Clinical phenotypes and outcomes of patients with left ventricular thrombus: an unsupervised cluster analysis.

BACKGROUND: Left ventricular thrombus (LVT) can develop in a diverse group of patients with various underlying causes, resulting in divergent natural histories and trajectories with treatment. Our aim was to use cluster analysis to identify unique clinical profiles among patients with LVT and then compare their clinical characteristics, treatment strategies, and outcomes. METHODS: We conducted a retrospective study involving 472 patients with LVT whose data were extracted from a tertiary center's echocardiography database, from March 2011 to January 2021. We used the TwoStep cluster analysis method, examining 19 variables. RESULTS: Our analysis of the 472 patients with LVT revealed two distinct patient clusters. Cluster 1, comprising 247 individuals (52.3%), was characterized by younger patients with a lower incidence of traditional cardiovascular risk factors and relatively fewer comorbidities compared with Cluster 2. Most patients had LVT attributed to an underlying ischemic condition, with a larger proportion being due to post-acute myocardial infarction in Cluster 1 (68.8%), and due to ischemic cardiomyopathy in Cluster 2 (57.8%). Notably, patients in Cluster 2 exhibited a reduced likelihood of LVT resolution (hazard ratio [HR] 0.58, 95% confidence interval [CI] 0.44-0.77, p < 0.001) and a higher risk of all-cause mortality (HR 2.27, 95% CI 1.43-3.60, p = 0.001). These associations persisted even after adjusting for variables such as anticoagulation treatment, the presence of left ventricular aneurysms, and specific LVT characteristics such as mobility, protrusion, and size. CONCLUSION: Through TwoStep cluster analysis, we identified two distinct clinical phenotypes among patients with LVT, each distinguished by unique baseline clinical attributes and varying prognoses.

What's the optimal duration of anticoagulation in patients with left ventricular thrombus?

INTRODUCTION: Left ventricular thrombus (LVT) occurs in acute myocardial infarction and in ischemic and non-ischemic cardiomyopathies. LVT may result in embolic stroke. Currently, the duration of anticoagulation for LVT is unclear. This is an important clinical question as prolonged anticoagulation is associated with increased bleeding risks, while premature discontinuation may result in embolic complications. AREAS COVERED: There are no randomized trial data regarding anticoagulation duration for LVT. Guidelines and expert consensus recommend anticoagulation for 3-6 months with cessation of anticoagulation if interval imaging demonstrates thrombus resolution. Cardiac magnetic resonance imaging (CMR) is more sensitive and specific compared to echocardiography for LVT detection, and may be appropriate for high-risk patients. Prolonged anticoagulation may be considered in unresolved protuberant or mobile LVT, and in patients with resolved LVT but persistent depressed left ventricular ejection fraction and/or myocardial akinesia or dyskinesia. EXPERT OPINION: CMR will likely be increasingly used for LVT surveillance to guide anticoagulation duration. Further research is needed to determine which patients with persistent LVT on CMR benefit from prolonged anticoagulation.

A case report: anteroseptal ST elevation due to acute isolated right ventricular infarction.

BACKGROUND: Electrocardiogram (ECG) is the first diagnostic tool physicians use in diagnosing acute myocardial infarction (MI). In this case report, we present a case where the initial ECG diagnosis was that of an acute anteroseptal MI but emergency coronary angiography showed that the infarct-related artery was a small non-dominant right coronary artery (RCA) instead of the anticipated left anterior descending artery (LAD). Isolated right ventricular (RV) infarction from a non-dominant RCA is rarely seen in clinical practice, and it may exhibit ECG changes that can be confused with an acute anteroseptal MI. It is important to appreciate the subtle differences in the ECG changes that occur in either of these two types of MI for appropriate diagnosis and treatment. CASE PRESENTATION: A 49-year-old non-smoking male with prior coronary stent implantation in LAD presented with acute chest pain and his pre-hospital ECG indicated an anteroseptal STEMI possibly due to stent thrombosis, but an emergency angiogram showed patent LAD and Circumflex arteries. There was however thrombotic occlusion of the right, non-dominant coronary artery, which was revascularized with a drug-eluting stent. The patient's chest pain and ST elevations resolved, and subsequent echo showed moderate RV systolic dysfunction in keeping with RV myocardial infarction. DISCUSSION: RV myocardial infarction is usually due to an occlusion of the dominant RCA proximal to the origin of its RV wall branch, which often results in inferior ST elevation with reciprocal anterior ST depression. The ST elevation over V1 which would accompany RV infarction is often masked due to the more dominant electrical forces of inferior and posterior LV wall infarction. Our case demonstrates that in isolated RV infarction due to non-dominant proximal RCA occlusion, anterior ST elevation can be seen over V1-3, being most prominent in V1, which overlies the right ventricle, and resolved after restoring flow to the RCA. Spatial vector analysis of the ECG or right-sided ECG leads would be helpful to aid the diagnosis of RV infarction when clinical suspicion is present, for example when there is significant hypotension, raised jugular venous pressure but clear lung fields or deterioration after nitrate administration.

Approach to bradyarrhythmias: A proposed algorithm.

Bradyarrhythmias are commonly encountered in clinical practice. While there are several electrocardiographic criteria and algorithms for tachyarrhythmias, there is no algorithm for bradyarrhythmias to the best of our knowledge. In this article, we propose a diagnostic algorithm that uses simple concepts: (1) the presence or absence of P waves, (2) the relationship between the number of P waves and QRS complexes, and (3) the regularity of time intervals (PP, PR and RR intervals). We believe this straightforward, stepwise method provides a structured and thorough approach to the wide differential diagnosis of bradyarrhythmias, and in doing so, reduces misdiagnosis and mismanagement.

Clinical characteristics, treatment and long-term outcomes of patients with right-sided cardiac thrombus.

OBJECTIVE: Right-sided cardiac thrombus is rare and may be caused by venous thromboembolism, in association with medical devices or stasis of blood in atrial fibrillation (AF) and cardiomyopathies. Complications include pulmonary embolism (PE) and paradoxical stroke. Current data are limited and mostly from case series and PE registries. We aimed to describe the clinical characteristics, echocardiographic features, treatments, and outcomes of right-sided cardiac thrombus patients. METHODS: This was a retrospective observational study of 97 consecutive patients with right-sided cardiac thrombus detected on echocardiography. We studied co-morbidities, predisposing factors, thrombus characteristics, and therapeutic interventions and assessed their associations with the development of PE, paradoxical stroke, circulatory collapse, and all-cause mortality. RESULTS: The mean age was 58.7 years, and 55/97 (56.7%) of the participants were female. Ischemic heart disease (IHD), heart failure, chronic kidney disease, and malignancy were common co-morbidities. Right atrial (RA) thrombus was often associated with medical devices, while right ventricular (RV) thrombus was more commonly associated with cardiomyopathy. Thrombus mobility did not affect embolic events but was associated with greater short-term mortality. On multivariable analysis, anticoagulation (HR 0.25, 95% CI 0.09-0.68) and thrombus resolution (HR 0.28, 95% CI 0.13-0.62) were associated with greater survival. CONCLUSION: Right-sided cardiac thrombus is rare but may have potentially life-threatening complications such as PE and paradoxical stroke. Further research is needed to determine the optimal therapeutic strategies for this poorly studied population.

Prevalence and incidence of cognitive impairment and dementia in heart failure - A systematic review, meta-analysis and meta-regression.

INTRODUCTION: The burden of cognitive impairment in heart failure (HF) patients is significant and leads to longer hospital stay, higher readmission rates, and increased mortality. This review seeks to synthesize the available studies to determine the prevalence and incidence of cognitive impairment and dementia in HF patients. METHODS: PubMed, Embase, PsychoINFO, and Cochrane databases were systematically searched from their inception through to May 3, 2021. Study and population characteristics, total patients with HF, prevalence of cognitive impairment and dementia in HF patients, and cognitive assessment tool were abstracted by two reviewers. RESULTS: In HF patients, the overall prevalence for cognitive impairment and dementia was 41.42% (CI) and 19.79% (dementia), respectively. We performed a meta-regression analysis, which demonstrated that the risk of cognitive impairment and dementia increased with age. DISCUSSION: Further research should investigate whether HF accelerates the rate of cognitive decline and the progression of dementia.

Cognitive Impairment in Heart Failure-A Review.

Cognitive impairment (CI) is common in heart failure (HF). Patients with HF demonstrate reduced global cognition as well as deficits in multiple cognitive domains compared to controls. Degree of CI may be related to HF severity. HF has also been associated with an increased risk of dementia. Anatomical brain changes have been observed in patients with HF, including grey matter atrophy and increased white matter lesions. Patients with HF and CI have poorer functional independence and self-care, more frequent rehospitalisations as well as increased mortality. Pathophysiological pathways linking HF and CI have been proposed, including cerebral hypoperfusion and impaired cerebrovascular autoregulation, systemic inflammation, proteotoxicity and thromboembolic disease. However, these mechanisms are poorly understood. We conducted a search on MEDLINE, Embase and Scopus for original research exploring the connection between HF and CI. We then reviewed the relevant literature and discuss the associations between HF and CI, the patterns of brain injury in HF and their potential mechanisms, as well as the recognition and management of CI in patients with HF.

Can too much exercise be dangerous: what can we learn from the athlete's heart?

Exercise prevents and aids treatment of coronary heart disease, hypertension, heart failure, diabetes mellitus, obesity and depression, reduces cardiac events and improves survival. However, evidence suggests that the relationship between exercise and mortality may be curvilinear, with modest additional benefit at higher levels. Intensive exercise has also been associated with increased atrial fibrillation risk, although its clinical implications are not well understood. Other proposed adverse effects of exercise on the heart, including reduced right ventricular function, elevated cardiac biomarkers, myocardial fibrosis and coronary artery calcification, are less substantiated. Current evidence cannot affirm that extreme exercise is dangerous and future studies should combine large cohorts to obtain a statistically reliable limit. Associations between features of the athlete's heart and cardiovascular morbidity and mortality should also be explored.

Cardiac sarcoma attached to pacemaker lead.

BACKGROUND AND AIM: Cardiac sarcoma is a rare condition and may mimic atrial myxoma. We present a case report of a man with a cardiac sarcoma. METHOD: Case report presentation. RESULTS: A 68-year-old man with a permanent pacemaker presented to us with a 4-month history of breathlessness. Echocardiography revealed a large right atrial mass adherent to the pacemaker lead and a provisional diagnosis of atrial myxoma was made based on echocardiographic appearance. A 60 x 30 x 30 mm irregular lobulated tumour was surgically resected from the right atrium. Upon histopathologic examination, the tumour was consistent with an undifferentiated pleomorphic sarcoma. CONCLUSION: Cardiac sarcomas have an extremely poor prognosis and more unfortunately this man developed a surgical site infection and died of acute mediastinitis. We discuss the presentation, imaging and current surgical approaches to cardiac sarcoma. Curative treatment is currently limited for this disease.

An Elderly Woman with Exertional Dyspnoea and T-Wave Inversions on Electrocardiography.

We present a case of a 75-year-old woman with cardiac dextroposition who presented for preoperative cardiac evaluation because of exertional dyspnoea. On examination, heart sounds were best appreciated on the right, and bowel sounds were heard over the left hemithorax. Electrocardiography showed widespread T-wave inversions. No coronary artery ischemia was found. A large congenital diaphragmatic hernia with displacement of the heart to the right was found on chest radiography and confirmed on computed tomography. Surgery was subsequently uneventful. In conclusion, thorough pulmonary auscultation to detect bowel sounds in the thorax increases clinical suspicion of cardiac dextroposition.

Retinoid X receptor gamma (RXRG) is an independent prognostic biomarker in ER-positive invasive breast cancer.

BACKGROUND: Retinoid X Receptor Gamma (RXRG) is a member of the nuclear receptor superfamily and plays a role in tumour suppression. This study aims to explore the prognostic significance of RXRG in breast cancer. METHODS: Primary breast cancer tissue microarrays (n = 923) were immuno-stained for RXRG protein and correlated with clinicopathological features, and patient outcome. RESULTS: Nuclear RXRG expression was significantly associated with smaller tumour size (p = 0.036), lower grade (p < 0.001), lobular histology (p = 0.016), lower Nottingham Prognostic Index (p = 0.04) and longer breast cancer-specific survival (p < 0.001), and longer time to distant metastasis (p = 0.002). RXRG expression showed positive association with oestrogen receptor (ER)-related biomarkers: GATA3, FOXA1, STAT3 and MED7 (all p < 0.001) and a negative correlation with the Ki67 proliferation marker. Multivariate analysis demonstrated RXRG protein as an independent predictor of longer breast cancer-specific survival and distant metastasis-free survival. In the external validation cohorts, RXRG expression was associated with improved patients' outcome (p = 0.025). In ER-positive tumours, high expression of RXRG was associated with better patient outcome regardless of adjuvant systemic therapy. ER signalling pathway was the top predicted master regulator of RXRG protein expression (p = 0.005). CONCLUSION: This study provides evidence for the prognostic value of RXRG in breast cancer particularly the ER-positive tumours.

Inhibition of amyloid-induced toxicity by ergothioneine in a transgenic Caenorhabditis elegans model.

The abnormal accumulation of ß-amyloid peptide (Aß) is recognized as a central component in the pathogenesis of Alzheimer disease. While many aspects of Aß-mediated neurotoxicity remain elusive, Aß has been associated with numerous underlying pathologies, including oxidative and nitrosative stress, inflammation, metal ion imbalance, mitochondrial dysfunction, and even tau pathology. Ergothioneine (ET), a naturally occurring thiol/thione-derivative of histidine, has demonstrated antioxidant and neuroprotective properties against various oxidative and neurotoxic stressors. This study investigates ET's potential to counteract Aß-toxicity in transgenic Caenorhabditis elegans overexpressing a human Aß peptide. The accumulation of Aß in this model leads to paralysis and premature death. We show that ET dose-dependently reduces Aß-oligomerization and extends the lifespan and healthspan of the nematodes.

Overexpression of the cancer stem cell marker CD133 confers a poor prognosis in invasive breast cancer.

PURPOSE: CD133/ prominin 1 is a cancer stem cell marker associated with cancer progression and patient outcome in a variety of solid tumours, but its role in invasive breast cancer (BC) remains obscure. The current study aims to assess the prognostic value of CD133 expression in early invasive BC. METHODS: CD133 mRNA was assessed in the METABRIC cohort and at the proteomic level using immunohistochemistry utilising a large well-characterised BC cohort. Association with clinicopathological characteristics, expression of other stem cell markers and patient outcome were evaluated. RESULTS: High expression of CD133 either in mRNA or protein levels was associated with characteristics of poor prognosis including high tumour grade, larger tumour size, high Nottingham Prognostic Index, HER2 positivity and hormonal receptor negativity (all; p < 0.001). High CD133 expression was positively associated with proliferation biomarkers including p16, Cyclin E and Ki67 (p < 0.01). Tumours expressing CD133 showed higher expression of other stem cell markers including CD24, CD44, SOX10, ALDHA3 and ITGA6. High expression of CD133 protein was associated with shorter BC-specific survival (p = 0.026). Multivariate analysis revealed that CD133 protein expression was an independent risk factor for shorter BC-specific survival (p = 0.038). CONCLUSION: This study provides evidence for the prognostic value of CD133 in invasive BC. A strong positive association of BC stem cell markers is observed at the protein level. Further studies to assess the value of stem cell markers individually or in combination in BC is warranted.