Coronary microvascular dysfunction, arrythmias, and sudden cardiac death: A literature review.

The coronary vascular system has a unique structure and function that is adaptive to myocardial demand. It is composed of a continuous network of vessels receding in size from epicardial arteries to the microvascular circulation. Failure to meet myocardial demand results in ischemia, angina, and adverse myocardial outcomes. It is evident that 50 % of patients with angina have a non-obstructive coronary disease and 66 % of these patients have coronary microvascular dysfunction (CMD). The impact of CMD on the atria and ventricles is exhibited through its association with atrial fibrillation and distortion of ventricular repolarization. Ultimately, this influence increases the risk of mortality, morbidity, and sudden cardiac arrest. CMD serves as an independent risk for atrial fibrillation, increases ventricular electrical inhomogeneity, and contributes to the progression of cardiac disease. The underlying pathogenesis may be attributed to oxidative stress evident through reactive oxygen species, impaired vasoactive function, and structural disorders such as fibrotic changes. Myocardial ischemia, brought about by a demand-supply mismatch in CMD, may create a milieu for ventricular arrythmia and sudden cardiac arrest through distortion of ventricular repolarization parameters such as QT dispersion and corrected QT dispersion.

Physiology and functional significance of the coronary microcirculation: An overview of its implications in health and disease.

Ischemic, Coronary Heart Disease (CHD) is a leading cause of morbidity and death worldwide.

The Burden of Skin Cancers in Saudi Arabia Through 2011-2022.

Introduction Skin cancers are classified into melanoma and non-melanoma or keratinocyte cancers. No recent data are found about the epidemiology of skin cancers in Saudi Arabia. The current study aims to determine the burden of skin cancer in the last 11 years from 2011 to 2022. Methods Patients who were diagnosed with any type of skin cancer were enrolled in the study. The diagnosis was conducted based on histopathology and immunohistochemistry. Different variables like age, type of cancer, type of lesions, and treatment approach used were measured. Results A total of 91 patients were diagnosed with skin cancers during the study period. The head and neck were the most common sites for skin cancers. Only 4/91 cases reported invasive melanoma. Both squamous cell carcinoma (SCC) (34/91) and basal cell carcinoma (BCC) (28/91) were found to be the most reported skin cancers. Other cancers including mycosis fungoides (MF) (10/91), Kaposi's sarcoma (6/91), and dermatofibrosarcoma protuberans (DFSP) (5/91) were also detected. The rest of the detected tumors were rarely detected. Aggressive CD4+/CD4+/CD8+ MF was more prevalent than CD3+/CD4+/CD8- MF cancer cases. CD34+ /S100- DFSP cancers were evident in most of the DFSP cases. Human herpes virus 8 was detected in all Kaposi's sarcoma cases and all of them were HIV-confirmed cases. Surgical treatment was the most frequently used approach to treat skin cancers, followed by phototherapy (9.9%), surgical/radiotherapy (5.5%), surgical/chemotherapy (4.4%), chemotherapy (3.3%), and then chemoradiotherapy immunotherapy (1.1%). Conclusion The incidences of SCC and BCC are relatively high in comparison to other types of skin cancers with the surgical intervention being most frequently used.

Genomic and Proteomic Study of the Inflammatory Pathway in Patients With Atrial Fibrillation and Cardiometabolic Syndrome.

Atrial fibrillation (AF) and cardiometabolic syndrome (CMS) have been linked to inflammation and fibrosis. However, it is still unknown which inflammatory cytokines contribute to the pathogenesis of AF. Furthermore, cardiometabolic syndrome (CMS) risk factors such as obesity, hypertension, insulin resistance/glucose intolerance are also associated with inflammation and increased level of cytokines and adipokines. We hypothesized that the inflammatory immune response is exacerbated in patients with both AF and CMS compared to either AF or CMS alone. We investigated inflammatory cytokines and fibrotic markers as well as cytokine genetic profiles in patients with lone AF and CMS. CMS, lone AF patients, patients with both lone AF and CMS, and control patients were recruited. Genetic polymorphisms in inflammatory and fibrotic markers were assessed. Serum levels of connective tissue growth factor (CTGF) were tested along with other inflammatory markers including platelet-to-lymphocyte ratio (PLR), monocyte-to-HDL ratio (MHR) in three groups of AF+CMS, AF, and CMS patients. There was a trend in the CTGF levels for statistical significance between the AF and AF+CMS group (P = 0.084). Genotyping showed high percentages of patients in all groups with high secretor genotypes of Interleukin-6 (IL-6) (P = 0.037). Genotyping of IFN-γ and IL-10 at high level showed an increase in expression in the AF + CMS group compared to AF and CMS alone suggesting an imbalance between the inflammatory and anti-inflammatory cytokines which is exacerbated by AF. Serum cytokine inflammatory cytokine levels showed that IL-4, IL-5, IL-10, IL-17F, and IL-22 were significant between the AF, AF+CMS, and CMS patients. Combination of both CMS and AF may be associated with a higher degree of inflammation than what is seen in either CMS or AF alone. Thus, the identification of a biomarker capable of identifying metabolic syndrome associated with disease will help in identification of a therapeutic target in treating this devastating disease.

Resource and Infrastructure-Appropriate Management of ST-Segment Elevation Myocardial Infarction in Low- and Middle-Income Countries.

The 143 low- and middle-income countries (LMICs) of the world constitute 80% of the world's population or roughly 5.86 billion people with much variation in geography, culture, literacy, financial resources, access to health care, insurance penetration, and healthcare regulation. Unfortunately, their burden of cardiovascular disease in general and acute ST-segment-elevation myocardial infarction (STEMI) in particular is increasing at an unprecedented rate. Compounding the problem, outcomes remain suboptimal because of a lack of awareness and a severe paucity of resources. Guideline-based treatment has dramatically improved the outcomes of STEMI in high-income countries. However, no such focused recommendations exist for LMICs, and the unique challenges in LMICs make directly implementing Western guidelines unfeasible. Thus, structured solutions tailored to their individual, local needs, and resources are a vital need. With this in mind, a multicountry collaboration of investigators interested in LMIC STEMI care have tried to create a consensus document that extracts transferable elements from Western guidelines and couples them with local realities gathered from expert experience. It outlines general operating principles for LMICs focused best practices and is intended to create the broad outlines of implementable, resource-appropriate paradigms for management of STEMI in LMICs. Although this document is focused primarily on governments and organizations involved with improvement in STEMI care in LMICs, it also provides some specific targeted information for the frontline clinicians to allow standardized care pathways and improved outcomes.

Towards Point-of-Care Heart Failure Diagnostic Platforms: BNP and NT-proBNP Biosensors.

Heart failure is a class of cardiovascular diseases that remains the number one cause of death worldwide with a substantial economic burden of around $18 billion incurred by the healthcare sector in 2017 due to heart failure hospitalization and disease management. Although several laboratory tests have been used for early detection of heart failure, these traditional diagnostic methods still fail to effectively guide clinical decisions, prognosis, and therapy in a timely and cost-effective manner. Recent advances in the design and development of biosensors coupled with the discovery of new clinically relevant cardiac biomarkers are paving the way for breakthroughs in heart failure management. Natriuretic neurohormone peptides, B-type natriuretic peptide (BNP) and N-terminal prohormone of BNP (NT-proBNP), are among the most promising biomarkers for clinical use. Remarkably, they result in an increased diagnostic accuracy of around 80% owing to the strong correlation between their circulating concentrations and different heart failure events. The latter has encouraged research towards developing and optimizing BNP biosensors for rapid and highly sensitive detection in the scope of point-of-care testing. This review sheds light on the advances in BNP and NT-proBNP sensing technologies for point-of-care (POC) applications and highlights the challenges of potential integration of these technologies in the clinic. Optical and electrochemical immunosensors are currently used for BNP sensing. The performance metrics of these biosensors-expressed in terms of sensitivity, selectivity, reproducibility, and other criteria-are compared to those of traditional diagnostic techniques, and the clinical applicability of these biosensors is assessed for their potential integration in point-of-care diagnostic platforms.

Impact of a hospital-based educational intervention on dietary salt-related knowledge and behaviour in a cardiac care unit population in Lebanon.

BACKGROUND: Cardiovascular disease is the most common cause of morbidity and mortality worldwide. Numerous strategies have been effective in reducing cardiovascular disease risk, from pharmacological approaches to lifestyle modification interventions. One of these strategies includes the reduction in dietary sodium which in turn reduces cardiovascular risk by reducing high blood pressure, perhaps the most important cardiovascular risk factor. METHODS: We evaluated an educational dietary salt reduction intervention in a cardiac care unit population in Lebanon, assessing salt related knowledge and behaviours before and after administering an evidence-based educational leaflet to patients. RESULTS: Salt-related knowledge improved significantly immediately post-intervention and subsequently fell on 4-week follow-up, but remained above baseline. Three of the four salt-related behaviours measured improved on 4-week follow-up: trying to buy low-salt foods increased from 54% to 74% (P=0.007), adding salt at the table reduced from 44% to 34% (P=0.03) and trying to buy food with no added salt increased from 24% to 52% (P=0.02) of the cohort. Adding salt during cooking did not differ significantly. A trend towards improved behavioural risk category in the cohort overall was observed on follow-up (P=0.07), 32% of participants were categorised as high behavioural risk pre-intervention, reducing to 17% on follow-up. Multi-ordered regression modelling identified being in the high-risk behavioural category at baseline as a predictor of being in the high-risk or moderate-risk category on follow-up. CONCLUSIONS: This hospital-based educational intervention had a modestly positive impact on salt-related knowledge and behaviour, with participants in the highest behavioural risk category at baseline being most resistant to behavioural improvement.

An Outflow Boundary Condition Model for Noninvasive Prediction of Fractional Flow Reserve in Diseased Coronary Arteries.

This paper reports on a new boundary condition formulation to model the total coronary myocardial flow and resistance characteristics of the myocardial vascular bed for any specific patient when considered for noninvasive diagnosis of ischemia. The developed boundary condition model gives an implicit representation of the downstream truncated coronary bed. Further, it is based on incorporating patient-specific physiological parameters that can be noninvasively extracted to account for blood flow demand to the myocardium at rest and hyperemic conditions. The model is coupled to a steady three-dimensional (3D) collocated pressure-based finite volume flow solver and used to characterize the "functional significance" of a patient diseased coronary artery segment without the need for predicting the hemodynamics of the entire arterial system. Predictions generated with this boundary condition provide a deep understanding of the inherent challenges behind noninvasive image-based diagnostic techniques when applied to human diseased coronary arteries. The overall numerical method and formulated boundary condition model are validated via two computational-based procedures and benchmarked with available measured data. The newly developed boundary condition is used via a designed computational methodology to (a) confirm the need for incorporating patient-specific physiological parameters when modeling the downstream coronary resistance, (b) explain the discrepancies presented in the literature between measured and computed fractional flow reserve (FFRCT), and

First and second generation DESs reduce diabetes adverse effect on mortality and re-intervention in multivessel coronary disease: 9-Year analysis.

BACKGROUND/PURPOSE: Diabetes portends an increased risk of adverse early and late outcomes in patients undergoing PCI. In this study, we aimed to investigate if the adverse effect of diabetes mellitus (DM) on early and late PCI outcomes is reduced with drug-eluting (DES) compared to bare-metal (BMS) stents. METHODS/MATERIALS: We reviewed the Mount Sinai Beth Israel Hospital first PCI experience for multivessel coronary artery disease (CAD, 1998-2009). Patients were excluded if they had single-vessel CAD, emergency, no stent, prior bypass graft or myocardial infarction <24h. Diabetes-effect was derived from 9-year all-cause mortality and re-intervention risk-adjusted hazard ratios [AHR (95% confidence intervals)] for DES (N=2679; 48% three-vessel; 39% DM) and BMS (N=2651; 40% three-vessel; 33% DM) and then stratified based on stent (DES/BMS) and vessel disease (two/three). RESULTS: Diabetes-effect on mortality was lower for DES (AHRDM/NoDM=1.41 [1.14-1.74]) versus BMS (AHRDM/NoDM=1.71 [1.50-2.01]), but this was predominantly driven by two-vessel patients. This diabetes effect was similar for first (DES1: AHRDM/NoDM=1.43 [1.14-1.79]) and second (DES2: AHRDM/NoDM=1.53 [0.77-3.07]) generation DES. Re-intervention comparisons were similarly increased by diabetes in all sub-cohorts. CONCLUSIONS: Our analysis of a large real-world PCI series indicates that diabetes is associated with worse 9-year mortality irrespective of stent type, albeit this is mitigated to varying degrees with DES, particularly in DES2 and in case of 2-vessel disease. A complementary stent-effect analysis confirmed DES-to-BMS and DES2-to-DES1 superiority in both diabetics and non-diabetics.

Normalization of biventricular strain post steroid treatment of effusive constrictive pericarditis.

Peak left ventricular strain measured by speckle tracking echocardiography has previously been shown to normalize following pericardectomy in constrictive pericarditis, as indicated by an increase of the strain ratio between the lateral wall and septum. Here we present a case of effusive constrictive pericarditis treated with corticosteroids. Pre-treatment we observed reduced contractility of the lateral walls of both ventricles as measured by peak strain, with sparing of overall septal function, but with hypercontractility of the basal septal segment. Septal and lateral wall function normalized with corticosteroid treatment. Our observations from this case prompts investigation into the value of lateral/septal wall strain ratios in both ventricles for quantitatively monitoring the response of constrictive pericarditis to medical therapy. .

Quantifying the impact of using Coronary Artery Calcium Score for risk categorization instead of Framingham Score or European Heart SCORE in lipid lowering algorithms in a Middle Eastern population.

BACKGROUND: The use of the Coronary Artery Calcium Score (CACS) for risk categorization instead of the Framingham Risk Score (FRS) or European Heart SCORE (EHS) to improve classification of individuals is well documented. However, the impact of reclassifying individuals using CACS on initiating lipid lowering therapy is not well understood. We aimed to determine the percentage of individuals not requiring lipid lowering therapy as per the FRS and EHS models but are found to require it using CACS and vice versa; and to determine the level of agreement between CACS, FRS and EHS based models. METHODS: Data was collected for 500 consecutive patients who had already undergone CACS. However, only 242 patients met the inclusion criteria and were included in the analysis. Risk stratification comparisons were conducted according to CACS, FRS, and EHS, and the agreement (Kappa) between them was calculated. RESULTS: In accordance with the models, 79.7% to 81.5% of high-risk individuals were down-classified by CACS, while 6.8% to 7.6% of individuals at intermediate risk were up-classified to high risk by CACS, with slight to moderate agreement. Moreover, CACS recommended treatment to 5.7% and 5.8% of subjects untreated according to European and Canadian guidelines, respectively; whereas 75.2% to 81.2% of those treated in line with the guidelines would not be treated based on CACS. CONCLUSION: In this simulation, using CACS for risk categorization warrants lipid lowering treatment for 5-6% and spares 70-80% from treatment in accordance with the guidelines. Current strong evidence from double randomized clinical trials is in support of guideline recommendations. Our results call for a prospective trial to explore the benefits/risks of a CACS-based approach before any recommendations can be made.

High residual platelet reactivity on clopidogrel: its significance and therapeutic challenges overcoming clopidogrel resistance.

Over the last decade, dual antiplatelet therapy has been the mainstay of the management of Acute Coronary Syndrome, with clopidogrel therapy providing clear benefits over aspirin monotherapy and becoming the agent of choice for the prevention of stent thrombosis. While newer antiplatelet agents have now become available, clopidogrel is still widely used due to its low cost and efficacy. However, many patients still experience recurrent ischemic events. A poor response of the platelets to clopidogrel, called High Residual Platelet Reactivity (HRPR), has been incriminated to account for this dilemma. Despite the absence of a universal definition of HRPR or the gold standard test to quantify it, persistent high platelet reactivity has consistently been associated with recurrence of ischemic events. Clopidogrel metabolism is highly variable, and genetics, comorbidities and drug interactions can affect it. In this article we review all definitions of HRPR, explore the available tests to quantify it, the clinical outcomes associated with it, as well as strategies that have shown success in overcoming it.

Use of dabigatran for periprocedural anticoagulation in patients undergoing catheter ablation for atrial fibrillation.

BACKGROUND: Pulmonary vein isolation (PVI) for atrial fibrillation is associated with a transient increased risk of thromboembolic and hemorrhagic events. We hypothesized that dabigatran can be safely used as an alternative to continuous warfarin for the periprocedural anticoagulation in PVI. METHODS AND RESULTS: A total of 999 consecutive patients undergoing PVI were included; 376 patients were on dabigatran (150 mg), and 623 patients were on warfarin with therapeutic international normalized ratio. [corrected] Dabigatran was held 1 to 2 doses before PVI and restarted at the conclusion of the procedure or as soon as patients were transferred to the nursing floor. Propensity score matching was applied to generate a cohort of 344 patients in each group with balanced baseline data. Total hemorrhagic and thromboembolic complications were similar in both groups, before (3.2% versus 3.9%; P=0.59) and after (3.2% versus 4.1%; P=0.53) matching. Major hemorrhage occurred in 1.1% versus 1.6% (P=0.48) before and 1.2% versus 1.5% (P=0.74) after matching in the dabigatran versus warfarin group, respectively. A single thromboembolic event occurred in each of the dabigatran and warfarin groups. Despite higher doses of intraprocedural heparin, the mean activated clotting time was significantly lower in patients who held dabigatran for 1 or 2 doses than those on warfarin. CONCLUSIONS: Our study found no evidence to suggest a higher risk of thromboembolic or hemorrhagic complications with use of dabigatran for periprocedural anticoagulation in patients undergoing PVI compared with uninterrupted warfarin therapy.

CYP2C19 genetic polymorphism, rabeprazole and esomeprazole have no effect on the antiplatelet action of clopidogrel.

The aim of this study is to investigate the effect of CYP2C19 polymorphism and cotherapy with rabeprazole or esomeprazole on the antiplatelet effect of clopidogrel. Patients receiving clopidogrel 75 mg ± rabeprazole or esomeprazole underwent genotyping for CYP2C19*2 and CYP2C19*3, and vasodilator-stimulated phosphoprotein testing to measure platelet reactivity index (PRI). Two hundred thirty-nine consecutive patients were enrolled as follows: 92 clopidogrel (C group), 94 clopidogrel + rabeprazole (CR), and 53 clopidogrel + esomeprazole (CE). Forty-five patients had loss of function (LOF) polymorphism (43 heterozygous; 2 homozygous mutant for CYP2C19*2). The mean PRI was 20.7% ± 21.9% in the C group, 19.1% ± 20.9% in the CR group, and 24.5% ± 22.9% in the CE group (P = NS). High on-treatment platelet reactivity (HPR), defined as PRI >50%, was observed in 12 (13.0%), 13 (13.8%), and 10 (18.9%) patients on C, CR, and CE, respectively (P = NS). HPR was similar in rapid metabolizers between groups. On multivariate logistic regression, neither CYP2C19 LOF alleles nor proton pump inhibitor cotherapy were associated with HPR. The use of proton pump inhibitors was indicated in 30.6% of recipients. As a conclusion, CYP2C19*2 LOF allele and the use of esomeprazole or rabeprazole have no effect on the action of clopidogrel.

First use of a drug-eluting balloon in the treatment of acute renal artery occlusion and in-stent restenosis.

In-stent restenosis in a renal artery (RA) of a solitary functioning kidney is a serious complication of RA stenting. Drug-eluting balloons (DEB) have emerged as a novel way to manage restenosis. In this paper, the authors reported the first use of a DEB in the treatment of severe in-stent restenosis and thrombosis of a drug-eluting stent deployed in a RA. The patient presented with oligo-anuria and a serum creatinine (Scr) of 9 mg/dL that improved back to baseline of 2 mg/dL after the successful procedure. The optimal use of DEB in similar cases will have to be determined by larger clinical trials.

Distribution and risk profile of paroxysmal, persistent, and permanent atrial fibrillation in routine clinical practice: insight from the real-life global survey evaluating patients with atrial fibrillation international registry.

BACKGROUND: There is a paucity of international data on the various types of atrial fibrillation (AF) outside the highly selected populations from randomized trials. This study aimed to describe patient characteristics, risk factors, comorbidities, symptoms, management strategy, and control of different types of AF in real-life practice. METHODS AND RESULTS: Real-life global survey evaluating patients with atrial fibrillation (RealiseAF) was a contemporary, large-scale, cross-sectional international survey of patients with AF who had ≥1 episode in the past 12 months. Investigators were randomly selected to avoid bias. Among 9816 eligible patients from 831 sites in 26 countries, 2606 (26.5%) had paroxysmal, 2341 (23.8%) had persistent, and 4869 (49.6%) had permanent AF. As AF progressed from paroxysmal to persistent and permanent forms, the prevalence of comorbidities, such as heart failure (32.9%, 44.3%, and 55.6%), coronary artery disease (30.0%, 32.9%, and 34.3%), cerebrovascular disease (11.7%, 10.8%, and 17.6%), and valvular disease (16.7%, 21.2%, and 35.8%), increased, and the prevalence of lone AF decreased. Similarly, there was an increase in mean CHADS(2) [cardiac failure, hypertension, age, diabetes, stroke (doubled)] score (1.7, 1.8, and 2.2), and more than half of patients (51.0%, 56.7%, and 67.3%) qualified for oral anticoagulants. Almost 90% of patients received ≥1 antiarrhythmic drug, but >60% had European Heart Rhythm Association symptom scores from II to IV. Furthermore, 40.7% of persistent and 49.8% of permanent AF patients were still in AF with a heart rate >80 beats per minute. CONCLUSIONS: This survey disclosed high cardiovascular risks and an unmet need in daily practice for patients with any type of AF, especially those with the permanent form.

Symptoms, functional status and quality of life in patients with controlled and uncontrolled atrial fibrillation: data from the RealiseAF cross-sectional international registry.

BACKGROUND: Rate control and rhythm control are accepted management strategies for atrial fibrillation (AF). OBJECTIVE: RealiseAF aimed to describe the success of either strategy and the impact of control on symptomatic status of patients with AF. METHODS: This international, observational, cross-sectional survey of patients with any history of AF in the previous year, recorded AF characteristics, management and frequency of control (defined as sinus rhythm or AF with resting heart rate ≤80 bpm). RESULTS: Overall, 9665 patients were evaluable for AF control, with 59.0% controlled (sinus rhythm 26.5%, AF ≤80 bpm 32.5%) and 41.0% uncontrolled. Symptom prevalence in the previous week was lower in controlled than uncontrolled AF (55.7% vs 68.4%; p<0.001) and similar for patients in sinus rhythm versus AF ≤80 bpm (54.8% vs 56.4%; p=0.23). At the visit, AF-related functional impairment (EHRA class >I) was seen in 67.4% of patients with controlled AF and 82.1% of patients with uncontrolled AF (p<0.001). Quality-of-life (QoL, measured using EQ-5D) was better for patients with controlled versus uncontrolled AF using the Visual Analogue Scale (mean (SD) score 67.1 (18.4) vs 63.2 (18.9); p<0.001), single index utility score (median 0.78 vs 0.73; p<0.001), or five dimensions of well-being (all p<0.001). Irrespective of AF control, cardiovascular events had led to hospitalisation in the past year in 28.1%. CONCLUSION: AF control is not optimal. Control appears to be associated with fewer symptoms and better QoL, but even patients with controlled AF have frequent symptoms, functional impairment, altered QoL and cardiovascular events. New treatments are needed to improve control and minimise the functional and QoL burden of AF.