Clinical Utility of Rilonacept for the Treatment of Recurrent Pericarditis: Design, Development, and Place in Therapy.

Recurrent pericarditis (RP) has been traditionally regarded as a "nightmare" for both clinicians and patients. Until approximately a decade ago, available treatments were thin on the ground with non-steroidal anti-inflammatory medications, glucocorticoids, colchicine, and classical immunosuppressants being the only options. The first important step in the tale of RP was the advent of colchicine in clinical practice, which has been shown to halve the rate of first and subsequent pericarditis recurrences. The second major breakthrough advance in this setting was the introduction of interleukin-1 inhibitors based on the recently unveiled autoinflammatory nature of pericarditis. At present, anti-interleukin-1 inhibitors available for clinical use in patients with refractory RP include anakinra and rilonacept, with the latter having obtained FDA approval for this indication. Apart from the remarkable efficacy and good safety profile which is a common feature of all anti-interleukin-1 compounds, rilonacept has the advantage of weekly administration (instead of daily compared to anakinra) which is important in terms of adherence to treatment and improved quality of life albeit at the expense of a higher cost. This review aims to summarize the available evidence on the role of rilonacept in the treatment of RP and the reduction of the recurrences risk.

Transcatheter Structural Heart Disease Interventions and Concomitant Left Atrial Appendage Occlusion: A State-of-the-Art Review.

Atrial fibrillation (AF) is the most common arrhythmia in patients with valvular heart disease, and it can be associated with adverse patient outcomes. However, the need of anticoagulation to counterbalance AF-associated stroke risk may further lead to suboptimal outcomes via increasing bleeding events, especially in high-risk individuals. Currently, the option to perform a concomitant to the index procedure for limiting stroke risk is emerging, in accordance to usual practice in cardiac surgery. In specific, as the vast majority of thrombi occur in the left atrial appendage, left atrial appendage occlusion (LAAO) is an established procedure for preventing ischemic stroke in patients with AF, while limiting anticoagulation-related bleeding events. Thus, the concept of combining an index procedure for a structural heart disease (SHD) with LAAO seems promising for preventing future stroke events. A combined procedure has been described in aortic stenosis (TAVI+LAAO), mitral regurgitation (TEER+LAAO) and atrial septal defects (PFO/ASD+LAAO). Evidence shows that a combined procedure can be safely performed in a "one-stop shop" fashion, without increased rates of procedural adverse events, with the potential to limit bleeding risk and provide prophylaxis against stroke events. Thus, this review is going to analyze indications and clinical evidence regarding the safety and efficacy of combined SHD+LAAO procedure, while also providing insights in gaps in knowledge and future directions for the evolvement of this field.

Atrial fibrillation burden: Stepping beyond the categorical characterization.

Traditional classifications categorize atrial fibrillation (AF) into paroxysmal, persistent, or permanent, but recent advancements in monitoring have revealed AF as a continuous variable, challenging existing paradigms. AF burden, defined basically as the amount of time spent in AF during a monitored period, has emerged as a crucial metric. This review assesses the evolving landscape of AF burden and its measurement methods, diagnostic modalities, and impact on outcomes. Guidelines suggest individualized approaches, combining AF burden with clinical scores (CHA2DS2-VASc), but studies have challenged this. Addressing the impact of AF burden on patients' quality of life before or after ablation is also crucial. Although continuous monitoring technologies offer promising avenues, the field faces challenges, such as defining clinically relevant thresholds. Future research should focus on refining these, designing trials centered around AF burden, and evaluating the efficacy of interventions in reducing AF burden, ultimately paving the way for personalized management strategies.

Efficacy and Safety of Direct Oral Anticoagulants versus Warfarin in Obese Patients (BMI ≥ 30 kg/m2) with Atrial Fibrillation or Venous Thromboembolism: An Updated Systematic Review and Meta-Analysis.

Background: Real-world data show limited utilization of direct oral anticoagulants (DOACs) in obese patients (body mass index [BMI] ≥ 30 kg/m2) due to concerns regarding their efficacy and safety in this demographic. Aim: This review aimed to consolidate current evidence on the efficacy and safety of DOACs versus warfarin in obese patients with non-valvular atrial fibrillation (AF) or venous thromboembolism (VTE). The primary efficacy outcome assessed a composite of all-cause mortality, stroke, systemic embolism (SE), and myocardial infarction (MI). Methods: A systematic search was conducted in MEDLINE, SCOPUS, and Cochrane databases from inception to December 28, 2023. Data were synthesized using random-effects meta-analysis. Results: A total of 35 studies involving 434,320 participants were analyzed. DOAC use was associated with a significant reduction in the risk of the composite outcome (RR = 0.80, 95% CI [0.65, 0.98], I2 = 95%), hemorrhagic stroke (RR = 0.58, 95% CI [0.38, 0.88], I2 = 92%), major bleeding (RR = 0.76, 95% CI [0.63, 0.92], I2 = 94%), gastrointestinal bleeding (RR = 0.59, 95% CI [0.49, 0.72], I2 = 88%), and intracranial bleeding (RR = 0.45, 95% CI [0.34, 0.60], I2 = 44%) compared to warfarin. A non-significant benefit of DOACs was observed for all-cause mortality, MI, the composite of stroke or SE, ischemic stroke, SE, VTE, and minor bleeding compared to warfarin. Subgroup analysis indicated no significant effect modification based on the indication for anticoagulation or study design. Conclusions: DOACs demonstrated a favorable efficacy and safety profile in obese individuals compared to warfarin.

The Efficacy of Coronary Sinus Reducer in Patients with Refractory Angina: A Systematic Review and Meta-Analysis.

Background: Refractory angina is a frequently encountered phenomenon in patients with coronary artery disease, often presenting therapeutic challenges to the clinical cardiologist. Novel treatment methods have been explored in this direction, with the coronary sinus reducer (CSR) being among the most extensively-investigated. Methods: We conducted a systematic review of the literature for studies assessing the efficacy of CSR in patients with refractory angina. The primary endpoints of interest were procedural success and the improvement in angina according to the Canadian Cardiovascular Society (CCS) by at least one class. Secondary endpoints were the rate of periprocedural adverse events, the improvement by at least 2 CCS classes, and the mean change in CCS class. A random-effects meta-analysis of proportions (procedural success, improvement by ≥ 1 or ≥ 2 classes, periprocedural adverse events) or means (mean CCS class change) were performed. I 2 was chosen as the metric for between-study heterogeneity. Publication bias was assessed by the inspection of funnel plots and Egger's regression test. We examined the risk of bias according to the Newcastle-Ottawa Scale. Results: From a total of 515 studies identified from the original search, 12 studies were finally included for data extraction. Based on their meta-analysis, we observed a high CSR procedural success (98%, 95% confidence interval (CI) 96 to 99%) with a low rate of periprocedural complications (6%, 95% CI 5 to 7%), while most patients exhibited an improvement by at least 1 CCS class (75%, 95% CI 66 to 83%) after the intervention. A significant proportion of patients demonstrated an improvement by at least 2 CCS classes (39%, 95% CI 34 to 45%), with a mean change of -1.24 CCS class (95% CI -1.40 to -1.08). Conclusions: CSR is associated with high implantation success rates and significant improvements in angina symptoms for patients with refractory angina.

Whispers of the Cath lab: "Cases we would rather forget".

In the dynamic field of interventional cardiology, significant strides have been made in reducing periprocedural complications. Echocardiography, particularly transesophageal echocardiography, plays a key role in ensuring the safety and success of structural heart interventions. Its real-time imaging capabilities allow for precise monitoring of device positioning, deployment, and procedural outcomes. By adhering to established imaging protocols and acquiring standard imaging planes, periprocedural echocardiography has become an essential tool for the successful performance of many structural heart interventions. In this manuscript, we present a series of unusual yet significant complications that we encountered during structural interventional procedures in our catheter laboratory. These complications, detected through echocardiography, underscore the critical role of imaging guidance in recognizing, and addressing unforeseen challenges, such as device malposition, thrombus formation in cardiac chambers during structural heart interventions, and cardiac tamponade during transcatheter mitral valve procedures. Through these cases, we highlight the effectiveness of transesophageal echocardiography in promptly identifying complications, allowing for timely intervention and resolution.

Intravascular lithotripsy in peripheral lesions with severe calcification and its use in TAVI procedure - a meta-analysis.

Background: Heavily calcified peripheral artery lesions increase the risk of vascular complications, constituting a severe challenge for the operator during catheter-based cardiovascular interventions. Intravascular Lithotripsy (IVL) technology disrupts subendothelial calcification by using localized pulsative sonic pressure waves and represents a promising technique for plaque modification in patients with severe calcification in peripheral arteries. Purpose: Our aim was to systematically review and summarize available data regarding the safety and efficacy of IVL in preparing severely calcified peripheral arteries and its use in Transcatheter Aortic Valve Implantation (TAVI). Patients and methods: This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL in the peripheral vasculature. The diameter of the vessel lumen before and after IVL was estimated. The occurrence of peri-procedural complications was assessed using a random-effects model. Results: 20 studies with a total of 1,223 patients with heavily calcified peripheral lesions were analysed. The mean age of the cohort was 70.6 ± 17.4 years. Successful IVL delivery achieved in 100% (95% CI: 100%-100%, I2 = 0%), with an increase in the luminal diameter (SMD: 4.66, 95% CI: 3.41-5.92, I2 = 90.8%) and reduction in diameter stenosis (SMD: -4.15, 95% CI: -4.75 to -3.55, I2 = 92.8%), and a concomitant low rate of complications. The procedure was free from dissection in 97% (95% CI: 91%-100%, I2 = 81.4%) while dissections of any type (A, B, C, or D) were observed in 6% (95% CI: 2%-10%, I2 = 85.3%) of the patients. Several rare cases of abrupt closure, no-reflow phenomenon, perforation, thrombus formation, and distal embolization were recorded. Finally, the subgroup analysis of patients who underwent a TAVI with IVL assistance presented successful implantation in 100% (95% CI: 100%-100%, I2 = 0%) of the cases, with only 4% (95% CI: 0%-12%, I2 = 68.96%) presenting dissections of any sort. Conclusions: IVL seems to be an effective and safe technique for modifying severely calcified lesions in peripheral arteries and it is a promising modality in TAVI settings. Future prospective studies are needed to validate our results.

Long-term effects of phosphodiesterase-5 inhibitors on cardiovascular outcomes and death: a systematic review and meta-analysis.

AIMS: Phosphodiesterase 5 inhibitors (PDE5i), which are widely used for the treatment of erectile dysfunction (ED), have been found to exhibit systemic vascular benefits by improving endothelial function. In this context, we sought to evaluate the effects of PDE5i on long-term cardiovascular outcomes and mortality. METHODS AND RESULTS: A comprehensive search of electronic databases was conducted up to 30 May 2023. Cohort studies comparing PDE5i treatment at any dose with other ED treatment, placebo or no treatment and minimum follow-up duration of 6 months were considered eligible. The primary endpoints were: (1) major adverse cardiovascular events (MACE) and (2) all-cause mortality. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated. Sixteen studies were included (1 257 759 subjects-10.5% treated with PDE5i). The majority of patients (99.4%) were men [median age 61.5 years (range 30-72.8)]. The median follow-up duration was 4.3 years (range 6 months-7.5 years). PDE5i use was associated with a significant reduction in the composite of MACE (RR 0.78, 95% CI 0.69-0.89). Moreover, the analysis of pooled data from 13 studies, demonstrated that the use of PDE5i was associated with a significantly lower risk of all-cause mortality (RR 0.70, 95% CI 0.56-0.87). CONCLUSION: The use of PDE5i primarily in men with or without known coronary artery disease was associated with a lower risk for cardiovascular events and overall mortality. This information underlines that PDE5i could provide clinical benefit beyond ED treatment and could instigate the conduction of further, large-scale randomized clinical trials.

Prediction of heart failure patients with distinct left ventricular ejection fraction levels using circadian ECG features and machine learning.

Heart failure (HF) encompasses a diverse clinical spectrum, including instances of transient HF or HF with recovered ejection fraction, alongside persistent cases. This dynamic condition exhibits a growing prevalence and entails substantial healthcare expenditures, with anticipated escalation in the future. It is essential to classify HF patients into three groups based on their ejection fraction: reduced (HFrEF), mid-range (HFmEF), and preserved (HFpEF), such as for diagnosis, risk assessment, treatment choice, and the ongoing monitoring of heart failure. Nevertheless, obtaining a definitive prediction poses challenges, requiring the reliance on echocardiography. On the contrary, an electrocardiogram (ECG) provides a straightforward, quick, continuous assessment of the patient's cardiac rhythm, serving as a cost-effective adjunct to echocardiography. In this research, we evaluate several machine learning (ML)-based classification models, such as K-nearest neighbors (KNN), neural networks (NN), support vector machines (SVM), and decision trees (TREE), to classify left ventricular ejection fraction (LVEF) for three categories of HF patients at hourly intervals, using 24-hour ECG recordings. Information from heterogeneous group of 303 heart failure patients, encompassing HFpEF, HFmEF, or HFrEF classes, was acquired from a multicenter dataset involving both American and Greek populations. Features extracted from ECG data were employed to train the aforementioned ML classification models, with the training occurring in one-hour intervals. To optimize the classification of LVEF levels in coronary artery disease (CAD) patients, a nested cross-validation approach was employed for hyperparameter tuning. HF patients were best classified using TREE and KNN models, with an overall accuracy of 91.2% and 90.9%, and average area under the curve of the receiver operating characteristics (AUROC) of 0.98, and 0.99, respectively. Furthermore, according to the experimental findings, the time periods of midnight-1 am, 8-9 am, and 10-11 pm were the ones that contributed to the highest classification accuracy. The results pave the way for creating an automated screening system tailored for patients with CAD, utilizing optimal measurement timings aligned with their circadian cycles.

Management of dyslipidemia in coronary artery disease: the present and the future.

Coronary artery disease (CAD) remains a leading cause of global morbidity and mortality, necessitating continuous refinement in the management of dyslipidemia, one of its major risk factors, to mitigate cardiovascular risks. Previous studies have proven the critical role of immediate and robust low-density lipoprotein cholesterol (LDL-C) reduction in the aftermath of acute coronary syndrome (ACS). Emphasizing the evidence supporting this approach, we delve into the impact of early intervention on cardiovascular outcomes and propose optimal strategies for achieving rapid LDL-C lowering, while also providing the rationale for early proprotein convertase subtilisin/kexin 9 inhibitor use after an ACS. Given the importance of the residual lipidemic risk, we present an overview of emerging therapeutic avenues poised to reshape dyslipidemia management, such as bempedoic acid, lipoprotein(a) inhibition, ApoC3 modulation, and angiopoietin-like protein 3 targeting. This comprehensive review amalgamates current evidence with future prospects, offering a holistic perspective on the management of dyslipidemia in CAD. By exploring both the urgency for immediate post-ACS LDL-C reduction and the exciting advancements on the horizon, this article provides a roadmap for clinicians navigating the intricate landscape of lipid-lowering therapies in CAD.

Intravascular ultrasound-guided, lithotrispy facilitated angioplasty for treating a heavily calcified renal artery stenosis.

A 63-year-old woman with uncontrolled hypertension despite taking 5 antihypertensive medications was referred for percutaneous renal artery intervention.

Efficacy of intravascular lithotripsy (IVL) in coronary stenosis with severe calcification: A multicenter systematic review and meta-analysis.

BACKGROUND: With heavily calcified coronary and peripheral artery lesions, lesion preparation is crucial before stent placement to avoid underexpansion, associated with stent thrombosis or restenosis and patency failure in the long-term. Intravascular lithotripsy (IVL) technology disrupts superficial and deep calcium by using localized pulsative sonic pressure waves, making it to a promising tool for patients with severe calcification in coronary bed. AIMS: The aim of the study is to systematically review and summarize available data regarding the safety and efficacy of IVL for lesion preparation in severely calcified coronary arteries before stenting. METHODS: This study was conducted according to the PRISMA guidelines. We systematically searched PubMed, SCOPUS, and Cochrane databases from their inception to February 23, 2023, for studies assessing the characteristics and outcomes of patients undergoing IVL before stent implantation. The diameter of the vessel lumen before and after IVL, as well as stent implantation, were analyzed. The occurrence of major adverse cardiovascular events (MACE) was assessed using a random-effects model. RESULTS: This meta-analysis comprised 38 studies including 2977 patients with heavily calcified coronary lesions. The mean age was 72.2 ± 9.1 years, with an overall IVL clinical success of 93% (95% confidence interval [CI]: 91%-95%, I2 = 0%) and procedural success rate of 97% (95% CI: 95%-98%, I2 = 73.7%), while the in-hospital and 30-days incidence of MACE, myocardial infarction (MI), and death were 8% (95% CI: 6%-11%, I2 = 84.5%), 5% (95% CI: 2%-8%, I2 = 85.6%), and 2% (95% CI: 1%-3%, I2 = 69.3%), respectively. There was a significant increase in the vessel diameter (standardized mean difference [SMD]: 2.47, 95% CI: 1.77-3.17, I2 = 96%) and a decrease in diameter stenosis (SMD: -3.44, 95% CI: -4.36 to -2.52, I2 = 97.5%) immediately after IVL application, while it was observed further reduction in diameter stenosis (SMD: -6.57, 95% CI: -7.43 to -5.72, I2 = 95.8%) and increase in the vessel diameter (SMD: 4.37, 95% CI: 3.63-5.12, I2 = 96.7%) and the calculated lumen area (SMD: 3.23, 95% CI: 2.10-4.37, I2 = 98%), after stent implantation. The mean acute luminal gain following IVL and stent implantation was estimated to be 1.27 ± 0.6 and 1.94 ± 1.1 mm, respectively. Periprocedural complications were rare, with just a few cases of perforations, dissection, or no-reflow phenomena recorded. CONCLUSIONS: IVL seems to be a safe and effective strategy for lesion preparation in severely calcified lesions before stent implantation in coronary arteries. Future prospective studies are now warranted to compare IVL to other lesion preparation strategies.

Circadian assessment of heart failure using explainable deep learning and novel multi-parameter polar images.

BACKGROUND AND OBJECTIVE: Heart failure (HF) is a multi-faceted and life-threatening syndrome that affects more than 64.3 million people worldwide. Current gold-standard screening technique, echocardiography, neglects cardiovascular information regulated by the circadian rhythm and does not incorporate knowledge from patient profiles. In this study, we propose a novel multi-parameter approach to assess heart failure using heart rate variability (HRV) and patient clinical information. METHODS: In this approach, features from 24-hour HRV and clinical information were combined as a single polar image and fed to a 2D deep learning model to infer the HF condition. The edges of the polar image correspond to the timely variation of different features, each of which carries information on the function of the heart, and internal illustrates color-coded patient clinical information. RESULTS: Under a leave-one-subject-out cross-validation scheme and using 7,575 polar images from a multi-center cohort (American and Greek) of 303 coronary artery disease patients (median age: 58 years [50-65], median body mass index (BMI): 27.28 kg/m2 [24.91-29.41]), the model yielded mean values for the area under the receiver operating characteristics curve (AUC), sensitivity, specificity, normalized Matthews correlation coefficient (NMCC), and accuracy of 0.883, 90.68%, 95.19%, 0.93, and 92.62%, respectively. Moreover, interpretation of the model showed proper attention to key hourly intervals and clinical information for each HF stage. CONCLUSIONS: The proposed approach could be a powerful early HF screening tool and a supplemental circadian enhancement to echocardiography which sets the basis for next-generation personalized healthcare.

Prevalence of subungual melanoma in patients with cutaneous malignant melanoma: A systematic review and meta-analysis.

BACKGROUND: Subungual melanoma (SUM) is a rare type of cutaneous malignant melanoma (CMM) associated with poor prognosis, while data regarding its prevalence are scarce. OBJECTIVES: We sought to provide a comprehensive systematic review and meta-analysis of the prevalence rates of SUM among all types of CMM, considering certain demographic and clinical characteristics. METHODS: The MEDLINE electronic database was searched systematically to identify eligible studies providing prevalence rate estimates of SUM in patients with CMM. Included studies were further analysed to estimate the relative prevalences of SUM according to study design, study years, geographical region and sex distribution. RESULTS: Twenty-eight studies met the inclusion criteria. The overall SUM prevalence was 1.9% (95% CI [1.5%-2.3%]). The prevalence of SUM did not differ significantly between population- and hospital-based studies and remained stable over time. However, it was found to be significantly higher in Asians compared to patients of other geographical regions as well as in studies with more men than women compared to those with female preponderance (p < 0.001). CONCLUSIONS: In all, the overall SUM prevalence among all subtypes of CMM was estimated at 1.9%, without significant changes over time, and was found to exhibit significant variability between subgroups of different geographical regions.

Interventional management of mitral regurgitation and sleep disordered breathing: "Catching two birds with one stone".

Sleep disordered breathing (SDB), mostly constituting of obstructive and central sleep apnea (OSA and CSA, respectively), is highly prevalent in the general population, and even more among patients with cardiovascular disease, heart failure (HF) and valvular heart disease, such as mitral regurgitation (MR). The coexistence of HF, MR and SDB is associated with worse cardiovascular outcomes and increased morbidity and mortality. Pulmonary congestion, as a result of MR, can exaggerate and worsen the clinical status and symptoms of SDB, while OSA and CSA, through various mechanisms that impair left ventricular dynamics, can promote left ventricular remodelling, mitral annulus dilatation and consequently MR. Regarding treatment, positive airway pressure devices used to ameliorate symptoms in SDB also seem to result in a reduction of MR severity, MR jet fraction and an improvement of left ventricular ejection fraction. However, surgical and transcatheter interventions for MR, and especially transcatheter edge to edge mitral valve repair (TEER), seem to also have a positive effect on SDB, by reducing OSA and CSA-related severity indexes and improving symptom control. The purpose of this review is to provide a comprehensive analysis of the common pathophysiology between SDB and MR, as well as to discuss the available evidence regarding the effect of SDB treatment on MR and the effect of mitral valve surgery or transcatheter repair on both OSA and CSA.

LOX-1 Receptor: A Diagnostic Tool and Therapeutic Target in Atherogenesis.

Low-density lipoprotein (LDL) and oxidized LDL (oxLDL) are major contributors to atherogenesis, as endogenous antigens, via several receptors such as LOX 1. A PubMed search was conducted in order to identify relevant articles regarding LOX-1's role in the atherosclerosis, diagnosis, prognostic use and molecules that could be used for therapy. The references of the manuscripts obtained were also reviewed, in order to find additional relevant bibliography. LOX-1 is a lectin-like pattern recognition receptor, mostly expressed in endothelial cells (ECs) which can bind a variety of molecules, including oxLDL and C-reactive protein (CRP). LOX-1 plays a key role in oxLDL's role as a causative agent of atherosclerosis through several pathologic mechanisms, such as oxLDL deposition in the subintima, foam cell formation and endothelial dysfunction. Additionally, LOX-1 acts a scavenger receptor for oxLDL in macrophages and can be responsible for oxLDL uptake, when stimulated. Serum LOX-1 (sLOX-1) has emerged as a new, potential biomarker for diagnosis of acute coronary syndromes, and it seems promising for use along with other common biomarkers in everyday clinical practice. In a therapeutic perspective, natural as well as synthetic molecules exert anti-LOX-1 properties and attain the receptor's pathophysiological effects, thus extensive research is ongoing to further evaluate molecules with therapeutic potential. However, most of these molecules need further trials in order to properly assess their safety and efficacy for clinical use. The aim of this review is to investigate LOX-1 role in atherogenesis and explore its potential as diagnostic tool and therapeutic target.

Investigating automated regression models for estimating left ventricular ejection fraction levels in heart failure patients using circadian ECG features.

Heart Failure (HF) significantly impacts approximately 26 million people worldwide, causing disruptions in the normal functioning of their hearts. The estimation of left ventricular ejection fraction (LVEF) plays a crucial role in the diagnosis, risk stratification, treatment selection, and monitoring of heart failure. However, achieving a definitive assessment is challenging, necessitating the use of echocardiography. Electrocardiogram (ECG) is a relatively simple, quick to obtain, provides continuous monitoring of patient's cardiac rhythm, and cost-effective procedure compared to echocardiography. In this study, we compare several regression models (support vector machine (SVM), extreme gradient boosting (XGBOOST), gaussian process regression (GPR) and decision tree) for the estimation of LVEF for three groups of HF patients at hourly intervals using 24-hour ECG recordings. Data from 303 HF patients with preserved, mid-range, or reduced LVEF were obtained from a multicentre cohort (American and Greek). ECG extracted features were used to train the different regression models in one-hour intervals. To enhance the best possible LVEF level estimations, hyperparameters tuning in nested loop approach was implemented (the outer loop divides the data into training and testing sets, while the inner loop further divides the training set into smaller sets for cross-validation). LVEF levels were best estimated using rational quadratic GPR and fine decision tree regression models with an average root mean square error (RMSE) of 3.83% and 3.42%, and correlation coefficients of 0.92 (p<0.01) and 0.91 (p<0.01), respectively. Furthermore, according to the experimental findings, the time periods of midnight-1 am, 8-9 am, and 10-11 pm demonstrated to be the lowest RMSE values between the actual and predicted LVEF levels. The findings could potentially lead to the development of an automated screening system for patients with coronary artery disease (CAD) by using the best measurement timings during their circadian cycles.

Management of Patients With Unexplained Syncope: Derivation and Validation of a Simplified 2-Step Diagnostic Approach.

BACKGROUND: The aim of this study was to develop a structured 2-step approach, based on noninvasive diagnostic criteria, that led to an electrophysiology study in patients with unexplained syncope. METHODS AND RESULTS: Two independent cohorts were used: the derivation cohort with 665 patients based on electronic health record data to develop our 2-step diagnostic approach, and the validation cohort based on 160 prospectively screened patients, presenting with unexplained syncope episodes. Noninvasive electrocardiographic and imaging markers and an electrophysiology study-based invasive assessment were combined. A positive diagnostic approach according to our study's prespecified criteria resulted in a decision to proceed with a permanent pacemaker/implantable cardioverter-defibrillator. The primary end point was the time until the event of recurrent syncope (syncope-free survival). Number needed to treat was calculated for patients with a positive diagnostic approach. The number of patients with unexplained syncope and borderline sinus bradycardia needed to treat was 5, and the number of patients with unexplained syncope and bundle branch block needed to treat was 3 over a mean follow-up of ≈4 years. After the structured 2-step approach, the primary outcome occurred in 14 of 82 (17.1%) with a pacemaker/implantable cardioverter-defibrillator and 19 of 57 (33%) with a negative approach, with a mean follow-up of ≈2.5 years (29.29±12.58 months, P=0.03). CONCLUSIONS: The low number needed to treat in the derivation cohort and the low percentage of syncope recurrence in the validation cohort supports the proposed 2-step electrophysiology-inclusive algorithm as a potentially low-cost, 1-day, structured tool for these patients.