Advanced ultrasound methods in assessment of carotid plaque instability: a prospective multimodal study.

BACKGROUND: A significant proportion of ischemic strokes are caused by emboli from atherosclerotic, unstable carotid artery plaques. The selection of patients for endarterectomy in current clinical practice is primarily based on the degree of carotid artery stenosis and clinical symptoms. However, the content of the plaque is known to be more important for stroke risk. Intraplaque neovascularization (IPN) has recently emerged as a possible surrogate marker for plaque instability. Neo-microvessels from the adventitial vasa vasorum grow into the full thickness of the vessel wall in an adaptive response to hypoxia, causing subsequent intraplaque haemorrhage and plaque rupture. Conventional ultrasound cannot detect IPN. Contrast-enhanced ultrasound and Superb Microvascular Imaging (SMI), have, however, shown promise in IPN assessment. Recent research using Shear Wave Elastography (SWE) has also reported reduced tissue stiffness in the artery wall (reduced mean Young's modulus) in unstable compared to stable plaques. The purpose of this study is to identify unstable carotid artery plaques at risk of rupture and future ischemic stroke risk using multimodal assessments. METHODS: Forty five symptomatic and 45 asymptomatic patients > 18 years, with > 50% carotid stenosis referred to Oslo University Hospital ultrasound lab will be included in this on-going project. Patients will undergo contrast enhanced ultrasound, SMI, carotid-MRI and PET-(18F-FDG). Contrast enhanced ultrasound will be analyzed semi-quantitatively (5-levels visual classification) and quantitatively by plotting time-intensity curve analyses to obtain plaque peak contrast enhancement intensity. Plaques removed at carotid endarterectomy will be assessed histologically and the number of microvessels, areas of inflammation, granulation, calcification, lipid and fibrosis will be measured. DISCUSSION: This multimodality study will primarily provide information on the clinical value of advanced ultrasound methods (SMI, SWE) for the detection of unstable carotid artery plaque in comparison with other methods including contrast-enhanced ultrasound, carotid-MRI and PET-(18F-FDG) using histology as the gold standard. Secondly, findings from the methods mentioned above will be related to cerebrovascular symptoms, blood tests (leukocytes, CRP, ESR, lipoproteins and inflammatory markers) and cardiovascular risk factors at inclusion and at 1-year follow-up. The overall aim is to optimize detection of plaque instability which can lead to better preventive decisions and reduced stroke rate.

Investigation and management of severe hyponatraemia in a hospital setting.

AIMS: To evaluate the assessment and management of severe hyponatraemia in a large teaching hospital. METHODS: Inpatients with serum sodium <125 mmol/l were identified prospectively from a laboratory database over a six month period. Notes were examined and data extracted. Case notes were carefully reviewed retrospectively by a consultant endocrinologist with regard to accuracy of the diagnosis and the appropriateness of investigations and management. RESULTS: 104 patients with a serum sodium <125 mmol/l were identified. Mean (SD) age was 69 (14), 52% were female, mean hospital stay was 16 (12) days, and overall mortality 27%. Adequate investigations were rarely performed. Only 28 (26%) had plasma osmolality measured, 29 (27%) urine osmolality, 11 (10%) urinary sodium, 8 (8%) plasma cortisol, and 2 (2%) a short Synacthen test. Comparing the "ward" and "specialist review" diagnoses, there were significant discrepancies for "no cause found" (49% v 27%, p<0.001), alcohol (6% v 11% p<0.01), and syndrome of inappropriate antidiuresis (20% v 32%, p = 0.001). Treatment was often illogical with significant management errors in 33%. These included fluid restriction and intravenous saline given together (4%) and fluid restriction in diuretic induced hyponatraemia (6%). Mortality was higher in the group with management errors (41% v 20% p = 0.002). CONCLUSION: Severe hyponatraemia is a serious condition, but its investigation and evaluation is often inadequate. Some treatment patterns seem to be arbitrary and illogical, and are associated with higher mortality.

First-pass radionuclide determination of cardiac output: an improved gamma camera method.

A technique for noninvasive determination of cardiac output by aid of first-pass radionuclide cardiography is described. After intravenous injection of 10-15 mCi technetium-99m-(99mTc) labeled red blood cells the method requires acquisition of a first passage time-activity curve recorded with a gamma camera over the left ventricle, the background corrected left ventricular count rate recorded after complete mixing of the tracer in the circulation, and determination of the distribution volume of the tracer. The method was applied in 14 patients with heart disease of various origins and evaluated against the conventional tracer dilution technique with arterial sampling of blood activity. Cardiac output determinations by external counting ranged from 2.30 to 8.56 l/min, mean +/- s.d. 4.50 +/- 1.66 l/min and by arterial blood sampling from 1.88 to 8.96 l/min, mean +/- s.d. 4.52 +/- 1.71 l/min. An excellent correlation was demonstrated between the two techniques, r = 0.978 (p less than 0.001). When no background subtraction was applied to the left ventricular counts at equilibrium, radionuclide cardiac output values were approximately 40% higher than those obtained by arterial sampling. The new first-pass radionuclide cardiographic technique may prove a useful tool in the noninvasive evaluation of cardiac function, especially in patients with arrhythmias and/or valvular incompetence.

The effect of ticlopidine on platelet functions in acute myocardial infarction. A double blind controlled trial.

A group of 43 consecutive patients with AMI were randomized to treatment with a novel platelet inhibitor, ticlopidine, or placebo in a double blind study. Treatment was started within 12 hr after onset of precordial pain. Patients who had taken drugs with known platelet inhibitory effect prior to the onset of therapy were excluded. Platelet survival time (PS) was measured 24-36 hr after onset of precordial pain and after 3 months of treatment in both groups. In the early phase of AMI CK-MB and ASAT were taken twice daily for estimation of infarction size. Platelet function, coagulation factors and fibrinolysis parameters were followed sequentially for 21 days and repeated after 3 months. In the placebo group a significant reduction in PS (5.62 +/- 1.63 S. D. days) was measured in the acute phase of AMI compared to PS 3 months after infarction (8.03 +/- 1.20 S.D. days). In the ticlopidine group PS was normal during the acute phase (8.35 +/- 1.82 S.D. days). After 3 months of treatment PS was normal in both groups. During the first two weeks after AMI significant changes in coagulation parameters and fibrinolysis indicated an increased risk of thrombosis in both groups. These parameters were unaffected by the platelet inhibitory therapy. Estimated by peak CK-MB and ASAT, infarction size was significantly reduced in the ticlopidine group.

Changes in platelet functions, coagulation and fibrinolysis in uncomplicated cases of acute myocardial infarction.

Platelet aggregation and serotonin-release in vitro and some coagulation and fibrinolysis parameters were studied closely in 12 patients with non-complicated acute transmural myocardial infarction from the very beginning, for 3 weeks. The aggregability with ADP, epinephrine and collagen and the serotonin-release was significantly reduced the first days. Significantly increased aggregability and serotonin-release developed after a week, with peak activity on days 14-16. Most patients still exhibited increased activity at the discharge on days 21-22. Positive ethanol gelation tests developed after day 1 in most patients with a peak at day 5, contemporary with peak activities of factor VIII and negatively correlated to factor XIII activity, quantitated biologically. These values were normalized on discharge. Antithrombin III (Xa) remained unchanged, normal to slightly elevated. The fibrinolytic activity decreased after day 1 with lowest activity on day 5, contemporary with peak activity of antiplasmin. Around 50% of the patients showed decreased activity on discharge.

Effect of ramipril on mitral regurgitation secondary to mitral valve prolapse.

Ramipril 10 mg/day reduced regurgitation in chronic mitral regurgitation secondary to mitral valve prolapse in patients with sinus rhythm.

Hemodynamic effects of alcohol at rest and during upright exercise in coronary artery disease.

The hemodynamic effects of acute alcohol intoxication were studied at rest and during upright exercise in 28 patients with coronary artery disease by right-sided heart catheterization and radionuclide cardiography. The mean arterial blood pressure at rest was reduced by 5% and the left ventricular ejection fraction at rest decreased 2% because of end-systolic dilation during intoxication (serum ethanol 21 mmol/liter). No changes were observed in heart rate, stroke volume, pulmonary artery pressure, pulmonary artery wedge pressure or total peripheral resistance. No significant changes occurred in plasma catecholamines, and no changes occurred in any variable during mild exercise corresponding to a 30 to 40% heart rate increase. Thus, alcohol ingested in moderate doses causes slight impairment of left ventricular emptying and a reduction in the arterial blood pressure at rest in patients with coronary artery disease. A mild exercise load can be tolerated during alcohol intoxication without hemodynamic changes.

Influence of gender on short- and long-term mortality after acute myocardial infarction. TRACE study group.

The aim of this study was to assess differences in short- and long-term mortality between male and female patients with acute myocardial infarction (AMI). The study population consisted of 6,676 consecutive patients admitted alive with an enzyme-confirmed AMI to 27 Danish hospitals from 1990 to 1992. Five patients were excluded because of missing information. Female patients (n = 2,170) were on average 5 years older than male patients (n = 4,501, p <0.001), had lower body mass index, and more often had diabetes, hypertension, and congestive heart failure. Left ventricular systolic function was the same for men and women. Women received thrombolytic therapy less often. The 1-year mortality for female patients was 28 +/- 1% and for men 21 +/- 1% (p <0.001). The unadjusted risk ratio associated with male gender in a proportional-hazards model was 0.76 (95% confidence intervals [CI] 0.70 to 0.83). Adjustment for age removed the importance of gender, and the risk ratio associated with male gender was 1.06 (95% CI 0.97 to 1.2, p = 0.2). An introduction of further variables in the model did not change this. Subdividing mortality into 6-day, 30-day, and late mortality demonstrated a significantly increased mortality in women in the short-term (6 and 30 days), with a risk ratio in men of 0.58 (95% CI 0.42 to 0.81) and 0.80 (95% CI 0.65 to 0.99), respectively. From day 30 onward there was an increased mortality in men with a risk ratio of 1.16 (95% CI 1.03 to 1.31, p = 0.01). Thus, women admitted alive to the hospital with an AMI have an increased long-term mortality that is explained by their older age. However, short-term mortality in women seems to increase independently of other risk factors, but is later followed by an increase in mortality in men.

Metoprolol abolishes exercise-induced left ventricular dysfunction in patients with silent ischemia.

Left ventricular systolic function is reduced during episodes of silent ischemia in patients with coronary artery disease (CAD). Left ventricular ejection fraction (LVEF) is increased at least 5 absolute percent during exercise in most normal subjects; however, in patients with CAD, LVEF often remains unchanged or decreases. The anti-ischemic effect of beta-adrenergic receptor blockade is well documented, including a reduction of exercise-induced electrocardiographic ST depressions; however, the effect of these drugs on left ventricular volume changes during exercise in patients with silent ischemia is unknown. The aim of this study was to evaluate the effect of a cardio-selective beta-blocking agent, metoprolol, on rest and exercise LVEF in patients with silent ischemia, using radionuclide cardiography. Fifteen patients with silent ischemia completed a double-blind, placebo-controlled crossover study at rest and during submaximal exercise. LVEF remained unchanged during exercise in the placebo phase (56% to 58%; p = NS), but even though LVEF tended to decrease 56% during rest after metoprolol versus 52% after placebo (p = NS), the LVEF increase from rest to exercise resembled a normal LVEF response, 52% to 58% (p = 0.005). Exercise-induced electrocardiographic ST depressions were also reduced during metoprolol treatment. In patients with silent ischemia, the exercise-induced change in LVEF rises significantly during metoprolol treatment. The mechanism may be a reduction in myocardial ischemia as indicated by a reduction in ischemic electrocardiographic findings.

Prognosis of late versus early ventricular fibrillation in acute myocardial infarction.

To determine the prognosis of late ventricular fibrillation (VF) after acute myocardial infarction (AMI), the length of the monitoring period after AMI was extended. All patients in this series were continuously monitored in a coronary care unit to ensure observation of all VF within 18 days of AMI. From 1977 to 1985, 4,269 patients were admitted with AMI and 413 (9.6%) had in-hospital VF. Of these 281 (6.8%) had early VF (less than 48 hours after AMI) and 132 (3.2%) had late VF (greater than or equal to 48 hours after AMI). In-hospital mortality was 50 and 54% for early and late VF, respectively (p = 0.31). Kaplan-Meier survival analysis showed better survival after discharge for patients with early versus late VF (p = 0.009) but this difference was fully explained by the presence of heart failure. Survival analysis showed the same prognosis after 1, 3 and 5 years for early and late VF, when VF was not associated with heart failure. When VF was associated with heart failure (secondary VF) early VF had a greater mortality than late VF after 2 and 5 years. Logistic regression analysis showed that heart failure (relative risk 1.9 [1.1 to 3.1]) and cardiogenic shock (relative risk 3.9 [1.8 to 8.5]) were significant risk factors for in-hospital death. Late VF compared to early VF had no prognostic implication (relative risk 1.0 [0.6 to 1.6]). For patients discharged from the hospital, risk factors were heart failure (1.8 [1.1 to 2.8]) and previous AMI (1.6 [1.3 to 2.1]).(ABSTRACT TRUNCATED AT 250 WORDS)

First passage radionuclide cardiography for determination of cardiac output: evaluation of an improved method.

A noninvasive method for determination of cardiac output by aid of first passage radionuclide cardiography is presented. As opposed to most other scintigraphic methods, a forward blood flow is measured, even in patients with valvar incompetence. In addition, the technique allows measurement of cardiac output in the presence of cardiac arrhythmias. No geometrical assumptions, corrections for radiation attenuation, loss of tracer, or empirical correction factors due to extracardiac radioactivity are required. We have evaluated the method in 19 patients with various heart diseases by comparison of the radionuclide cardiac outputs with those derived from the thermodilution technique performed simultaneously. Eight patients had valvar incompetence and 2 had cardiac arrhythmias. The mean radionuclide and thermodilution cardiac output values were 5.03 l/min (SD 1.21) and 5.18 l/min (SD 1.09), respectively. The 95% confidence interval for the bias was -0.40 to 0.10 l/min, and correlation analysis demonstrated an excellent correlation between results obtained with the two methods, r = 0.91 (P less than 0.001). This study shows that the improved gamma camera method represents a valid noninvasive technique for determination of cardiac output.

[Ultrasonically guided pericardiocentesis]. / Ultralydvejledt draenage af perikardiehulen.

Ultrasonically guided pericardiocentesis was performed on 25 occasions in 23 consecutive patients. Incipient cardiac tamponade was present in 22 patients and the procedure was performed for diagnostic purposes in one patient. In 21 cases, 5.7 French pig-tail catheters were employed and 1.2 mm lumbar puncture needles in four cases. In 19 out of 22 patients (86%) with incipient cardiac tamponade the ultrasonically guided pericardiocentesis was considered successful. In one patient, the catheter was misplaced in the right atrium, one patient developed pyopericardium and one patient developed transient tachycardia. In two cases, no material could be obtained. Ultrasonically guided pericardiocentesis is preferable to "blind" puncture and the procedure should be carried out by physicians with experience in interventional ultrasound.

[Prognosis in early and late ventricular fibrillation after acute myocardial infarction]. / Prognosen ved tidlig og sen ventrikelflimmer efter akut myokardieinfarkt.

Of 413 patients with in-hospital ventricular fibrillation complicating acute myocardial infarction 281 had early (less than 48 hours post infarction) ventricular fibrillation and 132 had late ventricular fibrillation. In-hospital and longterm prognoses were not influenced by time of ventricular fibrillation, but advanced age and signs of reduced left ventricular function were found to be independent significant risk factors for short and longterm prognoses.

Dosage dependent hormonal counter regulation to combination therapy in patients with left ventricular dysfunction.

UNLABELLED: The present study attempts to assess the efficacy combination therapy for heart failure. Genuine dose-response studies on combination therapy are not available and published studies involved adding one drug on top of 'usual treatment'. Sixteen different dosage combinations of trandolapril and bumetanide was tested in a double blind, double placebo-controlled, randomized, multiple cross-over study in a 16 times six balanced incomplete Latin square design. Patients reported optimal quality of life on the sub maximal dose bumetanide. Bumetanide decreased left ventricular function and increased heart rate and plasma noradrenaline in a dose dependent manner. Doses of bumetanide of more than 0.5 mg, given twice daily significantly decreased the quality of life and increased diuresis. Weight loss was maximal on 0.5 mg bumetanide twice daily. Trandolapril significantly reduced systolic blood pressure with the maximal effect at 0.5 mg daily. Both drugs significantly increased renin concentration with a significant potentiating interaction. It was not possible to detect beneficial effects of combination therapies. The optimal dosage of Bumetanide appeared to be 0.5 mg twice daily based on its effect on quality of life and weight loss. Estimated by the reduction in systolic blood pressure the optimal dosage of Trandolapril appeared to be 0.5 mg once daily. CONCLUSIONS: It appears that patients should be given less than the usually recommended dosages. Patients may be treated with a low dose loop diuretic, if signs of water retention are present or if symptomatic relief is desired.

Effect of locally applied subatmospheric pressure on subcutaneous blood flow during the course of acute myocardial infarction.

1. The effect of locally applied subatmospheric pressure on subcutaneous blood flow was studied in six patients with acute myocardial infarction. 2. Blood flow was measured by the local 133Xe washout technique. 3. Application of subatmospheric pressures of -80 and -150 mmHg to the labelled area induced no vasoconstriction on day 1. On day 7 pressures of -40, -80 and -150 mmHg induced a decrease in blood flow of about 40-50%. 4. The absence of a vasoconstrictor response to locally applied subatmospheric pressure on day 1 could not be due to decreased venous distensibility. The underlying mechanism may be neuronal inhibition, probably antidromic, in sympathetic fibres.

Effect of head-up tilt on subcutaneous blood flow during the course of acute myocardial infarction.

1. Central and local regulation of subcutaneous blood flow in the forearm was studied in the acute phase of myocardial infarction. 2. Blood flow was measured by the local 133Xe-washout technique. 3. The vasoconstrictor response to increase in venous transmural pressure was not present on day 1 after coronary occlusion but gradually recurred during days 2, 3 and 7. 4. Passive 30 degrees head-up tilt induced a vasoconstriction in subcutaneous tissue. There was no difference in this response at any time during the course of acute myocardial infarction. The vasoconstriction could be blocked by proximal nervous blockade. 5. Thus a decrease in baroreceptor activity induced by head-up tilt enabled a marked neurogenically mediated vasoconstriction in subcutaneous tissue, indicating that orthodromic impulse activity in sympathetic fibres can be further increased even on day 1 of acute myocardial infarction.