Left ventricular contractile function after distal protection in primary percutaneous coronary intervention: results from the Drug Elution and Distal Protection in ST-Elevation Myocardial Infarction trial.

BACKGROUND: Coronary intervention (PCI) may result in an increased infarct size. We evaluated the effect of distal protection during PCI for ST-segment elevation myocardial infarction (STEMI) on myocardial function. METHODS: Patients with STEMI were randomly referred within 12 h for PCI with (N = 312) or without distal protection (N = 314). Left ventricular (LV) contractile function was assessed with echocardiography 8 months after PCI. Global LV myocardial wall motion index (WMI) was calculated as the average wall motion score of all myocardial segments. The occurrence of death, nonfatal re-infarction, and stroke 8 months after PCI were also recorded. RESULTS: The occurrence of death, nonfatal re-infarction, and stroke 8 months after PCI was 7.1% after distal protection and 5.7% after conventional treatment (p = 0.17). WMI improved by 4.1% at 8 months in patients treated with distal protection compared to patients receiving conventional PCI (p < 0.01). In myocardium supplied by a culprit artery treated by distal protection regional LV function was 9-11% higher than myocardial regions treated conventionally ( p < 0.02). CONCLUSIONS: Routine use of distal protection during primary PCI is associated with a significant improvement in LV contractile function, with no detectable impact on intermediate term clinical outcome.

Myocardial infarction centres: the way forward.

In the era of primary PCI, a strategy of admitting patients to the nearest hospital should be obsolete. Instead, a prehospital diagnostic strategy should be implemented in order to: (1) refer patients directly to interventional centres, thereby eliminating delay at local hospitals; (2) alert the interventional centre, thereby reducing door to balloon times; (3) initiate adjunctive medication in the prehospital phase.

Six months' clinical and angiographic follow-up of a flexible, coiled stainless steel stent in long, native coronary artery lesions.

This study was conducted to evaluate the short- and long-term clinical and angiographic results of implantation of a flexible, coiled stainless steel stent, the Freedom Coronary Stent. During the study period this stent was used as an alternative to the Palmaz-Schatz PS153 coronary stent in long or tortuous lesions. The study was designed as a prospectively planned outcome analysis. Implantation of Freedom stents was attempted in 62 consecutive patients (56% males, mean age 63+/-10 years) with a total of 65 coronary lesions. Indications for stent implantation were: restenosis, 8%; recoil, 26%; visible dissection, 32%; threatening occlusion, 15%; chronic total occlusion, 18%. The average stent length was 30+/-16 mm and 67% of the lesions were type C. Rate of successful stent implantation, acute complications, angiographic restenosis after 6 months and major cardiac events (death, myocardial infarction, target vessel revascularization) during follow-up were assessed. The success rate of stent implantation was 94%. One patient died after an emergency bypass operation and one patient suffered a subacute stent thrombosis, which was successfully treated with re-percutaneous transluminal coronary angioplasty (PTCA). There were no Q- or non-Q myocardial infarctions. Clinical follow-up was carried out in 56 patients (97%) and 57 vessels were assessed by angiography (93%). Mean length of the follow-up period was 6.8+/-2.3 months. During the 6 months' follow-up period, one patient died, two patients suffered an acute non-Q myocardial infarction and eight patients had revascularization of the target vessel. Major cardiac event rate for all patients where stent implantation was intended was 23%. Angina CCS class declined from 3.0+/-0.9 to 1.1+/-0.8 (p < 0.01) before PTCA to follow-up. Overall restenosis rate was 28%. In 14 lesions with a stented segment length of <20 mm, the restenosis rate was 21%; in 31 lesions with a stented segment length > or =20 and <30 mm, the restenosis rate was 26%; and in 13 lesions with a stented segment length of > or =30 mm, the restenosis rate was 42%. Although there was a high procedural success rate after implantation of the Freedom stent in long or tortuous lesions, problems with high restenosis rates in long lesions remain unresolved.

Long-term renal and cardiovascular effects of antihypertensive treatment regimens based upon isradipine, perindopril and thiazide.

The aim of this study was to describe the renal function (renal hemodynamics, water and sodium handling) and its relation to cardiovascular structural changes in a population of essential hypertensive patients before and after antihypertensive treatment. Glomerular filtration rate and renal plasma flow were measured by a constant infusion technique. The reference substances used were [131I]iodohippurate (Hippuran) and [125I]iothalamate. The lithium clearance method was used for measuring renal water and sodium handling. Microalbuminuria was measured. A subcutaneous gluteal biopsy was taken and the media thickness to lumen diameter ratio of small resistance vessels was determined. Left ventricular mass index was determined by echocardiography. Thirty-seven patients with newly diagnosed or poorly controlled essential hypertension were randomized to treatment with regimens based upon either isradipine, perindopril or hydrochlorothiazide-amiloride. Atenolol and hydralazine were added as secondary and tertiary drugs, respectively, when needed for normalization of diastolic blood pressure. Investigations were performed before and after 9 months of normalization of blood pressure. Renal function in untreated hypertensive patients was characterized by increased renal vascular resistance, decreased renal blood flow, normal glomerular filtration fraction and normal serum creatinine. No association was found between peripheral resistance vessel structure in subcutaneous vessels and renal hemodynamic parameters. Patients with severe left ventricular hypertrophy (left ventricular mass >360 g) had lower glomerular filtration fraction, greater renal vascular resistance, lower renal blood flow and increased microalbuminuria in comparison with patients with less pronounced cardiac changes. After 1 year of treatment, which had a profound effect on heart and vessel structure, renal hemodynamics were unchanged in patients receiving antihypertensive treatment regimens based on the ACE inhibitor perindopril or the Ca-antagonist isradipine, whereas renal plasma flow was reduced, glomerular filtration rate preserved and filtration fraction significantly increased in those treated with a regimen based on diuretics. The serum creatinine concentration was decreased in the former group, whereas it was unchanged in the latter two. Significantly detrimental effect on uric acid homeostasis was only found in patients treated with a regimen based on diuretics.

Proximal tubular function in essential hypertensives on beta-blocker therapy with atenolol.

Renal plasma flow (RPF) and glomerular filtration rate (GFR) were measured during waterloading and constant infusion of [131I]hippuran and [125I]iothalamate in 24 mild to moderate essential hypertensive patients before and after 3.5 months treatment with atenolol. Clearances of sodium and potassium were measured 2-3 hours post-dosing and renal vascular resistance (RVR) and filtration fraction (FF) were calculated. Measurement of clearance of lithium (CLi) and uric acid (Curic acid) was employed to investigate specifically proximal tubular function. Beta-blockade with atenolol produced a borderline significant decrement in RPF but no change in GFR, RVR and FF. There was a significant reduction in CLi, fractional proximal escape of sodium and water, Curic acid and an increase in absolute proximal reabsorption of sodium, indicating an inhibition of proximal tubular function. The distal tubular parameters exhibited changes tending to normalize excretion of sodium, but not water. Changes in RVR were inversely related to changes in CLi and Curic acid, suggesting unopposed alfa-adrenergic stimulation to be implicated in the renal counterregulation at a proximal tubular site following long-term administration of atenolol in essential hypertension.

Silent pulmonary embolism in patients with deep venous thrombosis. Incidence and fate in a randomized, controlled trial of anticoagulation versus no anticoagulation.

OBJECTIVES: A high frequency of asymptomatic pulmonary embolism (PE) in patients with deep venous thrombosis (DVT) has been reported, but information about the outcome of the patients with PE remains sparse. The aims of the present study were to assess the prevalence of silent PE in patients with symptomatic, venographically proven DVT, and to evaluate the natural history of silent PE. DESIGN: Consecutive patients from one centre of primary care were included in a randomized, open study with blinded control. All patients gave written, informed consent. SUBJECTS: Eighty-seven consecutive patients with venographically proven DVT and with a perfusion-ventilation lung scintigraphy performed within 48 h of the DVT diagnosis were included. On the 10th and 60th days the lung scintigraphy was repeated in 80 and 60 patients, respectively. All the patients were followed for 3 months in the out-patient clinic. INTERVENTIONS: All patients were ambulated from the first day and were allocated randomly to no anticoagulant (non-AC) therapy or to AC therapy with intravenous heparin infusion for at least 6 days and oral AC therapy for 3 months. RESULTS: Forty-three of these patients had a high probability lung scintigraphy for PE. Distal vein and femoral vein thrombosis embolized in 33 and 53% of patients, respectively. The progression rate after 60 days was 3% in both the AC and the non-AC group and after 10 days the rates were 13 and 8%, respectively. CONCLUSIONS: A high frequency of silent PE in patients with DVT both above and below the knee is demonstrated. AC treatment did not influence the resolution rate of PE or the rate of clinical PE in a 3-month follow-up period.

Anticoagulant therapy in deep venous thrombosis. A randomized controlled study.

Ninety patients with venographically proven deep venous thrombosis(DVT) but without clinical signs of pulmonary embolism(PE) were randomized into two different treatment regimens to compare the safety and efficacy of continuous intravenous heparin and oral anticoagulant(AC) treatment versus non-AC treatment. All patients in the two treatment groups were actively mobilized from the day of admission and wore graduated compressing stockings. In the non-AC-group the patients were treated with phenylbutazone for ten days. Treatment with heparin was maintained for 6 days and oral AC treatment was given from the third day and continued for 3 months. Venography was repeated after 30 days. A perfusion-ventilation lung scan was performed on day 1-2, 10 and 60. In fifty-nine patients a revenography was performed, twenty nine in the AC-group and thirty in the non-AC group. For distal veins regression was found in nine and eight respectively (4.4% in favour of AC, 95% confidence limit 27.5% to -18.7%) and in proximal veins regression was found in five and eight, respectively (10.9% in favour of AC, 95% confidence limit 32.0% to -10.1%). No difference in lung scans was found after 10 days (0.8% in favour of AC, 95% confidence limit 21.5% to -19.9%) or after 60 days (3.3% in favour of non-AC treatment, 95% confidence limit 21.8% to -28.5%). In the AC group the incidence of bleeding complications was 8.3%. No side-effects of phenylbutazone was found. The present controlled clinical study demonstrated no effect of AC-treatment on DVT progression in actively mobilized patients wearing graduated compressing stockings when compared to a non-AC treated group receiving analgetic therapy with phenylbutazone. However, the patient population of the study is relatively small with wide confidence intervals for differences between groups. Before more general recommendations can be made, a large scale placebo-controlled study is needed to evaluate the possible effect of AC-treatment in DVT patients, who can be mobilized from the first day.

Observer variation in the interpretation of ventilation-perfusion lung scintigraphy.

The diagnosis of pulmonary embolism (PE) remains one of the most difficult in clinical medicine, and the diagnostic value of lung scintigraphy has been questioned. To evaluate the observer variation in the interpretation of ventilation-perfusion lung scanning in the diagnosis of PE, 87 lung scintigrams from consecutive patients with phlebography-proven deep venous thrombosis and without clinical signs of PE were randomly mixed with 50 reference lung scintigrams from patients with PE symptoms. The scintigrams were reevaluated blind by two experienced clinical physiologists. Each observer evaluated each lung scintigram twice and recorded whether the lung scan was normal or abnormal. If it was abnormal, the location and number of segment defects were registered. The intraobserver agreement, including number and location of segments, ranged from 0.77 to 0.85 and for the diagnosis of PE from 0.88 to 0.92 with a kappa of 0.80-0.84. The values for the interobserver agreement for the diagnosis of PE were 0.73-0.80 with a kappa of 0.56-0.67. It is concluded that in the interpretation of ventilation-perfusion lung scintigraphy the use of a simple scheme-deciding whether there is segmental ventilation-perfusion mismatch or not-has a good reproducibility with a high kappa for inter- and intraobserver variation and can serve as a simple routine method for diagnosing PE.

Proximal renal tubular pressure-natriuresis-relation in essential hypertensives following acute vasodilatation.

Blood pressure (BP) and excretory function including lithium clearance were investigated during water-loading and constant infusion of 131I-hippuran and 125I-iothalamate for measurement of renal haemodynamics in 8 untreated essential hypertensives (mean BP +/- SD: 169 +/- 14/107 +/- 6 mmHg) before and after vasodilatation with an i.v. bolus of the potassium-channel opener, pinacidil, 0.01 mg/kg. Systolic BP (-7 +/- 4%; p < 0.05) and diastolic BP (-13 +/- 8%; p < 0.01) decreased significantly and heart rate increased (11 +/- 8%; p < 0.01). Clearance (C) of lithium, sodium, urinary flow rate, potassium and absolute distal reabsorption of sodium all fell significantly. The changes of these variables were significantly correlated with the fall in BP (CLi:r = 0.92, CNa: r = 0.85, V: r = 0.81, CK:r = 0.84), despite no significant changes in renal haemodynamic parameters: glomerular filtration rate, renal plasma flow and renal vascular resistance. A proximal tubular effect was also indicated by a fall in Curic acid and fractional Curic acid. In conclusion, vasodilatation in essential hypertensives following administration of the potassium channel opener, pinacidil, induces a fall in blood pressure with a corresponding fall in fractional proximal tubular excretion of sodium and output of sodium and water from proximal to distal tubular segments, proposing an acute proximal tubular pressure-natriuresis relation.

Renal effects of xamoterol in patients with moderate heart failure.

The acute renal effects of xamoterol, a partial beta 1-agonist, were studied in 12 patients with congestive heart failure (NYHA II-III) in stable condition on diuretic therapy for at least 6 weeks. Each patient was given a single intravenous infusion of xamoterol (0.2 mg/kg) or placebo in random order 2 weeks apart. Using constant infusion and lithium clearance techniques, clearance and excretion measurements were made in the supine position at 30- to 60-min intervals before, during, and up to 6 hours after infusion. Blood pressure, heart rate, renal plasma flow, glomerular filtration rate, and urinary flow rate remained unchanged, but xamoterol lowered sodium excretion by 30% (p < 0.05). The decrease started 120 minutes after infusion. Proximal reabsorption of sodium increased after xamoterol infusion, whereas plasma values of aldosterone and angiotensin II were unaffected. It is concluded that the acute renal effects of xamoterol imply an impaired sodium excretion determined by the tubular actions of the drug. The present results suggest that xamoterol may aggravate one of the important abnormalities intrinsic to the pathology of congestive heart failure. These findings are in contrast to the beneficial effects of xamoterol demonstrated in many clinical trials where xamoterol was given orally for a longer period.

Combined actions of isradipine and captopril on renal function in hypertension.

The object of this study was to test the hypothesis that the natriuretic and uricosuric effect of calcium-entry blockers could be mediated through antagonism of angiotensin II dependent intrarenal mechanisms. The antihypertensive efficacy, haemodynamic and excretional effects of superimposed calcium blockade with isradipine were investigated in seven hypertensives with unsatisfactorally controlled blood pressure with captopril 50 mg twice daily. Glomerular filtration rate (GFR) and renal plasma flow (RPF), clearances (C) of sodium (Na), potassium (K), uric acid (UA) and lithium (Li), were measured before and after a low-dose bolus of isradipine, i.v. Subsequently, measurements were repeated during constant i.v. infusion of a higher dose with definite systemic haemodynamic effects. After 4 months of combined treatment with isradipine and captopril renal investigations were carried out again. The low isradipine dose induced a slight but statistically significant increment in CNa (22% +/- 28) and heart rate (4% +/- 4), whereas no other variables changed significantly. Infusion of the high isradipine dose caused a pronounced fall in renal vascular resistance (27% +/- 14), systolic (8% +/- 2) and diastolic blood pressure (17% +/- 5). RPF increased significantly (15% +/- 18) whereas no changes were noted in GFR, filtration fraction and urinary albumin excretion rate. In spite of the pronounced fall in BP during the high dose infusion, significant increments in natriuresis (91% +/- 63) and diuresis (41% +/- 27) were induced. The natriuresis was caused by a proximal tubular action as indicated by increased CLi and CLi/GFR.(ABSTRACT TRUNCATED AT 250 WORDS)

Alpha-adrenoceptor blockade in patients with mild to moderate hypertension: long-term renal effects of doxazosin.

Using constant infusion technique and a water-loading procedure, we investigated renal hemodynamic and excretional variables in 15 essential hypertensive patients [diastolic blood pressure (DBP) 102 +/- 10 mm Hg] after 3 weeks of placebo and after 16 weeks of treatment with a postjunctional alpha 1-adrenoceptor-antagonist, doxazosin (1-16 mg) once daily. A minor decrease in supine DBP (p less than 0.05) but no significant changes in systolic BP (SBP) and heart rate (HR) were observed. No significant changes were noted in glomerular filtration rate (GFR), renal plasma flow (RPF), and renal vascular resistance (RVR). The mean renal excretion rate of sodium, potassium, uric acid, and albumin for the entire group was unaffected by the treatment, but the individual changes in sodium clearance correlated significantly with changes in mean BP (r = 0.64, n = 15, p less than 0.05). Six patients showed an increase in sodium excretion after treatment, whereas nine showed a decrease. No decrease in mean body weight was noted, but the BP reduction after 5 months of treatment correlated significantly with the changes in body weight (r = 0.62, n = 15, p less than 0.01). The results indicate that long-term treatment with doxazosin had no deleterious effect on renal function, but the effects on BP were rather modest. The individual BP response is probably determined by the degree of fluid retention even if an intact pressure-natriuresis relationship could still be demonstrated during chronic therapy.

Normal serum levels of calcitonin gene-related peptide (CGRP) in mild to moderate essential hypertension.

Calcitonin gene-related peptide (CGRP), a highly potent vasodilator, is expressed from the calcitonin-gene and has been localized to nerve fibers of the cardiovascular system, suggesting involvement in the physiologic regulation of vascular tone. In this investigation serum concentrations of CGRP were measured in patients with untreated mild to moderate essential hypertension (WHO I-II) and compared with concentrations in sex- and age-matched normal controls to assess a possible relationship between changes in concentrations of CGRP and this condition. The study showed no significant difference in concentrations of CGRP between patients and the normotensive controls. However, a weak but significant positive correlation was found between systolic (SBP), diastolic (DBP), mean blood pressures (MBP), and circulating concentrations of CGRP when calculated for all individuals included in the study. No correlation was found between heart rates (HR) and concentrations of CGRP. In the normotensive control group, but not in patients with hypertension, a significant positive correlation was present between body weights and concentrations of CGRP. These findings do not support the hypothesis that low expression of CGRP plays a causal role in essential hypertension, but the results do not exclude a potential receptor defect for CGRP to be involved in the disease.

Acetylsalicylic acid 100 mg and 1000 mg daily in acute myocardial infarction suspects: a placebo-controlled trial.

Of 1078 patients admitted to the coronary care unit with acute chest pain, 293 who had possible acute myocardial infarction and symptoms of median 4 h duration were randomized to treatment with acetylsalicylic acid (ASA) 100 mg daily, 1000 mg daily or placebo for 3 months. During hospitalization, the combined incidence of cardiac death and non-fatal myocardial infarction on-treatment (withdrawals not included) was significantly lower (P less than 0.02) in the 100 mg group (7.1%) than in both the 1000 mg group (20.8%) and the placebo group (19.7%). During later time periods of treatment and at all time periods analysed according to the intention-to-treat principle (withdrawals included), data suggested the same trend, but differences were not statistically significant. Collagen-induced platelet aggregation and serum thromboxane B2 were reduced to the same degree in the two ASA groups and were normal in the placebo group. The data suggest that low-dose ASA could be cheap and safe as first-aid therapy in myocardial infarction suspects.

[Acetylsalicylic acid in the treatment of arterial thromboembolic diseases. 1. Pharmacologic aspects]. / Acetylsalicylsyrebehandling ved arterielle trombo-emboliske sygdomme. 1. Farmakologiske aspekter.

The possible antithrombotic potential of acetyl salicylic acid (ASA) has been established in recent years and the preparation has been employed extensively in ischaemic cardiac disease and cerebrovascular conditions. The inhibiting effect of ASA on platelet function by means of blocking of cyclo-oxygenase is mentioned and, similarly, the presumed role in thrombosis development and atherogenesis is mentioned. ASA's pharmacokinetics are illustrated with emphasis on optimal anti-thrombotic ASA dosage, in particular, in relation to the effects of the preparation on the thromboxan A2 (TxA2)/prostacyclin (PGI2)-ratio. This is probably best achieved by means of low oral dosage in the form of sustained-release ASA formulation where the inhibition of platelet function probably occurs mainly in the presystemic circulation. It is concluded that a daily dosage of 80-100 mg ASA ensures effective and rapid inhibition of TxA2 production. Administration of 30-50 mg ASA daily results in a corresponding blockage of TxA2 production but not until after treatment for three to four days.

[Acetylsalicylic acid in the treatment of arterial thromboembolytic diseases. 2. Clinical documentation]. / Acetylsalicylsyrebehandling ved arterielle tromboemboliske sygdomme. 2. Klinisk dokumentation.

A review of the literature is undertaken to account for the current status of acetylsalicylic acid (ASA) in the treatment of patients with arterial thrombo-embolic conditions. Employment of ASA monotherapy has been documented to be effective in clinically controlled investigations in patients with unstable angina pectoris, transient cerebral ischaemia, coronary by-pass and femoro-popliteal endarterectomy and introduction of vascular prostheses and, in addition, in primary and secondary prophylaxis of acute myocardial infarction (AMI). In combination with dipyridamol, ASA has been found to be effective in secondary AMI prophylaxis, coronary by-pass operation and in peripheral arteriosclerosis. In patients with cardiac valvular prostheses, conventional anticoagulation therapy must still constitute the basic treatment but dipyridamol may be employed to increase the antithrombotic efficacy of the treatment. The dosage of ASA in the majority of works has been about 1,000 mg daily while isolated investigations have shown good effect from doses as low as 60 mg daily. It appears to be important for the efficacy of the treatment with platelet inhibitors in the above-mentioned conditions that treatment is instituted rapidly and, in connection with operative intervention, preferably preoperatively. In other clinical conditions such as preeclampsia, hypertension in pregnancy, diabetic angiopathy and nephropathy, membranoproliferative glomerulonephritis and arterio-venous shunts with haemodialysis, treatment with ASA appears to be effective but documentation in extensive clinically-controlled investigations is not yet available. The duration of treatment with ASA in arterial thrombo-embolic disease does not appear to be illustrated unanimously in the articles published but, as the atherosclerotic lesion is not influenced by ASA, there are indications for life-long therapy.

Bepridil versus verapamil in stable angina pectoris--a controlled clinical trial.

The calcium antagonist bepridil (bepridil monohydrochloride monohydrate, Org 5730, Cordium) was investigated in comparison with verapamil in a double-blind cross-over design in patients with angina pectoris. Exercise parameters, frequency of anginal attacks, consumption of nitroglycerin and subjective preference were analysed for 36 patients. The exercise capacity, estimated by exercise time and total work load during standard bicycle testing, was significantly more improved with bepridil treatment than with verapamil treatment. No significant differences were observed in frequencies of anginal attack, consumption of nitroglycerin and subjective preference. Side effects were mild and equally divided over both treatment groups.

Long-term effects of isradipine on blood pressure and renal function.

The hemodynamic and renal effects of isradipine were investigated in 10 hypertensive patients treated for 3.5 months and in a further nine patients treated for two years. Both groups achieved significant and sustained reductions in systolic blood pressure/diastolic blood pressure (-15 percent/-12 percent and -15 percent/-20 percent, respectively; p less than 0.001). Renal parameters were investigated two to three hours after the morning dose of isradipine, using a water-loading procedure. After 3.5 months of treatment, the glomerular filtration rate and renal plasma flow showed small increases (+6 percent and +9 percent, respectively, p less than 0.05), whereas, after two years, these changes were no longer present (+4 percent and 0 percent). Clearance of sodium and uric acid was increased by 40 percent (p less than 0.01) and 21 percent (p less than 0.01), respectively, after 3.5 months, and by 45 percent (p less than 0.05) and 23 percent (p less than 0.01), respectively, after two years. Lithium clearance studies revealed the natriuretic effect to be located in the proximal tubule. After 3.5 months, a significant relationship was found between the blood pressure response and the change in sodium excretion, but this relationship also was no longer present after two years. In conclusion, because of a maintained blood pressure-lowering effect while preserving renal function, and sustained natriuretic and uricosuric actions, isradipine can be considered a promising agent in the long-term treatment of arterial hypertension.