Interleukin-6 inhibition in ST-elevation myocardial infarction: Immune cell profile in the randomised ASSAIL-MI trial.

BACKGROUND: We recently showed that interleukin (IL)-6 inhibition by tocilizumab improves myocardial salvage in ST-elevation myocardial infarction (STEMI). However, the mechanisms for this effect are not clear. METHODS: In this exploratory sub-study of the ASSAIL-MI trial, we examined leukocyte differential counts and their relation to myocardial salvage and peak troponin T (TnT) in STEMI patients randomised to tocilizumab (n = 101) or placebo (n = 98). We performed RNA-sequencing on whole blood (n = 40) and T cells (n = 20). B and T cell subpopulations were examined by flow cytometry (n = 69). FINDINGS: (i) STEMI patients had higher neutrophil counts at hospitalisation compared with stable angina patients. (ii) After percutaneous coronary intervention there was a gradual decline in neutrophils, which was significantly more pronounced in the tocilizumab group. (iii) The decrease in neutrophils in the tocilizumab group was associated with improved myocardial salvage and lower peak TnT. (iv) RNA-sequencing suggested that neutrophil function was also attenuated by tocilizumab. (v) B and T cell sub-populations changed only minimally after STEMI with minor effects of tocilizumab, supported as well by RNA-sequencing analyses of T cells. (vi) However, a low CD8+ count was associated with improved myocardial salvage in patients admitted to the hospital > 3 h after symptom onset. INTERPRETATION: Tocilizumab induced a rapid reduction in neutrophils and seemed to attenuate neutrophil function in STEMI patients potentially related to the beneficial effects of tocilizumab on myocardial salvage. FUNDING: South-Eastern Norway Regional Health Authority (Nos. 2019067, 2017084), the Central Norway Regional Health Authority and Norwegian Research Council (No. 283867).

Randomized Trial of Interleukin-6 Receptor Inhibition in Patients With Acute ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Prompt myocardial revascularization with percutaneous coronary intervention (PCI) reduces infarct size and improves outcomes in patients with ST-segment elevation myocardial infarction (STEMI). However, as much as 50% of the loss of viable myocardium may be attributed to the reperfusion injury and the associated inflammatory response. OBJECTIVES: This study sought to evaluate the effect of the interleukin-6 receptor inhibitor tocilizumab on myocardial salvage in acute STEMI. METHODS: The ASSAIL-MI trial was a randomized, double-blind, placebo-controlled trial conducted at 3 high-volume PCI centers in Norway. Patients admitted with STEMI within 6 h of symptom onset were eligible. Consenting patients were randomized in a 1:1 fashion to promptly receive a single infusion of 280 mg tocilizumab or placebo. The primary endpoint was the myocardial salvage index as measured by magnetic resonance imaging after 3 to 7 days. RESULTS: We randomized 101 patients to tocilizumab and 98 patients to placebo. The myocardial salvage index was larger in the tocilizumab group than in the placebo group (adjusted between-group difference 5.6 [95% confidence interval: 0.2 to 11.3] percentage points, p = 0.04). Microvascular obstruction was less extensive in the tocilizumab arm, but there was no significant difference in the final infarct size between the tocilizumab arm and the placebo arm (7.2% vs. 9.1% of myocardial volume, p = 0.08). Adverse events were evenly distributed across the treatment groups. CONCLUSIONS: Tocilizumab increased myocardial salvage in patients with acute STEMI. (ASSessing the effect of Anti-IL-6 treatment in Myocardial Infarction [ASSAIL-MI]; NCT03004703).

Left ventricular diastolic function: Effects of high-intensity exercise after acute myocardial infarction.

OBJECTIVES: Reduced left ventricular (LV) diastolic function indicates poor prognosis after acute myocardial infarction (AMI). Our aim was to study whether a twelve-week high-intensity interval training program could improve diastolic function in patients with a relatively recent AMI. DESIGN: Twenty-eight patients (mean age 56 (SD 8) years) with a recent AMI performed high-intensity interval training twice a week for 12 weeks. Each training session consisted of four 4-minute bouts at 85%-95% of peak heart rate, separated by 4-minute active breaks. A cardiopulmonary exercise test was performed to determine peak oxygen uptake (VO2peak ). Echocardiography was performed at rest and during an upright bicycle exercise test. RESULTS: There was a significant increase in mitral annulus early diastolic velocity (e') at peak exercise (75 W) from baseline to follow-up (7.9 (1.5) vs. 8.4 (1.7) cm/s, P = .012), but no change in e' at rest (7.1 (1.9) vs. 7.3 (1.7) cm/s, P = .42). There was a significant increase in VO2peak (mean (SD), 35.2 (7.3) vs. 38.9 (7.4) ml/kg/min, P < .001). e' at peak exercise correlated with VO2peak both at baseline and follow-up (r = 0.50, P = .007, and r = 0.41, P = .032). CONCLUSION: The present study shows that LV diastolic function during exercise is related to VO2peak . We also found an improvement of diastolic function after exercise training, even in a population with a relatively well preserved systolic and diastolic function. The results demonstrate the importance of obtaining measurements during exercise when evaluating the effects of exercise interventions.

Emerging concepts for myocardial late gadolinium enhancement MRI.

Late gadolinium enhancement is a useful tool for scar detection, based on differences in the volume of distribution of gadolinium, an extracellular agent. The presence of fibrosis in the myocardium amenable to be detected with late gadolinium enhancement MRI is found not only in ischemic cardiomyopathy, in which it offers information regarding viability and prognosis, but also in a wide variety of non-ischemic cardiomyopathies. In the following review we will discuss the methodological aspects of gadolinium-based imaging, as well as its applications and anticipated future developments.

Strain rate imaging combined with wall motion analysis gives incremental value in direct quantification of myocardial infarct size.

BACKGROUND: The study aimed to evaluate the diagnostic accuracy of a new method for direct echocardiographic quantification of the myocardial infarct size, using late enhancement magnetic resonance imaging (LE-MRI) as a reference method. METHODS AND RESULTS: Echocardiography and LE-MRI were performed on average 31 days after first-time myocardial infarction in 58 patients. Echocardiography was also performed on 35 healthy controls. Direct echocardiographic quantification of the infarct size was based on automated selection and quantification of areas with hypokinesia and akinesia from colour-coded strain rate data, with manual correction based on visual wall motion analysis. The left ventricular (LV) ejection fraction, speckle-tracking-based longitudinal global strain, wall motion score index (WMSI), longitudinal systolic motion and velocity, and the ratio of early mitral inflow velocity to mitral annular early diastolic velocity were also measured by echocardiography. The area under the receiver-operating characteristic curves for the identification of the infarct size >12% by LE-MRI was 0.84, using the new method for direct echocardiographic quantification of the infarct size. The new method showed significantly a higher correlation with the infarct size by LE-MRI both at the global (r = 0.81) and segmental (r = 0.59) level compared with other indices of LV function. CONCLUSION: Direct quantification of the percentage infarct size by strain rate imaging combined with wall motion analysis yields high diagnostic accuracy and better correlation to LE-MRI compared with other echocardiographic indices of global LV function. Echocardiography performed ~1 month after myocardial infarction showed ability to identify the patients with the infarct size >12%.

A 50-year-old man with eosinophilia and cardiomyopathy: need for endomyocardial biopsy?

A 50-year-old man was admitted with a suspected acute coronary syndrome. The coronary angiogram, however, was normal. He was found to have a cardiomyopathy and eosinophilia. The diagnosis was established as a perimyocarditis secondary to the Churg-Strauss syndrome. An important question is whether an endomyocardial biopsy should have been performed.

A comparison of retrospectively self-gated magnetic resonance imaging and high-frequency echocardiography for characterization of left ventricular function in mice.

Non-invasive imaging methods like echocardiography and magnetic resonance imaging (MRI) are very valuable in longitudinal follow-up studies of cardiac function in small animals. To be able to compare results from studies using different methods, and explain possible differences, it is important to know the agreement between these methods. As both self-gated high-field MRI and high-frequency echocardiography (hf-echo) M-mode are potential methods for evaluation of left ventricular (LV) function in healthy mice, our aim was to assess the agreement between these two methods. Fifteen healthy female C57BL/6J mice underwent both self-gated MRI and hf-echo during the same session of light isoflurane anaesthesia. LV dimensions were estimated offline, and agreement between the methods and reproducibility for the two methods assessed using Bland-Altman methods. In summary, hf-echo M-mode had better inter-observer repeatability than self-gated MRI for all measured parameters. Compared with hf-echo, systolic posterior wall thicknesses were significantly higher when measured by MRI, while diastolic anterior wall thicknesses were found to be significantly smaller. MRI measurements of diastolic LV diameter were also higher using MRI, resulting in larger fractional shortening values compared with the values obtained by hf-echo. In conclusion, hf-echo M-mode is easy to apply, has high temporal and spatial resolution, and good reproducibility. Self-gated MRI might be advantageous in cases of abnormal LV geometry and heterogeneous regional myocardial function, especially with improvements in spatial resolution. The moderate agreement between the methods must be taken into account when comparing studies using the two modalities.

Reproducibility in echocardiographic assessment of the left ventricular global and regional function, the HUNT study.

AIMS: The study aimed to compare the inter-observer reproducibility of new and traditional measurements of the left ventricular (LV) global and regional function. METHODS AND RESULTS: Two experienced echocardiographers performed 20 complete echo/Doppler examinations and 50 analyses on ten healthy subjects. All recordings were analysed for systolic and diastolic conventional and deformation measurements by both echocardiographers. Inter-observer mean error (absolute difference divided by the mean) was 4% and lowest (P = 0.001) for systolic M-mode annulus excursion. Mean error for the regional deformation indices was significantly higher than for all the global measurements (all P < 0.001). Mean error for analyses of the same recording was 34% (P = 0.002) lower for global systolic indices and 44% (P < 0.001) lower for global diastolic indices than inter-observer mean error for analyses made in separate recordings. CONCLUSION: Systolic M-mode annulus excursion showed better inter-observer reproducibility than other traditional and newer measurements of LV systolic and diastolic function. Repeated analyses of the same recordings underestimate the more clinically relevant inter-observer reproducibility by approximately 40% for most measurements of LV function.