Chronic Infarction Research Articles

Single Centre Experience in Open and Endovascular Treatment of Renal Artery Aneurysms

Background: The true incidence and natural history of renal artery aneurysm (RAA) remain unclear and still exists controversy over indication for treatment. Several techniques of conventional surgical reconstructions are described in literature, and more recently endovascular therapies have been reported with satisfying results and lower complication rate. This paper aims to investigate the outcomes of both endovascular and open repair of RAA achieved in a single institution involving 3 medical teams (urology, vascular surgery and neuroradiology). Material and Methods: We conducted a single-centre retrospective observational study about all patients surgically or endovascularly treated for RAA over a 15-year period. Pre-operative, procedural and post-operative data at the early, mid- and long-term follow-up were collected and analysed, focusing on operative technique used for repair and related outcomes. Results: A total of 27 patients (n = 17 (63%) women, mean age 58 ± 13.2, n = 26 saccular RAA) were included. Mean aneurysm was size was 18.8 ± 6.3 mm. Most diagnosis were accidental. Symptomatic RAA showed with macroscopic haematuria (n = 3, 25.9%), unstable hypertension (n = 2; 7%), chronic lumbar pain (n = 1, 3.7%) and renal infarct (n = 1, 3.7%).Conventional surgery (ex-vivo repair, aneurysmorraphy, aneurysm resection and end-to-end anastomosis) was performed in 14 (51.8%) cases and endovascular coiling embolization in 13 (48.2%). Mean hospital length of stay was 5.4 ± 3.6 days. Intensive Care Unit stay was needed only in the surgically treated patients (mean 1.1 ± 1.2 days). During the early follow-up, morbidity rate was 7/14 in surgically treated patients vs. 1/13 in endovascular group; it included bleeding, retroperitoneal hematoma, arterial thrombosis and bowel obstruction. The discharge imaging showed complete aneurysm exclusion and renal artery patency in all cases.At a mean follow-up of 39 ± 42 months, 3 patients (11%) were lost to follow up and 2 (7.4 %) died from unrelated cause. None of these patients required dialysis but a statistically significant (P = 0.09) decrease in GFR was noted between the preoperative period and last follow-up control. RAA repair neither showed blood pressure control improvement nor reduced the need for anti-hypertensive drug use. Conclusion: Open or endovascular techniques are both safe and efficient to treat RAA. Even though, surgical management is burdened with higher morbidity rate, the operative technique should be selected according to anatomical features, diameters and location of RRA; and the number of renal branches involved. Further larger studies are needed to define the feasibility and safety for a wider application of the endovascular approach.

Phenotypes of Chronic Covert Brain Infarction in Patients With First-Ever Ischemic Stroke: A Cohort Study.

The aim of this study was to assess the rate of chronic covert brain infarctions (CBIs) in patients with acute ischemic stroke (AIS) and to describe their phenotypes and diagnostic value. This is a single-center cohort study including 1546 consecutive patients with first-ever AIS on magnetic resonance imaging imaging from January 2015 to December 2017. The main study outcomes were CBI phenotypes, their relative frequencies, location, and association with vascular risk factors. Any CBI was present in 574/1546 (37% [95% CI, 35%-40%]) of patients with a total of 950 CBI lesions. The most frequent locations of CBI were cerebellar in 295/950 (31%), subcortical supratentorial in 292/950 (31%), and cortical in 213/950 (24%). CBI phenotypes included lacunes (49%), combined gray and white matter lesions (30%), gray matter lesions (13%), and large subcortical infarcts (7%). Vascular risk profile and white matter hyperintensities severity (19% if no white matter hyperintensity, 63% in severe white matter hyperintensity, P<0.001) were associated with presence of any CBI. Atrial fibrillation was associated with cortical lesions (adjusted odds ratio, 2.032 [95% CI, 1.041-3.967]). Median National Institutes of Health Stroke Scale scores on admission were higher in patients with an embolic CBI phenotype (median National Institutes of Health Stroke Scale, 5 [2-10], P=0.025). CBIs were present in more than a third of patients with first AIS. Their location and phenotypes as determined by MRI were different from previous studies using computed tomography imaging. Among patients suffering from AIS, those with additional CBI represent a vascular high-risk subgroup and the association of different phenotypes of CBIs with differing risk factor profiles potentially points toward discriminative AIS etiologies.

Anterior STEMI associated with decreased strain in remote cardiac myocardium

To assess (1) global longitudinal strain (GLS) by feature tracking cardiac magnetic resonance (CMR) in the sub-acute and chronic phases after ST-elevation infarction (STEMI) and compare to GLS in healthy controls, and (2) the evolution of GLS and regional longitudinal strain (RLS) over time, and their relationship to infarct location and size. Seventy-seven patients from the CHILL-MI-trial (NCT01379261) who underwent CMR 2–6 days and 6 months after STEMI and 27 healthy controls were included for comparison. Steady state free precession (SSFP) long-axis cine images were obtained for GLS and RLS, and late gadolinium enhancement (LGE) images were obtained for infarct size quantifications. GLS was impaired in the sub-acute (− 11.8 ± 3.0%) and chronic phases (− 14.3 ± 2.9%) compared to normal GLS in controls (− 18.4 ± 2.4%; p < 0.001 for both). GLS improved from sub-acute to chronic phase (p < 0.001). GLS was to some extent determined by infarct size (sub-acute: r2 = 0.2; chronic: r2 = 0.2, p < 0.001). RLS was impaired in all 6 wall-regions in LAD infarctions in both the sub-acute and chronic phase, while LCx and RCA infarctions had preserved RLS in remote myocardium at both time points. Global longitudinal strain is impaired sub-acutely after STEMI and improvement is seen in the chronic phase, although not reaching normal levels. Global longitudinal strain is only moderately determined by infarct size. Regional longitudinal strain is most impaired in the infarcted region, and LAD infarctions have effects on the whole heart. This could explain why LAD infarcts are more serious than the other culprit vessel infarctions and more often cause heart failure.

A-57 The Neuropsychological Impact of Antiphospholipid Antibody Syndrome: A Case Study

Abstract Objective Antiphospholipid Antibody Syndrome (APS), also known as Hughes Syndrome, is an autoimmune condition linked to various adverse medical and neurological outcomes affecting 5 in 100,000. APS results from antibodies (aPL) that attack blood proteins that bind to phospholipids (e.g., 2-glycoprotein I and prothrombin), which can cause blood flow problems, increased risk of blood clots, and recurrent vascular thrombotic events. Research suggests APS may lead to various neurologic/medical issues including memory loss, visual disturbances, and dementia. Method Neuropsychological evaluation of 48-year-old female with triple-positive APS and history of bilateral superior parietal chronic ischemic infarctions, multiple bilateral lacunar infarctions, and bilateral encephalomalacia. Reports progressive cognitive changes (&amp;lt; 1 year). Results Neuropsychological evaluation evidenced low average premorbid functioning and currently, extremely low overall cognitive ability. Memory was variable with significant visual and working memory impairment but preserved delayed recall of contextual information. While verbal abilities were intact, deficits were noted in executive functioning, attention, processing speed, visuomotor, visual–spatial, and fine motor skills. Conclusion This 48-year-old woman’s cognitive profile is consistent with findings in the APS literature and is indicative of an early onset major vascular neurocognitive disorder. Retrospective studies suggest that cognitive deficits often precede somatic symptoms of APS and abnormal neuroimaging findings; she presents atypically, as somatic symptoms and abnormal neuroimaging preceded cognitive decline. This case adds to the limited body of neuropsychological data regarding the effects of APS on cognitive functioning, as the pathogenesis of cognitive impairment in APS is unclear and leads to questions regarding differences in, and trajectories of, cognitive deficits in APS.

Cerebral perfusion changes in chronic dizziness: A single-photon emission computed tomography study.

Background and purposeDizziness may persist even after the causative vestibular imbalance subsides. Although the precise mechanism of chronic dizziness is unknown, various cerebral activity changes associated with it have been reported. To understand its mechanism in the absence of the causative vestibular imbalance, we compared cerebral changes in chronic dizziness with and without persistent vestibular imbalance.MethodsBetween September 2014 and March 2020, we examined regional cerebral blood flow (rCBF) in 12 patients having chronic post-lateral medullary infarction dizziness with persistent brainstem vestibular imbalance and 23 patients having chronic dizziness without currently active vestibular imbalance using single-photon emission computed tomography (SPECT) with 99m Technetium-ethyl cysteinate dimer. Further, we analyzed the SPECT images using a voxel-based group comparison.ResultsWe observed a decreased rCBF in the occipital lobe and increased rCBF in the medial and inferior parts of the temporal lobe in patients having chronic dizziness with and without active vestibular imbalance compared to healthy controls. However, only patients having chronic dizziness without active vestibular imbalance exhibited increased rCBF in the frontal lobe, including the orbitofrontal cortex.ConclusionThis is the first study to highlight the difference in rCBF changes between patients having chronic dizziness with and without active vestibular imbalance. Decreased occipital lobe activity and increased medial and inferior temporal lobe activity may be related to keeping dizziness perception triggered regardless of the presence or absence of active vestibular imbalance, whereas increased frontal lobe activity may explain the dizziness background to persist after the disappearance of vestibular imbalance.

Symptoms Based on Deficiency Syndrome in Traditional Chinese Medicine Might Be Predictor of Frailty in Elderly Community Dwellers.

Background The most widely used frailty phenotype and frailty indexes are either time-consuming or complicated, thus restricting their generalization in clinical practice; and therefore, an easier and faster screening tool is needed to be developed. Objective To select sensitive symptoms in traditional Chinese medicine (TCM) and study whether they can improve the risk prediction of frailty. Methods This is a cross-sectional study enrolling 2249 Chinese elderly community dwellers. Data were collected via face-to-face inquiries, anthropometric measurements, laboratory tests, and community health files. Frailty was the main outcome measure, and it was evaluated by Fried's frailty phenotype (FP). The ordinal logistic regression model was used to identify the factors associated with frailty. The risk assessment plot was used to compare the discriminative ability for frailty among models with and without TCM symptoms. Results The identified sensitive influential factors for frailty included age, education level, dietary habits, chronic obstructive pulmonary disease, diabetes, cerebral infarction, osteoporosis, cold limbs, lethargy and laziness in speaking and moving, weakness of lower limbs, slow movement, dry mouth and throat, and glazed expression. The risk prediction for “frailty cumulative components ≥1” was not significantly increased, while for “frailty cumulative components ≥2”, a new model developed with the above selected TCM symptoms had a higher AUC than the baseline model without it (0.79 VS 0.81, P=0.002). And the NRI and IDI for the new model were 41.4% (P=0.016) and 0.024% (P=0.041), respectively. Conclusion This research might provide an easier and faster way for early identification and risk prediction of frailty in elderly community dwellers.

A Novel Mutation in COL4A1 Gene in a Chinese Family with Pontine Autosomal Dominant Microangiopathy and Leukoencephalopathy

Pontine autosomal dominant microangiopathy and leukoencephalopathy (PADMAL) is a rare hereditary cerebral small vessel disease. We report a novel collagen type IV alpha 1 (COL4A1) gene mutation in a Chinese family with PADMAL. The index case was followed up for 6 years. Neuroimaging, whole-exome sequencing, skin biopsy, and pedigree analysis were performed. She initially presented with minor head injury at age 38. MRI brain showed chronic lacunar infarcts in the pons, left thalamus, and right centrum semiovale. Extensive workup was unremarkable except for a patent foramen ovale (PFO). Despite anticoagulation, PFO closure, and antiplatelet therapy, the patient had recurrent lacunar infarcts in the pons and deep white matter, as well as subcortical microhemorrhages. Whole-exome sequencing demonstrated a novel c.*34G > T mutation in the 3′ untranslated region of COL4A1 gene. Skin biopsy subsequently demonstrated thickening of vascular basement membrane, proliferation of endothelial cells, and stenosis of vascular lumen. Three additional family members had gene testing and 2 of them were found to have the same heterozygous mutation. Of the 18 individuals in the pedigree of 3 generations, 12 had clinical and MRI evidence of PADMAL. The mechanisms of both ischemic and hemorrhagic stroke are likely the overexpression of COLT4A1 in the basement membrane and frugality of the vessel walls. Our findings suggest that the novel c.*34G > T mutation appears to have the same functional consequences as the previously reported COL4A1 gene mutations in patients with PADMAL and multi-infarct dementia of Swedish type.

Effects of Combined Repetitive Peripheral Magnetic Stimulation and Occupational Therapy on Upper Limb Paresis and ADL in a Chronic Infarct Patient：A Case Report

Effects of Combined Repetitive Peripheral Magnetic Stimulation and Occupational Therapy on Upper Limb Paresis and ADL in a Chronic Infarct Patient：A Case Report

Vascular Involvement in Neurosarcoidosis

Background and ObjectivesCerebrovascular manifestations in neurosarcoidosis (NS) were previously considered rare but are being increasingly recognized. We report our preliminary experience in patients with NS who underwent high-resolution vessel wall imaging (VWI).MethodsA total of 13 consecutive patients with NS underwent VWI. Images were analyzed by 2 neuroradiologists in consensus. The assessment included segment-wise evaluation of larger- and medium-sized vessels (internal carotid artery, M1-M3 middle cerebral artery; A1-A3 anterior cerebral artery; V4 segments of vertebral arteries; basilar artery; and P1-P3 posterior cerebral artery), lenticulostriate perforator vessels, and medullary and deep cerebral veins. Cortical veins were not assessed due to flow-related artifacts. Brain biopsy findings were available in 6 cases and were also reviewed.ResultsMean patient age was 54.9 years (33–71 years) with an M:F of 8:5. Mean duration between initial diagnosis and VWI study was 18 months. Overall, 9/13 (69%) patients had vascular abnormalities. Circumferential large vessel enhancement was seen in 3/13 (23%) patients, whereas perforator vessel involvement was seen in 6/13 (46%) patients. Medullary and deep vein involvement was also seen in 6/13 patients. In addition, 7/13 (54%) patients had microhemorrhages in susceptibility-weighted imaging, and 4/13 (31%) had chronic infarcts. On biopsy, 5/6 cases showed perivascular granulomas with vessel wall involvement in all 5 cases.DiscussionOur preliminary findings suggest that involvement of intracranial vascular structures may be a common finding in patients with NS and should be routinely looked for. These findings appear concordant with previously reported autopsy literature and need to be validated on a larger scale.

Association of cardiovascular risk burden with risk of dementia and brain pathologies: A population-based cohort study.

The impact of cardiovascular risk burden on brain pathologies remains unclear. We aimed to examine the association of the Framingham General Cardiovascular Risk Score (FGCRS) with dementia risk, and brain pathologies. Within the Rush Memory and Aging Project, 1588 dementia-free participants were assessed on FGCRS at baseline and followed up to 21 years. During the follow-up, 621 participants died and underwent autopsies. The multi-adjusted hazard ratios (HRs) (95% confidence intervals [CIs]) of FGCRS were 1.03 (1.00-1.07) for dementia and 1.04 (1.01-1.07) for Alzheimer's disease (AD) dementia. Further, a higher FGCRS was associated with higher gross chronic cerebral infarctions (odds ratio [OR] 1.08, 95% CI 1.02-1.14), cerebral atherosclerosis (OR 1.10, 95% CI 1.03-1.17), and global AD pathology (OR 1.06, 95% CI 1.01-1.12). A higher FGCRS is associated with an increased risk of dementia and AD dementia. Both vascular and AD pathologies in the brain may underlie this association.

Prevalence of incidental brain MRI findings of clinical relevance in a diverse Hispanic/Latino population.

There is limited literature on the prevalence of incidental brain MRI findings in the Hispanic/Latino population, despite their increased prevalence of vascular disease and undertreatment of chronic conditions. The purpose of our study was to determine the prevalence of clinically relevant incidental findings on brain MRI examinations obtained as a part of the Study of Latinos-Investigation of NeuroCognitive Aging MRI (SOL-INCA-MRI) study. Brain MRI examinations were obtained on 1389 participants in the SOL-INCA-MRI study, a cross-sectional ancillary study of the Hispanic Community Health Study, Study of Latinos, which is a longitudinal, community-based study. Study design of SOL-INCA-MRI involves imaging cognitively normal and participants with mild cognitive impairment. Brain MRI findings were categorized as Level 1 (normal), Level 1.5 (findings of unclear medical significance), Level 2 (potential medical concern), or Level 3 (medically urgent). This article focuses on Level 2 and Level 3 findings. The average age of the sample was 60.8 years (+/- 10.3 years), 66.1% were females. Level 2 and 3 findings were identified in 117 participants, (8.4%), of which 109 (7.8%) were recommended for medical follow-up (Level 2), and 8 (0.6%) were recommended for immediate medical attention (Level 3). Brain MRI findings consisted of chronic infarction in 33 (2.4%), vascular abnormality in 27 (1.9%), intracranial mass in 20 (1.4%), other intracranial findings in 28 (2.0%), and skull base/extracranial findings in 26 (1.9%) patients. Incidental findings of clinical relevance were common among SOL-INCA-MRI participants, but rarely required urgent medical intervention.

The relationship between myocardial microstructure and strain in chronic infarcts, assessed using diffusion tensor imaging and feature tracking

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background Cardiac diffusion tensor imaging (cDTI) is a novel technique for the non-invasive assessment of myocardial microstructure. It allows in-vivo characterisation of microstructural changes post myocardial infarction (MI). Previously published evidence shows significant loss of sheetlet orientation as derived by cDTI secondary eigenvector (E2A), and loss of subendocardial cardiomyocytes derived by reductions in the proportions of myocytes with right-handed orientation (RHM) on helix angle (HA) maps. The assessment of myocardial strain by feature tracking (FT) allows the measurement of radial strain (RS), thought to be driven by the dynamic reorientation of laminar sheetlets, and longitudinal strain (LS), which is thought to relate to subendocardial function. We sought to explore the relationship between the strain and cDTI parameters in patients at 3 months following ST-elevation MI (STEMI). Methods Twenty five STEMI patients (M:F = 18:7, mean age 58 ± 9) underwent 3T CMR scan (mean interval 106 ± 17 days) with the following protocol: second order motion compensated (M2), free-breathing spin echo DTI (3 slices, 18 diffusion directions at b-values 100s/mm2, 200s/mm2 and 500s/mm2, acquired resolution was 2.20*2.27*8mm3; cine gradient echo and Late Gadolinium Enhancement (LGE) imaging. HA maps were described by dividing values into left-handed HA (LHM, -90&amp;lt; HA &amp;lt; -30), circumferential HA (CM, -30° &amp;lt; HA &amp;lt; 30°), and right-handed HA (RHM, 30° &amp;lt; HA &amp;lt; 90°) and reported as relative proportions. Segmental analysis were undertaken to derive: HA proportions, E2A, longitudinal strain and LGE%. Segments positive for LGE were classed as infarct segments. Results cDTI acquisition was successful in all patients (acquisition time 13 ± 5mins). Mean ejection fraction was 47 ± 8% with mean LGE in the infarcted segment of 57 ± 27%. Mean radial strain was 21 (95% confidence interval, 15-26). The mean E2A was 44 (95% confidence interval 41-47). There was a significant correlation between segmental radial strain and segmental E2A in infarcted segments (p &amp;lt; 0.001, figure 1). In addition, segmental longitudinal strain correlated with the proportion of RHM on HA maps (p &amp;lt; 0.02, figure 2). Conclusion Through the combined use of cDTI and FT in patients with chronic infarcts, our results show that the loss of sheetlet orientation assessed using E2A, correlates with worsening radial strain. Segments with less subendocardial cardiomyocytes, evidenced by a lower proportion of myocytes with right-handed orientation on HA maps, correlated with worse longitudinal strain. While this could potentially elucidate the complex association between myocardial microstructure and regional function, further studies are needed to define the incremental clinical value of cDTI.

Microstructural characteristics of chronic infarct segments assessed using diffusion tensor imaging

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): British Heart Foundation Background The microstructural changes following myocardial infarction (MI) can be characterised in-vivo with cardiac diffusion tensor imaging (cDTI) imaging, using mean diffusivity (MD), fractional anisotropy (FA), secondary eigenvector angle (E2A) and helix angle (HA) maps. In this study, we use cDTI to explore the microstructural differences between subendocardial and transmural chronic infarct segments. Method Twenty STEMI patients (15 men, 5 women, mean age 59) underwent 3T CMR scan at 3 months following presentation (mean interval 107 ± 18 days). Scan protocol included: second order motion compensated (M012) free-breathing spin echo DTI (3 slices, 18 diffusion directions at b-values 100s/mm2[3], 200s/mm2[3] and 500s/mm2[12], acquired resolution was 2.20x2.27x8mm3; cine gradient echo and LGE imaging. Average MD, FA, E2A and HA parameters were calculated on a 16-AHA-segmental level. HA maps were described by dividing values into left-handed HA (LHM, -90° &amp;lt; HA &amp;lt; -30°), circumferential HA (CM, -30° &amp;lt; HA &amp;lt; 30°), and right-handed HA (RHM, 30° &amp;lt; HA &amp;lt; 90°) and reported as relative proportions. Infarct segments were identified using LGE; patients were categorised according to the maximal transmurality of their infarct segments, into subendocardial (&amp;lt;50% LGE) or transmural (&amp;gt;50% LGE) MI. Results DTI acquisition was successful in all patients (acquisition time 13 ± 5mins). Ten patients had transmural MI. The results are shown in table 1. Transmurally infarcted segments had significantly lower FA (FA subendocardial MI = 0.27 ± 0.04, FA transmural MI = 0.23 ± 0.02, p &amp;lt; 0.01), lower E2A (E2A subendocardial MI = 47 ± 7°, E2A transmural MI = 38 ± 6°, p &amp;lt; 0.01) and lower proportions of right-handed cardiomyocytes (RHM subendocardial MI = 21 ± 5%, RHM transmural MI = 14 ± 5%, p &amp;lt; 0.01) than subendocardial infarct segments. Conclusion Compared to subendocardial MI segments, the diffusion of water molecules is more isotropic in transmurally infarcted myocardium as evidenced by lower FA values, signifying increased structural disarray. The significantly lower E2A values suggest that laminar sheetlets of transmural infarct segments remain fixed at shallower angles during systole and are unable to reach their usual contractile configuration. The lower proportions of RHM on HA maps highlight the significantly greater loss of subendocardial cardiomyocytes in transmural infarct segments. Further studies are required to assess if these segmental changes can be predictive of long-term LV remodelling.

Evaluation of intracranial vasculitis in tuberculous meningitis using magnetic resonance vessel wall imaging technique.

Tuberculous meningitis (TBM) is a global health problem with important complications such as acute infarcts secondary to vasculitis contributing to adverse outcomes. The objective of this study is to assess intracranial vasculitis in patients with TBM, either during their initial diagnosis or during follow-up while on standard antituberculous therapy. Ten patients with TBM underwent magnetic resonance (MR) based vessel wall imaging (VWI) to identify intracranial vasculitis (five patients during their initial presentation and the other five patients during their follow-up visit). Vasculitis was seen in 60% of the patients wherein 70% of their intracranial vessels were affected. Acute and chronic infarcts were seen in four and two patients respectively, one of whom had both acute and chronic infarcts. Leptomeningeal enhancement and basal cisternal tuberculomas were frequently seen in patients with vasculitis. Vasculitis was also seen many days after the commencement of the antituberculous therapy thus explaining late-onset infarcts in this disease. Intracranial vasculitis is common in the patient with TBM. MR-based VWI technique has the potential for infarct risk assessment and to help guide the treatment for its possible prevention.

Silent strokes after thoracoscopic epicardial ablation and catheter ablation for atrial fibrillation: not all lesions are permanent on follow-up magnetic resonance imaging.

Invasive treatments for atrial fibrillation (AF) pose a risk of ischemic stroke due to periprocedural brain embolization, which may be manifest or silent. The primary aim of our study was to compare the rate of silent strokes after percutaneous catheter-based and thoracoscopic epicardial ablation for AF. The secondary aim was to evaluate the development of silent strokes over time. We included 39 subjects (aged 64.1±8.9 years) treated for persistent symptomatic AF with thoracoscopic ablation and 30 subjects (aged 64.1±10.5 years) treated for paroxysmal or persistent symptomatic AF with catheter ablation. Subjects underwent brain MRI before and early after the ablation, moreover, the surgical group underwent late MRI 6 months after therapy. On early MRI, the presence of silent strokes and their number and size were evaluated. On late MRI, transformation of previously-detected acute ischemic lesions into chronic infarction or their reversibility were assessed. Initially, different chronic ischemic findings were found in 64% of patients from the surgical group and in 70% from catheter group. Early MRI results: acute ischemic lesions were detected in 2 (6.7%) subjects (overall 3 lesions sized <5 mm) in the catheter group and in 17 (43.6%) subjects in surgical group. Most subjects in the surgical group showed multiple lesions (88%); 195 lesions were detected, a median 6 (IQR 8) lesions per case. Eighty-two percent of lesions were <5 mm, 12% 5-10 mm, 5% 10-30 mm, and 2% were large territorial ischemia. Only 1 case was symptomatic, the rest were silent strokes. On late MRI, 53.5% of all acute lesions were reversible. Lesions <5 mm were reversible in 63.1% of cases, lesions 5-10 mm were reversible in 21.7% and all lesions larger than 10 mm persisted. In 29.4% of patients all acute ischemic lesions were fully reversible. Periprocedural silent strokes were significantly more common after thoracoscopic epicardial ablation compared to catheter ablation considering both the number of affected patients and number of lesions. The majority of acute ischemic brain lesions were small, up to 5 mm in diameter, roughly half of which were reversible. Reversibility of acute ischemic lesions decreased with size. However, in 29.4% of affected patients, all lesions were fully reversible.

Impact of Aldosterone on the Failing Myocardium: Insights from Mitochondria and Adrenergic Receptors Signaling and Function.

The mineralocorticoid aldosterone regulates electrolyte and blood volume homeostasis, but it also adversely modulates the structure and function of the chronically failing heart, through its elevated production in chronic human post-myocardial infarction (MI) heart failure (HF). By activating the mineralocorticoid receptor (MR), a ligand-regulated transcription factor, aldosterone promotes inflammation and fibrosis of the heart, while increasing oxidative stress, ultimately induding mitochondrial dysfunction in the failing myocardium. To reduce morbidity and mortality in advanced stage HF, MR antagonist drugs, such as spironolactone and eplerenone, are used. In addition to the MR, aldosterone can bind and stimulate other receptors, such as the plasma membrane-residing G protein-coupled estrogen receptor (GPER), further complicating it signaling properties in the myocardium. Given the salient role that adrenergic receptor (ARs)—particularly βARs—play in cardiac physiology and pathology, unsurprisingly, that part of the impact of aldosterone on the failing heart is mediated by its effects on the signaling and function of these receptors. Aldosterone can significantly precipitate the well-documented derangement of cardiac AR signaling and impairment of AR function, critically underlying chronic human HF. One of the main consequences of HF in mammalian models at the cellular level is the presence of mitochondrial dysfunction. As such, preventing mitochondrial dysfunction could be a valid pharmacological target in this condition. This review summarizes the current experimental evidence for this aldosterone/AR crosstalk in both the healthy and failing heart, and the impact of mitochondrial dysfunction in HF. Recent findings from signaling studies focusing on MR and AR crosstalk via non-conventional signaling of molecules that normally terminate the signaling of ARs in the heart, i.e., the G protein-coupled receptor-kinases (GRKs), are also highlighted.

Segmental strain analysis for the detection of chronic ischemic scars in non-contrast cardiac MRI cine images

Cardiac magnetic resonance imaging (MRI) with late gadolinium enhancement (LGE) is considered the gold standard for scar detection after myocardial infarction. In times of increasing skepticism about gadolinium depositions in brain tissue and contraindications of gadolinium administration in some patient groups, tissue strain-based techniques for detecting ischemic scars should be further developed as part of clinical protocols. Therefore, the objective of the present work was to investigate whether segmental strain is noticeably affected in chronic infarcts and thus can be potentially used for infarct detection based on routinely acquired non-contrast cine images in patients with known coronary artery disease (CAD). Forty-six patients with known CAD and chronic scars in LGE images (5 female, mean age 52 ± 19 years) and 24 gender- and age-matched controls with normal cardiac MRI (2 female, mean age 47 ± 13 years) were retrospectively enrolled. Global (global peak circumferential [GPCS], global peak longitudinal [GPLS], global peak radial strain [GPRS]) and segmental (segmental peak circumferential [SPCS], segmental peak longitudinal [SPLS], segmental peak radial strain [SPRS]) strain parameters were calculated from standard non-contrast balanced SSFP cine sequences using commercially available software (Segment CMR, Medviso, Sweden). Visual wall motion assessment of short axis cine images as well as segmental circumferential strain calculations (endo-/epicardially contoured short axis cine and resulting polar plot strain map) of every patient and control were presented in random order to two independent blinded readers, which should localize potentially infarcted segments in those datasets blinded to LGE images and patient information. Global strain values were impaired in patients compared to controls (GPCS p = 0.02; GPLS p = 0.04; GPRS p = 0.01). Patients with preserved ejection fraction showed also impeded GPCS compared to healthy individuals (p = 0.04). In patients, mean SPCS was significantly impaired in subendocardially (− 5.4% ± 2) and in transmurally infarcted segments (− 1.2% ± 3) compared to remote myocardium (− 12.9% ± 3, p = 0.02 and 0.03, respectively). ROC analysis revealed an optimal cut-off value for SPCS for discriminating infarcted from remote myocardium of − 7.2% with a sensitivity of 89.4% and specificity of 85.7%. Mean SPRS was impeded in transmurally infarcted segments (15.9% ± 6) compared to SPRS of remote myocardium (31.4% ± 5; p = 0.02). The optimal cut-off value for SPRS for discriminating scar tissue from remote myocardium was 16.6% with a sensitivity of 83.3% and specificity of 76.5%. 80.3% of all in LGE infarcted segments (118/147) were correctly localized in segmental circumferential strain calculations based on non-contrast cine images compared to 53.7% (79/147) of infarcted segments detected by visual wall motion assessment (p > 0.01). Global strain parameters are impaired in patients with chronic infarcts compared to controls. Mean SPCS and SPRS in scar tissue is impeded compared to remote myocardium in infarcts patients. Blinded to LGE images, two readers correctly localized 80% of infarcted segments in segmental circumferential strain calculations based on non-contrast cine images, in contrast to only 54% of infarcted segments detected due to wall motion abnormalities in visual wall motion assessment. Analysis of segmental circumferential strain shows a promising method for detection of chronic scars in routinely acquired, non-contrast cine images for patients who cannot receive or decline gadolinium.

Post myocardial infarction ionic remodelling promotes repolarisation dispersion and electrocardiogram abnormalities in acute and chronic stages

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Wellcome Trust Background Sudden cardiac death (SCD) occurs in both acute and chronic stages post myocardial infarction (MI), and the left ventricular ejection fraction (LVEF) and electrocardiogram (ECG) characteristics are important biomarkers for clinical decision making. While various ionic remodelling has been reported in literature at various stages post-MI, the effect of them on clinical biomarkers have not been fully explored. Purpose Evaluate the effects of cellular ionic remodelling in acute and chronic post myocardial infarction on ECG and LVEF biomarkers through computational modelling and simulations of human biventricular electromechanics. Methods An electromechanical coupled biventricular model with ToR-ORd (Tomek 2019) human electrophysiology coupled with human excitation-contraction machinery (Land 2017) and orthotropic passive mechanics (Holzapfel 2009) was used as baseline model. The 12-lead ECG were simulated at standard body-surface electrode locations, and the biventricular pressure volume loop was simulated to quantify the simulated LVEF. A cardiac magnetic resonance (CMR) derived human biventricular geometry (Strocchi 2020) was used in combination with rigidly aligned torso geometry (Minchole 2019). An anterior sub-endocardial infarction was delineated with infarct, border zone (BZ) and remote zone (RZ) regions. For acute infarction, three types of BZ ionic remodelling from literature, and their effects on simulated LVEF and ECG characteristics were quantified. For chronic infarction, a single chronic BZ ionic remodelling was combine with two different models of RZ ionic remodelling from literature, and the effects of these remodelling on the simulated LVEF and ECG were quantified. The electromechanical properties of the sub-endocardial infarct region did not significantly affect simulated ECG or LVEF biomarkers. Results For the acute phase, simulations showed pre-cordial ECG abnormalities for all three BZ models, with T-wave inversion and QT prolongation (80 ms) in BZ1, ST-segment elevation with T-wave inversion in BZ2, and decreased T-wave amplitude in BZ3. Activation maps showed conduction block in BZ2 simulations, leading to ST-segment elevation. Repolarisation maps showed high dispersion in BZ1 simulations, leading to T-wave inversion. LVEF for BZ2 decreased by 4% (from 57% in control) due to conduction block in BZ and lack of contraction in that region, LVEF remained constant for BZ1 and BZ3 simulations. For the chronic phase, there was QT prolongation in both RZ1 (80 ms) and RZ2 (170 ms) as well as decreased T-wave amplitude, reflected by elevated repolarisation dispersion. LVEF was not significantly altered for either simulations. Conclusions Post-MI ionic remodelling at the acute and chronic stages cause varying degrees of dispersion of repolarisation and T-wave and ST-segment abnormalities, with minimal effect on mechanical function, except in the case of severe conduction abnormality. Abstract Figure.

Cardiovascular magnetic resonance determinants of ventricular arrhythmic events after myocardial infarction

Abstract Funding Acknowledgements Type of funding sources: None. Background Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) permits to identify the arrhythmogenic substrate in chronic post-myocardial infarction (MI) patients. It is unknown why a minority of chronic post-MI patients develop sustained ventricular tachycardias (VT) over follow-up, regardless of their left ventricular ejection fraction (LVEF). Objectives To noninvasively characterize scar differences and potential predictors of VT occurrence in chronic post-MI patients. Methods A case-control study was designed through retrospective LGE-CMR data analysis of chronic post-MI patients i) consecutively referred for VT substrate ablation after a first VT episode (n = 66), and ii) from a control group (n = 84) with no arrhythmia evidence. The myocardium was characterized differentiating core, border zone (BZ) and BZ channels (BZC) using the ADAS 3D post-processing imaging platform. Clinical and scar characteristics, including a novel parameter, the BZC mass, were compared between both groups. Results 150 post-MI patients were included for analysis. Four multivariate Cox proportional hazards regression models were created for total scar mass (model 1), BZ mass (model 2), core mass (model 3), and BZC mass (model 4, see table). All of them were adjusted by age, sex, and LVEF. In the corresponding models, only total scar mass, BZ mass, core mass, and BZC mass were independent variables associated with the development of VT. BZC mass showed the best performance: a cut-off of 5.15 g identified the cases with 92.4% sensitivity and 86.9% specificity [AUC 0.93 (0.89–0.97); p &amp;lt; 0.001], with a significant increase in the AUC compared to the other scar parameters (p &amp;lt; 0.001 for all pairwise comparisons using the De Long’s test). By using BZC mass as a risk stratification parameter together with LVEF, the net reclassification improvement (NRI) was 33.3% for the cases, and 39.3% for the controls. The net proportion of patients reclassified correctly was 36.7% Conclusions The mass of BZC, automatically obtained with a commercially available CMR post-processing software, is the strongest independent variable associated with the occurrence of clinical SMVT in post-MI patients after covariate adjustment for age, sex, and LVEF. The measurement of BZC mass could permit a more accurate arrhythmia risk stratification than LVEF in chronic post-MI patients (NRI 36.7%). Scar characteristics analyzed from LGE-CMR imaging should be taken into consideration to better stratify ventricular arrhythmia risk in chronic post-MI patients. Abstract Figure. ROC curves for predicting VT occurrence

Safety of 3 Tesla Magnetic Resonance Imaging in Patients with Sickle Cell Disease.

Sickle cell disease (SCD) is a well-characterized hemoglobinopathy affecting more than 20 million individuals worldwide and carries an increased risk of cerebral vasculopathy, cerebral infarct, and stroke. As mechanisms of cerebral infarction in SCD are partly attributable to microvascular vaso-occlusive crises, manifesting as altered cerebral blood flow and associated impaired oxygen delivery, magnetic resonance imaging (MRI) methods that can quickly provide a comprehensive perspective on structural and functional disease status, without exogenous contrast administration or ionizing radiation, have emerged as crucial clinical tools for surveillance. However, early ex vivo MRI work in suspended erythrocytes containing hemoglobin S at 0.35 Tesla (T) suggested that sickled erythrocytes can orient preferentially in the presence of an external magnetic field, and as such, it was suggested that MRI exams in sickle cell hemoglobinopathy could induce vaso-occlusion. While this observation has generally not impacted clinical imaging in individuals with SCD, it has led to resistance for some sickle cell studies within the engineering community among some imaging scientists as this early observation has never been rigorously shown to be unconcerning. Here, we performed MRI at the clinical field strength of 3 T in 172 patients with SCD, which included standard anatomical and angiographic assessments together with gold standard diffusion-weighted imaging (DWI; spatial resolution = 1.8 × 1.8 × 4 mm; b-value = 1000 s/mm2) for acute infarct assessment (performed approximately 20 min after patient introduction to the field isocenter). The presence of vasculopathy, as well as chronic and acute infarcts, was evaluated by two independent board-certified radiologists using standard clinical criteria. In these patients (52.3% female; mean age = 19.6 years; age range = 6–44 years), hematocrit (mean = 25.8%; range = 15–36%), hemoglobin phenotype (87.8% HbSS variant), presence of silent infarct (44.2%), and overt chronic infarct (13.4%) were consistent with a typical SCD population; however, no participants exhibited evidence of acute infarction. These findings are consistent with 3 T MRI not inducing acute infarction or vaso-occlusion in individuals with SCD and suggest that earlier low-field ex vivo work of erythrocytes in suspension is not a sufficient cause to discourage MRI scans in patients with SCD.