Safety profile of proprotein convertase subtilisin/kexin type 9 inhibitors alirocumab and evolocumab: an updated meta-analysis and meta-regression.

BACKGROUND: The use of alirocumab and evolocumab is generally safe and well-tolerated. However, concerns remain about their long-term safety, especially with regard to new-onset or worsening diabetes mellitus (DM). We aim to assess the safety profile of alirocumab and evolocumab compared to comparator. METHODS: Studies were retrieved comparing the safety of PCSK9i vs. comparator (placebo or statin with or without ezetimibe). The primary outcome was adverse events leading to death. Secondary outcomes included serious adverse events, new onset diabetes mellitus (DM), worsening of DM, neurocognitive dysfunction, creatine kinase (CK) elevation, elevation of liver enzymes and local injection site reaction. Factors associated with the treatment effect were determined by meta-regression analysis. Subgroup analyses were done to explore potential treatment effect differences based on PCSK9i type and treatment duration. RESULTS: We identified 56 studies with 85,123 adults (29.14% females). PCSK9i was not associated with adverse events that lead to death (OR 0.94, 95% CI 0.84 to 1.04, p = 0.22). Between the two PCSK9i, alirocumab decreased adverse events leading to death (OR 0.79, 95% CI, 0.67 to 0.94, p = 0.008). PCSK9i was associated with less serious events compared to the comparator (OR 0.93, 95% CI 0.89 to 0.98, p < 0.001). This reduction was driven mainly by alirocumab (OR 0.89, 95% CI, 0.85 to 0.93, p < 0.001). Evolocumab worsened DM (OR 2.3, 95% CI 1.26 to 4.2, p = 0.041). Subgroup analysis showed worsening of DM in the first 24 weeks of treatment with odds being highest in the first 12 weeks of treatment (<12 weeks: OR 3.82, 95% CI 1.13 to 12.99, p = 0.03; 12-24 weeks OR 2.12, 95% CI 1.20 to 3.73, p = 0.01. On the other hand, therapy >24 weeks reduced the odds of worsening DM (OR 0.89, 95% CI 0.79 to 0.99, p = 0.04). PCSK9i did not increase cognitive dysfunction, (OR 1.02, 95% CI 0.88 to 1.18, p = 0.76), or cause elevations in liver enzyme (OR 0.91, 95% CI 0.81 to 1.03, p = 0.14), or CK (OR 0.82, 95% CI 0.65 to 1.04, p = 0.10). However, PCSK9i was associated with local injection site reaction (OR 1.54, 95% CI 1.37 to 1.73, p < 0.01). CONCLUSION: Alirocumab decreased adverse events leading to death. Alirocumab and Evolocumab both decreased serious adverse events. PCSK9i did not increase new onset DM however evolocumab worsened DM in the first 24 weeks of treatment. PCSK9i did not increase neurologic dysfunction, and did not elevate liver enzymes and CK, however it was associated with local injection site reaction.

The Roles of Non-Pharmacologic and Emerging Pharmacologic Management of Non-alcoholic Fatty Liver Disease and Sarcopenia: A Narrative Review.

Non-alcoholic fatty liver disease (NAFLD) is one of the most prevalent causes of chronic liver disease worldwide which is often seen in patients with metabolic abnormalities such as those with obesity and insulin resistance. On the other hand, sarcopenia is a generalized and progressive skeletal muscle disorder characterized by low muscle strength, low muscle quality, low physical performance, or a combination of the three. Both disease entities share several underlying risk factors and pathophysiologic mechanisms. These include: (1) cardiometabolic overlaps such as insulin resistance, chronic systemic inflammation, decreased vitamin D levels, sex hormone modifications; (2) muscle-related factors such as those mitigated by myostatin signaling, and myokines (i.e., irisin); and (3) liver-dysfunction related factors such as those associated with growth hormone/insulin-like growth factor 1 Axis, hepatokines (i.e., selenoprotein P and leukocyte cell-derived chemotaxin-2), fibroblast growth factors 21 and 19 (FGF21 and FGF19), and hyperammonemia. This narrative review will examine the pathophysiologic overlaps that can explain the links between NAFLD and sarcopenia. Furthermore, this review will explore the emerging roles of nonpharmacologic (e.g., weight reduction, diet, alcohol, and smoking cessation, and physical activity) and pharmacologic management (e.g., roles of ß-hydroxy-ß-methylbutyrate, branched-chain amino acid supplements, and testosterone therapy) to improve care, intervention sustainability, and acceptability for patients with sarcopenia-associated NAFLD.

Interrelationship of Sarcopenia and Cardiovascular Diseases: A Review of Potential Mechanisms and Management.

Sarcopenia refers to an age-related reduction of lean body mass. It showed a reciprocal relationship with cardiovascular diseases. Thus, it is imperative to explore pathophysiological mechanisms explaining the relationship between sarcopenia and cardiovascular diseases, along with the clinical assessment, and associated management. In this review, we discuss how processes such as inflammation, oxidative stress, endothelial dysfunction, neural and hormonal modifications, as well as other metabolic disturbances influence sarcopenia as well as its association with cardiovascular diseases. Moreover, this review provides an overview of both non-pharmacological and pharmacological management for patients with sarcopenia and cardiovascular diseases, with a focus on the potential role of cardiovascular drugs to mitigate sarcopenia.

Sex differences in transcatheter aortic valve replacement outcomes among patients with bicuspid aortic stenosis.

BACKGROUND: Despite comprising almost half of all patients undergoing valvular repair, data on transcatheter aortic valve replacement (TAVR) in patients with bicuspid aortic stenosis (BAS) are limited. OBJECTIVE: We aimed to evaluate whether there are any sex differences in trends and outcomes of TAVR in this population. METHODS: We utilized the National Inpatient Sample from 2012 to 2020 to identify admissions with BAS who underwent TAVR and analyzed trends and outcomes. Our primary outcome was in-hospital mortality and secondary outcomes were in-hospital complications. We used two models to adjust for demographics (A) and interventions (B). RESULTS: Between 2012 to 2020, there were 76,540 hospitalizations for BAS patients who underwent AVR, among which 6,010 (7.9 %) underwent TAVR. There was an overall increasing trend in number of TAVR cases with a decreasing trend in mortality (2013: 8.7 %, 2020: 1.3 %). TAVR was performed more in males (61.1% vs 38.9 %). Despite the worse baseline characteristics in males, in-hospital mortality (2.4% vs. 1.5 %; OR: 1.584; 95 % CI: 0.621-4.038; p = 0.335) and secondary outcomes were similar across both sexes, even after adjusting for demographics and interventions. CONCLUSION: TAVR in BAS has grown rapidly in the last decade. Males comprised the majority and had more comorbidities, but mortality and complications were similar in both sexes. Despite the increasing number of cases, a decreasing trend in mortality was observed for both sexes ultimately approaching that of SAVR, suggesting that TAVR may be a safe alternative among eligible males and females with bicuspid AS.

Cardiovascular and renal outcomes of glucagon-like peptide 1 receptor agonists among patients with and without type 2 diabetes mellitus: A meta-analysis of randomized placebo-controlled trials.

Background: Multiple cardiovascular outcomes trials (CVOTs) have shown the efficacy of GLP-1RAs in reducing major adverse cardiovascular events (MACEs) for high-risk patients. However, some CVOTs failed to demonstrate cardiovascular benefits. Objectives: We analyzed the impact of GLP-1RA on cardiovascular and renal outcomes in patients with or without T2DM, with subgroup analysis based on sex, estimated glomerular filtration rate (eGFR), body mass index (BMI), and history of cardiovascular disease (CVD). Methods: A comprehensive database search for placebo-controlled RCTs on GLP-1RA treatment was conducted until April 2024. Data extraction and quality assessment were carried out, employing a robust statistical analysis using a random effects model to determine outcomes with log odds ratios and 95 % confidence intervals (CIs). Results: A total of 13 CVOTs comprising 83,258 patients were included. GLP-1RAs significantly reduced MACE (OR 0.86, 95 % CI: 0.80 to 0.94, p < 0.01) all-cause mortality OR 0.87, 95 % CI: 0.82 to 0.93, p < 0.001, CV mortality (OR 0.87, 95 % CI: 0.81 to 0.94, p < 0.001), stroke (fatal: OR 0.74, 95 % CI: 0.56 to 0.96, p = 0.03; non-fatal: OR 0.87, 95 % CI: 0.79 to 0.96, p = 0.005), coronary revascularization (OR 0.86, 95 % CI: 0.74 to 0.99, p = 0.023), and composite kidney outcome (OR 0.76, 95 % CI: 0.67 to 0.85, p < 0.001. GLP-1RA significantly reduced MACE in both sexes. Furthermore, GLP-1RA reduced MACE regardless of CVD history, BMI, and eGFR level. Conclusion: Significant reductions in MACE, overall and CV mortality, stroke, coronary revascularization, and composite kidney outcome with GLP-1RA treatment were noted across all subgroups.

Sex differences in trends and in-hospital outcomes of acute myocardial infarction in patients with familial hypercholesterolemia: insights from a large national database.

BACKGROUND: Sex differences in clinical outcomes following acute myocardial infarction (AMI) are well known. However, data on sex differences among patients with familial hypercholesterolemia (FH) are limited. We aimed to explore sex differences in outcomes of AMI among patients with FH from a national administrative dataset. RESEARCH DESIGN AND METHODS: We utilized the National Inpatient Sample to identify admissions with a primary diagnosis of AMI and a secondary diagnosis of FH. Our primary outcome of interest was in-hospital mortality; secondary outcomes were performance of percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), respiratory complications, use of inotropes, use of mechanical circulatory support (MCS), bleeding complications, transfusion and facility discharge. We adjusted for demographics (model A), comorbidities (model B), and intervention (model C). RESULTS: Between October 2016 and December 2020, 5,714,993 admissions with a primary diagnosis of AMI were identified, of which 3,035 (0.05%) had a secondary diagnosis of FH. In-hospital mortality did not differ between men and women (Model C, adjusted OR = 0.85; 95% CI 0.28-2.60, p = 0.773). There was no sex difference in the secondary outcomes. CONCLUSION: Despite generally being older and having more comorbidities, women with FH fair equally with men with FH in terms of mortality during AMI admission.

Glucagon-like peptide-1 receptor agonists modestly reduced blood pressure among patients with and without diabetes mellitus: A meta-analysis and meta-regression.

AIM: The cardiovascular benefits provided by glucagon-like peptide-1 receptor agonists (GLP-1RAs) extend beyond weight reduction and glycaemic control. One possible mechanism may relate to blood pressure (BP) reduction. We aim to quantify the BP-lowering effects of GLP1-RAs. METHODS: A comprehensive database search for placebo-controlled randomized controlled trials on GLP-1RA treatment was conducted until December 2023. Data extraction and quality assessment were carried out, employing a robust statistical analysis using a random effects model to determine outcomes with a mean difference (MD) in mmHg and 95% confidence intervals (CIs). The primary endpoint was the mean difference in systolic BP (SBP) and diastolic BP. Subgroup analyses and meta-regressions were done to account for covariates. RESULTS: Compared with placebo, GLP-1RAs modestly reduced SBP [semaglutide: MD -3.40 (95% CI -4.22 to -2.59, p < .001); liraglutide: MD -2.61 (95% CI -3.48 to -1.74, p < .001); dulaglutide: MD -1.46 (95% CI -2.20 to -0.72, p < .001); and exenatide: MD -3.36 (95% CI -3.63 to -3.10, p < .001)]. This benefit consistently increased with longer treatment durations. Diastolic BP reduction was only significant in the exenatide group [MD -0.94 (95% CI -1.78 to -0.1), p = .03]. Among semaglutide cohorts, mean changes in glycated haemoglobin and mean changes in body mass index were directly associated with SBP reduction. CONCLUSION: Patients on GLP-1RA experienced modest SBP lowering compared with placebo. This observed effect was associated with weight/body mass index reduction and better glycaemic control, which suggests that BP-lowering is an indirect effect of GLP-1RA and unlikely to be responsible for the benefits.

Atherosclerotic coronary plaque regression from lipid-lowering therapies: A meta-analysis and meta-regression.

Background: Studies reporting collective and comprehensive data on plaque regression of different lipid-lowering therapies (LLTs) are limited. Objectives: We evaluated plaque regression of LLTs based on multiple markers and performed subgroup analyses based on LLT type and post-treatment LDL-C levels. Methods: A literature search was performed to identify studies assessing plaque regression from LLTs. The following LLTs groups were included: High-intensity statin (HIS), HIS+ eicosapentaenoic acid (EPA), HIS + ezetimibe, Low-intensity statin (LIS), LIS + EPA, LIS + Ezetimibe, and PCSK9 inhibitors. Our primary outcomes were change in percent atheroma volume (PAV). Secondary outcomes included mean differences in total atheroma volume (TAV), lumen, plaque, and vessel volumes, fibrous cap thickness (FCT), and lipid arc (LA). Subgroup analyses were performed on LLT type and post-treatment LDL-C levels. Meta-regression was performed to control for covariates. Results: We identified 51 studies with 9,113 adults (22 % females). LLTs reduced PAV levels (-1.10 % [-1.63, -0.56], p < 0.01), with significant reduction observed with HIS, LIS + ezetimibe, LIS + EPA, and PCSK9 inhibitors. LLTs reduced TAV levels (-5.84 mm3 [-8.64 to -3.04] p < 0.01), mainly driven by HIS (-7.60 mm3 [-11.89, -3.31] p < 0.01). LLTs reduced plaque volume and LA and increased FCT. Conclusion: The plaque regression associated with LLTs is observed to be mainly driven by HIS, reducing both TAV and PAV. This suggest that HIS is the most effective LLT for plaque regression. Unstructured abstract: We evaluated plaque regression of LLTs from 51 studies. We found that while reduction of PAV (-1.10 % [-1.63, -0.56], p < 0.01) were present across different LLT types, reduction of TAV (-5.84 mm3 [-8.64 to -3.04] p < 0.01) was mainly driven by HIS (-7.60 mm3 [-11.89, -3.31] p < 0.01). These results suggest that HIS is the most effective LLT for plaque regression.

Efficacy and Safety of Colchicine for the Prevention of Postoperative Atrial Fibrillation Among Patients Undergoing Major Cardiothoracic Surgery: A Meta-analysis and Meta-regression of Randomized Controlled Trials.

ABSTRACT: The role of colchicine for the prevention of postoperative atrial fibrillation (POAF) after cardiothoracic surgery is not well-established. We aimed to evaluate its potential in preventing POAF using data from randomized controlled trials (RCTs). A literature search was performed to identify studies reporting POAF as an outcome after cardiac or thoracic surgery in adult patients randomized to either colchicine or placebo. Primary outcome measured was incidence of POAF. Secondary outcomes included gastrointestinal (GI) adverse effects, sepsis, and length of stay. Subgroup analyses based on treatment durations and type of surgery were also performed, as well as regression analyses to control for covariates. We identified a total of 5377 patients (colchicine = 2,689, placebo = 2688). Although colchicine use was associated with a significantly reduced risk of POAF, risk of GI adverse effects were significantly higher. The rates of infection and length of stay were similar across the groups. Subgroup analyses showed that colchicine was effective for POAF prevention in cardiac surgery, but not in thoracic surgery. Prevention of POAF and incidence of GI adverse effects were similar in short-term and long-term colchicine treatment. Colchicine significantly reduces the incidence of POAF in patients undergoing cardiac surgery, but not in thoracic surgery.

Sex differences in trends and outcomes of acute myocardial infarction with mechanical complications in the United States.

BACKGROUND: Mechanical complications (MC) are rare but significant sequelae of acute myocardial infarction (AMI). Current data on sex differences in AMI with MC is limited. METHODS: We queried the National Inpatient Sample database to identify adult patients with the primary diagnosis of AMI and MC. The main outcome of interest was sex difference in-hospital mortality. Secondary outcomes were sex differences in the incidence of acute kidney injury (AKI), major bleeding, use of inotropes, permanent pacemaker implantation (PPMI), performance of percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), surgery (VSD repair and MV surgery), pericardiocentesis, use of mechanical circulatory support (MCS), ischemic stroke, and mechanical ventilation. RESULTS: Among AMI-MC cohort, in-hospital mortality was higher among females compared to males (41.24% vs 28.13%: aOR 1.39. 95% CI 1.079-1.798; p = 0.01). Among those who had VSD, females also had higher in-hospital mortality compared to males (56.7% vs 43.1%: aOR 1.74, 95% CI 1.12-2.69; p = 0.01). Females were less likely to receive CABG compared to males (12.03% vs 20%: aOR 0.49 95% CI 0.345-0.690; p < 0.001). CONCLUSION: Despite the decreasing trend in AMI admission, females had higher risk of MC and associated mortality. Significant sex disparities still exist in AMI treatment.

End-Of-Life Care for Patients With End-Stage Heart Failure, Comparisons of International Guidelines.

Heart failure (HF) is a chronic, debilitating condition associated with significant morbidity, mortality, and socioeconomic burden. Patients with end-stage HF (ESHF) who are not a candidate for advanced therapies will continue to progress despite standard medical therapy. Thus, the focus of care shifts from prolonging life to controlling symptoms and improving quality of life through palliative care (PC). Because the condition and prognosis of HF patients evolve and can rapidly deteriorate, it is imperative to begin the discussion on end-of-life (EOL) issues early during HF management. These include the completion of an advance directive, do-not-resuscitate orders, and policies on device therapy and discontinuation as part of advance care planning (ACP). ESHF patients who do not have indications for advanced therapies or those who wish not to have a left ventricular assist device (LVAD) or heart transplant (HT) often experience high symptom burden despite adequate medical management. The proper identification and assessment of symptoms such as pain, dyspnea, nausea, depression, and anxiety are essential to the management of ESHF and may be underdiagnosed and undertreated. Psychological support and spiritual care are also crucial to improving the quality of life during EOL. Caregivers of ESHF patients must also be provided supportive care to prevent compassion fatigue and improve resilience in patient care. In this narrative review, we compare the international guidelines and provide an overview of end-of-life and palliative care for patients with ESHF.

Sex differences in permanent pacemaker implantation after transcatheter aortic valve replacement: a systematic review and meta-analysis.

BACKGROUND: There is limited evidence on the effect of sex on permanent pacemaker implantation (PPMI) after transcatheter aortic valve replacement (TAVR). The primary objective of this meta-analysis was to determine the role of sex among patients requiring PPMI post-TAVR. METHODS: A literature search was conducted using the SCOPUS, MEDLINE, and CINAHL databases for studies published until October 2022. Eligible studies included published randomized controlled trials (RCTs) and Observational Cohort Studies (OCS) articles that reported PPMI as an outcome of pacemaker status following TAVR. This study was performed per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. Publication bias was estimated using a Funnel plot and Egger's test. Data were pooled using a random-effects model. The primary endpoint was the sex difference in PPMI after TAVR, with odds ratios and 95% confidence intervals (CIs) extracted. RESULTS: Data was obtained from 63 studies, and a total of 79,655 patients were included. The cumulative PPMI rate was 15.5% (95% CI, 13.6%-17.7%). The pooled analysis revealed that while there were more females than males undergoing TAVR (51.6%, 95% CI 50.4%-52.8%), males have a 14.5% higher risk for post-TAVR PPMI than females (OR 1.145, 95% CI 1.047-1.253, P < 0.01). CONCLUSIONS: Males are more likely to experience PPMI after TAVR than females. Further research needs to be done to better explain these observed differences in outcomes.

Cardiovascular disease in Filipino American men and women: A 2023 update.

With more than 4.2 million people, Filipino Americans are the third largest Asian group in the US and the largest Southeast Asian group in the country. Despite relatively favorable average socioeconomic indicators compared to the general US population, Filipino Americans face a significant burden of traditional cardiovascular risk factors, particularly among men. Moreover, Filipino Americans have high rates of cardiovascular death, often occurring at a younger age compared to other minority groups and Non-Hispanic White adults. In view of these trends, in 2010 the American Heart Association designated Filipino Americans as a high cardiovascular risk group. Despite this, in 2023, Filipino Americans remain underrepresented in landmark cardiovascular cohort studies and are often over looked as a group at increased cardiovascular risk. In this updated narrative review, we summarize the current state of knowledge about the burden of cardiovascular risk factors and diseases experienced by the Filipino American population. Our aim is to inform enhanced clinical, population, and policy-level prevention interventions and boost research in this space.

Sex differences in cardiovascular outcomes of SGLT-2 inhibitors in heart failure randomized controlled trials: A systematic review and meta-analysis.

Background: In patients with heart failure (HF), randomized controlled trials (RCTs) of sodium-glucose transporter-2 inhibitors (SGLT-2is) have proven to be effective in decreasing the primary composite outcome of cardiovascular death and hospitalizations for HF. A recently published meta-analysis showed that the use of SGLT-2is among women with diabetes resulted in less reduction in primary composite outcomes compared with men. This study aims to explore potential sex differences in primary composite outcomes among patients with HF treated with SGLT-2is. Methods: We systematically searched the medical database from 2017 to 2022 and retrieved all the RCTs using SGLT-2is with specified cardiovascular outcomes. We used the PRISMA (Preferred Reporting Items for a Review and Meta-analysis) method to screen for eligibility. We evaluated the quality of studies using the Cochrane Risk of Bias tool. We pooled the hazard ratio (HR) of the primary composite outcomes in both sexes, performed a meta-analysis, and calculated the odds ratio (OR) of the primary composite outcomes based on sex. Results: We included 5 RCTs with a total number of 21,947 patients. Of these, 7837 (35.7 %) were females. Primary composite outcomes were significantly lower in males and females taking SGLT-2is compared to placebo (males - HR 0.77; 95 % CI 0.72 to 0.84; p = 0.00001; females - HR 0.75; 95 % CI 0.67 to 0.84; p = 0.00001). Pooled data from four of the RCTs (n = 20,725) revealed a greater occurrence of the primary composite outcomes in females compared with males (OR 1.32; 95 % CI 1.17 to 1.48; p = 0.0002). Conclusion: SGLT-2is reduce the risk of primary composite outcomes in patients with HF, regardless of sex; however, the benefits were less pronounced in women. Further research needs to be done to better explain these observed differences in outcomes.

Chest Pain in Women: Considerations From the 2021 AHA/ACC Chest Pain Guideline.

Chest pain is a common concern of women evaluated in both the inpatient and outpatient setting. There are significant differences in pathophysiology when comparing coronary artery disease (CAD) in women and men, including a higher prevalence of nonobstructive CAD. Furthermore, significant sex disparities exist in the care of women with acute coronary syndromes that stem from factors such as delays in diagnosis and inconsistencies in treatment. The 2021 AHA/ACC/Multisociety Guideline for the Evaluation and Diagnosis of Chest pain is an important document comprised of recommendations for the assessment of acute and stable chest pain. In this review, we discuss key points from the guideline in the context of evaluating chest pain in women. We discuss the similarities and differences of chest pain presentation between the sexes, evaluation of chest pain in patients with known nonobstructive CAD and ischemia with no obstructive coronary arteries, and considerations for cardiac imaging during pregnancy.

Transcatheter Aortic Valve Replacement-Associated Acute Kidney Injury: An Update.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) is a relatively novel minimally invasive procedure for the treatment of symptomatic patients with severe aortic stenosis. Although it has been proven effective in improving mortality and quality of life, TAVR is associated with serious complications, such as acute kidney injury (AKI). SUMMARY: TAVR-associated AKI is likely due to several factors such as sustained hypotension, transapical approach, volume of contrast use, and baseline low GFR. This narrative review aims to present an overview of the latest literature and evidence regarding the definition of TAVR-associated AKI, its risk factors, and its impact on morbidity and mortality. The review used a systematic search strategy with multiple health-focused databases (Medline, EMBASE) and identified 8 clinical trials and 27 observational studies concerning TAVR-associated AKI. Results showed that TAVR-associated AKI is linked to several modifiable and nonmodifiable risk factors and is associated with higher mortality. A variety of diagnostic imaging modalities have the potential to identify patients at high risk for development of TAVR-AKI; however, there are no existing consensus recommendations regarding their use as of this time. The implications of these findings highlight the importance of identifying high-risk patients for which preventive measures may play a crucial role, and should be maximized. KEY MESSAGE: This study reviews the current understanding of TAVR-associated AKI including its pathophysiology, risk factors, diagnostic modalities, and preventative management for patients.

Aortic Stenosis and Aortic Valve Replacement among Patients with Chronic Kidney Disease: A Narrative Review.

BACKGROUND: Aortic stenosis (AS) can present with dyspnea, angina, syncope, and palpitations, and this presents a diagnostic challenge as chronic kidney disease (CKD) and other commonly found comorbid conditions may present similarly. While medical optimization is an important aspect in management, aortic valve replacement (AVR) by surgical aortic valve replacement (SAVR) or transcatheter aortic valve replacement (TAVR) is the definitive treatment. Patients with concomitant CKD and AS require special consideration as it is known that CKD is associated with progression of AS and poor long-term outcomes. AIMS AND OBJECTIVES: The aim of the study was to summarize and review the current existing literature on patients with both CKD and AS regarding disease progression, dialysis methods, surgical intervention, and postoperative outcomes. CONCLUSION: The incidence of AS increases with age but has also been independently associated with CKD and furthermore with hemodialysis (HD). Regular dialysis with HD versus peritoneal dialysis (PD) and female gender have been associated with progression of AS. Management of AS is multidisciplinary and requires planning and interventions by the heart-kidney team to decrease the risk of further inducing kidney injury among high-risk population. Both TAVR and SAVR are effective interventions for patients with severe symptomatic AS, but TAVR has been associated with better short-term renal and cardiovascular outcomes. IMPLICATIONS FOR PRACTICE: Special consideration must be given to patients with both CKD and AS. The choice of whether to undergo HD versus PD among patients with CKD is multifactorial, but studies have shown benefit regarding AS progression among those who undergo PD. The choice regarding AVR approach is likewise the same. TAVR has been associated with decreased complications among CKD patients, but the decision is multifactorial and requires a comprehensive discussion with the heart-kidney team as many other factors play a role in the decision including preference, prognosis, and other risk factors.

HIV-Associated Nephropathy in 2022.

Background: HIV-associated nephropathy (HIVAN) is a renal parenchymal disease that occurs exclusively in people living with HIV. It is a serious kidney condition that may possibly lead to end-stage kidney disease, particularly in the HIV-1 seropositive patients. Summary: The African-American population has increased susceptibility to this comorbidity due to a strong association found in the APOL1 gene, specifically two missense mutations in the G1 allele and a frameshift deletion in the G2 allele, although a "second-hit" event is postulated to have a role in the development of HIVAN. HIVAN presents with proteinuria, particularly in the nephrotic range, as with other kidney diseases. The diagnosis requires biopsy and typically presents with collapsing subtype focal segmental glomerulosclerosis and microcyst formation in the tubulointerstitial region. Gaps still exist in the definitive treatment of HIVAN - concurrent use of antiretroviral therapy and adjunctive management with like renal-angiotensin-aldosterone system inhibitors, steroids, or renal replacement therapy showed benefits. Key Message: This study reviews the current understanding of HIVAN including its epidemiology, mechanism of disease, related genetic factors, clinical profile, and pathophysiologic effects of management options for patients.

Maternal and neonatal outcomes among pregnant women with cardiovascular disease in the Philippines: a retrospective cross-sectional study from 2015-2019.

PURPOSE: Several studies link maternal cardiovascular disease (CVD) to maternal and fetal morbidity and mortality. This study describes the profile of maternal, obstetric, and neonatal outcomes among pregnant women with CVD in a tertiary hospital in the Philippines. It identifies the clinical and sociodemographic variables associated with these outcomes. MATERIALS AND METHODS: A single-center, retrospective analysis of pregnant women admitted for delivery at the Philippine General Hospital from 2015 to 2019 was performed. Of these patients, pregnant women with CVD were identified as the cohort for this study. Data on clinical and sociodemographic factors, maternal major adverse cardiovascular events, neonatal adverse clinical events, and obstetric complications were collected. Logistic regression analysis was performed to determine the odds ratio for the risk factors for small-for-gestational-age (SGA) babies and preterm birth. RESULTS: Among 30,053 delivery admissions in the Philippine General Hospital from 2015 to 2019, 293 (0.98%) pregnant women had CVD. Of the CVDs present in this cohort, congenital heart diseases (n = 119, 40.6%) were the most common, followed by rheumatic heart disease (n = 109, 37.2%). Maternal adverse events were rarely observed. Four women experienced symptomatic arrhythmias, two presented with worsening heart failure, three experienced thromboembolic events, and one had cerebrovascular infarction. There was no reported maternal death, cardiac arrest, shock, or acute renal failure. The majority (69.3%) of the women included in the study were delivered by spontaneous vaginal delivery and assisted vaginal delivery by vacuum or forceps; however, a significant portion of these women had undergone cesarean section. Almost all the study cohort delivered live births, with most neonates being delivered at 37-38 weeks gestational age (83.6%) and only 16.0% born preterm. However, a significant portion, a third of the neonates, were classified as having low birth weight. Around 17.4% of neonates born from gravidocardiac mothers were admitted neonatal intensive care unit. Conditions associated with preterm birth were low educational attainment, previous history of early neonatal death, maternal low ejection fraction, and abnormal maternal left ventricular geometry. The conditions associated with SGA babies were high gravidity and parity, a history of abortion/stillbirth, a history of previous cesarean section delivery, low ejection fraction, a history of multiple gestations, and higher BMI. CONCLUSION: In this cohort study, adverse maternal outcomes were rarely observed. CVD in pregnancy is associated with an increased risk of preterm birth and SGA babies. We identified certain maternal conditions and sociodemographic factors associated with these outcomes. Despite having CVD, our study cohort had no mortality from the pregnancy.

The Role of Serum Chloride in Acute and Chronic Heart Failure: A Narrative Review.

Clinical guidelines include diuretics for the treatment of heart failure (HF), not to decrease mortality but to decrease symptoms and hospitalizations. More attention has been paid to the worse outcomes, including mortality, associated with continual diuretic therapy due to hypochloremia. Studies have revealed a pivotal role for serum chloride in the pathophysiology of HF and is now a target of treatment to decrease mortality. The prognostic value of serum chloride in HF has been the subject of much attention. Mechanistically, the macula densa, a region in the renal juxtaglomerular apparatus, relies on chloride levels to sense salt and volume status. The recent discovery of with-no-lysine (K) (WNK) protein kinase as an intracellular chloride sensor sheds light on the possible reason of diuretic resistance in HF. The action of chloride on WNKs results in the upregulation of the sodium-potassium-chloride cotransporter and sodium-chloride cotransporter receptors, which could lead to increased electrolyte and fluid reabsorption. Genetic studies have revealed that a variant of a voltage-sensitive chloride channel (CLCNKA) gene leads to almost a 50% decrease in current amplitude and function of the renal chloride channel. This variant increases the risk of HF. Several trials exploring the prognostic value of chloride in both acute and chronic HF have shown mostly positive results, some even suggesting a stronger role than sodium. However, so far, interventional trials exploring serum chloride as a therapeutic target have been largely inconclusive. This study is a review of the pathophysiologic effects of hypochloremia in HF, the genetics of chloride channels, and clinical trials that are underway to investigate novel approaches to HF management.