Axel Sigurdsson

Short- and long-term neurohormonal activation following acute myocardial infarction

Plasma levels of atrial natriuretic peptide (ANP), angiotensin II, aldosterone, and catecholamines were followed for 1 month and then for 4 to 6 months in 55 patients with acute myocardial infarction. Plasma hormones were highest within the first 24 hours after the onset of infarction but normalized during the first few days in patients without heart failure. In patients with symptoms of heart failure, angiotensin II and norepinephrine remained elevated for 1 month and ANP remained elevated for 4 to 6 months. During head-up tilt, angiotensin II and norepinephrine increased most in patients with overt heart failure. Among patients with a first myocardial infarction, a positive correlation was found between infarct size and ANP, angiotensin II, and norepinephrine on day 5 to 7 and between infarct size and angiotensin II during head-up tilt at 1 month, and between infarct size and ANP at 1 month. A similar relationship was found when only patients without heart failure were studied. It is concluded that sustained neurohormonal activation after myocardial infarction mainly occurs in patients with clinical heart failure but is related to the magnitude of myocardial damage, even in patients without heart failure. Measurement of neurohormones during head-up tilt may be an additive assessment for the detection of neurohormonal activation.

The role of neurohormonal activation in chronic heart failure and postmyocardial infarction

Chronic heart failure is a disabling and lethal disorder with high incidence and prevalence in Western societies. Treatment with angiotensin-converting enzyme (ACE) inhibitors and heart transplantations diminish both mortality and morbidity, although both still remain high. Increased understanding of some of the pathophysiologic mechanisms involved in the development of left ventricular dysfunction and the transition from asymptomatic systolic dysfunction to symptomatic heart failure has opened gates to new dimensions for the treatment of this disorder. The initial event in the pathophysiologic process is damage to the myocardium, most frequently a myocardial infarction. Almost simultaneously, activation of different neurohormonal systems occurs. The renin-angiotensin system and sympathetic nervous system are activated. Increased concentrations of hormones with counteractive activity have also been found, such as ANP and BNP. Interestingly, prolonged neurohormonal activation seems to occur only in patients with large infarcts or in patients with poor systolic function of the left ventricle. Moreover, available data from an echocardiographic study indicates that in patients with high concentrations of neurohormones in plasma a week after their infarction, left ventricular dilatation and systolic dysfunction of the left ventricle are highly likely to develop during long-term follow-up. Several studies have showed that ACE inhibitors are efficacious in chronic heart failure and among patients with reduced ejection fraction after myocardial infarction. What these patients have in common is prolonged neurohormonal activation, which theoretically may be harmful to myocardial cell structure and function. ACE inhibitors reduce the breakdown of angiotensin I to angiotensin II and increase the concentration of circulating bradykinins and prostaglandins. Further modulation of neurohormonal activity might be beneficial. Therefore, future treatment of chronic heart failure or asymptomatic left ventricular dysfunction might include beta-adrenergic blockers, neutral endopeptidase inhibitors, ANP, BNP, angiotensin II receptor antagonists, and modulators of sympathetic activity.

Diagnostic accuracy of 64-slice multidetector CT for detection of in-stent restenosis in an unselected, consecutive patient population

OBJECTIVES To investigate the diagnostic accuracy of 64-slice multidetector computed tomography (64-CT) for detection of in-stent restenosis (ISR) in an unselected, consecutive patient population. BACKGROUND Detection of in-stent restenosis by cardiac CT would be a major advance for the evaluation of patients suspected of having ISR. However, the diagnostic accuracy of current generation 64-CT in this context is not fully established. METHODS We conducted a prospective study on patients with stable angina or acute coronary syndrome with no prior history of coronary artery disease. Six months after percutaneous coronary intervention (PCI) with stent placement they underwent a 64-CT scan (Toshiba Multi-Slice Aquilion 64) and consequently a repeat coronary angiography for comparison. Cardiac CT data sets were analyzed for the presence of in-stent restenosis by two independent expert readers blinded to the coronary angiographic data. RESULTS Ninety-three patients with a total of 140 stents were evaluated. Males comprised 82% of the study group and the mean age was 63±10 years. The mean time from PCI to the repeat coronary angiography was 208±37 days and the mean time from 64-CT to repeat coronary angiography was 3.7±4.9 days. The restenosis rate according to coronary angiography was 26%. Stent diameter, strut thickness, heart rate and body mass index (BMI) significantly affected image quality. The sensitivity, specificity, positive and negative predictive values of 64-CT for detection of in-stent restenosis were 27%, 95%, 67% and 78%, respectively. CONCLUSIONS Current generation, 64-slice CT, remains limited in its ability to accurately detect in-stent restenosis.

Enalaprilat in acute myocardial infarction: tolerability and effects on the renin-angiotensin system

We treated 48 patients with intravenous enalaprilat within 24 hours from the onset of acute myocardial infarction. Concomitant therapy included thrombolytic treatment (29), intravenous metoprolol (34), intravenous nitroglycerin (16) and intravenous furosemide (15). The first 40 patients included had systolic blood pressure at baseline greater than or equal to 110 mmHg. Intravenous bolus injections of 0.2-1.2 mg (mean 1.0 mg) enalaprilat in one hour were given to 20 patients and an intravenous infusion of 1 mg over two hours was administered to another 20 patients, as well as to a separate group of 8 patients with systolic blood pressure between 100-109 mmHg at baseline. The infusion was stopped in five cases when the systolic blood pressure fell below 100 and 90 mmHg, respectively, in the two infusion groups. No hypotensive reactions were symptomatic. Blood pressure decreased from a mean of 134/82, 131/79 and 106/72 mmHg to a minimum of 117/71, 118/73 and 97/63 mmHg, respectively, in the three groups. Almost complete suppression of plasma angiotensin converting enzyme activity was achieved within 30 minutes. No significant changes were found in plasma levels of angiotensin II, renin activity or atrial natriuretic peptide between baseline and 24 hours. Treatment was continued with oral enalapril 2.5-10 mg/day, which was generally well tolerated. We conclude that intravenous and oral enalapril added to conventional therapy in the early phase of acute myocardial infarction is well tolerated in selected patients, but should be carefully titrated.

Prevention of Congestive Heart Failure by ACE Inhibition in Patients with Acute Myocardial Infarction

Ischaemic heart disease is a major cause of chronic heart failure in Western societies. Despite some progress in the treatment of heart failure, it is still a disabling disorder with both high mortality and high morbidity. The incidence of chronic heart failure has increased over the past decade, probably as a result of the recent success in the management of patients with acute myocardial infarction. The importance of measures with potential capacity to prevent the devlopment of symptomatic heart failure may be best illustrated by the fact that, among patients with left ventricular dysfunction, the prognosis is much worse in those with symptomatic failure than in those who are asymptomatic. Recently, the efficacy of angiotensin converting enzyme (ACE) inhibitors after myocardial infarction has been studied in a number of large placebo-controlled trials. These studies indicate that patients with symptomatic or asymptomatic left ventricular dysfunction after an acute myocardial infarction should receive long-term treatment with an ACE inhibitor and that such treatment may improve survival, reduce the incidence of overt heart failure and reduce the risk of reinfarction.

Clinical In-Stent Restenosis is related to stent length and diameter but not to diabetes in an unselected cohort

In-Stent Restenosis (ISR) is the main limitation of the long term success of PCI. The causes of ISR have not been clearly identified even though an association has been suggested with a number of factors, including diabetes. Method: During an 11 year period (1993–2003) a complete registry of all stent implantations was held in Iceland. The follow-up period was at least 1 year after PCI. Angiographic restenosis (N50% of luminal diameter) was studied in all patients who underwent a second diagnostic angiogram during the follow-up period. Results: 2811 PCI procedures with stent implantation were performed in 2495 patients. A second coronary angiogram was performed in 747 patients (30%) because of recurrent symptoms of angina. The ISR rate was 257 (34%). ISR was found in 51% of long stents (20 mm or longer) and 32% of short stents (b20 mm) (p=0.001). ISR was found in 39% of small stents (b3.5 mm), and 28% of large stents (3.5 mm or larger) (p=0.002). The ISR rate was 37% for male and 27% for female patients (p=0.03). There was no statistical difference in the frequency of ISR when patients were classified according to smoking status, hypertension or diabetes. Conclusion: In this unselected cohort, clinical ISR was related to stent length and diameter rather than to diabetes or other conventional risk factors.