Human Papillomavirus as Nontraditional Cardiovascular Risk Factor: Fact or Fiction? Part 2.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the US and worldwide, with more than 42 million Americans infected with types of HPV that are known to cause disease. While the link between HPV and the development of a variety of cancers has been strongly established, recent literature has demonstrated a potential association between HPV and increased risk of cardiovascular disease. Nevertheless, despite plausible mechanisms for the development of cardiovascular disease with HPV infection, a causative relationship has yet to be firmly established, in part due to potential confounding risk factors between the two. In this 2-part series, we discuss the emerging relationship between HPV and cardiovascular disease. In part 2, we focus on novel risk factors for HPV infection and cardiovascular disease including adverse childhood events, socioeconomic status, and immunosuppression. We conclude with potential prevention and treatment strategies for HPV-related cardiovascular disease, as well as the future direction of the research.

Prognostic significance of exercise stress echocardiography using two and three diastolic variable approaches.

BACKGROUND: The prognostic utility of comprehensive, guideline-defined assessment of diastolic measures during routine exercise echocardiography remains unclear. OBJECTIVES: The purpose of the study was to pragmatically assess the prognostic role of obtainable Doppler-derived diastolic variables during treadmill exercise echocardiography. METHODS: In this retrospective study, the authors included 1910 patients undergoing exercise echocardiography. The guideline-defined diastolic measures included resting septal e' velocity, post-exercise E/e' ratio and post-exercise tricuspid regurgitant jet velocity. Since tricuspid regurgitant jet velocity is not routinely obtainable, the authors examined 2 approaches: 2 variable approach using only resting septal e' velocity and post-exercise E/e' ratio and 3 variable approach with all diastolic variables. RESULTS: The mean age of study subjects was 57.6 ± 16 years and 1068 (56 %) were women. The tricuspid jet velocity was not reliably obtained in 501(26 %) of patients. All 3 diastolic variables were associated with the hard outcomes (mortality, acute coronary syndrome, cardiac hospitalization), soft outcomes (subsequent revascularization and cardiac testing), as well as the composite outcome. In the 2-variable approach, the presence of 2 abnormal variables was associated with a worse composite outcome. In the 3 variable approach, the presence of 2 or 3 abnormal variables was associated with a worse composite outcome. The associations persisted after multivariable adjustment and in the propensity matched subgroups. CONCLUSIONS: Guideline-defined diastolic variables during treadmill exercise echocardiography offer prognostic utility when used in combination, especially if all 3 variables are obtainable.

Effects of SGLT2 Inhibitors on Cardiac Mechanics in Hispanic and Black Diabetic Patients.

Background: Clinical trials demonstrating improved cardiovascular outcomes with SGLT2 inhibitors have often had limited representation from Black and Hispanic populations. While the mechanisms of action are not well known, ethnicity- or gender-based receptor physiology may render SGLT2 inhibitors a better agent in certain populations over others. Methods: A medical records query yielded diabetic patients initiated on SGLT2 inhibitors between 2013 and 2020. Patients with coronary artery disease, cardiac arrhythmias, and heart failure were excluded. Transthoracic echocardiographic studies (TTE) before and after starting SGLT2 inhibitors were analyzed, and post-processing left ventricular global longitudinal strain (LV GLS) analysis was also performed on each echocardiographic study. Univariate outliers and patients with missing data were excluded. Results: Among 94 patients with TTE (mean age 60.7 years; 68% Hispanics, 22.3% Blacks; median follow up of 7 months), there were significant improvements in the mean LV GLS (-15.3 vs. -16.5; p = 0.01), LV mass (LVM) (198.4 ± 59.6 g vs. 187.05 ± 50.6 g; p = 0.04), and LV mass index (LVMI) (100.6 ± 26.6 g/m2 vs. 94.3 ± 25.4 g/m2; p = 0.03) before and after initiating SGLT2 inhibitors but no significant change in the ratio (MV E/E') of peak early diastolic mitral flow velocity (E) and spectral pulsed-wave Doppler-derived early diastolic velocity from the septal mitral annulus (E') (12.5 ± 5.7 vs. 12.7 ± 4.8; p = 0.38). Changes in HbA1c (r2 = 0.82; p = 0.026), LVM (r2 = 0.20; p = 0.04), and LVMI (r2 = 0.20; p = 0.04) were found to be independently associated with changes in values of LV GLS on follow-up echocardiograms, when compared to the pre-medication LV GLS number. Conclusion: Non-White diabetic patients receiving SGLT2 inhibitors against a backdrop of other cardioprotective medications demonstrate significant improvements in LV remodeling and LV GLS, driven in part by an improvement in glycemic control. Large, prospective studies are needed to explore the differences in the therapeutic actions of SGLT2 inhibitors among different populations.

Bivalirudin versus heparin in patients undergoing percutaneous coronary intervention in acute coronary syndromes.

INTRODUCTION: Data on outcomes between unfractionated heparin and bivalirudin anticoagulation during percutaneous coronary intervention (PCI) in acute coronary syndromes (ACS) remains inconclusive. We aimed to systematically analyze PCI outcomes comparing unfractionated heparin and bivalirudin. METHODS: We systematically searched Ovid MEDLINE, Ovid Embase, Ovid Cochrane Database of Systematic Reviews, Scopus, and Web of Science from database inception in 1966 through January 2024 for studies evaluating PCI outcomes comparing unfractionated heparin and bivalirudin. Two investigators independently reviewed data. Conflicts were resolved through consensus. Random-effects meta-analyses were used. RESULTS: Ten prospective trials were identified that enrolled 42,253 individuals who presented with an acute coronary syndrome. Our analysis found that heparin when compared to bivalirudin was associated with an increased risk of trial-based definition of major bleeding (RR 1.68, 95% CI 1.29-2.20), non-access site complications (RR 4.6, 95% CI 1.75-12.09), TIMI major bleeding (RR 1.70, 95% CI 1.20-2.41), major bleeding risks (RR 1.87, 95% CI 1.49-2.36), cardiovascular disease death (RR 1.26, 95% CI 1.02-1.57), and thrombocytopenia (RR 1.67, 95% CI 1.07-2.62). There were no statistically significant differences between heparin and bivalirudin for all-cause mortality, MACE, stroke, reinfarction, target vessel revascularization, acute or stent thrombosis. CONCLUSIONS: The present meta-analysis demonstrates bivalirudin reduces major bleeding when used for anticoagulation during PCI in patients with acute coronary syndromes and is not associated with an increased risk of stent thrombosis or MACE.

Left Atrial Appendage Occlusion as a Strategy for Reducing Stroke Risk in Nonvalvular Atrial Fibrillation.

Nonvalvular atrial fibrillation (AF) is a common rhythm disorder of middle-aged to older adults that can cause ischemic strokes and systemic embolism. Stroke prevention is a crucial aspect of management, considering the increasing AF population and the associated morbidity and mortality. The left atrial appendage (LAA) has been identified as a predominant source of AF-associated thrombus and stroke, with at least 90% of the thrombi originating from this anatomical structure. Lifelong use of oral anticoagulants reduces the risk of these ischemic events but increases the risk of major and clinically relevant hemorrhages. In addition, these medications also require strict compliance for efficacy and have high failure rates in higher-risk patients. LAA occlusion (LAAO) has emerged as an alternative strategy for stroke prevention with encompassing various percutaneous and surgical techniques. Randomized controlled trials evaluating this intervention have shown promising results in stroke reduction replacing anticoagulation therapy. In this review, we aim to provide a comprehensive overview on the anatomy of the LAA and its role in thrombus formation, the emergence of various LAAO techniques and devices, and provide evidence on the role of LAAO in the reduction of stroke risk among patients with nonvalvular AF.

Human Papillomavirus as Non-Traditional Cardiovascular Risk Factor: Fact or Fiction? Part 1.

Human papillomavirus (HPV) is the most common sexually transmitted infection in the United States and worldwide, with more than 42 million Americans infected with types of HPV that are known to cause disease. Although the link between HPV and the development of a variety of cancers has been strongly established, recent literature has demonstrated a potential association between HPV and increased risk of cardiovascular disease. Nevertheless, despite plausible mechanisms for the development of cardiovascular disease with HPV infection, a causative relationship has yet to be firmly established, in part due to potential confounding risk factors between the two. In this 2-part series, we discuss the emerging relationship between HPV and cardiovascular disease. In part 1, we focus on the pathophysiology of HPV infection and potential mechanisms for the development of cardiovascular disease.

Pharmacotherapy for Coronary Artery Disease and Acute Coronary Syndrome in the Aging Population.

PURPOSE OF REVIEW: To provide a comprehensive summary of relevant studies and evidence concerning the utilization of different pharmacotherapeutic and revascularization strategies in managing coronary artery disease and acute coronary syndrome specifically in the older adult population. RECENT FINDINGS: Approximately 30% to 40% of hospitalized patients with acute coronary syndrome are older adults, among whom the majority of cardiovascular-related deaths occur. When compared to younger patients, these individuals generally experience inferior clinical outcomes. Most clinical trials assessing the efficacy and safety of various therapeutics have primarily enrolled patients under the age of 75, in addition to excluding those with geriatric complexities. In this review, we emphasize the need for a personalized and comprehensive approach to pharmacotherapy for coronary heart disease and acute coronary syndrome in older adults, considering concomitant geriatric syndromes and age-related factors to optimize treatment outcomes while minimizing potential risks and complications. In the realm of clinical practice, cardiovascular and geriatric risks are closely intertwined, with both being significant factors in determining treatments aimed at reducing negative outcomes and attaining health conditions most valued by older adults.

Role of Colchicine in Cardiovascular Disorders.

Inflammation has played a pivotal role in atherosclerosis and other cardiovascular disorders, prompting the exploration of anti-inflammatory therapies to improve cardiovascular outcomes. Colchicine, a well-established agent in conditions such as gout and familial Mediterranean fever, has emerged as a promising novel anti-inflammatory agent in the realm of cardiovascular diseases. Its ability to target both traditional risk factors and residual inflammatory risk marks a significant advancement in cardiovascular prevention strategies, indicating a new era in cardiovascular care. Landmark trials have supported the efficacy and safety of low-dose colchicine in reducing major adverse cardiovascular events when combined with standard therapies. In addition, its endorsement by major cardiovascular societies underscores its significance as the first targeted anti-inflammatory therapy for cardiovascular disease. However, careful monitoring for drug interactions and adverse effects, particularly on kidney and liver function, is essential for safe use. In this review, we aim to comprehensively summarize the mechanisms of action of colchicine, its molecular and biochemical targets in various cardiovascular conditions, and its pharmacokinetics, and delve deeply into the existing evidence on its safety and efficacy in the treatment of cardiovascular disorders, including coronary artery disease, pericarditis, atrial fibrillation, and heart failure.

AABB recommends restrictive RBC transfusions for hospitalized adults and children.

SOURCE CITATION: Carson JL, Stanworth SJ, Guyatt G, et al. Red blood cell transfusion: 2023 AABB international guidelines. JAMA. 2023;330:1892-1902. 37824153.

Pharmacotherapy and revascularization strategies of peripheral artery disease.

The global epidemiological transition of atherosclerotic vascular diseases is witnessing a rapid redistribution of its burden, shifting from high-income to low- and middle-income countries. With a wide clinical spectrum, spanning from intermittent claudication to more complex critical limb threatening ischemia, nonhealing ulcers, gangrene as well as acute limb ischemia, peripheral artery disease is often faced with the challenges of under-diagnosis and under-treatment despite its high prevalence. The management of peripheral arterial disease in patients with multiple comorbidities presents a formidable challenge and remains a pressing global health concern. In this review, we aim to provide an in-depth overview of the pathophysiology of peripheral artery disease and explore evidence-based management strategies encompassing pharmacological, lifestyle, interventional, and surgical approaches. By addressing these challenges, the review contributes to a better understanding of the evolving landscape of peripheral artery disease, offering insights into effective and holistic management strategies.

Left Ventricular Unloading With Impella Versus IABP in Patients With VA-ECMO: A Systematic Review and Meta-Analysis.

Venoarterial extracorporeal membrane oxygenation (VA-ECMO) use for circulatory support in cardiogenic shock results in increased left ventricular (LV) afterload. The use of concomitant Impella or intra-aortic balloon pump (IABP) have been proposed as adjunct devices for LV unloading. The authors sought to compare head-to-head efficacy and safety outcomes between the 2 LV unloading strategies. We conducted a search of Medline, EMBASE, and Cochrane databases to identify studies comparing the use of Impella to IABP in patients on VA-ECMO. The primary outcome of interest was in-hospital mortality. The secondary outcomes included transition to durable LV assist devices/cardiac transplantation, stroke, limb ischemia, need for continuous renal replacement therapy, major bleeding, and hemolysis. Pooled risk ratios (RRs) with 95% confidence interval and heterogeneity statistic I2 were calculated using a random-effects model. A total of 7 observational studies with 698 patients were included. Patients on VA-ECMO unloaded with Impella vs IABP had similar risk of short-term all-cause mortality, defined as either 30-day or in-hospital mortality- 60.8% vs 64.9% (RR 0.93 [0.71 to 1.21], I2 = 71%). No significant difference was observed in transition to durable LV assist devices/cardiac transplantation, continuous renal replacement therapy initiation, stroke, or limb ischemia between the 2 strategies. However, the use of VA-ECMO with Impella was associated with increased risk of major bleeding (57.2% vs 39.7%) (RR 1.66 [1.12 to 2.44], I2 = 82%) and hemolysis (31% vs 7%) (RR 4.61 [1.24 to 17.17], I2 = 66%) compared with VA-ECMO, along with IABP. In conclusion, in patients requiring VA-ECMO for circulatory support, the concomitant use of Impella or IABP had comparable short-term mortality. However, Impella use was associated with increased risk of major bleeding and hemolysis.

Experimental drugs for supraventricular tachycardia: an analysis of early phase clinical trials.

INTRODUCTION: Supraventricular tachycardias (SVT) are a diverse group of commonly encountered arrhythmias arising at or above the atrioventricular (AV) node. Conventional anti-arrhythmic medications are restricted by extensive side-effect profiles and limited efficacy. Catheter ablation has emerged as a first-line therapy for many arrhythmias but is not a suitable option for all patients. This has prompted the exploration of novel pharmacological approaches targeting specific molecular mechanisms of SVT. AREAS COVERED: This review article aims to summarize recent advancements in pharmacological therapeutics for SVT and their clinical implications. The understanding of molecular mechanisms underlying these arrhythmias, particularly atrial fibrillation, has opened up new possibilities for targeted interventions. Beyond the manipulation of ion channels and membrane potentials, pharmacotherapy now focuses on upstream targets such as inflammation, oxidative stress, and structural remodeling. This review strives to provide a comprehensive overview of recent advancements in pharmacological therapeutics directed at the management of SVT. We begin by providing a brief summary of the mechanisms and management of commonly encountered SVT before delving into individual agents, which in turn are stratified based on their molecular treatment targets. EXPERT OPINION: The evolving landscape of pharmacologic therapy offers hope for more personalized and tailored interventions in the management of SVT.

Direct Oral Anticoagulants: An Overview of Indications, Pharmacokinetics, Comorbidities, and Perioperative Management.

Direct oral anticoagulants (DOACs) have catalyzed a significant paradigm shift in the landscape of anticoagulant therapy, emerging as pivotal agents for the prevention of stroke in atrial fibrillation and venous thromboembolism. Although the absolute advantages of DOACs over vitamin K antagonists (VKAs) may appear modest, clinical guidelines advocate for their preference across various indications, attributing this endorsement to their ease of administration and heightened safety. DOACs find application in preventing and treating diverse cardiovascular conditions. With the progressive expansion of DOAC utility, clinicians encounter intricate decisions concerning the selection of appropriate agents, determination of optimal treatment duration, and utilization within specialized patient subgroups. Extensive evidence has substantiated the noninferiority or superiority of DOACs compared with VKAs in both prophylaxis and treatment of thromboembolic events. Notably, routine monitoring to evaluate treatment efficacy is not mandated for DOACs; however, they exhibit interactions with co-administered drugs and exert influence on functional coagulation assessments. This review aims to synthesize existing literature, encompassing the delineation of appropriate clinical indications, tailored employment in patients with specific concurrent conditions, needs in monitoring parameters, seamless transitions during shifts between anticoagulant regimens, and a glimpse into forthcoming perspectives in this evolving field.

Genetic and Molecular Mechanisms in Brugada Syndrome.

Brugada syndrome is a rare hereditary arrhythmia disorder characterized by a distinctive electrocardiogram pattern and an elevated risk of ventricular arrhythmias and sudden cardiac death in young adults. Despite recent advances, it remains a complex condition, encompassing mechanisms, genetics, diagnosis, arrhythmia risk stratification, and management. The underlying electrophysiological mechanism of Brugada syndrome requires further investigation, with current theories focusing on abnormalities in repolarization, depolarization, and current-load match. The genetic basis of the syndrome is strong, with mutations found in genes encoding subunits of cardiac sodium, potassium, and calcium channels, as well as genes involved in channel trafficking and regulation. While the initial discovery of mutations in the SCN5A gene provided valuable insights, Brugada syndrome is now recognized as a multifactorial disease influenced by several loci and environmental factors, challenging the traditional autosomal dominant inheritance model. This comprehensive review aims to provide a current understanding of Brugada syndrome, focusing on its pathophysiology, genetic mechanisms, and novel models of risk stratification. Advancements in these areas hold the potential to facilitate earlier diagnosis, improve risk assessments, and enable more targeted therapeutic interventions.

Drug Reaction With Eosinophilia and Systemic Symptoms-Associated Perimyocarditis After Initiation of Anti-tuberculosis Therapy: A Case Report.

A 34-year-old female who was recently placed on anti-tuberculosis medication with rifampin, isoniazid, pyrazinamide, and levofloxacin therapy for suspected tuberculosis reinfection presented with subjective fevers, rash, and generalized fatigue. Labs showed signs of end-organ damage with eosinophilia and leukocytosis. One day later, the patient became hypotensive with a worsening fever, and an electrocardiogram showed new diffuse ST segment elevations with an elevated troponin. An echocardiogram revealed a reduction in ejection fraction with diffuse hypokinesis, and cardiac magnetic resonance imaging (MRI) showed circumferential myocardial edema with subepicardial and pericardial inflammation. Prompt diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome using the European Registry of Severe Cutaneous Adverse Reaction (RegiSCAR) criteria and discontinuation of therapy was initiated. Due to the hemodynamic instability of the patient, the patient was started on systemic corticosteroids and cyclosporine, with the improvement of her symptoms and rash. A skin biopsy was performed, which revealed perivascular lymphocytic dermatitis, consistent with DRESS syndrome. As the patient's ejection fraction improved spontaneously with corticosteroids, the patient was discharged with oral corticosteroids, and a repeat echocardiogram showed full recovery of ejection fraction. Perimyocarditis is a rare complication of DRESS syndrome that is associated with degranulation and the release of cytotoxic agents into myocardial cells. Early discontinuation of offending agents and initiation of corticosteroids are essential to rapid recovery of ejection fraction and improved clinical outcomes. Multimodality imaging, including MRI, should be used to confirm perimyocardial involvement and guide the necessity for mechanical support or transplant. Further research should be on the mortality of DRESS syndrome with and without myocardial involvement, with an increased emphasis on cardiac evaluation in DRESS syndrome.

Postural Orthostatic Tachycardia Syndrome in COVID-19: A Contemporary Review of Mechanisms, Clinical Course and Management.

The long-term implications of COVID-19 have garnered increasing interest in recent months, with Long-COVID impacting over 65 million individuals worldwide. Postural orthostatic tachycardia syndrome (POTS) has emerged as an important component of the Long-COVID umbrella, estimated to affect between 2 and 14% of survivors. POTS remains very challenging to diagnose and manage - this review aims to provide a brief overview of POTS as a whole and goes on to summarize the available literature pertaining to POTS in the setting of COVID-19. We provide a review of available clinical reports, outline proposed pathophysiological mechanisms and end with a brief note on management considerations.

Prognostic significance of incorporating exercise tissue doppler mitral annular early diastolic velocity in exercise diastolic dysfunction assessment.

BACKGROUND: The existing algorithm for defining exercise-induced diastolic dysfunction incorporates resting e' velocity as a surrogate of myocardial relaxation. The additive prognostic value of incorporating post-exercise e' velocity in definition of exercise-induced diastolic dysfunction is poorly studied. AIM: To define the additive prognostic value of post-exercise e' septal velocity in the assessment of exercise-induced diastolic dysfunction compared to the traditional approach. METHODS: This retrospective study included 1409 patients undergoing exercise treadmill echocardiography with available full set of diastolic variables. Doppler measures of diastolic function included resting septal e' velocity, post-exercise septal e' velocity, post-exercise E/e' ratio, and post-exercise tricuspid regurgitant jet velocity. Approaches incorporating resting septal e' velocity and post-exercise septal e' velocity were compared in defining exercise-induced diastolic dysfunction, and for association with adverse cardiovascular outcomes. RESULTS: The mean age of study subjects was 56.3 ± 16.5 years and 791 (56%) patients were women. A total of 524 patients had disagreement between resting and post exercise septal e' velocities, and these values showed only weak agreement (kappa statistics: .28, P = .02). All categories of the traditional exercise-induced DD approach incorporating resting septal e' velocity witnessed reclassification when exercise septal e' velocity was used. When both approaches were compared, increased event rates were only evident when both approaches agreed on exercise-induced diastolic dysfunction (HR: 1.92, P < .001, 95% CI: 1.37-2.69). This association persisted after multivariable adjustment and propensity score matching for covariates. CONCLUSION: Incorporation of post-exercise e' velocity into the set of variables defining exercise-induced diastolic dysfunction can improve the prognostic utility of diastolic function assessment.

Early diagnostic markers in predicting the severity of dengue disease.

The aim of the present study was to determine whether the serum ferritin, the biomarker of an acute phase reactant and the gall bladder wall edema, an early indicator of capillary leakage can predict the severity of dengue fever. This study included 131 patients, who were between the age group of 18-80 years. The patients presented to our department with an acute illness, within the first four days of high temperature. The statistical analysis of this study was performed by using the Chi-square and independent Student's t tests. The diagnostic markers are considered statistically significant, if the serum ferritin level is higher than 500 ng/ml and the gall bladder wall thickness is more than 3 mm. The present study observed that, 39 patients (89%) who had severe dengue (n = 44) revealed a significant gall bladder wall thickening, and this correlation was significant statistically (p < 0.000). It was also observed that, the ferritin levels have a highly significant positive correlation with the severity of dengue. The severe dengue patients had a mean ferritin level of 9125.34 µg/l, whereas the non-severe group had 4271 µg/l. This comparison was also statistically significant, as the p value was 0.003. We report that the serum ferritin levels have a highly significant positive correlation with the severity of dengue. The gall bladder wall edema during the third and fourth day of the illness was also associated with severe dengue. However, diffuse gall bladder wall thickening and high serum ferritin levels are also reported in various other conditions and their exact cause have to be determined by the correlation of associated clinical findings and imaging features.