Svend Aakhus

Regional myocardial systolic function during acute myocardial ischemia assessed by strain Doppler echocardiography

OBJECTIVES We sought to evaluate if echocardiographic strain measurements could detect acute myocardial ischemia, and to compare this new method with myocardial velocity measurements and wall motion score index. BACKGROUND Tissue Doppler echocardiography (TDE) is a promising method for assessing regional myocardial function. However, myocardial velocities measured by tissue Doppler echocardiography (TDE) vary throughout the left ventricle (LV) because of tethering effects from adjacent tissue. Strain Doppler echocardiography (SDE) is a new tool for measuring regional myocardial deformation excluding the effect of adjacent myocardial tissue. METHODS Seventeen patients undergoing angioplasty of the left anterior descending coronary artery (LAD) were studied. Left ventricular longitudinal wall motion was assessed by TDE and SDE from the apical four-chamber view before, during and after angioplasty from multiple myocardial segments simultaneously. RESULTS Systolic strain values were uniformly distributed in the different nonischemic LV segments, whereas systolic velocities decreased from basis to apex. During LAD occlusion, strain measurement showed expansion in the apical septal segment in 16 of 17 patients (7.5 +/- 6.5% vs. -17.7 +/- 7.2%, p < 0.001) and reduced compression in the mid-septal segment (p < 0.05) compared with baseline. Segments not supplied by LAD remained unchanged. Tissue Doppler echocardiography showed reduced velocities in all septal segments (p < 0.05) during angioplasty even though LAD does not supply the basal septal segment. Negative systolic velocities were present in 11 of 17 patients. Wall motion score index increased during ischemia (1.3 +/- 0.4, p < 0.05). CONCLUSIONS The new SDE approach might be a more accurate marker than TDE for detecting systolic regional myocardial dysfunction induced by LAD occlusion.

Global longitudinal strain measured by two-dimensional speckle tracking echocardiography is closely related to myocardial infarct size in chronic ischaemic heart disease

2D-STE (two-dimensional speckle tracking echocardiography) is a novel echocardiographic modality that enables angle-independent assessment of myocardial deformation indices. In the present study, we tested whether peak systolic epsilon(parallel) (longitudinal strain) values measured by 2D-STE could identify areas of MI (myocardial infarction) as determined by CE MRI (contrast-enhanced magnetic resonance imaging). Conventional echocardiographic apical long-axis recordings were performed in 38 patients, 9 months after a first MI. Peak systolic epsilon(parallel) measured by 2D-STE in 16 left ventricle segments was compared with segmental infarct mass and transmurality assessed by CE MRI. Segmental values were averaged to global and territorial values for assessment of global function and myocardial function in the coronary distribution areas. CE MRI identified transmural infarction in 27 patients, and a mean infarct size of 36+/-25 g. Peak systolic epsilon( parallel) correlated with the infarct mass at the global level (r=0.84, P<0.001). A strain value of -15% identified infarction with 83% sensitivity and 93% specificity at the global level and 76% and 95% at the territorial level, and a strain value of -13% identified transmural infarction with 80% sensitivity and 83% specificity at the segmental level. Global infarct mass correlates with the wall motion score index (r=0.70, P<0.001), and left ventricular ejection fraction measured by MRI or echocardiography (r=-0.71 and -0.58, both P<0.001). In chronic infarction, peak systolic epsilon(parallel) measured by 2D-STE correlates with the infarct mass assessed by CE MRI at a global level, and separates infarcted from non-infarcted tissue. Global strain is an excellent predictor of myocardial infarct size in chronic ischaemic heart disease.

Long-term results after intracoronary injection of autologous mononuclear bone marrow cells in acute myocardial infarction: the ASTAMI randomised, controlled study

Objective: To investigate long-term safety and efficacy after intracoronary injection of autologous mononuclear bone marrow cells (mBMCs) in acute myocardial infarction (AMI). Design: Randomised, controlled trial. Setting: Two university hospitals in Oslo, Norway. Patients: Patients from the Autologous Stem cell Transplantation in Acute Myocardial Infarction (ASTAMI) study were re-assessed 3 years after inclusion. Interventions: 100 patients with anterior wall ST-elevation myocardial infarction treated with acute percutaneous coronary intervention (PCI) were randomised to receive intracoronary injection of mBMCs (n = 50) or not (n = 50). Main outcome measures: Change in left ventricular (LV) ejection fraction (primary). Change in exercise capacity (peak VO2) and quality of life (secondary). Infarct size (additional aim), and safety. Results: The rates of adverse clinical events in the groups were low and equal. There were no significant differences between groups in change of global LV systolic function by echocardiography or magnetic resonance imaging (MRI) during the follow-up. On exercise testing, the mBMC-treated patients had larger improvement in exercise time from 2–3 weeks to 3 years (1.5 minutes vs 0.6 minutes, p = 0.05), but the change in peak oxygen consumption did not differ (3.0 ml/kg/min vs 3.1 ml/kg/min, p = 0.75). Conclusion: The results indicate that intracoronary mBMC treatment in AMI is safe in the long term. A small improvement in exercise time in the mBMC group was found, but no other effects of treatment could be identified 3 years after cell therapy.

Autologous stem cell transplantation in acute myocardial infarction: The ASTAMI randomized controlled trial. Intracoronary transplantation of autologous mononuclear bone marrow cells, study design and safety aspects

Objectives Intracoronary transplantation of different cell populations has been used in acute myocardial infarction (AMI) with promising results. The primary objective of the Autologous Stem cell Transplantation in Acute Myocardial Infarction (ASTAMI) study is to test whether intracoronary transplantation of autologous mononuclear bone marrow cells (mBMC) improves left ventricular ejection fraction (LVEF) after anterior wall AMI. Design The ASTAMI study is a randomized, controlled, prospective study. One hundred patients with acute anterior wall ST-elevation myocardial infarction (STEMI) treated with acute percutaneous coronary intervention (PCI) are randomized in a 1:1 way to either intracoronary transplantation of autologous mBMC 5–8 d after PCI or to control. Left ventricular function, exercise capacity, biochemical status, functional class, quality of life and complications are validated at baseline and during a 12-month follow-up. Results By August 2004, out of 1004 patients with STEMI, 49 patients have been included in the study. Twenty-four patients have been randomized to intracoronary mBMC transplantation. Twenty patients had chest pain and 16 patients had ischemic ECG changes during the mBMC transplantation procedure. One patient had ventricular fibrillation 24 h after transplantation. Conclusions Intracoronary transplantation of autologous mBMC in the acute phase after AMI is feasible and seems safe in the short term.

Invasive versus conservative strategy in patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris (After Eighty study): an open-label randomised controlled trial

BACKGROUND Non-ST-elevation myocardial infarction (NSTEMI) and unstable angina pectoris are frequent causes of hospital admission in the elderly. However, clinical trials targeting this population are scarce, and these patients are less likely to receive treatment according to guidelines. We aimed to investigate whether this population would benefit from an early invasive strategy versus a conservative strategy. METHODS In this open-label randomised controlled multicentre trial, patients aged 80 years or older with NSTEMI or unstable angina admitted to 16 hospitals in the South-East Health Region of Norway were randomly assigned to an invasive strategy (including early coronary angiography with immediate assessment for percutaneous coronary intervention, coronary artery bypass graft, and optimum medical treatment) or to a conservative strategy (optimum medical treatment alone). A permuted block randomisation was generated by the Centre for Biostatistics and Epidemiology with stratification on the inclusion hospitals in opaque concealed envelopes, and sealed envelopes with consecutive inclusion numbers were made. The primary outcome was a composite of myocardial infarction, need for urgent revascularisation, stroke, and death and was assessed between Dec 10, 2010, and Nov 18, 2014. An intention-to-treat analysis was used. This study is registered with ClinicalTrials.gov, number NCT01255540. FINDINGS During a median follow-up of 1·53 years of participants recruited between Dec 10, 2010, and Feb 21, 2014, the primary outcome occurred in 93 (40·6%) of 229 patients assigned to the invasive group and 140 (61·4%) of 228 patients assigned to the conservative group (hazard ratio [HR] 0·53 [95% CI 0·41-0·69], p=0·0001). Five patients dropped out of the invasive group and one from the conservative group. HRs for the four components of the primary composite endpoint were 0·52 (0·35-0·76; p=0·0010) for myocardial infarction, 0·19 (0·07-0·52; p=0·0010) for the need for urgent revascularisation, 0·60 (0·25-1·46; p=0·2650) for stroke, and 0·89 (0·62-1·28; p=0·5340) for death from any cause. The invasive group had four (1·7%) major and 23 (10·0%) minor bleeding complications whereas the conservative group had four (1·8%) major and 16 (7·0%) minor bleeding complications. INTERPRETATION In patients aged 80 years or more with NSTEMI or unstable angina, an invasive strategy is superior to a conservative strategy in the reduction of composite events. Efficacy of the invasive strategy was diluted with increasing age (after adjustment for creatinine and effect modification). The two strategies did not differ in terms of bleeding complications. FUNDING Norwegian Health Association (ExtraStiftelsen) and Inger and John Fredriksen Heart Foundation.

Noninvasive Separation of Large, Medium, and Small Myocardial Infarcts in Survivors of Reperfused ST-Elevation Myocardial Infarction A Comprehensive Tissue Doppler and Speckle-Tracking Echocardiography Study

Background—The objective of the study was to evaluate the ability of established and new parameters of global systolic left ventricle function to estimate myocardial infarct size. Increasing infarct extent is associated with impaired prognosis in chronic ischemic heart disease. Systolic myocardial deformation is a complex 3D process that is mainly influenced by the amount and transmural distribution of viable myocardium. Speckle-tracking echocardiography (2D-STE) enables deformation assessment along the 3 main cardiac axes independent of insonation angle. Methods and Results—Global longitudinal, circumferential, and radial strain and left ventricle twist by 2D-STE, global longitudinal strain rate and strain by tissue Doppler imaging, and left ventricle ejection fraction and wall motion score index were assessed in 40 patients 8.5±5.4 months after a first myocardial infarct and compared with global myocardial infarct mass assessed by contrast-enhanced MRI. Longitudinal and circumferential strain by 2D-STE and longitudinal strain and strain rate by tissue Doppler imaging significantly separated medium-sized infarcts from small or large infarcts at the global level (P<0.05). All deformation indices correlated significantly with global infarct mass (P<0.01). Circumferential and longitudinal strains by 2D-STE demonstrated the best ability to identify medium-sized global myocardial infarcts. Conclusions—Circumferential and longitudinal strains by 2D-STE correlate with myocardial infarct mass and significantly differentiate among large, medium, and small myocardial infarcts.

Impact of intracoronary bone marrow cell therapy on left ventricular function in the setting of ST-segment elevation myocardial infarction: a collaborative meta-analysis

AIMS The objective of the present analysis was to systematically examine the effect of intracoronary bone marrow cell (BMC) therapy on left ventricular (LV) function after ST-segment elevation myocardial infarction in various subgroups of patients by performing a collaborative meta-analysis of randomized controlled trials. METHODS AND RESULTS We identified all randomized controlled trials comparing intracoronary BMC infusion as treatment for ST-segment elevation myocardial infarction. We contacted the principal investigator for each participating trial to provide summary data with regard to different pre-specified subgroups [age, diabetes mellitus, time from symptoms to percutaneous coronary intervention, infarct-related artery, LV end-diastolic volume index (EDVI), LV ejection fraction (EF), infarct size, presence of microvascular obstruction, timing of cell infusion, and injected cell number] and three different endpoints [change in LVEF, LVEDVI, and LV end-systolic volume index (ESVI)]. Data from 16 studies were combined including 1641 patients (984 cell therapy, 657 controls). The absolute improvement in LVEF was greater among BMC-treated patients compared with controls: [2.55% increase, 95% confidence interval (CI) 1.83-3.26, P < 0.001]. Cell therapy significantly reduced LVEDVI and LVESVI (-3.17 mL/m², 95% CI: -4.86 to -1.47, P < 0.001; -2.60 mL/m², 95% CI -3.84 to -1.35, P < 0.001, respectively). Treatment benefit in terms of LVEF improvement was more pronounced in younger patients (age <55, 3.38%, 95% CI: 2.36-4.39) compared with older patients (age ≥ 55 years, 1.77%, 95% CI: 0.80-2.74, P = 0.03). This heterogeneity in treatment effect was also observed with respect to the reduction in LVEDVI and LVESVI. Moreover, patients with baseline LVEF <40% derived more benefit from intracoronary BMC therapy. LVEF improvement was 5.30%, 95% CI: 4.27-6.33 in patients with LVEF <40% compared with 1.45%, 95% CI: 0.60 to 2.31 in LVEF ≥ 40%, P < 0.001. No clear interaction was observed between other subgroups and outcomes. CONCLUSION Intracoronary BMC infusion is associated with improvement of LV function and remodelling in patients after ST-segment elevation myocardial infarction. Younger patients and patients with a more severely depressed LVEF at baseline derived most benefit from this adjunctive therapy.

Microbiota‐dependent metabolite trimethylamine‐N‐oxide is associated with disease severity and survival of patients with chronic heart failure

Recent metabolomic, experimental and clinical studies have demonstrated that trimethylamine‐N‐oxide (TMAO), a microbiota‐dependent metabolite from dietary phosphatidylcholine and carnitine, is a strong predictor of coronary artery disease (CAD). This finding suggests a link between the gut microbiota and atherosclerosis. The potential impact of TMAO in chronic heart failure (HF) is unknown. We hypothesized that TMAO levels would provide prognostic information about adverse outcomes in chronic HF.

Anterior myocardial infarction with acute percutaneous coronary intervention and intracoronary injection of autologous mononuclear bone marrow cells: safety, clinical outcome, and serial changes in left ventricular function during 12-months' follow-up.

To the Editor: Intracoronary injection of bone marrow cells (BMC) has been introduced for improvement of left ventricular (LV) function after acute myocardial infarction (AMI). In the randomized ASTAMI (Autologous Stem cell Transplantation in Acute Myocardial Infarction) study, BMC treatment did not

Cardiovascular disease in stable renal transplant patients in Norway: morbidity and mortality during a 5‐yr follow‐up

Abstract:  Background:  Although cardiovascular disease is a major cause of death after renal transplantation (Tx), predictors for cardiovascular events have not been well defined. Aims of this cross‐sectional study were first to assess cardiovascular morbidity and mortality in stable renal Tx patients, and to identify predictors for cardiovascular events during long‐term follow‐up.