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Abstract: Exercise-based cardiac rehabilitation (EBCR) is a treatment modality for patients with heart failure (HF) that has withstood the test of time. It has continued to show benefits even in the current era of pharmacotherapeutics for HF. Participation in a multidisciplinary comprehensive EBCR programme reduces mortality and morbidity, has a multitude of physiological benefits, and improves cardiovascular risk factor control and quality of life. Despite this, historical barriers to enrolment and uptake remain. Strategies to overcome these, as well as alternative delivery methods of EBCR in HF patients, are emerging and include telerehabilitation, focus on special groups and emphasis on behavioural change. This review provides oversight on the modalities of exercise training in HF as well as their benefits and gives an overview of barriers to the utilisation of EBCR along with future progress in the field.

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a debilitating and life-threatening condition with a heterogeneous clinical presentation. Recent guidelines from the United States and Europe have been published to guide clinical practice and to facilitate management conformity by covering current diagnostic and treatment strategies for patients with ATTR-CM. These guidelines highlight the importance of an early diagnosis to optimize therapeutic outcomes, specifying the use of tests and imaging techniques to allow accurate, noninvasive diagnosis of ATTR-CM. However, as regional practice variations across Asia may limit access to healthcare, availability of specific tests, and expertise in assessing diagnostic images, there is an ongoing need to provide an Asian perspective on these clinical guidelines. This review article provides practical recommendations for the diagnosis and monitoring of patients with ATTR-CM in Asia, highlighting the need for additional guidelines to support a broad and diverse population, consider differing healthcare systems and diagnostic testing availability, and provide a flexible yet robust algorithm.

In the Asia-Pacific region, heart failure (HF) is associated with significant health and socioeconomic burden. Given the differences in the epidemiology of HF, as well as the availability of healthcare resources between Asian and Western countries, an Asian Pacific Society of Cardiology (APSC) working group developed consensus recommendations on the management of chronic HF in the Asia-Pacific region. The APSC expert panel reviewed and appraised the available evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Consensus recommendations were developed and put to an online vote. Consensus was reached when 80% of votes for a given recommendation were either ‘agree’ or ‘neutral’. The resulting statements provide guidance on the diagnosis, assessment and treatment of patients with HF with reduced, mildly reduced or preserved ejection fraction in the Asia-Pacific region.

Background Cardiac amyloidosis (CA) is an increasingly recognised condition in patients with aortic stenosis (AS). However, there is large variation in the reported prevalence figures, due to differences in populations and diagnostic methods. We aimed to investigate the prevalence, risk factors and outcomes of concomitant CA and AS. Methods We performed a systematic review and meta-analysis of the literature searched on Medline, EMBASE, Scopus and CENTRAL. We analysed the prevalence of CA in AS grouped according to diagnostic techniques, and the risk factors and outcomes of concomitant CA and AS was analysed in AS patients referred for surgical or transcatheter aortic valve replacement (AVR). Results A total of 21 studies were included, involving 4,243 patients. The pooled prevalence of CA in patients with AS was 14.4%, with substantial heterogeneity. The pooled prevalence of AS in CA was 8.7%, with substantial heterogeneity. Patients with both AS and CA had higher all-cause mortality than those with AS or CA alone. In AS patients requiring AVR, CA was associated with increasing age, male sex, higher NT-proBNP levels, increased interventricular septal end diastole thickness and lower left ventricular ejection fraction. Concomitant AS and CA was associated with increased all-cause mortality and pacemaker implantation post-procedure. Study limitations included the heterogeneity of results and the fair to good quality of studies published. Conclusion Overall, a substantial proportion of patients with AS may have CA, and they have poorer prognosis. A high degree of clinical suspicion is needed to identify “red flags” and perform appropriate diagnostic imaging.

Objective: Recent studies have increasingly shown the benefits of using sodium/glucose cotransporter 2 inhibitor (SGLT2i). However, there are concerns regarding the initiation of SGLT2i during acute hospital admissions due to the potential increased risk of complications. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of SGLT2i initiation within 2 weeks of an acute hospital admission. Methods: Four electronic databases (PubMed, Embase, Cochrane, and Scopus) were searched for articles published from inception up to 27 March 2021 that evaluated the efficacy and/or safety of SGLT2i initiation within 2 weeks of an acute hospital admission. Random-effects pair-wise meta-analysis models were utilized to summarize the studies. The protocol was registered with PROSPERO (CRD42021245492). Results: Nine clinical trials were included with a combined cohort of 1,758 patients. Patients receiving SGLT2i had a mean increase in 24-h urine volume of +487.55 mL (95% CI 126.86–848.25; p = 0.008) compared to those not started on SGLT2i. Patients with heart failure treated with SGLT2i had a 27% relative risk reduction in rehospitalizations for heart failure, compared to controls (risk ratio 0.73; p = 0.005). There were no differences in other efficacy and safety outcomes examined. Conclusion: There was no increased harm with initiation of SGLT2i within 2 weeks of an acute hospital admission, and its use reduced the relative risk of rehospitalizations for heart failure in patients with heart failure. It was also associated with increased urine output. However, current evidence pool is limited, especially in specific population subtypes.

In recent trials, sodium-glucose cotransporter 2 (SGLT2) inhibitors proved effective as treatment for heart failure. However, the relative efficacy of sacubitril/valsartan against SGLT2 inhibitor in patients with heart failure remains unknown. Hence, we performed a network meta-analysis to compare the effects of sacubitril/valsartan against SGLT2 inhibitors on cardiovascular outcomes in patients with heart failure. Four electronic databases (PubMed, Embase, Cochrane, SCOPUS) were searched for randomised-controlled trials (RCTs) published from 1st January 2000 to 25th September 2021. Two additional systematic reviews were conducted for RCTs of enalapril and valsartan to establish a common comparator arm. Frequentist network meta-analysis models were utilised to summarise the studies. Twenty-five RCTs were included, comprising a combined cohort of 47,275 patients. Network meta-analysis demonstrated that compared to SGLT2 inhibitors, sacubitril/valsartan achieved a larger hazard rate reduction in the composite of heart failure hospitalisation and cardiovascular death (hazard ratio [HR]: 0.86; 95% CI 0.75–0.98), cardiovascular death (HR: 0.78; 95% CI 0.65–0.94), and a larger mean change in systolic blood pressure at 8 or more months (weighted mean difference [WMD]: − 7.08 mmHg; 95% CI − 8.28 to − 5.89). There were no significant differences in treatment effects across heart failure hospitalisation, all-cause mortality, diastolic blood pressure at 12 weeks, and systolic blood pressure at 2–4 months. In patients with heart failure with reduced ejection fraction, sacubitril/valsartan achieved a 20% hazard rate reduction for cardiovascular death compared to SGLT2 inhibitors. In patients with heart failure, sacubitril/valsartan was demonstrated to be superior to SGLT2 inhibitors in the treatment effect for the composite of heart failure hospitalisation and cardiovascular death, cardiovascular death, and long-term blood pressure.

The chela of the hermit crab protects its body against the attack from predators. Yet, a deep understanding of this mechanical defense is still lacking. Here, we investigate the chela of hermit crab, Coenobita brevimanus, and establish the relationships between the microstructures, chemical compositions and mechanical properties to gain insights into its biomechanical functions. We find that the chela is a multi-layered shell composed of five different layers with distinct features of the microstructures and chemical compositions, conferring different mechanical properties. Especially, an increase of the calcium carbonate content towards the layer furthest from the exterior, unlike the chemical gradients of many crustacean exoskeletons, provides a strong resistance to deformation. Nanoindentation measurements reveal that the overall gradient of the elastic modulus and hardness in the cross-section displays a sandwich profile, i.e., a soft core clamped by two stiff surface layers. Further mechanics modeling demonstrates that the high curvature and stiff innermost sublayer enhance the structural rigidity of the chela. In conjunction with the experimental observations, dynamic finite element analysis maps the time-spatial distribution of principal stress and indicates that fiber bridging might be the major mechanism against crack propagation at microscale. The lessons gained from the study of this multiphase biological composite could provide important insights into the design and fabrication of bioinspired materials for structural applications. STATEMENT OF SIGNIFICANCE: Multiple hierarchical structures have been discovered in a variety of exoskeletons. They are naturally designed to maintain the structural integrity and act as a protective layer for the animals. However, each kind of the hierarchical structures has its unique topology, chemical gradients as well as mechanical properties. We find that the chela is multi-layered shell composed of five different layers with distinct features of the microstructures and chemical compositions, conferring different mechanical properties. Especially, a large amount of helicoidal organic fibrils form highly organized 3D woven matrix in the innermost layer, providing a strong mechanical resistance to avoid catastrophic failure. The overall gradient of the elastic modulus and hardness in the cross-section display a sandwich profile, effectively minimizing the stress concentration and deformation. The lessons gained from the multiscale design strategy of the chela provide important insights into the design and fabrication of bioinspired materials.

Empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin have been shown in randomized controlled trials to improve cardiovascular, metabolic, and renal outcomes in heart failure patients. To date, there has not been any meta-analysis examining the differences in clinical outcomes across different SGLT2 inhibitors in heart failure patients. Four electronic databases (PubMed, Embase, Cochrane, SCOPUS) were searched on 13 September 2020 for articles published from 1 January 2000 to 13 September 2020 examining the effect of SGLT2 inhibitors on cardiovascular, renal, and metabolic outcomes in heart failure patients. Frequentist network meta-analysis was performed on extracted data. Ten randomized controlled trials were included with a combined cohort of 15,373 patients. In heart failure patients, frequentist network meta-analysis demonstrated no demonstrable difference in treatment effect across the SGLT2 inhibitors for heart failure hospitalization, cardiovascular deaths, composite of cardiovascular deaths and heart failure hospitalizations, all-cause mortality, and a composite of cardiovascular deaths and non-fatal myocardial infarction and non-fatal stroke. There was no demonstrable difference in treatment effect for worsening renal function or the weighted mean difference for weight, hemoglobin A1c, and systolic blood pressure. There were no demonstrable treatment differences across SGLT2 inhibitors across cardiovascular, renal, and metabolic outcomes, although this needs to be interpreted considering the wide confidence intervals, limited number of included studies, and heterogeneity present. Future research of different SGLT2 inhibitors in head-to-head studies is warranted to determine if there is a drug class effect.

The tail spike of the mantis shrimp is the appendage for counteracting the enemy from behind. Here, we investigate the correlations between the chemical compositions, the microstructures, and the mechanical properties of the spike. We find that the spike is a hollow beam with a varying cross section along the length. The cross section comprises four different layers with distinct features of microstructures and chemical compositions. The local mechanical properties of these layers correlate well with the microstructures and chemical compositions, a combination of which effectively restricts the crack propagation while maximizing the release of strain energy during deformation. Finite element analysis and mechanics modeling demonstrate that the optimized structure of the spike confines the mechanical damage in the region near the tip and prevents catastrophic breakage at the base. Furthermore, we use a 3D printing technique to fabricate multiple hollow cylindrical samples consisting of biomimetic microstructures of the spike and confirm that the combination of the Bouligand structure with radially oriented parallel sheets greatly improves the toughness and strength during compression tests. The multiscale design strategy of the spike revealed here is expected to be of great interest for the development of novel bioinspired materials.

Dysferlin is a sarcolemmal protein present in muscle cells. It is responsible for muscle membrane repair. Dysferlin gene (DYSF) mutation, resulting in deficiency in this protein, is termed dysferlinopathy. Clinically, it manifests as early adulthood onset of muscle weakness with markedly elevated creatine kinase levels. The main phenotypes are limb-girdle muscular dystrophy type 2B (LGMD2B), affecting proximal muscles, and Miyoshi myopathy (MM), affecting distal muscles. Dysferlin is also present in cardiomyocytes, and case reports have emerged of cardiac abnormalities in dysferlinopathy. While routine methods of cardiac screening, namely, electrocardiography or echocardiography, are convenient and noninvasive, they often exhibit insufficient diagnostic sensitivity for detecting subclinical cardiac remodeling during early stages of cardiomyopathy. Cardiac magnetic resonance imaging though can provide accurate assessment of cardiac chamber sizes and function. With gadolinium administration, it can also detect areas of myocardial scarring and fibrosis. Early diagnosis of neuromuscular disease-related cardiomyopathy is of clinical significance, as appropriate treatment can retard myocardial fibrosis, delaying cardiomyopathy progression. We present a case of a patient with MM incidentally diagnosed with concomitant cardiomyopathy.

Several studies have documented a relationship between non-alcoholic fatty liver disease (NAFLD) and structural heart disease, particularly diastolic function. This meta-analysis will be the first to examine the echocardiographic-derived cardiac function and structural characteristics in NAFLD patients, and its association with liver disease severity and metabolic profile.Medline and Embase were searched and pairwise meta-analysis was conducted in DerSimonian and Laird to obtain the odds ratio (OR) and mean difference (MD) for dichotomous and continuous variables, respectively, to compare the effects of NAFLD on the echocardiography parameters.Forty-one articles involving 33,891 patients underwent echocardiography. NAFLD patients had worse systolic indices with lower ejection fraction (EF, MD: - 0.693; 95% CI: - 1.112 to - 0.274; p = 0.001), and worse diastolic indices with higher E/e' (MD: 1.575; 95% CI: 0.924 to 2.227; p 0.001) compared to non-NAFLD patients. NAFLD patients displayed increased left ventricular mass (LVM, MD: 34.484; 95% CI: 26.236 to 42.732; p 0.001) and epicardial adipose thickness (EAT, MD: 0.1343; 95% CI: 0.055 to 0.214; p = 0.001). An increased severity of NAFLD was associated with worse diastolic indices (decreased E/A ratio, p = 0.007), but not with systolic indices.NAFLD is associated with impaired systolic and diastolic function with changes in cardiac structure. Concomitant metabolic risk factors and liver disease severity are independently associated with worsening systolic and diastolic function.

Heart failure (HF) is one of the leading causes of mortality worldwide. Heart failure is also one of the most common presentations of cardiac amyloidosis (CA). Contemporary epidemiological data of CA in HF patients is lacking. Hence, this systematic review and meta-analysis was conducted to determine the prevalence of amyloidosis in HF patients, and to clarify the risk factors of concomitant CA and HF.A systematic review and meta-analysis was performed. Studies were retrieved from Medline, EMBASE, Scopus and Cochrane library. The search was not restricted in time, type or language of publication. The prevalence of CA in HF grouped according to diagnostic techniques and risk factors of CA with HF was analysed.Eleven (11) studies were included, involving 3,303 patients. The pooled prevalence of CA in HF was 13.7%. The overall prevalence of CA in HF with preserved ejection fraction was 15.1%, and that of HF with reduced ejection fraction was 11.3%. The main factors associated with the diagnosis of CA in HF included older age, males, raised NT pro-BNP, increased interventricular septal thickness in diastole, apical sparing, and reduced left ventricular systolic function.A high index of clinical suspicion is required to identify HF patients with CA. Supportive investigations may be helpful when clinically correlated. A considerable proportion of HF patients have CA and certain risk factors may be helpful in increasing suspicion of CA in HF.

Atrial Fibrillation (AF) is the most commonly diagnosed cardiac arrhythmia. It is associated with significant morbidity and mortality, as it is a major risk factor for cerebral vascular accidents (CVA). Our aim was to determine the prevalence of pre-existing and new-onset AF among patients undergoing liver transplantation (LT) and its impact on post-transplant outcomes.Medline and Embase were searched. Single-arm analysis was conducted using the generalized linear mixed model to determine the prevalence of pre-existing and new-onset AF. Logistic regression was performed to analyze risk factors. Comparative meta-analysis in odds ratio was conducted for binary outcomes.Twenty articles were included, with 17 studies on pre-existing AF, and 7 including data on new-onset AF post-LT. The prevalence of pre-existing AF was 3.3% (CI 2.3-4.7) (14 studies, 45,070 patients) in pooled analysis. Significantly higher prevalence of pre-existing AF patients from North America was noted when compared to Europe (4.5%, CI 3.4-5.8 vs 1.5%, CI 0.8-2.7; p = 0.001). Body mass index (BMI), history of hypertension, diabetes, coronary artery disease (CAD), and cerebrovascular accidents (CVA) were risk factors for pre-existing AF. Pre-existing AF was significantly associated with major adverse cardiac or cerebrovascular events (MACCE) postoperatively (OR 8.02, 95%CI 5.40-11.90, p 0.001). New-onset AF post-LT had an incidence of 6.8% (CI 4.9-9.3), and was associated with increased risk of mortality (OR 2.31, 95% CI 1.76-3.02, p 0.001) and graft failure (OR 2.98, CI 1.99-4.47, p 0.001).AF is relatively more common among patients undergoing LT compared to the general non-transplant population. Additionally, it is associated with adverse outcomes including MACCE, thus warranting clinical attention. Thorough cardiac assessment, and close surveillance of post-operative AF may be clinically prudent.

Background Recent studies have increasingly shown that sodium‐glucose cotransporter 2 (SGLT2) inhibitors may have beneficial cardiovascular and metabolic effects in patients without diabetes mellitus. Hence, we conducted a systematic review and meta‐analysis to determine the effect of SGLT2 inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus. Methods and Results Four electronic databases (PubMed, Embase, Cochrane, and SCOPUS) were searched on August 30, 2020 for articles published from January 1, 2000 to August 30, 2020, for studies that examined the effect of SGLT2 inhibitors on cardiovascular and metabolic outcomes in patients without diabetes mellitus. A random‐effects pairwise meta‐analysis model was used to summarize the studies. A total of 8 randomized‐controlled trials were included with a combined cohort of 5233 patients. In patients without diabetes mellitus, those with heart failure treated with SGLT2 inhibitors had a 20% relative risk reduction in cardiovascular deaths and heart failure hospitalizations, compared with those who were not treated (risk ratio, 0.78; P P 2 ( P P =0.04), and fasting plasma glucose of −0.38 mmol/L ( P =0.05), compared with those without. There were no between‐group differences in NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) levels, waist circumference, diastolic blood pressure, glycated hemoglobin, low‐density lipoprotein cholesterol levels, and estimated glomerular filtration rates. Across our combined cohort of 5233 patients, hypoglycemia was reported in 22 patients. Conclusions SGLT2 inhibitors improve cardiovascular outcomes in patients without diabetes mellitus with heart failure. In patients without diabetes mellitus, SGLT2 inhibitors showed positive metabolic outcomes in weight and blood pressure control.

Dysferlin is a sarcolemmal protein present in muscle cells. It is responsible for muscle membrane repair. Dysferlin gene (DYSF) mutation, resulting in deficiency in this protein, is termed dysferlinopathy. Clinically, it manifests as early adulthood onset of muscle weakness with markedly elevated creatine kinase levels. The main phenotypes are limb-girdle muscular dystrophy type 2B (LGMD2B), affecting proximal muscles, and Miyoshi myopathy (MM), affecting distal muscles. Dysferlin is also present in cardiomyocytes, and case reports have emerged of cardiac abnormalities in dysferlinopathy. While routine methods of cardiac screening, namely, electrocardiography or echocardiography, are convenient and noninvasive, they often exhibit insufficient diagnostic sensitivity for detecting subclinical cardiac remodeling during early stages of cardiomyopathy. Cardiac magnetic resonance imaging though can provide accurate assessment of cardiac chamber sizes and function. With gadolinium administration, it can also detect areas of myocardial scarring and fibrosis. Early diagnosis of neuromuscular disease-related cardiomyopathy is of clinical significance, as appropriate treatment can retard myocardial fibrosis, delaying cardiomyopathy progression. We present a case of a patient with MM incidentally diagnosed with concomitant cardiomyopathy.

Empagliflozin, dapagliflozin, canagliflozin, and ertugliflozin have been shown in randomized controlled trials to improve cardiovascular, metabolic, and renal outcomes in heart failure patients. To date, there has not been any meta-analysis examining the differences in clinical outcomes across different SGLT2 inhibitors in heart failure patients.Four electronic databases (PubMed, Embase, Cochrane, SCOPUS) were searched on 13 September 2020 for articles published from 1 January 2000 to 13 September 2020 examining the effect of SGLT2 inhibitors on cardiovascular, renal, and metabolic outcomes in heart failure patients. Frequentist network meta-analysis was performed on extracted data.Ten randomized controlled trials were included with a combined cohort of 15,373 patients. In heart failure patients, frequentist network meta-analysis demonstrated no demonstrable difference in treatment effect across the SGLT2 inhibitors for heart failure hospitalization, cardiovascular deaths, composite of cardiovascular deaths and heart failure hospitalizations, all-cause mortality, and a composite of cardiovascular deaths and non-fatal myocardial infarction and non-fatal stroke. There was no demonstrable difference in treatment effect for worsening renal function or the weighted mean difference for weight, hemoglobin A1c, and systolic blood pressure.There were no demonstrable treatment differences across SGLT2 inhibitors across cardiovascular, renal, and metabolic outcomes, although this needs to be interpreted considering the wide confidence intervals, limited number of included studies, and heterogeneity present. Future research of different SGLT2 inhibitors in head-to-head studies is warranted to determine if there is a drug class effect.

Anomaly detection for dynamic graphs, with graphs changing over time, is essential in many real-world applications. Existing works did not consider the accurate community structures in a dynamic graph. This paper introduces CmaGraph, a TriBlocks framework using an innovative deep metric learning block to measure the distances between vertices within and between communities from an evolution community detection block. A one-class anomaly detection block can capture the dynamic graph’s anomalous edges after these two functional blocks. This method significantly enhances the capability to detect anomalous edges by reconstructing the distance between the evolutionary communities’ vertices. We demonstrate the implications on three real-world datasets and compare them with the state-of-the-art method.