Kjell Karp

Progression of cardiomyopathy after liver transplantation in patients with familial amyloidotic polyneuropathy, Portuguese type

BACKGROUND Transthyretin amyloidosis is today an accepted indication for orthotopic liver transplantation (OLT). For several mutations progression of the cardiomyopathy has been observed after OLT. The aim of this study was to assess the course of cardiac involvement in Swedish familial amyloidotic polyneuropathy (FAP), Portuguese type, after OLT. By comparison of the echocardiographic findings before OLT with those obtained after, the course of the heart involvement was followed. METHODS Twenty-three patients, who had undergone OLT and were examined with echocardiography 1-12 months before OLT, were available for the study. Twenty-one patients were examined 12-27 months after OLT, and 12 were re-examined 52-71 months after OLT. Two-dimensional and M-mode echocardiography were performed in accordance with the standards of the American Society of Echocardiography. RESULTS A significantly increased septal and left ventricular posterior wall thickness and a significantly increased left atrial dimension was observed at the post-OLT examinations, indicating a progression of the amyloid heart disease. This increase of the cardiac involvement was neither correlated to waiting time for OLT or to pre-operative signs of cardiomyopathy. CONCLUSIONS Even though the production of the amyloidogenic-mutated transthyretin is stopped by OLT, the cardiomyopathy may progress after the operation even for the Portuguese type of FAP. The increase of the septal and left ventricular posterior wall thickness after OLT is not restricted to patients with signs of left ventricular hypertrophy before the transplantation. The findings have important implications for the follow-up of FAP patients after OLT.

Atherosclerosis in early rheumatoid arthritis: very early endothelial activation and rapid progression of intima media thickness

IntroductionIn this study we aimed to investigate whether there are indications of premature atherosclerosis, as measured by endothelial dependent flow-mediated dilation (ED-FMD) and intima media thickness (IMT), in patients with very early RA, and to analyze its relation to biomarkers of endothelial dysfunction, taking inflammation and traditional cardiovascular disease (CVD) risk factors into account.MethodsPatients from the three northern counties of Sweden diagnosed with early RA are followed in an ongoing prospective study of CVD co-morbidity. Of these, all patients aged ≤60 years were consecutively included in this survey of CVD risk factors (n = 79). Forty-four age and sex matched controls were included. IMT of common carotid artery and ED-FMD of brachial artery were measured using ultrasonography. Blood was drawn for analysis of lipids, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA)-mass, VonWillebrand factor (VWF), soluble intercellular adhesion molecule-1 (sICAM), soluble vascular cell adhesion molecule-1 (sVCAM), sE-selectin, sL-selectin and monocyte chemotactic protein-1 (MCP-1). In a subgroup of 27 RA patients and their controls the ultrasound measurements were reanalysed after 18 months.ResultsThere were no significant differences between RA patients and controls in terms of IMT or ED-FMD at the first evaluation. However after 18 months there was a significant increase in the IMT among the patients with RA (P < 0.05). Patients with RA had higher levels of VWF, sICAM-1 (P < 0.05) and of MCP-1 (P = 0.001) compared with controls. In RA, IMT was related to some of the traditional CVD risk factors, tPA-mass, VWF (P < 0.01) and MCP-1 and inversely to sL-selectin (P < 0.05). In RA, ED-FMD related to sL-selectin (P < 0.01). DAS28 at baseline was related to PAI-1, tPA-mass and inversely to sVCAM-1 (P < 0.05) and sL-selectin (P = 0.001).ConclusionsWe found no signs of atherosclerosis in patients with newly diagnosed RA compared with controls. However, in patients with early RA, IMT and ED-FMD were, to a greater extent than in controls, related to biomarkers known to be associated with endothelial dysfunction and atherosclerosis. After 18 months, IMT had increased significantly in RA patients but not in controls.

Reassessment of valve area determinations in mitral stenosis by the pressure half-time method: Impact of left ventricular stiffness and peak diastolic pressure difference

Estimation of the orifice area is of major importance in the timing of valve dilation or surgery in patients with mitral stenosis. Determination of the area has traditionally been accomplished at cardiac catheterization by the Gorlin equation. The valve area can also be estimated noninvasively with Doppler echocardiographic measurements of the pressure half-time, which is inversely proportional to the area. This method has gained widespread acceptance, but its accuracy has recently been questioned and factors other than reduction of orifice area appear to modify the pressure half-time. In the present study, the influence of left ventricular stiffness (defined as diastolic pressure rise per milliliter of mitral flow) and peak atrioventricular pressure difference on the pressure half-time was examined both in a hydraulic model and by review of data from 35 patients with mitral stenosis. Left ventricular stiffness less than 0.13 mm Hg/ml was considered normal. In the model study, the orifice area correlated only moderately with inverted pressure half-time (1/PHT) (r = 0.67). By multiple linear regression, inverted pressure half-time was shown to be dependent on valve area, chamber stiffness and peak pressure difference (R = 0.89), area and stiffness being most important (R = 0.85). In the clinical study, an increased ventricular stiffness was found in 22 of the 35 patients. The pressure half-time method overestimated the Gorlin-derived area by an average of 72% in these patients compared with only 10% in 13 patients with normal stiffness (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Dipyridamole thallium-201 single-photon emission tomography in aortic stenosis: gender differences.

Dipyridamole single-photon emission tomography (SPET) is used for the detection of coronary artery disease (CAD) and the method has also been applied in patients with aortic stenosis. This study was undertaken to establish the gender-specific normal limits of thallium-201 distribution in patients with aortic stenosis and to apply these normal limits in a larger group of patiens with aortic stenosis to obtain the sensitivity and specificity for coexisting CAD. A low-dose dipyridamole protocol was used (0.56 mg/kg during 4 min). Thallium was injected 2 min later and tomographic imaging was performed. Following image reconstruction a basal, a mid-ventricular and an apical short-axis slice were selected. The highest activity in each 6° segment was normalised to the maximal acitivity of each slice. The normal uptake for patients with aortic stenosis was obtained from ten men and ten women with aortic stenosis and a normal coronary angiography. Eighty-nine patients were prospectively evaluated. An area reduction of at least 75% in a coronary artery was considered to be a significant coronary lesion and was found in 57 (64%) patients. With gender-specific curves (-2.5 SD) sensitivity for detecting CAD was 100% and specificity was 75% in men, while sensitivity was 61% and specificity 64% in women. It is concluded that the gender-specific normal distribution of201T1 uptake in patients with aortic stenosis, using dipyridamole SPET, yields a high sensitivity and specificity for coronary artery lesions in men but a lower sensitivity and specificity in women with aortic stenosis.

Quantitative assessment of aortic regurgitation by combined two‐dimensional, continuous‐wave and colour flow Doppler measurements

The width of the regurgitant jet at the aortic valve plane, i.e. the core flow diameter, the ratio of the jet width to the left ventricular outflow diameter, the regurgitant volume and regurgitant fraction were determined using two‐dimensional, continuous wave and colour flow Doppler echocardiography. The relationship between the non‐invasive measurements and semiquantitative angiographic grading of the regurgitant flow (1 + to 4 +) was examined in a primary group of 20 patients with chronic aortic regurgitation. Cut‐off points for the non‐invasive measurements were selected so as to separate patients with mild or moderate regurgitation (1 + or 2 +) from patients with moderately severe or severe regurgitation (3 + or 4 +). These cut‐off points were prospectively applied in a new group of 35 patients with aortic regurgitation to predict the angiographic grading. Jet width correctly predicted the angiographic grading in 86% of cases, the ratio of the jet width to the outflow diameter in 83% of cases, the regurgitant volume in 86% of cases and the regurgitant fraction in 91% of cases. We conclude that the severity of aortic regurgitation as determined by angiographic grading can be estimated with reasonable accuracy by non‐invasive techniques based on colour flow imaging.

Ultrasound screening for asymptomatic carotid stenosis in subjects with calcifications in the area of the carotid arteries on panoramic radiographs: a cross-sectional study

BackgroundDirected ultrasonic screening for carotid stenosis is cost-effective in populations with > 5% prevalence of the diagnosis. Occasionally, calcifications in the area of the carotid arteries are incidentally detected on odontological panoramic radiographs. We aimed to determine if directed screening for carotid stenosis with ultrasound is indicated in individuals with such calcifications.MethodsThis was a cross-sectional study. Carotid ultrasound examinations were performed on consecutive persons, with findings of calcifications in the area of the carotid arteries on panoramic radiography that were otherwise eligible for asymptomatic carotid endarterectomy.ResultsCalcification in the area of the carotid arteries was seen in 176 of 1182 persons undergoing panoramic radiography. Of these, 117 fulfilled the inclusion criterion and were examined with carotid ultrasound. Eight persons (6.8%; 95% CI 2.2-11.5%) had a carotid stenosis - not significant over the 5% pre-specified threshold (p = 0.232, Binomial test). However, there was a significant sex difference (p = 0.008), as all stenoses were found in men. Among men, 12.5% (95%CI 4.2-20.8%) had carotid stenosis - significantly over the 5% pre-specified threshold (p = 0.014, Binomial test).ConclusionsThe incidental finding of calcification in the area of the carotid arteries on panoramic radiographs should be followed up with carotid screening in men that are otherwise eligible for asymptomatic carotid endarterectomy.Trial Registration: The study was registered at http://www.clinicaltrials.gov; NCT00514644

Flow dependence of the aortic valve area in patients with aortic stenosis: Assessment by application of the continuity equation

It has been argued that the aortic valve area (AVA) in patients with aortic stenosis increases with flow. Others, however, have attributed the apparent increase to flow dependence of the empiric constant in the Gorlin formula. We examined the changes in AVA during changes in transvalvular flow induced by dipyridamole infusion in 34 patients with aortic stenosis. Two-dimensional and Doppler echocardiography was used and AVA was calculated according to the continuity equation, which does not include empiric constants. Flow increased in 29, decreased in four, and was unchanged in one patient. There was a linear correlation between percent change in flow and percent change in AVA: delta AVA% = 1.1 + delta flow%. 0.56 (r = 0.72; p < 0.001) In conclusion, AVA was found to be flow dependent. The magnitude of change in AVA observed by noninvasive recordings agrees with previous invasive studies according to the Gorlin formula.

Doppler echocardiographic assessment of the valve area in patients with atrioventricular valve stenosis by application of the continuity equation.

Abstract. The orifice area was non‐invasively assessed in 19 patients with mitral or mitral and tricuspid stenosis by combined cross‐sectional and Doppler echocardiography. Stroke volume was calculated as the product of aortic or pulmonic cross‐sectional area and the time velocity integral of the flow across that valve, and the stenotic valve area was obtained as the stroke volume divided by the time velocity integral of the stenotic valve. In addition, the mitral valve area was estimated by the pressure half‐time method of Hatle et al. The non‐invasive determinations were compared with those calculated by the Gorlin formula at cardiac catheterization.

Assessment of Myocardium at Risk with Computerized Vectorcardiography and Technetium-99m-Sestamibi-Single Photon Emission Computed Tomography during Coronary Angioplasty

Objective - To compare the myocardium at risk (MAR) as estimated by computerized vectorcardiography (cVCG) with MAR determined by Tc-99m-sestamibi-SPECT using coronary angioplasty as the model for transient transmural ischemia in humans. Methods and results - In 37 patients with stable angina pectoris, cVCG was recorded continuously during coronary angioplasty. The scintigraphic defect was quantified using an automated software program (CEqual). The ST vector magnitude (ST-VM) and the ST change vector magnitude (STC-VM) correlated well with MAR estimated by scintigraphy, ST-VM ( r = 0.71, p < 0.001) and STC-VM ( r = 0.84, p < 0.001). All patients with STC-VM <50 w V during occlusion had defects of less than 10% of the left ventricle. Conclusion - 1) ST-VM and STC-VM give a reasonable useful estimate of MAR size during transient coronary occlusion. 2) STC-VM <50 w V is a reliable limit to identify patients with MAR size less than 10%. 3) ST-VM does not add information to STC-VM with respect to detection of ischemia. 4) The existence of collateral vessels has great impact on both ST-vector changes and scintigraphic imaging of myocardial ischemia.

The Extent of Subclinical Atherosclerosis Is Partially Predicted by the Inflammatory Load: A Prospective Study over 5 Years in Patients with Rheumatoid Arthritis and Matched Controls.

Objective. This prospective followup study investigated subclinical atherosclerosis in relation to traditional cardiovascular disease (CVD) risk factors and inflammation in patients with rheumatoid arthritis (RA) recruited at diagnosis compared with controls. Methods. Patients diagnosed with early RA were consecutively recruited into a prospective study. From these, a subgroup aged ≤ 60 years (n = 71) was consecutively included for ultrasound measurement of intima-media thickness (IMT) and flow-mediated dilation (FMD) at inclusion (T0) and after 5 years (T5). Age- and sex-matched controls (n = 40) were also included. Results. In the Wilcoxon signed-rank test, both IMT and FMD were significantly aggravated at T5 compared to baseline in patients with RA, whereas only IMT was significantly increased in controls. In univariate linear regression analyses among patients with RA, the IMT at T5 was significantly associated with age, systolic blood pressure (BP), cholesterol, triglycerides, Systematic Coronary Risk Evaluation (SCORE), and Reynolds Risk Score at baseline (p < 0.05). Similarly, FMD at T5 was significantly inversely associated with age, smoking, systolic BP, SCORE, and Reynolds Risk Score (p < 0.05). A model with standardized predictive value from multiple linear regression models including age, smoking, BP, and blood lipids at baseline significantly predicted the observed value of IMT after 5 years. When also including the area under the curve for the 28-joint Disease Activity Score over 5 years, the observed value of IMT was predicted to a large extent. Conclusion. This prospective study identified an increased subclinical atherosclerosis in patients with RA. In the patients with RA, several traditional CVD risk factors at baseline significantly predicted the extent of subclinical atherosclerosis 5 years later. The inflammatory load over time augmented this prediction.