Right Ventricular Function in Arrhythmogenic Right Ventricular Cardiomyopathy: Potential Value of Strain Echocardiography.

Arrhythmogenic right ventricular cardiomyopathy is an inherited cardiomyopathy, characterized by abnormal cell adhesions, disrupted intercellular signaling, and fibrofatty replacement of the myocardium. These changes serve as a substrate for ventricular arrhythmias, placing patients at risk of sudden cardiac death, even in the early stages of the disease. Current echocardiographic criteria for diagnosing arrhythmogenic right ventricular cardiomyopathy lack sensitivity, but novel markers of cardiac deformation are not subject to the same technical limitations as current guideline-recommended measures. Measuring cardiac deformation using speckle tracking allows for meticulous quantification of global systolic function, regional function, and dyssynchronous contraction. Consequently, speckle tracking to quantify myocardial strain could potentially be useful in the diagnostic process for the determination of disease progression and to assist risk stratification for ventricular arrhythmias and sudden cardiac death. This narrative review provides an overview of the potential use of different myocardial right ventricular strain measures for characterizing right ventricular dysfunction in arrhythmogenic right ventricular cardiomyopathy and its utility in assessing the risk of ventricular arrhythmias.

Ratio of early transmitral inflow velocity to early diastolic strain rate predicts atrial fibrillation following acute myocardial infarction.

The ratio of early transmitral filling velocity to early diastolic strain rate (E/SRe) has been proposed as a new non-invasive measurement of left ventricular filling pressure. We aimed to investigate the ability of E/SRe to predict atrial fibrillation (AF) after ST-elevation myocardial infarction (STEMI). This was a prospective cohort study of patients (n = 369) with STEMI. Patients underwent an echocardiographic examination a median of two days after pPCI. By echocardiography, transmitral early filling velocity (E) was measured by pulsed-wave Doppler, and early diastolic strain rate (SRe) was measured by speckle tracking of the left ventricle. E was indexed to SRe and the early myocardial relaxation velocity (e') to obtain the E/SRe and E/e', respectively. The endpoint was new-onset AF. During follow-up (median 5.6 years, IQR: 5.0-6.1 years), 23 (6%) of the 369 patients developed AF. In unadjusted analyses, both E/SRe and E/e' were significantly associated with AF [E/SRe: HR = 1.06; (1.03-1.10); p < 0.001, per 10 increase] and [E/e': HR = 1.11 (1.05-1.17); p < 0.001, per 1 increase] and had equal Harrell's C-statistic of 0.71. However, only E/SRe remained an independent predictor after multivariable adjustments for clinical and echocardiographic parameters [E/SRe: HR = 1.06 (1.00-1.11); p = 0.044, per 10 increase]. E/SRe was further significantly associated with AF in patients with E/e' < 14 HR = 1.09 (1.01-1.17); p = 0.030, per 10 increase), also after multivariable adjustments. E/SRe is an independent predictor of AF in STEMI patients, even in subjects with seemingly normal filling pressure.

Strain Imaging and Ventricular Arrhythmia.

Ventricular arrhythmia is one of the main causes of sudden cardiac death. Hence, identifying patients at risk of ventricular arrhythmias and sudden cardiac death is important but can be challenging. The indication for an implantable cardioverter defibrillator as a primary preventive strategy relies on the left ventricular ejection fraction as a measure of systolic function. However, ejection fraction is flawed by technical constraints and is an indirect measure of systolic function. There has, therefore, been an incentive to identify other markers to optimize the risk prediction of malignant arrhythmias to select proper candidates who could benefit from an implantable cardioverter defibrillator. Speckle-tracking echocardiography allows for a detailed assessment of cardiac mechanics, and strain imaging has repeatedly been shown to be a sensitive technique to identify systolic dysfunction unrecognized by ejection fraction. Several strain measures, including global longitudinal strain, regional strain, and mechanical dispersion, have consequently been proposed as potential markers of ventricular arrhythmias. In this review, we will provide an overview of the potential use of different strain measures in the context of ventricular arrhythmias.

Impact of echocardiographic analyses of valvular event timing on myocardial work indices.

AIMS: Valvular event timing is an integral part of echocardiographic pressure-strain loop (PSL) analyses. The impact that different event timing modalities may have on myocardial work indices is unknown. METHODS AND RESULTS: A methodological study was performed on 200 subjects, including 50 healthy subjects, 50 with aortic valve sclerosis, 50 with atrial fibrillation, and 50 with reduced left ventricular ejection fraction. Valvular event timing was estimated by visual assessment, spectral Doppler, and colour tissue Doppler imaging (TDI) M-mode. These valvular event timings were added to the same PSL analyses sequentially to acquire myocardial work indices, including global work index (GWI). For the 200 participants, the median age was 72 years, 50% were men, and mean blood pressure was 143/80 mmHg. Valvular event timings differed between all three modalities and so did all myocardial work indices. Compared with visual assessment, spectral Doppler resulted in a significantly higher GWI (mean difference: 114 ± 93 mmHg%, P < 0.001), and so did TDI (mean difference: 83 ± 90 mmHg%, P < 0.001). A higher GWI by spectral Doppler than by TDI was also observed (mean difference: 30 ± 53 mmHg%, P < 0.001). In the healthy subgroup, a systematic bias was observed for spectral Doppler compared with visual assessment (mean difference: 160 ± 77 mmHg%, P < 0.001), and a similar trend was noted for TDI vs. visual assessment (mean difference: 124 ± 74 mmHg%, P < 0.001). CONCLUSION: Myocardial work indices differ depending on the event timing modality used, with visual assessment yielding lower GWI values compared with Doppler-based methods. Serial PSL analyses should apply the same event timing method.

Accuracy, analysis time, and reproducibility of dedicated 4D echocardiographic left atrial volume quantification software.

Four-dimensional (4D) echocardiography may provide more accurate estimations of left atrial (LA) volumes than 2-dimensional (2D) measures. We sought to compare the concordance of a novel 4D LA quantification software versus 2D echocardiography against cardiac magnetic resonance (CMR). This was a multimodality imaging substudy of a randomized clinical trial (the LOOP study). Elderly participants with stroke risk factors were included. A subgroup of this study population underwent transthoracic echocardiography (n = 1441) and a subset underwent CMR within two weeks (n = 73). The mean age of the echocardiographic study population was 74 years and 54% were men. The maximal LA volume (LAVmax) was 47 mL by 2D, 52 mL by 4D, and 104 mL by CMR. While 2D echocardiography showed a moderate correlation with 4D (R2 = 0.51) it yielded significantly lower values for LAVmax with a mean difference of 4.5 ± 11.9 mL, p < 0.001. 4D echocardiography correlated strongly with CMR measurements (R2 = 0.70), whereas 2D echocardiography showed a moderate correlation (R2 = 0.53). However, both modalities systematically underestimated LAVmax largely compared to CMR (2D vs. CMR: - 54.9 ± 21.3 mL; 4D vs. CMR: - 49.7 ± 18.6 mL). Similar observations were made for minimal LA volume and LA volume before atrial contraction. Analyses time by 4D was shorter than for 2D (90 ± 11 vs. 118 ± 16 s, p < 0.001). Intra- and interobserver variability was lower for 4D than 2D. Four-dimensional echocardiography is faster, more reproducible, and correlates more closely to CMR than 2D echocardiography. Both 4D and 2D echocardiography systematically underestimates LA volumes compared to CMR, emphasizing that values of LA volumes are not interchangeable between echocardiography and CMR.

Association between four-dimensional echocardiographic left atrial measures and left atrial fibrosis assessed by left atrial late gadolinium enhancement.

AIMS: Left atrial (LA) fibrosis is a hallmark of atrial cardiomyopathy, and non-invasive surrogate measures of LA fibrosis are therefore needed. We investigated the association between four-dimensional (4D) echocardiographic LA measures and LA fibrosis. METHODS AND RESULTS: A multimodality imaging substudy was performed in a randomized clinical trial (LOOP study), recruiting elderly participants with cardiovascular risk factors. LA late gadolinium enhancement (LGE) by cardiac magnetic resonance imaging was used as a surrogate for LA fibrosis. 4D echocardiographic LA quantification was used to measure maximal and minimal LA volume (LAVmax and LAVmin, respectively), LA emptying fractions (LAEFtotal), and strain. Logistic regression was used to relate LA measures to high LA LGE (≥17 cm2). Of the 44 participants (mean age 76 years, 64% men, median LA LGE 13.1 cm2), 14 exhibited high LA LGE. These participants exhibited abnormalities in several LA functional measures but not LAVmax. In linear regressions, only increasing LAVmin, and decreasing LAEFtotal, and reservoir strain were associated with increasing LA LGE. Furthermore, increasing LAVmin was associated with a higher likelihood of high LA LGE [odds ratio (OR) = 1.19 (1.04-1.37)]. Decreasing LAEFtotal and reservoir strain were also associated with higher likelihood of LA LGE [OR = 1.18 (1.05-1.33)] and OR = 1.15 (1.02-1.30), per 1% decrease in LAEFtotal and reservoir strain, respectively]. These findings were consistent after multivariable adjustments. LAEFtotal provided the highest performance for detecting high LA LGE (area under the curve of 0.78). CONCLUSION: LAVmin, LAEFtotal, and reservoir strain measured by 4D echocardiography are significantly associated with LA LGE. LAEFtotal provides the best performance for detecting high LA LGE.

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia: The COVID STEROID randomised, placebo-controlled trial.

BACKGROUND: In the early phase of the pandemic, some guidelines recommended the use of corticosteroids for critically ill patients with COVID-19, whereas others recommended against the use despite lack of firm evidence of either benefit or harm. In the COVID STEROID trial, we aimed to assess the effects of low-dose hydrocortisone on patient-centred outcomes in adults with COVID-19 and severe hypoxia. METHODS: In this multicentre, parallel-group, placebo-controlled, blinded, centrally randomised, stratified clinical trial, we randomly assigned adults with confirmed COVID-19 and severe hypoxia (use of mechanical ventilation or supplementary oxygen with a flow of at least 10 L/min) to either hydrocortisone (200 mg/d) vs a matching placebo for 7 days or until hospital discharge. The primary outcome was the number of days alive without life support at day 28 after randomisation. RESULTS: The trial was terminated early when 30 out of 1000 participants had been enrolled because of external evidence indicating benefit from corticosteroids in severe COVID-19. At day 28, the median number of days alive without life support in the hydrocortisone vs placebo group were 7 vs 10 (adjusted mean difference: -1.1 days, 95% CI -9.5 to 7.3, P = .79); mortality was 6/16 vs 2/14; and the number of serious adverse reactions 1/16 vs 0/14. CONCLUSIONS: In this trial of adults with COVID-19 and severe hypoxia, we were unable to provide precise estimates of the benefits and harms of hydrocortisone as compared with placebo as only 3% of the planned sample size were enrolled. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04348305. European Union Drug Regulation Authorities Clinical Trials (EudraCT) Database: 2020-001395-15.