Non-Vitamin K Antagonist Oral Anticoagulants versus Low Molecular Weight Heparin for Cancer-Related Venous Thromboembolic Events: Individual Patient Data Meta-Analysis.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in cancer patients. Low molecular weight heparin (LMWH) has been the standard of care but new guidelines have approved the use of non-vitamin K antagonist oral anticoagulants (NOAC). By conducting an individual patient data (IPD) meta-analysis of randomised controlled trials (RCTs) comparing the outcomes of NOAC versus LMWH in cancer patients, we aim to determine an ideal strategy for the prophylaxis of VTE and prevention of VTE recurrence. Three databases were searched from inception until 19 October 2022. IPD was reconstructed from Kaplan-Meier curves. Shared frailty, stratified Cox and Royston-Parmar models were fit to compare the outcomes of venous thromboembolism recurrence and major bleeding. For studies without Kaplan-Meier curves, aggregate data meta-analysis was conducted using random-effects models. Eleven RCTs involving 4844 patients were included. Aggregate data meta-analysis showed that administering NOACs led to a significantly lower risk of recurrent VTE (RR = 0.65; 95%CI: 0.50-0.84) and deep vein thrombosis (DVT) (RR = 0.60; 95%CI: 0.40-0.90). In the IPD meta-analysis, NOAC when compared with LMWH has an HR of 0.65 (95%CI: 0.49-0.86) for VTE recurrence. Stratified Cox and Royston-Parmar models demonstrated similar results. In reducing risks of recurrent VTE and DVT among cancer patients, NOACs are superior to LMWHs without increased major bleeding.

Trends and predictions of metabolic risk factors for acute myocardial infarction: findings from a multiethnic nationwide cohort.

Background: Understanding the trajectories of metabolic risk factors for acute myocardial infarction (AMI) is necessary for healthcare policymaking. We estimated future projections of the incidence of metabolic diseases in a multi-ethnic population with AMI. Methods: The incidence and mortality contributed by metabolic risk factors in the population with AMI (diabetes mellitus [T2DM], hypertension, hyperlipidemia, overweight/obesity, active/previous smokers) were projected up to year 2050, using linear and Poisson regression models based on the Singapore Myocardial Infarction Registry from 2007 to 2018. Forecast analysis was stratified based on age, sex and ethnicity. Findings: From 2025 to 2050, the incidence of AMI is predicted to rise by 194.4% from 482 to 1418 per 100,000 population. The largest percentage increase in metabolic risk factors within the population with AMI is projected to be overweight/obesity (880.0% increase), followed by hypertension (248.7% increase), T2DM (215.7% increase), hyperlipidemia (205.0% increase), and active/previous smoking (164.8% increase). The number of AMI-related deaths is expected to increase by 294.7% in individuals with overweight/obesity, while mortality is predicted to decrease by 11.7% in hyperlipidemia, 29.9% in hypertension, 32.7% in T2DM and 49.6% in active/previous smokers, from 2025 to 2050. Compared with Chinese individuals, Indian and Malay individuals bear a disproportionate burden of overweight/obesity incidence and AMI-related mortality. Interpretation: The incidence of AMI is projected to continue rising in the coming decades. Overweight/obesity will emerge as fastest-growing metabolic risk factor and the leading risk factor for AMI-related mortality. Funding: This research was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03) and National Medical Research Council Research Training Fellowship (MOH-001131). The SMIR is a national, ministry-funded registry run by the National Registry of Diseases Office and funded by the Ministry of Health, Singapore.

Association Between Breast Arterial Calcifications and Cardiovascular Disease: A Systematic Review and Meta-analysis.

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.

Symptomatic intracerebral hemorrhage after non-emergency percutaneous coronary intervention: Incidence, risk factors, and association with cardiovascular outcomes.

Objective: To investigate the incidence, risk factors, and association with cardiovascular outcomes of patients who developed symptomatic intracerebral hemorrhage (ICH) after non-emergency percutaneous coronary intervention (PCI). Methods: We conducted a single-institution retrospective study of patients who developed symptomatic ICH after non-emergency PCI. To identify associations between clinical variables and outcomes, Cox-proportional hazards regression models were constructed. Outcomes analyzed include (1) all-cause mortality, (2) acute ischemic stroke (AIS) or transient ischemic attack (TIA), and (3) major adverse cardiovascular events (MACE). Results: A total of 1,732 patients were included in the analysis. The mean (±SD) age was 61.1 (±11.3) years, and 1,396 patients (80.6%) were male. The cumulative incidence of symptomatic ICH after non-emergency PCI was 1.3% (22 patients). Age, chronic kidney disease, and prior coronary artery bypass graft surgery were independently associated with a higher risk of ICH after PCI, while hyperlipidemia was independently associated with a lower risk of ICH after PCI. ICH after PCI was independently associated with a higher risk of all-cause mortality and AIS or TIA after PCI. Conclusion: Patients who are older, who have chronic kidney disease, and who have had prior coronary artery bypass graft surgery should be monitored for symptomatic ICH after non-emergency PCI.

Long-term outcomes in acute coronary syndrome patients without standard modifiable risk factors: a multi-ethnic retrospective cohort study Of 5400 asian patients.

A sizeable number of patients without standard modifiable cardiovascular risk factors (SMuRFs), such as hypertension, diabetes, hypercholesterolemia and smoking, suffer from acute coronary syndrome (ACS). These SMuRF-less patients have high short-term morbidity and mortality. We compared both short- and long-term outcomes of SMuRF-less and SMuRF ACS patients in a multi-ethnic Asian cohort.This was a retrospective study of patients with first ACS from 2011 to 2017. The primary outcome was long-term all-cause mortality. Secondary outcomes were 30-day all-cause mortality, cardiac-mortality, unplanned cardiac readmission, cardiogenic shock, heart failure, and stroke. Subgroup analysis was carried out by sex and ACS type.Of 5400 patients, 8.6% were SMuRF-less. The median follow-up time was 6.3 years (interquartile range [IQR] 4.2-8.2 years). SMuRF-less patients were younger and tended to present with ST-segment elevation myocardial infarction (STEMI). They were more likely to require inotropic support, intubation, and have cardiac arrest. At 30 days, SMuRF-less patients had higher rates of all-cause mortality, cardiac-related mortality and cardiogenic shock, but lower rates of heart failure. At 6 years, all-cause mortality was similar in both groups (18.0% versus 17.1% respectively, p = 0.631). Kaplan-Meier curves showed increased early mortality in the SMuRF-less group, but the divergence in survival curves was no longer present in the long-term. The absence of SMuRF was an independent predictor of mortality, regardless of sex or ACS type.In a multi-ethnic cohort of patients with ACS, SMuRF-less patients were observed to have higher mortality than SMuRF patients during the early stages which was attenuated over time.

Prevalence and Risk Factors of Cardiac Amyloidosis in Heart Failure: A Systematic Review and Meta-Analysis.

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.

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.

Risk Factors for Mortality in Cardiac Implantable Electronic Device (CIED) Infections: A Systematic Review and Meta-Analysis.

BACKGROUND: Infections following cardiac implantable electronic device (CIED) implantation can require surgical device removal and often results in significant cost, morbidity, and potentially mortality. We aimed to systemically review the literature and identify risk factors associated with mortality following CIED infection. METHODS: Electronic searches (up to June 2021) were performed on PubMed and Scopus. Twelve studies (10 retrospective, 2 prospective cohort studies) were included for analysis. Meta-analysis was conducted with the restricted maximum likelihood method, with mortality as the outcome. The overall mortality was 13.7% (438/1398) following CIED infection. RESULTS: On meta-analysis, the male sex (OR 0.77, 95%CI 0.57-1.01, I2 = 2.2%) appeared to have lower odds for mortality, while diabetes mellitus appeared to be associated with higher mortality (OR 1.47, 95%CI 0.67-3.26, I2 = 81.4%), although these trends did not reach statistical significance. Staphylococcus aureus as the causative organism (OR 2.71, 95%CI 1.76-4.19, I2 = 0.0%), presence of heart failure (OR 1.92, 95%CI 1.42-4.19, I2 = 0.0%) and embolic phenomena (OR 4.00, 95%CI 1.67-9.56, I2 = 69.8%) were associated with higher mortality. Surgical removal of CIED was associated with lower mortality compared with conservative management with antibiotics alone (OR 0.22, 95%CI 0.09-0.50, I2 = 62.8%). CONCLUSION: We identified important risk factors associated with mortality in CIED infections, including Staphyloccocus aureus as the causative organism, and the presence of complications, such as heart failure and embolic phenomena. Surgery, where possible, was associated with better outcomes.

Long-Term Prognosis of Acute Myocardial Infarction Associated With Metabolic Health and Obesity Status.

OBJECTIVE: Emerging evidence supports the favorable cardiovascular health in nonobese subjects with healthy metabolism. However, little is known regarding the prognosis across the range of metabolic phenotypes once cardiovascular disease is established. We examined the prognosis of patients with acute myocardial infarction (AMI) stratified according to metabolic health and obesity status. METHODS: This is a retrospective study on consecutive patients with AMI admitted to a tertiary hospital between 2014 and 2021. Patients were allocated into the following 4 groups based on metabolic and obesity profile: (1) metabolically healthy obese (MHO), (2) metabolically healthy nonobese (MHNO), (3) metabolically unhealthy obese (MUO), and (4) metabolically unhealthy nonobese (MUNO). Metabolic health was defined in accordance to the Biobank Standardisation and Harmonisation for Research Excellence in the European Union Healthy Obese Project. The primary outcome was all-cause mortality. The Cox regression analysis examined the independent association between mortality and metabolic phenotypes, adjusting for age, sex, AMI type, chronic kidney disease, smoking status, and left ventricular ejection fraction. RESULTS: Of 9958 patients, the majority (68.5%) were MUNO, followed by MUO (25.1%), MHNO (5.6%), and MHO (0.8%). MHO had the lowest mortality (7.4%), followed by MHNO (9.7%), MUO (19.2%), and MUNO (22.6%) (P < .001). Compared with MHNO, MUO (hazard ratio [HR], 1.737; 95% confidence interval [CI], 1.282-2.355; P < .001) and MUNO (HR, 1.482; 95% CI, 1.108-1.981; P = .008) had a significantly higher mortality risk but not MHO (HR, 1.390; 95% CI, 0.594-3.251; P = .447), after adjusting for confounders. The Kaplan-Meier curves showed favorable survival in the metabolically healthy and obesity groups, with the highest overall survival in the MHO, followed by MHNO, MUO, and MUNO (P < .001). CONCLUSION: Metabolically healthy and obese patients with AMI have favorable prognosis compared with metabolically unhealthy and nonobese patients. It is equally important to prioritize intensive metabolic risk factor management to weight reduction in the early phase after AMI.

Utility and pitfalls of the electrocardiogram in the evaluation of cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis is a protein misfolding disorder involving deposition of amyloid fibril proteins in the heart. The associated fibrosis of the conduction tissue results in conduction abnormalities and arrhythmias. "Classical" electrocardiogram (ECG) findings in cardiac amyloidosis include that of low voltage complexes with increased left ventricular wall thickness on echocardiography. However, this "classical" finding is neither sensitive nor specific. As cardiac amyloidosis is associated with a generally poor prognosis, the need for early recognition of this disease is important given the availability of new treatment options. In this review, we highlight 3 cases of patients with cardiac amyloidosis. Although presenting with typical clinical signs and symptoms, ECG for all 3 patients was not consistent with the classical findings described. They underwent further diagnostic tests which clinched the diagnosis of cardiac amyloidosis, allowing patients to receive targeted treatment. Through the review of the literature, we will highlight the different ECG patterns in patients with different types of cardiac amyloidosis and clinical scenarios, as well as the pitfalls of using ECG to identify the condition. Lastly, we also emphasize the current paradigms in diagnosing cardiac amyloidosis through the non-invasive methods of echocardiography, cardiac magnetic resonance imaging, and nuclear technetium-pyrophosphate imaging. CONCLUSIONS: Electrocardiogram is often the first investigation used in evaluating many cardiac disorders, including cardiac amyloidosis. However, classical features of cardiac amyloidosis on ECG are often not present. A keen understanding on the ECG features of cardiac amyloidosis and knowledge of the diagnostic workflow is important to diagnose this condition.

Prognostic Outcomes in Acute Myocardial Infarction Patients Without Standard Modifiable Risk Factors: A Multiethnic Study of 8,680 Asian Patients.

Background: An increasing proportion of patients with acute myocardial infarction (AMI) are presenting without standard modifiable risk factors (SMuRFs) of hypertension, hypercholesterolemia, diabetes, and smoking, but with an unexpectedly increased mortality. This study examined the SMuRF-less patients presenting with AMI in a multiethnic Asian population. Methods: We recruited patients presenting with AMI from 2011 to 2021 and compared the prevalence, clinical characteristics, and outcomes of SMuRF-less and SMuRF patients. Multivariable analysis was used to compare the outcomes of 30-day cardiovascular mortality, all-cause mortality, readmission, cardiogenic shock, stroke, and heart failure. Kaplan-Meier curves were constructed for 30-day cardiovascular mortality, with stratification by ethnicity, gender and AMI type, and 10-year all-cause mortality. Results: Standard modifiable risk factor-less patients, who made up 8.6% of 8,680 patients, were significantly younger with fewer comorbidities that include stroke and chronic kidney disease, but higher rates of ventricular arrhythmias and inotropic or invasive ventilation requirement. Multivariable analysis showed higher rates of cardiovascular mortality (HR 1.48, 95% CI: 1.09-1.86, p = 0.048), cardiogenic shock (RR: 1.31, 95% CI: 1.09-1.52, p = 0.015), and stroke (RR: 2.51, 95% CI: 1.67-3.34, p = 0.030) among SMuRF-less patients. A 30-day cardiovascular mortality was raised in the SMuRF-less group, with similar trends in men, patients with ST-segment elevation myocardial infarction (STEMI), and the three Asian ethnicities. All-cause mortality remains increased in the SMuRF-less group for up to 5 years. Conclusion: There is a significant proportion of patients with AMI without standard risk factors in Asia, who have worse short-term mortality. This calls for greater focus on the management of this unexpectedly high-risk subgroup of patients.

Meta-Analysis of Percutaneous Coronary Intervention Versus Coronary Artery Bypass Grafting for Left Main Narrowing.

Randomized controlled trials (RCTs) comparing percutaneous coronary intervention (PCI) with drug-eluting stents and coronary artery bypass grafting (CABG) for patients with left main coronary artery disease (LMCAD) have reported conflicting results. We performed a systematic review up to May 23, 2021, and 1-stage reconstructed individual patient data meta-analysis (IPDMA) to compare outcomes between both groups. The primary outcome was 10-year all-cause mortality. Secondary outcomes included myocardial infarction (MI), stroke, and unplanned revascularization at 5 years. We performed individual patient data meta-analysis using published Kaplan-Meier curves to provide individual data points in coordinates and numbers at risk were used to increase the calibration accuracy of the reconstructed data. Shared frailty model or, when proportionality assumptions were not met, a restricted mean survival time model were fitted to compare outcomes between treatment groups. Of 583 articles retrieved, 5 RCTs were included. A total of 4,595 patients from these 5 RCTs were randomly assigned to PCI (n = 2,297) or CABG (n = 2,298). The cumulative 10-year all-cause mortality after PCI and CABG was 12.0% versus 10.6%, respectively (hazard ratio [HR] 1.093, 95% confidence interval [CI] 0.925 to 1.292; p = 0.296). PCI conferred similar time-to-MI (restricted mean survival time ratio 1.006, 95% CI 0.992 to 1.021, p=0.391) and stroke (restricted mean survival time ratio 1.005, 95% CI 0.998 to 1.013, p = 0.133) at 5 years. Unplanned revascularization was more frequent after PCI than CABG (HR 1.807, 95% CI 1.524 to 2.144, p <0.001) at 5 years. This meta-analysis using reconstructed participant-level time-to-event data showed no statistically significant difference in cumulative 10-year all-cause mortality between PCI versus CABG in the treatment of LMCAD.

Can glucose-lowering medications improve outcomes in non-diabetic heart failure patients? A Bayesian network meta-analysis.

AIMS: The cardioprotective effects of glucose-lowering medications in diabetic patients with heart failure (HF) are well known. Several large randomized controlled trials (RCTs) have recently suggested that the cardioprotective effects of glucose-lowering medications extend to HF patients regardless of diabetic status. The aim of this study was to conduct a Bayesian network meta-analysis to evaluate the impact of various glucose-lowering medications on the outcomes of non-diabetic HF patients. METHODS AND RESULTS: Medline and Embase were searched for RCTs investigating the use of glucose-lowering medications in non-diabetic HF patients in August 2021. Studies were included in accordance with the inclusion and exclusion criteria, and data were extracted with a pre-defined datasheet. Primary outcomes include serum N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, left ventricular ejection fraction (LVEF), and maximal oxygen consumption (PVO2 ). A Bayesian network meta-analysis was performed to compare the effectiveness of different classes of glucose-lowering medications in improving HF outcomes. Risk-of-bias was assessed using Cochrane Risk-of-Bias tool 2.0 for randomized trials (ROB2). Seven RCTs involving 2897 patients were included. Sodium-glucose transporter 2 inhibitor (SGLT2i) was the most favourable in lowering NT-proBNP, with the significant reduction in NT-proBNP when compared with glucagon-like peptide-1 receptor agonists (GLP1-RA) [mean differences (MD): -229.59 pg/mL, 95%-credible intervals (95%-CrI): -238.31 to -220.91], metformin (MD: -237.15 pg/mL, 95%-CrI: -256.19 to -218.14), and placebo (MD: -228.00 pg/mL, 95%-CrI: -233.99 to -221.99). SGLT2i was more effective in improving LVEF for HF with reduced ejection fraction patients relative to GLP1-RA (MD: 8.09%, 95%-CrI: 6.30 to 9.88) and placebo (MD: 6.10%, 95%-CrI: 4.37 to 7.84). SGLT2i and GLP1-RA were more favourable to placebo in improving PVO2 , with significant increase of PVO2 at a MD of 1.60 mL/kg/min (95%-CrI: 0.63 to 2.57) and 0.86 mL/kg/min (95%-CrI: 0.66 to 1.06), respectively. All three drugs had comparable safety profiles when compared with placebo. CONCLUSIONS: This Bayesian network meta-analysis demonstrated that SGLT2i, when compared with GLP1-RA and metformin, was superior in improving LVEF in HF with reduced ejection fraction patients, as well as improving PVO2 and NT-proBNP in non-diabetic HF patients. Further large-scale prospective studies are needed to confirm these preliminary findings.

Clinical outcomes of severe tricuspid valve infective endocarditis related to intravenous drug abuse - a case series.

BACKGROUND: Right-sided infective endocarditis (IE) related to intravenous drug use (IVDU) can follow an acute fulminant course. However, there is limited information on its longer-term clinical outcomes. AIM AND METHODS: We assessed a cohort of consecutive patients who presented with IVDU complicated by severe tricuspid valve regurgitation to determine their presentation, treatment, and long-term outcomes. In this study, severe tricuspid regurgitation (TR) was defined by the European Association of Cardiovascular Imaging criteria at initial presentation to the hospital. RESULTS: Thirty-three patients with a mean age of 35 ± 18 years (72% males) presented with IVDU associated with severe TR. At the initial presentation, 15 patients were in septic shock and required inotropes. 26 patients had septic pulmonary emboli; 10 patients had associated metastatic systemic sites of infection of which 5 patients had central nervous system (CNS) involvement. Three patients were in disseminated intravascular coagulation (DIC) and 1 patient had multi-organ failure (MOF), but not requiring dialysis or mechanical ventilation. Most patients had large tricuspid valve vegetations of >20mm. Eleven patients underwent surgery with 18% perioperative mortality. The Median follow-up was 6.4 years (0.5-11.4). Recurrent IE occurred in one-third of patients, the overall incidence of heart failure and Atrial fibrillation (AF) on follow-up was low in all 3 groups. Five-year survival was 94%. CONCLUSION: Acute severe TR following associated endocarditis IVDU results in a fulminant initial presentation, but a longer-term prognosis is good with surgical and medical treatment.

Inter-Ethnic Differences in Valvular Dysfunction, Aortopathy, and Progression of Disease of an Asian Bicuspid Aortic Valve Population.

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.

Prevalence and outcomes of concomitant cardiac amyloidosis and aortic stenosis: A systematic review and meta-analysis.

OBJECTIVE: Cardiac amyloidosis (CA) is an increasingly recognised condition in patients with aortic stenosis (AS). However, there is a 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 patients with AS grouped according to the diagnostic techniques, and the risk factors and outcomes of concomitant CA and AS were 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 patients 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 (IVSd) 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 heterogeneity of the results and the fair to good quality of the 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 the "red flags" and perform appropriate diagnostic imaging.

Prognostic implications of left atrial dilation in aortic regurgitation due to bicuspid aortic valve.

OBJECTIVE: To investigate the prognostic value of left atrial volume index (LAVI) in patients with moderate to severe aortic regurgitation (AR) and bicuspid aortic valve (BAV). METHODS: 554 individuals (45 (IQR 33-57) years, 80% male) with BAV and moderate or severe AR were selected from an international, multicentre registry. The association between LAVI and the combined endpoint of all-cause mortality or aortic valve surgery was investigated with Cox proportional hazard regression analyses. RESULTS: Dilated LAVI was observed in 181 (32.7%) patients. The mean indexed aortic annulus, sinus of Valsalva, sinotubular junction and ascending aorta diameters were 13.0±2.0 mm/m2, 19.4±3.7 mm/m2, 16.5±3.8 mm/m2 and 20.4±4.5 mm/m2, respectively. After a median follow-up of 23 (4-82) months, 272 patients underwent aortic valve surgery (89%) or died (11%). When compared with patients with normal LAVI (<35 mL/m2), those with a dilated LAVI (≥35 mL/m2) had significantly higher rates of aortic valve surgery or mortality (43% and 60% vs 23% and 36%, at 1 and 5 years of follow-up, respectively, p<0.001). Dilated LAVI was independently associated with reduced event-free survival (HR=1.450, 95% CI 1.085 to 1.938, p=0.012) after adjustment for LV ejection fraction, aortic root diameter, LV end-diastolic diameter and LV end-systolic diameter. CONCLUSIONS: In this large, multicentre registry of patients with BAV and moderate to severe AR, left atrial dilation was independently associated with reduced event-free survival. The role of this parameter for the risk stratification of individuals with significant AR merits further investigation.

Clinical and echocardiographic characteristics associated with the development of infective endocarditis in patients with significant mitral stenosis.

BACKGROUND: Infective endocarditis (IE) confers significant mortality and morbidity in patients with underlying mitral stenosis (MS), with both diseased native valves and after valvular procedures. PURPOSE: We examined the clinical and echocardiographic parameters in association with the development of IE on patients with significant MS. METHODS: A total of 478 consecutive patients with index echocardiographic diagnosis of significant mitral stenosis (mitral valve area <1.5 cm2 ) were included. Patients were grouped into those with or without IE on at least 5 years of follow-up. Baseline clinical, echocardiographic profile and clinical outcomes were compared. RESULTS: IE was observed in 4.4% (n = 21) of the cohort. These patients were younger (45.3 ± 14.6 vs. 53.2 ± 15.5 years, p = 0.022) at the time of MS diagnosis. NT-proBNP was higher in patients who developed IE (13529 ± 12230 vs. 4381 ± 5875 pg/ml, p < 0.001), with larger left atrial diameter (54.4 ± 10.1 vs. 49.9 ± 9.5 mm, p = 0.040) and elevated pulmonary artery systolic pressure (PASP, 62.3 ± 17.2 vs. 47.2 ± 16.5 mmHg, p = 0.026). There was no significant difference in terms of MS severity, other concomitant valvulopathies, or etiology (rheumatic or degenerative) of MS. Patients who smoked had higher incidence of IE (33.3% vs. 14.2%, log-rank 7.27, p = 0.007). After adjusting for age, valve procedure and PASP, patients who smoked remained at elevated risk of IE (adjusted hazards ratio 2.99, 95% confidence interval 1.18-7.56, p = 0.021). CONCLUSION: IE occurs in a proportion of patients with MS. Smoking, younger age of diagnosis of MS as well as dilated left atria with elevated PASP may be associated with an elevated risk of this complication.

Association between smoking status and outcomes in myocardial infarction patients undergoing percutaneous coronary intervention.

Smoking is one of the leading risk factors for cardiovascular diseases, including ischemic heart disease and hypertension. However, in acute myocardial infarction (AMI) patients, smoking has been associated with better clinical outcomes, a phenomenon termed the "smoker's paradox." Given the known detrimental effects of smoking on the cardiovascular system, it has been proposed that the beneficial effect of smoking on outcomes is due to age differences between smokers and non-smokers and is therefore a smoker's pseudoparadox. The aim of this study was to evaluate the association between smoking status and clinical outcomes in ST-segment elevation (STEMI) and non-STEMI (NSTEMI) patients treated by percutaneous coronary intervention (PCI), using a national multi-ethnic Asian registry. In unadjusted analyses, current smokers had better clinical outcomes following STEMI and NSTEMI. However, after adjusting for age, the protective effect of smoking was lost, confirming a smoker's pseudoparadox. Interestingly, although current smokers had increased risk for recurrent MI within 1 year after PCI in both STEMI and NSTEMI patients, there was no increase in mortality. In summary, we confirm the existence of a smoker's pseudoparadox in a multi-ethnic Asian cohort of STEMI and NSTEMI patients and report increased risk of recurrent MI, but not mortality, in smokers.