Common Cardiovascular Conditions Research Articles

Safety, tolerability, and basic pharmacokinetic parameters of AUX-001, a once-daily extended release nicorandil in healthy volunteers under fasting and fed conditions

Abstract Introduction Chronic-stable angina pectoris (CSAP) is one of the most common cardiovascular conditions in the developed world with a rising prevalence in both Europe and North America. Mounting evidence from chronic angina outcomes studies, including COURAGE, BARI, ORBITA and recently ISCHEMIA, has reemphasized optimized medical therapy (OMT) as first-line treatment for most chronic-stable angina pectoris (CSAP) patients over coronary revascularization. Yet, there has been a lack of development of new antianginal medications since 2006. To lessen polypharmacy and enable better long-term compliance in CSAP patients, AUX-001, a once-daily (QD), extended-release (ER) nicorandil is in clinical development for treating CSAP as an innovative, novel version of the immediate-release (IR) antianginal. Objective To test the safety, tolerability, and basic pharmacokinetic (PK) parameters of AUX-001 QD in fasting and fed conditions in healthy volunteers during this first-in-human phase 1a study. Methods 16 healthy adult volunteers were enrolled. Vital signs (HR, BP, respiratory rate) and any adverse events were collected during screening, pre-dose, 1, 2, 6, 12, 24-h, and 48-h post-dose and at end-of-study for the two respective periods (fasting and fed). Results Evaluable information was available on 16 patients for fasting and 15 for fed conditions with one patient excluded due to protocol violation. No patient discontinued due to safety or tolerability. No severe AEs were recorded. AEs observed during period 1 included headaches (n=12), asymptomatic hypotension (n=3), palpitation (n=1) and nasal congestion (n=1). In period 2, leading AEs were headaches (n=11), neck pain (n=1) and decreased hemoglobin (n=1). Most AEs were mild and transitory and did not trigger medical intervention or discontinuation. AUX-001 pharmacokinetics exhibited a reduced Cmax, a right-hand shift in Tmax, and an extension of T1/2 beyond 9 hours compared to the historical data of the commercially available IR nicorandil. AUX-001 had a small, temporary effect on heart rate and systolic and diastolic blood pressure but within the normal compensatory haemodynamic steady-state stability. The peak effect with the current AUX-001 prototype was at 6 hours, independent of the food effect. Conclusion AUX-001 was safe and well tolerated. Initial vasodilator-induced headaches were manageable by using simple OTC NSAIDs and led to no dropouts. No patients discontinued due to AEs or tolerability issues. There were no lasting significant haemodynamic effects of AUX-001 beyond 24hours. PK parameters of AUX-001 are characteristic of an ER formulation. Observed pharmacokinetics indicates that the achieved T1/2 is substantially longer than with IR nicorandil (~1hour vs >9h) and shows promise for a potential once daily treatment of exercise induced chronic angina.AUX-001 Study Data ESC Abstract 2024

Patient journey from the appearance of red flags to the diagnosis of transthyretin cardiac amyloidosis (ATTR-CM) in Japan: a nationwide retrospective study using a medical claims database

Abstract Introduction Transthyretin amyloid cardiomyopathy (ATTR-CM) is an under-recognized cause of common cardiovascular conditions in the elderly, with relatively high rates among patients diagnosed with heart failure (HF) with preserved ejection fraction. In addition to cardiac symptoms such as HF, extracardiac symptoms such as carpal tunnel syndrome (CTS) and lumbar spinal stenosis (LSS) are also red flags for ATTR-CM. Tafamidis is currently the only disease-modifying therapy approved for the treatment of patients with ATTR-CM and is likely to be more effective in the earlier stage. Patients with ATTR-CM often undergo a long and difficult diagnostic journey because of the nonspecificity of clinical manifestations, resulting in delays in establishing the correct diagnosis. Purpose To identify the timing of appearance of comorbidities in patients with ATTR-CM during diagnosis. Methods In this retrospective, non-interventional, observational study using a claims database (dataset period: April 1, 2014–August 31, 2021), adult patients with a diagnosis of ATTR-CM or prescription for tafamidis 80 mg were included. The index date was defined as the first date of recording ATTR-CM diagnosis or the prescription of tafamidis 80 mg, whichever was earlier. The baseline period was defined as the period between the index date and 6 months before the index date. The onset date was defined as the first date of recording diagnosis of the first red-flags that was suspicious for ATTR-CM. Results Of 11,101,578 patients in the database, 246 patients with ATTR-CM met the inclusion criteria. A total of 239 patients were included, of whom 139 had received tafamidis 80 mg. The median (range) age at the index date was 79.0 (46.0–95.0) years, and 79.9% (191/239) were male. The most frequently reported comorbidity defined as onset of ATTR-CM was conduction disorders (88.7%) followed by atrial fibrillation/atrial flutter (50.6%), hypertensive heart disease (19.7%), aortic stenosis (15.9%), and hypertrophic cardiomyopathy (11.7%), with the median (interquartile range [IQR]) time to the index date being 15.5 (5.0–24.5), 14.0 (5.0–22.0), 9.0 (2.0–18.0), 5.0 (2.0–16.0), and 12.0 (6.5–21.5) months, respectively (Fig. 1). LSS (23.9%), neuropathy (13.0%), and CTS (7.5%) were frequently observed as extracardiac symptoms at baseline, and the median (IQR) time from appearance to the index date was 19 (9.0–28.0), 5.0 (1.0–16.0), and 18.0 (14.0–25.0) months, respectively (Fig. 2). Conclusions This study elucidated the time lag between the appearance of cardiac and extracardiac complications of ATTR-CM and its diagnosis in real-world clinical settings. These novel findings highlight the potential for earlier detection of ATTR-CM.

Catheter Ablation of Atrial Fibrillation in Patients with Heart Failure: Focus on the Latest Clinical Evidence.

Atrial fibrillation and heart failure are two common cardiovascular conditions that frequently coexist, and it has been widely demonstrated that in patients with chronic heart failure, atrial fibrillation is associated with a significant increase in the risk of all-cause death and all-cause hospitalization. Nevertheless, there is no unanimous consensus in the literature on how to approach this category of patients and which therapeutic strategy (rhythm control or frequency control) is the most favorable in terms of prognosis; moreover, there is still a lack of data comparing the different ablative techniques of atrial fibrillation in terms of efficacy, and many of the current trials do not consider current ablative techniques such as high-power short-duration ablation index protocol for radiofrequency pulmonary vein isolation. Eventually, while several RCTs have widely proved that in patients with heart failure with reduced ejection fraction, ablation of atrial fibrillation is superior to medical therapy alone, there is no consensus regarding those with preserved ejection fraction. For these reasons, in this review, we aim to summarize the main updated evidence guiding clinical decision in this complex scenario, with a special focus on the most recent trials and the latest meta-analyses that examined the role of catheter ablation (CA) in rhythm control in patients with AF and HF.

Neighborhood Socioeconomic Disadvantage and 30-Day Outcomes for Common Cardiovascular Conditions.

Understanding the relationship between neighborhood environment and cardiovascular outcomes is important to achieve health equity and implement effective quality strategies. We conducted a population-based cohort study to determine the association of neighborhood socioeconomic deprivation and 30-day mortality and readmission rate for patients admitted with common cardiovascular conditions. We examined claims data from fee-for-service Medicare beneficiaries aged ≥65 years between 2017 and 2019 admitted for heart failure, valvular heart disease, ischemic heart disease, or cardiac arrhythmias. The primary exposure was the Area Deprivation Index; outcomes were 30-day all-cause death and unplanned readmission. More than 2 million admissions were included. After sequential adjustment for patient characteristics (demographics, dual eligibility, comorbidities), area health care resources (primary care clinicians, specialists, and hospital beds per capita), and admitting hospital characteristics (ownership, size, teaching status), there was a dose-dependent association between neighborhood socioeconomic deprivation and 30-day mortality rate for all conditions. In the fully adjusted model for death, estimated effect sizes of residence in the most disadvantaged versus least disadvantaged neighborhoods ranged from adjusted odds ratio 1.29 (95% CI, 1.22-1.36) for the heart failure group to adjusted odds ratio 1.63 (95% CI, 1.36-1.95) for the valvular heart disease group. Neighborhood deprivation was associated with increased adjusted 30-day readmission rates, with estimated effect sizes from adjusted odds ratio 1.09 (95% CI, 1.05-1.14) for heart failure to adjusted odds ratio 1.19 (95% CI, 1.13-1.26) for arrhythmia. Neighborhood socioeconomic disadvantage was associated with 30-day mortality rate and readmission for patients admitted with common cardiovascular conditions independent of individual demographics, socioeconomic status, medical risk, care access, or admitting hospital characteristics.

Cardiac physiology and pathophysiology in pregnancy.

Cardiovascular disease is the leading indirect cause of maternal morbidity and mortality, accounting for nearly one third of maternal deaths during pregnancy. The burden of cardiovascular disease in pregnancy is increasing, as are the incidence of maternal morbidity and mortality. Normal physiologic adaptations to pregnancy, including increased cardiac output and plasma volume, may unmask cardiac conditions, exacerbate previously existing conditions, or create de novo complications. It is important for care providers to understand the normal physiologic changes of pregnancy and how they may impact the care of patients with cardiovascular disease. This review outlines the physiologic adaptions during pregnancy and their pathologic implications for some of the more common cardiovascular conditions in pregnancy.

Identification of key genes and immune infiltration modulated in insomnia by integrated bioinformatics analysis and mendelian randomization study

Insomnia is a prevalent sleep disorder in modern times, often linked to various factors. Its occurrence, in turn, can lead to the development of several diseases, such as common cardiovascular conditions like coronary heart disease and hypertension. Moreover, insomnia can significantly impact the strength of the immune system. Traditional Chinese medicine (TCM) classifies sleep deprivation as a form of sleepiness, attributing prolonged sleepiness to Yin-Yang imbalance, resulting in Qi consumption and impairment of the five Zang-organs. Both Qi consumption and damage to the five Zang-organs mentioned in TCM research are correlated with the immune system in medical studies. Consequently, current research indicates that sleep deprivation escalates the risk of immune-related diseases. However, more research and analysis concerning immune infiltration related explicitly to insomnia are needed. Through gene differential analysis of sample files obtained from the Gene Expression Omnibus (GEO) dataset GSE208668 , we identified differentially expressed genes (DEGs) between the Insomnia and control groups. After screening these DEGs, we conducted GO and KEGG pathway analyses to identify insomnia-related gene pathways. Subsequently, I identified ten hub genes (IL2, CALML3, GATA3, EOMES, PTGS2, ESCO2, CXCL2, GPT, CRT, PRF1), and using a logistic regression model, I predicted insomnia based on the expression patterns of these ten genes. The analysis revealed that CALML3 and IL2, which showed the best performance in ROC curve analysis and had the highest degree, respectively, were selected for further investigation. Continuing the research, we further employed CIBERSORT to study immune infiltration in patients with insomnia, discovering an association between mast cells and insomnia partially correlated with the identified hub genes. In conclusion, these essential genes and immune infiltrations are relevant for treating and alleviating insomnia. Understanding these genes and immune cells could offer crucial insights for future therapeutic approaches to insomnia.

Hypertrophic cardiomyopathy and competitive sports: let 'em play?

Hypertrophic cardiomyopathy (HCM) is one of the most common cardiovascular genetic conditions. Although most patients with HCM typically do well clinically, there is a small but real incidence of sudden cardiac death. A diagnosis of HCM was previously a reason for complete exclusion in sports, particularly competitive sports.However, many of these recommendations are based on expert consensus, and much data has been published in the last decade furthering the scientific knowledge in this area, and allowing athletes who may have been previously excluded the potential to participate in strenuous activities and competitive sports. With recent publications on participation in sports with HCM, as well as an emphasis on shared decision-making, more athletes with HCM are participating in competitive sports, even at a professional level. Even contact sports in the presence of an implantable cardioverter-defibrillator are no longer mutually exclusive in the current era. Previous guidelines were likely overly restrictive for patients with HCM. Although there is a risk of sudden death that cannot be ignored, the potential for shared decision making as well as medical guidance are entering a new era in all aspects of medicine, particularly in sports participation.

RNA-binding proteins in cardiovascular biology and disease: the beat goes on.

Cardiac development and function are becoming increasingly well understood from different angles, including signalling, transcriptional and epigenetic mechanisms. By contrast, the importance of the post-transcriptional landscape of cardiac biology largely remains to be uncovered, building on the foundation of a few existing paradigms. The discovery during the past decade of hundreds of additional RNA-binding proteins in mammalian cells and organs, including the heart, is expected to accelerate progress and has raised intriguing possibilities for better understanding the intricacies of cardiac development, metabolism and adaptive alterations. In this Review, we discuss the progress and new concepts on RNA-binding proteins and RNA biology and appraise them in the context of common cardiovascular clinical conditions, from cell and organ-wide perspectives. We also discuss how a better understanding of cardiac RNA-binding proteins can fill crucial knowledge gaps in cardiology and might pave the way to developing better treatments to reduce cardiovascular morbidity and mortality.

Heart failure clinic: the role of nurses

Heart failure is one of the most common cardiovascular conditions with a steadily increasing incidence. Management of such patients only by general practitioners and cardiologists make it impossible to provide high-quality medical care. To ensure multidisciplinary monitoring of heart failure patients in many countries, including Russia, heart failure clinics are actively developing. Specially trained nursing staff play a particular role in the implementation of the clinics’ purposes. Working at Heart Failure Clinic requires advanced training, which in turn determines the priority for the development of new educational programs and expanding the competencies of nursing staff in our country. This article describes the foreign experience of nursing staff in outpatient monitoring of patients with heart failure.

Failure of Guidelines and Consensus Statements to Recommend Follow-up for Chronic Cardiovascular Conditions

BackgroundMany cardiac conditions require long-term clinical follow-up to monitor progression of disease and tolerance and adherence to therapies. Providers are often unsure as to the frequency of clinical follow-up and who should provide the follow-up. In the absence of formal guidance, patients may be seen more frequently than necessary — thereby limiting clinic space for other patients, or not frequently enough, potentially leading to undetected progression of disease. ObjectivesTo determine the extent to which guidelines (GL)/consensus statements (CS) provide guidance about appropriate follow-up for common cardiovascular conditions. MethodsWe identified 31 chronic cardiovascular disease conditions for which long-term (beyond 1 year) follow-up is indicated and used PubMed and professional society websites to identify all relevant GL/CS (n = 33) regarding these chronic cardiac conditions. ResultsOf the 31 cardiac conditions reviewed, GL/CS contained no recommendation or vague recommendation for long-term follow-up for 7 of the conditions. Of the 24 conditions with recommendations for follow-up, 3 had recommendations for imaging follow-up only without mention of clinical follow-up. Of the 33 GL/CS reviewed, 17 made any recommendations about long-term follow-up. When recommendations were made regarding follow-up, they were often vague, using terminology such as “as needed”. ConclusionsHalf of GL/CS fail to provide recommendations for clinical follow-up of common cardiovascular conditions. Writing groups for GL/CS should adopt a standard of routinely including recommendations for follow-up including specific advice about level of expertise needed (eg, primary care physician, cardiologist), need for imaging or testing, and frequency of follow-up.

Associations Between Extreme Temperatures and Cardiovascular Cause-Specific Mortality: Results From 27 Countries.

Cardiovascular disease is the leading cause of death worldwide. Existing studies on the association between temperatures and cardiovascular deaths have been limited in geographic zones and have generally considered associations with total cardiovascular deaths rather than cause-specific cardiovascular deaths. We used unified data collection protocols within the Multi-Country Multi-City Collaborative Network to assemble a database of daily counts of specific cardiovascular causes of death from 567 cities in 27 countries across 5 continents in overlapping periods ranging from 1979 to 2019. City-specific daily ambient temperatures were obtained from weather stations and climate reanalysis models. To investigate cardiovascular mortality associations with extreme hot and cold temperatures, we fit case-crossover models in each city and then used a mixed-effects meta-analytic framework to pool individual city estimates. Extreme temperature percentiles were compared with the minimum mortality temperature in each location. Excess deaths were calculated for a range of extreme temperature days. The analyses included deaths from any cardiovascular cause (32 154 935), ischemic heart disease (11 745 880), stroke (9 351 312), heart failure (3 673 723), and arrhythmia (670 859). At extreme temperature percentiles, heat (99th percentile) and cold (1st percentile) were associated with higher risk of dying from any cardiovascular cause, ischemic heart disease, stroke, and heart failure as compared to the minimum mortality temperature, which is the temperature associated with least mortality. Across a range of extreme temperatures, hot days (above 97.5th percentile) and cold days (below 2.5th percentile) accounted for 2.2 (95% empirical CI [eCI], 2.1-2.3) and 9.1 (95% eCI, 8.9-9.2) excess deaths for every 1000 cardiovascular deaths, respectively. Heart failure was associated with the highest excess deaths proportion from extreme hot and cold days with 2.6 (95% eCI, 2.4-2.8) and 12.8 (95% eCI, 12.2-13.1) for every 1000 heart failure deaths, respectively. Across a large, multinational sample, exposure to extreme hot and cold temperatures was associated with a greater risk of mortality from multiple common cardiovascular conditions. The intersections between extreme temperatures and cardiovascular health need to be thoroughly characterized in the present day-and especially under a changing climate.

Breaking the Cycle of Heart Failure With Preserved Ejection Fraction and Atrial Fibrillation.

Heart failure with preserved ejection fraction (HFpEF) and AF are two common cardiovascular conditions that are inextricably linked to each other's development and progression, often in multimorbid patients. Current management is often directed to specific components of each disease without considering their joint impact on diagnosis, treatment and prognosis. The result for patients is suboptimal on all three levels, restricting clinicians from preventing major adverse events, including death, which occurs in 20% of patients at 2 years and in 45% at 4 years. New trial evidence and reanalysis of prior trials are providing a glimmer of hope that adverse outcomes can be reduced in those with concurrent HFpEF and AF. This will require a restructuring of care to integrate heart failure and AF teams, alongside those that manage comorbidities. Parallel commencement and non-sequential uptitration of therapeutics across different domains will be vital to ensure that all patients benefit at a personal level, based on their own needs and priorities.

Abstract 12277: Impact of Telemedicine New Patient Visits on Total Visit Utilization at an Academic Cardiovascular Center: An Instrumental Variable Analysis

Introduction: Telemedicine use has increased, but little is known about the impact of telemedicine on downstream healthcare utilization. We sought to determine the effect of conducting new patient visits (NPVs) through telemedicine on the number of follow-up visits for common cardiovascular conditions. Methods: We extracted data for all visits at an academic cardiovascular center from Jan 2019 to Feb 2022. We evaluated the effect of telemedicine vs in-person NPVs on total follow-up visits within 6 months for patients seen for 8 common primary diagnoses between Jun 2020 and Aug 2021. We utilized variation in the rate of telemedicine use among clinicians as an instrumental variable, adjusting for patient characteristics, diagnosis, subspecialty, and site. We used two-stage least squares (2SLS) and instrumental causal forest (ICF) models. Results: There were 4,856 NPVs and 3,594 follow-up visits. NPVs were delivered by 120 clinicians with 58.8% provided by telemedicine (range 0-100% across clinicians). There was no association between the average number of follow-up visits before Mar 2020 and subsequent clinician telemedicine adoption. In 2SLS analysis, there was no significant overall effect of delivering NPVs through telemedicine on the number of follow-up visits within 6 months (-0.029 visits per patient, 95% CI -0.15, 0.089). The ICF analysis similarly showed no significant overall effect of telemedicine NPVs on the number of follow-up visits. In 2SLS subgroup analyses, the effect of telemedicine NPVs differed across diagnoses (Figure). Conclusions: At an academic cardiovascular center, use of telemedicine NPVs for several common diagnoses did not affect the total number of follow-up visits within 6 months. Telemedicine NPVs can successfully replace in-person visits though their impact on total visits may differ across cardiovascular conditions. Future research should evaluate the effect of visit modality on other domains of care utilization and outcomes.

Associations between pregnancy complications and incident cardiovascular disease: a nationwide data linkage study in Wales

Abstract Background Previous studies have associated pregnancy complications with a higher risk of cardiovascular disease. However, previous studies have not sufficiently evaluated the impact of broad range of pregnancy complications or common cardiovascular conditions individually. Furthermore, most previous studies have relied on data from hospital admission records only, which may not have adequately accounted for conditions that may not result in an inpatient hospital admission, such as atrial fibrillation. Purpose To examine the risk of ischemic heart disease (IHD), stroke, atrial fibrillation or heart failure among women after their first pregnancy with a history of pregnancy complications compared to women without pregnancy complications in a large nationwide study using linked routinely collected data. Methods A retrospective cohort study was conducted using the Secure Anonymised Information Linkage (SAIL) Databank and included women aged 16–45 years who had their first pregnancy between 2000 and 2018 in Wales. Data were extracted from various sources such as Office for National Statistics (ONS) birth and death extracts, hospital admission, outpatient, emergency department and General Practice data sources, and pregnancy related data such as maternal indicators and national community child health. Survival analyses were conducted using Cox proportional hazard regression models adjusted for hypertension, diabetes, hyperlipidaemia, congenital and valvular heart diseases, multifetal pregnancy ethnicity, maternal age, calendar year of first birth and index of multiple deprivation. Results A total of 298,515 women were included in the study, of which 74,832 (25.1%) had a history of any pregnancy complication during their first pregnancy. During a median of 9.7 years follow-up time, 2,484 women developed at least one cardiovascular condition. Among women with a history of pregnancy complication in their first pregnancy, IHD had the highest incidence rate at 4.94 (95% confidence interval (CI) 4.44–5.49) per 10,000 person-years, and atrial fibrillation was the lowest at 1.92 (95% CI 1.62–2.28). The history of any pregnancy complication during the first pregnancy was associated with a higher risk of all cardiovascular conditions examined, including heart failure [hazard ratio (HR) 1.93 95% CI 1.61–2.31)], IHD [HR 1.82 (95% CI 1.58–2.10)], stroke [HR 1.39 (95% CI 1.20–1.61)] and atrial fibrillation [HR 1.33 (95% CI 1.08–1.65) (Figure 1). Conclusion This population-scale study used anonymised individual-level linked data from multiple routinely collected data sources. A history of pregnancy complications during first pregnancy was associated with a higher risk of incident cardiovascular conditions, including heart failure, ischaemic heart disease, stroke and atrial fibrillation. Applying primary preventive measures and risk assessments for cardiovascular disease after the first pregnancy may mitigate the higher risk among these women. Funding Acknowledgement Type of funding sources: Other.

Cardiovascular Factors Associated with COVID-19 from an International Registry of Primarily Japanese Patients.

Aims: We developed an international registry to examine cardiovascular complications of COVID-19. Methods: A REDCap form was created in March 2020 at Mayo Clinic in collaboration with the International Society of Cardiomyopathy, Myocarditis and Heart Failure (ISCMF) and data were entered from April 2020 through April 2021. Results: Of the 696 patients in the COVID-19 Registry, 411 (59.2%) were male and 283 (40.8%) were female, with a sex ratio of 1.5:1 male to female. In total, 95.5% of the patients were from Japan. The average age was 52 years with 31.5% being >65 years of age. COVID-19 patients with a history of cardiovascular disease (CVD) had more pre-existing conditions including type II diabetes (p < 0.0001), cancer (p = 0.0003), obesity (p = 0.001), and kidney disease (p = 0.001). They also had a greater mortality of 10.1% compared to 1.7% in those without a history of CVD (p < 0.0001). The most common cardiovascular conditions in patients with a history of CVD were hypertension (33.7%), stroke (5.7%) and arrhythmias (5.1%). We found that troponin T, troponin I, brain natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), C-reactive protein (CRP), IL-6 and lambda immunoglobulin free light chains (Ig FLC) were elevated above reference levels in patients with COVID-19. Myocarditis is known to occur mainly in adults under the age of 50, and when we examined biomarkers in patients that were ≤50 years of age and had no history of CVD we found that a majority of patients had elevated levels of troponin T (71.4%), IL-6 (59.5%), creatine kinase/CK-MB (57.1%), D-dimer (57.8%), kappa Ig FLC (75.0%), and lambda Ig FLC (71.4%) suggesting myocardial injury and possible myocarditis. Conclusions: We report the first findings to our knowledge of cardiovascular complications from COVID-19 in the first year of the pandemic in a predominantly Japanese population. Mortality was increased by a history of CVD and pre-existing conditions including type II diabetes, cancer, obesity, and kidney disease. Our findings indicate that even in cases where no abnormalities are found in ECG or ultrasound cardiography that myocardial damage may occur, and cardiovascular and inflammatory biomarkers may be useful for the diagnosis.

Carvedilol- loaded Transdermal Ethosomal gel: Characterization, ex vivo/in vivo Evaluation

Carvedilol (CAR) is a cardiovascular drug commonly used for the management of hypertension, heart failure and angina pectoris. However, it has low oral bioavailability due to pre-systematic breakdown by liver enzymes which necessitates multiple doses per day. The present study investigates the development of sustained release transdermal carvedilol-loaded ethosomal formulation. CAR- ethosomal formulation was prepared by cold method with1% lipid, 50mg Carvedilol, 30% ethanol (v/v) and sonication time 3 min. The prepared formulation was characterized for vesicle size, polydispersity index (PDI) and entrapment efficiency (EE%). The formula showed small vesicle size (46.75±9.41nm) and high EE% (97%). Accordingly, it was subjected to stability study, TEM and zeta potential analysis. The formula showed good physical stability at refrigeration temperature after 90 days storage period as well as good zeta potential of +38.75mV. Our formula exhibited spherical unilamellar structure under TEM. Consequently, our formula was made as gel using HPMC polymer and was tested for pH, spreadability, drug content, skin permeation and pharmacokinetic study by HPLC-MS technique. Plasma drug levels were measured for rats after administration of both ethosomal gel and oral carvedilol tablet. The pharmacokinetic parameters were calculated and compared between the transdermal and oral dosage forms. Our formula showed lower t max and higher AUC0-24 than oral carvedilol tablet. Our findings affirm the potential of ethosomes as new vesicular carriers in sustained transdermal management of common cardiovascular conditions.

Convolutional Neural Network for Improvement of Heart Valve Disease Detection

Valvular heart disease (VHD) encompasses a number of common cardiovascular conditions that account for a significant percentage of heart diseases. At present, the acoustic phenomena generated by the abnormal functioning of the heart valves can be recorded and digitized using electronic stethoscopes known as phonocardiographs. The analysis of the phonocardiographic signals has made it possible to indicate that the normal and pathological records differ from each other in terms of both temporal and spectral characteristics. The present work describes the construction and implementation of a Deep Learning (DL) algorithm for the binary classification of normal and abnormal heart sounds. The performance of this approach reached an accuracy higher than 98 % and specificities in the ”Normal” class of up to 99 %.

Interventional Cardiac Procedures and Pregnancy.

As the average maternal age advances with increasing concurrent cardiovascular disease risk factors, more women are entering pregnancy with or at risk for various cardiovascular conditions. Although rare, pregnant patients may require various cardiac interventions in the catheterization laboratory. An understanding of indications for intervention in pregnant patients with conditions such as myocardial infarction, severe valvular disease, and cardiogenic shock is critical to optimizing both fetal and maternal outcomes. This document highlights the most common cardiovascular conditions that may be encountered during pregnancy that may require intervention and highlights indications for intervention and periprocedural considerations to facilitate favorable maternal and fetal outcomes.

The case of diabetes mellitus and atrial fibrillation: Underlining the importance of non-cardiovascular comorbidities

In the currently changing scenario, in which our patients are progressively older and more likely burdened by concomitant chronic long-term conditions [1], diabetes mellitus (DM) play a prominent role in determining the health state of patients worldwide [2]. In particular a strict relationship exists between DM and atrial fibrillation (AF), which is one of the most common cardiovascular conditions [3]. Indeed, DM is now recognized as one of the most important risk factors leading to the development of AF, with a number of mechanisms involved in determining this relationship [4,5].

Arrhythmias and Heart Failure in Pregnancy: A Dialogue on Multidisciplinary Collaboration.

The prevalence of CVD in pregnant people is estimated to be around 1 to 4%, and it is imperative that clinicians that care for obstetric patients can promptly and accurately diagnose and manage common cardiovascular conditions as well as understand when to promptly refer to a high-risk obstetrics team for a multidisciplinary approach for managing more complex patients. In pregnant patients with CVD, arrhythmias and heart failure (HF) are the most common complications that arise. The difficulty in the management of these patients arises from variable degrees of severity of both arrhythmia and heart failure presentation. For example, arrhythmia-based complications in pregnancy can range from isolated premature ventricular contractions to life-threatening arrhythmias such as sustained ventricular tachycardia. HF also has variable manifestations in pregnant patients ranging from mild left ventricular impairment to patients with advanced heart failure with acute decompensated HF. In high-risk patients, a collaboration between the general obstetrics, maternal-fetal medicine, and cardiovascular teams (which may include cardio-obstetrics, electrophysiology, adult congenital, or advanced HF)—physicians, nurses and allied professionals—can provide the multidisciplinary approach necessary to properly risk-stratify these women and provide appropriate management to improve outcomes.