Echocardiographic parameters of cardiac structure and function in the diagnosis of acute myocarditis in adult patients: A systematic review and meta-analysis.

BACKGROUND: Transthoracic echocardiography (TTE) plays a key role in the initial work-up of myocarditis where the identification of pathologic structural and functional changes may assist in its diagnosis and management. The aim of this systematic review was to appraise the evidence for the utility of echocardiographic parameters of cardiac structure and function in the diagnosis of myocarditis in adult populations. METHODS: A systematic literature search of medical databases was performed using PRISMA principles to identify all relevant studies assessing TTE parameters in adult patients with myocarditis (1995-2020; English only; PROSPERO registration CRD42021243598). Data for a range of structural and functional TTE parameters were individually extracted and those with low heterogeneity were then meta-analyzed using a random-effects model for effect size, and assessed through standardized mean difference (SMD). RESULTS: Available data from six studies (with a pooled total of 269 myocarditis patients and 240 controls) revealed that myocarditis can be reliably differentiated from healthy controls using echocardiographic measures of left ventricular (LV) size and systolic function, in particular LV end-diastolic diameter, LV ejection fraction (LVEF) and LV global longitudinal strain (LV-GLS) (p ≤ .01 for all). LV-GLS demonstrated the highest overall effect size, followed by LVEF and LVEDD (SMD: |0.46-1.98|). Two studies also demonstrated that impairment in LV-GLS was associated with adverse cardiovascular outcomes in this population, irrespective of LVEF. CONCLUSIONS: LV-GLS demonstrated the greatest overall effect size and therefore ability to differentiate myocarditis populations from healthy controls. GLS was also shown to be a predictor of adverse cardiovascular outcomes, in this population. HIGHTLIGHTS: What is already known on this subject? Myocarditis is a disease process that is often a diagnosis of exclusion, as it frequently mimics other acute cardiac pathologies. Transthoracic echocardiography is traditionally the initial imaging modality used for noninvasive structural assessment in populations with myocarditis. What might this study add? This study demonstrates that left ventricular (LV) global longitudinal strain, LV ejection fraction and LV end-diastolic diameter can differentiate between myocarditis patients and healthy controls. LV-GLS demonstrated the greatest overall effect size when comparing these two populations, in comparison to the other measures. How might this impact on clinical practice? This study demonstrates that assessment of myocardial deformation indices allows for sensitive discrimination between myocarditis patients from healthy controls. Routine assessment of LV-GLS may serve as an important diagnostic tool in the acute care setting.

Characterization of Subclinical Cardiac Dysfunction by Speckle Tracking Echocardiography in Patients With Non-severe Acute-Phase Myocarditis.

Subclinical changes in left ventricular (LV) function have been demonstrated in patients with acute-phase myocarditis (AM) despite normal LV ejection fraction. The impact of AM on right ventricular (RV) and left atrial (LA) function has not been well described. This study aimed to assess for subclinical chamber dysfunction by speckle tracking echocardiography and its clinical relevance in this population. Patients with a diagnosis of AM (as per the European Society of Cardiology Working Group on Myocardial and Pericardial Diseases) admitted to our institution from 2013 to 2018 were assessed. Patients with elevated serum troponin, normal coronary assessment, and normal LV ejection fraction on transthoracic echocardiogram were included. Clinical and echocardiographic parameters were compared with healthy age-, gender- and risk-factor matched controls. Global longitudinal strain assessed through speckle tracking echocardiography was performed using vendor independent software (v4.6; TomTec Arena, Munich, Germany). The final cohort consisted of 80 patients (40 AM patients and 40 controls). No significant differences in baseline clinical characteristics were observed between groups. Of the echocardiographic parameters, AM patients had lower LV-global longitudinal strain (p <0.01), lower RV free-wall strain (p = 0.02) and lower peak LA strain (p <0.01). There were no differences in traditional echocardiographic measures of LV, RV, and LA function appreciated between groups. The presence of multichamber involvement was associated with peak Troponin levels (p <0.01). In conclusion, our study demonstrates the presence of global subclinical myocardial dysfunction in patients with AM. Additionally, the presence of multichamber involvement was significantly associated with degree of myocardial necrosis.

Public attitudes towards automated external defibrillators: results of a survey in the Australian general population.

Background: Swift defibrillation by lay responders using automated external defibrillators (AEDs) increases survival in out-of-hospital cardiac arrest (OHCA). This study evaluated newly designed yellow-red vs. commonly used green-white signage for AEDs and cabinets and assessed public attitudes to using AEDs during OHCA. Methods: New yellow-red signage was designed to enable easy identification of AEDs and cabinets. A prospective, cross-sectional study of the Australian public was conducted using an electronic, anonymised questionnaire between November 2021 and June 2022. The validated net promoter score investigated public engagement with the signage. Likert scales and binary comparisons evaluated preference, comfort and likelihood of using AEDs for OHCA. Results: The yellow-red signage for AED and cabinet was preferred by 73.0% and 88%, respectively, over the green-white counterparts. Only 32% were uncomfortable with using AEDs, and only 19% indicated a low likelihood of using AEDs in OHCA. Conclusion: The majority of the Australian public surveyed preferred yellow-red over green-white signage for AED and cabinet and indicated comfort and likelihood of using AEDs in OHCA. Steps are necessary to standardise yellow-red signage of AED and cabinet and enable widespread availability of AEDs for public access defibrillation.

Incidence of immune checkpoint inhibitor mediated cardiovascular toxicity: A systematic review and meta-analysis.

BACKGROUND: Immune checkpoint inhibitors (ICI) are a novel class of anti-cancer therapy becoming increasingly associated with fatal cardiovascular toxicities (CVTs). The aim is to determine the incidence of CVTs in cohorts treated with ICIs as sole anti-cancer therapy. METHODS: A systematic literature search of scientific and medical databases was performed using PRISMA principles to identify relevant cohorts (PROSPERO registration CRD42021272470). Data for specific CVTs (pericardial disease, myocarditis, heart failure, arrhythmia, myocardial infarction/ischaemia and angina), CVT-related death and CV risk factors were extracted. Presence of CVTs in ICI-monotherapy versus combination-ICI therapy, and programmed death 1/programmed death ligand 1- (PD1/PDL1-) versus cytotoxic T-lymphocyte-associated protein 4- (CTLA4-) inhibitor groups were dichotomised and meta-analysed using random-effect models. RESULTS: Forty-eight studies (11,207 patients) were identified, from which 146 CVTs were observed (incidence 1.30%). ICI-monotherapy led to more CVTs than combination therapy (119/9009; 1.32% vs. 18/2086; 0.86%). Across monotherapies, PD1/PDL1-inhibitors had lower incidence of CVTs compared to CTLA4-inhibitors (62/6950; 0.89% vs. 57/2059; 2.77%). Based on eight studies that were meta-analysed, no significant difference was observed comparing monotherapy versus combination-ICI therapy (RR-0.69, 95% CI -1.47 to 0.09) for all CVTs, or PD1/PDL1- to CTLA4-inhibitors (RR-0.27, 95% CI -2.06 to 1.53), for all CVTs including CVT-death. CV risk factors could not be attributed to an ICI group as data was population based rather than individual based. CONCLUSION: ICI-mediated CVTs are rare and potentially fatal. The role of CV risk factors in their development remains unclear.

The utility of cardiac magnetic resonance imaging in the diagnosis of adult patients with acute myocarditis: a systematic review and meta-analysis.

BACKGROUND: The presence of myocardial late gadolinium enhancement (LGE) indicates myocyte necrosis, and assists with the diagnosis of acute myocarditis (AM). Cardiac magnetic resonance (CMR) measures other than LGE i.e. tissue characterization and myocardial structural and functional parameters, play an important diagnostic role in assessment for inflammation, as seen in AM. The aim of this systematic review was to appraise the evidence for the use of quantitative CMR measures to identify myocardial inflammation in order to diagnose AM in adult patients. METHODS: A systematic literature search of medical databases was performed using PRISMA principles to identify relevant CMR studies on AM in adults (2005-2020; English; PROSPERO registration CRD42020180605). Data for a range of quantitative CMR measures were extracted. Continuous variables with low heterogeneity were meta-analyzed using a random-effects model for overall effect size measured as the standard mean difference (SMD). RESULTS: Available data from 25 studies reporting continuous quantitative 1.5-T CMR measures revealed that AM is most reliably differentiated from healthy controls using T1 mapping (SMD 1.80, p<0.01) and T2 mapping (SMD 1.63, p<0.01), respectively. All other measures examined including T2-weighted ratio, extracellular volume, early gadolinium enhancement ratio, right ventricular ejection fraction, and LV end-diastolic volume, mass, ejection fraction, longitudinal strain, circumferential strain, and radial strain also had discriminatory ability although with smaller standard mean difference values (|SMD| 0.32-0.96, p < 0.01 for all). CONCLUSIONS: Meta-analysis shows that myocardial tissue characterization (T1 mapping>T2 mapping) followed by measures of left ventricular structure and function demonstrate diagnostic discriminatory ability in AM.

Does vascular endothelial dysfunction play a role in physical frailty and sarcopenia? A systematic review.

BACKGROUND: Frailty is strongly associated with adverse cardiovascular outcomes; however, the underlying pathophysiological processes are largely unknown. Vascular endothelial dysfunction (VED) is the earliest stage of cardiovascular disease (CVD) progression and predicts long-term CVD outcomes. Both these conditions share an elevated inflammatory state as a common pathological factor. OBJECTIVE: Systematic literature review was conducted to examine the evidence supporting an association between VED and physical frailty and/or sarcopenia, in electronic databases including Scopus, Ovid Medline, CINAHL, ScienceDirect, ProQuest Health & Medicine and Embase from January 1980 to August 2019. RESULTS: A total of 18 studies met the inclusion criteria. VED is independently associated with increased frailty phenotypes and measures of sarcopenia. Several markers of VED, including higher levels of asymmetric dimethylarginine, abnormal ankle brachial index, pulse wave velocity, pulse pressure and lower levels of flow-mediated dilatation, peripheral blood flow and endothelial progenitor cell counts, have been associated with frailty/sarcopenia measurements. Some studies demonstrated the effect of inflammation on the association. CONCLUSIONS: Recent studies, although limited, showed that VED could be one of the underlying mechanisms of frailty. It is entirely possible that inflammation-related pathological changes in the vascular endothelium are involved in the early causative mechanisms in physical frailty. The exact mechanism(s) underlying this association are still unclear and will need to be evaluated. The outcomes of these future research studies could potentially inform early preventative strategies for physical frailty and sarcopenia.

Vascular endothelial dysfunction may be an early predictor of physical frailty and sarcopenia: A meta-analysis of available data from observational studies.

BACKGROUND: Physical frailty and sarcopenia (PF & S) are major public health problems in the older population and promising predictors of adverse cardiovascular outcomes. However, the underlying mechanisms linking physical frailty, sarcopenia and adverse cardiovascular outcomes are not well defined. We recently published a systematic review which highlighted early-stage vascular endothelial dysfunction (VED) as one of the potential underlying mechanisms of physical frailty and the role of inflammation in modulating this association. OBJECTIVE AND METHOD: A meta-analysis was performed to estimate the pooled effect size of studies examining the relationship between VED and PF & S. RESULTS: Out of 18 cross-sectional studies selected for the original review, 13 studies were excluded due to lack of available data for pooled analysis. The five remaining studies had a total of 6616 participants, of which the pooled sample size of the frail or sarcopenic cohort was 607 and robust or pre-frail or non-sarcopenic cohort was 6009. Mean age of the participants ranging from 64 to 80 years or over. In this analysis, high heterogeneity was observed among studies (99.35% of the variation between studies was due to heterogeneity). Parameters used to assess both PF & S and VED were very different across the studies. CONCLUSION: The absence of a standardized and valid operational definition of frailty and sarcopenia is a principal limiting factors for frailty research and this is clearly reflected in our study findings. This limits the ability to interpret and define the effects of vascular endothelial dysfunction on these different parameters of frailty and sarcopenia. Similarly, assessment of vascular endothelial dysfunction was very heterogeneous with different parameters utilized across these studies.

Incidence and treatment of arrhythmias secondary to coronavirus infection in humans: A systematic review.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide resulting in significant morbidity and mortality. Arrhythmias are prevalent and reportedly, the second most common complication. Several mechanistic pathways are proposed to explain the pro-arrhythmic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. A number of treatment approaches have been trialled, each with its inherent unique challenges. This rapid systematic review aimed to examine the current incidence and available treatment of arrhythmias in COVID-19, as well as barriers to implementation. METHODS: Our search of scientific databases identified relevant published studies from 1 January 2000 until 1 June 2020. We also searched Google Scholar for grey literature. We identified 1729 publications of which 1704 were excluded. RESULTS: The incidence and nature of arrhythmias in the setting of COVID-19 were poorly documented across studies. The cumulative incidence of arrhythmia across studies of hospitalised patients was 6.9%. Drug-induced long QT syndrome secondary to antimalarial and antimicrobial therapy was a significant contributor to arrhythmia formation, with an incidence of 14.15%. Torsades de pointes (TdP) and sudden cardiac death (SCD) were reported. Treatment strategies aim to minimise this through risk stratification and regular monitoring of corrected QT interval (QTc). CONCLUSION: Patients with SARS-CoV-2 are at an increased risk of arrhythmias. Drug therapy is pro-arrhythmogenic and may result in TdP and SCD in these patients. Risk assessment and regular QTc monitoring are imperative for safety during the treatment course. Further studies are needed to guide future decision-making.

Buddhist meditation for vascular function: A narrative review.

BACKGROUND: High blood pressure represents an important risk factor for diseases related to cardiovascular system and is directly associated with high oxidative stress, inflammation and vascular endothelial dysfunction. Recently, there is promising data available to suggest that meditation-based low-cost and low-risk lifestyle modification strategies may provide beneficial effects on chronic inflammation, oxidative stress and maintenance of blood pressure, both in young and older adults. This review aims to summarize the evidence regarding the effectiveness of Buddhist meditation for vascular endothelial function and blood pressure. METHOD: A search was conducted using Ovid MEDLINE, Scopus, CINAHL and PsycINFO for articles published from 1990 to 2018. RESULTS: Relevant articles (n = 407) were reviewed and 5 met selection criteria. Several lines of studies have provided compelling data showing that Buddhist meditation approach was effective in improving inflammation and vascular function (endothelial vasodilation and arterial stiffness) in both young and elderly cohorts. Particularly, Buddhist meditation approach has shown to be effective in reducing plasma inflammatory markers, increasing nitric oxide concentration and improving vascular endothelial function and glycemic control, which in turn can be favorable factors for demonstrated positive effects of Buddhist meditation on blood pressure and vascular function. CONCLUSION: This paper presents brief overview of clinical outcomes of complementary therapeutic approach of Buddhist meditation in vascular function. In future, well-structured systematic reviews are essential to report specificity of Buddhist mindfulness-based approach on vascular function, blood pressure and other cardiovascular risk factors.

Vitamin D supplementation lowers thrombospondin-1 levels and blood pressure in healthy adults.

INTRODUCTION: Vitamin D insufficiency, defined as 25-hydroxyvitamin D (25(OH)D) levels < 75nmol/L is associated with cardio-metabolic dysfunction. Vitamin D insufficiency is associated with inflammation and fibrosis, but it remains uncertain whether these anomalies are readily reversible. Therefore, we aimed to determine the effects of vitamin D supplementation on markers of: 1) nitric oxide (NO) signaling, 2) inflammation, and 3) fibrosis, in healthy volunteers with mild hypovitaminosis. METHODS: Healthy volunteers (n = 35) (mean age: 45 ± 11 years) with 25(OH)D levels <75nmol/L, received vitamin D supplementation (Ostelin ® capsules 2000IU) for 12 weeks. Resting systolic and diastolic blood pressures (BP) were assessed. Routine biochemistry was examined. Plasma concentrations of asymmetric dimethylarginine (ADMA), thrombospondin-1 (TSP-1), plasminogen activator inhibitor-1 (PAI-1), hs-CRP, activin-A, and follistatin-like 3 (FSTL3) were quantitated. RESULTS: Vitamin D administration for 12 weeks significantly increased 25-(OH)D levels (48.8 ± 16 nmol/L to 100.8 ± 23.7 nmol/L, p<0.001). There was significant lowering of systolic and diastolic BP, while there was no significant change in lipid profiles, or fasting insulin. Plasma concentrations of ADMA, hs-CRP, PAI-1, activin A, and FSTL-3 did not change with vitamin D supplementation. However, there was a marked reduction of TSP-1 (522.7 ± 379.8 ng/mL vs 206.7 ± 204.5 ng/mL, p<0.001). CONCLUSIONS: Vitamin D supplementation in vitamin D insufficient, but otherwise healthy individuals markedly decreased TSP-1 levels and blood pressure. Since TSP-1 suppresses signaling of NO, it is possible that the fall in BP is engendered by restoration of NO effect.

Suppression of neutrophil superoxide generation by BNP is attenuated in acute heart failure: a case for 'BNP resistance'.

AIMS: The release of the B-type natriuretic peptide (BNP) is increased in heart failure (HF), a condition associated with oxidative stress. BNP is known to exert anti-inflammatory effects including suppression of neutrophil superoxide (O2(-)) release. However, BNP-based restoration of homeostasis in HF is inadequate, and the equivocal clinical benefit of a recombinant BNP, nesiritide, raises the possibility of attenuated response to BNP. We therefore tested the hypothesis that BNP-induced suppression of neutrophil O2(-) generation is impaired in patients with acute HF. METHODS AND RESULTS: We have recently characterized suppression of neutrophil O2(-) generation (PMA- or fMLP-stimulated neutrophil burst) by BNP as a measure of its physiological activity. In the present study, BNP response was compared in neutrophils of healthy subjects (n = 29) and HF patients (n = 45). Effects of BNP on fMLP-induced phosphorylation of the NAD(P)H oxidase subunit p47phox were also evaluated. In acute HF patients, the suppressing effect of BNP (1 µmol/L) on O2(-) generation was attenuated relative to that in healthy subjects (P < 0.05 for both PMA and fMLP). Analogously, BNP inhibited p47phox phosphorylation in healthy subjects but not in HF patients (P < 0.05). However, O2(-)-suppressing effects of the cell-permeable cGMP analogue (8-pCPT-cGMP) were preserved in acute HF. Conventional HF treatment for 5 weeks partially restored neutrophil BNP responsiveness (n = 25, P < 0.05), despite no significant decrease in plasma NT-proBNP levels. CONCLUSIONS: BNP inhibits neutrophil O2(-) generation by suppressing NAD(P)H oxidase assembly. This effect is impaired in acute HF patients, with partial recovery during treatment.