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Hypertrophic cardiomyopathy predisposes to acute cerebrovascular events including ischaemic stroke, transient ischaemic attack and systemic thromboembolism. Atrial fibrillation confers even higher risk. We aim to report the incidence of these complications and to investigate the impact of atrial fibrillation on the ischaemic risk in patients with hypertrophic cardiomyopathy. A literature search was performed on PubMed, Scopus, Embase/Ovid and Cochrane library from inception to 20th March 2021. We compared the incidence of ischaemic strokes, transient ischaemic attack, non-specified thromboembolism events and systemic thromboembolism in hypertrophic cardiomyopathy patients with or without atrial fibrillation. Non-specified thromboembolism events in our paper referred to thromboembolic events whereby types were not specified in the studies. Meta-analysis was performed using StataSE 16 software, and heterogeneity was assessed using I2 test. A total of 713 studies were identified. Thirty-five articles with 42,570 patients were included. The pooled incidence of stroke/ transient ischaemic attack was 7.45% (95% confidence interval [CI] 5.80-9.52, p < 0.001) across 24 studies with a total of 37,643 hypertrophic cardiomyopathy patients. Atrial fibrillation significantly increased the risk of total stroke/ transient ischaemic attack (Risk Ratio 3.26, 95% CI 1.75-6.08, p < 0.001, I2 = 76.0). The incidence of stroke/ transient ischaemic attack was 9.30% (95% CI 6.64-12.87, p = 0.316) in the apical hypertrophic cardiomyopathy subgroup. Concomitant atrial fibrillation in hypertrophic cardiomyopathy increases the risk of thromboembolic events including ischaemic stroke and transient ischaemic attack. The apical subgroup shows a similar risk of acute cerebrovascular events as the overall hypertrophic cardiomyopathy population.
Subject(s)
Atrial Fibrillation , Brain Ischemia , Cardiomyopathy, Hypertrophic , Ischemic Attack, Transient , Ischemic Stroke , Stroke , Thromboembolism , Humans , Stroke/etiology , Atrial Fibrillation/complications , Atrial Fibrillation/epidemiology , Brain Ischemia/complications , Thromboembolism/etiology , Thromboembolism/complications , Ischemic Stroke/complications , Cardiomyopathy, Hypertrophic/complications , Risk FactorsABSTRACT
BACKGROUND: Some observational studies and randomised controlled trials (RCTs) have reported an association between calcium supplementation and increased risk of cardiovascular disease. Previous meta-analyses on the topic, based on data from RCTs and observational studies, have contradictory findings. This meta-analysis was conducted to determine the difference in associated risks of calcium supplementation with cardiovascular disease and stroke in RCTs. METHODS: Relevant studies published from database inception to 6 August 2021 were sourced from PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. Any RCTs focusing on the relationship between calcium supplementation and incidence of cardiovascular disease or stroke were included. Articles were screened independently by two authors, according to the PICO criteria, with disagreements resolved by a third author. RESULTS: Twelve RCTs were included in the meta-analysis. Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and all-cause/cardiovascular mortality. Subgroup analysis focusing on calcium monotherapy/calcium co-therapy with vitamin D, female sex, follow-up duration, and geographical region did not affect the findings. CONCLUSION: Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and cardiovascular/all-cause mortality. Further studies are required to examine and understand these associations.
Subject(s)
Cardiovascular Diseases , Heart Failure , Myocardial Infarction , Stroke , Female , Humans , Cardiovascular Diseases/epidemiology , Calcium , Stroke/epidemiology , Stroke/etiology , Stroke/prevention & control , Dietary SupplementsABSTRACT
INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are increasingly utilized in the treatment of diabetes mellitus as well as therapeutic extra-glycemic effects. However, there are still concerns over complications such as amputation events, given the results from the Canagliflozin Cardiovascular Assessment Study (CANVAS) trial. Hence, we conducted a systematic review and meta-analysis of randomized-controlled trials to investigate the effect of SGLT2 inhibitors on amputation events. METHODS: Four electronic databases (PubMed, Embase, Cochrane, and SCOPUS) were searched on November 21, 2020, for articles published from January 1, 2000, up to November 21, 2020, for studies that examined the effect of SGLT2 inhibitors on amputation events. Random-effect pair-wise meta-analysis for hazard ratios and fixed-effect Peto odds ratio meta-analysis were utilized to summarize the studies. RESULTS: A total of 15 randomized-controlled trials were included with a combined cohort of 63,716 patients. We demonstrated that there was no significant difference in amputation events across different types of SGLT2 inhibitors, different baseline populations, and different duration of SGLT2 inhibitor use. DISCUSSION/CONCLUSIONS: In this meta-analysis, SGLT2 inhibitors were not associated with a significant difference in amputation events.
Subject(s)
Diabetes Mellitus, Type 2 , Amputation, Surgical , Blood Glucose , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/surgery , Humans , Randomized Controlled Trials as Topic , Sodium , Sodium-Glucose Transporter 2/therapeutic useABSTRACT
During V(D)J recombination of immunoglobulin genes, p53 and nonhomologous end-joining (NHEJ) suppress aberrant rejoining of DNA double-strand breaks induced by recombinase-activating genes (Rags)-1/2, thus maintaining genomic stability and limiting malignant transformation during B-cell development. However, Rag deficiency does not prevent B-cell leukemogenesis in p53/NHEJ mutant mice, revealing that p53 and NHEJ also suppress Rag-independent mechanisms of B-cell leukemogenesis. Using several cytogenomic approaches, we identified a novel class of activating mutations in Fms-like tyrosine kinase 3 (Flt3), a receptor tyrosine kinase important for normal hematopoiesis in Rag/p53/NHEJ triple-mutant (TM) B-cell leukemias. These mutant Flt3 alleles were created by complex genomic rearrangements with Moloney leukemia virus (MuLV)-related endogenous retroviral (ERV) elements, generating ERV-Flt3 fusion genes encoding an N-terminally truncated mutant form of Flt3 (trFlt3) that was transcribed from ERV long terminal repeats. trFlt3 protein lacked most of the Flt3 extracellular domain and induced ligand-independent STAT5 phosphorylation and proliferation of hematopoietic progenitor cells. Furthermore, expression of trFlt3 in p53/NHEJ mutant hematopoietic progenitor cells promoted development of clinically aggressive B-cell leukemia. Thus, repetitive MuLV-related ERV sequences can participate in aberrant end-joining events that promote development of aggressive B-cell leukemia.
Subject(s)
B-Lymphocytes/cytology , Leukemia/genetics , Moloney murine leukemia virus/genetics , Recombination, Genetic , fms-Like Tyrosine Kinase 3/genetics , fms-Like Tyrosine Kinase 3/metabolism , Animals , B-Lymphocytes/pathology , Cell Proliferation , DNA End-Joining Repair/genetics , Gene Expression Regulation, Leukemic , Hematopoietic Stem Cells/cytology , Leukemia/pathology , Mice , Moloney murine leukemia virus/metabolism , Mutation , Phosphorylation , Protein Structure, Tertiary , STAT5 Transcription Factor/metabolism , Signal Transduction , Tumor Cells, CulturedABSTRACT
AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
Subject(s)
Amyloidosis , Heart Failure , Male , Humans , Prevalence , Heart Failure/diagnosis , Stroke Volume , Amyloidosis/complications , Amyloidosis/epidemiology , Risk FactorsABSTRACT
BACKGROUND: There are differences in bicuspid aortic valve (BAV) characteristics between Asian and European populations, but little is known about the inter-ethnic differences in bicuspid valve function and aortic root dimensions within the diverse Asian population. METHODS: From 1992-2017, 562 patients with index echocardiographic diagnosis of BAV in a tertiary health care institution in Singapore were analysed according to their ethnic groups: Chinese, Malay, Indian, and Eurasian. Study outcomes included BAV complications (infective endocarditis, aortic dissection) and clinical outcomes (aortic valve surgery, aortic root surgery, all-cause mortality). Total events were defined as composite outcome of all BAV complications and outcomes. Aortic dimensions and aortic dilatation rates were also studied. RESULTS: There were 379 (67.5%) Chinese, 79 (14.0%) Malay, 73 (13.0%) Indian, and 31 (5.5%) Eurasian patients. Type 1 BAV (58.5%) was the most prevalent BAV morphology, with moderate-to-severe aortic stenosis (AS) (36.8%) being the most common complication in the overall population. There was a higher prevalence of type 0 BAV in Chinese and Indian groups, and type 1 BAV with fusion of left-right coronary cusp in Eurasian and Malay groups (p=0.082). There was no difference in significant AS among groups. The highest prevalence of moderate-to-severe aortic regurgitation was observed amongst the Eurasian group, followed by Chinese, Indian, and Malay groups (p=0.033). The Chinese group had the largest mean indexed diameters of the aortic root. Multivariable linear regression demonstrated that only the Chinese had significantly larger indexed diameters in the aortic annulus, sinotubular junction (STJ), and ascending aorta (AA), relative to the Eurasian group, after adjusting for age, sex, smoking, hypertension, hyperlipidaemia, diabetes, and aortic regurgitation. On follow-up echocardiography, there was a trend towards the highest dilatation rates of sinus of Valsalva and STJ amongst Indian, and AA amongst Malay groups. Kaplan-Meier curves showed the highest incidence of total events amongst Chinese, followed by Malay, Indian and Eurasian (log-rank=9.691; p=0.021) patients. CONCLUSION: There were differences in BAV morphology, valve dysfunction, aortopathy, and prognosis within the Asian population. Chinese patients had one of the highest prevalence of significant aortic regurgitation, with the largest aortic dimensions and worst outcomes compared with other Asian ethnicities. Closer surveillance is warranted in BAV patients within the Asian population.
Subject(s)
Aortic Valve Insufficiency , Bicuspid Aortic Valve Disease , Heart Valve Diseases , Aortic Valve/surgery , Aortic Valve Insufficiency/epidemiology , Aortic Valve Insufficiency/etiology , Heart Valve Diseases/diagnosis , Humans , Retrospective StudiesABSTRACT
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.
Subject(s)
Heart Failure , Sodium-Glucose Transporter 2 Inhibitors , Humans , Heart Failure/drug therapy , Heart Failure/etiology , Hospitals , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Clinical Trials as TopicABSTRACT
PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Subject(s)
Heart Failure/drug therapy , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Aged , Aged, 80 and over , Blood Pressure , Body Weight , Cardiovascular Diseases/mortality , Female , Glycated Hemoglobin , Hospitalization , Humans , Kidney Function Tests , Male , Middle Aged , Network Meta-Analysis , Randomized Controlled Trials as TopicABSTRACT
BACKGROUND: Current guidelines on the management strategy for patients with asymptomatic severe aortic stenosis (AS) remain unclear. This uncertainty stems from the lack of data regarding the natural history of these patients. To address this gap, we performed a systematic review and meta-analysis examining the natural history of asymptomatic severe AS patients receiving conservative treatment. METHODS: The PubMed, Cochrane, and Embase databases were searched from inception to 24 January 2024 using the keywords "asymptomatic" AND "aortic" AND "stenosis". We included studies examining patients with asymptomatic severe AS. In interventional trials, only data from conservatively managed arms were collected. A one-stage meta-analysis was conducted using individual patient data reconstructed from published Kaplan-Meier curves. Sensitivity analysis was performed for major adverse cardiovascular outcomes in patients who remained asymptomatic throughout follow-up. RESULTS: A total of 46 studies were included (n = 9545). The median time to the development of symptoms was 1.11 years (95% CI 0.90-1.53). 49.36% (40.85-58.59) of patients who were asymptomatic had suffered a major adverse cardiovascular event by 5 years. The median event-free time for heart failure hospitalization (HFH) was 5.50 years (95% CI 5.14-5.91) with 36.34% (95% CI 33.34-39.41) of patients experiencing an HFH by year 5. By 5 years, 79.81% (95% CI 69.26-88.58) of patients developed symptoms (angina, dyspnoea, syncope and others) and 12.36% (95% CI 10.01-15.22) of patients died of cardiovascular causes. For all-cause mortality, the median survival time was 9.15 years (95% CI 8.50-9.96) with 39.43% (CI 33.41-36.40) of patients dying by 5 years. The median time to AVR was 4.77 years (95% CI 4.39-5.17), with 52.64% (95% CI 49.85-55.48) of patients requiring an AVR by 5 years. CONCLUSION: Our results reveal poor cardiovascular outcomes for patients with asymptomatic severe AS on conservative treatment. A significant proportion eventually requires an AVR. Further research is needed to determine if early intervention with AVR is more effective than conservative treatment.
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Background: Cardiogenic shock (CS) complicating myocardial infarction is associated with poor outcomes. Data among Asian populations are scarce. We aimed to investigate the long-term outcomes, prognostic factors, and predictors of CS among Asian ST elevation myocardial infarction (STEMI) patients. Methods: This was a retrospective cohort study of consecutive patients undergoing primary percutaneous coronary intervention (PPCI) for STEMI within our regional STEMI network between 2015 and 2019. The long-term outcomes of those with and without CS were compared. Clinical predictors of outcomes and development of CS were investigated. Results: A total of 1791 patients who underwent PPCI were included. Patients completed at least 2 years' follow-up with a median follow-up period of 2.6 years (IQR 1.0, 3,9). Overall, 208/1791 (11.6 %) STEMI patients developed CS. These patients were older (61.1 ± 12.5 vs 57.8 ± 12.2, P < 0.001) and mostly men (87.0 %). All-cause mortality (59.9 % vs 4.7 % P < 0.001), cardiac mortality (43.8 % vs 2.2 %, P < 0.001) and major adverse cardiovascular events (MACE) was significantly higher in the CS group (59.1 % vs 14.0 %, P < 0.001). Independent predictors of survival were higher index LVEF (adjusted hazards ratio [aHR] 0.967, 95 %CI 0.951-0.984, p < 0.001) and higher arterial pH at onset of shock (aHR 0.750, 0.626-0.897, p = 0.002). Increased serum lactate concentration independently predicts poor prognosis (aHR 1.084, 95 % CI 1.046-1.124, p < 0.001). Conclusion: In Asian STEMI patients who underwent PPCI, CS was associated with poor outcomes. Higher LVEF on index admission was associated with better outcomes; while lactic acidosis independently predicted mortality.
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INTRODUCTION: A middle-aged male developed right-sided endocarditis from an infection of an implantable cardiac defibrillator (ICD) system. Following percutaneous device and lead explantation, a very large pedunculated vegetation (19 mm × 14 mm) was found on the Eustachian valve. We decided to remove the vegetation percutaneously using a wire snare instead of open heart surgery. CASE REPORT: Real-time three-dimensional transesophageal echocardiography and fluoroscopy were used to guide the procedure. Access was from the right femoral vein. Using a triple-loop wire snare through a deflectable sheath, the vegetation was successfully removed in its entirety without complications. CONCLUSION: Percutaneous snare vegetectomy is feasible and may be a viable option in place of open heart surgery in selected patients.
Subject(s)
Cardiac Catheterization , Defibrillators, Implantable/adverse effects , Endocarditis, Bacterial/therapy , Prosthesis-Related Infections/therapy , Staphylococcal Infections/therapy , Anti-Bacterial Agents/therapeutic use , Device Removal , Echocardiography, Three-Dimensional , Echocardiography, Transesophageal , Endocarditis, Bacterial/diagnosis , Endocarditis, Bacterial/microbiology , Fluoroscopy , Humans , Male , Middle Aged , Patient Selection , Prosthesis-Related Infections/diagnosis , Prosthesis-Related Infections/microbiology , Prosthesis-Related Infections/surgery , Radiography, Interventional/methods , Reoperation , Staphylococcal Infections/diagnosis , Staphylococcal Infections/microbiology , Staphylococcus epidermidis/isolation & purification , Treatment Outcome , Ultrasonography, Interventional/methodsABSTRACT
BACKGROUND: Recent studies have shown that breast arterial calcification (BAC) detected on screening mammography is linked to cardiovascular diseases via medial calcification. However, its effect on cardiovascular outcomes remains unclear. Therefore, we conducted a meta-analysis to determine the effect of BAC on cardiovascular outcomes in patients. METHODS: Three electronic databases (Pubmed, Embase, and Scopus) were searched on May 1, 2022, for studies examining the relationship between BAC and cardiovascular outcomes including cardiac death, acute myocardial infarction, ischemic heart disease, stroke, peripheral artery disease, and heart failure. A random-effects meta-analysis model was used to summarise the studies. RESULTS: A total of 5 longitudinal studies were included with a combined cohort of 87,865 patients. Significantly, the pooled risk ratio (RR) of the association between BAC and cardiac death was 2.06 (P < 0.00001). BAC was associated with a significantly increased risk of developing other cardiovascular diseases, such as ischemic/hemorrhagic stroke (RR 1.51; P = 0.003), ischemic stroke (RR 1.82; P < 0.00001), peripheral vascular disease (RR 1.24; P = 0.003), and heart failure (RR 1.84; P < 0.00001). There was no significant relationship for developing myocardial infarction or for total cardiovascular diseases. CONCLUSIONS: Our findings suggest that BAC was associated with an increased risk of cardiovascular mortality, and certain cardiovascular outcomes. There is thus a potential to use BAC as a sex-specific cardiovascular risk assessment tool. Furthermore, there is a need for more widespread reporting of BAC to better understand the pathophysiologic mechanisms behind its correlation with cardiovascular disease and to apply it in clinical practice.
Subject(s)
Breast Diseases , Breast Neoplasms , Cardiovascular Diseases , Heart Failure , Myocardial Infarction , Female , Male , Humans , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/complications , Breast/diagnostic imaging , Breast/blood supply , Mammography , Breast Neoplasms/complications , Risk Factors , Early Detection of Cancer , Breast Diseases/complications , Myocardial Infarction/complications , Heart Failure/complications , DeathABSTRACT
BACKGROUND: There are four known pericentromeric euchromatic variants of chromosome 9 in the literature that are increasingly being observed in diagnostic cytogenetic laboratories. These variants pose diagnostic and counselling dilemmas, especially in prenatal settings, as distinction of a pathogenic alteration from a euchromatic variant is difficult. The molecular characterisation of three of these four variants has been reported. In this study, the genomic structure of the fourth variant, an additional G-positive band at 9q13-q21, is characterised. METHODS: Two unrelated families with the 9q13-q21 duplication variant, and a third individual with a cytogenetically visible 9q13-q21 deletion, were studied using conventional and molecular cytogenetics techniques, as well as microarrays. The highly repetitive nature of the segmental duplications in the region also necessitated the use of both interphase and metaphase fluorescence in situ hybridisation (FISH). RESULTS: It was determined that the DNA that constitutes this variant was â¼ 15-20 megabases in size and tandemly repeated as 3-4 cassettes of intrachromosomal segmental duplication. The variant appeared constitutively similar in sequence content and organisation between the two unrelated individuals, and it was inherited without apparent change. Sequences found amplified in the two duplication carriers were absent in the carrier of the deletion variant. CONCLUSIONS: The sequences involved in both the 9q13-q21 duplication and deletion appear the same, implying reciprocity and suggesting non-allelic homologous recombination as the underlying mechanism. All four known euchromatic variants of chromosome 9 have now been shown to encompass segmental duplications. Importantly, a set of validated FISH probes was defined for the detection and characterisation of this 9q13-q21 amplification in the context of other chromosome 9 variants, allowing apparently benign variants to be distinguished from pathogenic changes.
Subject(s)
Chromosome Deletion , Chromosome Duplication/genetics , Chromosomes, Human, Pair 9/genetics , Gene Amplification/genetics , Adult , DNA Copy Number Variations/genetics , Fetus , Humans , In Situ Hybridization, Fluorescence , Microarray AnalysisABSTRACT
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.
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BACKGROUND AND OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Subject(s)
Biphenyl Compounds , Heart Failure , Aminobutyrates , Drug Combinations , Glucose , Heart Failure/drug therapy , Humans , Network Meta-Analysis , Sodium , Stroke Volume , Tetrazoles/therapeutic use , ValsartanABSTRACT
Objectives: Sodium-glucose cotransporter-2 (SGLT2) inhibitors have been found to reduce serum urate in patients with type 2 diabetes mellitus. To evaluate if this effect applies to both patients with and without diabetes, we conducted a systematic review and meta-analysis of SGLT2 inhibitors on serum urate levels in this population. Methods: Four electronic databases (PubMed, Embase, Cochrane and SCOPUS) were searched on 25 September 2021 for articles published from 1 January 2000 up to 25 September 2021, for studies that examined the effect of SGLT2 inhibitors on serum urate in study subjects. Random-effects meta-analysis was performed, with subgroup analyses on the type of SGLT2 inhibitor agent administered, presence of type 2 diabetes mellitus, presence of chronic kidney disease and drug dose. Results: A total of 43 randomized controlled trials, with a combined cohort of 31,921 patients, were included. Both patients with [-31.48 µmol/L; 95% confidence interval (CI): -37.35 to -25.60] and without diabetes (-91.38 µmol/L; 95% CI: -126.53 to -56.24) on SGLT2 inhibitors had significantly lower urate levels when compared with placebo. This treatment effect was similarly observed across different types of SGLT2 inhibitors. However, in type 2 diabetes mellitus (T2DM) patients with chronic kidney disease, the reduction in serum urate with SGLT2 inhibitors became insignificant (95% CI: -22.17 to 5.94, p < 0.01). Conclusion: This study demonstrated that SGLT2 inhibitors are beneficial in reducing serum urate in patients with and without diabetes. SGLT2 inhibitors could therefore contribute to the general treatment of hyperuricaemia.
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BACKGROUND: Patients with atrial fibrillation (AF) have a higher risk of developing thromboembolic events. Current guidelines recommend the use of oral anticoagulants for stroke prevention in these patients. Several clinical trials demonstrated that direct oral anticoagulants (DOACs) have similar efficacy and are safer alternatives to traditional oral anticoagulants. However, patients with concomitant liver cirrhosis were excluded from these trials. OBJECTIVE: We aimed to systematically identify and review published clinical studies on the use of DOACs in patients with AF and liver cirrhosis and assess the efficacy and safety of DOACs in these patients. METHODS: A systematic review of clinical trials and retrospective studies was conducted by searching the PubMed, Cochrane Library, Embase, SCOPUS, and Web of Science databases up to September 2020. RESULTS: Three retrospective studies were included, involving 4011 patients with AF and liver cirrhosis. The use of DOACs was associated with a significant reduction in ischemic stroke (hazard ratio [HR] 0.62; 95% confidence interval [CI] 0.42-0.90; p = 0.01), major bleeding events (HR 0.64; 95% CI 0.57-0.72; p < 0.001), and intracranial hemorrhage (HR 0.49; 95% CI 0.40-0.59; p < 0.001). CONCLUSIONS: Compared with warfarin in patients with AF and liver cirrhosis, DOACs appear to be associated with improved efficacy and safety outcomes. Randomized controlled trials are warranted to confirm these findings.
Subject(s)
Atrial Fibrillation , Stroke , Administration, Oral , Anticoagulants/adverse effects , Atrial Fibrillation/complications , Atrial Fibrillation/drug therapy , Humans , Liver Cirrhosis/chemically induced , Liver Cirrhosis/complications , Liver Cirrhosis/drug therapy , Retrospective Studies , Stroke/complications , Stroke/prevention & control , Vitamin KABSTRACT
Literature of patients with severe high-gradient aortic stenosis (HG AS) (mean pressure gradient [MPG] ≥ 40 mmHg and aortic valve area [AVA] ≥ 1.0 cm2) remains limited. This study seeks to compare the prognostic outcomes of patients with high-gradient concordant (HGCON-AS) and discordant AS (HGDIS-AS) in an Asian cohort. From 2010 to 2015, patients with moderate-to-severe AS with preserved left ventricular ejection fraction (LVEF ≥ 50%) were recruited and stratified into 3 groups based on index echocardiogram-(1) HGDIS-AS, (2) HGCON-AS and (3) moderate AS (MOD-AS). The primary study endpoints was all-cause mortality, with secondary endpoints of congestive heart failure (CHF) admissions and aortic valve replacement (AVR). Multivariable Cox regression was used and Kaplan-Meier curves were constructed to evaluate associations between HGDIS-AS, HGCON-AS and MOD-AS, and the study outcomes. A total of 467 patients were studied, comprising of 6.2% HGDIS-AS, 13.9% HGCON-AS and 79.9% MOD-AS patients. There was significantly higher AVR rates in the HGCON-AS group (58.5%), followed by HGDIS-AS (31.0%) and MOD-AS (4.6%), p < 0.001) groups. After adjusting for confounders, HGCON-AS was significantly associated with all-cause mortality (HR 3.082, 95% CI 1.479-6.420, p = 0.003) and CHF admissions (HR 12.728, 95% CI 2.922-55.440 p = 0.001) but not HGDIS-AS, with MOD-AS as the reference group. Both HGDIS-AS (HR 7.715, 95% CI 2.927-20.338; p < 0.001) and HGCON-AS (HR 21.960, 95% CI 10.833-44.515, p < 0.001) were independent predictors of AVR. After exclusion of reversible high-flow states, HGDIS-AS patients appear to have a more favourable prognostic profile compared to HGCON-AS patients. Large prospective interventional studies examining the prognostic differences between the two groups will be the next important step.
ABSTRACT
Introduction: Heart failure (HF) is associated with ischemic stroke (IS). However, there are limited studies on the prevalence of IS, white matter hyperintensities (WMHs), and silent brain infarcts (SBIs). Furthermore, interaction with ejection fraction (EF) is unclear. Methods: We searched three databases (viz., PubMed, Embase, and Cochrane) for studies reporting the incidence or prevalence of IS, WMHs, and SBIs in HF. A total of two authors independently selected included studies. We used random-effects models, and heterogeneity was evaluated with I2 statistic. Meta-regression was used for subgroup analysis. Results: In total, 41 articles involving 870,002 patients were retrieved from 15,267 records. Among patients with HF, the pooled proportion of IS was 4.06% (95% CI: 2.94-5.59), and that of WMHs and SBIs was higher at 15.67% (95% CI: 4.11-44.63) and 23.45% (95% CI: 14.53-35.58), respectively. Subgroup analysis of HFpEF and HFrEF revealed a pooled prevalence of 2.97% (95% CI: 2.01-4.39) and 3.69% (95% CI: 2.34-5.77), respectively. Subgroup analysis of WMH Fazekas scores 1, 2, and 3 revealed a decreasing trend from 60.57 % (95% CI: 35.13-81.33) to 11.57% (95% CI: 10.40-12.85) to 3.07% (95% CI: 0.95-9.47). The relative risk and hazard ratio of patients with HF developing IS were 2.29 (95% CI: 1.43-3.68) and 1.63 (95% CI: 1.22-2.18), respectively. Meta-regression showed IS prevalence was positively correlated with decreasing anticoagulant usage. Conclusion: We obtained estimates for the prevalence of IS, WMH, and SBI in HF from systematic review of the literature. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=255126, PROSPERO [CRD42021255126].