The acute effects of furosemide in acute heart failure assessed by remote dielectric sensing. A protocol.

INTRODUCTION: Intravenous loop diuretics have been a key component in treating pulmonary oedema since the 1960s and have a Class 1 recommendation in the 2021 guidelines for acute heart failure (AHF). While the diuretic effect of loop diuretics is well established, it remains unclear how furosemide influences pulmonary congestion and cardiac filling pressures in the hyperacute phase before significant diuresis occurs. METHODS: This was a prospective study of adult patients with AHF and objective signs of pulmonary congestion admitted to the cardiac ward. Remote dielectric sensing (ReDS) will directly measure lung fluid content, and cardiac filling pressures will be assessed by echocardiography with Doppler and strain analysis. CONCLUSIONS: This study will examine if furosemide leads to a hyperacute reduction in pulmonary congestion assessed by ReDS independent of diuretic effects in patients with AHF. We hypothesise that the haemodynamic effect of furosemide shown on pulmonary congestion may explain the subjective instant relief in patients with AHF receiving furosemide. FUNDING: Dr. Grand's salary during this project is supported by a research grant from the Danish Cardiovascular Academy funded by Novo Nordisk Foundation grant number NNF20SA0067242 and by the Danish Heart Foundation. TRIAL REGISTRATION: This protocol was approved by the Scientific Ethical Committee, H-23029822, and the Danish Data Protection Agency P-2013-14703. The protocol was registered with ClinicalTrial.org on 29 August 2023 (Identifier: NCT06024889).

Vasodilators for Acute Heart Failure - A Systematic Review with Meta-Analysis.

BACKGROUND: Acute heart failure is a public health concern. This study systematically reviewed randomized clinical trials (RCTs) to evaluate vasodilators in acute heart failure. METHODS: The search was conducted across the databases of Medline, Embase, Latin American and the Caribbean Literature on Health Sciences, Web of Science, and the Cochrane Central Register of Controlled Trials. Inclusion criteria consisted of RCTs that compared vasodilators versus standard care, placebo, or cointerventions. The primary outcome was all-cause mortality; secondary outcomes were serious adverse events (SAEs), tracheal intubation, and length of hospital stay. Risk of bias was assessed in all trials. RESULTS: The study included 46 RCTs that enrolled 28,374 patients with acute heart failure. Vasodilators did not reduce the risk of all-cause mortality (risk ratio, 0.95; 95% confidence interval [CI], 0.87 to 1.04; I2=9.51%; P=0.26). No evidence of a difference was seen in the risk of SAEs (risk ratio, 1.01; 95% CI, 0.97 to 1.05; I2=0.94%) or length of hospital stay (mean difference, -0.10; 95% CI, -0.28 to 0.08; I2=69.84%). Vasodilator use was associated with a lower risk of tracheal intubation (risk ratio, 0.54; 95% CI, 0.30 to 0.99; I2=51.96%) compared with no receipt of vasodilators. CONCLUSIONS: In this systematic review with meta-analysis of patients with acute heart failure, vasodilators did not reduce all-cause mortality.

No difference in postprandial mesenteric blood flow between healthy younger and elderly individuals.

We recently used phase-contrast magnetic resonance imaging (PC-MRI) to demonstrate an attenuated postprandial blood flow response in the superior mesenteric artery (SMA) in patients with Parkinson's disease compared to age- and sex-matched healthy controls. Since both groups showed substantial inter-individual variations, we extended the cohort of controls with a group of young individuals to investigate possible age-related effects. Seventeen healthy young subjects aged < 30 years and 17 elderly subjects aged > 50 years underwent serial PC-MRI to measure the postprandial blood flow response in the SMA after ingestion of a standardized liquid test meal (∼400 kcal). Postprandial blood flow dynamics in SMA did not differ between young and elderly subjects. A noticeable inter-individual variation in postprandial intestinal blood flow increase was found, and approximately 30% of the variation could be explained by the preprandial blood flow. Regardless of age, some subjects showed a remarkable transient SMA blood flow increase immediately after meal intake. This study provides tentative evidence that postprandial blood flow dynamics in SMA in healthy young and elderly subjects do not substantially differ, indicating that age is without impact on vascular response in SMA as an indicator for regulation of mesenteric perfusion in response to food intake.

Combination of diuretics for acute heart failure: a protocol for a systematic review of randomised clinical trials with network meta-analysis and trial sequential analysis.

INTRODUCTION: Acute heart failure (AHF) is a critical, costly condition with high mortality rates, affecting millions annually. Despite advances in cardiovascular care, AHF treatment lacks robust evidence. AHF commonly manifests with sudden heart failure symptoms such as pulmonary congestion, and the pathophysiology involves fluid overload. Initial treatment is based on intravenous diuretics typically, but the optimal combination of drugs remains uncertain. METHODS AND ANALYSIS: We will systematically review randomised controlled trials enrolling patients with AHF and volume overload undergoing in-hospital diuretic treatment. We aim to investigate any diuretic intervention. Our search strategy includes the following databases: Embase, Medline, Latin American and Caribbean Health Sciences Literature, Web of Science and the Cochrane Central Register of Controlled Trials. The primary outcome is all-cause mortality. Secondary outcomes are serious adverse events, hospital readmission and kidney failure. Study results reported at the most extended follow-up will be used for all outcomes. If appropriate, we will conduct meta-analysis, trial sequential analysis and network meta-analysis. ETHICS AND DISSEMINATION: No ethics approval is required for this study. The results will be published in a peer-reviewed journal in this field. PROSPERO REGISTRATION NUMBER: CRD42023463979.

The importance of nonobstructive plaque characteristics in symptomatic and asymptomatic coronary artery disease.

BACKGROUND: We examined obstructive and nonobstructive plaque volumes in populations with subclinical and clinically manifested coronary artery disease (CAD) using quantitative computed tomography (QCT). METHODS: 855 participants with CAD (274 asymptomatic individuals, 254 acute chest pain patients without acute coronary syndrome (ACS), and 327 patients with ACS) underwent QCT of proximal coronary segments to assess participant-level plaque volumes of dense calcium, fibrous, fibrofatty, and necrotic core tissue. RESULTS: Nonobstructive (<50% stenosis) plaque volumes were greater than obstructive plaque volumes, irrespective of population (all p<0.0001): Asymptomatic individuals (mean (95% CI)): 218 [190-250] vs. 16 [12-22] mm3; acute chest pain patients without ACS: 300 [263-341] vs. 51 [41-62] mm3; patients with ACS: 370 [332-412] vs. 159 [139-182] mm3. After multivariable adjustment, nonobstructive fibrous and fibrofatty tissue volumes were greater in acute chest pain patients without ACS compared to asymptomatic individuals (fibrous tissue: 122 [107-139] vs. 175 [155-197] mm3, p<0.01; fibrofatty tissue: 44 [38-50] vs. 71 [63-80] mm3, p<0.01. Necrotic core tissue was greater in ACS patients (29 [26-33] mm3) compared to both asymptomatic individuals (15 [13-18] mm3, p<0.0001) and acute chest pain patients without ACS (21 [18-24] mm3, p<0.05). Nonobstructive dense calcium volumes did not differ between the three populations: 29 [24-36], 29 [23-35], and 41 [34-48] mm3, p>0.3 respectively. CONCLUSION: Nonobstructive CAD was the predominant contributor to total atherosclerotic plaque volume in both subclinical and clinically manifested CAD. Nonobstructive fibrous, fibrofatty and necrotic core tissue volumes increased with worsening clinical presentation, while nonobstructive dense calcium tissue volumes did not.

How non-alcoholic fatty liver disease and cirrhosis affect the heart.

Liver diseases affect the heart and the vascular system. Cardiovascular complications appear to be a leading cause of death in patients with non-alcoholic fatty liver disease (NAFLD) and cirrhosis. The predominant histological changes in the liver range from steatosis to fibrosis to cirrhosis, which can each affect the cardiovascular system differently. Patients with cirrhotic cardiomyopathy (CCM) and NAFLD are at increased risk of impaired systolic and diastolic dysfunction and for suffering major cardiovascular events. However, the pathophysiological mechanisms behind these risks differ depending on the nature of the liver disease. Accurate assessment of symptoms by contemporary diagnostic modalities is essential for identifying patients at risk, for evaluating candidates for treatment, and prior to any invasive procedures. This review explores current perspectives within this field.

Changes in weight, body composition and metabolic parameters after switch to dolutegravir/lamivudine compared with continued treatment with dolutegravir/abacavir/lamivudine for virologically suppressed HIV infection (The AVERTAS trial): a randomised, open-label, superiority trial in Copenhagen, Denmark.

INTRODUCTION: With longer life expectancy in people living with HIV (PLWH) on antiretroviral therapy, cardiovascular disease (CVD) has become a common cause of mortality among them. Abacavir has been associated with an increased risk of myocardial infarction, but the mechanism is unknown. Additionally, abacavir may be obesogenic which could mediate an additional risk factor of CVD. We aim to investigate if discontinuation of abacavir will have a favourable impact on body weight and cardiac parameters in PLWH. METHODS AND ANALYSIS: Randomised, controlled, superiority trial of virologically suppressed PLWH on dolutegravir, abacavir and lamivudine (DTG/ABC/3TC) for ≥6 months. In total, 70 PLWH will be randomised 1:2 to either continue DTG/ABC/3TC or to switch to dolutegravir and lamivudine (DTG/3TC) providing the power of 80% at alpha 5% to detect a mean difference in weight change of 2 kg (Δ) given an SD of 2.7 kg. Follow-up will be 48 weeks. Data will be collected at baseline and week 48. Primary outcome will be change in mean body weight from baseline to week 24 and 48 evaluated in a linear mixed model. Secondary outcomes will be changes in cardiac, inflammatory and metabolic parameters, fat distribution, coagulation, endothelial, platelet function, quality of life and virological control from baseline to week 48. Measurements include CT of thorax and abdomen, external carotid artery ultrasound, liver elastography and dual energy X-ray absorptiometry and blood analysis. Plasma HIV RNA will be measured at baseline, week 4, 24 and 48. Forty participants (20 from each arm) will be included in a substudy involving cardiac MRI at baseline and week 48. Twenty non-HIV-infected controls will be included with a single scan to compare with baseline scan data. ETHICS AND DISSEMINATION: Result from this study will lead to a better understanding of the association between antiretroviral therapy and the impact on weight and risk of CVD. Findings will be useful for both clinicians and PLWH in the guidance of a more individualised HIV treatment. Results from the main study and the substudies will be submitted for publication in a peer-reviewed journal(s). The AVERTAS study is approved by the Ethics Committee of the Capital Region, Denmark (H-20011433), Danish Medicines Agency (EudraCT no. 2019-004999-19) and Regional Data Protection Centre (P-2020-207). TRIAL REGISTRATION NUMBER: Pre-results registration at ClinicalTrials.gov Identifier: NCT04904406, registered 27 May 2021. PROTOCOL VERSION: Protocol version 9.0, 4 April 2023, approved 10-05-2023 by Ethics Committee of the Capital Region, Denmark (H-20011433). Danish Medicines Agency (EudraCT no. 2019-004999-19). Regional Data Protection Centre (P-2020-207) ClinicalTrials.gov.

Prognostic value of myocardial performance index in individuals with type 1 and type 2 diabetes: Thousand&1 and Thousand&2 studies.

AIMS: Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in type 1 (T1D) and type 2 diabetes (T2D). Despite diabetes affects the myocardium, risk prediction models do not include myocardial function parameters. Myocardial performance index (MPI) reflects left ventricular function. The prognostic value of MPI has not been evaluated in large-scale diabetes populations. METHODS AND RESULTS: We evaluated two prospective cohort studies: Thousand&1 (1093 individuals with T1D) and Thousand&2 (1030 individuals with T2D). Clinical data, including echocardiography, were collected at baseline. We collected follow-up data from national registries. We defined major adverse cardiovascular events (MACE) as incident events of hospital admission for acute coronary syndrome, heart failure, stroke, or all-cause mortality. For included individuals (56% male, 54 ± 15 years, MPI 0.51 ± 0.1, 63% T1D), follow-up was 100% after median of 5.3 years (range: 4.8-6.3). MPI was associated with MACE (HR 1.2, 95%CI 1.0-1.3, P = 0.012, per 0.10-unit increase) and heart failure (HR 1.3, 95%CI 1.1-1.6, P = 0.005, per 0.10-unit increase) after adjusting for clinical and echocardiographic variables. MPI predicted MACE and heart failure better in T1D than T2D (P = 0.031 for interaction). MPI added discriminatory power to the Steno T1 Risk Engine, based on clinical characteristics, in predicting MACE [area under the curve (AUC) from 0.77 to 0.79, P = 0.030] and heart failure (AUC from 0.77 to 0.83, P = 0.009) in T1D. CONCLUSION: MPI is independently associated with MACE and heart failure in T1D but not T2D and improves prediction in T1D. Echocardiographic assessment in T1D may enhance risk prediction.

Effect of beta-blockers on multiple haemodynamics in cirrhosis: A cross-over study by MR-imaging and hepatic vein catheterization.

BACKGROUND: Non-selective beta-blockers (NSBB) are widely used in the treatment of patients with cirrhosis. Only about 50% respond with a sufficient reduction in their hepatic venous pressure gradient (HVPG) and NSBB may induce detrimental cardiac and renal effects in the presence of severe decompensation. We aimed to assess the effects of NSBB on haemodynamics using magnetic resonance imaging (MRI) and to assess if these haemodynamic changes were related to the disease severity and HVPG response. METHOD: A prospective cross-over study of 39 patients with cirrhosis. Patients underwent hepatic vein catheterization and MRI with assessments of HVPG, cardiac function, systemic and splanchnic haemodynamics before and after propranolol infusion. RESULTS: Propranolol induced significant decreases in cardiac output (-12%) and blood flow of all vascular compartments, with the largest reductions seen in the azygos venous (-28%), portal venous (-21%), splenic (-19%) and superior mesenteric artery (-16%) blood flow. Renal artery blood flow fell by -5% in the total cohort, with a more pronounced reduction in patients without ascites than in those with ascites (-8% vs. -3%, p = .01). Twenty-four patients were NSBB responders. Their changes in HVPG after NSBB were not significantly associated with other haemodynamic changes. CONCLUSION: The changes in cardiac, systemic and splanchnic haemodynamics did not differ between NSBB responders and non-responders. The effects of acute NSBB blockade on renal flow seem to depend on the severity of the hyperdynamic state, with the largest reduction in renal blood flow in compensated patients compared to decompensated patients with cirrhosis. However, future studies are needed to assess the effects of NSBB on haemodynamics and renal blood flow in patients with diuretic-resistant ascites.

Altered serum bile acid composition is associated with cardiac dysfunction in cirrhosis.

BACKGROUND: Elevated serum bile acids (BA) are harmful to the heart and alterations in the BA composition have been suggested to cause cardiovascular disturbances in cirrhosis. AIM: To investigate any associations between specific groups or individual serum BA and structural and functional cardiac abnormalities in patients with cirrhosis. METHODS: An explorative study in 86 patients with cirrhosis. All participants underwent extensive cardiac assessment, including cardiac MRI with quantification of myocardial extracellular volume (ECV), which is indicative of diffuse myocardial fibrosis. A panel of 15 individual serum BA and C4, a marker of de novo bile acid synthesis, were assessed. RESULTS: Patients with advanced cirrhosis had higher levels of total BA and conjugated BA, as well as lower C4 levels (p < 0.001). Conjugated BA levels were higher in patients with a high cardiac index (p < 0.001), increased left atrial volume index (LAVI) (p < 0.001), and in those with an abnormal myocardial ECV (p < 0.05). We also found several strong correlations between conjugated BA, both as a group and individually, and parameters of cardiac dysfunction. In a model adjusted for sex, age, BMI and MELD, conjugated BA remained significantly associated with LAVI, septal e', left ventricular volumes and cardiac index. In addition, taurocholic acid correlated closely with hepatic venous pressure gradient (HVPG) (p = 0.01). CONCLUSIONS: Increased serum concentrations of conjugated BA are associated with several cardiac parameters, indicating a potential role in the development of hyperdynamic circulation and cardiac dysfunction in cirrhosis. Moreover, taurine-conjugated BA are associated with portal hypertension.

Clinical outcomes of a short-term family-focused intervention for patients with atrial fibrillation-A randomised clinical trial.

AIMS: To evaluate a family-focused intervention for patients with atrial fibrillation (AF) in addition to conventional care and to establish its effect on health-related quality of life (HRQoL), anxiety, depression, AF symptoms, and family support. BACKGROUND: AF is a widespread heart disease affecting the well-being of patients and their family members physically and psychologically. Supporting patients and their family members could potentially facilitate regaining family strength and improve HRQoL. METHODS: Patients with newly diagnosed AF were randomised to standard care or additional family-focused intervention with change in global score of the Atrial Fibrillation Quality of Life Questionnaire (AFEQT) as primary outcome after six months' follow-up. Secondary outcomes included the Hospital Anxiety and Depression Score, the European Heart Rhythm Association score, the Ice Expressive Family Functioning Questionnaire, and the Ice Family-Perceived Support Questionnaire (ICE-FPSQ). RESULTS: Sixty-eight patients received standard care (n = 35) or family focused intervention (n = 33). The median change at the six-month follow-up on the global AFEQT score was 4.17 (-1.46-9.17) in the control group and 5.83 (-2.5-30) in the intervention group, yielding a median difference of -1.67 (p = 0.500). Change in ICE-FPSQ showed significant positive scores in favour of intervention (p < 0.001); other secondary outcome changes were non-significant. CONCLUSION: The family-focused intervention had a small positive but non-significant effect on HRQoL compared to standard care. To address the impact of AF on the patients and family members seems to improve anxiety and depression scores and perceived family support.

Automated versus manual oxygen administration for patients admitted with acute cardiovascular disease - a study protocol of a randomised controlled trial.

INTRODUCTION: Oxygen treatment of hypoxaemia is considered an essential part of the treatment of patients who are acutely admitted with medical conditions affecting cardiovascular and/or pulmonary function. Despite the important role of oxygen administration for these patients, clinical evidence on how to control supplemental oxygen to avoid hypoxaemia and hyperoxia is limited. We aim to investigate whether an automatic closed-loop oxygen administration system (O2matic) may maintain normoxaemia better than usual care. METHODS: This study will be an investigator-initiated, prospective, randomised clinical trial. The patients are randomised during admission after informed consent is obtained, at a 1:1 ratio with conventional oxygen treatment or O2matic oxygen treatment for 24 hours. The primary outcome is time within the desired peripheral capillary oxygen saturation interval: 92-96%. CONCLUSION: This study will examine the clinical applicability of a novel automated feedback device termed O2matic and assess whether the device is superior to standard care in keeping the patients in the optimal saturation interval. We hypothesise that the O2matic will increase time within the desired saturation interval. FUNDING: Johannes Grand's salary during this project is supported by a research grant from the Danish Cardiovascular Academy funded by Novo Nordisk Foundation grant number NNF20SA0067242 and by The Danish Heart Foundation. CLINICALTRIALS: gov (ClinicalTrials.gov Identifier: NCT05452863). Registered on 11 July 2022.

The Danish-American Research Exchange (DARE): a cross-sectional study of a binational research education program.

BACKGROUND: Most medical educational programs emphasize clinical observation or clinical skill acquisition, fewer focus upon research. The Danish-American Research Exchange (DARE) program, sponsored by the Lundbeck Foundation, is unique in that the medical student initiates biomedical research collaboration between Danish and US medical institutions. To achieve this, Danish medical students (DARE students) conduct binational mentored research projects while based in the United States for 10 months. In addition, DARE students are introduced to interdisciplinary thinking about how to develop ultra-low-cost healthcare interventions through the '$10 Challenge'. METHODS: We conducted a cross-sectional study of DARE alumni over five consecutive years (2015-2020, n = 24). Research metrics included completion of a research project, primary authorship, and co-authorship of publications. The number of publications, prior to and after the DARE program were enumerated. For the first four cohorts, graduation from medical school and acceptance or intention to enter a joint MD-PhD program also were assessed. Two focus groups were conducted using constructivist grounded theory. Discussions were transcribed, redacted, and coded using Dedoose software. RESULTS: DARE Medical students were 31.2 years (range 24-35), the majority were women (67%;16/24). The majority (17/24;71%) completed a first author publication in a peer-reviewed journal with a median of 3.9 per DARE alumnus. DARE alumnus reported increased proficiency in biostatistics, epidemiology, coding and public speaking as well as stronger research qualities in creativity, critical thinking, comfort in approaching scientist in both the US and Denmark (p < 0.001 for all). Qualitative key themes included: increased confidence, a deepening of research inquiry and linkage to a research network. CONCLUSIONS: Preliminarily, this study suggests that medical students can initiate binational collaboration in medicine. Benefits include research productivity, intention to pursue academic medical careers, as well as positive impacts on motivation. This medical student-initiated research model lays the groundwork for using this model across other country pairs to promote binational collaboration.

Danish phase II trial using adipose tissue derived mesenchymal stromal cells for patients with ischaemic heart failure.

AIMS: Patients suffering from chronic ischaemic heart failure with reduced left ventricular ejection fraction (HFrEF) have reduced quality-of-life, repetitive hospital admissions, and reduced life expectancy. Allogeneic cell therapy is currently investigated as a potential treatment option after initially encouraging results from clinical autologous and allogeneic trials in patients with HFrEF. We aimed to investigate the allogeneic Cardiology Stem Cell Centre Adipose tissue derived mesenchymal Stromal Cell product (CSCC_ASC) as an add-on therapy in patients with chronic HFrEF. METHODS AND RESULTS: This is a Danish multi-centre double-blinded placebo-controlled phase II study with direct intra-myocardial injections of allogeneic CSCC_ASC. A total of 81 HFrEF patients were included and randomized 2:1 to CSCC_ASC or placebo injections. The inclusion criteria were reduced left ventricular ejection fraction (LVEF ≤ 45%), New York Heart Association (NYHA) class II-III despite optimal anti-congestive heart failure medication and no further revascularization options. Injections of 0.3 mL CSCC_ASC (total cell dose 100 × 106 ASCs) (n = 54) or isotonic saline (n = 27) were performed into the viable myocardium in the border zone of infarcted tissue using the NOGA Myostar® catheter (Biological Delivery System, Cordis, Johnson & Johnson, USA). The primary endpoint, left ventricular end systolic volume (LVESV), was evaluated at 6-month follow-up. The safety was measured during a 3-years follow-up period. RESULTS: Mean age was 67.0 ± 9.0 years and 66.6 ± 8.1 years in the ASC and placebo groups, respectively. LVESV was unchanged from baseline to 6-month follow-up in the ASC (125.7 ± 68.8 mL and 126.3 ± 72.5 mL, P = 0.827) and placebo (134.6 ± 45.8 mL and 135.3 ± 49.6 mL, P = 0.855) group without any differences between the groups (0.0 mL (95% CI -9.1 to 9.0 mL, P = 0.992). Neither were there significant changes in left ventricular end diastolic volume or LVEF within the two groups or between groups -5.7 mL (95% CI -16.7 to 5.3 mL, P = 0.306) and -1.7% (95% CI -4.4. to 1.0, P = 0.212), respectively). NYHA classification and 6-min walk test did not alter significantly in the two groups (P > 0.05). The quality-of-life, total symptom, and overall summary score improved significantly only in the ASC group but not between groups. There were 24 serious adverse events (SAEs) in the ASC group and 11 SAEs in the placebo group without any significant differences between the two groups at 1-year follow-up. Kaplan-Meier plot using log-rank test of combined cardiac events showed an overall mean time to event of 30 ± 2 months in the ASC group and 29 ± 2 months in the placebo group without any differences between the groups during the 3 years follow-up period (P = 0.994). CONCLUSIONS: Intramyocardial CSCC_ASC injections in patients with chronic HFrEF were safe but did not improve myocardial function or structure, nor clinical symptoms.

Cardiovascular Mapping in Cirrhosis From the Compensated Stage to Hepatorenal Syndrome: A Magnetic Resonance Study.

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 HRS-AKI. Finally, magnetic resonance imaging seems an accurate and reliable noninvasive method to assess hemodynamics and has potential as a diagnostic tool in patients with cirrhosis.

Blunted cardiovascular effects of beta-blockers in patients with cirrhosis: Relation to severity?

AIMS: Patients with cirrhosis and portal hypertension are at high risk of developing complications such as variceal hemorrhage, ascites, and cardiac dysfunction, the latter of which is known as cirrhotic cardiomyopathy. Since non-selective beta-blockers (NSBB) may aggravate hemodynamic complications we investigated the effect of real-time propranolol infusion on cardiac function in patients with varying degrees of cirrhosis. METHODS: Thirty-eight patients with Child-Pugh A (n = 17), B (n = 17) and C (n = 4) underwent liver vein catheterization and cardiac magnetic resonance imaging. We assessed the effect of real-time propranolol infusion on the hepatic venous pressure gradient, cardiac index, stroke volume, ejection fraction, heart rate, and contractility. RESULTS: Nineteen patients were classified as responders to beta-blocker therapy. In pooling Child-Pugh B and C patients, the reduction in cardiac index by beta-blockade was weaker than in Child-Pugh A patients (-8.5% vs. -20.5%, p = 0.043). The effect of NSBB on portal pressure was inversely correlated to changes in the left atrium where the left atrial volume changed by 4 mL±18 in responders compared to 15 mL±11 in non-responders (p = 0.03). Finally, the baseline ejection fraction correlated inversely with the reduction in portal pressure (r = -0.39, p = 0.02). CONCLUSION: We found the effect of beta-blockade on cardiac index in patients with advanced cirrhosis to be less potent than in patients with early cirrhosis, indicating that underlying cirrhotic cardiomyopathy increases, and the cardiac compensatory reserve becomes more compromised, with disease progression. The differential effects of beta-blockade in the left atrium may be used to predict the effect of beta-blockers on portal pressure, but further studies are needed to investigate this possibility.

Gastric Emptying Is Not Delayed and Does Not Correlate With Attenuated Postprandial Blood Flow Increase in Medicated Patients With Early Parkinson's Disease.

Background: We have recently used phase-contrast magnetic resonance imaging (PC-MRI) to demonstrate an attenuated postprandial blood flow response in the superior mesenteric artery (SMA) in 23 medicated patients with Parkinson's disease (PD) compared to 23 age- and sex-matched healthy controls. Objective: To investigate in a sub-sample of the original cohort whether the observed blood flow response in SMA after oral food intake is related to a delay in gastric emptying. Methods: We studied 15 patients with PD in an "ON-medication" state with a mean disease duration of 3.9 ± 2.2 years and 15 healthy age- and sex-matched individuals. Participants underwent dynamic gastric scintigraphy 0, 30, 60, 120, 180 and 240 minutes after the intake of a standardized radiolabeled test meal. Gastric emptying was compared between groups. 14 of the 15 PD patients and 12 of the 15 healthy control subjects had previously undergone serial postprandial PC-MRI measurements. In these individuals, we tested for a relationship between gastric emptying and postprandial blood flow response in the SMA. Results: The dynamics of gastric emptying did not differ between groups (p = 0.68). There was substantial inter-subject variability of gastric emptying in PD patients and healthy participants. Only a single PD patient had delayed gastric emptying. In those participants who had undergone PC-MRI, postprandial increase in SMA blood flow was attenuated in PD compared to healthy controls as reported previously (p = 0.006). Gastric emptying did not correlate with the timing and amplitude of postprandial blood flow increase in SMA. Conclusion: Our preliminary results, obtained in a small group of early-stage PD patients who continued their usual dopamine replacement therapy, suggest that variations in gastric emptying after solid meal intake is within the normal range in the majority of cases. There is also no evidence for a tight relationship between the attenuated postprandial blood flow response in the SMA and normal variations in gastric emptying.