Does infection predispose to thrombosis during long-term ventricular assist device support?

BACKGROUND: Infections and thrombotic events remain life-threatening complications in patients with ventricular assist devices (VAD). METHODS: We describe the relationship between both events in our cohort of patients (n = 220) supported with the HeartWare VAD (HVAD). This is a retrospective analysis of patients undergoing HVAD implantation between July 2009 and March 2019 at the Freeman Hospital, Newcastle upon Tyne, United Kingdom. RESULTS: Infection was the most common adverse event in HVAD patients, with 125 patients (56.8%) experiencing ≥ one infection (n = 168, 0.33 event per person year (EPPY)), followed by pump thrombosis (PT) in 61 patients (27.7%, 0.16 EPPY). VAD-specific infections were the largest group of infections. Of the 125 patients who had an infection, 66 (53%) had a thrombotic event. Both thrombotic events and infections were related to the duration of support, though there was only limited evidence that infections predispose to thrombosis. Those with higher than median levels of C-reactive protein during the infection were more likely to have an ischaemic stroke (IS) (34.5% vs 16.7%, p = .03), though not PT or a combined thrombotic event (CTE: first PT or IS). However, in multivariate analysis, there was no significant effect of infection predisposing to CTE. CONCLUSIONS: Infection and thrombotic events are significant adverse events related to the duration of support in patients receiving HVADs. Infections do not clearly predispose to thrombotic events.

A retrospective evaluation of catheter ablation in atrial flutter post cardiac transplantation.

BACKGROUND: Atrial flutter is the most common arrhythmia post cardiac transplantation. Observational studies in the non-transplant population have shown prognostic benefit with catheter ablation; however, there are no data in the heart transplant population. OBJECTIVES: This study evaluated the experience of catheter ablation in atrial flutter post cardiac transplantation. METHODS: A retrospective review of experience of late onset atrial flutter at the Freeman Hospital, Newcastle-upon-Tyne, UK, between 1985 and January 2020. RESULTS: Sixty eight of the 722 patients who survived 6 months post cardiac transplantation developed late atrial flutter giving an incidence of 9.4%. Thirty-two patients were managed with ablation with treatment largely determined by time of flutter onset. Kaplan Meier estimates for arrhythmia free survival post first ablation for organized atrial arrhythmias was 83.3% at 1 year. Kaplan-Meier estimates for median survival post onset of atrial arrhythmias treated with ablation was 11.34 years (95% CI 8.00-14.57), compared to 5.79 years in patients managed medically (95%CI 2.26-9.32) (P = .026). CONCLUSIONS: Atrial flutter is an important late complication of cardiac transplantation. Patients treated with ablation in the modern era had increased survival compared to a historical cohort.

Cardiovascular magnetic resonance measures of aortic stiffness in asymptomatic patients with type 2 diabetes: association with glycaemic control and clinical outcomes.

BACKGROUND: We aimed to investigate in patients with type 2 diabetes whether aortic stiffness is: (i) associated with glycaemic control, (ii) associated with adverse outcomes and (iii) can be reversed on treatment with RAAS inhibition. METHODS: Patients with type 2 diabetes (N = 94) and low vascular risk underwent assessment of cardiovascular risk and CMR assessment of ascending aortic distensibility (AAD), descending aortic distensibility (DAD) and aortic pulse wave velocity (PWV). Of these patients a subgroup with recent onset microalbuminuria (N = 25) were treated with renin-angiotensin-aldosterone system (RAAS) inhibition and imaging repeated after 1 year. All 94 patients were followed up for 2.4 years for major adverse cardiovascular disease (CVD) events including myocardial infarction detected on late gadolinium enhancement CMR. RESULTS: Ascending aortic distensibility, DAD and PWV all had a significant association with age and 24 h systolic blood pressure but only AAD had a significant association with glycaemic control, measured as HbA1c (Beta - 0.016, P = 0.04). The association between HbA1c and AAD persisted even after correction for age and hypertension. CVD events occurred in 19/94 patients. AAD, but not DAD or PWV, was associated with CVD events (hazard ratio 0.49, 95% confidence interval 0.25-0.95, P = 0.01). On treatment with RAAS inhibition, AAD, but not DAD or PWV, showed significant improvement from 1.51 ± 1.15 to 1.97 ± 1.07 10-3 mmHg-1, P = 0.007. CONCLUSIONS: Ascending aortic distensibility measured by CMR is independently associated with poor glycaemic control and adverse cardiovascular events. Furthermore it may be reversible on treatment with RAAS inhibition. AAD is a promising marker of cardiovascular risk in asymptomatic patients with type 2 diabetes and has potential use as a surrogate cardiovascular endpoint in studies of novel hypoglycaemic agents. Clinical trials registration https://clinicaltrials.gov/ct2/show/NCT01970319.

Taxonomy of segmental myocardial systolic dysfunction.

The terms used to describe different states of myocardial health and disease are poorly defined. Imprecision and inconsistency in nomenclature can lead to difficulty in interpreting and applying trial outcomes to clinical practice. In particular, the terms 'viable' and 'hibernating' are commonly applied interchangeably and incorrectly to myocardium that exhibits chronic contractile dysfunction in patients with ischaemic heart disease. The range of inherent differences amongst imaging modalities used to define myocardial health and disease add further challenges to consistent definitions. The results of several large trials have led to renewed discussion about the classification of dysfunctional myocardial segments. This article aims to describe the diverse myocardial pathologies that may affect the myocardium in ischaemic heart disease and cardiomyopathy, and how they may be assessed with non-invasive imaging techniques in order to provide a taxonomy of myocardial dysfunction.

Effect of cellular and extracellular pathology assessed by T1 mapping on regional contractile function in hypertrophic cardiomyopathy.

BACKGROUND: Regional contractile dysfunction is a frequent finding in hypertrophic cardiomyopathy (HCM). We aimed to investigate the contribution of different tissue characteristics in HCM to regional contractile dysfunction. METHODS: We prospectively recruited 50 patients with HCM who underwent cardiovascular magnetic resonance (CMR) studies at 3.0 T including cine imaging, T1 mapping and late gadolinium enhancement (LGE) imaging. For each segment of the American Heart Association model segment thickness, native T1, extracellular volume (ECV), presence of LGE and regional strain (by feature tracking and tissue tagging) were assessed. The relationship of segmental function, hypertrophy and tissue characteristics were determined using a mixed effects model, with random intercept for each patient. RESULTS: Individually segment thickness, native T1, ECV and the presence of LGE all had significant associations with regional strain. The first multivariable model (segment thickness, LGE and ECV) demonstrated that all strain parameters were associated with segment thickness (P < 0.001 for all) but not ECV. LGE (Beta 2.603, P = 0.024) had a significant association with circumferential strain measured by tissue tagging. In a second multivariable model (segment thickness, LGE and native T1) all strain parameters were associated with both segment thickness (P < 0.001 for all) and native T1 (P < 0.001 for all) but not LGE. CONCLUSION: Impairment of contractile function in HCM is predominantly associated with the degree of hypertrophy and native T1 but not markers of extracellular fibrosis (ECV or LGE). These findings suggest that impairment of contractility in HCM is mediated by mechanisms other than extracellular expansion that include cellular changes in structure and function. The cellular mechanisms leading to increased native T1 and its prognostic significance remain to be established.

Cardiovascular magnetic resonance evaluation of symptomatic severe aortic stenosis: association of circumferential myocardial strain and mortality.

BACKGROUND: It is unknown whether circumferential strain is associated with prognosis after treatment of aortic stenosis (AS). We aimed to characterise strain in severe AS, using myocardial tagging cardiovascular magnetic resonance (CMR), prior to and following Transcatheter Aortic Valve Implantation (TAVI) and Surgical Aortic Valve Replacement (SAVR), and determine whether abnormalities in strain were associated with outcome. METHODS: CMR was performed pre- and 6 m post-intervention in 98 patients (52 TAVI, 46 SAVR; 77 ± 8 years) with severe AS. TAVI patients were older (80.9 ± 6.4 vs. 73.0 ± 7.0 years, p < 0.01) with a higher STS score (2.06 ± 0.6 vs. 6.03 ± 3.4, p < 0.001). Tagged cine images were acquired at the basal, mid and apical LV levels with a complementary spatial modulation of magnetization (CSPAMM) pulse sequence. Circumferential strain, strain rate and rotation were calculated using inTag© software. RESULTS: No significant change in basal or mid LV circumferential strain, or of diastolic strain rate, was seen following either intervention. However, a significant and comparable decline in LV torsion and twist was observed (SAVR: torsion 14.08 ± 8.40 vs. 7.81 ± 4.51, p < 0.001, twist 16.17 ± 7.01 vs.12.45 ± 4.78, p < 0.01; TAVI: torsion 14.43 ± 4.66 vs. 11.20 ± 4.62, p < 0.001, twist 16.08 ± 5.36 vs. 12.36 ± 5.21, p < 0.001) which likely reflects an improvement towards normal physiology following relief of AS. Over a maximum 6.0y follow up, there were 23 (16%) deaths following valve intervention. On multivariable Cox analysis, baseline mid LV circumferential strain was significantly associated with all-cause mortality (hazard ratio, 1.03; 1.01-1.05; p = 0.009) independent of age, LV ejection fraction and STS mortality risk score. ROC analysis indicated a mid LV circumferential strain > -18.7% was associated with significantly reduced survival. CONCLUSION: TAVI and SAVR procedures are associated with comparable declines in rotational LV mechanics at 6 m, with largely unchanged strain and strain rates. Pre-operative peak mid LV circumferential strain is associated with post-operative mortality.

Extra-cellular expansion in the normal, non-infarcted myocardium is associated with worsening of regional myocardial function after acute myocardial infarction.

BACKGROUND: Expansion of the myocardial extracellular volume (ECV) is a surrogate measure of focal/diffuse fibrosis and is an independent marker of prognosis in chronic heart disease. Changes in ECV may also occur after myocardial infarction, acutely because of oedema and in convalescence as part of ventricular remodelling. The objective of this study was to investigate changes in the pattern of distribution of regional (normal, infarcted and oedematous segments) and global left ventricular (LV) ECV using semi-automated methods early and late after reperfused ST-elevation myocardial infarction (STEMI). METHODS: Fifty patients underwent cardiovascular magnetic resonance (CMR) imaging acutely (24 h-72 h) and at convalescence (3 months). The CMR protocol included: cines, T2-weighted (T2 W) imaging, pre-/post-contrast T1-maps and LGE-imaging. Using T2 W and LGE imaging on acute scans, 16-segments of the LV were categorised as normal, oedema and infarct. 800 segments (16 per-patient) were analysed for changes in ECV and wall thickening (WT). RESULTS: From the acute studies, 325 (40.6%) segments were classified as normal, 246 (30.8%) segments as oedema and 229 (28.6%) segments as infarct. Segmental change in ECV between acute and follow-up studies (Δ ECV) was significantly different for normal, oedema and infarct segments (0.8 ± 6.5%, -1.78 ± 9%, -2.9 ± 10.9%, respectively; P < 0.001). Normal segments which demonstrated deterioration in wall thickening at follow-up showed significantly increased Δ ECV compared with normal segments with preserved wall thickening at follow up (1.82 ± 6.05% versus -0.10 ± 6.88%, P < 0.05). CONCLUSION: Following reperfused STEMI, normal myocardium demonstrates subtle expansion of the extracellular volume at 3-month follow up. Segmental ECV expansion of normal myocardium is associated with worsening of contractile function.

Sex-related differences in left ventricular remodeling in severe aortic stenosis and reverse remodeling after aortic valve replacement: A cardiovascular magnetic resonance study.

BACKGROUND: Cardiac adaptation to aortic stenosis (AS) appears to differ according to sex, but reverse remodeling after aortic valve replacement has not been extensively described. The aim of the study was to determine using cardiac magnetic resonance imaging whether any sex-related differences exist in AS in terms of left ventricular (LV) remodeling, myocardial fibrosis, and reverse remodeling after valve replacement. METHODS: One hundred patients (men, n = 60) with severe AS undergoing either transcatheter or surgical aortic valve replacement underwent cardiac magnetic resonance scans at baseline and 6 months after valve replacement. RESULTS: Despite similar baseline comorbidity and severity of AS, women had a lower indexed LV mass than did men (65.3 ± 18.4 vs 81.5 ± 21.3 g/m(2), P < .001) and a smaller indexed LV end-diastolic volume (87.3 ± 17.5 vs 101.2 ± 28.6 mL/m(2), P = .002) with a similar LV ejection fraction (58.6% ± 10.2% vs 54.8% ± 12.9%, P = .178). Total myocardial fibrosis mass was similar between sexes (2.3 ± 4.1 vs 1.3 ± 1.1 g, P = .714), albeit with a differing distribution according to sex. After aortic valve replacement, men had more absolute LV mass regression than did women (18.3 ± 10.6 vs 12.7 ± 8.8 g/m(2), P = .007). When expressed as a percentage reduction of baseline indexed LV mass, mass regression was similar between the sexes (men 21.7% ± 10.1% vs women 18.4% ± 11.0%, P = .121). There was no sex-related difference in postprocedural LV ejection fraction or aortic regurgitation. Sex was not found to be a predictor of LV reverse remodeling on multiple regression analysis. CONCLUSIONS: There are significant differences in the way that male and female hearts adapt to AS. Six months after aortic valve replacement, there are no sex-related differences in reverse remodeling, but superior reverse remodeling in men as a result of their more adverse remodeling profile at baseline.

Relationship between cardiac deformation parameters measured by cardiovascular magnetic resonance and aerobic fitness in endurance athletes.

BACKGROUND: Athletic training leads to remodelling of both left and right ventricles with increased myocardial mass and cavity dilatation. Whether changes in cardiac strain parameters occur in response to training is less well established. In this study we investigated the relationship in trained athletes between cardiovascular magnetic resonance (CMR) derived strain parameters of cardiac function and fitness. METHODS: Thirty five endurance athletes and 35 age and sex matched controls underwent CMR at 3.0 T including cine imaging in multiple planes and tissue tagging by spatial modulation of magnetization (SPAMM). CMR data were analysed quantitatively reporting circumferential strain and torsion from tagged images and left and right ventricular longitudinal strain from feature tracking of cine images. Athletes performed a maximal ramp-incremental exercise test to determine the lactate threshold (LT) and maximal oxygen uptake (V̇O2max). RESULTS: LV circumferential strain at all levels, LV twist and torsion, LV late diastolic longitudinal strain rate, RV peak longitudinal strain and RV early and late diastolic longitudinal strain rate were all lower in athletes than controls. On multivariable linear regression only LV torsion (beta = -0.37, P = 0.03) had a significant association with LT. Only RV longitudinal late diastolic strain rate (beta = -0.35, P = 0.03) had a significant association with V̇O2max. CONCLUSIONS: This cohort of endurance athletes had lower LV circumferential strain, LV torsion and biventricular diastolic strain rates than controls. Increased LT, which is a major determinant of performance in endurance athletes, was associated with decreased LV torsion. Further work is needed to understand the mechanisms by which this occurs.

Assessment of aortic stiffness by cardiovascular magnetic resonance following the treatment of severe aortic stenosis by TAVI and surgical AVR.

BACKGROUND: Aortic stiffness is increasingly used as an independent predictor of adverse cardiovascular outcomes. We sought to compare the impact of transcatheter aortic valve implantation (TAVI) and surgical aortic valve replacement (SAVR) upon aortic vascular function using cardiovascular magnetic resonance (CMR) measurements of aortic distensibility and pulse wave velocity (PWV). METHODS AND RESULTS: A 1.5 T CMR scan was performed pre-operatively and at 6 m post-intervention in 72 patients (32 TAVI, 40 SAVR; age 76 ± 8 years) with high-risk symptomatic severe aortic stenosis. Distensibility of the ascending and descending thoracic aorta and aortic pulse wave velocity were determined at both time points. TAVI and SAVR patients were comparable for gender, blood pressure and left ventricular ejection fraction. The TAVI group were older (81 ± 6.3 vs. 72.8 ± 7.0 years, p < 0.05) with a higher EuroSCORE II (5.7 ± 5.6 vs. 1.5 ± 1.0 %, p < 0.05). At 6 m, SAVR was associated with a significant decrease in distensibility of the ascending aorta (1.95 ± 1.15 vs. 1.57 ± 0.68 × 10(-3)mmHg(-1), p = 0.044) and of the descending thoracic aorta (3.05 ± 1.12 vs. 2.66 ± 1.00 × 10(-3)mmHg(-1), p = 0.018), with a significant increase in PWV (6.38 ± 4.47 vs. 11.01 ± 5.75 ms(-1), p = 0.001). Following TAVI, there was no change in distensibility of the ascending aorta (1.96 ± 1.51 vs. 1.72 ± 0.78 × 10(-3)mmHg(-1), p = 0.380), descending thoracic aorta (2.69 ± 1.79 vs. 2.21 ± 0.79 × 10(-3)mmHg(-1), p = 0.181) nor in PWV (8.69 ± 6.76 vs. 10.23 ± 7.88 ms(-1), p = 0.301) at 6 m. CONCLUSIONS: Treatment of symptomatic severe aortic stenosis by SAVR but not TAVI was associated with an increase in aortic stiffness at 6 months. Future work should focus on the prognostic implication of these findings to determine whether improved patient selection and outcomes can be achieved.

Patient adaptive maximal resolution magnetic resonance myocardial stress perfusion imaging.

PURPOSE: To demonstrate the feasibility of an automatic adaptive acquisition sequence. Magnetic resonance perfusion pulse sequences often leave potential acquisition time unused in patients with lower heart-rates (HR) and smaller body size. MATERIALS AND METHODS: A perfusion technique was developed that automatically adapts to HR and field-of-view by maximizing in-plane spatial resolution while maintaining temporal resolution every cardiac cycle. Patients (n = 10) and volunteers (n = 10) were scanned with both a standard resolution and adaptive method. Image quality was scored, signal-to-noise ratio (SNR) calculated, and width of dark-rim artifact (DRA) measured. RESULTS: The acquired spatial resolution of the adaptive sequence (1.92 × 1.92 mm(2) ± 0.34) was higher than the standard resolution (2.42 × 2.42 mm(2) ) (P < 0.0001). Mean DRA width was reduced using the adaptive pulse sequence (1.94 ± 0.60 mm vs. 2.82 ± 0.65 mm, P < 0.0001). The signal-to-noise ratio (SNR) was higher with the standard pulse sequence (6.7 ± 2.2 vs. 3.8 ± 1.8, P < 0.0001). There was no difference in image quality score between sequences in either volunteers (1.1 ± 0.31 vs. 1.0 ± 0.0, P = 0.34) or patients (1.3 ± 0.48 vs. 1.3 ± 0.48, P = 1.0). CONCLUSION: Optimizing the use of available imaging time during first-pass perfusion with a magnetic resonance imaging pulse sequence that adapts image acquisition duration to HR and patient size is feasible. Acquired in-plane spatial resolution is improved, the DRA is reduced, and while SNR is reduced with the adaptive sequence consistent with the lower voxel size used, image quality is maintained.

Single bolus versus split dose gadolinium administration in extra-cellular volume calculation at 3 Tesla.

BACKGROUND: Diffuse myocardial fibrosis may be quantified with cardiovascular magnetic resonance (CMR) by calculating extra-cellular volume (ECV) from native and post-contrast T1 values. Accurate ECV calculation is dependent upon the contrast agent having reached equilibrium within tissue compartments. Previous studies have used infusion or single bolus injections of contrast to calculate ECV. In clinical practice however, split dose contrast injection is commonly used as part of stress/rest perfusion studies. In this study we sought to assess the effects of split dose versus single bolus contrast administration on ECV calculation. METHODS: Ten healthy volunteers and five patients ( 4 ischaemic heart disease, 1 hypertrophic cardiomyopathy) were studied on a 3.0 Tesla (Philips Achieva TX) MR system and underwent two (patients) or three (volunteers) separate CMR studies over a mean of 12 and 30 days respectively. Volunteers underwent one single bolus contrast study (Gadovist 0.15mmol/kg). In two further studies, contrast was given in two boluses (0.075mmol/kg per bolus) as part of a clinical adenosine stress/rest perfusion protocol, boluses were separated by 12 minutes. Patients underwent one bolus and one stress perfusion study only. T1 maps were acquired pre contrast and 15 minutes following the single bolus or second contrast injection. RESULTS: ECV agreed between bolus and split dose contrast administration (coefficient of variability 5.04%, bias 0.009, 95% CI -3.754 to 3.772, r2 = 0.973, p = 0.001)). Inter-study agreement with split dose administration was good (coefficient of variability, 5.67%, bias -0.018, 95% CI -4.045 to 4.009, r2 = 0.766, p > 0.001). CONCLUSION: ECV quantification using split dose contrast administration is reproducible and agrees well with previously validated methods in healthy volunteers, as well as abnormal and remote myocardium in patients. This suggests that clinical perfusion CMR studies may incorporate assessment of tissue composition by ECV based on T1 mapping.

Susceptibility-weighted cardiovascular magnetic resonance in comparison to T2 and T2 star imaging for detection of intramyocardial hemorrhage following acute myocardial infarction at 3 Tesla.

BACKGROUND: Intramyocardial hemorrhage (IMH) identified by cardiovascular magnetic resonance (CMR) is an established prognostic marker following acute myocardial infarction (AMI). Detection of IMH by T2-weighted or T2 star CMR can be limited by long breath hold times and sensitivity to artefacts, especially at 3T. We compared the image quality and diagnostic ability of susceptibility-weighted magnetic resonance imaging (SW MRI) with T2-weighted and T2 star CMR to detect IMH at 3T. METHODS: Forty-nine patients (42 males; mean age 58 years, range 35-76) underwent 3T cardiovascular magnetic resonance (CMR) 2 days following re-perfused AMI. T2-weighted, T2 star and SW MRI images were obtained. Signal and contrast measurements were compared between the three methods and diagnostic accuracy of SW MRI was assessed against T2w images by 2 independent, blinded observers. Image quality was rated on a 4-point scale from 1 (unusable) to 4 (excellent). RESULTS: Of 49 patients, IMH was detected in 20 (41%) by SW MRI, 21 (43%) by T2-weighted and 17 (34%) by T2 star imaging (p = ns). Compared to T2-weighted imaging, SW MRI had sensitivity of 93% and specificity of 86%. SW MRI had similar inter-observer reliability to T2-weighted imaging (κ = 0.90 and κ = 0.88 respectively); both had higher reliability than T2 star (κ = 0.53). Breath hold times were shorter for SW MRI (4 seconds vs. 16 seconds) with improved image quality rating (3.8 ± 0.4, 3.3 ± 1.0, 2.8 ± 1.1 respectively; p < 0.01). CONCLUSIONS: SW MRI is an accurate and reproducible way to detect IMH at 3T. The technique offers considerably shorter breath hold times than T2-weighted and T2 star imaging, and higher image quality scores.

The distribution and prognosis of anomalous coronary arteries identified by cardiovascular magnetic resonance: 15 year experience from two tertiary centres.

BACKGROUND: Aberrant coronary arteries represent a diverse group of congenital disorders. Post-mortem studies reveal a high risk of exercise-related sudden cardiac death in those with an anomalous coronary artery originating from the opposite sinus of Valsalva (ACAOS) with an inter-arterial course. There is little documentation of lifetime history and long-term follow-up of patients with coronary artery anomalies. METHODS: Patients with anomalous coronary arteries undergoing cardiovascular magnetic resonance over a 15-year period were identified and classified by anatomy and course. Medical records were reviewed for major adverse cardiovascular events (MACE). Revascularisation or myocardial infarction counted only if occurring in the distribution of the anomalous artery. RESULTS: Consecutive patients with coronary artery anomalies were retrospectively identified (n = 172). Median follow-up time was 4.3 years (IQR 2.5-7.8, maximum 15.6). 116 patients had ACAOS of which 64 (55%) had an inter-arterial course (IAC) and 52 (45%) did not. During follow up 110 ACAOS patients were alive, 5 died and 1 lost to follow-up.ACAOS patients experienced 58 MACE events (5 cardiovascular deaths, 5 PCI, 24 CABG and 24 had myocardial infarction). 47 MACE events occurred in ACAOS with IAC and 11 in those without (p < 0.0001), the statistical difference driven by surgical revascularisation and myocardial infarction. CONCLUSIONS: In life, patients with an anomalous coronary artery originating from the opposite sinus of Valsalva taking an IAC have higher rates of both myocardial infarction and surgical revascularisation during long-term follow up, compared to those without IAC.

Arrhythmias and cardiac MRI associations in patients with established cardiac dystrophinopathy.

AIMS: Some patients with cardiac dystrophinopathy die suddenly. Whether such deaths are preventable by specific antiarrhythmic management or simply indicate heart failure overwhelming medical therapies is uncertain. The aim of this prospective, cohort study was to describe the occurrence and nature of cardiac arrhythmias recorded during prolonged continuous ECG rhythm surveillance in patients with established cardiac dystrophinopathy and relate them to abnormalities on cardiac MRI. METHODS AND RESULTS: A cohort of 10 patients (36.3 years; 3 female) with LVEF<40% due to Duchenne (3) or Becker muscular (4) dystrophy or Duchenne muscular dystrophy-gene carrying effects in females (3) were recruited, had cardiac MRI, ECG signal-averaging and ECG loop-recorder implants. All were on standard of care heart medications and none had prior history of arrhythmias.No deaths or brady arrhythmias occurred during median follow-up 30 months (range 13-35). Self-limiting episodes of asymptomatic tachyarrhythmia (range 1-29) were confirmed in 8 (80%) patients (ventricular only 2; ventricular and atrial 6). Higher ventricular arrhythmia burden correlated with extent of myocardial fibrosis (extracellular volume%, p=0.029; native T1, p=0.49; late gadolinium enhancement, p=0.49), but not with LVEF% (p=1.0) on MRI and atrial arrhythmias with left atrial dilatation. Features of VT episodes suggested various underlying arrhythmia mechanisms. CONCLUSIONS: The overall prevalence of arrhythmias was low. Even in such a small sample size, higher arrhythmia counts occurred in those with larger scar burden and greater ventricular volume, suggesting key roles for myocardial stretch as well as disease progression in arrhythmogenesis. These features overlap with the stage of left ventricular dysfunction when heart failure also becomes overt. The findings of this pilot study should help inform the design of a definitive study of specific antiarrhythmic management in dystrophinopathy. TRIAL REGISTRATION NUMBER: ISRCTN15622536.

Viability and Outcomes With Revascularization or Medical Therapy in Ischemic Ventricular Dysfunction: A Prespecified Secondary Analysis of the REVIVED-BCIS2 Trial.

Importance: In the Revascularization for Ischemic Ventricular Dysfunction (REVIVED-BCIS2) trial, percutaneous coronary intervention (PCI) did not improve outcomes for patients with ischemic left ventricular dysfunction. Whether myocardial viability testing had prognostic utility for these patients or identified a subpopulation who may benefit from PCI remained unclear. Objective: To determine the effect of the extent of viable and nonviable myocardium on the effectiveness of PCI, prognosis, and improvement in left ventricular function. Design, Setting, and Participants: Prospective open-label randomized clinical trial recruiting between August 28, 2013, and March 19, 2020, with a median follow-up of 3.4 years (IQR, 2.3-5.0 years). A total of 40 secondary and tertiary care centers in the United Kingdom were included. Of 700 randomly assigned patients, 610 with left ventricular ejection fraction less than or equal to 35%, extensive coronary artery disease, and evidence of viability in at least 4 myocardial segments that were dysfunctional at rest and who underwent blinded core laboratory viability characterization were included. Data analysis was conducted from March 31, 2022, to May 1, 2023. Intervention: Percutaneous coronary intervention in addition to optimal medical therapy. Main Outcomes and Measures: Blinded core laboratory analysis was performed of cardiac magnetic resonance imaging scans and dobutamine stress echocardiograms to quantify the extent of viable and nonviable myocardium, expressed as an absolute percentage of left ventricular mass. The primary outcome of this subgroup analysis was the composite of all-cause death or hospitalization for heart failure. Secondary outcomes were all-cause death, cardiovascular death, hospitalization for heart failure, and improved left ventricular function at 6 months. Results: The mean (SD) age of the participants was 69.3 (9.0) years. In the PCI group, 258 (87%) were male, and in the optimal medical therapy group, 277 (88%) were male. The primary outcome occurred in 107 of 295 participants assigned to PCI and 114 of 315 participants assigned to optimal medical therapy alone. There was no interaction between the extent of viable or nonviable myocardium and the effect of PCI on the primary or any secondary outcome. Across the study population, the extent of viable myocardium was not associated with the primary outcome (hazard ratio per 10% increase, 0.98; 95% CI, 0.93-1.04) or any secondary outcome. The extent of nonviable myocardium was associated with the primary outcome (hazard ratio, 1.07; 95% CI, 1.00-1.15), all-cause death, cardiovascular death, and improvement in left ventricular function. Conclusions and Relevance: This study found that viability testing does not identify patients with ischemic cardiomyopathy who benefit from PCI. The extent of nonviable myocardium, but not the extent of viable myocardium, is associated with event-free survival and likelihood of improvement of left ventricular function. Trial Registration: ClinicalTrials.gov Identifier: NCT01920048.

Cardiovascular magnetic resonance assessment of left atrial size and function in endurance athletes.

Background: Left atrial (LA) dilatation is linked to cardiovascular disease and atrial fibrillation but its associations in athletes are unknown. The authors investigated whether aerobic fitness and clinical parameters are associated with LA dilatation and emptying fraction (EF) in endurance athletes. Materials & methods: 65 endurance athletes underwent cardiovascular magnetic resonance to assess LA size and function along with fitness assessment. 25 sedentary controls underwent an identical cardiovascular magnetic resonance protocol. Results: In athletes, LA volume index was elevated, while total and passive LAEFs were decreased versus sedentary controls. Increasing age and maximal oxygen uptake were associated with LA volume index. Only older age was associated with decreased total LAEF. Conclusion: LA dilatation in athletes is associated with increasing age and aerobic fitness rather than conventional cardiovascular risk factors.

Markers of Right Ventricular Dysfunction Predict Maximal Exercise Capacity After Left Ventricular Assist Device Implantation.

Although left ventricular assist device (LVAD) improves functional capacity, on average LVAD patients are unable to achieve the aerobic capacity of normal healthy subjects or mild heart failure patients. The aim of this study was to examine if markers of right ventricular (RV) function influence maximal exercise capacity. This was a single-center prospective study that enrolled 20 consecutive HeartWare ventricular assist device patients who were admitted at the Freeman Hospital (Newcastle upon Tyne, United Kingdom) for a heart transplant assessment from August 2017 to October 2018. Mean peak oxygen consumption (Peak VO2) was 14.0 ± 5.0 ml/kg/min, and mean peak age and gender-adjusted percent predicted oxygen consumption (%VO2) was 40.0% ± 11.5%. Patients were subdivided into two groups based on the median peak VO2, so each group consisted of 10 patients (50%). Right-sided and pulmonary pressures were consistently higher in the group with poorer exercise tolerance. Patients with poor exercise tolerance (peak VO2 below the median) had higher right atrial pressures at rest (10.6 ± 6.4 vs. 4.3 mmHg ± 3.2; p = 0.02) and the increase with passive leg raising was significantly greater than those with preserved exercise tolerance (peak VO2 above the median). Patients with poor functional capacity also had greater RV dimensions (4.4 cm ± 0.5 vs. 3.7 cm ± 0.5; p = 0.02) and a higher incidence of significant tricuspid regurgitation (moderate or severe tricuspid regurgitation in five patients in the poor exercise capacity group vs. none in the preserved exercise capacity group; p = 0.03). In conclusion, echocardiographic and hemodynamic markers of RV dysfunction discriminate between preserved and nonpreserved exercise capacity in HeartWare ventricular assist device patients.

Myocardial Effects of Aldosterone Antagonism in Heart Failure With Preserved Ejection Fraction.

Background Spironolactone may have prognostic benefit in selected patients with heart failure with preserved ejection fraction. This study assessed the myocardial tissue effects of spironolactone in heart failure with preserved ejection fraction. Methods and Results A 1:1 randomized controlled study of 6 months of spironolactone versus control in heart failure with preserved ejection fraction. The primary outcome was change in myocardial extracellular volume fraction by cardiovascular magnetic resonance as a surrogate of diffuse fibrosis. Of 55 randomized patients, 40 (20 women; age, 75.2±5.9 years) completed follow-up (19 treatment, 21 control). A significant change in extracellular volume over the study period was not seen (treatment, 28.7±3.7% versus 27.7±3.4% [P=0.14]; controls, 27.6±3.4% versus 28.3±4.4% [P=0.14]); however, the rate of extracellular volume expansion was decreased by spironolactone (-1.0±2.4% versus 0.8±2.2%). Indexed left ventricular mass decreased with treatment (104.4±26.6 versus 94.0±20.6 g/m2; P=0.001) but not in controls (101.4±29.4 versus 104.0±32.8 g/m2; P=0.111). Extracellular mass decreased by 13.8% (15.1±4.8 versus 13.0±3.4 g/m2; P=0.003), and cellular mass decreased by 8.3% (37.6±10.0 versus 34.3±7.9 g/m2; P=0.001) with spironolactone, but was static in controls. Conclusions Spironolactone did not lead to significant change in extracellular volume. However, spironolactone did decrease rate of extracellular expansion, with a decrease in the mass of both cellular and extracellular myocardial compartments. These data point to the mechanism of action of spironolactone in heart failure with preserved ejection fraction, including a direct tissue effect with a reduction in rate of myocardial fibrosis.

Quantitative deformation analysis differentiates ischaemic and non-ischaemic cardiomyopathy: sub-group analysis of the VINDICATE trial.

Aims: To test the hypothesis that patients with ischaemic cardiomyopathy (ICM) and non-ischaemic cardiomyopathy (NICM) have different torsion and strain parameters, and compare to healthy, age-matched controls. VINDICATE investigated efficacy of high-dose vitamin D on patients with heart failure (HF) secondary to left ventricular (LV) systolic dysfunction of any aetiology. It is important to differentiate ICM and NICM as treatment and prognosis varies significantly. Cardiovascular magnetic resonance (CMR) reliably determines aetiology of HF and tissue tagging techniques are recognized as the reference standard measures of strain and torsion. Methods and results: Fifty three patients (31 ICM, 22 NICM) from VINDICATE and 25 controls underwent CMR at 3.0T, including cine imaging in multiple planes and tissue tagging by spatial modulation of magnetization. CMR data were analysed blinded, by quantitatively reporting circumferential strain and torsion from tagged images and global longitudinal strain from feature tracking. HF patients had larger ventricles indexed to body surface area, lower left ventricular ejection fraction (LVEF), LV torsion, twist, and strain parameters compared to controls. There were no significant differences between ICM and NICM in age, blood pressure, heart rhythm, or NYHA status. There was no significant difference in LV dimensions, EF, and strain parameters between ICM and NICM. NICM patients had significantly lower LV twist (6.0 ± 3.7° vs. 8.8 ± 4.3°, P = 0.023) and torsion (5.9 ± 3.5° vs. 8.8 ± 4.7°, P = 0.017) compared to ICM. Conclusion: Twist, torsion, and strain are reduced in HF patients compared to controls. Torsion and twist are significantly lower in patients with NICM compared to ICM, despite similar volumetric dimensions, circumferential and longitudinal strain parameters, and LVEF.