Jens C. Nilsson

Stem Cell Mobilization Induced by Subcutaneous Granulocyte-Colony Stimulating Factor to Improve Cardiac Regeneration After Acute ST-Elevation Myocardial Infarction Result of the Double-Blind, Randomized, Placebo-Controlled Stem Cells in Myocardial Infarction (STEMMI) Trial

Background— Phase 1 clinical trials of granulocyte-colony stimulating factor (G-CSF) treatment after myocardial infarction have indicated that G-CSF treatment is safe and may improve left ventricular function. This randomized, double-blind, placebo-controlled trial aimed to assess the efficacy of subcutaneous G-CSF injections on left ventricular function in patients with ST-elevation myocardial infarction. Methods and Results— Seventy-eight patients (62 men; average age, 56 years) with ST-elevation myocardial infarction were included after successful primary percutaneous coronary stent intervention <12 hours after symptom onset. Patients were randomized to double-blind treatment with G-CSF (10 &mgr;g/kg of body weight) or placebo for 6 days. The primary end point was change in systolic wall thickening from baseline to 6 months determined by cardiac magnetic resonance imaging (MRI). An independent core laboratory analyzed all MRI examinations. Systolic wall thickening improved 17% in the infarct area in the G-CSF group and 17% in the placebo group (P=1.0). Comparable results were found in infarct border and noninfarcted myocardium. Left ventricular ejection fraction improved similarly in the 2 groups measured by both MRI (8.5 versus 8.0; P=0.9) and echocardiography (5.7 versus 3.7; P=0.7). The risk of severe clinical adverse events was not increased by G-CSF. In addition, in-stent late lumen loss and target vessel revascularization rate in the follow-up period were similar in the 2 groups. Conclusions— Bone marrow stem cell mobilization with subcutaneous G-CSF is safe but did not lead to further improvement in ventricular function after acute myocardial infarction compared with the recovery observed in the placebo group.

Antiremodeling effects on the left ventricle during beta-blockade with metoprolol in the treatment of chronic heart failure.

OBJECTIVES The purpose of the study was to investigate the effects of beta1-blockade on left ventricular (LV) size and function for patients with chronic heart failure. BACKGROUND Large-scale trials have shown that a marked decrease in mortality can be obtained by treatment of chronic heart failure with beta-adrenergic blocking agents. Possible mechanisms behind this effect remain yet to be fully elucidated, and previous studies have presented insignificant results regarding suspected LV antiremodeling effects. METHODS In this randomized, placebo-controlled and double-blind substudy to the Metoprolol CR/XL Randomized Intervention Trial in Heart Failure (MERIT-HF), 41 patients were examined with magnetic resonance imaging three times in a six-month period, assessing LV dimensions and function. RESULTS Decreases in both LV end-diastolic volume index (150 ml/m2 at baseline to 126 ml/m2 after six months, p = 0.007) and LV end-systolic volume index (107 ml/m2 to 81 ml/m2, p = 0.001) were found, whereas LV ejection fraction increased in the metoprolol CR/XL group (29% to 37%, p = 0.005). No significant changes were seen in the placebo group regarding these variables. Left ventricular stroke volume index remained unchanged, whereas LV mass index decreased in both groups (175 g/m2 to 160 g/m2 in the placebo group [p = 0.005] and 179 g/m2 to 164 g/m2 in the metoprolol CR/XL group [p = 0.011). CONCLUSIONS This study is the first randomized study to demonstrate that the beta1-blocker metoprolol CR/XL has antiremodeling effects on the LV in patients with chronic heart failure and consequently provides an explanation for the highly significant decrease in mortality from worsening heart failure found in the MERIT-HF trial.

Evaluation of impaired left ventricular ejection fraction and increased dimensions by multiple neurohumoral plasma concentrations

A range of neurohumoral substances have been suggested as diagnostic markers in heart failure. It is, however, undetermined which marker has the greatest diagnostic potential, and whether additional information is gained by a comprehensive neurohumoral evaluation.

First report on intraoperative vector flow imaging of the heart among patients with healthy and diseased aortic valves

The vector velocity method Transverse Oscillation (TO) implemented on a conventional ultrasound (US) scanner (ProFocus, BK Medical, Herlev, Denmark) can provide real-time, angle-independent estimates of the cardiac blood flow. During cardiac surgery, epicardial US examination using TO was performed on (A) 3 patients with healthy aortic valve and (B) 3 patients with aortic valve stenosis. In group B, the systolic flow of the ascending aorta had higher velocities, was more aliased and chaotic. The jet narrowed to 44% of the lumen compared to 75% in group A and with a vector concentration, a measure of flow complexity, of 0.41 compared to 0.87 in group A. The two groups had similar secondary flow of the ascending aorta with an average rotation frequency of 4.8 Hz. Simultaneous measurements were obtained with spectral Doppler (SD) and a thermodilution technique (TD). The mean difference in peak systolic velocity compared to SD in group A was 22% and 45% in B, while the mean difference in volume flow compared to TD in group A was 30% and 32% in B. TO can potentially reveal new information of cardiac blood flow, and may become a valuable diagnostic tool in the evaluation of patients with cardiovascular diseases.

Intraoperative cardiac ultrasound examination using vector flow imaging.

Conventional ultrasound (US) methods for blood velocity estimation only provide one-dimensional and angle-dependent velocity estimates; thus, the complexity of cardiac flow has been difficult to measure. To circumvent these limitations, the Transverse Oscillation (TO) vector flow method has been proposed. The vector flow method implemented on a commercial scanner provided real-time, angle-independent estimates of cardiac blood flow. Epicardiac and epiaortic, intraoperative US examinations were performed on three patients with stenosed coronary arteries scheduled for bypass surgery. Repeating cyclic beat-to-beat flow patterns were seen in the ascending aorta and pulmonary artery of each patient, but these patterns varied between patients. Early systolic retrograde flow filling the aortic sinuses was seen in the ascending aorta as well as early systolic retrograde flow in the pulmonary artery. In diastole, stable vortices in aortic sinuses of the ascending aorta created central antegrade flow. A stable vortex in the right atrium was seen during the entire heart cycle. The measurements were compared with estimates obtained intraoperatively with conventional spectral Doppler US using a transesophageal and an epiaortic approach. Mean differences in peak systole velocity of 11% and 26% were observed when TO was compared with transesophageal echocardiography and epiaortic US, respectively. In one patient, the cardiac output derived from vector velocities was compared with pulmonary artery catheter thermodilution technique and showed a difference of 16%. Vector flow provides real-time, angle-independent vector velocities of cardiac blood flow. The technique can potentially reveal new information of cardiovascular physiology and give insight into blood flow dynamics.

Measurements of cardiac output obtained with transesophageal echocardiography and pulmonary artery thermodilution are not interchangeable.

Echocardiography is increasingly becoming an integrated tool for circulatory evaluation in the intensive care unit and the operating room. Therefore, it is imperative to know the reproducibility of measurements obtained by echocardiography. In this study, a comparison of cardiac output (CO) measurements obtained with transesophageal echocardiography (TEE) and pulmonary artery catheter (PAC) thermodilution (TD) was carried out to test the precision, accuracy and trending ability of CO measurements obtained with TEE.

Acute Kidney Injury Is Independently Associated With Higher Mortality After Cardiac Surgery

OBJECTIVES To investigate the incidence of acute kidney injury after cardiac surgery and its association with mortality in a patient population receiving ibuprofen and gentamicin perioperatively. DESIGN Retrospective study with Cox regression analysis to control for possible preoperative, intraoperative and postoperative confounders. SETTING University hospital-based single-center study. PARTICIPANTS All patients who underwent coronary artery bypass grafting ± valve surgery during 2012. INTERVENTIONS None. MEASUREMENT AND MAIN RESULTS Acute surgery within 24 hours of coronary angiography, previous nephrectomy, preoperative sCr >2.26 mg/dL and selective cerebral perfusion during cardiopulmonary bypass were used as exclusion criteria. Acute kidney injury was defined, using the Acute Kidney Injury Network (AKIN) criteria. Six hundred eight patients were included in the study. Mean age was 68.2 ± 9.7 years, and 81% were males. Acute kidney injury was seen in 28.1% of the patients. Overall mortality at one year was 7% and 3% in the no-AKI group. At one year, mortality was 15% in patients with AKIN stage 1 and AKIN stage 2 compared to 70% in AKIN stage 3. A hazard ratio of 2.34 (95% CI: 1.21-4.51, p = 0.011) and 5.62 (95% CI: 2.42-13.06), p<0.0001) were found for AKIN stage 1 and 2/3 combined, respectively. CONCLUSIONS More than 28% of the patients undergoing elective or subacute cardiac surgery developed AKI in this contemporary cohort. Furthermore, acute kidney injury was an independent predictor of increased mortality irrespective of the perioperative risk factors.

Neurohumoral prediction of left-ventricular morphologic response to β-blockade with metoprolol in chronic left-ventricular systolic heart failure

In order to tailor therapy in heart failure, a solution might be to develop sensitive and reliable markers that can predict response in individual patients or monitor effectiveness of therapy.

Right ventricular failure after implantation of a continuous-flow left ventricular assist device: early haemodynamic predictors †

OBJECTIVES Right ventricular failure (RVF) is a significant complication after implantation of a left ventricular assist device. We aimed to identify haemodynamic changes in the early postoperative phase that predicted subsequent development of RVF in a cohort of HeartMate II (HMII) implanted patients. METHODS This was a single-centre observational study of consecutive placement of HMII devices at Rigshospitalet, Copenhagen. Preoperative data (right heart catheterization, biochemistry and clinical status) and postoperative readings from the first 72 h after implantation (haemodynamics, inotropic and vasoactive therapy) were included in the analysis. The data set was examined for significant differences between patients who developed RVF (RVF group, n = 11)-defined as need for inotropic or vasodilator therapy >14 days, nitric oxide therapy ≥ 48 h or right ventricular assist device therapy-and those who did not (non-RVF group, n = 22). RESULTS Preoperative right heart catheterization data were similar in the two groups. Immediately after HMII implantation, the increase in cardiac index (CI) was significantly larger in the non-RVF than in the RVF group (0.96 ± 0.8 vs 0.2 ± 0.5 L/min, respectively; P = 0.018), whereas right ventricular stroke work index (RVSWI) decreased significantly more in the RVF group (-4.3 ± 2.0 vs -0.9 ± 2.0 g m/m(2); P < 0.001). These differences were present in spite of the RVF group receiving larger doses of catecholaminergic agents (P = 0.034). Over the ensuing 72 h, the CI of the RVF group gradually approached that of the non-RVF group; concurrently, however, the differences in inotropic therapy were further enhanced. Pump settings were similar in the two groups. CONCLUSIONS The haemodynamic alterations characterizing RVF were present already immediately after HMII implantation. RVF development was not related to pump flow and settings.

Measures of right ventricular function after transcatheter versus surgical aortic valve replacement

Objectives Describe changes in measures of right ventricular (RV) function in patients treated for aortic stenosis using open-chest surgery (SAVR) or transcatheter treatment (TAVR). Methods Patients in the Nordic Aortic Valve Intervention (NOTION) trial were randomized 1:1 to TAVR (n = 114) or SAVR (n = 106). Echocardiography was performed at baseline and 3 and 12 months post-procedure. Tricuspid annular plane systolic excursion (TAPSE) and right ventricular fractional area change (RVFAC) were used as measures of longitudinal and transverse RV contraction. Left ventricular ejection fraction (LVEF) and LV atrioventricular plane displacement (AVPD) were recorded as measures of LV function. Association to NYHA class was examined. Results There were no differences in echocardiographic measurements between TAVR and SAVR at baseline. In the SAVR group, TAPSE was reduced after 3 months (2.4 ± 0.5 cm vs 1.6 ± 0.4 cm; P < 0.001), and 12 months (2.4 ± 0.5 cm vs 1.7 ± 0.4 cm; P < 0.001). RVFAC was reduced after 3 months (44% ± 11% vs 39% ± 10%; P = 0.001), but recovered at 12 months (43% ± 10%; P = 0.39). AVPD lateral increased during follow-up (1.4 ± 0.3 cm vs 1.6 ± 0.4 cm (P = 0.001) and 1.7 ± 0.4 cm, respectively; P < 0.001), whereas AVPD medial remained stable (baseline vs 3 months: P = 0.06 and baseline vs 12 months: P = 0.59). In the TAVR group, all echocardiographic measures remained unchanged from baseline to 12 months postoperatively. We found no association between echocardiographic changes and NYHA class. Conclusions TAPSE and AVPD lateral differed between TAVR and SAVR at 3 and 12 months follow-up, but these findings were not related to any changes in NYHA class. These observations indicate that following SAVR, echocardiographic changes may not reflect right ventricular function, but merely a change in the physiological conditions. Clinicaltrials.gov identifier NCT01057173.