Rebecca Kozor

Use of multi-velocity encoding 4D flow MRI to improve quantification of flow patterns in the aorta.

To show that the use of a multi‐velocity encoding (VENC) 4D‐flow approach offers significant improvements in the characterization of complex flow in the aorta. Four‐dimensional flow magnetic resonance imaging (MRI) (4D‐flow) can be used to measure complex flow patterns and dynamics in the heart and major vessels. The quality of the information derived from these measures is dependent on the accuracy of the vector field, which is limited by the vector‐to‐noise ratio.

Regular cocaine use is associated with increased systolic blood pressure, aortic stiffness and left ventricular mass in young otherwise healthy individuals

Background The cardiovascular impact of cocaine use in otherwise healthy individuals who consider themselves ‘social’ users is not well established. Methods/Results Twenty regular cocaine users and 20 control subjects were recruited by word-of-mouth. Cardiovascular magnetic resonance was performed to assess cardiac and vascular structure and function. Cocaine users had higher systolic blood pressure compared to non-users (134±11 vs 126±11 mmHg, p = 0.036), a finding independent of age, body surface area, smoking and alcohol consumption. Cocaine use was associated with increased arterial stiffness - reflected by reduced aortic compliance (1.3±0.2 vs 1.7±0.5 cm2×10−2.mmHg−1, p = 0.004), decreased distensibility (3.8±0.9 vs 5.1±1.4 mmHg−1.10−3, p = 0.001), increased stiffness index (2.6±0.6 vs 2.1±0.6, p = 0.005), and higher pulse wave velocity (5.1±0.6 vs 4.4±0.6 m.s−1, p = 0.001). This change in aortic stiffness was independent of vessel wall thickness. Left ventricular mass was 18% higher in cocaine users (124±25 vs 105±16 g, p = 0.01), a finding that was independent of body surface area, and left atrial diameter was larger in the user group than controls (3.8±0.6 vs 3.5±0.3 cm, p = 0.04). The increased left ventricular mass, systolic blood pressure and vascular stiffness measures were all associated with duration and/or frequency of cocaine use. No late gadolinium enhancement or segmental wall motion abnormalities were seen in any of the subjects. Conclusions Compared with the non-user control cohort, cocaine users had increased aortic stiffness and systolic blood pressure, associated with greater left ventricular mass. These measures are all well known risk factors for premature cardiovascular events, highlighting the dangers of cocaine use, even in a ‘social’ setting, and have important public health implications.

Cardiac involvement in genotype-positive Fabry disease patients assessed by cardiovascular MR

Objective Cardiac magnetic resonance (CMR) has the potential to provide early detection of cardiac involvement in Fabry disease. We aimed to gain further insight into this by assessing a cohort of Fabry patients using CMR. Methods/results Fifty genotype-positive Fabry subjects (age 45±2 years; 50% male) referred for CMR and 39 matched controls (age 40±2 years; 59% male) were recruited. Patients had a mean Mainz severity score index of 15±2 (range 0–46), reflecting an overall mild degree of disease severity. Compared with controls, Fabry subjects had a 34% greater left ventricular mass (LVM) index (82±5 vs 61±2 g/m2, p=0.001) and had a significantly greater papillary muscle contribution to total LVM (13±1 vs 6±0.5%, p<0.001), even in the absence of left ventricular hypertrophy (LVH). Late gadolinium enhancement (LGE) was present in 15 Fabry subjects (9/21 males and 6/23 females). The most common site for LGE was the basal inferolateral wall (93%, 14/15). There was a positive association between LVM index and LGE. Despite this, there were two males and three females with no LVH that displayed LGE. Of Fabry subjects who were not on enzyme replacement therapy at enrolment (n=28), six were reclassified as having cardiac involvement (four LVH-negative/LGE-positive, one LVH-positive/LGE-positive and one LVH-positive/LGE-negative). Conclusions CMR was able to detect cardiac involvement in 48% of this Fabry cohort, despite the overall mild disease phenotype of the cohort. Of those not on ERT, 21% were reclassified as having cardiac involvement allowing improved risk stratification and targeting of therapy.

Procedural and in-patient outcomes in patients aged 80 years or older undergoing contemporary primary percutaneous coronary intervention

AIMS Patients aged ≥80 years are often excluded or under-represented in trials assessing treatment modalities in STEMI. We assessed in-patient outcomes in elderly patients undergoing contemporary primary PCI (PPCI). METHODS AND RESULTS From Sept 2005 to July 2011 patients undergoing PPCI in our centre were identified. Demographic details, procedural data and in-patient outcomes were collated. Those aged ≥80 years were compared with those aged <80 years. In the study period 1,218 patients required PPCI, of which 224(18.4%) were ≥80 years. The elderly cohort were more likely to be female (44.3% vs. 20.3%; p<0.001), and have significant comorbidities. Times from first medical contact until TIMI 3 flow were similar between the two groups (medien 102 min vs. 109 min; p=0.19). There was no difference in rates of PCI success (97.3% vs. 98.3%; p=0.24), drug-eluting stent use (63.5% vs. 63.3%; p=1.00) and number of stents used. In-patient outcomes were worse in the elderly cohort with significantly higher rates of death (11.2% vs. 3.7%; p<0.001) and acute kidney injury (12.9% vs. 4.0%; p<0.001), with a trend towards more post-procedure cardiovascular accidents (CVA), access site complications and reinfarction. Length of stay was significantly longer in the elderly cohort (median days 5 vs. 3; p<0.001). CONCLUSIONS Important demographic differences exist in very elderly patients presenting with STEMI compared to younger patients though procedural data and PCI success rates are similar between the two groups. Those aged ≥80 years have significantly worse in-patient outcomes though death rates are not as high as historical data suggests.

Global Myocardial Edema in Antisynthetase Syndrome Detected by Cardiovascular Magnetic Resonance Mapping Techniques

A 56-year-old man presented with 7 months of fever, breathlessness, cough, and proximal muscle weakness with tenderness. His medical history was hypertension. His examination was unremarkable except for peripheral edema and a new, scaly, fissured erythematous rash on the hands and fingers (Figure 1). Blood tests revealed normocytic anemia, low total protein, raised inflammatory markers (C-reactive protein, 59 mg/L [normal, 0–5 mg/L]; erythrocyte sedimentation rate, 43 mm/h [normal, 1–20 mm/h]), and negative infective screen. The ECG was normal. Chest radiography and subsequent computed tomography showed interstitial lung disease. Echocardiography was normal (Movie IA in the online-only Data Supplement), but N-terminal pro-brain natriuretic peptide was very elevated at 245 …

Left Ventricular Hypertrophy Revisited: Cell and Matrix Expansion Have Disease-Specific Relationships

Left ventricular hypertrophy (LVH), a common pathway in health and disease, occurs because of cellular hypertrophy and expansion of extracellular matrix. Myocardial biopsy can identify extracellular matrix expansion (fibrosis, amyloid) from cellular hypertrophy and disarray and infiltration (iron, amyloid, inflammatory cells), but its invasive nature restricts its use to specific cases. Histology recognizes these cellular (cell death/hypertrophy) and extracellular matrix (fibrosis/infiltration) processes, but conventional cardiac imaging combines them into 1 compartment: the left ventricular mass (LVM). Cardiovascular magnetic resonance (CMR) using T1 mapping can split LVM into cellular and matrix components by measuring the extracellular volume fraction (ECV). The cell volume is LVM/1.05×[1–ECV], and the matrix volume is LVM/1.05×ECV, 1.05 being the specific gravity of the myocardium. We used this approach to explore the biology of LVH. The study was approved by the ethical committee of the UK National Research Ethics Service (07/H0715/101) and conformed to the principles of the Helsinki Declaration. All subjects gave written consent to participate; 190 subjects underwent CMR, including healthy volunteers (HV; n=30, male 44%, 41±11 years of age, no cardiovascular history, and …

Cardiac Phenotype of Prehypertrophic Fabry Disease

Background: Fabry disease (FD) is a rare and treatable X-linked lysosomal storage disorder. Cardiac involvement determines outcomes; therefore, detecting early changes is important. Native T1 by cardiovascular magnetic resonance is low, reflecting sphingolipid storage. Early phenotype development is familiar in hypertrophic cardiomyopathy but unexplored in FD. We explored the prehypertrophic cardiac phenotype of FD and the role of storage. Methods and Results: A prospective, international multicenter observational study of 100 left ventricular hypertrophy–negative FD patients (mean age: 39±15 years; 19% male) and 35 age- and sex-matched healthy volunteers (mean age: 40±14 years; 25% male) who underwent cardiovascular magnetic resonance, including native T1 and late gadolinium enhancement, and 12-lead ECG. In FD, 41% had a low native T1 using a single septal region of interest, but this increased to 59% using a second slice because early native T1 lowering was patchy. ECG abnormalities were present in 41% and twice as common with low native T1 (53% versus 24%; P=0.005). When native T1 was low, left ventricular maximum wall thickness, indexed mass, and ejection fraction were higher (maximum wall thickness 9±1.5 versus 8±1.4 mm, P<0.005; indexed left ventricular mass 63±10 versus 58±9 g/m2, P<0.05; and left ventricular ejection fraction 73±8% versus 69±7%, P<0.01). Late gadolinium enhancement was more likely when native T1 was low (27% versus 6%; P=0.01). FD had higher maximal apical fractal dimensions compared with healthy volunteers (1.27±0.06 versus 1.24±0.04; P<0.005) and longer anterior mitral valve leaflets (23±2 mm versus 21±3 mm; P<0.005). Conclusions: There is a detectable prehypertrophic phenotype in FD consisting of storage (low native T1), structural, functional, and ECG changes.

Sex Dimorphism in the Myocardial Response to Aortic Stenosis

Objectives The goal of this study was to explore sex differences in myocardial remodeling in aortic stenosis (AS) by using echocardiography, cardiac magnetic resonance (CMR), and biomarkers. Background AS is a disease of both valve and left ventricle (LV). Sex differences in LV remodeling are reported in AS and may play a role in disease phenotyping. Methods This study was a prospective assessment of patients awaiting surgical valve replacement for severe AS using echocardiography, the 6-min walking test, biomarkers (high-sensitivity troponin T and N-terminal pro–brain natriuretic peptide), and CMR with late gadolinium enhancement and extracellular volume fraction, which dichotomizes the myocardium into matrix and cell volumes. LV remodeling was categorized into normal geometry, concentric remodeling, concentric hypertrophy, and eccentric hypertrophy. Results In 168 patients (age 70 ± 10 years, 55% male, indexed aortic valve area 0.40 ± 0.13 cm2/m2, mean gradient 47 ± 4 mm Hg), no sex or age differences in AS severity or functional capacity (6-min walking test) were found. CMR captured sex dimorphism in LV remodeling not apparent by using 2-dimensional echocardiography. Normal geometry (82% female) and concentric remodeling (60% female) dominated in women; concentric hypertrophy (71% male) and eccentric hypertrophy (76% male) dominated in men. Men also had more evidence of LV decompensation (pleural effusions), lower left ventricular ejection fraction (67 ± 16% vs. 74 ± 13%; p < 0.001), and higher levels of N-terminal pro–brain natriuretic peptide (p = 0.04) and high-sensitivity troponin T (p = 0.01). Myocardial fibrosis was higher in men, with higher focal fibrosis (late gadolinium enhancement 16.5 ± 11.2 g vs. 10.5 ± 8.9 g; p < 0.001) and extracellular expansion (matrix volume 28.5 ± 8.8 ml/m2 vs. 21.4 ± 6.3 ml/m2; p < 0.001). Conclusions CMR revealed sex differences in associations between AS and myocardial remodeling not evident from echocardiography. Given equal valve severity, the myocardial response to AS seems more maladaptive in men than previously reported. (Regression of Myocardial Fibrosis After Aortic Valve Replacement [RELIEF-AS]; NCT02174471)

Insight into hypertrophied hearts: a cardiovascular magnetic resonance study of papillary muscle mass and T1 mapping.

Aims Left ventricular papillary muscles (LVPM) can appear disproportionately hypertrophied, particularly in Fabry disease (FD) where storage appears detectable by cardiovascular magnetic resonance (CMR) T1 mapping. The aim of the study was to measure LVPM mass in heart diseases with left ventricular hypertrophy (LVH) and to gain insight into the mechanisms of LVPM hypertrophy in FD. Methods and results Four hundred and seventy-eight cases were retrospectively recruited: 125 FD, 85 hypertrophic cardiomyopathy (HCM), 67 amyloid, 82 aortic stenosis (AS), 40 hypertension, 79 controls. LVPM contribution to LVM was manually contoured on CMR short axis cines. T1 values (septal, LVPM) were measured using ShMOLLI sequences in FD and controls. LVPM contribution to LVM was highest in LVH+ve FD and significantly increased compared to all other LVH+ve groups (FD 13 ± 3%, HCM 10 ± 3%, amyloid 8 ± 2%, AS 7 ± 3%, hypertension 7 ± 2%, controls 7 ± 1%; P < 0.001). LVH+ve HCM also had significantly increased LVPM. In LVH-ve cohorts, only FD had significantly increased LVPM (11 ± 3%; P < 0.001). In FD there was concordant septal and LVPM T1. LVH+ve FD: when septal T1 was low, LVPM T1 was low in 90%. LVH-ve FD: when septal T1 was normal, LVPM T1 was normal in 70% (indicating no detectable storage); when septal T1 was low, 75% had low LVPM T1 (indicating storage). LVPM hypertrophy was similar between the low and normal septal T1 groups (11 ± 3% vs. 10 ± 3%, P = 0.08). Conclusion Disproportionate hypertrophy of LVPMs in LVH+ve hearts occurred in FD and HCM. This phenomenon also occurred in LVH-ve FD. Low T1 was not always present in FD LVPM hypertrophy, implying additional mechanisms activating hypertrophy signalling pathways.

Ventricular arrhythmia and sudden cardiac death in Fabry disease: a systematic review of risk factors in clinical practice

Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficiency of α-galactosidase A enzyme. Cardiovascular (CV) disease is a common cause of mortality in FD, in particular as a result of heart failure and arrhythmia, with a significant proportion of events categorized as sudden. There are no clear models for risk prediction in FD. This systematic review aims to identify the risk factors for ventricular arrhythmia (VA) and sudden cardiac deaths (SCD) in FD. A systematic search was performed following PRISMA guidelines of EMBASE, Medline, PubMed, Web of Science, and Cochrane from inception to August 2016, focusing on identification of risk factors for the development of VA or SCD. Thirteen studies were included in the review (n = 4185 patients) from 1189 articles, with follow-up of 1.2-10 years. Weighted average age was 37.6 years, and 50% were male. Death from any cause was reported in 8.3%. Of these, 75% was due to CV problems, with the majority being SCD events (62% of reported deaths). Ventricular tachycardia was reported in 7 studies, with an average prevalence of 15.3%. Risk factors associated with SCD events were age, male gender, left ventricular hypertrophy, late gadolinium enhancement on CV magnetic resonance imaging, and non-sustained ventricular tachycardia. Although a multi-system disease, FD is a predominantly cardiac disease from a mortality perspective, with death mainly from SCD events. Limited evidence highlights the importance of clinical and imaging risk factors that could contribute to improved decision-making in the management of FD.