Highlights of Cardiovascular Disease Prevention Studies Presented at the 2024 American College of Cardiology Conference.

PURPOSE OF REVIEW: To summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2024 Scientific Session of the American College of Cardiology (ACC) conference. RECENT FINDINGS: The LIBerate-HR trial showed the efficacy and safety of lerodalcibep, a subcutaneous injection that prevents binding of Pro-Protein Convertase Subtilisin/Kexin (PCSK) 9 to low-density lipoprotein (LDL)-receptors resulting in LDL-cholesterol (LDL-C) lowering in patients at very high risk or high risk of atherosclerotic CV disease (ASCVD). The AEGIS-II randomized patients with type 1 myocardial infarction (MI) with multivessel coronary artery disease and additional CV risk factors and found no benefit in major adverse CV events (MACE) with CSL112, an apolipoprotein A1 infusion shown to increase cholesterol efflux capacity. The Bridge-TIMI 73a trial showed a significant reduction in triglyceride (TG) levels with olezarsen, an antisense mRNA, in patients with moderate hyperTG with elevated CV risk. The BE ACTIVE trial showed significant improvement in step counts in patients given behavioral and financial incentives. The DRIVE study showed a significant increase in the prescription of either sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes mellitus (T2DM) at elevated CV or renal risk with a remote team-based, non-licensed navigator and clinical pharmacist approach. The TACTiC trial showed increased and sustained use of statin therapy by patient-driven use of a web-based portal that calculated the ASCVD risk score and gave prompts. The VICTORIAN-INITIATE trial showed efficacy and safety in early use of inclisiran in patients with ASCVD who did not reach target LDL-C < 70 mg/dL despite maximally tolerated statin therapy. The ARISE-HF trial showed no difference in change of peak oxygen consumption with the use of an oral aldose reductase inhibitor, AT-001, in patients with well-controlled T2DM and diabetic cardiomyopathy with high-risk features compared to placebo. The PREVENT trial showed a significant reduction in target vessel failure at 2 years in patients with non-flow limiting vulnerable plaques with percutaneous coronary intervention and optimal medical therapy (OMT) compared to OMT alone. The late-breaking clinical science presented at the 2024 Scientific Session of the ACC paves the way for an evidence-based alternative to statin therapy and provides data on several common clinical scenarios encountered in daily practice.

Association of Electrocardiographic P-Wave Markers and Atrial Fibrillation in Embolic Stroke of Undetermined Source.

BACKGROUND: Several P-wave indices are thought to represent underlying atrial remodeling and have been associated with ischaemic stroke even in the absence of atrial fibrillation (AF). However, the utility of these P-wave indices in predicting outcomes in patients with embolic stroke of undetermined source (ESUS) has not been studied. The aim of this study is to examine these different P-wave indices towards predicting new-onset AF and stroke recurrence in a cohort of patients with ESUS, thereby demonstrating the value of these electrocardiographic markers for stroke risk stratification. METHODS: Between October 2014 and October 2017, consecutive patients diagnosed with ESUS were followed for new-onset AF and ischaemic stroke recurrence. The various P-wave indices, namely, the P-terminal force in the precordial lead V1 (PTFV1), P-wave duration, P-wave dispersion, interatrial blocks, and P-wave axis, were assessed on the initial electrocardiogram on presentation and studied for their relation to eventual AF detection and recurrent stroke. RESULTS: 181 ischaemic stroke patients with ESUS were recruited and followed up for a median duration of 2.1 years. An abnormal PTFV1 was associated with occult AF detection but not with recurrent ischaemic strokes. No significant association was observed between the other P-wave indices with either occult AF or stroke recurrence. CONCLUSION: PTFV1 is associated with AF detection but not recurrent strokes in ESUS patients and can be a useful electrocardiographic marker for further risk stratification in ESUS patients.

Left Atrial Volume Index Predicts New-Onset Atrial Fibrillation and Stroke Recurrence in Patients with Embolic Stroke of Undetermined Source.

INTRODUCTION: It is unclear which surrogate of atrial cardiopathy best predicts the risk of developing a recurrent ischemic stroke in embolic stroke of undetermined source (ESUS). Left atrial diameter (LAD) and LAD index (LADi) are often used as markers of left atrial enlargement in current ESUS research, but left atrial volume index (LAVi) has been found to be a better predictor of cardiovascular outcomes in other patient populations. OBJECTIVE: We aim to compare the performance of LAVi, LAD, and LADi in predicting the development of new-onset atrial fibrillation (AF) and stroke recurrence in ESUS. METHODS: Between October 2014 and October 2017, consecutive patients diagnosed with ESUS were followed for new-onset AF, ischemic stroke recurrence, and a composite outcome of occult AF and stroke recurrence. LAVi and LADi were measured by transthoracic echocardiogram; "high" LAVi was defined as ≥35 mL/m2 in accordance with American Society of Echocardiography guidelines. RESULTS: 185 ischemic stroke patients with ESUS were recruited and followed for a median duration of 2.1 years. Increased LAVi was associated with new-onset AF detection (aOR 1.08; 95% CI 1.03-1.14; p = 0.003) and stroke recurrence (aOR 1.05; 95% CI 1.01-1.10; p = 0.026). Patients with "high" LAVi had a higher likelihood of developing a composite of AF detection and stroke recurrence (HR 3.45; 95% CI 1.55-7.67; p = 0.002). No significant association was observed between LADi and either occult AF or stroke recurrence. CONCLUSIONS: LAVi is associated with new-onset AF and stroke recurrence in ESUS patients and may be a better surrogate of atrial cardiopathy.

A Population-wide study of electrocardiographic (ECG) norms and the effect of demographic and anthropometric factors on selected ECG characteristics in young, Southeast Asian males-results from the Singapore Armed Forces ECG (SAFE) study.

BACKGROUND: Routine use of pre-participation electrocardiograms (ECGs) has been used by the Singapore Armed Forces, targeting early detection of significant cardiac diseases. We aim to describe the impact of demographic and anthropometric factors on ECG variables and establish a set of electrocardiographic reference ranges specific to a young male multiethnic Southeast Asian cohort. METHODS AND RESULTS: Between November 1, 2009, and December 31, 2014, 144,346 young male conscripts underwent pre-participation screening that included a 12-lead ECG, demographic and anthropometric measurements. The Chinese population had the longest PR interval (146.7 ± 19.7 vs. 145.21 ± 19.2 in Malays vs. 141.2 ± 18.8 ms in Indians), QRS duration (94.5 ± 9.8 vs. 92.6 ± 9.7 in Malays vs. 92.5 ± 9.4 ms in Indians) and QTcB interval (408.3 ± 21.3 vs. 403.5 ± 21.6 in Malays vs. 401.2 ± 21.4 ms in Indians) (all p < 0.001). Body mass index (BMI) >25 kg/m2 and body fat >25% were independently associated with lower prevalence of increased QRS voltage on ECG. Systolic blood pressure of >140 mmHg or diastolic blood pressure of >90 mmHg independently increased the prevalence of increased QRS voltage on ECG. CONCLUSIONS: Electrocardiographic parameters vary across different ethnicities and in comparison with international norms. In our population, diagnosis of increased QRS voltage by ECG is less prevalent with obesity and increased body fat. Further analysis of gold standard measurements for the diagnosis of LVH in our population is ongoing, to improve the accuracy of the ECG screening process.

Association between Bilateral Infarcts Pattern and Detection of Occult Atrial Fibrillation in Embolic Stroke of Undetermined Source (ESUS) Patients with Insertable Cardiac Monitor (ICM).

BACKGROUND AND AIMS: Increasingly, insertable cardiac monitors (ICM) have been used to detect Atrial Fibrillation (AF) in patients with cryptogenic stroke or embolic strokes of undetermined source (ESUS). We aim to examine the characteristics of these patients who were subsequently found to have AF. METHODS: We studied 83 consecutive patients who were comprehensively evaluated using neuroimaging and vessel imaging (computed tomography angiography, magnetic resonance angiography, or transcranial and extracranial Doppler sonography) to have met the previously established ESUS criteria. All 83 patients had ICM implanted between 2015 and 2017. All patients were followed up for at least 1 year, with a median follow-up period of 1.5 ± .5 years. We compared the baseline clinical, laboratory, echocardiographic, neuro-imaging profiles, and clinical outcomes in terms of functional recovery, recurrent stroke, and mortality in patients with and without detected AF. RESULTS: AF detection rate in this ESUS cohort was 12% over the study period. Patients with detected AF were associated with bilateral infarcts pattern at presentation (30% versus 5.5%, P = .035). Infarcts involving multiple vascular territories was not significantly associated with the detection of AF. There were no significant differences in the other clinical characteristics and outcomes between the AF group compared to the group without detected AF. Echocardiographic parameters including left ventricular ejection fraction and left atrial diameter were also not shown to be significantly different. CONCLUSION: Our study found that a neuroimaging profile of bilateral infarcts was associated with AF detection using insertable cardiac monitor in ESUS patients. Larger prospective studies are needed to validate our findings.

Quality of life and related factors of nursing home residents in Singapore.

BACKGROUND: Litter is known about the well-being of nursing home (NH) residents in Singapore. This study aimed to identify predictors of self-reported quality of life (QOL) of NH residents in Singapore. METHODS: In face-to-face interviews, trained medical students assessed each consenting resident recruited from 6 local NHs using a modified Minnesota QOL questionnaire, and rating scales and questions assessing independence, cognitive function, depression, and communication. Predictors of residents' QOL in five aspects (comfort, dignity, food enjoyment, autonomy, and security) were identified using the censored least absolute deviations (CLAD) models. RESULTS: A total of 375 residents completed the interviews. A higher score on comfort was negatively associated with major depression while a higher score on dignity was positively associated with no difficulty in communication with staff. Higher scores in food enjoyment were negatively associated with major depression and poorer cognitive function. Higher scores in autonomy were negatively associated with major depression, greater dependence, and difficulty in communication with staff. A higher score on security were negatively associated with major depression. CONCLUSION: It appears that depression and difficulty in communication with staff are the two main modifiable risk factors of poor quality of life of local NH residents.

The intersection of heart failure and cancer in women: a review.

Cancer and cardiovascular disease represent the two leading causes of morbidity and mortality worldwide. Women continue to enjoy a greater life expectancy than men. However, this comes at a cost with more women developing diabetes, hypertension and coronary artery disease as they age. These traditional cardiovascular risk factors not only increase their lifetime risk of heart failure but also their overall risk of cancer. In addition to this, many of the cancers with female preponderance are treated with potentially cardiotoxic therapies, adding to their increased risk of developing heart failure. As a result, we are faced with a higher risk population, potentially suffering from both cancer and heart failure simultaneously. This is of particular concern given the coexistence of heart failure and cancer can confer a worse prognosis than either a single diagnosis of heart failure or cancer alone. This review article explores the intersection of heart failure and cancer in women at multiple levels, including traditional cardiovascular risk factors, cardiovascular toxicity derived from antineoplastic and radiation therapy, shared pathophysiology and HF as an oncogenic process. This article further identifies opportunities and strategies for intervention and optimisation, whilst highlighting the need for contemporary guidelines to better inform clinical practice.

Incorporating AI into cardiovascular diseases prevention-insights from Singapore.

Improved upstream primary prevention of cardiovascular disease (CVD) would enable more individuals to lead lives free of CVD. However, there remain limitations in the current provision of CVD primary prevention, where artificial intelligence (AI) may help to fill the gaps. Using the data informatics capabilities at the National University Health System (NUHS), Singapore, empowered by the Endeavour AI system, and combined large language model (LLM) tools, our team has created a real-time dashboard able to capture and showcase information on cardiovascular risk factors at both individual and geographical level- CardioSight. Further insights such as medication records and data on area-level socioeconomic determinants allow a whole-of-systems approach to promote healthcare delivery, while also allowing for outcomes to be tracked effectively. These are paired with interventions, such as the CHronic diseAse Management Program (CHAMP), to coordinate preventive cardiology care at a pilot stage within our university health system. AI tools in synergy allow the identification of at-risk patients and actionable steps to mitigate their health risks, thereby closing the gap between risk identification and effective patient care management in a novel CVD prevention workflow.

Public acceptance of using artificial intelligence-assisted weight management apps in high-income southeast Asian adults with overweight and obesity: a cross-sectional study.

Introduction: With in increase in interest to incorporate artificial intelligence (AI) into weight management programs, we aimed to examine user perceptions of AI-based mobile apps for weight management in adults with overweight and obesity. Methods: 280 participants were recruited between May and November 2022. Participants completed a questionnaire on sociodemographic profiles, Unified Theory of Acceptance and Use of Technology 2 (UTAUT2), and Self-Regulation of Eating Behavior Questionnaire. Structural equation modeling was performed using R. Model fit was tested using maximum-likelihood generalized unweighted least squares. Associations between influencing factors were analyzed using correlation and linear regression. Results: 271 participant responses were analyzed, representing participants with a mean age of 31.56 ± 10.75 years, median (interquartile range) BMI, and waist circumference of 27.2 kg/m2 (24.2-28.4 kg/m2) and 86.4 (80.0-94.0) cm, respectively. In total, 188 (69.4%) participants intended to use AI-assisted weight loss apps. UTAUT2 explained 63.3% of the variance in our intention of the sample to use AI-assisted weight management apps with satisfactory model fit: CMIN/df = 1.932, GFI = 0.966, AGFI = 0.954, NFI = 0.909, CFI = 0.954, RMSEA = 0.059, SRMR = 0.050. Only performance expectancy, hedonic motivation, and the habit of using AI-assisted apps were significant predictors of intention. Comparison with existing literature revealed vast variabilities in the determinants of AI- and non-AI weight loss app acceptability in adults with and without overweight and obesity. UTAUT2 produced a good fit in explaining the acceptability of AI-assisted apps among a multi-ethnic, developed, southeast Asian sample with overweight and obesity. Conclusion: UTAUT2 model is recommended to guide the development of AI-assisted weight management apps among people with overweight and obesity.

Long-Term Prognosis of Patients With Coexisting Obesity and Malnutrition After Acute Myocardial Infarction: A Cohort Study.

BACKGROUND: The double burden of malnutrition, described as the coexistence of malnutrition and obesity, is a growing global health issue. This study examines the combined effects of obesity and malnutrition on patients with acute myocardial infarction (AMI). METHODS: Patients presenting with AMI to a percutaneous coronary intervention-capable hospital in Singapore between January 2014 and March 2021 were retrospectively studied. Patients were stratified into the following: (1) nourished nonobese, (2) malnourished nonobese, (3) nourished obese, and (4) malnourished obese. Obesity and malnutrition were defined according to the World Health Organization definition (body mass index ≥27.5 kg/m2) and Controlling Nutritional Status score, respectively. The primary outcome was all-cause mortality. The association between combined obesity and nutritional status with mortality was examined using Cox regression, adjusted for age, sex, AMI type, previous AMI, ejection fraction, and chronic kidney disease. Kaplan-Meier curves for all-cause mortality were constructed. RESULTS: The study included 1829 AMI patients, of which 75.7% were male and mean age was 66 years. Over 75% of patients were malnourished. Majority were malnourished nonobese (57.7%), followed by malnourished obese (18.8%), nourished nonobese (16.9%), and nourished obese (6.6%). Malnourished nonobese had highest all-cause mortality (38.6%), followed by the malnourished obese (35.8%), nourished nonobese (21.4%), and nourished obese (9.9%, P<0.001). Kaplan-Meier curves demonstrated least favorable survival in malnourished nonobese group, followed by malnourished obese, nourished nonobese, and nourished obese. With nourished nonobese group as the reference, malnourished nonobese had higher all-cause mortality (hazard ratio, 1.46 [95% CI, 1.10-1.96], P=0.010), but only a nonsignificant increase in mortality was observed in the malnourished obese (hazard ratio, 1.31 [95% CI, 0.94-1.83], P=0.112). CONCLUSIONS: Among AMI patients, malnutrition is prevalent even in the obese. Compared to nourished patients, malnourished AMI patients have a more unfavorable prognosis especially in those with severe malnutrition regardless of obesity status, but long-term survival is the most favorable among nourished obese patients.

Socioeconomic deprivation and prognostic outcomes in acute coronary syndrome: A meta-analysis using multidimensional socioeconomic status indices.

BACKGROUND: Low socioeconomic status (SES) is an important prognosticator amongst patients with acute coronary syndrome (ACS). This paper analysed the effects of SES on ACS outcomes. METHODS: Medline and Embase were searched for articles reporting outcomes of ACS patients stratified by SES using a multidimensional index, comprising at least 2 of the following components: Income, Education and Employment. A comparative meta-analysis was conducted using random-effects models to estimate the risk ratio of all-cause mortality in low SES vs high SES populations, stratified according to geographical region, study year, follow-up duration and SES index. RESULTS: A total of 29 studies comprising of 301,340 individuals were included, of whom 43.7% were classified as low SES. While patients of both SES groups had similar cardiovascular risk profiles, ACS patients of low SES had significantly higher risk of all-cause mortality (adjusted HR:1.19, 95%CI: 1.10-1.1.29, p < 0.001) compared to patients of high SES, with higher 1-year mortality (RR:1.08, 95%CI:1.03-1.13, p = 0.0057) but not 30-day mortality (RR:1.07, 95%CI:0.98-1.16, p = 0.1003). Despite having similar rates of ST-elevation myocardial infarction and non-ST-elevation ACS, individuals with low SES had lower rates of coronary revascularisation (RR:0.95, 95%CI:0.91-0.99, p = 0.0115) and had higher cerebrovascular accident risk (RR:1.25, 95%CI:1.01-1.55, p = 0.0469). Excess mortality risk was independent of region (p = 0.2636), study year (p = 0.7271) and duration of follow-up (p = 0.0604) but was dependent on the SES index used (p < 0.0001). CONCLUSION: Low SES is associated with increased mortality post-ACS, with suboptimal coronary revascularisation rates compared to those of high SES. Concerted efforts are needed to address the global ACS-related socioeconomic inequity. REGISTRATION AND PROTOCOL: The current study was registered with PROSPERO, ID: CRD42022347987.

General Public's knowledge, awareness, and perception of Cardiometabolic diseases: data from a Singapore study population.

Background: Health literacy and illness perception play crucial roles in tackling the cardiometabolic disease epidemic. We aim to compare the attitudes, knowledge, self-perceived risks and actions taken, between individuals with and without metabolic risk factors (MFs). Methods: From 5 June to 5 October 2022, participants of the general public were invited to complete a self-administered questionnaire. MF status was defined as the presence of hypertension, hyperlipidemia, diabetes mellitus and/or current/previous smoking. Participants were assessed based on four categories (knowledge-based, attitude-based, perceived risk, and action-based) of questions pertaining to four cardiometabolic diseases - diabetes mellitus, hypertension, hyperlipidemia, and non-alcoholic fatty liver disease. Results: A total of 345 participants were enrolled, of whom 34.5% had at least one MF. Compared to those without MFs, participants with MFs had lower knowledge scores, but higher perceived risk scores across all cardiometabolic diseases. The largest knowledge gap pertained to hypertension-related questions. After adjustment, linear regression demonstrated that the presence of MFs (ß:2.752, 95%CI: 0.772-4.733, p = 0.007) and higher knowledge scores (ß:0.418, 95%CI: 0.236-0.600, p < 0.001) were associated with higher perceived risk. Despite increased perceived risk in those with MFs, this translated to only few increased self-reported preventive actions, when compared to those without MFs, namely the reduction in red meat/processed food consumption (p = 0.045) and increase in fruits/vegetables consumption (p = 0.009). Conclusion: This study identified a vulnerable subpopulation living with MFs, with high perceived risks, and discordant levels of knowledge and preventive actions taken. Nationwide efforts should be channeled into addressing the knowledge-to-action gap.

Outcomes of Investigating T Wave Inversion With Echocardiography in an Unselected Young Male Preparticipation Cohort.

BACKGROUND Electrocardiography (ECG) may be performed as part of preparticipation sports screening. Recommendations on screening of athletes to identify individuals with previously unrecognized cardiac disease are robust; however, data guiding the preparticipation screening of unselected populations are scarce. T wave inversion (TWI) on ECG may suggest an undiagnosed cardiomyopathy. This study aims to describe the prevalence of abnormal TWI in an unselected young male cohort and the outcomes of an echocardiography-guided approach to investigating these individuals for structural heart diseases, focusing on the yield for cardiomyopathies. METHODS AND RESULTS Consecutive young male individuals undergoing a national preparticipation cardiac screening program for 39 months were studied. All underwent resting supine 12-lead ECG. Those manifesting abnormal TWI, defined as negatively deflected T waves of at least 0.1 mV amplitude in any 2 contiguous leads, underwent echocardiography. A total of 69 714 male individuals with a mean age of 17.9±1.1 years were studied. Of the individuals, 562 (0.8%) displayed abnormal TWI. This was most frequently observed in the anterior territory and least so in the lateral territory. A total of 12 individuals (2.1%) were diagnosed with a cardiomyopathy. Cardiomyopathy diagnoses were significantly associated with deeper maximum TWI depth and the presence of abnormal TWI in the lateral territory, but not with abnormal TWI in the anterior and inferior territories. No individual presenting with TWI restricted to solely leads V1 to V2, 2 inferior leads or both was diagnosed with a cardiomyopathy. CONCLUSIONS Cardiomyopathy diagnoses were more strongly associated with certain patterns of abnormal TWI. Our findings may support decisions to prioritize echocardiography in these individuals.

Platform for the interdisciplinary study of cardiovascular, metabolic and neurovascular diseases (PICMAN) protocol.

Through extensive multisystem phenotyping, the central aim of Project PICMAN is to correlate metabolic flexibility to measures of cardiometabolic health, including myocardial diastolic dysfunction, coronary and cerebral atherosclerosis, body fat distribution and severity of non-alcoholic fatty liver disease. This cohort will form the basis of larger interventional trials targeting metabolic inflexibility in the prevention of cardiovascular disease. Participants aged 21-72 years with no prior manifest atherosclerotic cardiovascular disease (ASCVD) are being recruited from a preventive cardiology clinic and an existing cohort of non-alcoholic fatty liver disease (NAFLD) in an academic medical centre. A total of 120 patients will be recruited in the pilot phase of this study and followed up for 5 years. Those with 10-year ASCVD risk ≥ 5% as per the QRISK3 calculator are eligible. Those with established diabetes mellitus are excluded. Participants recruited undergo a detailed assessment of health behaviours and physical measurements. Participants also undergo a series of multimodality clinical phenotyping comprising cardiac tests, vascular assessments, metabolic tests, liver and neurovascular testing. Blood samples are also being collected and banked for plasma biomarkers, 'multi-omics analyses' and for generation of induced pluripotent stem cells (iPSC). Extensive evidence points to metabolic dysregulation as an early precursor of cardiovascular disease, particularly in Asia. We hypothesise that quantifiable metabolic inflexibility may be representative of an individual in his/her silent, but high-risk progression towards insulin resistance, diabetes and cardiovascular disease. The platform for interdisciplinary cardiovascular-metabolic-neurovascular diseases (PICMAN) is a pilot, prospective, multi-ethnic cohort study.

Effect of Surgical Mask use on Peak Physical Performance During Exercise Treadmill Testing-A Real World, Crossover Study.

Background: Mask wearing is an essential strategy to combat the spread of SARS-CoV-2. Some individuals may wear masks during physical activity to reduce disease transmission. This study aimed to investigate the real-world effect of wearing a surgical face mask on physiological parameters at peak exercise in healthy individuals. Methods: In this crossover design study, participants underwent maximal treadmill electrocardiogram exercise tests using the Bruce protocol on two separate occasions, once with a standard 3-ply surgical face mask and once without. Heart rate, oxygen saturation, blood pressure, rate pressure product, metabolic equivalents (METS) and total exercise time were measured. Subjective rate of perceived exertion was also assessed using the modified Borg Scale. Results: 50 adults (mean age = 31.7 ± 6.5 years; 27 males) completed both treadmill tests. Mask wearing resulted in a significant reduction in peak METS by 1.5 units, maximum speed by 0.5 km/h, exercise time by 68.4 s with a significantly lower peak heart rate by 4.4 bpm, and lower percentage of age-predicted maximum heart rate by 2.5% (p < 0.001 for all parameters). During each corresponding stage of the Bruce protocol, the average modified Borg score was found to be significantly higher in subjects exercising with mask after adjusting for age, gender and body mass index (p < 0.03). Conclusion: In a cohort of healthy individuals, wearing of a surgical face mask during maximal treadmill exercise lead to reduced physical performance and increased rate of perceived exertion. Individuals exercising with surgical masks need to be mindful of these limitations while undergoing physical training in order to differentiate these physiological responses from symptoms of early respiratory illness.

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.

Hypertension is prevalent in non-alcoholic fatty liver disease and increases all-cause and cardiovascular mortality.

Background and aims: Hypertension (HTN) is a common comorbidity in non-alcoholic fatty liver disease (NAFLD) affecting up to 40% of individuals. However, the impact of HTN and its control on outcomes in NAFLD remains unclear. Therefore, we aimed to examine the impact of HTN on survival outcomes in a longitudinal cohort of NAFLD patients. Methods: The analysis consisted of adults in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2018 with data on socio-demographic characteristics and comorbidities. NAFLD was diagnosed with fatty liver index (FLI) and United States-FLI at a cut-off of 60 and 30, respectively in the substantial absence of alcohol use. A multivariate regression analysis was conducted to adjust for confounders. Results: A total of 45,302 adults were included, and 27.83% were identified to have NAFLD. Overall, 45.65 and 35.12% of patients with NAFLD had HTN and uncontrolled HTN, respectively. A multivariate analysis with confounders demonstrated that hypertensive NAFLD had a significantly increased risk of all-cause mortality (HR: 1.39, CI: 1.14-1.68, p < 0.01) and cardiovascular disease (CVD) mortality (HR: 1.85, CI: 1.06-3.21, p = 0.03). Untreated HTN remained to have a significantly increased risk in all-cause (HR: 1.59, CI: 1.28-1.96, p < 0.01) and CVD mortality (HR: 2.36, CI: 1.36-4.10, p < 0.01) while treated HTN had a non-significant increased risk of CVD mortality (HR: 1.51, CI: 0.87-2.63, p = 0.14) and a lower magnitude of increase in the risk of all-cause mortality (HR: 1.26, CI: 1.03-1.55, p = 0.03). Conclusion: Despite the significant burden of HTN in NAFLD, up to a fifth of patients have adequate control, and the lack thereof significantly increases the mortality risk. With the significant association of HTN in NAFLD, patients with NAFLD should be managed with a multidisciplinary team to improve longitudinal outcomes.

Association of Global Cardiac Calcification with Atrial Fibrillation and Recurrent Stroke in Patients with Embolic Stroke of Undetermined Source.

BACKGROUND: Calcium deposits in the heart have been associated with cardiovascular events, mortality, stroke, and atrial fibrillation (AF). However, there is no accepted standard method for scoring cardiac calcifications. Existing methods have also not been validated for the assessment of patients with embolic stroke of undetermined source (ESUS). The aim of this study was to evaluate the association of various cardiac calcification scores with new-onset AF and stroke recurrence in a cohort of patients with ESUS. METHODS: In this study, 181 consecutive patients with stroke diagnosed with ESUS were identified and evaluated. They were followed for new-onset AF and ischemic stroke recurrence for a median duration of 2.1 years. Various echocardiographic cardiac calcification scores were assessed on transthoracic echocardiography performed during the evaluation of ESUS and subsequently assessed for their relation to AF detection and recurrent stroke. The echocardiographic calcium scores assessed were the (1) global cardiac calcium score (GCCS), (2) echocardiographic calcium score (eCS), (3) echocardiographic calcification score, (4) echocardiographic composite cardiac calcium score, and (5) total heart calcification score. Only two of these scoring schemes, GCCS and eCS, quantified the cardiac calcium burden. RESULTS: Higher calcium scores as measured by GCCS and eCS were found to be significantly associated with subsequent AF detection as well as recurrent ischemic stroke in patients with ESUS. The association with recurrent stroke remained significant even after adjustment for comorbidities and AF. CONCLUSIONS: Higher cardiac calcification measured using the GCCS and eCS is independently associated with AF detection and recurrent ischemic stroke in patients with ESUS, and these scores can be useful markers for further risk stratification in patients with ESUS.