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Current guidelines advocate viability assessment before revascularization of chronic coronary total occlusions (CTO). The present study evaluated associations between coronary collaterals and myocardial viability assessed by cardiac magnetic resonance (CMR) imaging in patients with a CTO. Patients

A myocardial ischemic burden (IB) of 10% or more denotes high risk patients who benefit from revascularization. This threshold has been assessed by SPECT, the higher resolution of PET presumably results in a better detection of the extent and severity of ischemia. As such, a PET-derived IB might

Contains fulltext : 202703.pdf (Publisher’s version ) (Closed access) Aims: Patients with acute coronary syndrome who present initially with ST-elevation on the electrocardiogram but, subsequently, show complete normalization of the ST-segment and relief of symptoms before reperfusion therapy are referred to as transient ST-segment elevation myocardial infarction (STEMI) and pose a therapeutic challenge. It is unclear what the optimal timing of revascularization is for these patients and whether they should be treated with a STEMI-like or a non-ST-segment elevation myocardial infarction (NSTEMI)-like invasive approach. The aim of the study is to determine the effect of an immediate vs. a delayed invasive strategy on infarct size measured by cardiac magnetic resonance imaging (CMR). Methods and results: In a randomized clinical trial, 142 patients with transient STEMI with symptoms of any duration were randomized to an immediate (STEMI-like) [0.3 h; interquartile range (IQR) 0.2-0.7 h] or a delayed (NSTEMI-like) invasive strategy (22.7 h; IQR 18.2-27.3 h). Infarct size as percentage of the left ventricular myocardial mass measured by CMR at day four was generally small and not different between the immediate and the delayed invasive group (1.3%; IQR 0.0-3.5% vs. 1.5% IQR 0.0-4.1%, P = 0.48). By intention to treat, there was no difference in major adverse cardiac events (MACE), defined as death, reinfarction, or target vessel revascularization at 30 days (2.9% vs. 2.8%, P = 1.00). However, four additional patients (5.6%) in the delayed invasive strategy required urgent intervention due to signs and symptoms of reinfarction while awaiting angiography. Conclusion: Overall, infarct size in transient STEMI is small and is not influenced by an immediate or delayed invasive strategy. In addition, short-term MACE was low and not different between the treatment groups.

Aims: Despite high variability in coronary anatomy, quantitative positron emission tomography (PET) perfusion in coronary territories is traditionally calculated according to the American Heart Association (AHA) 17-segments model. This study aimed to assess the impact of individualized segmentation of myocardial segments on the diagnostic accuracy of hyperaemic myocardial blood flow (MBF) values for haemodynamically significant coronary artery disease (CAD).Methods and results: Patients with suspected CAD (n = 204) underwent coronary computed tomography angiography (CCTA) and [15O]H2O PET followed by invasive coronary angiography with fractional flow reserve assessment of all major coronary arteries. Hyperaemic MBF per vascular territory was calculated using both standard segmentation according to the AHA model and individualized segmentation, in which CCTA was used to assign coronary arteries to PET perfusion territories. In 122 (59.8%) patients, one or more segments were redistributed after individualized segmentation. No differences in mean MBF values were seen between segmentation methods, except for a minor difference in hyperaemic MBF in the LCX territory (P = 0.001). These minor changes resulted in discordant PET-defined haemodynamically significant CAD between the two methods in only 5 (0.8%) vessels. The diagnostic value for detecting haemodynamically significant CAD did not differ between individualized and standard segmentation, with area under the curves of 0.79 and 0.78, respectively (P = 0.34).Conclusions: Individualized segmentation using CCTA-derived coronary anatomy led to redistribution of standard myocardial segments in 60% of patients. However, this had little impact on [15O]H2O PET MBF values and diagnostic value for detecting haemodynamically significant CAD did not change. Therefore, clinical impact of individualized segmentation seems limited.

Contains fulltext : 207076.pdf (Publisher’s version ) (Closed access) To evaluate aortic stiffness in patients with ankylosing spondylitis (AS) using cardiovascular magnetic resonance (CMR) and to assess its association with AS characteristics and left ventricular (LV) remodeling. In this prospective study, 14 consecutive AS patients were each matched to two controls without cardiovascular symptoms or known cardiovascular disease who underwent CMR imaging for the assessment of aortic arch pulse wave velocity (PWV) at 1.5 Tesla. To enhance comparability of the samples, matching was done with replacement resulting in 20 unique controls. Only AS patients with abnormal findings on screening echocardiography were included in this exploratory study. Cine CMR was used to assess LV geometry and systolic function, and late gadolinium enhancement was performed to determine the presence of myocardial hyperenhancement (i.e., fibrosis). Aortic arch PWV was significantly higher in the AS group compared with the control group (median 9.7 m/s, interquartile range [IQR] 7.1 to 11.8 vs. 6.1 m/s, IQR 4.6 to 7.6 m/s; p < 0.001). PWV was positively associated with functional disability as measured by BASFI (R: 0.62; p = 0.018). Three patients (21%) with a non-ischemic pattern of hyperenhancement showed increased PWV (11.7, 12.3, and 16.5 m/s) as compared to the 11 patients without hyperenhancement (9.0 m/s, IQR 6.6 to 10.5 m/s; p = 0.022). PWV was inversely associated with LV ejection fraction (R: - 0.63; p = 0.015), but was not found to be statistically correlated to LV volumes or mass. Aortic arch PWV was increased in our cohort of patients with AS. Higher PWV in the aortic arch was associated with functional disability, the presence of non-ischemic hyperenhancement, and reduced LV systolic function.

Chronotropic incompetence (CI) is generally defined as the inability to increase the heart rate (HR) adequately during exercise to match cardiac output to metabolic demands. In patients with heart failure (HF), however, this definition is unsuitable because metabolic demands are unmatched to cardiac output in both conditions. Moreover, HR dynamics in patients with HF differ from those in healthy subjects and may be affected by β-blocking medication. Nevertheless, it has been demonstrated that CI in HF is associated with reduced functional capacity and poor survival. During exercise, the normal heart increases both stroke volume and HR, whereas in the failing heart, contractility reserve is lost, thus rendering increases in cardiac output primarily dependent on cardioacceleration. Consequently, insufficient cardioacceleration because of CI may be considered a major limiting factor in the exercise capacity of patients with HF. Despite the profound effects of CI in this specific population, the issue has drawn limited attention during the past years and is often overlooked in clinical practice. This might partly be caused by a lack of standardized approach to diagnose the disease, further complicated by changes in HR dynamics in the HF population, which render reference values derived from a normal population invalid. Cardiac implantable electronic devices (implantable cardioverter defibrillator; cardiac resynchronization therapy) now offer a unique opportunity to study HR dynamics and provide treatment options for CI by rate-adaptive pacing using an incorporated sensor that measures physical activity. This review provides an overview of disease mechanisms, diagnostic strategies, clinical consequences, and state-of-the-art device therapy for CI in HF.

Infectious myocarditis is the result of an immune response to a microbial infection of the heart. The blood vessels of the heart, both the intramyocardial microvasculature and the large epicardial coronary arteries, play an important role in the pathogenesis of infectious myocarditis. First of all, in addition to cardiomyocytes, endothelial cells of the cardiac (micro)vasculature are direct targets for infection. Moreover, through the expression of adhesion molecules and antigen presenting Major Histocompatibility Complex molecules, the blood vessels assist in shaping the cellular immune response in infectious myocarditis. In addition, damage and dysfunction of the cardiac (micro)vasculature are associated with thrombus formation as well as aberrant regulation of vascular tone including coronary vasospasm. These in turn can cause cardiac perfusion abnormalities and even myocardial infarction. In this review, we will discuss the role of the cardiac (micro)vasculature in the pathogenesis of infectious myocarditis. Electronic supplementary material The online version of this article (10.1007/s10741-018-9688-x) contains supplementary material, which is available to authorized users.

Background: The main goal of coronary revascularization is to restore myocardial perfusion in case of ischemia, causing coronary artery disease. Yet, little is known on the effect of revascularization on absolute myocardial blood flow (MBF). Therefore, the present prospective study assesses the impact of coronary revascularization on absolute MBF as measured by [ 15 O]H 2 O positron emission tomography and fractional flow reserve (FFR) in patients with stable coronary artery disease. Methods and Results: Fifty-three patients (87% men, mean age 58.7±9.0 years) with suspected coronary artery disease were included prospectively. All patients underwent serial [ 15 O]H 2 O positron emission tomography perfusion imaging at baseline and after revascularization by either percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery. FFR was routinely measured at baseline and directly post-PCI. After revascularization, regional rest and stress MBF improved from 0.77±0.16 to 0.86±0.25 mL/min/g and from 1.57±0.59 to 2.48±0.91 mL/min/g, respectively, yielding an increase in coronary flow reserve from 2.02±0.69 to 2.94±0.94 ( P P r = 0.74 and r = 0.71, respectively, P P =0.02). However, patients undergoing bypass grafting had a more advanced stage of coronary artery disease and more incomplete revascularizations. Conclusion: Successful coronary revascularization has a significant and positive impact on absolute myocardial perfusion as assessed by serial quantitative [ 15 O]H 2 O positron emission tomography. Notably, improvement of FFR after PCI was directly related to the increase in hyperemic MBF.

This study sought to compare Doppler flow velocity reserve (CFRCoronary flow reserve (CFR) is an important parameter for assessing coronary vascular function. To date, 2 techniques are available for invasive assessment of CFR: Doppler flow velocity and thermodilution. Although these techniques have been compared with each other, neither has been compared with [CFR was assessed in 98 vessels of 40 consecutive stable patients with suspected coronary artery disease. Patients underwent [The quality of Doppler flow velocity traces was significantly lower than that of thermodilution curves (p 0.001). A moderate correlation was observed between CFRCoronary flow reserve, determined using Doppler flow velocity, has superior agreement with [

Contains fulltext : 209425.pdf (Publisher’s version ) (Closed access) Aims: The longitudinal myocardial blood flow (MBF) gradient derived from positron emission tomography (PET) has been proposed as an emerging non-invasive index of haemodynamically significant coronary artery disease (CAD). This study aimed to investigate the diagnostic value of longitudinal MBF gradient for the presence of haemodynamically significant CAD. Methods and results: A total of 204 patients (603 vessels) with suspected CAD underwent [15O]H2O PET followed by invasive coronary angiography with fractional flow reserve (FFR) of all major coronary arteries. Longitudinal base-to-apex MBF gradients were assessed by two methods, using MBF in apical and mid (Method 1) or in apical and basal (Method 2) myocardial segments to calculate the gradient. The hyperaemic longitudinal MBF gradient was only weakly correlated with FFR (Method 1: r = 0.12, P = 0.02; Method 2: r = 0.22, P < 0.001). The hyperaemic longitudinal MBF gradient (by both methods), had lower diagnostic value when compared with hyperaemic MBF for the presence of haemodynamically significant CAD, defined as an FFR

Background: Fractional fow reserve (FFR) is, next to lesion severity, affected by plaque vulnerability as assessed by coronary computed tomography angiography (CCTA) and associated with imminent acute coronary syndromes. Instantaneous wave-free ratio (iFR) has recently emerged as an alternative for FFR to interrogate coronary lesions for ischemia. It is, however, unknown whether vasodilator free assessment with iFR is associated with plaque stability similarly as FFR. The current substudy of the PACIFIC trial explores the impact of CCTA derived unfavorable plaque features on both hyperemic and non-hyperemic fow indices in order to detect vulnerable plaques. Methods: Of 119 patients (62% men, age 58 ± 8.6 years) with suspected coronary artery disease, 257 vessels were prospectively evaluated. Each patient underwent 256-slice CCTA to assess stenosis severity and plaque features (positive remodeling (PR), low attenuation plaque (LAP), spotty calcifcation (SC) and napkin ring sign (NRS)), as well as intracoronary pressure measurements (FFR, iFR, resting Pd/Pa and pressure ratio during adenosine within the wave-free period (iFRa)). CCTA derived plaque characteristics were related to these invasive pressure measurements. Results: Atherosclerotic plaques were present in 170 (66%) coronary arteries. On a per-vessel basis, luminal stenosis severity was signifcantly associated with impaired FFR, iFR, resting Pd/Pa and iFRa. Multivariable analysis revealed that PR and LAP were independently related to an impaired FFR (p = 0.006 and p = 0.038, respectively) and iFRa (p = 0.005 and p = 0.027, respectively), next to stenosis severity (p

Objectives Native T1 mapping and late gadolinium enhancement (LGE) imaging offer detailed characterisation of the myocardium after acute myocardial infarction (AMI). We evaluated the effects of microvascular injury (MVI) and intramyocardial haemorrhage on local T1 and T2* values in patients with a reperfused AMI. Methods Forty-three patients after reperfused AMI underwent cardiovascular magnetic resonance imaging (CMR) at 4 [3-5] days, including native MOLLI T1 and T2* mapping, STIR, cine imaging and LGE. T1 and T2* values were determined in LGE-defined regions of interest: the MI core incorporating MVI when present, the core-adjacent MI border zone (without any areas of MVI), and remote myocardium. Results Average T1 in the MI core was higher than in the MI border zone and remote myocardium. However, in the 20 (47%) patients with MVI, MI core T1 was lower than in patients without MVI (MVI 1048±78ms, no MVI 1111±89ms, p=0.02). MI core T2* was significantly lower in patients with MVI than in those without (MVI 20 [18-23]ms, no MVI 31 [26-39]ms, p

Contains fulltext : 200408.pdf (Publisher’s version ) (Open Access) OBJECTIVES: The aim of the present study was to evaluate the diagnostic performances of strain and wall thickening analysis in discriminating among three types of myocardium after acute myocardial infarction: non-infarcted myocardium, infarcted myocardium without microvascular obstruction (MVO) and infarcted myocardium with MVO. METHODS: Seventy-one patients with a successfully treated ST-segment elevation myocardial infarction underwent cardiovascular magnetic resonance imaging at 2-6 days after reperfusion. The imaging protocol included conventional cine imaging, myocardial tissue tagging and late gadolinium enhancement. Regional circumferential and radial strain and associated strain rates were analyzed in a 16-segment model as were the absolute and relative wall thickening. RESULTS: Hyperenhancement was detected in 418 (38%) of 1096 segments and was accompanied by MVO in 145 (35%) of hyperenhanced segments. Wall thickening, circumferential and radial strain were all significantly diminished in segments with hyperenhancement and decreased even further if MVO was also present (all p < 0.001). Peak circumferential strain (CS) surpassed all other strain and wall thickening parameters in its ability to discriminate between hyperenhanced and non-enhanced myocardium (all p < 0.05). Furthermore, CS was superior to both absolute and relative wall thickening in differentiating infarcted segments with MVO from infarcted segments without MVO (p = 0.02 and p = 0.001, respectively). CONCLUSIONS: Strain analysis is superior to wall thickening in differentiating between non-infarcted myocardium, infarcted myocardium without MVO and infarcted myocardium with MVO. Peak circumferential strain is the most accurate marker of regional function. KEY POINTS: * CMR can quantify regional myocardial function by analysis of wall thickening on cine images and strain analysis of tissue tagged images. * Strain analysis is superior to wall thickening in differentiating between different degrees of myocardial injury after acute myocardial infarction. * Peak circumferential strain is the most accurate marker of regional function.

Background: In patients with left bundle branch block (LBBB), QRS duration (QRSd) depends on left ventricular (LV) dimension. Previously, we demonstrated that normalizing QRSd to LV dimension, to adjust for variations in LV size, improved prediction of hemodynamic response to cardiac resynchronization therapy (CRT). In addition, sex-specific differences in CRT outcome have been attributed to normalized QRSd. The present study evaluates the effect of normalization of QRSd to LV dimension on prediction of survival after CRT implantation. Methods: In this 2-center study, we studied 250 heart failure patients with LV ejection fraction ≤35% and QRSd ≥120 ms who underwent cardiac magnetic resonance imaging before CRT implantation. LV end-diastolic volumes were used for QRSd normalization (ie, QRSd/LV end-diastolic volumes). The primary end point was a combined end point of death, LV assist device, or heart transplantation. Results: During a median follow-up of 3.9 years, 79 (32%) patients reached the primary end point. Using univariable Cox regression, unadjusted QRSd was unrelated to CRT outcome ( P =0.116). In contrast, normalized QRSd was a strong predictor of survival (hazard ratio, 0.81 per 0.1 ms/mL; P =0.008). Women demonstrated higher normalized QRSd than men (0.62±0.17 versus 0.55±0.17 ms/mL; P =0.003) and showed better survival after CRT (hazard ratio, 0.52; P =0.018). A multivariable prognostic model included normalized QRSd together with age, atrial fibrillation, renal function, and heart failure cause, whereas sex, diabetes mellitus, strict left bundle branch block morphology, and LV end-diastolic volumes were expelled from the model. Conclusions: Normalization of QRSd to LV dimension improves prediction of survival after CRT implantation. In addition, sex-specific differences in CRT outcome might be attributed to the higher QRSd/LV end-diastolic volumes ratio that was found in selected women, indicating more conduction delay.

Monocytes are involved in adverse left ventricular (LV) remodelling following myocardial infarction (MI). To provide therapeutic opportunities we aimed to identify gene transcripts in monocytes that relate to post-MI healing and evaluated intervention with the observed gene activity in a rat MI model. In 51 MI patients treated by primary percutaneous coronary intervention (PCI), the change in LV end-diastolic volume index (EDVi) from baseline to 4-month follow-up was assessed using cardiovascular magnetic resonance imaging (CMR). Circulating monocytes were collected at day 5 (Arterioscler Thromb Vasc Biol 35:1066–1070, 2015; Cell Stem Cell 16:477–487, 2015; Curr Med Chem 13:1877–1893, 2006) after primary PCI for transcriptome analysis. Transcriptional profiling and pathway analysis revealed that patients with a decreased LV EDVi showed an induction of type I interferon (IFN) signalling (type I IFN pathway: P value

Chronotropic incompetence (CI) is generally defined as the inability to increase the heart rate (HR) adequately during exercise to match cardiac output to metabolic demands. In patients with heart failure (HF), however, this definition is unsuitable because metabolic demands are unmatched to cardiac output in both conditions. Moreover, HR dynamics in patients with HF differ from those in healthy subjects and may be affected by β-blocking medication. Nevertheless, it has been demonstrated that CI in HF is associated with reduced functional capacity and poor survival. During exercise, the normal heart increases both stroke volume and HR, whereas in the failing heart, contractility reserve is lost, thus rendering increases in cardiac output primarily dependent on cardioacceleration. Consequently, insufficient cardioacceleration because of CI may be considered a major limiting factor in the exercise capacity of patients with HF. Despite the profound effects of CI in this specific population, the issue has drawn limited attention during the past years and is often overlooked in clinical practice. This might partly be caused by a lack of standardized approach to diagnose the disease, further complicated by changes in HR dynamics in the HF population, which render reference values derived from a normal population invalid. Cardiac implantable electronic devices (implantable cardioverter defibrillator; cardiac resynchronization therapy) now offer a unique opportunity to study HR dynamics and provide treatment options for CI by rate-adaptive pacing using an incorporated sensor that measures physical activity. This review provides an overview of disease mechanisms, diagnostic strategies, clinical consequences, and state-of-the-art device therapy for CI in HF.

This review and meta-analysis reviews the prognostic value of cardiac magnetic resonance (CMR) in nonischemic dilated cardiomyopathy (DCM).Late gadolinium-enhanced (LGE) CMR is a noninvasive method to determine the underlying cause of DCM and previous studies reported the prognostic value of the presence of LGE to identify patients at risk of major adverse cardiovascular events.PubMed was searched for studies describing the prognostic implication of LGE in patients with DCM for the specified endpoints cardiovascular mortality, major ventricular arrhythmic events including appropriate implantable cardioverter-defibrillator therapy, rehospitalization for heart failure, and left ventricular reverse remodeling.Data from 34 studies were included, with a total of 4,554 patients. Contrast enhancement was present in 44.8% of DCM patients. Patients with LGE had increased cardiovascular mortality (odds ratio [OR]: 3.40; 95% confidence interval [CI]: 2.04 to 5.67), ventricular arrhythmic events (OR: 4.52; 95% CI: 3.41 to 5.99), and rehospitalization for heart failure (OR: 2.66; 95% CI: 1.67 to 4.24) compared with those without LGE. Moreover, the absence of LGE predicted left ventricular reverse remodeling (OR: 0.15; 95% CI: 0.06 to 0.36).The presence of LGE on CMR substantially worsens prognosis for adverse cardiovascular events in DCM patients, and the absence indicates left ventricular reverse remodeling.

Reactive oxygen species (ROS) control forkhead box O (FOXO) transcription factor activity by influencing their nuclear translocation. However, knowledge of the ROS cellular source(s) involved herein remains scarce. Recently, we have shown p47phox-dependent activation of ROS-producing NADPH oxidase (NOX) at the nuclear pore in H9c2 rat cardiomyoblasts in response to ischemia. This localizes NOX perfectly to affect protein nuclear translocation, including that of transcription factors. In the current study, involvement of p47phox-dependent production of ROS in the nuclear translocation of FOXO1 was analyzed in H9c2 cells following 4 h of metabolic inhibition (MI), which mimics the effects of ischemia. Nuclear translocation of FOXO1 was determined by quantitative digital-imaging fluorescence and western blot analysis. Subsequently, the effect of inhibiting p47phox-dependent ROS production by short hairpin RNA (shRNA) transfection on FOXO1 translocation was analyzed by digital-imaging microscopy. MI induced a significant translocation of FOXO1 into the nucleus. Transfection with p47phox-shRNA successfully knocked-down p47phox expression, reduced nuclear nitrotyrosine production, an indirect marker for ROS production, and inhibited the nuclear translocation of FOXO1 following MI. With these results, we show for the first time that nuclear import of FOXO1 induced by MI in H9c2 depends critically on p47phox-mediated ROS production.

Aims: Pressure-controlled intermittent coronary sinus occlusion (PICSO) may improve myocardial perfusion after pPCI. We evaluated the safety and feasibility of PICSO after pPCI for STEMI, and explored its effects on infarct size and myocardial function. Methods and results: Thirty patients were enrolled following successful pPCI of a left anterior descending coronary artery culprit lesion for anterior STEMI, in whom PICSO for 90 minutes was attempted. Infarct size and myocardial function were assessed by cardiovascular magnetic resonance (CMR) at two to five days and four months post pPCI. An independent core laboratory selected matched historical control patients with CMR data for comparison. PICSO was initiated in 19 patients (63%), and could be maintained for 90 (±2) minutes in 12 patients (40%). Major adverse safety events occurred in one patient (3%). Comparing all PICSO-treated patients to matched controls demonstrated no significant differences in infarct size or myocardial recovery. However, infarct size reduction from two to five days to four months was greater for patients successfully treated with PICSO compared with matched controls (41.6±8.2% vs. 27.7±9.9%, respectively; p=0.04). Conclusions: PICSO is safe in the setting of STEMI, although feasibility was limited. Administration of sufficient PICSO therapy may be associated with enhanced myocardial recovery during follow-up, warranting further evaluation of this novel therapy.

Item does not contain fulltext OBJECTIVES: This study reports the long-term follow-up of the randomised controlled HEBE trial. The HEBE study is a multicentre trial that randomised 200 patients with large first acute myocardial infarction (AMI) treated with primary percutaneous coronary intervention to either intracoronary infusion of bone marrow mononuclear cells (BMMCs) (n=69), peripheral blood mononuclear cells (PBMCs) (n=66) or standard therapy (n=65). METHODS: In addition to 3-5 days, and 4 months after AMI, all patients underwent cardiac MRI after 2 years. A follow-up for 5 years after AMI was performed to assess clinical adverse events, including death, myocardial reinfarction and hospitalisation for heart failure. RESULTS: Of the 200 patients enrolled, 9 patients died and 12 patients were lost to follow-up at 5 years after AMI. BMMC group showed less increase in LV end-diastolic volume (LVEDV) (3.5+/-16.9 mL/m(2)) compared with (11.2+/-19.8 mL/m(2), p=0.03) in the control group, with no difference between the PBMC group (9.2+/-20.9 mL/m(2)) and controls (p=0.69). Moreover, the BMMC group showed a trend for decrease in LV end systolic volume (-1.8+/-15.0 mL/m(2)) as compared with controls (3.0+/-16.3 mL/m(2), p=0.07), with again no difference between PBMC (3.3+/-18.8 mL/m(2)) and controls (p=0.66). The combined endpoint of death and hospitalisation for heart failure was non-significantly less frequent in the BMMC group compared with the control group (n=4 vs n=1, p=0.20), with no difference between PBMC and controls (n=6 vs n=4, p=0.74). The composite endpoint of death or recurrent myocardial infarction was significantly higher in the PBMC group compared with controls (14 patients vs 3 patients, p=0.008), with no difference between the BMMC group and controls (2 vs 3 patients, p=0.67). CONCLUSIONS: Long-term follow-up of the HEBE trial showed that increase in LVEDV was lower in the BMMC group. This study supports the long-term safety of intracoronary BMMC therapy. However, major clinical cardiovascular adverse events were significantly more frequent in the PBMC group. TRIAL REGISTRATION NUMBER: The Netherlands Trial Register #NTR166 (http://www.trialregister.nl) and the International Standard Randomised Controlled Trial, #ISRCTN95796863 (http://isrctn.org).

Aims The pathophysiology underlying aortic valve stenosis (AVS)-induced cardiac dysfunction and reduced exercise capacity is unclear. We hypothesize that improvement of myocardial external efficiency (MEE)—the ratio between external work and myocardial oxygen consumption (MVO2)—underlies functional improvement of AVS patients after aortic valve replacement (AVR). Therefore, the aim of this proof-of-concept study was to investigate whether myocardial efficiency is reduced in patients with cardiac hypertrophy caused by AVS and to assess the effect of AVR on myocardial efficiency in relation to exercise capacity. Methods and results Echocardiography, cardiopulmonary exercise test, [11C]-acetate positron emission tomography and cardiovascular magnetic resonance imaging were performed in 10 AVS patients prior to (pre-AVR) and 4 months after AVR (post-AVR). Fourteen healthy individuals served as control group. MEE was significantly lower in pre-AVR patients (32 ± 7%) than in controls (49 ± 6%). AVR significantly decreased left ventricle mass and MVO2. Also, external work significantly decreased post-AVR reaching similar values as in controls. AVR significantly improved MEE from 32 ± 7 to 37 ± 5% ( P = 0.02). Moreover, significant correlations were present between the AVR-induced increase in MEE and changes in both exercise work ( r = 0.74, P = 0.01) and peak VO2 ( r = 0.67, P = 0.03). However, four AVS patients did not show improved MEE, which was associated with no or minimal improvement in exercise parameters. Conclusion MEE is significantly reduced in patients with AVS-induced hypertrophy. Improved MEE is an important predictor of AVR-induced improvement of exercise capacity in AVS patients. Future investigation is needed to confirm our observations in a large prospective, multicenter clinical trial.

Alcohol septal ablation (ASA) is successful in most but not in all patients with obstructive hypertrophic cardiomyopathy (HCM). We therefore sought to investigate the relation between infarct location versus infarct size with outcome after ASA in patients with obstructive HCM. Baseline characteristics, procedural characteristics, and cardiovascular magnetic resonance findings at baseline and 4-6 month follow-up after ASA were analysed in 47 patients with obstructive HCM in a single-center retrospective study. Infarct size was determined using late gadolinium enhancement. Infarct location was divided into "basal infarction" and "distal infarction" based on an optimal cut-of value of the distance from the basal septum to the beginning of the infarction. A "successful" outcome was defined as 80 % reduction of the invasive gradient with a post-procedural gradient of

The main eligibility criterion for primary prevention implantable cardioverter defibrillator (ICD) therapy, that is, left ventricular ejection fraction (LVEF), is based on large clinical trials using primarily 2-dimensional echocardiography (2DE). Presently, cardiac magnetic resonance imaging (MRI) is considered the gold standard for LVEF assessment. It has been demonstrated that cardiac MRI assessment results in lower LVEFs compared with 2DE. Consequently, cardiac MRI-LVEF assessment may lead to more patients eligible for ICD implantation with potential clinical consequences. The aim of this study was to evaluate the clinical impact of cardiac MRI-LVEF versus 2DE-LVEF assessment for ICD eligibility. A total of 149 patients with cardiac MRI-LVEF ≤35% referred for primary prevention ICD implantation who underwent both 2DE and cardiac MRI-LVEF assessment were retrospectively included. 2DE-LVEF was computed by Simpson's biplane method. Cardiac MRI-LVEF was computed after outlining the endocardial contours in short-axis cine images. Appropriate device therapy (ADT) and all-cause mortality were evaluated during 2.9 ± 1.7 years of follow-up. The present study found that cardiac MRI-LVEF was significantly lower compared with 2DE-LVEF (23 ± 8% vs 30 ± 8%, respectively, p0.001), resulting in 29 (19%) more patients eligible for ICD implantation according to the current guidelines (LVEF ≤35%). Patients with 2DE-LVEF35% but cardiac MRI-LVEF ≤35% experienced a lower ADT rate compared with patients having 2DE-LVEF ≤35% (2.1% vs 10.4% per year, respectively, p = 0.02). Application of cardiac MRI-LVEF cutoff of 30% resulted in 119 eligible patients experiencing 9.9% per year ADT, comparable with 2DE-LVEF cut-off value of 35%. In conclusion, cardiac MRI-LVEF assessment resulted in more patients eligible for ICD implantation compared with 2DE who showed a relatively low event rate during follow-up. The event rate in patients with cardiac MRI-LVEF ≤30% was comparable with patients having a 2DE-LVEF ≤35%. This study suggests the need for re-evaluation of cardiac MRI-based LVEF cut-off values for ICD eligibility.

Aims Sympathetic denervation typically occurs in the infarcted myocardium and is associated with sudden cardiac death. Impaired innervation was also demonstrated in non-infarcted myocardium in ischaemic and dilated cardiomyopathy (ICMP and DCMP). Factors affecting sympathetic nerve integrity in remote myocardium are unknown. Perfusion abnormalities, even in the absence of epicardial coronary artery disease, may relate to sympathetic dysfunction. This study was aimed to assess the interrelations of myocardial blood flow (MBF), contractile function, and sympathetic innervation in non-infarcted remote myocardium. Methods and results Seventy patients with ICMP or DCMP and LVEF ≤35% were included. [15O]H2O- and [11C]hydroxyephedrine (HED) PET was performed to quantify resting MBF, hyperaemic MBF, and sympathetic innervation. Cardiovascular magnetic resonance (CMR) imaging was performed to assess left ventricular function, mass, wall thickening, and scar size. Wall thickening, [11C]HED retention index (RI), and MBF were assessed in remote segments without scar, selected on CMR. [11C]HED RI was correlated with resting MBF ( r = 0.41, P < 0.001) and hyperaemic MBF ( r = 0.55, P < 0.001) in remote myocardium in both ICMP and DCMP. In addition, LV volumes ( r = −0.40, P = 0.001), LV mass ( r = −0.31, P = 0.008), and wall thickening ( r = 0.45, P < 0.001) correlated with remote [11C]HED RI. Multivariable analysis revealed that hyperaemic MBF ( B = 0.79, P < 0.001), wall thickening ( B = 0.01, P = 0.03), and LVEDV ( B = −0.03, P = 0.02) were independent predictors for remote [11C]HED RI. Conclusion Hyperaemic MBF is independently associated with sympathetic innervation in non-infarcted remote myocardium in patients with ICMP and DCMP. This suggests that microvascular dysfunction might be an important factor related to sympathetic nerve integrity. Whether impaired hyperaemic MBF is the primary cause of this relation remains unclear.

Exclusion of pulmonary hypertension secondary to left-sided heart disease (left heart failure (LHF)) is pivotal in the diagnosis of pulmonary arterial hypertension (PAH). In case of doubt, invasive measurements are recommended. The aim of the present study was to investigate whether it is possible to diagnose LHF using noninvasive parameters in a population suspected of PAH.300 PAH and 80 LHF patients attended our pulmonary hypertension clinic before August 2010, and were used to build the predictive model. 79 PAH and 55 LHF patients attended our clinic from August 2010, and were used for prospective validation.A medical history of left heart disease, S deflection in V1 plus R deflection in V6 in millimetres on ECG, and left atrial dilation or left valvular heart disease that is worse than mild on echocardiography were independent predictors of LHF. The derived risk score system showed good predictive characteristics: R2=0.66 and area under the curve 0.93. In patients with a risk score ≥72, there is 100% certainty that the cause of pulmonary hypertension is LHF. Using this risk score system, the number of right heart catheterisations in LHF may be reduced by 20%.In a population referred under suspicion of PAH, a predictive model incorporating medical history, ECG and echocardiography data can diagnose LHF noninvasively in a substantial percentage of cases.

BACKGROUND: Diagnosing lymphocytic myocarditis (LM) is challenging because of the large variation in clinical presentation and the limitations inherent in current diagnostic tools. The objective of this study was to analyze infiltration of inflammatory cells in quadriceps skeletal muscle of LM patients and investigate the potential diagnostic value of assaying infiltrating inflammatory cells.METHODS: Quadriceps muscle tissue, obtained at autopsy from control patients (n = 9) and LM patients (n = 21), was analyzed using immunohistochemistry for infiltration of lymphocytes (CD45), macrophages (CD68), neutrophilic granulocytes (myeloperoxidase), and several lymphocyte subtypes (CD3, CD4, CD8, CD20) and using polymerase chain reaction for a panel of myocarditis-associated viruses. Additionally, quadriceps muscle from mice with acute coxsackievirus B3-induced myocarditis and control mice was analyzed for presence of lymphocytes and virus.RESULTS: In quadriceps muscle of LM patients the number of infiltrating lymphocytes were significantly increased and LM was diagnosed with specificity of 100% and sensitivity of 71%. Parvovirus B19 was the primary virus found in our patient groups, found in quadriceps tissue of 3 LM patients (although it was also found in 1 control patient). In the mice, enteroviral RNA was present in the quadriceps muscle, although enteroviral capsid proteins and lymphocyte infiltration were found primarily in the adipose tissue within and directly adjacent to the myocyte tissue, rather than in the myocyte tissue itself.CONCLUSIONS: LM is associated with lymphocyte infiltration and viral presence in quadriceps muscle. This indicates that skeletal muscle biopsy/lymphocyte quantification might be a potential diagnostic tool for LM patients.

Importance: At present, the choice of noninvasive testing for a diagnosis of significant coronary artery disease (CAD) is ambiguous, but nuclear myocardial perfusion imaging with single-photon emission tomography (SPECT) or positron emission tomography (PET) and coronary computed tomography angiography (CCTA) is predominantly used for this purpose. However, to date, prospective head-to-head studies are lacking regarding the diagnostic accuracy of these imaging modalities. Furthermore, the combination of anatomical and functional assessments configuring a hybrid approach may yield improved accuracy.Objectives: To establish the diagnostic accuracy of CCTA, SPECT, and PET and explore the incremental value of hybrid imaging compared with fractional flow reserve.Design, Setting, and Participants: A prospective clinical study involving 208 patients with suspected CAD who underwent CCTA, technetium 99m/tetrofosmin-labeled SPECT, and [15O]H2O PET with examination of all coronary arteries by fractional flow reserve was performed from January 23, 2012, to October 25, 2014. Scans were interpreted by core laboratories on an intention-to-diagnose basis. Hybrid images were generated in case of abnormal noninvasive anatomical or functional test results.Main Outcomes and Measures: Hemodynamically significant stenosis in at least 1 coronary artery as indicated by a fractional flow reserve of 0.80 or less and relative diagnostic accuracy of SPECT, PET, and CCTA in detecting hemodynamically significant CAD.Results: Of the 208 patients in the study (76 women and 132 men; mean [SD] age, 58 [9] years), 92 (44.2%) had significant CAD (fractional flow reserve ≤0.80). Sensitivity was 90% (95% CI, 82%-95%) for CCTA, 57% (95% CI, 46%-67%) for SPECT, and 87% (95% CI, 78%-93%) for PET, whereas specificity was 60% (95% CI, 51%-69%) for CCTA, 94% (95% CI, 88%-98%) for SPECT, and 84% (95% CI, 75%-89%) for PET. Single-photon emission tomography was found to be noninferior to PET in terms of specificity (P .99) using the predefined absolute margin of 10%. Diagnostic accuracy was highest for PET (85%; 95% CI, 80%-90%) compared with that of CCTA (74%; 95% CI, 67%-79%; P = .003) and SPECT (77%; 95% CI, 71%-83%; P = .02). Diagnostic accuracy was not enhanced by either hybrid SPECT and CCTA (76%; 95% CI, 70%-82%; P = .75) or by PET and CCTA (84%; 95% CI, 79%-89%; P = .82), but resulted in an increase in specificity (P = .004) at the cost of a decrease in sensitivity (P = .001).Conclusions and Relevance: This controlled clinical head-to-head comparative study revealed PET to exhibit the highest accuracy for diagnosis of myocardial ischemia. Furthermore, a combined anatomical and functional assessment does not add incremental diagnostic value but guides clinical decision-making in an unsalutary fashion.

Item does not contain fulltext Aims: Previous studies on invasive assessment of collateral function in patients with a chronic total occlusion (CTO) have displayed only a limited increase in collateral flow and high occurrence of coronary steal during pharmacological stress. This could question the necessity for ischaemia testing prior to revascularization of CTOs in the presence of myocardial viability. The purpose of the present study was to determine the prevalence of perfusion impairments in patients with a CTO as assessed by [15O]H2O positron emission tomography (PET). Methods and results: Seventy-six consecutive patients (60 men, 62 +/- 10 years) with a documented CTO and preserved left ventricular ejection fraction (LVEF) were included. All patients underwent PET to assess (hyperaemic) myocardial blood flow (MBF) and coronary flow reserve (CFR). Collateral connection score was 0 in 7 (9%), 1 in 13 (17%), and 2 in 56 (74%) of the cases, with predominantly a high Rentrop grade (96% >/=2). MBF of the target area during hyperaemia was significantly lower when compared with the remote area (1.37 +/- 0.37 vs. 2.63 +/- 0.71 mL min-1 g-1, P < 0.001). Target to remote ratio during hyperaemia was on average 0.54 +/- 0.13, and 73 (96%) patients demonstrated a significantly impaired target to remote ratio (/=2.50, whereas coronary steal (CFR

Contains fulltext : 177040.pdf (Publisher’s version ) (Closed access) OBJECTIVE: To determine the impact of right ventricular side branch (RVB) occlusion, during percutaneous coronary interventions (PCIs) of chronic total occlusions (CTOs) of the right coronary artery (RCA), on right ventricular (RV) function. BACKGROUND: Developments in PCI techniques have expanded PCI CTO feasibility. However, the utilization of dissection and reentry techniques and extensive stent implantation increases the risk of coronary side branch occlusion. METHODS: Fifty-four patients (80% male, 63+/-10years) evaluated with cardiac magnetic resonance imaging (CMR) prior and three months after successful PCI CTO RCA (median: 99days, IQR: 92-105days) were included. Right ventricular end-diastolic volume (RVEDV), end-systolic volume (RVESV), and ejection fraction (RVEF) were quantified on CMR images. Occurrence of RVB occlusion and/or RVB recruitment was assessed using procedural angiograms. RESULTS: RVB occlusion was observed in 12 patients (22%), while RVB recruitment occurred in seven patients (13%). Overall, RVEF was comparable between baseline and follow-up (53.8+/-5.8 vs. 53.9+/-5.8%, p=0.95). RVB occlusion was not associated with a significant change in RVEDV or RVEF (156.9+/-36.3 vs. 162.1+/-35.5mL, p=0.30 and 54.2+/-3.9 vs. 52.7+/-4.4%, p=0.19, respectively); however a trend was observed for an increase of RVESV (72.5+/-20.0 vs. 77.4+/-20.7mL, p=0.05) at follow-up. RVB recruitment did not result in a significant improvement of RVEF (55.4+/-4.6 vs. 56.1+/-5.3%, p=0.75). CONCLUSION: RVB occlusion was not associated with a significant decreased RVEF at follow-up, although the results suggested a limited increase of RVESV.

Contains fulltext : 190389.pdf (Publisher’s version ) (Closed access) Myocardial inflammation in autoimmune rheumatic diseases (ARDs) is the endpoint of various pathophysiologic processes. The Lake Louise-criteria is the most popular approach for the diagnosis of myocarditis. However, due to the diversity of myocardial inflammation in ARDs, some issues should be acknowledged. Of the three Lake Louise indices, early and late gadolinium enhancement (EGE and LGE respectively) measurements may be affected by co-existing disease processes or be present due to a fibrotic ARD like systemic sclerosis, leaving T2-ratio as the only uniformly robust measurement across ARDs. It thus becomes apparent that the Lake Louise criteria suffer from a number of limitations when ARD patients are assessed based on them. The introduction of T1/T2 mapping allowed the quantification of intramyocardial fibrosis missed by LGE and the detection of myocardial oedema respectively, both commonly found in ARDs. The Lake Louise criteria play an important role in the evaluation of AIMI in ARDs. However, the pathophysiologic background of cardiac involvement in ARDs should always be acknowledged in their evaluation. Even though the inclusion of T1/T2 mapping and ECV may better describe diffuse oedema and fibrosis, further investigation pertaining to their implementation in ARD assessment algorithms through multicenter studies is needed.

Item does not contain fulltext There is evidence for a beneficial effect of aerobic exercise on cognition, but underlying mechanisms are unclear. In this study, we test the hypothesis that aerobic exercise increases cerebral blood flow (CBF) in patients with vascular cognitive impairment (VCI). This study is a multicenter single-blind randomized controlled trial among 80 patients with VCI. Most important inclusion criteria are a diagnosis of VCI with Mini-Mental State Examination >/=22 and Clinical Dementia Rating

Item does not contain fulltext OBJECTIVE: To evaluate cardiac involvement in patients with ankylosing spondylitis using cardiac magnetic resonance (CMR). METHODS: Patients with ankylosing spondylitis without cardiovascular symptoms or known cardiovascular disease were screened by transthoracic echocardiography (TTE) for participation in this exploratory CMR study. We prospectively enrolled 15 ankylosing spondylitis patients with an abnormal TTE for further tissue characterisation using late gadolinium enhancement (LGE) and T1 mapping. T1 mapping was used to calculate myocardial extracellular volume (ECV). Disease activity was assessed by C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) measurements. RESULTS: In the total of 15 included patients, 14 had a complete CMR exam (mean age 62 years, 93% male and mean disease duration 21 years). Left ventricular (LV) diastolic dysfunction was the most common finding on TTE (79%), followed by aortic root dilatation (14%), right ventricular (RV) dilatation (7%) and RV dysfunction (7%). CMR revealed focal hyperenhancement in three patients (21%), all with a particular pattern of enhancement. LV dysfunction, as defined by a LV ejection fraction below 55%, was observed in five patients (36%). Myocardial ECV was correlated with the CRP concentration (R=0.78, p

Background— Reduced myocardial efficiency represents a target for therapy in hypertrophic cardiomyopathy although therapeutic benefit may depend on disease stage. Here, we determined disease stage–dependent changes in myocardial efficiency and effects of myectomy surgery. Methods and Results— Myocardial external efficiency (MEE) was determined in 27 asymptomatic mutation carriers (genotype positive/phenotype negative), 10 patients with hypertrophic obstructive cardiomyopathy (HOCM), 10 patients with aortic valve stenosis, and 14 healthy individuals using [ 11 C]-acetate positron emission tomography and cardiovascular magnetic resonance imaging. Follow-up measurements were performed in HOCM and aortic valve stenosis patients 4 months after surgery. External work did not differ in HOCM compared with controls, whereas myocardial oxygen consumption was lower in HOCM. Because of a higher cardiac mass, total cardiac oxygen consumption was significantly higher in HOCM than in controls and genotype positive/phenotype negative. MEE was significantly lower in genotype positive/phenotype negative than in controls (28±6% versus 42±6%) and was further decreased in HOCM (22±5%). In contrast to patients with aortic valve stenosis, MEE was not improved in patients with HOCM after surgery, which was explained by opposite changes in the septum (decrease) and lateral (increase) wall. Conclusions— Different mechanisms underlie reduced MEE at the early and advanced stage of hypertrophic cardiomyopathy. The initial increase and subsequent reduction in myocardial oxygen consumption during disease progression indicates that energy deficiency is a primary mutation-related event, whereas mechanisms secondary to disease remodeling underlie low MEE in HOCM. Our data highlight that the benefit of therapies to improve energetic status of the heart may vary depending on the disease stage and that treatment should be initiated before cardiac remodeling.

Item does not contain fulltext AIMS: The aim of the present study was to investigate the effects of successful PCI CTO on absolute myocardial blood flow (MBF) and functional recovery. METHODS AND RESULTS: Patients with a documented CTO were prospectively examined for ischaemia and viability with [15O]H2O positron emission tomography (PET) and late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR). Sixty-nine consecutive patients, in whom PCI was successful, underwent follow-up PET and CMR after approximately 12 weeks to evaluate potential improvement of MBF as well as systolic function. After PCI, stress MBF in the CTO area increased from 1.22+/-0.36 to 2.40+/-0.90 mL.min-1.g-1 (p

Objectives Although myocardial strain analysis is a potential tool to improve patient selection for cardiac resynchronization therapy (CRT), there is currently no validated clinical approach to derive segmental strains. We evaluated the novel segment length in cine (SLICE) technique to derive segmental strains from standard cardiovascular MR (CMR) cine images in CRT candidates. Methods Twenty-seven patients with left bundle branch block underwent CMR examination including cine imaging and myocardial tagging (CMR-TAG). SLICE was performed by measuring segment length between anatomical landmarks throughout all phases on short-axis cines. This measure of frame-to-frame segment length change was compared to CMR-TAG circumferential strain measurements. Subsequently, conventional markers of CRT response were calculated. Results Segmental strains showed good to excellent agreement between SLICE and CMR-TAG (septum strain, intraclass correlation coefficient (ICC) 0.76; lateral wall strain, ICC 0.66). Conventional markers of CRT response also showed close agreement between both methods (ICC 0.61–0.78). Reproducibility of SLICE was excellent for intra-observer testing (all ICC ≥0.76) and good for interobserver testing (all ICC ≥0.61). Conclusions The novel SLICE post-processing technique on standard CMR cine images offers both accurate and robust segmental strain measures compared to the ‘gold standard’ CMR-TAG technique, and has the advantage of being widely available. Key Points • Myocardial strain analysis could potentially improve patient selection for CRT. • Currently a well validated clinical approach to derive segmental strains is lacking. • The novel SLICE technique derives segmental strains from standard CMR cine images. • SLICE-derived strain markers of CRT response showed close agreement with CMR-TAG. • Future studies will focus on the prognostic value of SLICE in CRT candidates. Electronic supplementary material The online version of this article (doi:10.1007/s00330-017-4890-0) contains supplementary material, which is available to authorized users.

Contains fulltext : 176975.pdf (Publisher’s version ) (Open Access) OBJECTIVES: To characterize the temporal alterations in native T1 and extracellular volume (ECV) of remote myocardium after acute myocardial infarction (AMI), and to explore their relation to left ventricular (LV) remodeling. METHODS: Forty-two patients with AMI successfully treated with primary PCI underwent cardiovascular magnetic resonance after 4-6 days and 3 months. Cine imaging, late gadolinium enhancement, and T1-mapping (MOLLI) was performed at 1.5T. T1 values were measured in the myocardial tissue opposite of the infarct area. Myocardial ECV was calculated from native- and post-contrast T1 values in 35 patients, using a correction for synthetic hematocrit. RESULTS: Native T1 of remote myocardium significantly decreased between baseline and follow-up (1002 +/- 39 to 985 +/- 30ms, p

Contains fulltext : 176884.pdf (Publisher’s version ) (Open Access) OBJECTIVE: Left ventricular remodelling following a ST-segment elevated myocardial infarction (STEMI) is an adaptive response to maintain the cardiac output despite myocardial tissue loss. Limited studies have evaluated long term ventricular function using cardiac magnetic resonance imaging (CMR) after STEMI. METHODS: Study population consisted of 155 primary percutaneous coronary intervention treated first STEMI patients. CMR was performed at 4+/-2 days, 4 months and 24 months follow-up. Patients were treated with beta-blockers, ACE-inhibitors or AT-II- inhibitors, statins and dual antiplatelet according to current international guidelines. RESULTS: Mean left ventricular ejection fraction (LVEF) at baseline was 44%+/-8%. Twenty-one per cent of the study population had an increase of more than 5.0% after 4 months of follow-up and 21% of the cohort had a decrease of more than 5.0%. Patients with long-term LVEF deterioration have significantly larger end-systolic volumes than patients with improvement of LVEF (61+/-23 mL/m2 compared with 52+/-21 mL/m2, p=0.02) and less wall thickening in the remote zone. Patients with LVEF improvement had significantly greater improvement in wall thickening in the infarct areas and in the non-infarct or remote zone. CONCLUSION: Contrary to previous studies, we demonstrate that myocardial remodelling after STEMI is a long-term process. Long-term LVEF deterioration is characterised by an increase in end-systolic volume and less wall thickening in the remote zones. Patients with LVEF improvement exhibit an increase in left ventricular wall thickening both in the infarct as well as in the remote zones. TRIAL REGISTRATION: The HEBE study is registered in The Netherlands Trial Register #NTR166 (www.trialregister.nl) and the International Standard Randomised Controlled Trial, #ISRCTN95796863 (https://c-d-qn9pqajji.sec.amc.nl).

Item does not contain fulltext AIMS: It is unclear whether microvascular dysfunction following ST-elevation myocardial infarction (STEMI) is prognostic for long-term left ventricular function (LVF), and whether recovery of the microvasculature status is associated with LVF improvement. The aim of this study was to assess whether microvascular dysfunction in the infarct-related artery (IRA), as assessed by coronary flow reserve (CFR) within one week after PPCI, was associated with LVF at both four months and two years. METHODS AND RESULTS: In 62 patients, CFR and hyperaemic microvascular resistance index (HMRI) in the IRA were assessed by intracoronary Doppler flow measurements within one week and at four months. CMR was performed at the same time points and also at two years. CFR at baseline was associated with left ventricular ejection fraction (LVEF) at four months (beta=4.66, SE=2.10; p=0.03) and at two-year follow-up (beta=5.84, SE=2.45; p=0.02). HMRI was not associated with LVF. In large infarcts, absolute improvement of CFR in the first four months was associated with LVEF improvement (beta=5.09, SE=1.86, p=0.01). CONCLUSIONS: Microvascular dysfunction, assessed by CFR, in the subacute phase of STEMI is prognostic for LVEF at four months and two years. This underlines the pivotal role of microvascular dysfunction following STEMI.

Background: Hemodynamic balance in the heart-brain axis is increasingly recognized as a crucial factor in maintaining functional and structural integrity of the brain and thereby cognitive functioning. Patients with heart failure (HF), carotid occlusive disease (COD), and vascular cognitive impairment (VCI) present themselves with complaints attributed to specific parts of the heart-brain axis, but hemodynamic changes often go beyond the part of the axis for which they primarily seek medical advice. The Heart-Brain Study hypothesizes that the hemodynamic status of the heart and the brain is an important but underestimated cause of VCI. We investigate this by studying to what extent hemodynamic changes contribute to VCI and what the mechanisms involved are. Here, we provide an overview of the design and protocol. Methods: The Heart-Brain Study is a multicenter cohort study with a follow-up measurement after 2 years among 645 participants (175 VCI, 175 COD, 175 HF, and 120 controls). Enrollment criteria are the following: 1 of the 3 diseases diagnosed according to current guidelines, age ≥50 years, no magnetic resonance contraindications, ability to undergo cognitive testing, and independence in daily life. A core clinical dataset is collected including sociodemographic factors, cardiovascular risk factors, detailed neurologic, cardiac, and medical history, medication, and a physical examination. In addition, we perform standardized neuropsychological testing, cardiac, vascular and brain MRI, and blood sampling. In subsets of participants we assess Alz­heimer biomarkers in cerebrospinal fluid, and assess echocardiography and 24-hour blood pressure monitoring. Follow-up measurements after 2 years include neuropsychological testing, brain MRI, and blood samples for all participants. We use centralized state-of-the-art storage platforms for clinical and imaging data. Imaging data are processed centrally with automated standardized pipelines. Results and Conclusions: The Heart-Brain Study investigates relationships between (cardio-)vascular factors, the hemodynamic status of the heart and the brain, and cognitive impairment. By studying the complete heart-brain axis in patient groups that represent components of this axis, we have the opportunity to assess a combination of clinical and subclinical manifestations of disorders of the heart, vascular system and brain, with hemodynamic status as a possible binding factor.

Reactive oxygen species (ROS) produced by different NADPH oxidases (NOX) play a role in cardiomyocyte hypertrophy induced by different stimuli, such as angiotensin II and pressure overload. However, the role of the specific NOX isoforms in phenylephrine (PE)-induced cardiomyocyte hypertrophy is unknown. Therefore we aimed to determine the involvement of the NOX isoforms NOX1, NOX2 and NOX4 in PE-induced cardiomyocyte hypertrophy. Hereto rat neonatal cardiomyoblasts (H9c2 cells) were incubated with 100 μM PE to induce hypertrophy after 24 and 48h as determined via cell and nuclear size measurements using digital imaging microscopy, electron microscopy and an automated cell counter. Digital-imaging microscopy further revealed that in contrast to NOX1 and NOX4, NOX2 expression increased significantly up to 4h after PE stimulation, coinciding and co-localizing with ROS production in the cytoplasm as well as the nucleus. Furthermore, inhibition of NOX-mediated ROS production with apocynin, diphenylene iodonium (DPI) or NOX2 docking sequence (Nox2ds)-tat peptide during these first 4h of PE stimulation significantly inhibited PE-induced hypertrophy of H9c2 cells, both after 24 and 48h of PE stimulation. These data show that early NOX2-mediated ROS production is crucial in PE-induced hypertrophy of H9c2 cells.

Objectives The current study evaluates the incremental value of transluminal attenuation gradient (TAG), TAG with corrected contrast opacification (CCO), and TAG with exclusion of calcified coronary segments (ExC) over coronary computed tomography angiogram (CTA) alone using fractional flow reserve (FFR) as the gold standard. Background TAG is defined as the contrast opacification gradient along the length of a coronary artery on a coronary CTA. Preliminary data suggest that TAG provides additional functional information. Interpretation of TAG is hampered by multiple heartbeat acquisition algorithms and coronary calcifications. Two correction models have been proposed based on either dephasing of contrast delivery by relating coronary density to corresponding descending aortic opacification (TAG-CCO) or excluding calcified coronary segments (TAG-ExC). Methods Eighty-five patients with intermediate probability of coronary artery disease were prospectively included. All patients underwent step-and-shoot 256-slice coronary CTA. TAG, TAG-CCO, and TAG-ExC analyses were performed followed by invasive coronary angiography in conjunction with FFR measurements of all major coronary branches. Results Thirty-four patients (40%) were diagnosed with hemodynamically-significant coronary artery disease (i.e., FFR ≤0.80). On a per-vessel basis (n = 253), 59 lesions (23%) were graded as hemodynamically significant, and the diagnostic accuracy of coronary CTA (diameter stenosis ≥50%) was 95%, 75%, 98%, and 54% for sensitivity, specificity, negative predictive value, and positive predictive value, respectively. TAG and TAG-ExC did not discriminate between vessels with or without hemodynamically significant lesions (-13.5 ;plusmn& 17.1 HU [Hounsfield units] ;times&10 mm;bsupesup&vs. -11.6 ;plusmn&13.3 HU ;times&10 mm;bsupesup&, p = 0.36; and 13.1 ;plusmn&15.9 HU ;times&10 mm;bsupesup&vs. -11.4 ;plusmn&11.7 HU ;times&10 mm;bsupesup&, p = 0.77, respectively). TAG-CCO was lower in vessels with a hemodynamically-significant lesion (-0.050 ;plusmn&0.051 10 mm;bsupesup&vs. -0.036 ;plusmn&0.034 10 mm;bsupesup&, p = 0.03) and TAG-ExC resulted in a slight improvement of the net reclassification index (0.021, p ≤ 0.05). Conclusions TAG did not provide incremental diagnostic value over 256-slice coronary CTA alone in assessing the hemodynamic consequences of a coronary stenosis. Correction for temporal nonuniformity of contrast delivery or exclusion of calcified coronary segments slightly enhanced the results. © 2014 by the American College of Cardiology Foundation.

Acute myocardial infarction (AMI) is accompanied by increased expression of Toll like receptors (TLR)-2 and TLR4 on circulating monocytes. In animal models, blocking TLR2/4 signaling reduces inflammatory cell influx and infarct size. The clinical consequences of TLR activation during AMI in humans are unknown, including its role in long-term cardiac functional outcome Therefore, we analyzed gene expression in whole blood samples from 28 patients with an acute ST elevation myocardial infarction (STEMI), enrolled in the EXenatide trial for AMI patients (EXAMI), both at admission and after 4-month follow-up, by whole genome expression profiling and real-time PCR. Cardiac function was determined by cardiac magnetic resonance (CMR) imaging at baseline and after 4-month follow-up. TLR pathway activation was shown by increased expression of TLR4 and its downstream genes, including IL-18R1, IL-18R2, IL-8, MMP9, HIF1A, and NFKBIA. In contrast, expression of the classical TLR-induced genes, TNF, was reduced. Bioinformatics analysis and in vitro experiments explained this noncanonical TLR response by identification of a pivotal role for HIF-1α. The extent of TLR activation and IL-18R1/2 expression in circulating cells preceded massive troponin-T release and correlated with the CMR-measured ischemic area (R=0.48, p=0.01). In conclusion, we identified a novel HIF-1-dependent noncanonical TLR activation pathway in circulating leukocytes leading to enhanced IL-18R expression which correlated with the magnitude of the ischemic area. This knowledge may contribute to our mechanistic understanding of the involvement of the innate immune system during STEMI and may yield diagnostic and prognostic value for patients with myocardial infarction.

Background— Risk stratification for ventricular arrhythmias (VAs) is important to refine selection criteria for primary prevention implantable cardioverter defibrillator therapy. Impaired hyperemic myocardial blood flow (MBF) is associated with increased mortality rate in ischemic and nonischemic cardiomyopathy, which may be attributed to electric instability inducing VAs. The aim of this pilot study was to assess whether hyperemic MBF impairment may be related with VA inducibility in patients with ischemic cardiomyopathy. Methods and Results— Thirty patients with ischemic cardiomyopathy referred for primary prevention implantable cardioverter defibrillator implantation were prospectively included (26 men; 65±8 years old; left ventricular ejection fraction, 29±6%). [ 15 O]H 2 O positron-emission tomography was performed to quantify resting MBF, hyperemic MBF, and coronary flow reserve. Left ventricular dimensions, function, and scar burden were assessed with cardiovascular magnetic resonance imaging. An electrophysiological study was performed to test VA inducibility. Positive electrophysiological study patients (n=12) showed reduced hyperemic MBF (1.25±0.30 versus 1.66±0.38 mL·min −1 ·g −1 ; P P 75% transmurality was higher ( P Conclusions— In this pilot study, impaired hyperemic MBF and coronary flow reserve were associated with VA inducibility in patients with ischemic cardiomyopathy. These results are hypothesis generating for a potential role of quantitative positron-emission tomography perfusion imaging in risk stratification for VAs.

Purpose: To investigate the effects of cell therapy on myocardial perfusion recovery after treatment of acute myocardial infarction (MI) with primary percutaneous coronary intervention (PCI).Materials and Methods: In this HEBE trial substudy, which was approved by the institutional review board (trial registry number IS-RCTN95796863), the authors assessed the effects of intra-coronary infusion with bone marrow-derived mononuclear cells (BMMCs) or peripheral blood-derived mononuclear cells (PBMCs) on myocardial perfusion recovery by using cardiac magnetic resonance (MR) imaging after revascularization. In 152 patients with acute MI treated with PCI, cardiac MR imaging was performed after obtaining informed consent-before randomization to BMMC, PBMC, or standard therapy (control group)-and repeated at 4-month follow-up. Cardiac MR imaging consisted of cine, rest first-pass perfusion, and late gadolinium enhancement imaging. Perfusion was evaluated semiquantitatively with signal intensity-time curves by calculating the relative upslope (percentage signal intensity change). The relative upslope was calculated for the MI core, adjacent border zone, and remote myocardium. Perfusion differences among treatment groups or between baseline and follow-up were assessed with the Wilcoxon signed rank or Mann-Whitney U test.Results: At baseline, myocardial perfusion differed between the MI core (median, 6.0%; interquartile range [IQR], 4.1%-8.0%), border zone (median, 8.4%; IQR, 6.4%-10.2%), and remote myocardium (median, 12.2%; IQR, 10.5%-15.9%) (P