Right Ventricular Dysfunction on Transthoracic Echocardiography and Long-Term Mortality in the Critically Unwell: A Systematic Review and Meta-Analysis.

OBJECTIVE: Right ventricular dysfunction (RVD) is common in the critically ill. To date studies exploring RVD sequelae have had heterogenous definitions and diagnostic methods, with limited follow-up. Additionally much literature has been pathology specific, limiting applicability to the general critically unwell patient. METHOD AND STUDY DESIGN: We conducted a systematic review and meta-analysis to evaluate the impact of RVD diagnosed with transthoracic echocardiography (TTE) on long-term mortality in unselected critically unwell patients compared to those without RVD. A systematic search of EMBASE, Medline and Cochrane was performed from inception to March 2022. All RVD definitions using TTE were included. Patients were those admitted to a critical or intensive care unit, irrespective of disease processes. Long-term mortality was defined as all-cause mortality occurring at least 30 days after hospital admission. A priori subgroup analyses included disease specific and delayed mortality (death after hospital discharge/after the 30th day from hospital admission) in patients with RVD. A random effects model analysis was performed with the Dersimionian and Laird inverse variance method to generate effect estimates. RESULTS: Of 5985 studies, 123 underwent full text review with 16 included (n = 3196). 1258 patients had RVD. 19 unique RVD criteria were identified. The odds ratio (OR) for long term mortality with RVD was 2.92 (95% CI 1.92-4.54, I2 76.4%) compared to no RVD. The direction and extent was similar for cardiac and COVID19 subgroups. Isolated RVD showed an increased risk of delayed mortality when compared to isolated left/biventricular dysfunction (OR 2.01, 95% CI 1.05-3.86, I2 46.8%). CONCLUSION: RVD, irrespective of cause, is associated with increased long term mortality in the critically ill. Future studies should be aimed at understanding the pathophysiological mechanisms by which this occurs. Commonly used echocardiographic definitions of RVD show significant heterogeneity across studies, which contributes to uncertainty within this dataset.

The Effect of Obesity on Echocardiographic Image Quality.

BACKGROUND: Increased body mass index (BMI) may reduce transthoracic echocardiogram (TTE) image quality, resulting in increased requirements for ultrasound enhancing agents (UEA), as recommended by the American Society of Echocardiography (ASE), and a greater incidence of non-diagnostic studies. METHODS: Over a 5-month period 1,108 TTEs were analysed as to (1) whether they could answer the clinical question posed by the ordering physician (i.e. were diagnostic vs non diagnostic), and (2) whether they required UEAs according to the ASE guidelines. Patient characteristics were gathered from the medical record. RESULTS: 12.9% of TTEs were non-diagnostic (21.0% of TTEs in the obese population [BMI≥30 kg/m2] vs 7.8% in the non-obese [p<0.001]). Predictors of a non-diagnostic study were BMI (OR 1.09, [95% CI 1.06-1.11], p<0.0001), male gender (OR 1.54, [1.06-2.25], p=0.02), and inpatient status (OR 1.75, [1.20-2.55], p=0.004). Obesity (BMI≥30) was strongly associated with non-diagnostic studies (OR 3.22, [2.23-4.51], p<0.001). Factors associated with increased requirement of UEAs were BMI (OR 1.10, [1.08-1.12], p<0.0001), age (OR 1.02, [1.01-1.03], p<0.0001) and inpatient status (OR 1.7, [1.29-2.24], p<0.05). Obesity (BMI>30) was strongly associated with contrast requirement (OR 3.16, [2.43-4.10], p<0.0001). CONCLUSIONS: Body mass index, male gender and inpatient status were associated with an increased incidence of non-diagnostic studies. Body mass index, age and inpatient status were associated with an increased requirement for UEAs.

Simultaneous Cardiopulmonary Exercise Testing and Echocardiography for Investigation of Cardiopulmonary Dysfunction in Outpatients: Protocol for a Scoping Review.

BACKGROUND: Cardiopulmonary dysfunction is a complex process with a broad range of etiologies. Investigations performed either at rest or those that only assess the function of a single organ (heart or lungs) are often insufficient. A simultaneous cardiopulmonary exercise test with stress echocardiography is a new approach to assessing cardiopulmonary dysfunction as it provides anatomical and functional imaging simultaneously while under increasing stress. To date, the application of cardiopulmonary exercise test-stress echocardiography (CPET-SE) has been broad and without structure, and its effect on patient outcomes is unclear. OBJECTIVE: The objective of this scoping review is to explore and analyze the evidence regarding the role of simultaneous CPET-SE in investigating cardiopulmonary dysfunction in outpatients. It will include any published study in which adult (older than or equal to 18 years of age) patients have completed a CPET-SE for the investigation of cardiopulmonary dysfunction. METHODS: This review will follow the Arksey and O'Malley framework, supported by the Joanna Briggs Institute methodology for scoping reviews. It will use the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) checklist. Data sources will include MEDLINE, Scopus, Embase, and Cochrane (including reviews, trials, and protocols) electronic databases, with no date range defined. The search will be limited to the English language with no restrictions regarding pathology. Secondary references of the included sources will also be assessed by a hand search for suitability. A 2-person title-abstract screen and data charting process will be used. Independent experts will be used for consultation including an academic librarian and clinicians. The Covidence software will be used for article screening. RESULTS: This scoping review will provide a unified and detailed description of the applications of CPET-SE in investigating cardiopulmonary dysfunction. This will provide a platform for future research harnessing this investigatory method. The results will be presented in both tabular and graphical formats to ensure clarity. The results of this scoping review will be submitted to a relevant peer-reviewed academic journal for publication. CONCLUSIONS: The CPET-SE is a powerful tool for investigating cardiopulmonary dysfunction but remains in its infancy with a patchwork approach to indications, data reporting, and interpretation. This scoping review will unify the literature and provide a platform for future researchers and the development of a comprehensive application guideline. TRIAL REGISTRATION: Open Science Framework; https://osf.io/98r3e. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/52076.

A novel echocardiographic risk score for light-chain amyloidosis.

Aims: The prognosis of light-chain (AL) amyloidosis, a plasma cell dyscrasia, is largely determined by the presence of cardiac involvement. Conventional staging is achieved using cardiac biomarkers (high-sensitivity troponin, N-terminal pro-beta natriuretic peptide) and free light-chain difference (Mayo staging). We sought to evaluate the role of echocardiographic parameters as prognostic markers in AL amyloidosis and examine their utility compared with conventional staging. Methods and results: Seventy-five consecutive patients with AL amyloidosis reviewed at a referral amyloid clinic who underwent comprehensive echocardiographic assessment were retrospectively identified. The evaluated echocardiographic parameters included left ventricular (LV) ejection fraction, mass, diastolic function parameters, global longitudinal strain (GLS), and left atrial (LA) volume. Mortality was assessed through a review of clinical records. During a median follow-up of 51 months, 29/75 (39%) patients died. Patients who died had a larger LA volume (47 ± 12 vs. 35 ± 10 mL/m2, P < 0.001) and a higher E/e' (18 ± 10 vs. 14 ± 6, P = 0.026). Univariate clinical and echocardiographic predictors of survival included LA volume, E/e', e', LVGLS, and Mayo stage (at significance of P < 0.1). Left atrial volume and LVGLS were significant determinants of mortality when examined using clinical cut-offs, although E/e' was not. A composite echocardiographic risk score comprising LA volume and LVGLS provided similar prognostic performance to Mayo stage [area under the curve (AUC) 0.75, 95% confidence interval (CI) 0.64-0.85 vs. AUC 0.75, 95% CI 0.65-0.858, P = 0.91]. Conclusion: Left atrial volume and LVGLS were independent predictors of mortality in AL amyloidosis. A composite echocardiographic score combining LA volume and LVGLS has similar prognostic power to Mayo stage for all-cause mortality.

Alterations in multi-layer strain in AL amyloidosis.

BACKGROUND: Cardiac involvement in AL amyloidosis portends a poor prognosis. 2D-speckle tracking echocardiography (2D-STE) strain can identify subclinical cardiac involvement. This study performed multilayer and multiplanar 2D-STE myocardial strain analysis. METHODS: We compared 75 AL amyloidosis patients to 49 hypertensive patients and 49 healthy controls. Longitudinal strain was obtained from epicardial, mid-myocardial and endocardial layers; segmental strain was measured from mid-myocardial basal, mid and apical segments. RESULTS: Global longitudinal strain was reduced in epicardial (-14.3 ± -4.0% vs. -17.4 ± 2.2% vs. -17.5 ± -2.0%, p < .001), mid-myocardial (-16.3 ± -4.5% vs. -19.7 ± 2.5% vs. -19.7 ± -2.2%, p < .001) and endocardial layers (-18.7 ± -4.9% vs. -22.2 ± 3.0% vs. -22.3 ± -2.6%, p < .001) in amyloid patients compared to hypertensive and healthy controls. Segmental strain confirmed significant reduction in basal (-11.2 ± -3.9% vs. -17.6 ± 2.7% vs. -20.9 ± -3.4%, p < .001) and mid (-14.8 ± -4.3% vs. -19.2 ± 2.5% vs. -19.6 ± -2.2%, p < .001) LV segments in the AL amyloid group. Receiver operating curve analysis demonstrated that an optimal cut-off of -16% for basal segmental strain better differentiated AL amyloid from hypertensive group (sensitivity 96%, specificity 70%, AUC 0.93), compared to relative apical sparing (AUC of 0.85). CONCLUSION: Strain demonstrated myocardial involvement in all layers in AL amyloidosis, with reduced basal segmental longitudinal strain a likely marker of early disease.

Management of Multivessel Disease and Physiology Testing in ST Elevation Myocardial Infarction.

For decades, advances in ST elevation myocardial infarction (STEMI) care have been driven by timely reperfusion of the occluded culprit vessel. More recently, however, the focus has shifted to revascularization of nonculprit vessels in STEMI patients. Five landmark randomized trials, all published in the past 7 years, have highlighted the importance of complete revascularization in STEMI treatment. This review focuses on evidence-based management of STEMI in the setting of multivessel disease, highlighting contemporary data that investigate the impact of complete revascularization.

Cardiotoxic Effect of Modern Anthracycline Dosing on Left Ventricular Ejection Fraction: A Systematic Review and Meta-Analysis of Placebo Arms From Randomized Controlled Trials.

Background Anthracyclines are a key chemotherapeutic agent used against hematological and solid organ malignancies. However, their benefits in cancer survival are limited by cumulative, dose-related cardiotoxicity. The impact of anthracyclines on left ventricular ejection fraction (LVEF), in the era of modern chemotherapy regimens, remains unclear. Methods and Results Three databases (CENTRAL, MEDLINE, and SCOPUS) were systematically searched for randomized trials evaluating cardioprotective agents against placebo, in preventing cardiotoxicity. Echocardiography or magnetic resonance measured LVEF pre- and post-anthracycline-based chemotherapy was abstracted from placebo trial arms. The key terms included "anthracycline," "cardiotoxicity" and "randomized." A doxorubicin equivalent anthracycline dose metric was calculated to compare different anthracyclines. A random-effects model was used to pool mean difference in LVEF after anthracycline. Meta-regressions were calculated to identify variation sources. We included 660 patients from 19 trials. The weighted mean baseline LVEF across studies was 62.6%, and follow-up LVEF assessment was performed at 6 months. The pooled mean decline in LVEF among placebo arms was 5.4% (95% CI, 3.5%-7.3%) with a doxorubicin equivalent anthracycline dose of 385 mg/m2. Meta-regression analysis showed no significant difference in LVEF against doxorubicin equivalent anthracycline dose as continuous (P=0.29) or against published cut-offs for cardiotoxicity (250 mg/m2, P=0.21; 360 mg/m2, P=0.40; and 400 mg/m2, P=0.66). The differences in mean LVEF were not associated with sex, adjunct chemotherapy, or cancer type. Conclusions The magnitude of LVEF impairment post-anthracycline therapy appears less than previously described with modern dosing regimens. This may improve the accuracy of power calculation for future clinical trials assessing the role of cardioprotective therapy.

A Systematic Review of Scaling Left Atrial Size: Are Alternative Indexation Methods Required for an Increasingly Obese Population?

BACKGROUND: Left atrial (LA) size indexed to body surface area (BSA) is a clinically important marker of cardiovascular prognosis. However, indexation using a scaling variable such as BSA has inherent flaws, particularly in an obese population. The aim of this study was to determine whether alternative indexation methods may more accurately scale for LA size. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used to execute a structured search of medical databases, to identify articles discussing alternative methods of LA indexation in echocardiography. Articles that stratified indexed LA size by obesity class were also included. Two independent reviewers identified relevant articles and extracted baseline characteristics, alternative indexation methods, scaling variables, obesity class characteristics, and correlation coefficients. RESULTS: A total of 3,804 articles were found in the database search after removing duplicates. After abstract and full-text screening, 13 relevant articles were identified. Twelve studies used alternative methods of LA indexation, of which nine reported allometric indices. Seven of the included studies reported LA size by obesity class, of which six reported alternative indices. Correlation coefficients plotted for indexed LA size against absolute measured LA size showed that allometric indices (specifically to height) were more likely to maintain proportionality to body size compared with isometric indices such as BSA. Allometric indices were less likely to overcorrect for body size compared with isometric indices. CONCLUSIONS: Compared with isometric indexation to BSA, allometric indexation (specifically to height) improves scaling of LA volumes to maintain proportionality and avoid overcorrection for body size.