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INTRODUCTION:Arterial vasodilation and hyperdynamic circulation are considered hallmarks of the pathophysiological mechanisms of decompensation in cirrhosis. However, detailed characterization of peripheral, splanchnic, renal, and cardiac hemodynamic have not previously been published in a spectrum from healthy stage to advanced decompensated liver disease with hepatorenal syndrome-acute kidney injury (HRS-AKI).METHODS:We included 87 patients with cirrhosis and 27 healthy controls in this prospective cohort study. The population comprised patients with compensated cirrhosis (n = 27) and decompensated cirrhosis (n = 60); patients with decompensated cirrhosis were further separated into subsets of responsive ascites (33), refractory ascites (n = 16), and HRS-AKI (n = 11). We measured portal pressure and assessed regional blood flow by magnetic resonance imaging.RESULTS:Patients with compensated cirrhosis experienced higher azygos venous flow and higher hepatic artery flow fraction of cardiac index than controls (P < 0.01), but other flow parameters were not significantly different. Patients with decompensated cirrhosis experienced significantly higher cardiac index (P < 0.01), higher superior mesenteric artery flow (P = 0.01), and lower systemic vascular resistance (P < 0.001) compared with patients with compensated cirrhosis. Patients with HRS-AKI had the highest cardiac output and lowest renal flow of all groups (P < 0.01 and P = 0.02, respectively). Associations of single hemodynamic parameters were stronger with model for end-stage liver disease than with portal pressure.DISCUSSION:The regional cardiocirculatory changes seem closely linked to clinical symptoms with 3 distinguished hemodynamic stages from compensated to decompensated cirrhosis and, finally, to HRS-AKI. The attenuated renal perfusion despite high cardiac output in patients with HRS-AKI challenges the prevailing pathophysiological hypothesis of cardiac dysfunction as a causal factor in

Background In patients with type 2 diabetes, cardiovascular disease (CVD) is the major cause of morbidity and mortality. We evaluated the combination of NT-proBNP and coronary artery calcium score (CAC) for prediction of combined fatal and non-fatal CVD and mortality in patients with type 2 diabetes and microalbuminuria (>30 mg/24-h), but without known coronary artery disease. Moreover, we assessed the predictive value of a predefined categorisation of patients into a high- and low-risk group at baseline. Methods Prospective study including 200 patients. All received intensive multifactorial treatment. Patients with baseline NT-proBNP >45.2 ng/L and/or CAC ≥400 were stratified as high-risk patients (n = 133). Occurrence of fatal- and nonfatal CVD (n = 40) and mortality (n = 26), was traced after 6.1 years (median). Results High-risk patients had a higher risk of the composite CVD endpoint (adjusted hazard ratio [HR] 10.6 (95 % confidence interval [CI] 2.4-46.3); p = 0.002) and mortality (adjusted HR 5.3 (95 % CI 1.2-24.0); p = 0.032) compared to low-risk patients. In adjusted continuous analysis, both higher NT-proBNP and CAC were strong predictors of the composite CVD endpoint and mortality (p ≤ 0.0001). In fully adjusted models mutually including NT-proBNP and CAC, both risk factors remained associated with risk of CVD and mortality (p ≤ 0.022). There was no interaction between NT-proBNP and CAC for the examined endpoints (p ≥ 0.31). Conclusions In patients with type 2 diabetes and microalbuminuria but without known coronary artery disease, NT-proBNP and CAC were strongly associated with fatal and nonfatal CVD, as well as with mortality. Their additive prognostic capability holds promise for identification of patients at high risk., BACKGROUND: In patients with type 2 diabetes, cardiovascular disease (CVD) is the major cause of morbidity and mortality. We evaluated the combination of NT-proBNP and coronary artery calcium score (CAC) for prediction of combined fatal and non-fatal CVD and mortality in patients with type 2 diabetes and microalbuminuria (>30 mg/24-h), but without known coronary artery disease. Moreover, we assessed the predictive value of a predefined categorisation of patients into a high- and low-risk group at baseline.METHODS: Prospective study including 200 patients. All received intensive multifactorial treatment. Patients with baseline NT-proBNP > 45.2 ng/L and/or CAC ≥ 400 were stratified as high-risk patients (n = 133). Occurrence of fatal- and nonfatal CVD (n = 40) and mortality (n = 26), was traced after 6.1 years (median).RESULTS: High-risk patients had a higher risk of the composite CVD endpoint (adjusted hazard ratio [HR] 10.6 (95 % confidence interval [CI] 2.4-46.3); p = 0.002) and mortality (adjusted HR 5.3 (95 % CI 1.2-24.0); p = 0.032) compared to low-risk patients. In adjusted continuous analysis, both higher NT-proBNP and CAC were strong predictors of the composite CVD endpoint and mortality (p ≤ 0.0001). In fully adjusted models mutually including NT-proBNP and CAC, both risk factors remained associated with risk of CVD and mortality (p ≤ 0.022). There was no interaction between NT-proBNP and CAC for the examined endpoints (p ≥ 0.31).CONCLUSIONS: In patients with type 2 diabetes and microalbuminuria but without known coronary artery disease, NT-proBNP and CAC were strongly associated with fatal and nonfatal CVD, as well as with mortality. Their additive prognostic capability holds promise for identification of patients at high risk.

OBJECTIVE. Presence of cardiac dysfunction in patients with advanced cirrhosis is widely accepted, but data in early stages of cirrhosis are limited. Systolic and diastolic functions, dynamics of QT-interval, and pro-atrial natriuretic peptide (pro-ANP) are investigated in patients with early stage cirrhosis during maximal β-adrenergic drive. MATERIAL AND METHODS. Nineteen patients with Child A (n = 12) and Child B cirrhosis (n = 7) and seven matched controls were studied during cardiac stress induced by increasing dosages of dobutamine and atropine. RESULTS. Pharmacological responsiveness was similar in cirrhosis and controls and the heart rate (HR) increased by 66 ± 15 versus 67 ± 8 min(-1). HR-blood pressure product increased equally by 115% in both cirrhotic patients and controls. However, time to resume HR of 100 beats/min was significantly longer in cirrhosis, p < 0.01. The QTc interval increased after dobutamine infusion in cirrhosis (0.41 ± 0.02 vs. 0.43 ± 0.02 s, p = 0.001) but similar electrophysiological changes were seen in controls. Cardiac volumes increased with the severity of disease. The increased cardiac output was primarily attributed to increased stroke volume. The ejection fraction was similar in patients and controls. Peak filling rate was longer in cirrhosis compared to controls (1.8 ± 0.4 and 1.4 ± 0.2 end-diastolic volume/s, p < 0.01). Pro-ANP was higher in cirrhosis and increased during stress by 13% compared to 0% in controls, p < 0.01. CONCLUSIONS. These findings indicate that patients with early stage cirrhosis exhibit early diastolic and autonomic dysfunction as well as elevated pro-ANP. However, the cardiac chronotropic and inotropic responses to dobutamine stress were normal. The dynamics of ventricular repolarization appears normal in patients with early stage cirrhosis.

BACKGROUND AND AIM: Cardiac dysfunction in patients with early cirrhosis is debated. We investigated potential cardiac dysfunction by assessing left ventricular systolic performance during a dobutamine stress test in patients with early cirrhosis.PATIENTS AND METHODS: Nineteen patients with Child A and B cirrhosis (9 with non-alcoholic cirrhosis) and 7 matched controls were included. We used cardiac magnetic resonance imaging to assess left ventricular volumes and cardiac output (CO) at rest and during maximal heart rate induced by increasing dosages of dobutamine and atropine.RESULTS: Patients with cirrhosis and controls had an equal stress response, the heart rate and ejection fraction increased similarly and maximal heart rate was reached in all. At rest CO was higher in Child B patients than controls. During maximal stress, Child B patients had higher CO (10.6±2.7 vs. 8.0±1.8 L/min), left ventricle end diastolic volume (90±25 vs. 67±16 mL), left ventricular end diastolic volume (10±4 vs. 6±2 mL) and stroke volume (80±23 vs. 61±15 mL) than Child A patients. The systemic vascular resistance was lower in Child B than Child A patients (670±279 vs. 911±274 dyne*s*cm(-5)). The left ventricle mass increased by 5.6 gram per model for end stage liver disease (MELD) point. MELD score correlated with the end diastolic and systolic volume, CO, and stroke volume at rest and at stress (all p<0.05).CONCLUSION: In patients with early cirrhosis the chronotropoic and inotropic response to pharmacological stress induced by dobutamine is normal. With progression of the disease, the mass of the heart increases along with increase in cardiac volumes.

The aim of our study was to perform a prospective study that compared the diagnostic ability of V/Q single photon emission computer tomography (V/Q-SPECT), V/Q-SPECT combined with low-dose computed tomography (CT) and pulmonary multidetector computed tomography(MDCT)-angiography in patients suspected of having pulmonary embolism (PE) using a dedicated combined SPECT/MDCT-scanner. V/Q-SPECT in combination with low-dose CT had a sensitivity of 97% and a specificity of 100%. MDCT angiography had a sensitivity of 68% and a specificity of 100%. We conclude that V/Q-SPECT in combination with low-dose CT without contrast has an excellent diagnostic performance and should be considered the first-line imaging technique in the work-up of PE in most cases.

Planar ventilation/perfusion (V/Q) scintigraphy is currently the standard method for the diagnosis of pulmonary embolism (PE) in most nuclear medicine centers. However, recent studies have shown a superior sensitivity and specificity when applying V/Q single photon emission computed tomography (SPECT) in diagnosing PE. This study evaluated the diagnostic performance of three-dimensional V/Q SPECT in comparison with planar V/Q scintigraphy.

Udgivelsesdato: 2009-Dec, The diagnosis of pulmonary embolism (PE) is usually established by a combination of clinical assessment, D-dimer testing, and imaging with either pulmonary ventilation-perfusion (V/Q) scintigraphy or pulmonary multidetector CT (MDCT) angiography. Both V/Q SPECT and MDCT angiography seem to have high diagnostic accuracy. However, only limited data directly comparing these 2 modalities are available. Hybrid gamma-camera/MDCT systems have been introduced and allow simultaneous 3-dimensional lung V/Q SPECT and MDCT angiography, suitable for diagnosing PE. The aim of our study was to compare, in a prospective design, the diagnostic ability of V/Q SPECT, V/Q SPECT combined with low-dose CT, and pulmonary MDCT angiography obtained simultaneously using a combined SPECT/MDCT scanner in patients suspected of having PE. METHODS: Consecutive patients from June 2006 to February 2008 suspected of having acute PE were referred to the Department of Nuclear Medicine at Rigshospitalet or Frederiksberg Hospital, Denmark, for V/Q SPECT as a first-line imaging procedure. The number of eligible patients was 196. Patients with positive D-dimer results (>0.5 mmol/mL) or a clinical assessment with a Wells score greater than 2 were included and underwent V/Q SPECT, low-dose CT, and pulmonary MDCT angiography in a single session. Patient follow-up was 6 mo. RESULTS: A total of 81 simultaneous studies were available for analysis, of which 38% were from patients with PE. V/Q SPECT had a sensitivity of 97% and a specificity of 88%. When low-dose CT was added, the sensitivity was still 97% and the specificity increased to 100%. Perfusion SPECT with low-dose CT had a sensitivity of 93% and a specificity of 51%. MDCT angiography alone had a sensitivity of 68% and a specificity of 100%. CONCLUSION: We conclude that V/Q SPECT in combination with low-dose CT without contrast enhancement has an excellent diagnostic performance and should therefore probably be considered first-line imaging in the wor

The haemostatic effect of recombinant activated factor VII (rFVIIa;NovoSeven) in thrombocytopenic patients has been a matter of controversy. Haemostasis by rFVIIa occurs via FVIIa-mediated thrombin generation in a platelet-dependent manner and may therefore be suboptimal in patients without functional platelets. Under such conditions, a clot-stabilizing agent, such as factor XIII (FXIII), may supplement the effect ofrFVIIa and improve haemostasis. Recombinant factor XIII (rFXIII-A2) is produced as an A2 homodimer of the FXIII A subunit and is equivalent to cellular FXIII normally found in platelets. The combined effects of rFVIIa andrFXIII-A2 were evaluated in clot lysis assays using factor XIII-deficient plasma and by whole blood thrombelastography (TEG) analysis from normal donors and thrombocytopenic stem cell transplantation patients. Clotting time was shortened by rFVIIa (0.6-10 microg/ml). rFVIIa only modestly improved anti-fibrinolysis,whereas rFXIII-A2 (0-20 microg/ml) enhanced anti-fibrinolysis without effect on clotting time. TEG analysis showed rFVIIa shortened the clotting time, and enhanced clot development, maximal mechanical strength and resistance to fibrinolysis, whereas, rFXIII-A2 enhanced clot development,maximal mechanical strength and markedly enhanced resistance to fibrinolysis. These data illustrate that rFVIIa and rFXIII-A2 contribute to clot formation and stability by different mechanisms suggesting enhanced haemostatic efficacy by combining these agents Udgivelsesdato: 2008/11

Udgivelsesdato: 2006-Dec, AIMS: Radionuclide techniques, and recently MRI, have been used for clinical evaluation of right ventricular (RV) volumes function (RVEF) and volumes; but with the introduction of 3D echocardiography, new echocardiographic possibilities for RV evaluation independent of geometrical assumptions have emerged. This study compared classic and new echocardiographic and radionuclide estimates, including gated blood pool single-photon emission computed tomography (SPECT) of RV size and function to RV volumes, and ejection fraction (RVEF) measured by magnetic resonance imaging (MRI). METHODS AND RESULTS: Thirty-four subjects with (a) prior inferior ST-elevation myocardial infarction (n=17), (b) a history of pulmonary embolism and persistent dyspnea (n=7) or (c) normal subjects (n=10) had 2D and 3D echocardiography, SPECT and MRI within 24h. End-diastolic volume and peak tricuspid regurgitation velocity were increased in patients with a history of pulmonary embolism compared to healthy subjects, 130+/-26 ml vs. 94+/-26 ml, P<0.05, and 3.3+/-1.1m/s vs. 2.3+/-0.3m/s, P<0.05, respectively, whereas no differences in RVEF were seen in the three groups. Echocardiographic as well as SPECT estimates of RV volume showed significant correlation to RV volumes by MRI. Tricuspid annular plane systolic excursion (TAPSE) had the better correlation to RVEF by MRI, r=0.48, P<0.01; whereas 3D echocardiography had a correlation of 0.42, P<0.05. Compared to MRI, 3D echocardiography underestimated RVEF by 5.9%, 95% limits of agreement 1.6-10.2%. CONCLUSION: 3D echocardiographic estimates of RV size and RVEF show only moderate correlation to MRI measures of these parameters, and simple 2D echocardiographic estimates of RV size and function show similar correlations. For routine clinical purposes the simple TAPSE may be preferred over 3D and SPECT techniques for RVEF estimation.

Udgivelsesdato: 2005-Mar-21

Udgivelsesdato: 2005-Nov, BACKGROUND: Right ventricular (RV) function is of interest in an array of cardiopulmonary diseases. First-pass radionuclide ventriculography (FP), gated blood-pool single photon emission tomography (GBPS) and cardiac magnetic resonance imaging (MRI) are three currently used non-invasive methods for evaluation of right-sided cardiac function. The aim of our study was to compare the agreement between these methods when measuring right-sided cardiac function. METHODS: Twenty-four healthy volunteers were included. Mean age was 44 years (range: 25-60) and 29% were females. All participants had FP, GBPS and breath-hold cine MRI performed according to standard protocols. RESULTS: Normal ranges for RV ejection fraction (RVEF) defined as mean +/- 2SD were 0.49-0.72, 0.44-0.66 and 0.40-0.69 when measured by MRI, FP and GBPS respectively. Bland-Altman analysis showed a mean difference (bias) between MRI and FP of 0.05 (95% CI: 0.03-0.08) and of 0.06 (95% CI: 0.02-0.10) between MRI and GBPS. No systematic bias was found between FP and GBPS. Normal values for RV end-diastolic volume index (RVEDVI) were 37-95 and 29-91 ml m(-2) when measured by MRI and GBPS respectively. The mean difference between RVEDVI was 6 ml m(-2) (95% CI: 0-11). CONCLUSIONS: (i) Normal values of RVEF differ between MRI, FP and GBPS with wide limits of agreement, accordingly it is difficult to evaluate changes over time if measured by different methods, (ii) RV volumes are in the same range when measured by MRI or GBPS but with wide limits of agreement, and (iii) if MRI is considered gold standard then FP is more accurate than GBPS for RVEF measurements.

Udgivelsesdato: 2005-Mar-18, BACKGROUND: It is now well accepted that neuroendocrine activation is of pathophysiological and prognostic importance in patients with chronic heart failure (CHF). We hypothesized that the different neuroendocrine factors reflect different aspects of the cardiac dysfunction in CHF patients and that neuroendocrine profiling could be of value. In order to study this, we investigated the relationship between hormones and cardiac dimensions and function of both the right and left ventricle. METHODS: Twenty-three patients with newly diagnosed, untreated CHF were included. Right (RVEF) and left ventricular ejection fractions (LVEF) and volumes were measured by means of first-pass and equilibrium radionuclide ventriculography. RESULTS: LVEF was 0.29 (range: 0.11-0.55). Two-thirds of the patients had dilated left ventricles with volumes above upper reference limit. Right ventricular ejection fraction was normal in all subjects as well as right ventricular volumes. Likewise, on average, the lung transit time (LTT) was normal. Brain natriuretic peptide (BNP) significantly correlated with LVEF, left ventricular end-diastolic volume index (LVEDVI) and left ventricular end-systolic volume index (LVESVI). Adrenaline correlated significantly with both right ventricular end-diastolic volume index and right ventricular end-systolic volume index. Lung transit time correlated with atrial natriuretic peptide (ANP) and BNP (only ANP in multivariate analysis). CONCLUSIONS: (1) BNP reflects the LVEF as well as diastolic and systolic dimensions; (2) adrenaline reflects the right ventricular systolic and diastolic dimensions; and (3) ANP reflects the lung transit time. We conclude that "neuroendocrine profiling" may potentially be of diagnostic and therapeutic use.

Udgivelsesdato: 2004-Jan, BACKGROUND: Neuroendocrine activation is a pathophysiological response and an important prognostic marker in patients with chronic heart failure (CHF). Although chronic activation is well described, data on the responsiveness of the hormone systems are more limited. Most previous studies have looked at activation during maximal exercise, whereas we believe that activation at a submaximal level might be more pathophysiologically relevant. AIM: To compare exercise-induced neurohormonal activation between CHF patients and normal subjects using the same relative and submaximal workload. Subjects: Twenty-three newly-diagnosed CHF patients and 18 age- and gender-matched healthy subjects were exercised at two workloads, which were calculated to correspond to 50 and 75% of each individual's heart rate response. RESULTS: In CHF patients, baseline levels of ANP, BNP, AVP, PRA and ET-1 were elevated compared to healthy subjects. Exercise induced an increase in ANP, A and NA in both CHF patients and in normal subjects, however BNP was only increased in CHF patients and not in normal subjects. CONCLUSION: When CHF patients exercise at the same relative and submaximal level as age-matched healthy subjects, the relative increases in ANP, A and NA were similar, however, BNP levels only increased in the CHF group.

Udgivelsesdato: 2003-May-19

Udgivelsesdato: 2003-Jan, A questionnaire was sent to all departments of nuclear medicine in Denmark (n=20) asking for details of myocardial perfusion imaging (MPI), including the number of patients examined each year from 1997 to 2001 and the current clinical and technical practice. All (100%) departments replied, and the survey thus covers all MPI performed in Denmark during the period in question. The number of MPI studies (examined patients) was 2,531 in 1997 (0.47 MPI/1,000/year) and 4,961 (0.93 MPI/1,000/year) in 2001, which is a doubling in activity in 5 years. Nineteen (95%) of the Danish departments performed MPI in 2001, and 14 (74%) of these reported that activity had increased over the past 5 years. MPI activity was unevenly distributed between hospitals and regions. In 2001, the university hospitals in the central Copenhagen region (capital) accounted for the highest MPI activity (2.00/1,000/year), while the non-university hospitals in general had the lowest activity rate (0.73/1,000/year). The most pronounced increment found in the period was observed in the university hospitals outside Copenhagen, where activity increased by 300% from 0.44/1,000/year in 1997 to 1.33/1,000/year in 2001. All departments providing MPI used tomographic acquisition technique and all departments used technetium tracers. The more sophisticated techniques of MPI - gated acquisition, attenuation correction and iterative reconstruction - were used in 74%, 32% and 42% of departments, respectively. The stress mode in perfusion studies was dipyridamole/adenosine in 76%, exercise in 18% and dobutamine in 6%. Despite these encouraging figures, MPI activity for 2001 remained well below what is recommended by other national and international societies. The anticipated further increase in nuclear cardiology is encouraging, but the nuclear medicine community needs to address the issues that prevent it from keeping up with demand. In general, the restricted camera time and the limited number of trained personnel

Udgivelsesdato: 2002-Dec, Metaiodobenzylguanidine (MIBG) scintigraphy is a well-established functional imaging method for localizing pheochromocytomas. However, the morphologic information revealed on the scintigram is often too sparse and thus, accordingly, supplemental computed tomography (CT) or magnetic resonance imaging are often performed. Recently, gamma cameras with built-in low-dose CT were introduced. The authors describe a patient with a high likelihood of pheochromocytoma who had simultaneous MIBG scintigraphy and low-dose CT performed as the primary examinations. The scan revealed pheochromocytomas in both adrenal glands and one extra-adrenal pheochromocytoma located in the liver. The combined imaging ensured the final diagnosis without any need for further imaging. Based on the findings of this case, the authors believe that combined MIBG scintigraphy and low-dose CT is a promising future single imaging technique for pheochromocytomas.