Global longitudinal strain detects trastuzumab induced cardiotoxicity early in a clinical population (2020)

Type of publication:
Conference abstract

Author(s):
*Grylls, J., *Ellis, C., *Ingram, T., *Lee, E.

Citation:
European Heart Journal – Cardiovascular Imaging 2020; Volume 21, Issue Supplement 1

Abstract:
Background: Trastuzumab is highly effective in the treatment of breast cancer, and is often used as an adjuvant therapy. Due to its potential cardiotoxicity, serial monitoring of cardiac function is vital. Ejection fraction (EF) by two-dimensional echocardiography is routinely used but has limitations in measurement variability. Myocardial deformation imaging, in particular Global Longitudinal Strain (GLS), can detect pre-clinical myocardial dysfunction. However, its use is not yet adopted into routine clinical practice.
Aims: Our aim was to ascertain if a clinically significant reduction in GLS (≥11% from baseline) occurred before the onset of EF reduction, in patients who developed cardiotoxicity whilst receiving trastuzumab.
Methods: Between January 2014 and January 2019, 235 consecutive patients received trastuzumab and underwent serial echocardiography at 3 monthly intervals at our institute. Cardiotoxicity is defined as a ≥10% EF reduction from baseline or an EF <50%. Women who developed cardiotoxicity as defined by this change in EF were retrospectively studied.Two-dimensional speckle tracking was used to derive peak longitudinal strain in each myocardial segment from the apical four-, three- and two-chamber view images. GLS was taken as the average value of all these segments. The median time to ≥11% GLS reduction and ≥10% EF reduction or EF <50% was compared.
Results: Thirteen women (mean age 53 ± 9.5 years) developed cardiotoxicity. EF was 61.8 ± 4.4% at baseline and 45.7 ± 7.5% following therapy (p = 0.00). A ≥11% reduction in GLS from baseline was observed in all patients: GLS -20.2 ± 1.5% and -15.6 ± 2.1%, p = 0.00. The median time to cardiotoxicity as defined by EF and GLS was 6 months and 3 months, respectively (p = 0.031), as shown in Table 1. Repeatability analysis showed both EF and GLS measurements in our cohort have good measurement reproducibility. Inter-observer intraclass correlation (ICC) for EF and GLS were 0.912 and 0.913, respectively. Intra-observer ICC for EF and GLS were 0.925 and 0.900, respectively.
Conclusion: Cardiotoxicity developed in a significant portion (6%) of our patients receiving trastuzumab. As a reduction in GLS was detectable early and preceded that of EF by 3 months, this may represent a therapeutic window for initiation of cardio-protective medication, if and when the use of GLS is incorporated into routine practice for cardiotoxicity surveillance.

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CT Calcium Score In The Elderly With Aortic Stenosis (2020)

Type of publication:
Conference abstract

Author(s):
*Pastfield E.; *Botley S.; *Pakala V.; *Ingram T.; *Lee E.

Citation:
Journal of Cardiovascular Computed Tomography; 2020; vol. 14 (no. 1)

Abstract:
Introduction: Degenerative aortic stenosis is a common condition. Many elderly frail patients with multiple comorbidities now have an alternative to conventional surgery since the availability of transcutaneous aortic valve implantation (TAVI). Echocardiography (echo) remains the key tool for the diagnosis of aortic stenosis. CT calcium scoring, has proven a useful adjunct to diagnosis, when there are discordant echo measurements. The current societies’ consensus propose a cut-off score (>2000 for men and >1200 for women) above which ‘severe aortic stenosis is likely’. However, many elderly patients have discordant echo measurements, low calcium score despite having severe aortic stenosis. We propose that the adverse event rates in elderly patients, regardless of calcium score category, are not significantly different. Method(s): We retrospectively examined the records of consecutive patients undergoing CT calcium score between Jan 2017 and Sep 2019. These investigations were done, either for TAVI procedure planning or as an adjunct to assessing the severity of aortic stenosis (in the case of discordant echo measurements). All these patients were followed up for adverse events, defined as a composite of heart failure, chest pain or death. Statistical analysis was performed using SPSS 25 (IBM). Result(s): 88 patients, age 82+/-6 years, 55% men, underwent CT aortic valve calcium scoring and echo. Peak aortic velocity 3.9 +/- 0.8 m/s, mean gradient 35 +/- 13 mmHg, aortic valve area 0.8 +/- 0.2cm2, stroke volume index (SVI) 38 +/- 11 ml/m2. 52.4% of the study population had discordant echo measurements and 43.6% had SVI<35ml/m2. The calcium score for women and men were 2230 +/- 1250 and 3866 +/- 1997 respectively. 24% of these patients had calcium score below the cut-off value for ‘likely severe aortic stenosis’. Median follow up was 382 days (range 66-1381 days) from the initial echo. Adverse events occurred in 20+/-4% and 29+/-5% in the ‘high’ and ‘low’ calcium score groups, independent t-test, p=0.40. Using Kaplan-Meier survival curve, there is no difference in the event free survival days between the two groups, 888 days for the ‘low’ and 702 days for the ‘high’ calcium score groups, Log rank Chi-square=0.26, p=0.61. Conclusion(s): In an elderly population with aortic stenosis, there is no difference in short term adverse event rates (composite of heart failure/death/chest pain) as categorised by their calcium scores. Therefore, the current diagnostic approach may under estimate the severity of aortic stenosis in some patients. [Formula presented]

Targeting dyslipidaemia to prevent cardiovascular disease (2019)

Type of publication:
Journal article

Author(s):
Viljoen A.; Fuat A.; Takhar A.; Williams S.; *Capps N.

Citation:
Prescriber; Jul 2019; vol. 30 (no. 7); p. 23-26

Abstract:
Dyslipidaemia is a key risk factor for cardiovascular disease, and its identification and treatment is important for both primary and secondary prevention. This article discusses how to screen for dyslipidaemia and optimise lipid-lowering therapy to improve cardiovascular outcomes.

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Coronary heart disease mortality in severe and non-severe familial hyper-cholesterolaemia : data from the UK Simon Broome FH register (2019)

Type of publication:
Conference abstract

Author(s):
Humphries S.; Cooper J.; *Capps N.; Durrington P.; Jones B.; McDowell I.; Soran H.; Neil A.

Citation:
Atherosclerosis; Aug 2019; vol. 287

Abstract:
Background and Aims: Background: In 2016 the International Atherosclerosis Society (IAS) proposed that patients with “severe” FH (SFH) should be identified since they might warrant early and more aggressive cholesterol-lowering treatment such as with PCSK9 inhibitors. SFH is diagnosed if LDL-cholesterol (LDLC) >10 mmol/L, or LDLC >8.0 mmol/L plus one high-risk feature, or LDLC >5 mmol/L plus two high-risk features. Here we compare CHD mortality in SFH and non-SFH patients in the UK Simon Broome Register since 1991, when
statin use became routine.
Method(s): 2929 Definite or Possible patients (51% women) aged 20-79 years recruited from 21 UK lipid clinics were followed between 1992-2016. The excess CHD standardised mortality ratio (SMR) compared to the population in England and Wales was calculated (95% Confidence intervals).
Result(s): (67.7%) patients met the SFH definition. Post 1991, the SMR for CHD mortality was significantly (p=0.007) higher for SFH (220(184-261) (34,134 person years, 129 deaths observed, vs 59 expected) compared to non-SFH of 144(98-203) (15,432 person years, 32 observed vs 22 expected). After adjustment for traditional risk factors, the Hazard Ratio for CHD mortality in SFH vs non-SFH was 122 (80-187) p=0.36. Applying UK guidelines for the use of PCSK9i agents, overall ~24% of those in the register are likely to be eligible, but if this were restricted to those with SFH, overall ~16% would qualify.
Conclusion(s): CHD mortality remains elevated in treated FH, especially for SFH, emphasising the importance of optimal lipid-lowering, including the use of novel agents, and management of other risk factors

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Comparison of the size of persistent foramen ovale and atrial septal defects in divers with shunt-related decompression illness and in the general population (2015)

Type of publication:
Journal article

Author(s):
Wilmshurst P.T., Morrison W.L., Walsh K.P., Pearson M.J., Nightingale S.

Citation:
Diving and Hyperbaric Medicine, June 2015, vol./is. 45/2(89-93)

Abstract:
Introduction: Decompression illness (DCI) is associated with a right-to-left shunt, such as persistent foramen ovale (PFO), atrial septal defect (ASD) and pulmonary arteriovenous malformations. About one-quarter of the population have a PFO, but considerably less than one-quarter of divers suffer DCI. Our aim was to determine whether shunt-related DCI occurs mainly or entirely in divers with the largest diameter atrial defects. Methods: Case control comparison of diameters of atrial defects (PFO and ASD) in 200 consecutive divers who had transcatheter closure of an atrial defect following shunt-related DCI and in an historic group of 263 individuals in whom PFO diameter was measured at post-mortem examination. Results: In the divers who had experienced DCI, the median atrial defect diameter was 10 mm and the mean (standard deviation) was 9.9 (3.6) mm. Among those in the general population who had a PFO, the median diameter was 5 mm and mean was 4.9 (2.6) mm. The difference between the two groups was highly significant (P < 0.0001). Of divers with shuntrelated DCI, 101 (50.5%) had an atrial defect 10 mm diameter or larger, but only 1.3% of the general population studied had a PFO that was 10 mm diameter of larger. Conclusions: The risk of a diver suffering DCI is related to the size of the atrial defect rather than just the presence of a defect.

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