Vassilis Vassiliou

Left Ventricular Hypertrophy with Strain and Aortic Stenosis

Background— ECG left ventricular hypertrophy with strain is associated with an adverse prognosis in aortic stenosis. We investigated the mechanisms and outcomes associated with ECG strain. Methods and Results— One hundred and two patients (age, 70 years [range, 63–75 years]; male, 66%; aortic valve area, 0.9 cm2 [range, 0.7–1.2 cm2]) underwent ECG, echocardiography, and cardiovascular magnetic resonance. They made up the mechanism cohort. Myocardial fibrosis was determined with late gadolinium enhancement (replacement fibrosis) and T1 mapping (diffuse fibrosis). The relationship between ECG strain and cardiovascular magnetic resonance was then assessed in an external validation cohort (n=64). The outcome cohort was made up of 140 patients from the Scottish Aortic Stenosis and Lipid Lowering Trial Impact on Regression (SALTIRE) study and was followed up for 10.6 years (1254 patient-years). Compared with those without left ventricular hypertrophy (n=51) and left ventricular hypertrophy without ECG strain (n=30), patients with ECG strain (n=21) had more severe aortic stenosis, increased left ventricular mass index, more myocardial injury (high-sensitivity plasma cardiac troponin I concentration, 4.3 ng/L [interquartile range, 2.5–7.3 ng/L] versus 7.3 ng/L [interquartile range, 3.2–20.8 ng/L] versus 18.6 ng/L [interquartile range, 9.0–45.2 ng/L], respectively; P<0.001) and increased diffuse fibrosis (extracellular volume fraction, 27.4±2.2% versus 27.2±2.9% versus 30.9±1.9%, respectively; P<0.001). All patients with ECG strain had midwall late gadolinium enhancement (positive and negative predictive values of 100% and 86%, respectively). Indeed, late gadolinium enhancement was independently associated with ECG strain (odds ratio, 1.73; 95% confidence interval, 1.08–2.77; P=0.02), a finding confirmed in the validation cohort. In the outcome cohort, ECG strain was an independent predictor of aortic valve replacement or cardiovascular death (hazard ratio, 2.67; 95% confidence interval, 1.35–5.27; P<0.01). Conclusion— ECG strain is a specific marker of midwall myocardial fibrosis and predicts adverse clinical outcomes in aortic stenosis.

Atypical case of post-partum cardiomyopathy: an overlap syndrome with arrhythmogenic right ventricular cardiomyopathy?

A middle-aged female patient presented with increasing dyspnoea following delivery of her second child. Echocardiography showed left ventricular (LV) dilatation and severe global impairment of systolic function (ejection fraction < 10%) but normal right ventricular (RV) dimensions. Plasma B-type natriuretic peptide level was elevated. Post-partum cardiomyopathy (PPCM) was considered and after initiating appropriate heart failure pharmacotherapy, her symptoms improved significantly. Cardiovascular MR showed RV free wall dyskinesia and aneurysms at the LV apex, RV free wall and RV outflow tract. Genetic analysis showed a C11842T substitution in the titin gene (TTN). This is the first case to propose an overlap syndrome of PPCM and arrhythmogenic RV cardiomyopathy.

93 Ejection Fraction by Cardiovascular Magnetic Resonance Predicts Adverse Outcomes Post Aortic Valve Replacement

Introduction Predicting prognosis following aortic valve replacement (AVR) in patients with aortic stenosis (AS) remains challenging. Current guidelines recommend that surgery should be offered when ejection fraction (EF) is <50%. We sought to investigate the prognostic significance of EF calculated by cardiovascular magnetic resonance (CMR) in the long term survival of patients following AVR. Methods 80 patients (69 ± 11 years old at time of surgery; 55 male) scheduled for AVR underwent CMR assessment. 52 patients had severe AS (area <1cm2), 28 patients had moderate AS (area 1.0–1.5cm2) and other qualifying reasons for AVR. 44 patients had additional coronary artery disease.Patients were categorised into three groups according to EF prior to surgery: Group 1 (EF <50%; n = 26), Group 2 (EF of 50–70%; n = 26) and Group 3 (EF >70%; n = 28). A median 5.0 ± 1.8 years follow-up was completed using the National Strategic Tracing Scheme and hospital notes. Results Univariate analysis of all cause mortality using the Kaplan-Meier estimator demonstrated significantly higher mortality in patients with Group 1 (EF <50%) compared to those in group 3 (EF >70%; .03).There was no statistical difference between group 2 (EF of 50–70%) and the remaining 2 groups. Abstract 93 Figure 1 Kaplan-Meier survival curve of all cause mortality in Group 1 (EF <50%), Group 2 (EF 50–70%) and Group 3 (EF >70%) Conclusion Pre-operative EF is a significant predictor of mortality following AVR. Patients with EF <50% have the worst prognosis whereas those with EF >70% have the best prognosis. We aim to incease the sample size to determine whether a progressive decrease in EF per se even when above 50% should initiate consideration for AVR.

Mechanisms of Myocardial Ischemia in Hypertrophic Cardiomyopathy: Insights From Wave Intensity Analysis and Magnetic Resonance

Background Angina is common in hypertrophic cardiomyopathy (HCM) and is associated with abnormal myocardial perfusion. Wave intensity analysis improves the understanding of the mechanics of myocardial ischemia. Objectives Wave intensity analysis was used to describe the mechanisms underlying perfusion abnormalities in patients with HCM. Methods Simultaneous pressure and flow were measured in the proximal left anterior descending artery in 33 patients with HCM and 20 control patients at rest and during hyperemia, allowing calculation of wave intensity. Patients also underwent quantitative first-pass perfusion cardiac magnetic resonance to measure myocardial perfusion reserve. Results Patients with HCM had a lower coronary flow reserve than control subjects (1.9 ± 0.8 vs. 2.7 ± 0.9; p = 0.01). Coronary hemodynamics in HCM were characterized by a very large backward compression wave during systole (38 ± 11% vs. 21 ± 6%; p < 0.001) and a proportionately smaller backward expansion wave (27% ± 8% vs. 33 ± 6%; p = 0.006) compared with control subjects. Patients with severe left ventricular outflow tract obstruction had a bisferiens pressure waveform resulting in an additional proximally originating deceleration wave during systole. The proportion of waves acting to accelerate coronary flow increased with hyperemia, and the magnitude of change was proportional to the myocardial perfusion reserve (rho = 0.53; p < 0.01). Conclusions Coronary flow in patients with HCM is deranged. Distally, compressive deformation of intramyocardial blood vessels during systole results in an abnormally large backward compression wave, whereas proximally, severe left ventricular outflow tract obstruction is associated with an additional deceleration wave. Perfusion abnormalities in HCM are not simply a consequence of supply/demand mismatch or remodeling of the intramyocardial blood vessels; they represent a dynamic interaction with the mechanics of myocardial ischemia that may be amenable to treatment.

Markers of left ventricular decompensation in aortic stenosis

Calcified aortic stenosis is a condition that affects the valve and the myocardium. As the valve narrows, left ventricular hypertrophy occurs initially as an adaptive mechanism to maintain cardiac output. Ultimately, the ventricle decompensates and patients transition towards heart failure and adverse events. Current guidelines recommend aortic valve replacement in patients with severe aortic stenosis and evidence of decompensation based on either symptoms or an impaired ejection fraction <50%. However, symptoms can be subjective and correlate only modestly with the severity of aortic stenosis whilst impaired ejection fraction is an advanced manifestation and often irreversible. In this review, the authors will discuss the pathophysiology of left ventricular hypertrophy and the transition to heart failure. Subsequently, the authors will examine novel biomarkers that may better identify the transition from hypertrophy to heart failure and therefore guide the optimal timing for aortic valve replacement.

Original InvestigationMechanisms of Myocardial Ischemia in Hypertrophic Cardiomyopathy: Insights From Wave Intensity Analysis and Magnetic Resonance

Background Angina is common in hypertrophic cardiomyopathy (HCM) and is associated with abnormal myocardial perfusion. Wave intensity analysis improves the understanding of the mechanics of myocardial ischemia. Objectives Wave intensity analysis was used to describe the mechanisms underlying perfusion abnormalities in patients with HCM. Methods Simultaneous pressure and flow were measured in the proximal left anterior descending artery in 33 patients with HCM and 20 control patients at rest and during hyperemia, allowing calculation of wave intensity. Patients also underwent quantitative first-pass perfusion cardiac magnetic resonance to measure myocardial perfusion reserve. Results Patients with HCM had a lower coronary flow reserve than control subjects (1.9 ± 0.8 vs. 2.7 ± 0.9; p = 0.01). Coronary hemodynamics in HCM were characterized by a very large backward compression wave during systole (38 ± 11% vs. 21 ± 6%; p < 0.001) and a proportionately smaller backward expansion wave (27% ± 8% vs. 33 ± 6%; p = 0.006) compared with control subjects. Patients with severe left ventricular outflow tract obstruction had a bisferiens pressure waveform resulting in an additional proximally originating deceleration wave during systole. The proportion of waves acting to accelerate coronary flow increased with hyperemia, and the magnitude of change was proportional to the myocardial perfusion reserve (rho = 0.53; p < 0.01). Conclusions Coronary flow in patients with HCM is deranged. Distally, compressive deformation of intramyocardial blood vessels during systole results in an abnormally large backward compression wave, whereas proximally, severe left ventricular outflow tract obstruction is associated with an additional deceleration wave. Perfusion abnormalities in HCM are not simply a consequence of supply/demand mismatch or remodeling of the intramyocardial blood vessels; they represent a dynamic interaction with the mechanics of myocardial ischemia that may be amenable to treatment.

Clinical value of cardiovascular magnetic resonance in patients with MR-conditional pacemakers

AIMS Magnetic resonance (MR) conditional pacemakers are increasingly implanted into patients who may need cardiovascular MR (CMR) subsequent to device implantation. We assessed the added value of CMR for diagnosis and management in this population. METHODS AND RESULTS CMR and pacing data from consecutive patients with MR conditional pacemakers were retrospectively reviewed. Images were acquired at 1.5 T (Siemens Magnetom Avanto). The indication for CMR and any resulting change in management was recorded. The quality of CMR was rated by an observer blinded to clinical details, and data on pacemaker and lead parameters were collected pre- and post-CMR. Seventy-two CMR scans on 69 patients performed between 2011 and 2015 were assessed. All scans were completed successfully with no significant change in lead thresholds or pacing parameters. Steady-state free precession (SSFP) cine imaging resulted in a greater frequency of non-diagnostic imaging (22 vs. 1%, P < 0.01) compared with gradient echo sequences (GRE). Right-sided pacemakers were associated with less artefact than left-sided pacemakers. Late gadolinium enhancement imaging was performed in 59 scans with only 2% of segments rated of non-diagnostic quality. The CMR data resulted in a new diagnosis in 27 (38%) of examinations; clinical management was changed in a further 18 (25%). CONCLUSIONS CMR in patients with MR conditional pacemakers provided diagnostic or management-changing information in the majority (63%) of our cohort. The use of gradient echo cine sequences can reduce rates of non-diagnostic imaging. Right-sided device implantation may be considered in patients likely to require CMR examination.

Renal denervation for the management of resistant hypertension

Renal sympathetic denervation (RSD) as a therapy for patients with resistant hypertension has attracted great interest. The majority of studies in this field have demonstrated impressive reductions in blood pressure (BP). However, these trials were not randomized or sham-controlled and hence, the findings may have been overinflated due to trial biases. SYMPLICITY HTN-3 was the first randomized controlled trial to use a blinded sham-control and ambulatory BP monitoring. A surprise to many was that this study was neutral. Possible reasons for this neutrality include the fact that RSD may not be effective at lowering BP in man, RSD was not performed adequately due to limited operator experience, patients’ adherence with their anti-hypertensive drugs may have changed during the trial period, and perhaps the intervention only works in certain subgroups that are yet to be identified. Future studies seeking to demonstrate efficacy of RSD should be designed as randomized blinded sham-controlled trials. The efficacy of RSD is in doubt, but many feel that its safety has been established through the thousands of patients in whom the procedure has been performed. Over 90% of these data, however, are for the Symplicity™ system and rarely extend beyond 12 months of follow-up. Long-term safety cannot be assumed with RSD and nor should it be assumed that if one catheter system is safe then all are. We hope that in the near future, with the benefit of well-designed clinical trials, the role of renal denervation in the management of hypertension will be established.

Incremental benefit in correlation with histology of native T1 mapping, partition coefficient and extracellular volume fraction in patients with aortic stenosis

Incremental benefit in correlation with histology of native T1 mapping, partition coefficient and extracellular volume fraction in patients with aortic stenosis Vassilis Vassiliou, Katharina Wassilew, Tamir Malley, Claire E Raphael, Rebecca S Schofield, Kevin Kirby, Alex D Bowman, Karen Symmonds, Bruce S Spottiswoode, Andreas Greiser, Iain Pierce, David Firmin, Peter Gatehouse, Dudley J Pennell, Sanjay Prasad

Reproducibility of T1 mapping 11-heart beat MOLLI Sequence

Methods 15 healthy volunteers (31±5 years, 8 males) with no known medical conditions, on no medication, underwent CMR scans (Avanto, Siemens, 1.5T) on two separate attendances with an 11 heart beat MOLLI 5(3)3. Following frequency adjustment, native T1 maps were obtained twice on a basal and a mid-ventricular slice respectively. 15 mins following GBCA administration (0.1 mmol/kg, Gadobutrol, Bayer, Germany) both image planes were acquired again twice. Pixel-wise T1 maps were analyzed offline by 2 independent blinded operators. A Region Of Interest was manually drawn in the septum for myocardium and blood in native and post gad images as shown in fig 1.