriography: the place of cardiac surgery.

The records of the catheter laboratory at St George's Hospital between 1983-1988 were reviewed to determine how often emergency coronary bypass surgery was performed because of a complication arising during elective coronary arteriography. A total of 11,216 cardiac procedures were performed; 5781 were confined to left ventricular angiography and coronary arteriography in patients with suspected coronary artery disease. Fourteen patients, whose investigation had been considered routine, suffered profound circulatory collapse during the procedure. Emergency cardiac surgery was undertaken in 13, with long term survival in 10. This experience suggests that, even in patients considered to be at low risk, there were major complications requiring emergency coronary surgery in at least 2.4 per 1000 coronary arteriograms performed. Survival after emergency cardiac surgery in these patients was 77%. These findings and the access to cardiac surgery should be considered when the development of facilities for cardiac catheterisation is planned.

Relative power of clinical, exercise test, and angiographic variables in predicting clinical outcome after myocardial infarction: the Newham and Tower Hamlets study.

The interrelations of clinical, exercise test, and angiographic variables and their relative values in predicting specific clinical outcomes after myocardial infarction have not been fully established. Of 302 consecutive stable survivors of infarction, 262 performed a predischarge submaximal exercise test. In the first year after infarction patients with a "positive" exercise test were 13 times more likely to die, 2.8 times more likely to have an ischaemic event, and 2.3 times more likely to develop left ventricular failure than patients with negative tests. Patients with positive exercise tests underwent cardiac catheterization. Features of the history, 12 lead electrocardiogram, in-hospital clinical course, exercise test, and left ventricular and coronary angiograms that predicted these clinical end points were identified by univariate analysis. Then multivariable analysis was used to assess the relative powers of all variables in predicting end points. Certain features of the exercise test remained independent predictors of future ischaemic events and the development of overt left ventricular failure, but clinical and angiographic variables were more powerful predictors of mortality. Because the exercise test is also used to select patients for angiography, however, the results of this study strongly support the use of early submaximal exercise testing after infarction.

Rupture of the sinus of Valsalva during pregnancy.

A case is described in which rupture of the right sinus of Valsalva occurred at 37 weeks' gestation. The ruptured sinus was successfully repaired one week after the delivery of a healthy infant by caesarean section.

Aortic dissection during pregnancy.

Aortic dissection occurred in a nineteen year old woman during the thirty seventh week of pregnancy. Immediate elective delivery of a normal baby by caesarean section was followed by aortic root replacement 48 hours later. It was decided not to proceed immediately to operation on the aortic root because it was believed that the anticoagulation necessary for cardiopulmonary bypass might provoke dangerous haemorrhage from the raw placental site.

The platelet release reaction in cardiovascular disease: evaluation of plasma betathromboglobulin as a marker of a prothrombotic state.

Plasma betathromboglobulin as a marker of in vivo platelet release was found to be significantly higher in 131 patients with prosthetic cardiac valves and 104 patients with coronary artery disease, compared with 133 normal individuals. Patients with double mechanical valves had a higher mean betathromboglobulin than those with single mechanical valves, who in turn had higher values than those with single heterograft valves. Thirteen patients adequately anticoagulated at the time of a thromboembolic event had significantly higher betathromboglobulin levels than 5 with thromboemboli when not anticoagulated, suggesting platelets were responsible for the emboli in the former group. The presence of coronary risk factors in normal individuals did not affect betathromboglobulin; however, when two or more risk factors were present in patients with ischaemic heart disease, mean betathromboglobulin was higher than when only one or no risk factors were present. This suggests greater platelet activation in the presence of more widespread atherosclerotic disease. Thus mean plasma betathromboglobulin is higher in groups of patients with disorders known to have thrombotic complications, but the wide range of values, which overlap with normals, prevent the clinical interpretation of the plasma betathromboglobulin level found in any individual patient.

Aortic and mitral valve incompetence: long-term follow-up (10 to 19 years) of patients treated with the Starr-Edwards prosthesis.

The long-term course (mean 15 years) of 336 patients with valvular incompetence who underwent Starr-Edwards ball valve implantation between 1962 and 1971 was reviewed. Eighteen patients (10%) with aortic valve replacement and 24 (16%) with mitral valve replacement died early postoperatively. Mortality remained high (31%) in the first 3 years after aortic valve replacement; it was highest (13%) in the first year after mitral valve replacement and then approached the normal rate. The most common mode of death was sudden death after aortic and cardiac failure after mitral valve replacement. At follow-up, 76% of survivors had improved symptomatically. Three instances of primary valve malfunction occurred. The probability of freedom from thromboembolism at 15 years postoperatively was 56% for aortic valve replacement and 52% for mitral valve replacement. The Starr-Edwards valve prosthesis is durable over prolonged follow-up period, but thromboembolism remains a persistent problem. Survival may be normal for patients surviving the early postoperative years.

Platelet alpha granule depletion: findings in patients with prosthetic heart valves and following cardiopulmonary bypass surgery.

The alpha granule content of platelets, as indicated by the amount of beta-thromboglobulin (beta-TG) in lysed platelet rich plasma was measured to determine whether platelet stimulation resulted in a circulating population of granule-depleted platelets. In 101 normal controls, with a mean platelet count of 242.6 +/- 6.5 X 10(9)/1, the mean platelet beta-TG content was 55.9 +/- 1.2 ng/10(6) platelets. There was a significant reduction in both these parameters (mean platelet count 195.5 +/- 5.8 X 10(9)/1 (P less than 0.001), mean platelet beta-TG 50.0 +/- 1.2 ng/10(6) platelets (P less than 0.01)) in 74 patients with prosthetic cardiac valves. In 24 patients, cardiopulmonary bypass surgery caused a much greater reduction in median platelet count from 210 X 10(9)/1 to 11.1 X 10(9)/1, two hours after surgery (P less than 0.001) but no overall change in platelet beta-TG. However, five patients who experienced diffuse haemorrhage in the postoperative period had a lower median platelet beta-TG (35.5 ng/10(6) platelets) than the other 19 patients (51.0 ng/10(6) platelets) (P less than 0.05).

In vivo quantitation of platelet deposition on human peripheral arterial bypass grafts using indium-111-labeled platelets. Effect of dipyridamole and aspirin.

Indium-111-labeled autologous platelets, injected 48 hours after operation, were used to evaluate the thrombogenicity of prosthetic material and the effect of platelet inhibitor therapy in vivo. Dacron double-velour (Microvel) aortofemoral artery bifurcation grafts were placed in 16 patients and unilateral polytetrafluoroethylene femoropopliteal grafts were placed in 10 patients. Half the patients in each group received platelet inhibitors before operation (dipyridamole, 100 mg 4 times a day) and after operation (dipyridamole, 75 mg, and acetylsalicylic acid, 325 mg 3 times a day); the rest of the patients served as control subjects. Five-minute scintigrams of the graft region were taken with a gamma camera interfaced with a computer 48, 72, and 96 hours after injection of the labeled platelets. Platelet deposition was estimated from the radioactivities of the grafts and expressed as counts per 100 pixels per microcurie injected. Dipyridamole and aspirin therapy significantly reduced the number of platelets deposited on Dacron grafts and prevented platelet accumulation over 3 days. With the small amount of platelet deposition on polytetrafluoroethylene femoropopliteal artery grafts even in control patients, platelet inhibitor therapy had no demonstrable effect on platelet deposition on these grafts. It is concluded that (1) platelet deposition on vascular grafts in vivo can be quantitated by noninvasive methods, and (2) dipyridamole and aspirin therapy reduced platelet deposition on Dacron aortofemoral artery grafts.

Comparison of the antithrombotic action of calcium antagonist drugs with dipyridamole in dogs.

Because platelet activation is associated with fluxes of intracellular calcium, calcium antagonist drugs such as verapamil and nifedipine may have useful platelet inhibitor effects. Accordingly, the effect of these drugs was compared with that of dipyridamole, an established platelet inhibitor, in preventing the deposition of indium-111-labeled autologous platelets and thrombus development in polytetrafluoroethylene (Gore-Tex) grafts interposed in both femoral arteries in mongrel dogs. Eight dogs received verapamil 7.5 micrograms/kg/min perioperatively, 8 dogs received nifedipine 4 micrograms/kg/h perioperatively, 8 dogs received dipyridamole 50 mg orally given twice during the 24 hours before operation, and 16 control dogs received isotonic saline solution perioperatively. After 3 hours of perfusion, the median weight of the grafts and luminal thrombus was less in dogs treated with dipyridamole (465.1 mg), verapamil (453.7 mg), or nifedipine (389.7 mg) than in control dogs (680.2 mg) (p less than 0.001). In addition, the estimated total platelet deposition along the graft was reduced in dogs treated with dipyridamole was reduced in dogs treated with dipyridamole (2,073.2 X 10(6)) (p less than 0.01), verapamil (1,898.9 X 10(6)) (p less than 0.001), and nifedipine (1,474.8 X 10(6)) (p less than 0.001) as compared with controls (3,056.2 X 10(6)). When the mural thrombus was removed from 14 grafts, a median 73% of the platelets were located in the interface between thrombus and graft. We conclude that all 3 drugs prevent thrombus formation by inhibiting platelet activity in this model, and that the calcium antagonist drugs are as effective as dipyridamole.

A new in vivo model of arterial thrombosis: the effect of administration of ticlopidine and verapamil in dogs.

An in vivo model of arterial thrombosis was developed in which either polytetrafluoroethylene (PTFE [Gore-Tex]) or autologous vein grafts were used to replace a segment of the femoral arteries of dogs. In one series of studies, 5 cm of PTFE and 5 cm of autologous femoral vein were used in each animal and blood flow was resumed for 1 hour. 111In-labeled autologous platelets accumulated in greater amounts on the PTFE grafts (93.6 X 10(6) platelets/cm) than on the vein grafts (2.6 X 10(6) platelets/cm) (P less than 0.001). Orally administered ticlopidine (30 mg/kg/day for 2 days), an established inhibitor of platelets, reduced platelet deposition on the PTFE grafts to 10.5 X 10(6) platelets/cm (P less than 0.01). In a second series of studies, PTFE grafts were interposed on both sides in each animal, and blood flow was resumed for 3 hours. With intravenously administered verapamil, a calcium antagonist, given perioperatively at 7.5 ug/kg/min, 12 of 16 grafts in eight dogs were patent compared with only 2 of 16 grafts in eight control dogs (P less than 0.001). Furthermore, platelet deposition on the grafts was reduced from 1,090 X 10(6) platelets/cm to 303 X 10(6) platelets/cm (P less than 0.001). Thus, both ticlopidine and verapamil are effective antithrombotic agents as a result of their inhibition of platelet activity in this model, and these results provide further evidence of a central role for calcium in platelet activation.

Plasma beta-thromboglobulin as a measure of platelet activity. Effect of risk factors and findings in ischemic heart disease and after acute myocardial infarction.

The plasma concentration of beta-thromboglobulin (BTG), a platelet-specific protein released during platelet aggregation, is considered a sensitive marker of in vivo platelet activity. The mean plasma level in 133 asymptomatic individuals was 32.3 +/- 1.1 ng/ml, and there was no difference between those with no risk factors (32.2 +/- 1.2 ng/ml, n = 56), those who smoked (31.8 +/- 1.8 ng/ml, n = 45), those with hyperlipidemia (32.8 +/- 1.7 ng/ml, n = 15), and those exposed to both of these risk factors (34.1 +/- 2.7 ng/ml, n = 17). The mean plasma BTG level in 104 patients with symptomatic ischemic heart disease was significantly elevated (40.9 +/- 1.4 ng/ml, p less than 0.01), but there was considerable overlap with normal levels. Although no difference was found between patients with no risk factors (38.1 +/- 4.0 ng/ml, n = 13) and those with only 1 risk factor (37.0 +/- 1.8 ng/ml, n = 44), patients with 2 or more risk factors ahd a significantly elevated plasma BTG level (45.2 +/- 2.2 ng/nl, n = 47, p less than 0.01). It is concluded that risk factors themselves do not increase platelet activity, but that patients with vascular disease have activated platelets that may contribute to the progression of the disease. Plasma BTG was also measured serially for 10 days in 29 patients after hospitalization with acute ischemic cardiac pain. Although the median plasma level was elevated above normal there were no acute changes in plasma BTG after either acute infarction (n = 22) or acute ischemia (n = 7), except in 2 patients in whom pericardial friction rubs developed. Thus, measurement of systemic plasma BTG did not detect platelet involvement in acute coronary occlusion or acute ischemia.

Systemic thromboembolism in mitral and aortic Starr-Edwards prostheses: a 10-19 year follow-up.

Our study comprised 302 consecutive patients seen between 1962 and 1971 who underwent mitral (MVR) (132 patients) or aortic valve replacement (AVR) (170 patients) with a Starr-Edwards prosthesis because of advanced mitral or aortic incompetence. The follow-up interval was 10-19 years. For more recent valve models (1200/1260 aortic or 6120/6310 mitral), the probability of a surviving patient remaining free of systemic thromboembolism after 10 years was 70% for MVR and 74% for AVR. The probability of freedom from thromboembolism was less than this for the earlier valve models; the probability for the entire group at 10 years was 66% and at 15 years was 58%, with no significant difference between AVR and MVR. About one-fourth of the patients with an embolism (20% MVR, 27% AVR) had more than one embolic event. Of all emboli, most (86% MVR, 84% AVR) were cerebral, about half (48% MVR, 57% AVR) left a neurologic deficit, and about one-tenth (11% MVR, 10% AVR) led to death. Of the predictive factors reviewed, the incidence of emboli was significantly higher only in patients with MVR considered to have inadequate anticoagulation (p less than 0.01) and in patients receiving model 6000 mitral prosthesis (p less than 0.02). This long-term follow-up study of patients with a Starr-Edwards prosthesis reveals that systemic embolism is a persistent and significant problem.