The combination of carboxy-terminal propeptide of procollagen type I blood levels and late gadolinium enhancement at cardiac magnetic resonance provides additional prognostic information in idiopathic dilated cardiomyopathy - A multilevel assessment of myocardial fibrosis in dilated cardiomyopathy.

AIMS: To determine the prognostic value of multilevel assessment of fibrosis in dilated cardiomyopathy (DCM) patients. METHODS AND RESULTS: We quantified fibrosis in 209 DCM patients at three levels: (i) non-invasive late gadolinium enhancement (LGE) at cardiac magnetic resonance (CMR); (ii) blood biomarkers [amino-terminal propeptide of procollagen type III (PIIINP) and carboxy-terminal propeptide of procollagen type I (PICP)], (iii) invasive endomyocardial biopsy (EMB) (collagen volume fraction, CVF). Both LGE and elevated blood PICP levels, but neither PIIINP nor CVF predicted a worse outcome defined as death, heart transplantation, heart failure hospitalization, or life-threatening arrhythmias, after adjusting for known clinical predictors [adjusted hazard ratios: LGE 3.54, 95% confidence interval (CI) 1.90-6.60; P < 0.001 and PICP 1.02, 95% CI 1.01-1.03; P = 0.001]. The combination of LGE and PICP provided the highest prognostic benefit in prediction (likelihood ratio test P = 0.007) and reclassification (net reclassification index: 0.28, P = 0.02; and integrated discrimination improvement index: 0.139, P = 0.01) when added to the clinical prediction model. Moreover, patients with a combination of LGE and elevated PICP (LGE+/PICP+) had the worst prognosis (log-rank P < 0.001). RNA-sequencing and gene enrichment analysis of EMB showed an increased expression of pro-fibrotic and pro-inflammatory pathways in patients with high levels of fibrosis (LGE+/PICP+) compared to patients with low levels of fibrosis (LGE-/PICP-). This would suggest the validity of myocardial fibrosis detection by LGE and PICP, as the subsequent generated fibrotic risk profiles are associated with distinct cardiac transcriptomic profiles. CONCLUSION: The combination of myocardial fibrosis at CMR and circulating PICP levels provides additive prognostic value accompanied by a pro-fibrotic and pro-inflammatory transcriptomic profile in DCM patients with LGE and elevated PICP.

Clinical assessment of aortic valve stenosis: Comparison between 4D flow MRI and transthoracic echocardiography.

BACKGROUND: The prevalence of valvular aortic stenosis (AS) increases as the population ages. Echocardiographic measurements of peak jet velocity (Vpeak ), mean pressure gradient (Pmean ), and aortic valve area (AVA) determine AS severity and play a pivotal role in the stratification towards valvular replacement. A multimodality imaging approach might be needed in cases of uncertainty about the actual severity of the stenosis. PURPOSE: To compare four-dimensional phase-contrast magnetic resonance (4D PC-MR), two-dimensional (2D) PC-MR, and transthoracic echocardiography (TTE) for quantification of AS. STUDY TYPE: Prospective. POPULATION: Twenty patients with various degrees of AS (69.3 ± 5.0 years). FIELD STRENGTH/SEQUENCES: 4D PC-MR and 2D PC-MR at 3T. ASSESSMENT: We compared Vpeak , Pmean , and AVA between TTE, 4D PC-MR, and 2D PC-MR. Flow eccentricity was quantified by means of normalized flow displacement, and its influence on the accuracy of TTE measurements was investigated. STATISTICAL TESTS: Pearson's correlation, Bland-Altman analysis, paired t-test, and intraclass correlation coefficient. RESULTS: 4D PC-MR measured higher Vpeak (r = 0.95, mean difference + 16.4 ± 10.7%, P <0.001), and Pmean (r = 0.92, mean difference + 14.9 ± 16.0%, P = 0.013), but a less critical AVA (r = 0.80, mean difference + 19.9 ± 20.6%, P = 0.002) than TTE. In contrast, unidirectional 2D PC-MR substantially underestimated AS severity when compared with TTE. Differences in Vpeak between 4D PC-MR and TTE showed to be strongly correlated with the eccentricity of the flow jet (r = 0.89, P <0.001). Use of 4D PC-MR improved the concordance between Vpeak and AVA (from 0.68 to 0.87), and between PGmean and AVA (from 0.68 to 0.86). DATA CONCLUSION: 4D PC-MR improves the concordance between the different AS parameters and could serve as an additional imaging technique next to TTE. Future studies should address the potential value of 4D PC-MR in patients with discordant echocardiographic parameters. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:472-480.

Adding Speckle-Tracking Echocardiography to Visual Assessment of Systolic Wall Motion Abnormalities Improves the Detection of Myocardial Infarction.

BACKGROUND: The aim of this study was to investigate whether speckle-tracking echocardiography (STE) improves the detection of myocardial infarction (MI) over visual assessment of systolic wall motion abnormalities (SWMAs) using delayed enhancement cardiac magnetic resonance imaging as a reference. METHODS: Transthoracic echocardiography was performed in 95 patients with first ST segment elevation MI 110 days (interquartile range, 97-171 days) after MI and in 48 healthy control subjects. Two experienced observers independently assessed SWMAs. Separately, longitudinal peak negative, peak systolic, end-systolic, global strain, and strain rate were measured and averaged for the American Heart Association-recommended coronary artery perfusion territories. Receiver operating characteristic analysis was used to determine a single optimal cutoff value for each strain parameter. The diagnostic accuracy of an algorithm combining visual assessment and STE was evaluated. RESULTS: Median infarct size and transmurality were 15% (interquartile range, 7%-24%) and 64% (interquartile range, 46%-78%), respectively. Sensitivity, specificity, and accuracy of visual assessment to detect MI were 74% (95% CI, 63%-82%), 85% (95% CI, 72%-93%), and 78% (95% CI, 70%-84%), respectively. Among the strain parameters, SR had the highest diagnostic accuracy (area under the curve, 0.88; 95% CI, 0.83-0.94; cutoff value, -0.97 sec-1). The combination with STE improved sensitivity compared with visual assessment alone (94%; 95% CI, 86%-97%; P < .001), minimally affecting specificity (79%; 95% CI, 65%-89%; P = .607). Overall accuracy improved to 89% (95% CI, 82%-93%; P = .011). Multivariate analysis accounting for age and sex demonstrated that SR was independently associated with MI (odds ratio, 2.0; 95% CI, 1.6-2.7). CONCLUSIONS: The sensitivity and diagnostic accuracy of visually detecting chronic MI by assessing SWMAs are moderate but substantially improve when adding STE.

Non-invasive assessment of microvascular dysfunction in patients with microvascular angina.

BACKGROUND: We aimed to evaluate the microvascular function in patients with microvascular angina (MVA) by assessing 1) the endothelial glycocalyx barrier properties using sublingual microscopy, and 2) the myocardial perfusion reserve using cardiovascular magnetic resonance (CMR) imaging. METHODS: Sublingual microscopy was performed in 13 MVA patients (angina pectoris, ST-depression on treadmill testing, normal coronary angiogram) and compared with 2 control groups of 13 volunteers and 14 patients with known obstructive coronary artery disease (CAD). To test the glycocalyx-mediated microvascular responsiveness, the erythrocyte perfused boundary region (PBR) was assessed at baseline and after nitroglycerin challenge. RESULTS: The baseline PBR of MVA patients was similar to controls with CAD (p=0.72), and larger than in volunteers (p=0.02). Only the volunteers demonstrated a significant increase in PBR after nitroglycerin (p=0.03). In the 13 MVA patients, adenosine stress CMR perfusion imaging was performed. Although a significant increase in myocardial perfusion was observed in both the subendocardium and subepicardium during stress, the subendocardial perfusion reserve was significantly lower (p=0.02). The PBR responsiveness of the sublingual microvasculature showed a strong correlation with the transmural myocardial perfusion reserve (r=0.86, p<0.001). CONCLUSIONS: Patients with MVA can be characterized by microvascular glycocalyx dysfunction using sublingual microscopy. The strong correlation between sublingual PBR responsiveness and myocardial perfusion reserve suggests that the glycocalyx may play an important role in the regulation of microvascular volume for myocardial perfusion and supports the concept of impaired glycocalyx barrier properties in MVA.

Activity and Life After Survival of a Cardiac Arrest (ALASCA) and the effectiveness of an early intervention service: design of a randomised controlled trial.

BACKGROUND: Cardiac arrest survivors may experience hypoxic brain injury that results in cognitive impairments which frequently remain unrecognised. This may lead to limitations in daily activities and participation in society, a decreased quality of life for the patient, and a high strain for the caregiver. Publications about interventions directed at improving quality of life after survival of a cardiac arrest are scarce. Therefore, evidence about effective rehabilitation programmes for cardiac arrest survivors is urgently needed. This paper presents the design of the ALASCA (Activity and Life After Survival of a Cardiac Arrest) trial, a randomised, controlled clinical trial to evaluate the effects of a new early intervention service for survivors of a cardiac arrest and their caregivers. METHODS/DESIGN: The study population comprises all people who survive two weeks after a cardiac arrest and are admitted to one of the participating hospitals in the Southern part of the Netherlands. In a two-group randomised, controlled clinical trial, half of the participants will receive an early intervention service. The early intervention service consists of several consultations with a specialised nurse for the patient and their caregiver during the first three months after the cardiac arrest. The intervention is directed at screening for cognitive problems, provision of informational, emotional and practical support, and stimulating self-management. If necessary, referral to specialised care can take place. Persons in the control group will receive the care as usual. The primary outcome measures are the extent of participation in society and quality of life of the patient one year after a cardiac arrest. Secondary outcome measures are the level of cognitive, emotional and cardiovascular impairment and daily functioning of the patient, as well as the strain for and quality of life of the caregiver. Participants and their caregivers will be followed for twelve months after the cardiac arrest.A process evaluation will be performed to gain insight into factors that might have contributed to the effectiveness of the intervention and to gather information about the feasibility of the programme. Furthermore, an economic evaluation will be carried out to determine the cost-effectiveness and cost-utility of the intervention. DISCUSSION: The results of this study will provide evidence on the effectiveness of this early intervention service, as well as the cost-effectiveness and its feasibility. TRIAL REGISTRATION: Current Controlled Trials [ISRCTN74835019].