Search

Renal dysfunction is a prognostic factor in heart failure (HF) and is associated with an increased mortality risk and increased risk for re–admission. We examined risk and predictors of end–stage renal disease (ESRD) requiring renal replacement therapy in patients with HF followed in outpatient

1. The acute effect and effect of 14 days' treatment with isosorbide dinitrate (ISDN) and nifedipine (NIF) was evaluated by radionuclide cardiography in patients with chronic mitral regurgitation and sinus rhythm. 2. In 23 patients with clinically stable disease blood pressure was lowered by 15% and left ventricular volume was reduced by 16-20% after 20 mg sublingual ISDN causing combined pre- and afterload reduction. Afterload reduction alone induced by 10 mg NIF resulted in an acute 9% decrease in left ventricular endsystolic volume, whereas forward stroke volume increased by 30%, and regurgitation fraction tended to decrease. No haemodynamic effects could be detected after 14 days' treatment with 20 mg ISDN orally twice daily (preload reduction), whereas 20 mg NIF twice daily (afterload reduction) caused an increase in forward stroke volume (18%) and a decrease in both regurgitant volume (20%) and regurgitation fraction (22%) without affecting blood pressure or heart rate. 3. ISDN and NIF have beneficial acute haemodynamic effects in patients with chronic mitral regurgitation probably due to their pre- and afterload reducing properties. The reduction in regurgitation induced by NIF appears to be sustained after 14 days therapy.

Valve area and cardiac output were determined with magnetic resonance (MR) velocity mapping in 12 patients with aortic stenosis. Heart catheterization, Doppler echocardiography, and indicator dilution were performed for comparison. Left ventricle could be catheterized in only nine patients; in these cases, MR measured a mean valve area of 1.2 cm2 compared with 0.9 cm2 derived from catheterization data, with a mean difference of 0.2 cm2 between the 2 methods. The limits of agreement were [0.0, +0.5] cm2, less in patients with an important degree of concomitant regurgitation. In the whole material, MR measured a mean area of 1.1 cm2 compared with 1.2 cm2 derived from Doppler echocardiography data, with a mean difference of 0.1 cm2 and [-0.5, +0.6] cm2 as limits of agreement. In 11 patients the cardiac output was quantified by MR to a mean of 4.9 L/min and by indicator dilution to 5.0 L/min, with a mean difference of 0.2 L/min, and [-0.6, +0.8] L/min as limits of agreement. In addition, MR offers the major advance of simultaneous quantification of regurgitant volume in cases of concomitant regurgitation. In conclusion, because the two important prognostic determinants in aortic stenosis--the valvular area and the cardiac output--may be quantified, MR has potential to become a clinical tool in assessment of severity in aortic stenosis.

Objective— To determine the influence of local adiposity on insulin depot size during CSII at basal rate. Research Design and Methods— In 27 diabetic patients, a constant infusion of 125I-labeled Actrapid insulin was given, with U-40 insulin at a rate of 1.12 IU/h in 20 patients, and U-100 at a rate of 1 IU/h in 7 patients. After 16 h of infusion, the steady-state depot size was measured by external counting, and the local skin fold was measured with a Harpenden skin-fold caliper. Results— U-40 insulin infusion resulted in a steady-state depot size of 5.1 U (2.1–10.9 U), and a corresponding skin-fold thickness of 17.8 mm (5–34 mm). A positive correlation was found between depot size and skin-fold thickness. A similar correlation was observed with U-100 insulin. Conclusions— During basal rate CSII, large variations in local skin-fold thickness create large variations in the steady-state depot size, which is partly predictable just by lifting the skin fold.

That diabetes is a risk factor for congestive heart failure has been established for decades, but knowledge of the pathophysiology and treatment of heart failure in diabetes is limited. The prevalence of diabetes in different surveys and clinical trials of heart failure ranges from 10 to > 30% (1). In the community setting, data from the Framingham Heart Study have shown an increased incidence of congestive heart failure in diabetic subjects irrespective of coronary heart disease and hypertension (2). The relative impact of diabetes on developing heart failure was found to be greater in women. In the Studies of Left Ventricular Dysfunction (SOLVD) Trials and Registry, diabetes was found to be an independent risk factor for mortality and morbidity in both symptomatic and asymptomatic heart failure (3). A common finding in diabetic patients enrolled in clinical trials of myocardial infarction is a discrepancy between left ventricular systolic function and heart failure symptoms (4,5). Despite similar left ventricular systolic function, patients with diabetes have more pronounced heart failure symptoms, use more diuretics, and have an adverse prognosis compared with those without diabetes. One putative explanation for this discrepancy is diastolic dysfunction of the left ventricle. In over heart failure, diastolic dysfunction often coexists with systolic dysfunction as a consequence of ischemic …

Observational studies and surveys have shown that lipid-lowering treatment is not optimal neither with regard to number of patients treated nor with number of patients achieving recommended goals. To address this issue in the Nordic countries, we evaluated the published literature on lipid-lowering therapies in preventive cardiology in this region.Nordic papers published from 2000 throughout 2006 dealing with lipid-lowering management in coronary heart disease prevention were identified. In total, 19 studies were analyzed.Approximately half of the patients are inadequately treated and have not achieved recommended treatment goals of total cholesterol5.0 and LDL-cholesterol3.0 mmol/L. Statins were prescribed most often in low or medium doses. The predictive factors for treatment were cholesterol level, risk of cardiovascular disease, previous cardiovascular disease, age, and gender.There is a considerable need to improve standards of preventive cardiology. Statins have to be given evidence based to achieve treatment goals according to lipid levels, and higher doses of statins or combination therapy with a statin and a cholesterol absorption inhibitor or niacin is often needed.

Background Whether N-terminal pro B-type natriuretic peptide (NT-proBNP) is a useful screening tool for angiographic coronary artery disease in patients with angina is not known. Therefore, the purpose of this study was to assess the diagnostic test performance of NT-proBNP in detecting coronary atherosclerotic lesions, as assessed by coronary angiography. Methods We examined 1034 patients referred for diagnostic angiography because of symptoms or signs of coronary artery disease. The diagnostic value of NT-proBNP in predicting clinically significant coronary disease was assessed. Results In a multiple logistic regression model, NT-proBNP above the upper normal limit (125 pg/mL) predicted clinically significant coronary disease at angiography independently of traditional cardiovascular risk factors and invasive measurements of left ventricular function (odds ratio 2.1, 95% CI 1.3-3.2, P = .001). The ability of NT-proBNP in detecting clinically significant coronary disease at angiography was modest, however, with sensitivity of 0.61, specificity 0.60, accuracy 61 (95% CI 58-64), positive likelihood ratio 1.5 (95% CI 1.3-1.8), negative likelihood ratio 0.7 (95% CI 0.6-0.8), and area under the ROC curve 0.61 (95% CI 0.58-0.64). Conclusions NT-proBNP is associated with clinically significant coronary disease at angiography, independently of left ventricular dysfunction. However, NT-proBNP is not a useful screening test for diagnosing significant angiographic lesions in patients with stable coronary disease.

P-286 Key Words: Arterial Compliance, Ambulatory Blood Pressure, Hypertension:ABS>

Background: Diabetes is an independent prognostic factor in heart failure (HF) patients, and furthermore, the frequency of diabetes in HF patiemts seems to be large. We examined the real prevalence of diabetes and prediabetes in patients with chronic heart failure, attending a HF clinic. Furthermore we examined relationship of diabetes to plasma NT-proBNP levels, functional capacity and systolic cardiac function. Methods: Between September 1999 and January 2003, 406 consecutive patients with documented systolic heart failure (left ventricular ejections fraction (LVEF) 45%) were admitted to the heart failure clinic at Frederiksberg University Hospital, Denmark, on an open access basis. All the patients attending the heart failure clinic were registered in a heart failure database. The patients were classified according to the NYHA classification and had an echocardiography performed. Plasma NT-pro BNP and fasting blood glucose (FBG) were measured in a random sample of 210 patients. These patients were similar to the other 196 patients in the heart failure clinic with respect to age, sex, LVEF, NYHA class and duration of HF. Results: In the total population (n 406) LVEF was 0.29 0.1 (mean SD), age was 72.2 ( 10.3)years, 84%was classifiedasNYHAII-III, and themajority of the patients (70%) were male. The patients with known diabetes were classified in higher NYHA classes (P 0.01); LVEFwas similar: DM (28.6 8.5%) vs. non-DM (29.3 8.9%), P 0.77; log10NT-proBNP: DM (2.19 0.65) vs.non-DM (2.14 0.55), P 0.64. In the sample population (n 198), 20% had known type 2 diabetes, 12% had unknown diabetes (FBG 6.1 mmol/l), and 12% of the patients showed IFG (Impaired Fasting Glycemia, FBG: 5.6–6.0 mmol/l). The diabetic patients where similar with respect to sex and age compared to the non-diabetics but had a higher frequency of ischemic heart disease (P 0.05). Conclusions: Abnormal glucose metabolism is extremely common in heart failure patients in this population 44%. Patients with known type 2 diabetes, as compared to non-diabetics had similar systolic cardiac function and plasma NT-pro BNP level, but lower functional status (higher NYHA class). This suggests, that LVEF and plasma BNP level do not completely describe the functional impairment in type 2 diabetic patients with HF.

Summary. A TV-game of tennis of 20 min duration was used to study the influence of mild mental stress on subcutaneous blood-flow (SBF), blood-pressure and heart rate in nine insulin-dependent diabetics and nine healthy subjects. SBF was measured on the thigh by local clearance of xenon-133. Measurements were made before, during and after the period of stress. During stress, SBF increased significantly by 26% in the healthy subjects, while SBF remained unchanged in the diabetics. The difference between the two groups was significant (P

Norepinephrine-induced vasoconstriction, which is mediated by alpha-adrenergic receptors, is accentuated in patients with autonomic neuropathy. In contrast, responses mediated by beta-adrenergic receptors, including vasodilatation and metabolic changes, have not been evaluated in these patients. To study these responses, we administered epinephrine in a graded intravenous infusion (0.5 to 5 micrograms per minute) to seven diabetic patients without neuropathy, seven diabetic patients with autonomic neuropathy, and seven normal subjects. Mean arterial pressure decreased significantly in the patients with autonomic neuropathy (P less than 0.01) but was unchanged in the other groups. Since cardiac output increased to a similar extent in the three groups, the decrease in blood pressure was due to a significantly larger decrease (P less than 0.01) in total peripheral vascular resistance in the patients with autonomic neuropathy. The heart rate increased significantly more during the infusions in the patients with neuropathy than in those without neuropathy. Epinephrine produced a greater increase in blood glucose, the glucose-appearance rate, lactate, glycerol, and free fatty acids in the patients with autonomic neuropathy than in the other groups (P less than 0.05). These findings indicate that several beta-receptor-mediated responses to epinephrine are enhanced in patients with diabetic autonomic neuropathy. The underlying mechanism remains to be elucidated.

OBJECTIVES This study evaluated the efficacy of long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor trandolapril in diabetic patients with left ventricular dysfunction after acute myocardial infarction (AMI). BACKGROUND Patients with diabetes mellitus have a high mortality following AMI, probably due to a high risk of congestive heart failure and reinfarction. Because ACE inhibition effectively reduces progression of heart failure, it could be particularly beneficial in diabetic patients after AMI. METHODS The study is a retrospective analysis using data from the Trandolapril Cardiac Evaluation (TRACE) study, which was a randomized, double-blind, placebo-controlled trial of trandolapril in 1,749 patients with AMI and ejection fraction ≤35%. The mean follow-up time was 26 months. RESULTS A history of diabetes was found in 237 (14%) of the 1,749 patients. Treatment with trandolapril resulted in a relative risk (RR) of death from any cause for the diabetic group of 0.64 (95% confidence interval 0.45 to 0.91) versus 0.82 (0.69 to 0.97) for the nondiabetic group. In the diabetic group, trandolapril reduced the risk of progression to severe heart failure markedly (RR, 0.38 [0.21 to 0.67]), and no significant reduction of this end point was found in the nondiabetic group. CONCLUSIONS The ACE inhibition after myocardial infarction complicated by left ventricular dysfunction appears to be of considerable importance in patients with diabetes mellitus by saving lives and substantially reducing the risk of progression to severe heart failure.

Eight insulin-dependent diabetic patients were simultaneously given subcutaneous infusions (1.12 IU/h each) of 1251-labeled Actrapid insulin in each side of the abdominal wall. After 24 h of infusion, the size of the infused insulin depots was measured by external counting for 5 h. The basal infusion rate was then doubled in one side and halved in the other for the next 4 h. Finally, 1.12 IU/h of insulin was given in both sides of the abdominal wall for an additional 3 h. The changes in the size of the depots were measured, and the absorption rates for each hour were calculated. During the first 5 h of infusion, the depot size was almost constant (∼5 IU) with an absorption rate that equaled the infusion rate. Doubling the infusion rate led to a significant increase in depot size, but the absorption rate remained unchanged for the first 3 h, and only thereafter was a significant increase seen. When the infusion rate was reduced to the initial 1.12 IU/h, the absorption rate remained elevated during the next 3 h. Correspondingly, when the infusion rate was decreased, the depot size also decreased, but the absorption rate remained unchanged for the first 3 h. The results show that a change in the basal insulin infusion rate does not lead to any immediate change in the insulin absorption rate. This should be considered when planning an insulin-infusion program that includes alteration(s) in the basal-rate setting.

The effect of injection technique on the absorption of subcutaneously injected short-acting insulin [125I labeled Actrapid (MC), Novo, Copenhagen, Denmark] was investigated in insulin-dependent diabetic patients. In one side of the abdomen insulin was given with a fixed standard technique. In the other side of the abdomen the temperature of the injected insulin, the depth of injection, and the duration of injection were varied. Furthermore, we compared the absorption of U40 and U100 insulin by giving either 8 U of the two insulins or 0.1 ml of both insulins simultaneously to the patients in either side of the abdomen. With regard to the injection technique the only significant finding was a faster absorption rate with deep (12 mm) than with superficial (3 mm) injection. The absorption of U100 insulin was significantly slower than of U40 insulin, when given in the same amount (8 U) as well as in the same volume (0.1 ml).

The subcutaneous absorption of 125I-labelled semisynthetic human ultralente insulin was compared with that of 125I-labelled beef ultralente in eight insulin-dependent diabetic patients using a balanced cross-over design. In randomized order, 6 U of human ultralente was given in the thigh and in the abdominal wall while 24 U was given in the contralateral thigh and 6 U of bovine ultralente in the abdominal wall. On a second occasion the injection sites of human and bovine ultralente were reversed. Human ultralente was absorbed significantly faster than bovine ultralente. Thus, the 50% disappearance time of the radioactivity in the thigh was 15 +/- 3 h versus 44 +/- 9 h for the high dose, and 13 +/- 2 h versus 21 +/- 5 h for the small dose for human and bovine ultralente, respectively. Correspondingly, values for the abdomen (6U) were 9 +/- 1 h and 16 +/- 2 h. The difference between the absorption rates for 6 U and 24 U was statistically significant for bovine ultralente only. Human ultralente, but not bovine ultralente showed faster absorption from the abdomen than from the thigh. The absorption rate of human ultralente insulin, though faster than bovine ultralente insulin, makes it suitable as the basal insulin preparation for multiple insulin injection regimens.

Albumin-kinetic studies were performed in nine uraemic patients without oedema on chronic haemodialysis and in seven normal controls in order to determine microvascular leakiness and thereby, during steady state, lymph drainage of albumin. Transvascular escape rate of albumin [TERalb i.e. the fraction of intravascular mass (IVMalb) passing into, or returning from, the extravascular space per unit time] and the distribution ratio (DRalb) between IVMalb and total albumin mass were determined from intravenously injected radioiodinated serum albumin. Before haemodialysis, TERalb was significantly elevated (mean 9 X 6% IVMalb h-1, range 5 X 9-14) as compared to the value 15 h after haemodialysis (mean 7 X 3, range 5 X 2-11, P less than 0 X 02) and to controls (mean 5 X 9, range 4 X 3-7 X 4, P less than 0 X 01). Average DRalb (mean 0 X 54, range 0 X 44-0 X 69) was clearly elevated in patients with respect to controls (mean 0 X 44, range 0 X 42-0 X 48, P less than 0 X 01), and the extravascular mass of albumin was significantly decreased (mean 27 X 9 mumol kg-1, range 14.1 - 41.2 v. mean 35.9, range 27.1 - 43.8, P less than 0.05). We interpret the results as to indicate increased transvascular filtration of albumin in microcirculatory beds with permeable capillaries (splanchnic organs), in between the haemodialysis treatment, and filtration of protein-poor fluid in areas with 'tight' capillaries (skeletal muscle, cutis) resulting in interstitial space protein depletion here. As the patients were considered to be in steady state during the measurements, the increased TERalb indicates increased lymph flux of albumin. The interstitial space protein 'wash-down' and increased lymph drainage probably serve as oedema prevention.