Cardiovascular Magnetic Resonance Imaging in Familial Dilated Cardiomyopathy

Dilated cardiomyopathy (DCM) is a common cause of non-ischaemic heart failure, conferring high morbidity and mortality, including sudden cardiac death due to systolic dysfunction or arrhythmic sudden death. Within the DCM cohort exists a group of patients with familial disease. In this article we review the pathophysiology and cardiac imaging findings of familial DCM, with specific attention to known disease subtypes. The role of advanced cardiac imaging cardiovascular magnetic resonance is still accumulating, and there remains much to be elucidated. We discuss its potential clinical roles as currently known, with respect to diagnostic utility and risk stratification. Advances in such risk stratification may help target pharmacological and device therapies to those at highest risk

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

Empirical correlation of triggered activity and spatial and temporal re-entrant substrates with arrhythmogenicity in a murine model for Jervell and Lange-Nielsen syndrome

KCNE1 encodes the β-subunit of the slow component of the delayed rectifier K+ current. The Jervell and Lange-Nielsen syndrome is characterized by sensorineural deafness, prolonged QT intervals, and ventricular arrhythmogenicity. Loss-of-function mutations in KCNE1 are implicated in the JLN2 subtype. We recorded left ventricular epicardial and endocardial monophasic action potentials (MAPs) in intact, Langendorff-perfused mouse hearts. KCNE1−/− but not wild-type (WT) hearts showed not only triggered activity and spontaneous ventricular tachycardia (VT), but also VT provoked by programmed electrical stimulation. The presence or absence of VT was related to the following set of criteria for re-entrant excitation for the first time in KCNE1−/− hearts: Quantification of APD90, the MAP duration at 90% repolarization, demonstrated alterations in (1) the difference, ∆APD90, between endocardial and epicardial APD90 and (2) critical intervals for local re-excitation, given by differences between APD90 and ventricular effective refractory period, reflecting spatial re-entrant substrate. Temporal re-entrant substrate was reflected in (3) increased APD90 alternans, through a range of pacing rates, and (4) steeper epicardial and endocardial APD90 restitution curves determined with a dynamic pacing protocol. (5) Nicorandil (20 µM) rescued spontaneous and provoked arrhythmogenic phenomena in KCNE1−/− hearts. WTs remained nonarrhythmogenic. Nicorandil correspondingly restored parameters representing re-entrant criteria in KCNE1−/− hearts toward values found in untreated WTs. It shifted such values in WT hearts in similar directions. Together, these findings directly implicate triggered electrical activity and spatial and temporal re-entrant mechanisms in the arrhythmogenesis observed in KCNE1−/− hearts

Acute atrial arrhythmogenicity and altered Ca(2+) homeostasis in murine RyR2-P2328S hearts.

AIMS: The experiments explored for atrial arrhythmogenesis and its possible physiological background in recently developed hetero-(RyR2(+/S)) and homozygotic (RyR2(S/S)) RyR2-P2328S murine models for catecholaminergic polymorphic ventricular tachycardia (VT) for the first time. They complement previous clinical and experimental reports describing increased ventricular arrhythmic tendencies associated with physical activity, stress, or catecholamine infusion, potentially leading to VT and ventricular fibrillation. METHODS AND RESULTS: Atrial arrhythmogenic properties were compared at the whole animal, Langendorff-perfused heart, and single, isolated atrial myocyte levels using electrophysiological and confocal fluorescence microscopy methods. This demonstrated that: (i) electrocardiographic parameters in intact anaesthetized wild-type (WT), RyR2(+/S) and RyR2(S/S) mice were statistically indistinguishable both before and after addition of isoproterenol apart from increases in heart rates. (ii) Bipolar electrogram and monophasic action potential recordings showed significantly higher incidences of arrhythmogenesis in isolated perfused RyR2(S/S), but not RyR2(+/S), relative to WT hearts during either regular pacing or programmed electrical stimulation. The addition of isoproterenol increased such incidences in all three groups. (iii) However, there were no accompanying differences in cardiac anatomy or action potential durations at 90% repolarization and refractory periods. (iv) In contrast, episodes of diastolic Ca(2+) release were observed under confocal microscopy in isolated fluo-3-loaded RyR2(S/S), but not RyR2(+/S) or WT, atrial myocytes. The introduction of isoproterenol resulted in significant diastolic Ca(2+) release in all three groups. CONCLUSIONS: These findings establish acute atrial arrhythmogenic properties in RyR2-P2328S hearts and correlate these with altered Ca(2+) homeostasis in an absence of repolarization abnormalities for the first time

Acute atrial arrhythmogenicity and altered Ca(2+) homeostasis in murine RyR2-P2328S hearts.

AIMS: The experiments explored for atrial arrhythmogenesis and its possible physiological background in recently developed hetero-(RyR2(+/S)) and homozygotic (RyR2(S/S)) RyR2-P2328S murine models for catecholaminergic polymorphic ventricular tachycardia (VT) for the first time. They complement previous clinical and experimental reports describing increased ventricular arrhythmic tendencies associated with physical activity, stress, or catecholamine infusion, potentially leading to VT and ventricular fibrillation. METHODS AND RESULTS: Atrial arrhythmogenic properties were compared at the whole animal, Langendorff-perfused heart, and single, isolated atrial myocyte levels using electrophysiological and confocal fluorescence microscopy methods. This demonstrated that: (i) electrocardiographic parameters in intact anaesthetized wild-type (WT), RyR2(+/S) and RyR2(S/S) mice were statistically indistinguishable both before and after addition of isoproterenol apart from increases in heart rates. (ii) Bipolar electrogram and monophasic action potential recordings showed significantly higher incidences of arrhythmogenesis in isolated perfused RyR2(S/S), but not RyR2(+/S), relative to WT hearts during either regular pacing or programmed electrical stimulation. The addition of isoproterenol increased such incidences in all three groups. (iii) However, there were no accompanying differences in cardiac anatomy or action potential durations at 90% repolarization and refractory periods. (iv) In contrast, episodes of diastolic Ca(2+) release were observed under confocal microscopy in isolated fluo-3-loaded RyR2(S/S), but not RyR2(+/S) or WT, atrial myocytes. The introduction of isoproterenol resulted in significant diastolic Ca(2+) release in all three groups. CONCLUSIONS: These findings establish acute atrial arrhythmogenic properties in RyR2-P2328S hearts and correlate these with altered Ca(2+) homeostasis in an absence of repolarization abnormalities for the first time

A longitudinal study of mitral regurgitation detected after acute myocardial infarction

Background: Mitral regurgitation (MR) is common following myocardial infarction (MI). However, the subsequent trajectory of MR, and its impact on long-term outcomes are not well understood. This study aimed to examine the change in MR severity and associated clinical outcomes following MI. Methods: Records of patients admitted to a single centre between 2016 and 2017 with acute MI treated by percutaneous coronary intervention (PCI) were retrospectively examined. Results: 294/1000 consecutive patients had MR on baseline (pre-discharge) transthoracic echocardiography (TTE), of whom 126 (mean age: 70.9 ± 11.4 years) had at least one follow-up TTE. At baseline, most patients had mild MR (n = 94; 75%), with n = 30 (24%) moderate and n = 2 (2%) severe MR. Significant improvement in MR was observed at the first follow-up TTE (median 9 months from baseline; interquartile range: 3–23), with 36% having reduced severity, compared to 10% having increased MR severity (p < 0.001). Predictors of worsening MR included older age (mean: 75.2 vs. 66.7 years; p = 0.003) and lower creatinine clearance (mean: 60 vs. 81 mL/min, p = 0.015). Change in MR severity was significantly associated with prognosis: 16% with improving MR reached the composite endpoint of death or heart failure hospitalisation at 5 years, versus 44% (p = 0.004) with no change, and 59% (p < 0.001) with worsening MR. Conclusions: Of patients with follow-up TTE after MI, MR severity improved from baseline in approximately one-third, was stable in around half, with the remainder having worsening MR. Patients with persistent or worsening MR had worse clinical outcomes than those with improving MR