Left ventricular T1-mapping in diastole versus systole in patients with mitral regurgitation

Cardiovascular magnetic resonance T1-mapping enables myocardial tissue characterisation, and is capable of quantifying both intracellular and extracellular volume. T1-mapping is conventionally performed in diastole, however, we hypothesised that systolic readout would reduce variability due to a reduction in myocardial blood volume. This study investigated whether T1-mapping in systole alters T1 values compared to diastole and whether reproducibility alters in atrial fibrillation compared to sinus rhythm. We prospectively identified 103 consecutive patients recruited to the Mitral FINDER study who had T1 mapping in systole and diastole. These patients had moderate or severe mitral regurgitation and a high incidence of ventricular dilatation and atrial fibrillation. T1, ECV and goodness-of-fit (R2) values of the T1 times were calculated offline using Circle cvi42 and in house-developed software. Systolic T1 mapping was associated with fewer myocardial segments being affected by artefact compared to diastolic T1 mapping [217/2472 (9%) vs 515/2472 (21%)]. Mean native T1 values were not significantly different when measured in systole and diastole (985 ± 26 ms vs 988 ± 29 respectively; p = 0.061) and mean post-contrast values showed similar good agreement (462 ± 32 ms vs 459 ± 33 respectively, p = 0.052). No clinically significant differences in ECV, native T1 and post-contrast T1 were identified between diastolic and systolic T1 maps in males versus females, or in patients with permanent atrial fibrillation versus sinus rhythm. A statistically significant improvement in R2 value was observed with systolic over diastolic T1 mapping in all analysed maps (n = 411) (96.2 ± 1.4% vs 96.0 ± 1.4%; p &lt; 0.001) and in subgroup analyses [Sinus rhythm: 96.1 ± 1.4 vs 96.3 ± 1.4 (n = 327); p &lt; 0.001. AF: 95.5 ± 1.3 vs 95.9 ± 1.2 (n = 80); p &lt; 0.001] [Males: 95.8 ± 1.4 vs 96.1 ± 1.3 (n = 264); p &lt; 0.001; Females: 96.2 ± 1.3 vs 96.4 ± 1.4 (n = 143); p = 0.009]. In conclusion, myocardial T1 mapping is associated with similar T1 and ECV values in systole and diastole. Furthermore, systolic acquisition is less prone to gating artefact in arrhythmia.</p

Arrhythmic effects of Epac-mediated ryanodine receptor activation in Langendorff-perfused murine hearts are associated with reduced conduction velocity.

Recent papers have attributed arrhythmic substrate in murine RyR2-P2328S hearts to reduced action potential (AP) conduction velocities (CV), reflecting acute functional inhibition and/or reduced expression of sodium channels. We explored for acute effects of direct exchange protein directly activated by cAMP (Epac)-mediated ryanodine receptor-2 (RyR2) activation on arrhythmic substrate and CV. Monophasic action potential (MAP) recordings demonstrated that initial steady (8 Hz) extrinsic pacing elicited ventricular tachycardia (VT) in 0 of 18 Langendorff-perfused wild-type mouse ventricles before pharmacological intervention. The Epac activator 8-CPT (8-(4-chlorophenylthio)-2′-O-methyladenosine-3′,5′-cyclic monophosphate) (VT in 1 of 7 hearts), and the RyR2 blocker dantrolene, either alone (0 of 11) or with 8-CPT (0 of 9) did not then increase VT incidence (P>.05). Both progressively increased pacing rates and programmed extrasystolic (S2) stimuli similarly produced no VT in untreated hearts (n=20 and n=9 respectively). 8-CPT challenge then increased VT incidences (5 of 7 and 4 of 8 hearts respectively; P.05). 8-CPT but not dantrolene, whether alone or combined with 8-CPT, correspondingly increased AP latencies (1.14±0.04 (n=7), 1.04±0.03 (n=10), 1.09±0.05 (n=8) relative to respective control values). In contrast, AP durations, conditions for 2:1 conduction block and ventricular effective refractory periods remained unchanged throughout. We thus demonstrate for the first time that acute RyR2 activation reversibly induces VT in specific association with reduced CV.We thank the Medical Research Council (UK) (CLH), Wellcome Trust (UK) (CLH), British Heart Foundation (UK) (CLH), McVeigh Benefaction (CLH and AG), and Sudden Arrhythmic Death Syndrome (SADS) UK (CLH and AG) for support

Conduction velocities in amphibian skeletal muscle fibres exposed to hyperosmotic extracellular solutions

Early quantitative analyses of conduction velocities in unmyelinated nerve studied in a constantly iso-osmotic volume conductor were extended to an analysis of the effects of varying extracellular osmolarities on conduction velocities of surface membrane action potentials in Rana esculenta skeletal muscle fibres. Previous papers had reported that skeletal muscle fibres exposed to a wide range of extracellular sucrose concentrations resemble perfect osmometers with increased extracellular osmolarity proportionally decreasing fibre volume and therefore diminishing fibre radius, a. However, classical electrolyte theory (Robinson and Stokes 1959, Electrolyte solutions 2nd edn. Butterworth & Co. pp 41–42) would then predict that the consequent increases in intracellular ionic strength would correspondingly decrease sarcoplasmic resistivity, Ri. An extension of the original cable analysis then demonstrated that the latter would precisely offset its expected effect of alterations in a on the fibre axial resistance, ri, and leave action potential conduction velocity constant. In contrast, other reports (Hodgkin and Nakajima J Physiol 221:105–120, 1972) had suggested that Riincreased with extracellular osmolarity, owing to alterations in cytosolic viscosity. This led to a prediction of a decreased conduction velocity. These opposing hypotheses were then tested in muscle fibres subject to just-suprathreshold stimulation at a Vaseline seal at one end and measuring action potentials and their first order derivatives, dV/dt, using 5–20 MΩ, 3 M KCl glass microelectrodes at defined distances away from the stimulus sites. Exposures to hyperosmotic, sucrose-containing, Ringer solutions then reversibly reduced both conduction velocity and maximum values of dV/dt. This was compatible with an increase in Ri in the event that conduction depended upon a discharge of membrane capacitance by propagating local circuit currents through initially passive electrical elements. Conduction velocity then showed graded decreases with increasing extracellular osmolarity from 250–750 mOsm. Action potential waveforms through these osmolarity changes remained similar, including both early surface and the late after-depolarisation events reflecting transverse tubular activation. Quantitative comparisons of reduced-χ 2 values derived from a comparison of these results and the differing predictions from the two hypotheses strongly favoured the hypothesis in which Riincreased rather than decreased with hyperosmolarity

A patient-centred model to quality assure outputs from an echocardiography department: consensus guidance from the British Society of Echocardiography

Background: Quality assurance (QA) of echocardiographic studies is vital to ensure that clinicians can act on findings of high quality to deliver excellent patient care. To date, there is a paucity of published guidance on how to perform this QA. The British Society of Echocardiography (BSE) has previously produced an Echocardiography Quality Framework (EQF) to assist departments with their QA processes. This article expands on the EQF with a structured yet versatile approach on how to analyse echocardiographic departments to ensure high-quality standards are met. In addition, a process is detailed for departments that are seeking to demonstrate to external bodies adherence to a robust QA process. Methods: The EQF consists of four domains. These include assessment of Echo Quality (including study acquisition and report generation); Reproducibility & Consistency (including analysis of individual variability when compared to the group and focused clinical audit), Education & Training (for all providers and service users) and Customer & Staff Satisfaction (of both service users and patients/their carers). Examples of what could be done in each of these areas are presented. Furthermore, evidence of participation in each domain is categorised against a red, amber or green rating: with an amber or green rating signifying that a quantifiable level of engagement in that aspect of QA has been achieved. Conclusion: The proposed EQF is a powerful tool that focuses the limited time available for departmental QA on areas of practice where a change in patient experience or outcome is most likely to occur

Impact of Right Ventricular Dysfunction on Mortality in Patients Hospitalized with COVID-19 according to Race.

Background Epidemiological studies suggest that black, Asian and minority ethnic (BAME) patients may be at risk of worse outcomes from Coronavirus-19 (COVID-19) but the pathophysiological drivers for this association are unknown. This study sought to investigate the relationship between findings on echocardiography, mortality and race in COVID-19 pneumonia. Methods This was a multicenter, retrospective, observational study including 164 adults (61±13years; 78% male; 36% BAME) hospitalized with COVID-19 undergoing echocardiography between March 16 and May 9, 2020 at 3 days (IQR 2 - 5) from admission. The primary outcome was all-cause mortality. Results After a median follow up of 31 days (IQR 14 - 42 days), 58 (35%) patients had died. The right ventricle (RV) was dilated in 62 (38%) patients, and 58 (35%) patients had RV systolic dysfunction. Only 2 (1%) patients had left ventricular (LV) dilatation and 133 (81%) had normal or hyperdynamic LV systolic function. Reduced tricuspid annulus planar systolic excursion was associated with elevated D-dimer (ρ = -0.18, p = 0.025) and high-sensitivity cardiac Troponin (ρ = -0.30, p < 0.0001). Reduced RV systolic function (HR, 1.80; 95% CI, 1.05 - 3.09; p = 0.032) was an independent predictor of all-cause mortality after adjustment for demographic and clinical risk factors. Comparing white and BAME individuals, there were no differences in echocardiography findings, biomarkers or mortality. Conclusions In patients hospitalized with COVID-19 pneumonia, reduced RV systolic function is prevalent and associated with all-cause mortality. There is however, no racial variation in the early findings on echocardiography, biomarkers or mortality

Cangrelor vs. Ticagrelor in Patients Treated with Primary Percutaneous Coronary Intervention: Impact on Platelet Activity, Myocardial Microvascular Function and Infarct Size: A randomized controlled trial

This is an accepted manuscript of an article published by Thieme in Thrombosis and Haemostasis on 26/05/2019, available online: https://doi.org/10.1055/s-0039-1688789 The accepted version of the publication may differ from the final published version.Background Oral P2Y12 inhibitors take more than 2 hours to achieve full effect in healthy subjects and this action is further delayed in patients with acute myocardial infarction. Intravenous P2Y12 inhibition might lead to more timely and potent anti-platelet effect in the context of emergency primary angioplasty, improving myocardial recovery. Objectives This article compares the efficacy of intravenous cangrelor versus ticagrelor in a ST-elevation myocardial infarction (STEMI) population treated with primary percutaneous coronary intervention (PPCI). Materials and Methods In an open-label, prospective, randomized controlled trial, 100 subjects with STEMI were assigned 1:1 to intravenous cangrelor or oral ticagrelor. The co-primary endpoints were platelet P2Y12 inhibition at infarct vessel balloon inflation time, 4 and 24 hours. Secondary endpoints included indices of coronary microcirculatory function: index of microvascular resistance (IMR), initial infarct size (troponin at 24 hours) and final infarct size at 12 weeks (cardiac magnetic resonance). Secondary endpoints included indices of coronary microcirculatory function (index of microvascular resistance [IMR]), initial infarct size (troponin at 24 hours), final infarct size at 12 weeks (cardiac magnetic resonance), corrected thrombolysis in myocardial infarction (TIMI) frame count, TIMI flow grade, myocardial perfusion grade, and ST-segment resolution (ClinicalTrials.gov NCT02733341). Results P2Y12 inhibition at first balloon inflation time was significantly greater in cangrelor-treated patients (cangrelor P2Y12 reaction unit [PRU] 145.2 ± 50.6 vs. ticagrelor 248.3 ± 55.1). There was no difference in mean PRU at 4 and 24 to 36 hours post-dosing. IMR, final infarct size, angiographic and electrocardiographic measures of reperfusion were all similar between groups. Conclusion Cangrelor produces more potent P2Y12 inhibition at the time of first coronary balloon inflation time compared with ticagrelor. Despite this enhanced P2Y12 inhibition, coronary microvascular function and final infarct size did not differ between groups.This work was supported by the South Staffordshire Medical Foundation, the Rotha Abraham Bequest and the Royal Wolverhampton Trust (RE/2015005). This study was sponsored by the Royal Wolverhampton NHS Trust. C.B. and T.F. received funding support from the British Heart Foundation (PG/17/2532884; RE/13/5/30177; RE/18/6134217)