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Background: Paroxysmal atrial fibrillation (PAF) significantly impacts patients' lives, contributing to morbidity, reduced quality of life (QoL), and psychological distress. Conventional treatment approaches primarily focus on rhythm control through pharmacologic therapy, often overlooking the patient's holistic well-being., Hypothesis: Cognitive behavioral therapy (CBT), a well-established intervention for modifying dysfunctional thoughts and behaviors, may provide a beneficial nonpharmacological approach to improving QoL in symptomatic PAF patients., Methods: A systematic review was conducted in accordance with Cochrane methodology and PRISMA guidelines. A comprehensive search was performed using PubMed, Scopus, and Google Scholar to identify relevant studies on the effects of CBT on QoL in PAF patients. Various CBT interventions, including exposure-based, internet-delivered, and mindfulness-based approaches, were analyzed. Study quality was assessed using JBI and Cochrane tools to evaluate the risk of bias., Results: The review found that CBT interventions led to statistically significant improvements in several QoL domains, including physical and emotional well-being. Psychological well-being and self-management skills were notably enhanced, as CBT helped address maladaptive cognitive patterns and improved coping strategies. The studies reviewed consistently demonstrated a low risk of bias, indicating reliability in the findings., Conclusions: CBT shows promise as a holistic, nonpharmacological intervention for managing PAF, improving both psychological and physical QoL. However, future research is needed to establish standardized protocols, increase sample sizes, and conduct long-term follow-ups to further validate its effectiveness in this population. Incorporating CBT into PAF management could substantially enhance patient outcomes and well-being., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals, LLC.)

As the incidence of cardiovascular diseases (CVDs) continues to rise among women of childbearing age, the pregnant population with pre-existing heart conditions presents a complex and heterogeneous profile. These women face varying degrees of risk concerning maternal cardiovascular, obstetric, and fetal complications. Effectively managing adverse cardiovascular events during pregnancy presents substantial clinical challenges. The uncertainties surrounding diagnostic and therapeutic approaches create a dynamic landscape with potential implications for maternal and fetal health. Cardio-obstetrics has become increasingly recognized as a vital multidisciplinary field necessitating a collaborative approach to managing cardiovascular conditions during pregnancy. In this review, we aim to provide a thorough and up-to-date examination of the existing evidence, offering a comprehensive overview of strategies and considerations in the management of cardiovascular complications during pregnancy. Special emphasis is placed on the safety assessment of diagnostic procedures and the exploration of treatment options designed to prioritize the well-being of the mother and fetus. We also explore the significance of a multidisciplinary cardio-obstetrics team in providing comprehensive care for women of childbearing age with or at risk for CVD., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Sensory processing disruptions are a core symptom of autism spectrum disorder (ASD) and other neurological disorders. The acoustic startle response and prepulse inhibition (PPI) are common metrics used to assess disruptions in sensory processing and sensorimotor gating in clinical studies and animal models. However, often there are inconsistent findings on ASD-related PPI deficits across different studies. Here, we used a novel method for assessing changes in startle and PPI in rodents, using the Cntnap2 knock-out (KO) rat model for neurodevelopmental disorder/ASD that has consistently shown PPI disruptions in past studies. We discovered that not only sex and prepulse intensity but also the intensity of the startle stimulus profoundly impacts whether PPI deficits are evident in the Cntnap2 KO rat or not. We show that rats do not universally exhibit a PPI deficit; instead, impaired PPI is contingent on specific testing conditions. Notably, at lower startle stimulus intensities, Cntnap2 KO rats not only demonstrated intact PPI but also exhibited evidence of enhanced PPI compared with their wild-type counterparts. This finding emphasizes the importance of considering specific testing conditions when evaluating startle and PPI in the context of ASD and other neuropsychiatric conditions and might explain some of the inconsistencies between different studies., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Doornaert et al.)

Purpose: Heme oxygenase-1 (HO-1) is a crucial enzyme in heme metabolism, facilitating the breakdown of heme into biliverdin, carbon monoxide, and free iron. Renowned for its potent cytoprotective properties, HO-1 showcases notable antioxidant, anti-inflammatory, and anti-apoptotic effects. In this review, the authors aim to explore the profound impact of HO-1 on cardiac senescence and its potential implications in myocardial infarction (MI)., Results: Recent research has unveiled the intricate role of HO-1 in cellular senescence, characterized by irreversible growth arrest and functional decline. Notably, cardiac senescence has emerged as a pivotal factor in the development of various cardiovascular conditions, including MI. Notably, cardiac senescence has emerged as an important factor in the development of various cardiovascular conditions, including myocardial infarction (MI). The accumulation of senescent cells, spanning vascular endothelial cells, vascular smooth muscle cells, cardiomyocytes, and progenitor cells, poses a significant risk for cardiovascular diseases such as vascular aging, atherosclerosis, myocardial infarction, and ventricular remodeling. Inhibition of cardiomyocyte senescence not only reduces senescence-associated inflammation but also impacts other myocardial lineages, hinting at a broader mechanism of propagation in pathological remodeling. HO-1 has been shown to improve heart function and mitigate cardiomyocyte senescence induced by ischemic injury and aging. Furthermore, HO-1 induction has been found to alleviate H 2 O 2 -induced cardiomyocyte senescence. As we grow in our understanding of antiproliferative, antiangiogenic, anti-aging, and vascular effects of HO-1, we see the potential to exploit potential links between individual susceptibility to cardiac senescence and myocardial infarction., Conclusions: This review investigates strategies for upregulating HO-1, including gene targeting and pharmacological agents, as potential therapeutic approaches. By synthesizing compelling evidence from diverse experimental models and clinical investigations, this study elucidates the therapeutic potential of targeting HO-1 as an innovative strategy to mitigate cardiac senescence and improve outcomes in myocardial infarction, emphasizing the need for further research in this field., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Psychological autopsies refer to retrospective interviews between researchers and informants who were close to a person who died by suicide, to explore and better understand the circumstances and contributing factors to that suicide. However, several issues persist with psychological autopsy as a methodology. We assessed the academic literature regarding psychological autopsies and extracted key themes about methodological limitations and weaknesses. The aim was to formulate recommendations and present suggestions for future methodology that would protect the benefits of psychological autopsy, particularly the personal narratives, while addressing methodological limitations. A literature review of nine relevant healthcare research databases yielded twenty-two relevant papers. Each of these publications were reviewed and themes regarding methodological limitations of psychological autopsies were identified and collated. Limitations identified from the review included issues of validity and reliability, lack of standardisation, biases, control variables, cultural considerations, ethics, and data handling. New limitations regarding cultural nuance, modern communication channels, and 'invisible informants' were identified. Recommendations for the future development of the psychological autopsy method include embracing modern communication methods and 'invisible informants', cultural intersections, safeguarding of reliability and validity, and the use of feasibility trials. The emphasis remains upon collating the raw narratives at the core of these interviews which make the psychological autopsy such a unique and insightful tool.

Background: Dietary modification plays a pivotal role in the prevention of cardiovascular disease (CVD), with particular emphasis on the potential benefits associated with adopting a Mediterranean diet (MedDiet). Numerous observational studies have explored the impact of the MedDiet on CVD prevention, addressing both primary and secondary prevention. However, a substantial portion of the primary evidence comes from specific Randomized Controlled Trials (RCTs), such as the Lyon Diet Heart Study, the Indo-Mediterranean Diet Heart Study, the PREDIMED Study, and the recent CORDIOPREV Study. To provide a comprehensive assessment of the long-term clinical effects, we conducted a meta-analysis, systematically synthesizing findings from RCTs to better understand the preventive impact of MedDiet on cardiovascular health., Methods: We searched for RCTs exploring the efficacy of MedDiet on CVD prevention from inception until January 2024, utilizing databases such as MEDLINE (via PubMed), Google Scholar, the Cochrane Library, ClinicalTrials.gov, and the ScienceDirect portal. Statistical analysis used RevMan 5.4 with a random-effects model, presenting dichotomous outcomes as odds ratios (OR) with a 95 % confidence interval (CI) and assessing heterogeneity using the I 2 test., Results: Our analysis incorporated four RCTs involving a total of 10,054 participants, with an average age of 57 years and a mean follow-up duration ranging from 2 to 7 years. In our pooled analysis, the composite endpoint of major adverse cardiovascular events (MACE) demonstrated a statistically significant reduction in incidence in participants on MedDiet versus control diet with an OR of 0.52 (95 % CI: 0.32 to 0.84, p = 0.008; I 2 = 87 %). Additionally, our study revealed a notable decrease in the incidence of cardiovascular events, both myocardial infarction (MI) and stroke in the the MedDiet group, with an OR of 0.62 (95 % CI: 0.41 to 0.92, p = 0.02; I 2 = 56 %) and 0.63 (95 % CI: 0.48 to 0.87, p = 0.002; I 2 = 0 %), respectively. However, no statistically significant change in the rate of revascularization was observed, with an OR of 0.74 (95 % CI: 0.30 to 1.27, p = 0.06; I 2 = 16 %). Concerning mortality rates, MedDiet significantly reduced the risk of cardiovascular death with an OR of 0.54 (95 % CI: 0.31 to 0.94, p = 0.03; I 2 = 55 %), while no significant change was noted in all-cause mortality, with an OR of 0.77 (95 % CI: 0.51 to 1.15, p = 0.20; I 2 = 58 %)., Conclusion: MedDiet serves as an effective intervention for both primary and secondary prevention of CVD, demonstrating a substantial and long-term impact in reducing the incidence of MACE, MI, stroke, and cardiovascular-related mortality while showing no observed effect on all-cause mortality. Nevertheless, it is essential to acknowledge the current limitations in available clinical trial evidence, emphasizing the need for additional trials to substantiate and strengthen these findings., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Heart failure with preserved ejection fraction (HFpEF) represents a prevalent and increasingly common condition. Recognized for its high incidence, there is a growing interest in exploring effective interventions, with exercise emerging as a critical component in the rehabilitation of HFpEF patients. We aim to update evidence on the impact of supervised exercise training on exercise capacity, diastolic function, arterial stiffness, and health-related quality of life (QoL) of individuals diagnosed with HFpEF., Methods: We systematically reviewed the literature, searching from inception to December 2023, utilizing databases such as MEDLINE (via PubMed), Google Scholar, the Cochrane Library, ClinicalTrials.gov, and the ScienceDirect portal. Statistical analyses utilized RevMan 5.4 with a random-effects model. Outcomes were presented as the weighted mean difference (WMD) alongside corresponding 95 % confidence intervals (CI), and heterogeneity was assessed using the I 2 test., Results: Our final analysis included 7 randomized controlled trials (RCTs) of 346 participants, with an exercise follow-up duration of 12 to 48 weeks. In our pooled analysis, diastolic function, measured by E/A (WMD 0.01, 95 % CI: -0.04 to 0.05, p = 0.79; I 2 = 0 %) and E/e' (WMD 0.87, 95 % CI: -11.09 to 12.83, p = 0.89; I 2 = 69 %), showed no significant change post-exercise training. However, exercise capacity, measured by peak V̇o2 significantly improved (WMD 2.57, 95 % CI: 1.38 to 3.75, p < 0.0001; I 2 = 14 %). The QoL assessed by the Minnesota Living with Heart Failure (MLWHF) score remained unchanged (WMD -3.12, 95 % CI: -8.73 to 2.50, p = 0.28; I 2 = 0 %), but the SF-36 physical functioning scale indicated significant improvement (WMD 9.84, 95 % CI: 2.94 to 16.73, p < 0.005; I 2 = 0 %). Arterial stiffness and vascular function remained unaffected, as evidenced by arterial elastance (WMD -0.13, 95 % CI: -0.36 to 0.10, p = 0.26; I 2 = 0 %) and total arterial compliance (WMD 0.12, 95 % CI: -0.26 to 0.49, p = 0.54; I 2 = 0 %)., Conclusion: Exercise training is safe and significantly enhances exercise capacity and QoL in HFpEF, with no significant impact on diastolic function, arterial stiffness, or vascular function., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: Arterial stiffness has gained recognition as a stand-alone risk factor for cardiovascular disease (CVD). Obesity is intricately linked to elevated arterial stiffness, the development of left ventricular (LV) hypertrophy, and the emergence of diastolic dysfunction, all of which collectively contribute substantially to an unfavorable prognosis. Weight loss has become a standard recommendation for all patients with CVD concurrent with morbid obesity; however, randomized evidence to support this recommendation was limited earlier. The latest scientific studies revealed dynamic changes in aortic stiffness after substantial weight loss by bariatric surgery, also known as metabolic surgery, in patients with obesity. There is also a favorable evolution in LV hypertrophy and a significant impact on arterial hypertension and other promising cardiovascular outcomes in obese people after bariatric surgery., Methods/results: We aimed to examine the cardiovascular effects of various metabolic surgeries in morbidly obese individuals, especially their role in improving arterial health, the potential impact on surrogate markers of atherosclerotic vascular disease, and consequently reducing the likelihood of cardiovascular events., Conclusion: In conclusion, metabolic surgery is associated with a significant decrease in the occurrence of major adverse cardiovascular events (MACE) and all-cause mortality among obese individuals, alongside remarkable enhancement of arterial health. These findings underscore the critical importance of implementing strategies to combat obesity and reduce adiposity within the general population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

In the United States, a patient succumbs to cardiovascular disease (CVD) every 33 seconds and costs the healthcare system close to $240 billion dollars annually. Social determinants of health (SDOH) are key factors responsible in structuring the well-being of individuals and communities. It significantly influences health outcomes and is reliant on several factors such as economic stability, education, healthcare access, community composition, and governmental policies. This review explores the impact of SDOH on the escalating global burden of CVD and identifies potential modifiable risk factors that contribute to acute coronary syndrome (ACS) among underserved communities. In addition, it also addresses the necessity for interventions to narrow healthcare related disparities ensuring improvement in CVD outcomes in this subgroup of population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The correlation between obesity, type 2 diabetes mellitus (DM), cardiovascular disease (CVD), and chronic kidney disease (CKD) is an escalating and widely acknowledged epidemic in industrialized nations. Recently, this complex web of interrelated health conditions has been collectively defined as the Cardiovascular-Kidney-Metabolic (CKM) syndrome by the American Heart Association (AHA). The molecular mechanisms underlying CKM disease contain a spectrum of interconnected factors, including hyperglycemia, insulin resistance, heightened activity of the renin-angiotensin-aldosterone system (RAAS), the generation of advanced glycation end-products, oxidative stress, lipotoxicity, endoplasmic reticulum stress, abnormalities in calcium handling, malfunctioning of mitochondria and impaired energy production, as well as persistent chronic inflammation. Addressing their prevention, management, and treatment is of paramount importance to promote better patient health outcomes. The objective of this review is to provide a comprehensive and critical examination of the current state-of-the-art regarding the recently defined CKM syndrome. This includes an exploration of epidemiological evidence establishing connections between cardio-renal-metabolic diseases, an examination of the underlying pathophysiological mechanisms, and a comprehensive overview of existing treatment modalities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Heart failure (HF) is a common clinical condition encountered in various healthcare settings with a vast socioeconomic impact. Recent advancements in pharmacotherapy have led to the evolution of novel therapeutic agents with a decrease in hospitalization and mortality rates in HF with reduced left ventricular ejection fraction (HFrEF). Lately, the introduction of artificial intelligence (AI) to construct decision-making models for the early detection of HF has played a vital role in optimizing cardiovascular disease outcomes. In this review, we examine the newer therapies and evidence behind goal-directed medical therapy (GDMT) for managing HF. We also explore the application of AI and machine learning (ML) in HF, including early diagnosis and risk stratification for HFrEF., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Sudden alterations in the heart rate may be associated with diverse symptoms. Sinus node dysfunction (SND), also known as sick sinus syndrome, is a sinoatrial (SA) node disorder. SND is primarily caused by the dysfunction of the pacemaker, as well as impaired impulse transmission resulting in a multitude of abnormalities in the heart rhythms, such as bradycardia-tachycardia, atrial bradyarrhythmias, and atrial tachyarrhythmias. The transition from bradycardia to tachycardia is generally referred to as "tachy-brady syndrome" (TBS). Although TBS is etiologically variable, the manifestations remain consistent throughout. Abnormal heart rhythms have the propensity to limit tissue perfusion resulting in palpitations, fatigue, lightheadedness, presyncope, and syncope. In this review, we examine the physiology of tachy-brady syndrome, the practical approach to its diagnosis and management, and the role of adenosine in treating SND., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare that are relevant to the content of this article., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Canada has the highest level of immigration, with one in four Canadians being immigrants. And little is known about the ethnic differences and cardiovascular disease (CVD) risk in the Canadian immigrant population. The high level of immigration has resulted in significant ethnic diversity in Canada, with each presenting a CVD risk profile unique to their ethnicity and country of birth. A better understanding of the ethnic differences in the risk of CVD could help navigate effective health promotion and targeted interventions, which can mitigate the burden of morbidity and mortality associated with the disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide, and its prevention is more cost-effective than the treatment of its complications. Although cardiovascular (CV) risk assessment based on conventional risk factors is the general recommendation, a significant percentage of the population, irrespective of these risk factors, present with subclinical atherosclerosis during carotid Doppler ultrasound (US) imaging. Subclinical atherosclerotic lesions at the carotid bifurcations may be related to the incidence of future CV events and occult atherosclerotic coronary disease. Such patients might benefit from preventive measures if the carotid Doppler US is allowed as a screening tool to detect the extent of carotid stenosis. We aimed to conduct a comprehensive and systematic evaluation of the impact of carotid US screening on CV risk stratification., Methods: We searched PubMed, Scopus, and ScienceDirect from inception until July 2023. We included literature that examined the impact of carotid US screening on cardiovascular risk factor (CVRF) prevention, CV events, and mortality in adults of all age groups free of symptomatic carotid artery disease., Results: We identified 2 randomized controlled trials (RCTs) and 9 observational studies, including 21,046 participants. The mean age of the participants was 49, and 53% were female. Two RCTs, with 7,064 participants, examined the impact of pictorial knowledge about subclinical carotid atherosclerosis using carotid US versus traditional CVD risk evaluation without any US evidence in primary cardiovascular prevention. Both studies reported remarkable improvement in medication adherence at 1 to 3-year follow-up after carotid US screening with a decrease in Framingham risk score (FRS). Nine observational studies with 13, 982 participants analyzed the evidence of atherosclerosis on carotid US screening and demonstrated that it is a beneficial tool in the early identification of subclinical atherosclerosis and effective therapeutic intervention., Conclusion: This systematic review found that pictorial presentation of silent atherosclerosis using carotid US screening has a contributory role in CV risk stratification and prevention of CVD., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Sudden cardiac death (SCD) is one of the leading causes of death worldwide, usually involving young people. SCD remains a critical public health problem accounting for 185,000-450,000 deaths annually, representing around 7%-18% of all deaths globally. As per evidence, ∼2%-54% of sudden unexpected deaths in people under the age of 35 years fail to show evidence of structural cardiac abnormalities at autopsy, making ion channelopathies the probable causes in such cases. The most generally recognized cardiac ion channelopathies with genetic testing are long QT syndrome (LQTS), Brugada syndrome (BrS), short QT syndrome (SQTS), and catecholaminergic polymorphic ventricular tachycardia (CPVT). The substantial progress in understanding the genetics of ion channelopathies in the last 2 decades has obliged the early diagnosis and prevention of SCD to a certain extent. In this review, we analyze the critical challenges and recent advancements in the identification, risk stratification, and clinical management of potentially fatal cardiac ion channel disorders. We also emphasize the application of precision medicine (PM) and artificial intelligence (AI) for comprehending the underlying genetic mechanisms, especially the role of human induced pluripotent stem cell (iPSC) based platforms to unravel the primary refractory clinical problems associated with channelopathies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Myocardial regeneration has been a topic of interest in literature and research in recent years. An evolving approach reported is glucocorticoid (GC) receptor antagonism and its role in the regeneration of cardiomyocytes. The authors of this study aim to explore the reported literature on GC receptor antagonism and its effects on cardiomyocyte remodeling, hypertrophy, scar formation, and ongoing cardiomyocyte death following cardiac injury. This article overviews cellular biology, mechanisms of action, clinical implications, challenges, and future considerations. The authors of this study conducted a systematic review utilizing the Cochrane methodology and PRISMA guidelines. This study includes data collected and interpreted from 30 peer-reviewed articles from 3 databases with the topic of interest. The mammalian heart has regenerative potential during its embryonic and fetal phases which is lost during its developmental processes. The microenvironment, intrinsic molecular mechanisms, and systemic and external factors impact cardiac regeneration. GCs influence these aspects in some cases. Consequently, GC receptor antagonism is emerging as a promising potential target for stimulating endogenous cardiomyocyte proliferation, aiding in cardiomyocyte regeneration following a cardiac injury such as a myocardial infarction (MI). Experimental studies on neonatal mice and zebrafish have shown promising results with GC receptor ablation (or brief pharmacological antagonism) promoting the survival of myocardial cells, re-entry into the cell cycle, and cellular division, resulting in cardiac muscle regeneration and diminished scar formation. Transient GC receptor antagonism has the potential to stimulate cardiomyocyte regeneration and help prevent the dreaded complications of MI. More trials based on human populations are encouraged to justify their applications and weigh the risk-benefit ratio., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Aficamten is a novel cardiac myosin inhibitor that has demonstrated its ability to safely lower left ventricular outflow tract (LVOT) gradients and improve heart failure symptoms in patients with obstructive hypertrophic cardiomyopathy (HCM). Based on the REDWOOD-HCM open label extension (OLE) study, participants receiving aficamten had significantly reduced resting and Valsalva LVOT gradient within 2 weeks after initiating treatment, with ongoing improvements over 24 weeks, and recent evidence suggests effects can sustain up to 48 weeks. While beta-blockers, calcium channel blockers, and disopyramide have shown some benefits in managing HCM, they have limited direct impact on the underlying disease process in patients with obstructive HCM. Aficamten achieves its therapeutic effect by reducing hypercontractility and improving diastolic function in obstructive HCM. Mavacamten was the first cardiac myosin inhibitor approved for symptomatic obstructive HCM. However, aficamten has a shorter human half-life (t 1/2 ) and fewer drug-drug interactions, making it a preferable treatment option. This review evaluates the long-term clinical value and safety of aficamten in patients with obstructive HCM based on available data from completed and ongoing clinical trials. Additionally, the molecular basis of sarcomere-targeted therapy in reducing LVOT gradients is explored, and its potential in managing obstructive HCM is discussed., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Cardiac Amyloidosis (CA) is a manifestation of a systemic disorder resulting from the deposition of transthyretin (TTR) in the myocardium. This leads to a myriad of manifestations ranging from conduction defects to heart failure. Previously CA was considered a rare disease, but recent advances in diagnostics and therapeutics have revealed the prevalence to be higher than estimated. There are two major classes of treatments for TTR cardiac amyloidosis (ATTR-CA): TTR stabilizers, such as tafamidis and AG10, and RNA interference (siRNA), such as patisiran and vutrisiran. Clustered regularly interspaced short palindromic repeats of genetic information-Cas9 endonuclease (CRISPR-Cas9) utilizes an RNA-guided endonuclease to target specific locations in the genome. Until recently, CRISPR-Cas9 was studied in small animal models for its ability to decrease extracellular deposition and accumulation of amyloid in tissues. Gene editing has demonstrated some early clinical promise as an emerging therapeutic modality in the treatment of CA. In an introductory human trial involving 12 subjects with TTR amyloidosis and amyloid cardiomyopathy (ATTR-CM), CRISPR-Cas9 therapy has demonstrated a reduction in approximately 90% of serum TTR proteins after 28 days. In this article, the authors review the current literature on therapeutic gene editing as a prospective curative treatment modality for CA., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The Seattle Angina Questionnaire (SAQ-7) quantifies the impact of angina on patient functionality and quality of life. There is scarce data on the impact of social determinants and comorbidities on SAQ-7 in patients undergoing percutaneous coronary intervention (PCI) with planned staged PCI., Methods: Patients completed a SAQ-7 before each PCI. Multivariable regression analysis was performed to study the impact of social determinants, comorbidities, and procedural characteristics on SAQ-7 scores at index PCI and at the time of the staged PCI., Results: 531 patients were studied. Female sex, non-White race, coronary artery bypass graft history (CABG), and chronic lung disease were associated with lower baseline SAQ-7 scores. Overall, SAQ-7 increased between index procedure and staged PCI (11.9 ± 23.4). Body mass index (BMI) and the treatment of bifurcation lesions were independently associated with improvement of SAQ-7 between PCIs. Post-intervention, neither sex nor race was independently associated with changes in SAQ-7 scores., Conclusion: Different disparities and comorbid factors affect SAQ-7 before and after PCI. After revascularization, sex and race were not independent predictors of SAQ-7 improvement., Competing Interests: Declaration of competing interest Our conflicts of interest are as follows: George Dangas: Consulting: Albany Medical Center, CERC, Piedmont Liability Trust, University at Albany – SUNY; Equity: Elixir Medical Corporation, STEL, ControlRad; Other Activities: ACT 1 Torrance CA, Asan University South Korea, Gaffney Events, John Wiley and Sons, Inc., Samin Sharma Foundation; Scientific Advisory Board: Society for Cardiovascular Angiography and Interventions (SCAI). Annapoorna Kini: Industry-Sponsored Lectures: Miscellaneous teaching and lectures at academic institutions. Roxana Mehran: Consulting: Witt Kieffer; Equity: Elixir Medical Corporation, STEL, ControlRad; Industry-Sponsored Lectures: Asan University South Korea, Brazilian Cardiology Society, COLOMBIA webinar, China Cardiology Conference, Europa Group, Gaffney Events, India Webinar, India Webinar Mumbai, Samin Sharma Foundation, Society for Cardiovascular Angiography and Interventions (SCAI), St. Francis Hospital, Taiwan Cardiology Conference, Tarsus, University of Florence, University of Purchase, WebMD, Webinar APSCJCS; Scientific Advisory Board: American College of Cardiology. Samin K. Sharma: Equity: Eternal Heart Care Centre and Research Institute Private Limited (EHCRI); Industry-Sponsored Lectures: Abbott Laboratories, Boston Scientific Corporation, Cardiovascular Systems, Inc. (CSI), miscellaneous teaching and lectures at academic institutions. All other authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: As transcatheter aortic valve replacement (TAVR) procedures become more widely available, there is a growing need to monitor and evaluate postoperative outcomes accurately. The energy loss index (ELI) of the ascending aorta has been commonly used to examine the agreement between the echocardiographic and Gorlin measurement of the aortic valve area., Objectives: This project aims to demonstrate a link between ELI values and mortality following implanted TAVR valves and determine an ELI cutoff value associated with post-TAVR events., Method: We retrospectively reviewed patients undergoing TAVR from 2012 to 2017. We calculated ELI values for patients immediately postoperative after a TAVR procedure. Using Receiver-Operator Characteristic and Cox Regression analyses, we identified a cutoff value to distinguish between "High ELI" (≥ 1.34) and "Low ELI" (< 1.34) patients., Results: This study showed low ELI (hazard ratio, 2.30; 95% confidence interval 1.57-3.36, p < .001) as representative of patients with a high risk of mortality post-TAVR. Additionally, post-TAVR, ejection fraction increased by 3.6% (p < .001), and the aortic valve effective orifice area increased by 1.41 cm squared (p < .001) while the mean transvalvular gradient decreased by 32.8 mmHg (p < .001) and the peak transvalvular gradient decreased by 49.0 mmHg (p < .001)., Conclusion: ELI is an additional prognostic factor that should be considered during risk assessment before TAVR. This study shows that patients with Low ELI had decreased cumulative survival post-TAVR. These patients almost had a fivefold increased risk of death following TAVR., (© 2023 Wiley Periodicals LLC.)

Hypertrophic cardiomyopathy (HCM) is a disease involving the cardiac sarcomere. It is associated with various disease-causing gene mutations and phenotypic expressions, managed with different therapies with variable prognoses. The heterogeneity of the disease is evident in the fact that it burdens patients of all ages. HCM is the most prevalent cause of sudden death in athletes. However, several technological advancements and therapeutic options have reduced mortality in patients with HCM to 0.5% per year. In addition, rapid advances in our knowledge of the molecular defects accountable for HCM have strengthened our awareness of the disorder and recommended new approaches to the assessment of prognosis. Despite all these evolutions, a small subgroup of patients with HCM will experience sudden cardiac death, and risk stratification remains a critical challenge. This review provides a practical guide to the updated recommendations for patients with HCM, including clinical updates for diagnosis, family screening, clinical imaging, risk stratification, and management., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Eligibility criteria for clinical trials are intended to select suitable study subjects but can limit trial participation and generalization of results. While reported for other cancers, non-enrollment rates and evolution of eligibility criteria over time have so far not been studied for randomized controlled trials (RCTs) involving adults with acute myeloid leukemia (AML). Among 3698 studies published between 2010 and 2020, including 447 involving prospective clinical trials, we identified 75 phase three RCTs testing non-transplant therapies for adults with AML. Only 31 studies (41%) provided information on non-enrollment; in these studies, the median non-enrollment rate was 23%, primarily attributed to restrictive eligibility criteria. In 95% of trials, eligibility criteria were reported with the total number per trial increasing over time (P < 0.001), particularly in industry-funded trials. A total of 27 eligibility criteria were used across trials, mostly concerning comorbidities or performance status, with eight of them becoming more common over time. The concordance with recent ASCO - Friends of Cancer Research eligibility criteria recommendations greatly varied, from 35% to 99%. Together, our analyses suggest that the ability to generalize results from non-transplant RCTs may be increasingly limited because of high non-enrollment rates and increasingly restrictive eligibility criteria., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Purpose of Review: The catheter-based coronary intervention has become a well-established therapeutic modality for obstructive coronary artery disease. However, in-stent restenosis remains a significant limitation of coronary intervention despite the use of newer devices. Intravascular brachytherapy was introduced to treat recurrent in-stent restenosis but only modestly adopted. This review will discuss the mechanism of intracoronary brachytherapy, available clinical evidence of brachytherapy in recurrent in-stent restenosis treatment, and the future of coronary brachytherapy in coronary intervention., Recent Findings: Drug-eluting stents have an inherent limitation as they leave a permanent metal layer inside an artery when deployed. Recently, drug-coated balloon technology has emerged to treat coronary artery disease as a combination of balloon angioplasty and local drug delivery without leaving a metal layer behind. Recent European guidelines recommended using drug-coated balloons when treating in-stent restenosis treatment, while the US guidelines have not yet addressed the use of drug-coated balloons in such cases. Coronary brachytherapy is a valuable addition to treat these challenging diseases despite several logistic issues. If there are newer technologies with easier setup, such as drug-coated balloons, coronary brachytherapy resurgence is improbable in the contemporary era, although it may not become obsolete., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The nuclear pore complex (NPC) regulates the movement of macromolecules between the nucleus and cytoplasm. Dysfunction of many components of the NPC results in human genetic diseases, including triple A syndrome (AAAS) as a result of mutations in ALADIN. Here, we report a nonsense mutation in the maize ortholog, aladin1 (ali1-1), at the orthologous amino acid residue of an AAAS allele from humans, alters plant stature, tassel architecture, and asymmetric divisions of subsidiary mother cells (SMCs). Crosses with the stronger nonsense allele ali1-2 identified complex allele interactions for plant height and aberrant SMC division. RNA-seq analysis of the ali1-1 mutant identified compensatory transcript accumulation for other NPC components as well as gene expression consequences consistent with conservation of ALADIN1 functions between humans and maize. These findings demonstrate that ALADIN1 is necessary for normal plant development, shoot architecture, and asymmetric cell division in maize., (© The Author(s) 2021. Published by Oxford University Press on behalf of Genetics Society of America.)

The maize gene Rp1-D21 is a mutant form of the gene Rp1-D that confers resistance to common rust. Rp1-D21 triggers a spontaneous defense response that occurs in the absence of the pathogen and includes a programed cell death called the hypersensitive response (HR). Eleven plants heterozygous for Rp1-D21, in four different genetic backgrounds, were identified that had chimeric leaves with lesioned sectors showing HR abutting green nonlesioned sectors lacking HR. The Rp1-D21 sequence derived from each of the lesioned portions of leaves was unaltered from the expected sequence whereas the Rp1-D21 sequences from nine of the nonlesioned sectors displayed various mutations, and we were unable to amplify Rp1-D21 from the other two nonlesioned sectors. In every case, the borders between the sectors were sharp, with no transition zone, suggesting that HR and chlorosis associated with Rp1-D21 activity was cell autonomous. Expression of defense response marker genes was assessed in the lesioned and nonlesioned sectors as well as in near-isogenic plants lacking and carrying Rp1-D21 . Defense gene expression was somewhat elevated in nonlesioned sectors abutting sectors carrying Rp1-D21 compared with near-isogenic plants lacking Rp1-D21 . This suggests that, whereas the HR itself was cell autonomous, other aspects of the defense response initiated by Rp1-D21 were not.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Objectives: The aim of this study was to evaluate post-percutaneous coronary intervention (PCI) outcomes in relation to pre-procedural glycated hemoglobin (HbA 1c ) levels from a large, contemporary cohort., Background: There are limited data evaluating associations between HbA 1c , a marker of glycemic control, and ischemic risk following PCI., Methods: All patients with known HbA 1c levels undergoing PCI at a single institution between 2009 and 2017 were included. Patients were divided into 5 groups on the basis of HbA 1c level: ≤5.5%, 5.6% to 6.0%, 6.1% to 7.0%, 7.1% to 8.0%, and >8.0%. The primary endpoint was major adverse cardiac events (MACE), a composite of all-cause death or myocardial infarction (MI), at 1-year follow-up., Results: A total of 13,543 patients were included (HbA 1c  ≤5.5%, n = 1,214; HbA 1c 5.6% to 6.0%, n = 2,202; HbA 1c 6.1% to 7.0%, n = 4,130; HbA 1c 7.1% to 8.0%, n = 2,609; HbA 1c >8.0%, n = 3,388). Patients with both low (HbA 1c  ≤5.5%) and high (HbA 1c >8.0%) levels displayed an increased risk for MACE compared with those with values between 6.1% and 7.0%. Excess risk was driven primarily by higher rates of all-cause death among those with low HbA 1c levels, while higher values were strongly associated with greater MI risk. Patterns of risk were unchanged among patients with serial HbA 1c levels and persisted after multivariate adjustment., Conclusions: Among patients undergoing PCI, pre-procedural HbA 1c levels display a U-shaped association with 1-year MACE risk, a pattern that reflects greater risk for death in the presence of low HbA 1c (≤5.5%) and higher risk for MI with higher values (>8.0%)., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021. Published by Elsevier Inc.)

Objectives: Bilateral Institutional Health Partnerships (IHPs) are a means of strengthening health systems and are becoming increasing prevalent in global health. Nigeria Centre for Disease Control (NCDC) and Public Health England (PHE) have engaged in one such IHP as part of Public Health England's International Health Regulations Strengthening project. Presently, there have been limited evaluations of IHPs resulting in limited evidence of their effectiveness in strengthening health systems despite the concept being used across the world., Study Design: Qualitative, using a validated tool., Methods: The ESTHER EFFECt tool was used to evaluate the IHP between NCDC and PHE. Senior leadership from both organisations participated in a two-day workshop where their perceptions of various elements of the partnership were evaluated. This was done through an initial quantitative survey followed by a facilitated discussion to further explore any arising issues., Results: This evaluation is the first published evaluation of a bilateral global health partnership undertaken by NCDC and PHE. NCDC scores were consistently higher than PHE scores. Key strengths and weaknesses of the partnership were identified such as having wide ranging institutional engagement, however needing to improve dissemination mechanisms following key learning activity., Conclusions: There is a dearth of evidence measuring the effectiveness of international health partnerships; of the studies that exist, many are lacking in academic rigour. We used the ESTHER EFFECt tool as it is an established method of evaluating the progress of the partnership, with multiple previous peer-reviewed publications. This will hopefully encourage more organisations to publish evaluations of their international health partnerships and build the evidence base., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Competing interests – None, there was no patient, public or commercial involvement in the study design or conduct of the study., (© 2021 The Authors.)

Introduction: Numerous case series have reported on the baseline characteristics and in-hospital mortality of patients with COVID-19, however, these studies included patients localized in a specific geographic region. The purpose of our study was to identify differences in the clinical characteristics and the in-hospital mortality of patients with a laboratory-confirmed diagnosis of COVID-19 internationally., Methods: A comprehensive search of all published literature on adult patients with laboratory-confirmed diagnosis of COVID-19 that reported on the clinical characteristics and in-hospital mortality was performed. Groups were compared using a Chi-square test with Yates correction of continuity. A two-tailed p value of less than 0.05 was considered as statistically significant., Results: After screening 516 studies across the globe, 43 studies from 12 countries were included in our final analysis. Patients with COVID-19 in America and Europe were older compared to their Asian counterparts. Europe had the highest percentage of male patients. American and European patients had a higher incidence of co-morbid conditions (p < 0.05 for all variables). In-hospital mortality was significantly higher in America (22.23%) and Europe (22.9%) compared to Asia (12.65%) (p < 0.0001), but no difference was seen when compared with each other (p = 0.49)., Conclusions: There is a significant variation in the clinical characteristics in patients diagnosed with COVID-19 across the globe. In-hospital mortality is similar between America and Europe, but considerably higher than Asia.