Elevated endothelin concentrations are associated with reduced coronary vasomotor responses in patients with chest pain and normal coronary arteriograms.

OBJECTIVES: The purpose of this study was to investigate the relationship between arterial and coronary sinus endothelin (ET) concentrations and coronary vasomotor responses during rapid atrial pacing in patients with chest pain and normal coronary arteriograms (CPNA). BACKGROUND: Plasma ET concentrations are significantly higher in CPNA patients than in healthy control subjects. METHODS: We investigated 19 carefully characterized CPNA patients (14 women; mean age 53 +/- 9 years) of whom 10 had positive electrocardiographic responses to exercise. The percentage fall in coronary vascular resistance (%d.CVR) after 10 min of rapid atrial pacing was determined using a thermodilution pacing catheter. Plasma ET concentrations were measured by radioimmunoassay on simultaneously drawn arterial and coronary sinus samples. RESULTS: No significant differences in ET concentrations were observed between men and women, but a strong statistical trend suggested that %d.CVR was lower in women than men (27[23 to 31]% vs. 34[29 to 45]%--median[interquartile range]; p = 0.07). Simple regression analysis including only the women (n = 14) suggested a significant relationship between baseline arterial ET concentrations and %d.CVR (R2 = 0.34; p = 0.06). Furthermore, stepwise multivariate regression analysis of the group as a whole indicated that both gender (p = 0.03) and baseline arterial ET concentration (p = 0.02) were independently predictive of %d.CVR (R2 = 0.44; overall p = 0.02); this relationship predicts that women with high ET levels would have the lowest %d.CVR during pacing. CONCLUSIONS: These data support the hypothesis that elevated ET activity may be associated with reduced coronary flow responses during rapid atrial pacing in CPNA patients.

Propranolol-induced increments in total and free serum thyroxine in patients with essential hypertension.

The effect of propranolol on serum levels of total and free thyroxine, total and free triiodothyronine, and thyroid-stimulating hormone (TSH) was investigated in 15 clinical euthyroid patients with essential hypertension. Oral propranolol in dosages from 80 to 480 mg/day for a 30-day period induced an average increase in total serum thyroxine of 15.5 +/- 2.2% (mean +/- SEM, 2 p = 0.00002) and in free thyroxine of 17.7 +/- 3.5% (2 p = 0.00009). The oral dose of propranolol correlated positively with serum propranolol (r = 0.70, 2 p = 0.007). No significant correlation between serum propranolol and changes in serum thyroxine could be demonstrated. Total and free triiodothyronine, as well as TSH, remained unchanged during propranolol treatment. The most likely explanation is a propranolol-induced decreased degradation of thyroxine. A practical consequence is that in patients with an uncertain clinical picture and slightly elevated serum thyroxine, propranolol intake should be considered.

Propranolol withdrawal and thyroid hormones in patients with essential hypertension.

The effect of abrupt withdrawal of propranolol on serum concentrations of triiodothyronine (T3) and thyroxine (T4) was investigated in 5 patients with uncomplicated essential hypertension. The patients had been treated from 2 to 18 mo before the study was begun. Doses varied from 160 to 480 mg propranolol daily. Four of the patients studied developed tachycardia, sweating, or tremor within 2 to 6 days after withdrawal of propranolol. In 1 patient reversible ischemic ECG changes were recorded. The serum concentrations of free T3 increased in the 4 patients suffering from withdrawal symptoms. The mean increase on the day the symptoms started was 51% (range, 22 to 74, 2 p = 0.01). This increase in serum-free T3 correlated positively with the serum propranolol concentration on the last day propranolol was given (r = 0.91, 2 p = 0.03). In the one patient, who did not develop withdrawal symptoms, the serum concentration of propranolol was very low, and the free T3 level remained unchanged. No significant changes in serum concentrations of free T4 or total thyroid hormones were found in any of the patients. We suggest that the propranolol withdrawal symptoms are, at least partially, caused by an increase in the thyroid hormone, T3.

Autoantibodies and vascular events in essential hypertension: a five-year longitudinal study.

The relationship between serum autoantibodies and vascular events was investigated in 140 patients with essential hypertension during a five-year period. The influence of time upon incidence of autoantibodies was assessed in 55 normotensive controls of roughly the same distribution of age and sex. Thirty-four patients experienced a vascular event, which was fatal in 10 cases (7.1%). Eight of these 10 patients had autoantibodies in serum before the events, and the presence of autoantibodies at entry to the study tripled the five-year relative risk for vascular events. Antinuclear antibodies (ANA) and smooth muscle antibodies (SMA) especially contributed to this increased risk. The vascular events were followed by a significantly increased occurrence of ANA. In the control subjects no events occurred and no significant increases in the presence of autoantibodies were found during the five years. ANA and SMA positive sera showed no significant complement fixing properties, and the autoantibodies studied seemed to be secondary to tissue damage. Despite this, they seemed to reflect an ongoing injury of the vascular bed.

Thrombus organization plays no major role in late neointimal formation after angioplasty in porcine coronary arteries.

Thrombus organization has been suggested to play a major role in late neointimal formation after coronary angioplasty. We sought to describe the time sequence of lesion formation after angioplasty in porcine coronary arteries and to quantify the relation between early thrombosis and late neointimal formation. Deep vessel wall injury was induced by conventional balloon angioplasty in the circumflex (CX) and right coronary (RCA) arteries and by retraction of a chain-encircled balloon in the left anterior descendent artery (LAD). Lesions were assessed by histomorphometry at days 0, 1, 4, 7, 14, 28, and 56 after angioplasty. A response-to-injury index (lesion area/injury length) was determined for each artery. Angioplasty led to rupture/removal of media. Thrombus was present at the exposed adventitia at days 0, 1, and 4. From day 7, neointima was observed on the luminal side of the arterial wall. All thrombus had disappeared at day 28, at which only neointima was observed. Histomorphometry revealed that lesion formation after angioplasty was a gradually increasing process from day 0 to day 28 with no further growth from day 28 to day 56. Maximal thrombus size (day 4, RCA: 0.07+/-0.04 mm, CX: 0.23+/-0.16 mm, LAD: 0.15+/-0.11 mm) was significantly smaller than late neointimal formation (day 28, RCA: 0.68+/-0.18 mm, CX: 0.63+/-0.23 mm, LAD: 0.71+/-0.18 mm) in all three arteries (p < .03). Lesion formation after angioplasty is a gradually increasing process for 4 weeks. Maximal thrombus size is about four times smaller than late neointimal formation. Thus, thrombus organization plays no major role in late neointimal formation.

Measurement of left ventricular volumes by 3-dimensional echocardiography with tissue harmonic imaging: a comparison with magnetic resonance imaging.

We hypothesized that tissue harmonic imaging (THI) in comparison with fundamental imaging (FI) would improve endocardial border detection, and therefore in combination with 3-dimensional echocardiography (3D echo), it would be a precise method for left ventricular (LV) volume measurement. Ten healthy subjects and 18 consecutive patients with dilated hearts underwent estimation of LV volumes by magnetic resonance imaging (MRI) and transthoracic 3D echo with THI and FI. In patients, the agreement between MRI and 3D echo was closer with THI in comparison with FI for assessment of LV volumes. Thus the mean +/- 2 SD of differences between MRI and 3D echo with THI versus FI, respectively, was -6.4 +/- 40.0 mL versus -17.4 +/- 57.6 mL (P <.01) for the end-diastolic volume (EDV), and 0.0 +/- 26.6 mL versus -8.1 +/- 35.6 mL (P <.01) for the end-systolic volume (ESV). In patients, THI in comparison with FI approximately halved observer variation on EDV and ESV. In healthy subjects, only ESV showed significantly reduced observer variation by THI. In conclusion, because THI demonstrated a clinically relevant reduction in observer variation and a closer agreement to the MRI technique in patients with dilated hearts, it should replace FI in LV volume measurements.

Immune complexes and complement activation following rupture of intracranial saccular aneurysms.

Circulating immune complexes (CIC) and complement activation (plasma C3d levels) were monitored during a 2-week period in patients with ruptured cerebral aneurysms and also in patients with cerebral hematoma unrelated to saccular aneurysms. Thirteen of 18 aneurysm patients were found to have CIC on admission as compared to three of 21 healthy blood donors (p less than 0.001). The presence of CIC in aneurysm patients was associated with a poor prognosis. Eight of nine patients who developed angiographic vasospasm had CIC on admission compared with one of four without vasospasm. Patients with vasospasm showed a twofold increase in plasma C3d levels at the time when the spasm occurred, whereas no significant changes in the C3d concentration could be demonstrated in aneurysm patients without spasm or in patients with hematoma unrelated to aneurysm rupture. These findings suggest that immunological processes involving complement-activating immune complexes are involved in the pathogenesis of cerebral vasospasm following rupture of saccular aneurysms.

Time course of vascular remodeling, formation of neointima and formation of neoadventitia after angioplasty in a porcine model.

BACKGROUND: Vascular remodeling is the major cause of restenosis after coronary balloon angioplasty but the pathophysiology of this process is not known. OBJECTIVE: To examine the time courses of vascular remodeling, formation of neointima and adventitial changes after coronary angioplasty. DESIGN: An experimental study on pigs using coronary angiography, intravascular ultrasound (IVUS), and histology. METHODS: Deep vessel-wall injury was induced by conventional balloon angioplasty in the circumflex and right coronary arteries, and by retraction of a chain-encircled balloon in the left anterior descending artery. Angiography in all three arteries and IVUS measurements in circumflex and left anterior descending arteries were performed before and after angioplasty, and at follow-up on days 0, 1, 4, 7, 14, 28, and 56 (n = 5 in each group). Serial IVUS measurements were used to determine vascular remodeling. Formation of neointima and neoadventitia was measured by histomorphometry. RESULTS: Angiographically evident loss of lumen and ultrasonographically detectable constrictive remodeling occurred between day 7 and day 28. IVUS measurements showed that late loss of lumen (days 28 and 56) was correlated to vascular remodeling but not to the increase in wall area (neointima plus media). Histomorphometry revealed that neointima was present from day 7 and that amount of neointima increased up to day 28. Area of adventitia increased during the first 4 days and remained unchanged thereafter. Adventitial neovascularization by vasa vasorum was observed from day 4 onward. CONCLUSIONS: Formation of neoadventitia precedes late loss of lumen, constrictive remodeling, and formation of neointima. The time course of vascular remodeling coincides with growth of neointima rather than with changes in the adventitia.

Importance of abstention from alcohol in alcoholic heart disease.

A case of alcohol-associated heart disease, presenting with congestive heart failure, was followed for 36 months. After abstinence from alcohol, fractional shortening rose from 13 to 60%. After 1 1/2 years of abstinence and normal physical capacity, the alcoholic abuse was resumed. Eleven months later, the patient was again in overt heart failure. Withdrawal of alcohol was again associated with significant clinical improvement, but despite being in functional NYHA class I, fractional shortening only increased from 14 to 29%. Endomyocardial morphology was unrelated to the severity of the disease. Alcoholic heart disease is partially reversible, but total abstinence is necessary to preserve cardiac function.

Mitral valve prolapse in 3-year-old healthy Cavalier King Charles Spaniels. An echocardiographic study.

Clinical studies have shown that Cavalier King Charles Spaniels (CKCS) have a high prevalence of mitral valvular insufficiency (MVI). Echocardiography has the potential to disclose early valvular changes, and the present prospective study was designed to investigate the occurrence of mitral valve prolapse (MVP) in young CKCS without heart murmurs, and to correlate the degree of MVP with the clinical status of the dogs by including CKCS with MVI as well. The study was based on blinded evaluations of echocardiographic recordings of mitral valves from 34 CKCS and 30 control dogs. Thirteen (87%) of 15 three-year-old CKCS without heart murmurs had MVP (2 total and 11 partial), as compared with 1 (7%) of 15 three-year-old normal Beagle dogs (P < 0.0001), and none of 15 three-year-old normal Medium Size Poodles (P < 0.0001). Of 19 CKCS with MVI, MVP was found in 84% of the entire group and in 100% of dogs with pulmonary congestion or edema. The occurrence of total MVP tended to be higher in the group with MVI (47%, 9/19), when compared with the younger CKCS without heart murmurs (13%, 2/15, P = 0.06). MVP was positively associated with excessive heart rate variability (P = 0.003). The radius of curvature of the anterior mitral valve leaflet in systole was significantly reduced in dogs with MVP when compared with those without (P < 0.0001). In conclusion, this study shows that CKCS at an early age have a high occurrence of MVP. This suggests: 1) A genetic predisposition of CKCS to MVP; and 2) That MVP is a pathogenetic factor in the development of mitral valvular insufficiency. Follow up studies may add further support to these proposals, and clarify whether echocardiography may be an aid in selecting CKCS for future breeding.

Echocardiographic mitral valve prolapse in cavalier King Charles spaniels: epidemiology and prognostic significance for regurgitation.

This study investigated the epidemiology and prognostic significance of mitral valve prolapse, detected by ultrasonography, in 153 cavalier King Charles spaniels which were screened consecutively during a period of one year. Seventy-five of the dogs, which had either no murmur or a grade I murmur on screening, were reexamined three years later. The screening revealed that 82 per cent of the dogs aged one to three years and 97 per cent of the dogs over three years had various degrees of mitral valve prolapse. The presence and severity of the condition were independent of gender but correlated positively with age and negatively with bodyweight. The degree of mitral valve prolapse at screening correlated with the regurgitation status (murmur intensity and size of the regurgitant jets) at re-examination and with the percentage increase in the left ventricular end diastolic diameter over the three-year period. The presence of a grade I murmur was not a useful prognostic indicator.

[Hemicraniectomy in malignant mid-cerebral infarction. Further trials needed before its acceptance in clinical practice]. / Hemikraniektomi vid malign media-infarkt. Flera prövningar före allmän acceptans i klinisk praxis.

In cases of completed middle cerebral artery territory stroke, prognosis is very poor and the clinical course is characterised by a rapid decline in consciousness and signs of herniation 2-4 days after the onset of symptoms due to a space-occupying mass. Failure of conservative therapy is the rule, and herniation is the usual cause of death, occurring in almost 80 per cent of cases. Recently published results have suggested that hemicraniectomy may improve survival in patients with massive hemisphericstroke, decreasing mortality to less than 35 per cent. The article presents what is probably the first case to be reported in Sweden, where hemicraniectomy was performed on a 45-year-old woman with right hemispheric completed middle cerebral artery infarction.

[Percutaneous mitral balloon valvuloplasty in a patient with mitral stenosis]. / Perkutan mitral ballonvalvuloplastik hos en patient med mitralstenose.

Percutaneous balloon valvuloplasty of mitral stenosis was described in 1984. The subsequent results were promising and the method appears to be capable of replacing surgical valvotomy. Mitral balloon valvuloplasty in a patient with non-calcified rheumatic mitral stenosis is described here.

[Thromboendarterectomy of chronic thromboembolic pulmonary hypertension]. / Trombendarterektomi af kronisk tromboembolisk pulmonal hypertension.

Chronic thromboembolic pulmonary hypertension has a five year survival rate of less than 10% in patients with a systolic pulmonary artery pressure of 50 mmHg with no convincing effect of medical treatment. The operative mortality from pulmonary thrombendarterectomy in specialised centres has been reduced to 9%, suggesting this treatment as being an option. The results from thrombendarterectomy of two Danish patients are reported. The first patient, a 34 year-old woman was operated at the centre in San Diego with the assistance of a Danish thoracic surgeon. The second, a 60 year-old man was operated at our institution by this surgeon. Following removal of sufficient amount of embolic masses and intimal tissue, the patients were discharged from hospital with a substantial improvement in their clinical status and near normalisation of pulmonary artery pressure, which remained at the latest follow-up (3 to 22 months).

[Left ventricular hypertrophy in patients with aortic stenosis. A comparison between electrocardiography and echocardiography]. / Venstre ventrikel-hypertrofi hos patienter med aortastenose. En sammenligning mellem elektrokardiografi og ekkokardiografi.

Using echocardiography (ECHO) as the reference method, the aim of this study was to determine the sensitivity, specificity, and predictive value of the electrocardiogram (ECG) in detection of left ventricular hypertrophy (LVH) in patients with aortic stenosis. Forty-one patients, 18 men and 23 women aged 25-80 years (mean 49 years) with uncomplicated aortic stenosis were studied. ECG-LVH was estimated by standard fixed voltage criteria. ECHO-LVH was defined according to left ventricular mass (LV mass) calculated by the Penn method. In the total material, the correlation between ECG-LVH and ECHO-mass was poor (r = 0.56, p < 0.05). The sensitivity and specificity of the ECG was respectively 50% and 100%. The positive predictive value of the ECG in detection of LVH was high (100%). We conclude that the sensitivity of the ECG in detection of LV hypertrophy is unsatisfactorily low. Accordingly, it is recommended that echocardiography be performed in all patients suspected of aortic stenosis.

[Intracoronary ultrasonography--a supplement to coronary arteriography]. / Intrakoronar ultralydundersøgelse--et supplement til koronararteriografi.

Intracoronary ultrasound is a new technique, by means of which it is possible for the first time to visualise coronary artery wall structures in vivo. Compared to conventional coronary angiography the advances of this new modality appear to be: 1) Improved diagnosis of minimal and non-obstructive atherosclerosis; 2) Characterisation of plaque morphology, thereby being an aid in decision on interventional procedures (PTCA, atherectomy, stent placement); 3) Better delineation of coronary artery lumen area, which improves the accuracy of stenosis graduation both before and after interventional procedures. The examination can be performed in up to 95% of cases. The procedure appears to be safe with a reported complication rate of myocardial infarction and bypass surgery of 0.16% in 1837 cases; transient coronary artery spasms occurred in about 3%. Complications are predominantly associated with interventional procedures. Although intracoronary ultrasound has mainly been used for research purposes, results of ongoing trials assessing its clinical utility, as well as technological improvement providing more consistent image quality, suggest that the procedure will evolve into an important adjunct to coronary angiography.

[Chronic thromboembolic pulmonary hypertension]. / Kronisk tromboembolisk pulmonal hypertension.

Acute pulmonary hypertension has a high mortality at the onset. Patients surviving the first phase will usually recanalize the pulmonary arteries through intrinsic thrombolytic mechanisms and medical treatment. However, in some cases there is insufficient resolution of the emboli with subsequent thrombotic and fibrotic reorganization, leading to a worsening of the pulmonary obstruction. In the open pulmonary arteries the disease may lead to hypertrophy of the media and intimal proliferation, thus leading to a further increase in the pulmonary vascular resistance. This again leads to hypertrophy of the right ventricle and ultimately to right-sided heart failure. Untreated, chronic thromboembolic pulmonary hypertension has a five-year mortality approaching 100%, but extensive pulmonary thrombendarterectomy using extracorporeal circulation and deep hypothermia has been shown to lower the pulmonary vascular resistance and thereby improve the prognosis significantly. Operative treatment can now be offered in Denmark, and the purpose of this review is to draw attention to the disease, its symptoms, diagnosis and the surgical treatment.

[Transesophageal echocardiography for registration of hemodynamics. A new tool in anesthesiology]. / Transøsofageal ekkokardiografi til haemodynamisk registrering. Et nyt anoestesiologisk redskab.

During the last ten years, transesophageal echocardiography has become an important tool for cardiac monitoring. In other countries it is widely applied, especially in cardiac surgery, but the areas of application are still expanding. Transesophageal echocardiography is a non-invasive technique in contrast to most other methods available for monitoring central haemodynamics. The complication frequency is extremely low. However, correct therapeutic decisions depend on profound experience with the equipment and image interpretation. The scope of transoesophageal echocardiography as a new tool in haemodynamic monitoring is described in this paper together with preliminary results.

[Percutaneous pulmonary balloon valvuloplasty in Denmark]. / Perkutan pulmonal ballonvalvuloplastik i Danmark.

Percutaneous balloon valvuloplasty of valvular pulmonary stenosis (PPB) was carried out for the first time in 1982 and is now regarded as the primary method of treatment of this condition. The results of the first PPB treatments in Denmark are presented here. PPB was planned in 28 patients and was carried out in 25 (22 children and 3 adults). PPB was carried out on two occasions in one patient. Twenty-three patients had isolated valvular pulmonary stenosis and two patients had Fallot's anomaly. No complications of significance occurred after the treatments. The average gradient for all dilatations was 77 +/- 24 mm Hg prior to and 36 +/- 23 (p less than 0.0001) immediately after PPB. The gradient was reduced by more than 50% in 68% of the patients. In 14 patients, the gradients over the pulmonary valve was measured by Doppler technique or by cardiac catheterization greater than 6 months after PPB. In these patients, the average gradient was 69 +/- 21 mm Hg prior to PPB, 29 +/- 12 mm Hg (p less than 0.0001) immediately after PPB and 27 +/- 9 mm Hg (p less than 0.0001) at the most recent control examination, on an average 12 months (range 6-24 months) after PPB. In the same patient group, significant reduction of the electrocardiographic right-sided hypertrophy was found at the most recent control examination. It is concluded that PPB is an effective and safe treatment of valvular pulmonary stenosis.

[Diagnosis of suspected thoracic aortic dissection. Focused on transesophageal echocardiography]. / Diagnostik ved mistaenkt torakal aortadissektion. Fokus på transøsofageal ekkokardiografi.

Over a five-year period (1990-1994), 72 consecutive patients were referred to transoesophageal echocardiography (TEE) on suspicion of thoracic aortic dissection. TEE was performed as the only or last investigation in 42 patients (58%). In 44 patients one or more other investigations were carried out before final clinical decision making: aortography (n = 30), X-ray computer tomography (CT, n = 18), and magnetic resonance imaging (MRI, n = 12). The final diagnosis was based on the combination of clinical information, the available examination results, and findings at surgery or autopsy; 31 of the patients were diagnosed as having aortic dissection. One patient with aortic dissection died during TEE while none of the other patients suffered major complications. The sensitivity (demonstration of dissection including correct classification in type A or B) was 81%, 80%, 45%, and 83% for TEE, aortography. CT, and MRI, respectively. The specificities were 88%, 93%, 71%, and 100%, respectively. Dissection of the thoracic aorta is a life-threatening condition demanding prompt and accurate diagnosis. None of the four techniques employed in the present study is ideal. Although TEE is adequate for immediate bedside examination our results show that more time-consuming and resource demanding investigations are sometimes required. Proper training and improved equipment may, however, increase the usefulness of TEE in patients with suspected aortic dissection.