Dermatological Manifestations in Patients With Chronic Kidney Disease: A Review.

Chronic kidney disease (CKD) is a progressive disease and has multiple clinical manifestations; when CKD reaches the end stage, at least one cutaneous manifestation appears due to some increased toxin levels or a constant proinflammatory state. Nonspecific manifestations include pruritus, xerosis, pigmentation disorders, acquired ichthyosis, purpuric spots, and nail disorders. Some specific manifestations are bullous dermatoses, acquired perforating dermatoses (APD), eruptive xanthoma, access site infections, calcifying disorders, and nephrogenic systemic fibrosis (NSF). All these cutaneous changes negatively impact patients; early recognition and diagnosis of these dermatoses will make a difference in their quality of treatment. Exploring a patient's skin is fundamental to suspect some diseases and increased toxin levels; pruritus occurs when uremic toxins are raised, and nail disorders are associated with hypoalbuminemia. This review provides the clinician with information on the clinical manifestations that occur in CKD, including epidemiology, pathophysiology, clinical manifestations, diagnosis, histopathology, treatment, and life impact of the dermatoses in CKD.

Common Cardiovascular Diseases in Women.

Cardiovascular disease is a leading cause of death for women in the United States. This article encompasses the epidemiology/etiology, clinical presentation, diagnostic assessment, management, and prognosis of some common cardiovascular disorders seen in women with a special focus on pregnancy.

Hemodynamic indices in pulmonary hypertension: a narrative review.

Background and Objective: Pulmonary hypertension (PH) is defined as a mean pulmonary artery pressure (mPAP) >20 mmHg and its presence is associated with worse outcomes. A comprehensive hemodynamic evaluation of the pulmonary circulation is essential for diagnosis, hemodynamic classification, and prognostication. A multitude of indices assess different aspects of the pulmonary circulation but there are no reviews that describe their specific value in PH. Methods: We performed a thorough literature search of relevant articles in English from 1970-2021 using PubMed. Key Content and Findings: In this article, we present both static and dynamic indices used for the hemodynamic assessment of PH. While some of these indices are routinely used in clinical practice, including cardiac index (CI), stroke volume (SV), and pulmonary vascular resistance (PVR); others such as pulmonary artery compliance (PAC), pulmonary effective arterial elastance (Ea), and pulmonary artery pulsatility index (PAPi) are gaining popularity by enhancing the understanding of different aspects of the pulmonary circulation. We described the advantages and pitfalls of various indices, including when to use them in the hemodynamic evaluation of patients with PH. Conclusions: A variety of indices measuring different aspects of the right ventricle (RV)-pulmonary arteries (PA) system provide valuable information in patients with PH. However, it remains important to develop and validate indices that provide a comprehensive hemodynamic evaluation to improve outcomes in patients with PH.

In-Hospital Outcome In Patients With Acyanotic Congenital Heart Disease Undergoing Transcatheter Aortic Valve Replacement.

The purpose of the study was to determine the in-hospital outcome and resource utilization in patients with acyanotic congenital heart disease (ACHD) undergoing transcatheter aortic valve replacement (TAVR). Current guidelines from professional societies do not support TAVR in patients with ACHD, likely from a lack of supportive evidence. Temporal trends in patients with ACHD undergoing TAVR were determined using the 2016-2018 National Inpatient Sample database appropriate ICS-10-PCS code. Stata 16.0 was used for statistical analysis. 0.87% of patients undergoing TAVR had concomitant ACHD, with ASD being the most common (78%). After matching, there was no increased risk of mortality in ACHD patients undergoing TAVR compared to patients without ACHD (OR 1.43, P = 0.59). Additionally, no difference was found in the incidence of overall cardiac complications between patients with ACHD and patients without ACHD, except STEMI (OR 4.16, 95% CI, 1.08-16.00, P = 0.038), which is likely due to more comorbidity burden in the later cohort. Complications such as acute kidney injury, ischemic stroke, and bleeding were similar. Hospital resource utilization was higher in the ACHD group in the form of increased length of stay and higher mean total cost. The comparable in-hospital all-cause mortality and complication rate in ACHD patients undergoing TAVR compared to patients without ACHD is encouraging and will be helpful to design future randomized controlled trials.

Bempedoic acid and its role in contemporary management of hyperlipidemia in atherosclerosis.

Atherosclerotic heart disease is the leading cause of mortality and morbidity in the USA. Low density lipoprotein (LDL) has been the target for many hypolipidemic agents to modify atherosclerotic risk. Bempedoic acid is a novel hypolipidemic drug that inhibits the enzymatic activity of ATP citrate lyase in the cholesterol synthesis pathway. CLEAR Harmony, CLEAR Wisdom, CLEAR Tranquillity and CLEAR Serenity have shown safety and efficacy associated with long term administration of this drug. Studies have shown effectiveness in reducing LDL-C in both statin intolerant patients and in patients on maximally tolerated doses of statin. The fixed drug combination of bempedoic acid and ezetimibe in a recent phase III showed significant reduction in LDL compared with placebo, which might be a promising future for LDL reduction among statin intolerant patients. Bempedoic acid also reduced inflammatory markers like hs-CRP. Given these results, bempedoic acid alone and in combination with ezetimibe received the USA FDA approval for adults with heterozygous familial hypercholesterolaemia or established atherosclerotic cardiovascular disease. We present a comprehensive review exploring the underlying mechanism, pre-clinical studies, and clinical trials of bempedoic acid and discuss the potential future role of the drug in treating hyperlipidaemia.

Prevention and Management of Hypertriglyceridemia-Induced Acute Pancreatitis During Pregnancy: A Systematic Review.

Severe gestational hypertriglyceridemia can lead to acute pancreatitis, with maternal mortality rate of approximately 20%. The recent National Lipid Association part 2 expert panel recommendations provide guidance on monitoring pregnant women at high risk for hyperlipidemia. We suggest that high-risk women have triglyceride levels checked once every trimester. Fasting triglycerides >250 mg/dL should prompt monthly triglyceride levels, screening for gestational diabetes, and implementing a strict low-carbohydrate, low-fat diet, exercise. Fasting triglycerides >500 mg/dL, despite a strict dietary and lifestyle modifications, should prompt treatment with omega-3-fatty acids and continue a fat-restricted diet (<20 g total fat/d or <15% total calories) under the guidance of a registered dietician. The use of fibrates should be considered as a second-line therapy due to their unclear risk versus benefit and potential teratogenic effects. Plasmapheresis should be considered early in asymptomatic pregnant women with fasting triglyceride levels >1000 mg/dL or in pregnant women with clinical signs and symptoms of pancreatitis and triglyceride levels >500 mg/dL despite maximal lifestyle changes and pharmacologic therapy.

A Brief Overview of Recurrent Pericarditis Management and the Potential of Rilonacept as a New Therapeutic Option.

Recurrent pericarditis affects 15-30% of patients after acute pericarditis. A large number of the patients with recurrent pericarditis can become corticosteroid dependent, leading to disease chronicity and drug dependence, with additional morbidity from long-term steroid use. Recent randomized trials indicate the efficacy of the interleukin-1 inhibitors anakinra and rilonacept in recurrent pericarditis, including colchicine-resistant and corticosteroid-dependent cases. In particular, rilonacept was assessed in the RHAPSODY clinical trial and found to be a potential treatment option that would decrease recurrent episodes, enabling patients to be weaned off steroids. Additionally, new data indicate that rilonacept should be considered as an option for patients with recurrent pericarditis, as add-on therapy to colchicine and nonsteroidal anti-inflammatory drugs, in place of steroids. We review the current management options for recurrent pericarditis as well as rilonacept as a prospective new addition to our armamentarium.

Eosinophilic Myocarditis: When Allergies Attack the Heart!

Eosinophilic myocarditis is a clinical condition whereby myocardial injury is mediated by eosinophilic infiltration. A number of underlying causes, including reactive, clonal, or idiopathic hypereosinophilic syndrome, may trigger eosinophilia. Disease presentation may vary from mild subclinical variants to fulminant myocarditis with thromboembolic complications, and in some cases, endomyocardial and valvular fibrosis may be seen. A detailed examination coupled with the use of multimodality imaging, and endomyocardial biopsy may help establish diagnosis. Treatment is aimed at symptomatic management and treating the underlying cause of eosinophilia, such as withdrawal of implicated drugs, antihelminthic therapy for infection, immunosuppression for autoimmune conditions, and targeted therapy with tyrosine kinase inhibitors in cases with clonal myeloid disorders.

Proposed Pathogenesis, Characteristics, and Management of COVID-19 mRNA Vaccine-Related Myopericarditis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the novel coronavirus causing coronavirus disease 2019 (COVID-19), has affected human lives across the globe. On 11 December 2020, the US FDA granted an emergency use authorization for the first COVID-19 vaccine, and vaccines are now widely available. Undoubtedly, the emergence of these vaccines has led to substantial relief, helping alleviate the fear and anxiety around the COVID-19 illness for both the general public and clinicians. However, recent cases of vaccine complications, including myopericarditis, have been reported after administration of COVID-19 vaccines. This article discusses the cases, possible pathogenesis of myopericarditis, and treatment of the condition. Most cases were mild and should not yet change vaccine policies, although prospective studies are needed to better assess the risk-benefit ratios in different groups.

The Role of Dapagliflozin in the Management of Heart Failure: An Update on the Emerging Evidence.

The burden and cost of heart failure management, primarily in the form of hospitalization in the setting of decompensated heart failure, continue to be some of the biggest clinical challenges in cardiovascular medicine. In recently published randomized controlled trials, including DAPA-HF, sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin was shown to reduce hospitalization from heart failure or mortality associated with cardiovascular causes, when added to existing guideline-directed medical therapy. The American College of Cardiology (ACC) released a Clinical Pathway guideline that recommends the use of dapagliflozin in clinical management of heart failure, with or without diabetes. Furthermore, the results of the DAPA-CKD trial broaden the utility of dapagliflozin as a therapeutic option in patients with advanced kidney disease. In this article, the authors explore the existing evidence on dapagliflozin in heart failure with reduced ejection fraction and highlight the need for further research on uses of dapagliflozin in the world of heart failure.

Contemporary narrative review on left atrial strain mechanics in echocardiography: cardiomyopathy, valvular heart disease and beyond.

Left atrial (LA) strain mechanics refer to the measurement of LA myocardial deformation expressed as a percentage, and have been gathering interest over the last decade with expanding research supporting their utility in multiple cardiovascular disorders. Measured through advanced dynamic imaging techniques which include tissue Doppler imaging (TDI) and two-dimensional (2D) speckle tracking echocardiography (STE), LA strain mechanics are affected by left ventricular diastolic dysfunction prior to the onset of functional and structural changes in the left ventricle (LV). There is a need for practising cardiologists to become more familiar with the clinical utility of LA strain mechanics. In this article, we begin by reviewing the physiologic function of the LA, using this as a basis for understanding LA strain mechanics. The focus of this review article is to provide a contemporary update on the utility of LA strain mechanics in a range of cardiovascular disorders, including atrial fibrillation (AF), hypertrophic cardiomyopathy (HCM), valvular pathologies, coronary artery disease (CAD) as well as systemic diseases, such as hypertension (HTN), obesity and diabetes mellitus (DM). This article also highlights the current limitations in more widespread clinical applications of LA strain mechanics, as well as outlining the future perspectives on the clinical applications of LA strain mechanics.

Submassive Pulmonary Embolism in Mild COVID-19 Without Lung Infiltrates.

A 66-year-old man who had been diagnosed with mild coronavirus 2019 (COVID-19) infection nine days prior presented to the emergency room with acute-onset chest pain and shortness of breath. Chest CT angiogram (CTA) revealed pulmonary emboli (PE) in the right and left pulmonary arteries with right heart strain; lung parenchyma showed no infiltrates. Although severe COVID-19 infection is associated with thrombotic complications, data regarding the occurrence of PE in mild cases of COVID-19 is scarce. However, even mild cases of COVID-19 are reported to have revealed lung infiltrates, particularly ground-glass opacities, on imaging. The possibility of the lungs being the primary source of COVID-19-associated coagulopathy has been raised. We report an uncommon case of submassive PE occurring in mild COVID-19, without any associated lung infiltrates. This case indicates that mild COVID-19, without significant lung parenchymal involvement, can also cause a hypercoagulable state, resulting in venous thromboembolism (VTE).

Gout Pharmacotherapy in Cardiovascular Diseases: A Review of Utility and Outcomes.

Hyperuricemia and gout have been linked to an increased risk for cardiovascular (CV) disease, stroke, hypertension, heart failure, and chronic kidney disease, possibly through a proinflammatory milieu. However, not all the drugs used in gout treatment improve CV outcomes; colchicine has shown improved CV outcomes in patients with recent myocardial infarction and stable coronary artery disease independent of lipid-lowering effects. There is resurging interest in colchicine following publication of the COLCOT, LoDoCo, LoDoCo2, LoDoCo-MI trials, and COLCORONA trial which will shed light on its utility in COVID-19. Our aim is to review the CV use of colchicine beyond pericardial diseases, as well as CV outcomes of the available gout therapies, including allopurinol and febuxostat. The CARES trial and its surrounding controversies, which lead to the US FDA 'black box' warning on febuxostat, in addition to the recent FAST trial which contradicts this and finds febuxostat to be non-inferior, are discussed in this paper.

Aspirin for Primary Prevention of Coronary Artery Disease.

Primary prevention of coronary artery disease (CAD) is an important means to reduce the burden of the disease. Aspirin has been widely prescribed over the last several decades as part of primary CAD prevention strategy. However, 3 recent hallmark trials - ARRIVE, ASCEND and ASPREE have raised serious questions about this common practice. Although, aspirin reduced incidence of non-fatal MI and stroke in these recent studies, bleeding risk was higher. In the present era, where regular exercise, healthy diet, smoking cessation, and statins are used to manage the risk factors of CAD, additional prescription of aspirin seems more harmful than beneficial. The guidelines of major societies such as European Society of Cardiology (ESC), American College of Cardiology (ACC), and American Heart Association (AHA) also reflect this shift. In this article, the authors aim to highlight the current evidence on aspirin use for primary prevention of CAD, in the context of evolving contrasting clinical trial data from the last 2 decades. We also highlight the pertinent sections of the most recent clinical guidelines of European Society of Cardiology, American College of Cardiology, and American Heart Association in this article.

Sex Differences in In-Hospital Outcomes of Transcatheter Aortic Valve Replacement.

Since the introduction of transcatheter aortic valve replacement (TAVR), there has been a paradigm shift in the management of severe aortic stenosis. While women represent almost half of the patients undergoing TAVR, there are limited data on sex-based comparisons in hospital outcomes and predictors of mortality in women and men. The National Inpatient Sample database from 2012 to 2015 was used to identify TAVR using international classification of diseases-9 clinical modification procedure codes 35.05 and 35.06. We identified 61,239 patients who underwent TAVR between 2012 and 2015. After adjusting for potential confounders, women had higher odds of all-cause mortality as compared to men [odds ratio (OR) 1.25, 95% confidence interval (CI): 1.01-1.54; P = 0.036]. Moreover, women had significantly increased odds of cardiac complications [OR 2.41, 95% CI: 1.67-3.49; P ≤ 0.01], respiratory complications [OR 1.20 95% CI: 1.07-1.34; P = 0.001], major hemorrhage requiring transfusion [OR 1.51, 95% CI: 1.37-1.67; P ≤ 0.001], neurological complications [OR 1.38, 95% CI: 0.95-1.99; P = 0.08], need for vasopressor treatment [OR 1.33, 95% CI: 1.01-1.75; P = 0.04], and vascular complications [OR 1.73, 95% CI: 1.19-2.52; P = 0.004]. On the contrary, the odds of pacemaker requirement [OR 0.85, 95% CI: 0.75-0.97; P = 0.02], and acute kidney injury [OR 0.80, 95% CI: 0.71-0.91; P = 0.001] were significantly lower in women. Among patients undergoing TAVR, women were more likely to have in-hospital complications and mortality as compared with men. Further studies are needed to identify the discrepancy in in-hospital outcomes with sex-specific factors being considered.

COVID-19 Pandemic: Cardiovascular Complications and Future Implications.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now a global pandemic with the highest number of affected individuals in the modern era. Not only is the infection inflicting significant morbidity and mortality, but there has also been a significant strain to the health care system and the economy. COVID-19 typically presents as viral pneumonia, occasionally leading to acute respiratory distress syndrome (ARDS) and death. However, emerging evidence suggests that it has a significant impact on the cardiovascular (CV) system by direct myocardial damage, severe systemic inflammatory response, hypoxia, right heart strain secondary to ARDS and lung injury, and plaque rupture secondary to inflammation. Primary cardiac manifestations include acute myocarditis, myocardial infarction, arrhythmia, and abnormal clotting. Several consensus documents have been released to help manage CV disease during this pandemic. In this review, we summarize key cardiac manifestations, their management, and future implications.

Novel emerging therapies in atherosclerosis targeting lipid metabolism.

INTRODUCTION: Recent years have brought significant developments in lipid and atherosclerosis research. Although statins are a cornerstone in hyperlipidemia management, new non-statin therapies have had an impact. The reduction of low-density lipoprotein cholesterol (LDL-C) further translates into the lowering of cardiovascular mortality. Additionally, lipid research has progressed beyond LDL-C reduction and this has brought triglyceride (TG) and other apoprotein-B containing lipids into focus. AREAS COVERED: Inclisiran and pemafibrate, with expected approval soon, come under the spotlight. We discuss other therapeutics such as lomitapide, mipomersen, volanesorsen, and evinacumab and newly approved non-statin-based therapies such as ezetimibe, icosapent ethyl (IPE), and bempedoic acid. EXPERT OPINION: New options now exist for the prevention of atherosclerosis in patients that are not optimized on statin therapy. Multiple guidelines endorse ezetimibe, PCSK9 inhibitors, bempedoic, and IPE as add-on therapy. Recently approved bempedoic acid/ezetimibe combination might gain popularity among clinicians. Inclisiran and pemafibrate show promise in the reduction of LDL-C and TG, respectively, and results are pending in cardiovascular outcome trials. Combination strategies could improve outcomes, but the challenge will be balancing cost and selecting the correct patient population for each treatment modality to maximize benefit with the fewest medications.

Peri-transplant renal dysfunction in patients with non-alcoholic steatohepatitis undergoing liver transplantation.

Non-alcoholic fatty liver disease (NAFLD) is currently the most common etiology of chronic liver disease (CLD) caused by an accumulation of fat in the liver and globally is the leading indication of liver transplantation. Emerging data has recognized an increased association of NAFLD with risk of other metabolic liver diseases like type 2 diabetes mellitus, chronic kidney disease (CKD) and cardiovascular diseases. Pathophysiologically, NAFLD patients have a state of low-grade systemic inflammation, insulin resistance and atherogenic dyslipidemia which causes renal dysfunction. Patients with NAFLD cirrhosis awaiting liver transplant (LT) face unique challenges and have a significantly higher requirement of simultaneous-liver-kidney transplant as compared to other etiologies. Further, NAFLD not only recurs but also occurs as a de novo manifestation post-LT. There is also a significantly higher risk of waiting list stagnation and dropouts due to burdensome cardiometabolic disorders in NAFLD patients. The current review aims to understand the prevalence and pathogenetic basis of renal dysfunction in NAFLD. Additionally, the review describes the choice of immunosuppression protocols and use of intraoperative renal replacement therapy in context of intra and post-operative renal dysfunction in NAFLD patients. Prospective controlled trials focusing on NAFLD and development of CKD are needed to assess the existence of a causal and/or a bidirectional relationship between NAFLD and CKD.