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.

The impact of body mass index on cardiac structure and function in a cohort of obese patients without traditional cardiovascular risk factors.

Background: Obesity has been linked with alterations in hemodynamic, autonomic, and hormonal pathways in the body, leading to a spectrum of cardiovascular changes. We sought to evaluate the effects of obesity on structural and functional changes of the heart in the absence of cardiac disease and associated risk factors. Methods: We identified healthy outpatients without any cardiovascular disease or risk factors from our institution's echocardiography database (2017-2020). Patients were stratified by body mass index (BMI; normal: 18.5-25 kg/m2; overweight: 25-30 kg/m2; class 1 obesity: 30-35 kg/m2; class 2 obesity: 35-40 kg/m2; class 3 obesity: >40 kg/m2). Traditional and advanced echocardiographic parameters of cardiac chamber size and function including left ventricular global longitudinal strain (LV-GLS), left atrial reservoir strain (LASr), and right ventricular free wall strain (RV-FWS) were examined. The optimal cut-off BMI for discriminating LV-GLS (>-17.5%), LASr (<23%), and RV-FWS (>-23%) impairment was calculated using ROC curves. Results: 307 patients were assessed (41.5 ± 13.3yrs; 36.5%male; LVEF 61.3 ± 4.8%). No significant differences in indexed chamber volumes or LVEF were appreciated across BMI groups (p > 0.05 for all). LV-GLS, LASr, and RV-FWS were all significant on one-way ANOVA for differences from the group mean (all p < 0.01). Jonckheere-Terpstra test confirmed a significant trend of lower absolute LV-GLS, LASr and RV-FWS values across the rising BMI groups. On ROC curve analysis, a BMI value of 29.9 kg/m2, 35.1 kg/m2, and 37.3 kg/m2 were associated with LASr (AUC: 0.75), RV-FWS (AUC: 0.72), and LV-GLS (AUC: 0.75) impairment respectively. Conclusion: Obesity is linked with subclinical reduction of cardiac function in otherwise healthy subjects without cardiovascular risk factors, with reduction of left atrial function occurring at lower BMI, followed by the right and left ventricular function.

Diagnostic and Prognostic Value of Left Atrial Function in Identification of Cardioembolism and Prediction of Outcomes in Patients with Cryptogenic Stroke.

BACKGROUND: Stroke of undetermined source, commonly termed cryptogenic stroke (CS), accounts for a significant proportion of ischemic stroke etiology and have high rates of stroke recurrence. The heterogeneous etiology of CS makes decisions regarding treatment for such patients challenging. The aim of this study was to evaluate the diagnostic and prognostic value of left atrial (LA) function in the identification of cardioembolism and prediction of outcomes in patients with CS. METHODS: Consecutive patients admitted to a tertiary institution with ischemic stroke or transient ischemic attack (TIA) who underwent transthoracic echocardiography were recruited, with comprehensive evaluation of LA metrics including LA strain. Ischemic strokes and TIAs were classified as noncardioembolic, cryptogenic, or cardioembolic. A total of 709 patients (mean age, 66.0 ± 15.1 years; 55% men) were recruited. Two hundred ninety-one patients had CS, 189 had noncardioembolic stroke, and 229 had cardioembolic stroke. Patients with CS were followed for 20.0 ± 13.8 months for recurrent ischemic stroke or TIA. RESULTS: Receiver operating characteristic curves showed LA reservoir and contractile strain to be strong discriminators of cardioembolic strokes, and log-rank tests showed both measures to be significantly associated with the distribution of time to recurrent ischemic stroke or TIA in patients with CS. Multivariable hazard models showed LA reservoir and contractile strain to be independent predictors of recurrent ischemic stroke or TIA in patients with CS, in addition to estimated glomerular filtration rate and active smoking. CONCLUSIONS: LA reservoir and contractile strain were strong discriminators of cardioembolic stroke and independently predicted recurrent ischemic stroke or TIA in patients with CS. Use of LA strain may improve risk stratification and decision-making in patients with CS, with particular regard to prolonged ambulatory heart rhythm monitoring and/or empiric anticoagulation.

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.

Prognostic implications of traditional and non-traditional cardiovascular risk factor profiles in patients with non-valvular atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a prevalent disease with associated mortality risk, mediated in large part through its associated cardiovascular risk factors. Standard modifiable cardiovascular risk factors (SMuRFs; hypercholesterolaemia, hypertension, diabetes and smoking) are established drivers of cardiovascular disease; however, the importance of non-traditional mediators of cardiovascular risk (NTRFs) such as chronic renal impairment, obstructive sleep apnoea and obesity is emerging. The differential impact of these risk factors on outcomes in patients with AF is not well studied. METHODS: Consecutive patients admitted to our service between January 2013 and January 2018 with a primary diagnosis of non-valvular AF were assessed. Assessment of demographic, anthropometric, risk factor profile and pharmacotherapeutics was performed. The clinical course of these patients was followed for up to five years for the composite outcome of all-cause death and major adverse cardiovascular events. RESULTS: Of the 1010 patients (62.29 ± 16.81 years, 51% men) included, 154 (15%) had no risk factors, 478 (47%) had only SMuRFs, 59 (6%) had only NTRFs and 319 (32%) had both SMuRFs and NTRFs. Over a mean follow-up period of 33.18 ± 21.27 months, a total of 288 patients met the composite outcome. On Cox regression, the coexistence of SMuRFs and NTRFs was an independent predictor of the composite outcome (HR 1.40; 95%CI 1.09-1.82, p = .01). Other independent predictors included age, heart failure, CHA2 DS2 VASc score, persistent AF and anaemia. CONCLUSIONS: The presence of both SMuRFs and NTRFs has prognostic implications in patients with non-valvular AF.

Persistent pathology of the patent foramen ovale: a review of the literature.

A patent foramen ovale (PFO) is an interatrial shunt, with a prevalence of 20-34% in the general population. While most people do not have secondary manifestations of a PFO, some reported sequelae include ischaemic stroke, migraine, platypnoea-orthodeoxia syndrome and decompression illness. Furthermore, in some cases, PFO closure should be considered for patients before neurosurgery and for patients with concomitant carcinoid syndrome. Recent trials support PFO closure for ischaemic stroke patients with high risk PFOs and absence of other identified stroke mechanisms. While PFOs can be associated with migraine with auras, with some patients reporting symptomatic improvement after closure, the evidence from randomised controlled trials is less clear in supporting the use of PFO closure for migraine treatment. PFO closure for other indications such as platypnoea-orthodeoxia syndrome, decompression illness and paradoxical embolism are based largely on case series with good clinical outcomes. PFO closure can be performed as a day surgical intervention with high procedural success and low risk of complications.

Association of Left Atrial Metrics with Atrial Fibrillation Rehospitalization and Adverse Cardiovascular Outcomes in Patients with Nonvalvular Atrial Fibrillation following Index Hospitalization.

BACKGROUND: Atrial fibrillation (AF) is the most common arrhythmia encountered in clinical practice, with significant clinical and economic burdens, largely driven by adverse cardiovascular outcomes and AF-related hospitalization. Left atrial (LA) parameters have been shown to have prognostic value in cardiovascular disease states. We sought to evaluate the prognostic value of measures of LA size and function, as measured through LA volume index and LA emptying fraction (LAEF), respectively, for AF rehospitalization and long-term adverse outcomes in patients with nonvalvular AF following index hospitalization. METHODS: In this retrospective study, 594 consecutive patients (mean age, 67.8 ± 13.6 years, 53% men) admitted to a tertiary referral center with nonvalvular AF were assessed. Patients who underwent transthoracic echocardiography during their index admission and had complete follow-up data were included and followed for a mean period of 33.18 ± 21.27 months for the primary outcome of AF rehospitalization. The secondary outcome was a composite of all-cause death and major adverse cardiovascular events. RESULTS: The primary outcome occurred in 250 (42%) patients, and the secondary outcome occurred in 219 (37%) patients. On multivariable regression analysis, LAEF had an independent association with AF rehospitalization (hazard ratio [HR] = 0.967; 95% CI, 0.953-0.982; P < .01), and time-dependent receiver operating characteristic curves demonstrated LAEF to have strong diagnostic accuracy in predicting early and intermediate AF rehospitalization. Both LA volume index (HR = 1.014; 95% CI, 1.003-1.026; P = .01) and LAEF (HR = 0.982; 95% CI, 0.970-0.993; P < .01) were associated with all-cause death and major adverse cardiovascular events. CONCLUSIONS: Adverse LA remodeling, as reflected through LA enlargement and reduced LA mechanical function, is associated with AF rehospitalization and long-term adverse cardiovascular outcomes in hospitalized patients with nonvalvular AF.

Uraemic Cardiomyopathy: A Review of Current Literature.

Uraemic Cardiomyopathy (UC) is recognised as an intricate and multifactorial disease which portends a significant burden in patients with End-Stage Renal Disease (ESRD). The cardiovascular morbidity and mortality associated with UC is significant and can be associated with the development of arrythmias, cardiac failure and sudden cardiac death (SCD). The pathophysiology of UC involves a complex interplay of traditional implicative factors such as haemodynamic overload and circulating uraemic toxins as well as our evolving understanding of the Chronic Kidney Disease-Mineral Bone Disease pathway. There is an instrumental role for multi-modality imaging in the diagnostic process; including transthoracic echocardiography and cardiac magnetic resonance imaging in identifying the hallmarks of left ventricular hypertrophy and myocardial fibrosis that characterise UC. The appropriate utilisation of the aforementioned diagnostics in the ESRD population may help guide therapeutic approaches, such as pharmacotherapy including beta-blockers and aldosterone-antagonists as well as haemodialysis and renal transplantation. Despite this, there remains limitations in effective therapeutic interventions for UC and ongoing research on a cellular level is vital in establishing further therapies.

Integrated Care in Atrial Fibrillation: A Road Map to the Future.

Atrial fibrillation (AF) is the most commonly encountered arrhythmia in clinical practice with an epidemiological coupling appreciated with advancing age, cardiometabolic risk factors, and structural heart disease. This has resulted in a significant public health burden over the years, evident through increasing rates of hospitalization and AF-related clinical encounters. The resultant gap in health care outcomes is largely twinned with suboptimal rates of anticoagulation prescription and adherence, deficits in symptom identification and management, and insufficient comorbid cardiovascular risk factor investigation and modification. In view of these shortfalls in care, the establishment of integrated chronic care models serves as a road map to best clinical practice. The expansion of integrated chronic care programs, which include multidisciplinary team care, nurse-led AF clinics, and use of telemedicine, are expected to improve AF-related outcomes in the coming years. This review will delve into current gaps in AF care and the role of integrated chronic care models in bridging fragmentations in its management.

Coronary artery vasculitis: a review of current literature.

Cardiac vasculitis is recognized as a heterogeneous disease process with a wide spectrum of manifestations including pericarditis, myocarditis, valvular heart disease and less frequently, coronary artery vasculitis (CAV). CAV encompasses an emerging field of diseases which differ from conventional atherosclerotic disease and have a proclivity for the younger population groups. CAV portends multiple complications including the development of coronary artery aneurysms, coronary stenotic lesions, and thrombosis, all which may result in acute coronary syndromes. There are several aetiologies for CAV; with Kawasaki's disease, Takayasu's arteritis, Polyarteritis Nodosa, and Giant-Cell Arteritis more frequently described clinically, and in literature. There is a growing role for multi-modality imaging in assisting the diagnostic process; including transthoracic echocardiography, cardiac magnetic resonance imaging, computed tomography coronary angiography, fluorodeoxyglucose-positron emission tomography and conventional coronary angiogram with intravascular ultrasound. Whilst the treatment paradigms fundamentally vary between different aetiologies, there are overlaps with pharmacological regimes in immunosuppressive agents and anti-platelet therapies. Interventional and surgical management are is a consideration in select populations groups, within a multi-disciplinary context. Further large-scale studies are required to better appropriately outline management protocols in this niche population.

Clinical and cardiac structural predictors of atrial fibrillation persistence.

AIMS: The persistence of atrial fibrillation (AF) has been associated with differential clinical outcomes, with studies showing that persistent and permanent AF results in increased morbidity and mortality when compared to the paroxysmal subtype. Given the established prognostic implications of AF subtype, we sought to discern the clinical and structural cardiac parameters associated with persistent/ permanent AF. MATERIALS AND METHODS: Consecutive patients admitted to our institution between January 2013 and January 2018 with a primary diagnosis of non-valvular AF who underwent comprehensive transthoracic echocardiography were retrospectively appraised. Assessment of clinical and echocardiographic parameters was undertaken and compared according to AF subtype. RESULTS: Of 1010 patients, 665 (mean age 66.8 ± 13.5 years, 53% men) had comprehensive transthoracic echocardiography on index admission and were included in the primary analysis. The majority of patients (n = 468; 70%) had paroxysmal AF while 197 (30%) had persistent/ permanent AF. Multivariable logistic regression analysis showed that heart failure (adjusted OR 3.135; 95% CI 2.099 to 4.682, P < .001), right atrial (RA) area ≥18 cm2 (adjusted OR 2.147; 95% CI 1.413 to 3.261, P < .001) and left atrial emptying fraction (LAEF) ≤34% (adjusted OR 2.959; 95% CI 1.991 to 4.398, P < .001) were independent predictors of persistent /permanent AF. CONCLUSIONS: The presence of heart failure, increased RA size and impaired LA function were associated with persistent/ permanent AF. These clinical and cardiac structural risk markers of AF persistence may identify a target population for early intervention to prevent adverse cardiovascular outcomes.

The Role of Multi-modality Imaging in the Diagnosis of Cardiac Amyloidosis: A Focused Update.

Cardiac amyloidosis (CA) is a unique disease entity involving an infiltrative process, typically resulting in a restrictive cardiomyopathy with diastolic heart failure that ultimately progresses to systolic heart failure. The two most common subtypes are light-chain and transthyretin amyloidosis. Early diagnosis of this disease entity, especially light-chain CA subtype, is crucial, as it portends a poorer prognosis. This review focuses on the clinical utility of the various imaging modalities in the diagnosis and differentiation of CA subtypes. This review also aims to highlight the key advances in each of the imaging modalities in the diagnosis and prognostication of CA.

Ventricular Arrhythmias in Cardiac Amyloidosis: A Review of Current Literature.

Cardiac Amyloidosis is an infiltrative cardiomyopathy which occurs secondary to deposition of mis-folded protein in the myocardium, with the two most common subtypes being AL amyloidosis and TTR amyloidosis. The pathogenesis of the disease is multifaceted and involves a variety of mechanisms including an inflammatory response cascade, oxidative stress and subsequent separation of myocyte fibrils. Cardiac Amyloidosis frequently results in congestive cardiac failure and arrhythmias, from a disruption in cardiac substrate with subsequent electro-mechanical remodelling. Disease progression is usually demonstrated by development of progressive pump failure, which may be seen with a high arrhythmic burden, usually portending a poor prognosis. There is a paucity of literature on the clinical implications of ventricular arrhythmias in the context of cardiac amyloidosis. The important diagnostic investigations for these patients include transthoracic echocardiography, cardiac magnetic resonance imaging and an electrophysiology study. Whilst there are no robust management guidelines, studies have indicated benefits from contemporary pharmacological therapy and case-by-case catheter ablation. There are novel directed therapies available for TTR amyloidosis that have shown to improve overall survival. The role of ICD therapy in cardiac amyloidosis is controversial, with benefits seen predominantly in early phases of the disease process. The only definitive surgical therapy includes heart transplantation, but is largely indicated for progressive decompensated heart failure (Figure 1). Further large-scale studies are required to better outline management paradigms for treating ventricular arrhythmias in cardiac amyloidosis.

Left Ventricular Sphericity Index is a reproducible bedside echocardiographic measure of geometric change between acute phase Takotsubo's syndrome and acute anterior myocardial infarction.

•TS and AMI are separate cardiac conditions with similar clinical presentations.•TS have a higher LVSI than AMI, indicating a more spherical left ventricle.•LVSI may be utilised acutely to assist differentiation of acute phase TS and AMI.

Drivers of hospitalization in atrial fibrillation: A contemporary review.

Atrial fibrillation (AF)-related hospitalization has risen over the last 2 decades and is the most influential determinant of total disease-related expenditure. In this review article, we describe several identified drivers of hospitalization from several registries and large-scale clinical trials, including key cardiovascular and non-traditional risk factors. We also discuss available assessment tools for discerning overall risk of hospitalization, including AF symptom scores, thrombosis and bleeding disposition, and non-invasive cardiac structural assessment. Finally, we highlight the different treatment paradigms that have been proven to reduce AF burden, progression, and hospitalization in the literature.

Impairment of left atrial function and cryptogenic stroke: Potential insights in the pathophysiology of stroke in the young.

BACKGROUND: Stroke is one of the leading causes of morbidity and mortality with a significant percentage classified as cryptogenic. Left atrial (LA) remodelling, a substrate for atrial fibrillation (AF) and stroke development, may play a role in identification of the aetiology of cryptogenic stroke. We aimed to examine LA function to gain mechanistic insights into the pathophysiology of cryptogenic stroke in young patients otherwise at low risk for cardiovascular disease. METHODS: Patients aged <60 years without traditional cardiovascular risk factors and who were diagnosed with ischaemic cryptogenic stroke or TIA were evaluated and compared to healthy controls and patients with paroxysmal AF with a CHA2DS2-VA score of 0. Conventional and novel left ventricular (LV) and LA echocardiographic parameters between the three groups were assessed. RESULTS: Each group consisted of thirty patients. There were no significant differences in LV parameters (LVEF, LV endoGLS) between groups. LA strain in stroke patients was significantly lower compared to the controls (median 33%; interquartile range (IQ) [32/39] vs 31 [27/34]; p = 0.008). LA strain was significantly lower in AF patients compared to stroke patients (median 21% [19/22] vs 31% [27/34]; p < 0.0001). CONCLUSION: A stepwise reduction in measures of LA function was appreciated between controls, young stroke and paroxysmal AF groups. This may indicate dynamic LA remodelling occurring in the young stroke population and suggest a shared causal mechanism for stroke development in this group. LA strain may further refine the risk for cardioembolic stroke.