Pulmonary vasodilation by sildenafil in acute intermediate-high risk pulmonary embolism: a randomized explorative trial.

BACKGROUND: To investigate if acute pulmonary vasodilation by sildenafil improves right ventricular function in patients with acute intermediate-high risk pulmonary embolism (PE). METHODS: Single center, explorative trial. Patients with PE were randomized to a single oral dose of sildenafil 50 mg (n = 10) or placebo (n = 10) as add-on to conventional therapy. The time from hospital admission to study inclusion was 2.3 ± 0.7 days. Right ventricular function was evaluated immediately before and shortly after (0.5-1.5 h) randomization by right heart catheterization (RHC), trans-thoracic echocardiography (TTE), and cardiac magnetic resonance (CMR). The primary efficacy endpoint was cardiac index measured by CMR. RESULTS: Patients had acute intermediate-high risk PE verified by computed tomography pulmonary angiography, systolic blood pressure of 135 ± 18 (mean ± SD) mmHg, increased right ventricular/left ventricular ratio 1.1 ± 0.09 and increased troponin T 167 ± 144 ng/L. Sildenafil treatment did not improve cardiac index compared to baseline (0.02 ± 0.36 l/min/m2, p = 0.89) and neither did placebo (0.00 ± 0.34 l/min/m2, p = 0.97). Sildenafil lowered mean arterial blood pressure (- 19 ± 10 mmHg, p < 0.001) which was not observed in the placebo group (0 ± 9 mmHg, p = 0.97). CONCLUSION: A single oral dose of sildenafil 50 mg did not improve cardiac index but lowered systemic blood pressure in patients with acute intermediate-high risk PE. The time from PE to intervention, a small patient sample size and low pulmonary vascular resistance are limitations of this study that should be considered when interpreting the results. TRIAL REGISTRATION: The trial was retrospectively registered at www.clinicaltrials.gov (NCT04283240) February 2nd 2020, https://clinicaltrials.gov/ct2/show/NCT04283240?term=NCT04283240&draw=2&rank=1 .

Stroke Related to Transcatheter Heart Valve Thrombosis.

Non-obstructive transcatheter heart valve (THV) thrombosis as a potential mechanism after stroke after transapical transcatheter aortic valve replacement (TAVR) is demonstrated by the present case report. By performing cardiac computed tomography (CT) in addition to standard transthoracic echocardiography (TTE) follow up after TAVR, it has been shown recently that non-obstructive THV thrombosis may be more common than previously anticipated. However, the clinical implications of non-obstructive THV thrombosis remain unclear. In the present patient, post-TAVR TTE and transeophageal echocardiography demonstrated normal THV function, and showed no evidence of THV thrombosis. In contrast, cardiac CT revealed findings consistent with THV thrombosis. The patient subsequently developed acute ischemic stroke that was treated with thrombolysis. Follow up cardiac CT and echocardiography demonstrated complete THV thrombus resolution.

Computed tomographic-based three-dimensional printing of giant coronary artery fistulas to guide surgical strategy: a case series.

Background: Coronary artery fistulas (CAFs) are abnormal communications between the coronary arteries and the heart chambers, arteries, or veins, potentially leading to significant shunting, myocardial ischaemia and heart failure. Computed tomographic (CT) angiography or conventional invasive angiography is the reference standard for the diagnosis of coronary fistulas. The fistula anatomy can become very complex, which makes surgical or interventional planning challenging. Case summary: We report two cases of hugely dilated and tortuous coronary circumflex artery fistulas draining into the coronary sinus. Both patients were followed up for more than 10 years because of very complex coronary fistula anatomy and mild symptoms. From two-dimensional (2D) sliced CT images alone it, was uncertain whether surgery was feasible. However, since both patients had symptom progression (Patient 1 developed heart failure, and Patient 2 had recurrent pericardial effusions), three-dimensional (3D) heart models were printed for better understanding of the complex fistula anatomy and improved surgical planning. Both patients had successful surgery and symptomatic relief at follow-up. Discussion: The delay in surgery, until clinical deterioration, may partly be a consequence of a general reluctance in performing complex surgery in patients with CAFs. As of now, CT-based 3D printing has primarily been used in isolated cases. However, 3D printing is evolving rapidly and supplementing 2D sliced CT images with a physical 3D heart model may improve the anatomical understanding and pre-surgical planning that could lead to better surgical outcome.

Pulmonary Valve Replacement in Tetralogy of Fallot: Procedural Volume and Durability of Bioprosthetic Pulmonary Valves.

BACKGROUND: Robust data on changes in pulmonary valve replacement (PVR) procedural volume and predictors of bioprosthetic pulmonary valve (BPV) durability in patients with tetralogy of Fallot (TOF) are scarce. OBJECTIVES: This study sought to assess temporal trends in PVR procedural volume and BPV durability in a nationwide, retrospective TOF cohort. METHODS: Data were obtained from patient records. Robust linear regression was used to assess temporal trends in PVR procedural volume. Piecewise exponential additive mixed models were used to estimate BPV durability, defined as the time from implantation to redo PVR with death as a competing risk, and to assess risk factors for reduced durability. RESULTS: In total, 546 PVR were performed in 384 patients from 1976 to 2021. The annual number of PVR increased from 0.4 to 6.0 per million population (P < 0.001). In the last decade, the transcatheter PVR volume increased by 20% annually (P < 0.001), whereas the surgical PVR volume did not change significantly. The median BPV durability was 17 years (Q1: 10-Q3: 10 years-not applicable). There was no significant difference in the durability of different BPV after adjustment for confounders. Age at PVR (HR: 0.78 per 10 years from <1 year; 95% CI: 0.63-0.96; P = 0.02) and true inner valve diameter (9-17 mm vs 18-22 mm HR: 0.40; 95% CI: 0.22-0.73; P = 0.003 and 18-22 mm vs 23-30 mm HR: 0.59; 95% CI: 0.25-1.39; P = 0.23) were associated with reduced BPV durability in multivariate models. CONCLUSIONS: The PVR procedural volume has increased over time, with a greater increment in transcatheter than surgical PVR during the last decade. Younger patient age at PVR and a smaller true inner valve diameter predicted reduced BPV durability.

Temporal changes in the surgical management of patients with tetralogy of Fallot in Denmark: a nationwide cohort study.

OBJECTIVES: To assess temporal changes in the surgical management of patients with tetralogy of Fallot including the timing of interventions, surgical techniques, reinterventions and survival in a nationwide cohort. METHODS: Patients with tetralogy of Fallot in Denmark were divided into 3 eras based on their year of birth: early (1977-1991), intermediate (1992-2006) and late (2007-2021). RESULTS: The cohort consisted of 745 patients. Median follow-up was 21.2 years (13.7-30.5). There was a temporal trend towards less shunt palliation (-0.3% per year, 95% CI -0.05 to -0.1). Median age at intracardiac repair was 2.9 years (1.8-5.0), 0.8 years (0.5-1.3) and 0.5 years (0.4-0.7) (P < 0.001) in the early, intermediate and late era, respectively. There was a temporal trend towards less valve-sparing repair (-0.7% per year, 95% CI -0.5 to -1.0) and more repair with transannular patches (0.7% per year, 95% CI 0.5-1.0). Survival at 10 years was 79% (64-76), 90% (87-93) and 95% (92-98) (P < 0.001) and pulmonary valve replacement within the first 10 years after intracardiac repair was performed in 3% (1-6), 12% (8-16) and 21% (13-29) (P < 0.001) in the early, intermediate and late era, respectively. CONCLUSIONS: There was a temporal trend towards less shunt palliation and intracardiac repair at a younger age with more use of transannular patches. While survival throughout childhood and adolescence has improved, more patients undergo pulmonary valve replacement during the first 10 years after intracardiac repair.

[Preoperative risk assessment of patients with congenital heart disease in non-cardiac surgery].

Over the last decades, remarkable advances in survival in patients with congenital heart disease (CHD) have been reported. Currently, 90% of infants born with CHD can expect to reach adulthood. Moderate and severe CHD is associated with increased perioperative mortality. To ensure optimal management of CHD patients undergoing non-cardiac surgery, preoperative risk assessment is pivotal, along with a multidisciplinary approach and collaboration across hospitals. The objective of this review is to provide a simple model to identify CHD patients at risk prior to non-cardiac surgery.

Lack of cardioprotection from subcutaneously and preischemic administered liraglutide in a closed chest porcine ischemia reperfusion model.

BACKGROUND: Glucagon-like peptide 1 (GLP1) analogues are promising new treatment options for patients with type 2 diabetes, but may have both potentially beneficial and harmful cardiovascular effects. This may also be the case for the analogues of GLP1 for clinical use. The present study examined the effect of treatment with liraglutide, a long-acting GLP1 analogue, on myocardial ischemia and reperfusion in a porcine model. METHODS: Danish Landrace Pigs (70-80 kg) were randomly assigned to liraglutide (10 mug/kg) or control treatment given daily for three days before ischemia-reperfusion. Ischemia was induced by balloon occlusion of the left anterior descending artery for 40 minutes followed by 2.5 hours of reperfusion. The primary outcome parameter was infarct size in relation to the ischemic region at risk. Secondary endpoints were the hemodynamic parameters mean pulmonary pressure, cardiac output, pulmonary capillary wedge pressure as measured by a Swan-Ganz catheter as well as arterial pressure and heart rate. RESULTS: The infarct size in relation to ischemic risk region in the control versus the liraglutide group did not differ significantly: 0.46 +/- 0.14 and 0.54 +/- 0.12) (mean and standard deviation (SD), p = 0.21). Heart rate was significantly higher in the liraglutide group during the experiment, while the other hemodynamic parameters did not differ significantly. CONCLUSION: Liraglutide has a neutral effect on myocardial infarct size in a porcine ischemia-reperfusion model.

[Diagnosis, monitoring and treatment of tuberous sclerosis complex].

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder with highly varying disease manifestations, many of which cause extensive morbidity. There are international consensus criteria for the diagnosis, monitoring and treatment of TSC, and approved medical treatment for some of the most serious disease manifestations. However, organisation of a rational and coordinated care of TSC patients involves many different medical specialities and is only sparsely described. This review describes the interdisciplinary care of TSC patients at Aarhus University Hospital, Denmark.

Transcatheter Mitral Paravalvular Leak Closure Facilitated by Preprocedural Cardiac CT for Simulation of Fluoroscopic Anatomy and Paravalvular Defect Localization.

Paravalvular leakage (PVL) occurs in 6%-15% of cases after surgical heart valve replacement. A percutaneous approach is increasingly used to close PVLs as an alternative to repeat surgery. Computed tomography (CT) can be used for simulation of fluoroscopic cardiac anatomy. This technique allows preprocedural definition of optimal C-arm angulations and PVL localization in reference to fluoroscopic views. It is very helpful for guidewire crossing of the PVL and positioning of the closure device. We report a case with the first use of dedicated software for fluoroscopic simulation (FluoroCT) in transcatheter mitral PVL closure.

Myocardial injury with biomarker elevation in diabetic ketoacidosis.

We report of two patients with severe ketoacidosis, minute elevations of myocardial biomarkers (troponin T and CK-MB) and initial ECG changes compatible with myocardial infarction (MI). All successive investigations, including coronary arteriography, were normal, and the patients recovered fully without further evidence of ischemic heart disease. We suggest that acidosis and very high levels of free fatty acids could cause membrane instability and biomarker leakage. Regardless of the pathogenesis, these two case stories suggest that nonspecific myocardial injury may occur in severe diabetic ketoacidosis and that the presence of minute biomarker elevation and ECG changes does not necessarily signify MI.

Lack of acute cardioprotective effect from preischaemic erythropoietin administration in a porcine coronary occlusion model.

BACKGROUND: Recombinant human erythropoietin (rhEPO) has been proposed to possess important tissue protective, apart from haematopoietic, effects. Cardioprotective effects have thus been reported in rodents exposed to myocardial ischaemia. Pathways common to the mediation of ischaemic preconditioning may be involved. Before clinical testing such possible cardioprotective effects needs assessment in an experimental large animal model with closer similarity to human ischaemic pathophysiology. METHODS: A control group and two rhEPO groups were studied. EPO1 pigs were given EPO corresponding to the early window and EPO2 pigs to the early and late window of ischaemic preconditioning in a closed chest, catheter-based, porcine coronary occlusion model (45 min of occlusion of the left anterior descending artery). Infarct size as a proportion of the ischaemic area (IS/AAR) was measured in vivo by myocardial perfusion imaging (MPI) and postmortem by a histochemical procedure (at 150 min of reperfusion). RESULTS: IS/AAR did not differ significantly between control (C), EPO1 and EPO2 groups, neither measured by MPI (mean+/-SD for C: 0.87+/-0.13; EPO1: 0.92+/-0.08; EPO2: 0.87+/-0.11), nor histochemically (mean+/-SD for C: 0.64+/-0.20; EPO1: 0.75+/-0.17; EPO2: 0.80+/-0.07). In the EPO2 group mean arterial pulmonary pressure and dP/dtmax were increased compared with control group. CONCLUSION: Despite promising results from studies in rodents, rhEPO did not reduce infarct size measured after 2.5 h of reperfusion in our porcine model.

[Consensus on national criteria for transthoracic echocardiography competence]. / National konsensus om krav til kompetenceniveau i transtorakal ekkokardiografi.

Standardised competence assessment in transthoracic echocardiography (TTE) is increasingly demanded. Danish Cardiology Society working group on echocardiography initiated a Delphi study among departments involved in resident TTE training to obtain consensus on national criteria for TTE competence. Consensus was obtained on a list of 21 items relevant for TTE competence assessment. Three items should be performed with great routine after two years and 16 items after five years of training. The working group recommends the list being used for competence assessment of cardiology residents.

Myocardial perfusion imaging with 99mTc sestamibi early after reperfusion reliably reflects infarct size reduction by ischaemic preconditioning in an experimental porcine model.

OBJECTIVE: Reliable methods for assessment of tissue reperfusion early after revascularizing therapy for acute myocardial infarction are needed. Myocardial perfusion imaging with Tc sestamibi (MIBI MPI) may serve this purpose. Usage during early reperfusion may be problematic e.g. due to ischaemic preconditioning (IP), which is important in inducing ischaemic tolerance. It is mediated through the opening of mitochondrial K ATP channels, reducing mitochondrial membrane potential. This may, as well as ischaemia per se, affect cellular uptake of Tc sestamibi. We therefore studied the reliability of MIBI MPI during early reperfusion as a measure of infarct size and its reduction by ischaemic preconditioning. METHODS AND RESULTS: We compared MIBI MPI (cut-off, 45% of maximum pixel count) with a histochemical method in a porcine model, nine controls and eight IP pigs, using 45 min catheter based coronary occlusion of the left anterior descending artery. Infarct size (IS) was determined relative to the area at risk (AAR). The relative infarct size (IS/AAR) after 120 min reperfusion estimated by MPI was 0.83 (0.17) in controls vs 0.07 (0.12) in the IP group (mean (SD), P<0.001). The corresponding values for histochemistry were controls 0.77 (0.19) vs IP 0.07 (0.11), P<0.001. IS/AAR measured by MPI and histochemistry were correlated significantly (r=0.93, P<0.001). Furthermore, IS relative to left ventricular mass (IS/LV) determined by autoradiography and histochemistry correlated (r=0.93, P<0.001). MPI overestimated IS/LV and AAR/LV by approximately a factor of 2 compared with histochemistry or autoradiography. CONCLUSION: MIBI MPI during early reperfusion is a reliable measure of relative infarct size reduction after ischaemic preconditioning, supporting use for stratification for adjunctive therapy and for assessment of prognosis.

[Consensus on national criteria for transthoracic echocardiography competence].

Standardised competence assessment in transthoracic echocardiography (TTE) is increasingly demanded. Danish Cardiology Society working group on echocardiography initiated a Delphi study among departments involved in resident TTE training to obtain consensus on national criteria for TTE competence. Consensus was obtained on a list of 21 items relevant for TTE competence assessment. Three items should be performed with great routine after two years and 16 items after five years of training. The working group recommends the list being used for competence assessment of cardiology residents.

Hypothermia during reperfusion does not reduce myocardial infarct size in pigs.

We previously described a method for regional myocardial cooling that reaches the target temperature within 4 min. The present study evaluated whether this method for regional myocardial cooling during reperfusion reduces myocardial infarct size (IS) in 75-kg pigs. Myocardial infarction was induced by inflation of an angioplasty balloon in the left anterior descendent artery for 45 min followed by 3 h reperfusion. First, 15 pigs were randomized to regional myocardial cooling during reperfusion (n = 8) or control (n = 7). As further control experiments, systemic hypothermia was induced prior to ischemia (n = 3) and during reperfusion (n = 3). IS and area at risk (AAR) were evaluated in vivo by single photon emission cardiac tomography (SPECT) and by standard histochemical staining. Regional cooling during reperfusion did not reduce IS/AAR as assessed by histochemistry (cooling: 0.71 +/- 0.8; control: 0.68 +/- 0.10; p = ns) and SPECT (cooling: 0.90 +/- 0.20; control: 0.88 +/- 0.32; p = ns). Systemic hypothermia during ischemia reduced IS/AAR (histochemistry: 0.09 +/- 0.11; SPECT: 0.25 +/- 0.22; p < 0.001 and p = 0.01 vs control, respectively). Induction of systemic hypothermia during reperfusion had no significant effect on IS/AAR (histochemistry: 0.63 +/- 0.07; SPECT: 0.74 +/- 0.09; p = ns vs control for both comparisons). In conclusion, hypothermia during ischemia is strongly myocardioprotective while hypothermia during reperfusion does not reduce myocardial infarct size in human-sized pigs.

A phase of increased ST elevation during coronary occlusion following ischemic preconditioning.

UNLABELLED: ATP-sensitive potassium channels are opened during the course of ischemic preconditioning (IP). As experimental data suggest that opening of sarcolemmal ATP-sensitive potassium channels underlie ST elevation during myocardial ischemia, one would expect to observe increased ST elevation during ischemia following IP. However, clinical studies have reported IP to attenuate ST elevation during repeated brief coronary occlusions. The objective of this study was to characterize the temporal course of ST elevation during coronary occlusion following IP. Twenty-eight closed-chest pigs were subject to catheter-based left anterior descending coronary artery occlusion/ reperfusion for 45/120 minutes. Thirteen animals were preconditioned by two occlusion/reperfusion cycles of 10/30 minutes. Fifteen pigs served as controls. The electrocardiographic ST vector magnitude was continuously monitored. IP reduced the infarct size normalized for area at risk (IP 9.6 +/- 15.8%; control 71.2 +/- 14.7%; p < 0.001). IP increased the time between coronary artery occlusion and appearance of significant rise in ST vector magnitude from 51 +/- 17 to 94 +/- 33 seconds (p < 0.01). IP reduced the rise in ST vector magnitude after 120 seconds of occlusion from 202 +/- 85 microV to 68 +/- 28 microV (p < 0.001) and increased the rise in ST vector magnitude after 600 seconds from 265 +/- 106 microV to 427 +/- 232 microV (p < 0.001). CONCLUSION: Ischemic preconditioning reduced and delayed early ST elevation during subsequent coronary artery occlusion, but increased late ST elevation. Thus, ischemic preconditioning causes a dynamic and critically time-dependent biphasic pattern of ST elevation during repeated coronary occlusions.

Effects of levosimendan on myocardial infarct size and hemodynamics in a closed-chest porcine ischemia-reperfusion model.

INTRODUCTION: Levosimendan is a positive inotropic drug with vasodilator action and proposed myocardioprotective properties. In a canine model, levosimendan increased coronary collateral flow and reduced myocardial infarct size (IS). We investigated the effect of levosimendan on IS and hemodynamics in the closed-chest porcine ischemia-reperfusion model, which is devoid of coronary collaterals. METHODS: Infusion with levosimendan (0.2 microg/kg/min following a bolus of 24 microg/kg) or saline was initiated 30 min prior to ischemia in anaesthetized pigs (n = 10 in both groups). Balloon occlusion of the left anterior descending coronary artery for 45 min was followed by 2 1/2 h of reperfusion. Hemodynamics were monitored with a Swan-Ganz catheter and a left ventricular pressure micromanometer. Left ventricular systolic and diastolic function was estimated by dP/dt(max) and tau, respectively. Myocardial area at risk (AAR) and IS were assessed in vivo by myocardial perfusion imaging (MPI) and ex vivo by histopathology (fluorescein staining for AAR, tetrazolium staining for IS). RESULTS: Prior to ischemia, levosimendan improved left ventricular systolic and diastolic function with coincident preload and afterload reduction. Cardiac output increased by 10 +/- 4% (p = 0.04), dP/dt(max) by 15 +/- 5% (p = 0.01). Pulmonary capillary wedge pressure decreased by 18 +/- 3% (p = 0.04), tau by 11 +/- 2% (p = 0.001), and mean arterial pressure by 11 +/- 2% (p < 0.001). A similar trend was observed during ischemia-reperfusion. The ratio of IS/AAR was not reduced by levosimendan compared to saline as evaluated by histopathology (76 +/- 4% vs. 64 +/- 7%, p = 0.12) and by MPI (94 +/- 2% vs. 87 +/- 5%, p = 0.14). CONCLUSION: Levosimendan improves hemodynamics but does not reduce IS in an ischemia-reperfusion model without coronary collaterals.

Lack of cardioprotection from metabolic support with glutamine or glutamate in a porcine coronary occlusion model.

OBJECTIVE: Previous experimental studies indicate that glutamine or glutamate may provide cardioprotection by improving the oxidative metabolism in myocardial ischemia. We investigated the effect of glutamine or glutamate, given during reperfusion, on resulting infarct size and hemodynamic recovery. DESIGN: A porcine coronary occlusion model was applied. Infusions were initiated 15 min before reperfusion and supplemented with intracoronary bolus doses at reperfusion. The primary outcome measure was infarct size in relation to area at risk determined by a standard tissue staining procedure. Secondary outcome measures were the hemodynamic variables. RESULTS: The infarct sizes as a proportion of the area at risk (mean+/-SD) were: control group, 0.64 +/- 0.19 (n = 9); glutamine group, 0.87 +/- 0.07 (p < 0.05 vs control group) (n = 8); glutamate group, 0.72 +/- 0.11 (n = 9). Glutamine increased systemic vascular resistance, while glutamate preserved cardiac output during infusion. CONCLUSION: Substrate supplementation with the anaplerotic precursors glutamine and glutamate is ineffective as adjunctive therapy for severe myocardial ischemia. Beneficial effects documented in less complex experimental systems could not be transferred to a more pathophysiological relevant model.

Glibenclamide blunts coronary flow reserve induced by adenosine and dipyridamole.

OBJECTIVE: A reduced coronary flow reserve is considered indicative of significant coronary stenosis. As experimental data suggest that adenosine and dipyridamole induce vasodilatation by opening of ATP-sensitive potassium channels, we sought to determine the effect of glibenclamide, an antidiabetic blocker of ATP-sensitive potassium channels, on adenosine- and dipyridamole-induced coronary flow reserve. DESIGN: Coronary flow velocities were measured in 15 pigs using a Doppler flow wire. The effect of increasing glibenclamide concentrations (0.1-10 microM) on adenosine-induced coronary flow reserve was examined in five animals. Ten pigs served as time controls. The time controls were subsequently treated by 3 microM glibenclamide (n = 5) or corresponding vehicle (n = 5) and the flow response to 0.56 mg/kg dipyridamole determined. RESULTS: Glibenclamide elicited a concentration-dependent inhibition of adenosine-induced coronary flow reserve, reaching significance at glibenclamide concentrations of 3 and 10 microM. The coronary flow reserve stimulated by dipyridamole was reduced significantly by 3 microM glibenclamide. CONCLUSION: Glibenclamide blunts coronary flow reserve stimulated by adenosine and dipyridamole. This interaction may have clinical implications in diabetics undergoing adenosine- or dipyridamole-dependent diagnostic procedures.