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Background: Cardiovascular disease (CVD) is the leading cause of mortality and disability worldwide. While sex differences in CVD have been well documented, the physiological mechanisms of those sex differences remain unclear. As important components of the cardiovascular system, cardiac vagal control and baroreflex serve as mechanisms of sex differences in CVD and are modifiable factors for gender-specific CVD preventions. Methods: Ninety-four healthy adults (18–44 years of age; M_age = 21.09 years; 46 female) were recruited to complete the assessments of heart rate variability (HRV) at a resting baseline and the cardiac timing effect on an R-wave-locked reaction time (RT) task, which were used as the indicator of cardiac vagal control and a novel behavioral measure of baroreflex activity, respectively. HRV metrics (including the root mean square of successive R-R interval differences, high frequency and low frequency heart rate variability, and low frequency-to-high frequency ratio), the cardiac timing effect (the inhibition of RT response at the phase of cardiac systole compared to diastole), and their associations were compared between female and male participants. Results: Female participants showed higher levels of vagally mediated HRV after adjusting for basal resting heart rate. Importantly, the cardiac timing effect on RT responses was positively correlated with vagally mediated HRV among males but not among females. Conclusions: Females and males exhibited different physiological processes to regulate cardiovascular functions and behavioral outcomes. The present findings will help to reduce gender disparities in the preventive care of CVD and improve cardiovascular health for both women and men. Full article

Background: Coronary microvascular disease is associated with adverse prognosis in a range of cardiovascular diseases, but its prognostic role in patients with aortic stenosis (AS) is unclear. The aim of this systematic review and meta-analysis is to determine the prognostic role of myocardial perfusion and coronary flow reserve, assessed using non-invasive imaging modalities, in patients with AS. Methods: We conducted a systematic review and meta-analysis of all studies assessing myocardial perfusion reserve (MPR) or coronary flow reserve (CFR) in patients with AS and reporting clinical outcomes, from inception to January 2024. The definition of abnormal MPR/CFR and major adverse cardiovascular events (MACE) was that used in each study. Estimates of effect were calculated from hazard ratios (HRs) and 95% confidence intervals (CIs) using a random-effects model. Results: Four studies comprising 384 participants met the inclusion criteria. Myocardial/coronary blood flow was assessed using Doppler echocardiography (n = 2), PET (n = 1), or cardiac magnetic resonance (n = 1). The median optimal cutoff for MPR/CFR across all studies was 2.01 (range 1.85–2.13), with 109 events. Impaired MPR/CFR was associated with a higher incidence of MACE (HR 3.67, 95% CI: 1.66, 8.09, I² = 63%) in the overall population. Conclusions: Reduced MPR/CFR is associated with increased risk of MACE in patients with AS, although significant heterogeneity exists in published studies. Further studies are required to establish its role in the risk stratification of asymptomatic patients with AS. Full article

Background/objectives: Acute coronary syndrome (ACS) is a major global health issue primarily caused by the rupture or erosion of vulnerable coronary plaques. Non-invasive identification of these plaques through coronary computed tomography angiography (CCTA) can be improved with radiomics, which extracts and analyses quantitative features from medical images. This systematic review aims to comprehensively evaluate the literature surrounding the role of radiomics in assessing coronary plaques via CCTA. Methods: A systematic search of Medline, EMBASE, and Web of Science was conducted up to July 2024. Nine studies met the inclusion criteria, and their methodological quality was assessed using the radiomic quality score (RQS) and the QUADAS-2 tool. Results: All studies that evaluated radiomic models for plaque vulnerability reported area under the curve (AUC) values exceeding 0.7, indicating at least modest diagnostic performance. In the four studies that made direct comparisons, radiomic models consistently outperformed conventional CCTA markers. However, RQS scores ranged from 2.7% to 41.7%, reflecting variability in study quality and underscoring the need for more robust validation. Conclusions: Radiomics has the potential to enhance CCTA-based identification of vulnerable coronary plaques, offering a promising non-invasive approach to predicting major adverse cardiovascular events. However, the current body of research is limited by the lack of external validation, reliance on small, single-centre retrospective studies, and methodological inconsistencies, which impact the generalisability and reproducibility of findings. Future research should prioritise prospective, multi-centre studies with standardised protocols and rigorous validation frameworks to effectively incorporate radiomics into clinical practice. Full article

Background: Recent studies have suggested an increased risk of acute myocardial infarction (AMI) following daylight saving time (DST) transitions in cohorts of American and European patients. We aim to validate this finding in a Canadian population. Methods: We performed a retrospective cohort study of patients admitted to the Hôpital du Sacré-Coeur de Montréal with a diagnosis of AMI requiring a coronary angiogram from 28 February 2016 to 3 December 2022. The transition period was defined as two weeks following DST, while the control periods were two weeks before and two weeks after the transition period. Patients aged 18 years or older were included. The primary endpoint was the incidence rate ratio (IRR) of AMI following DST transitions while the secondary endpoint was infarct size by biomarkers. A subgroup analysis compared the pre-COVID-19 period (2016–2019) to the post-COVID-19 period (2020–2022). Results: A total of 1058 patients were included (362 in the transition group and 696 in the control group). The baseline clinical characteristics were comparable between both groups. The rate of AMI per day following the DST transitions was 1.85 compared to 1.78 during control periods. The DST transitions were not associated with an increase in AMI (IRR = 1.04, 95% CI 0.91–1.18, p = 0.56) nor with infarct size. In the subgroup analysis, DST was associated with a significant increase in the incidence of AMI only in the pre-COVID-19 period, with a rate of 2.04 AMI per day in the transition group compared to 1.71 in the control group (IRR = 1.19, 95% CI 1.01–1.41, p = 0.041). In contrast, there was a significant increase in the size of AMI following DST in the post-COVID-19 period subgroup, with a creatine phosphokinase-MB (CK-MB) concentration of 137 ± 229 µg/L compared to 93 ± 142 µg/L (p = 0.013). Conclusions: In this Canadian cohort, there was a significant increase in the incidence of AMI in the pre-COVID-19 period, and infarct sizes were significantly larger following the DST transitions in the post-COVID-19 period. No significant associations emerged when pre- and post-COVID-19 periods were pooled. Full article

Background/Objectives: Few studies have analyzed in-hospital complications and events following percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) procedures for patients who underwent these interventions for single-vessel coronary artery disease (CAD). This study aims to compare the outcomes of PCI and CABG in such patients using a large propensity-matched real-world database based on procedural codes. Methods: Adult patients receiving PCI or CABG for single-vessel CAD were identified from the 2016–2020 National Inpatient Sample (NIS) database. Any cases targeting multi-vessel disease or employing a multi-treatment approach were excluded using appropriate procedural codes. Differences in events and complications from admission to discharge were studied between the two procedures (PCI vs. CABG) via logistic regression analysis. Results: After propensity matching with 273,380 patients in both groups, complication risks such as cardiac tamponade (aOR: 3.6 [3.27–3.96]), acute kidney injury (aOR: 1.53 [1.51–1.56]), cardiogenic shock (aOR: 1.38 [1.34–1.40]), procedural bleeding (aOR: 1.75 [1.67–1.83]), acute ischemic stroke (aOR: 1.89 [1.80–1.97]), and all-cause mortality (aOR: 1.05 [1.02–1.08]) were higher among CABG patients. No differences were observed for events of cardiac perforation (aOR: 0.92, [0.84–1.01]). Conclusions: In this large real-world propensity-matched analysis, CABG was associated with higher risks of multiple in-hospital complications and all-cause mortality compared to PCI following a single-vessel coronary intervention. Full article

Background/Objectives: Heart failure presents a significant public health challenge, affecting millions in the US, with projections of increasing prevalence and economic burdens. Obstructive sleep apnea (OSA) is highly prevalent among HF patients. This study analyzes the impact of OSA on the outcomes in patients admitted with acute decompensated heart failure. Methods: We conducted a retrospective cohort study using the National Inpatient Sample database (NIS) 2020, focusing on patients admitted with acute heart failure. Patient outcomes were compared between those with and without a secondary diagnosis of OSA, identified via validated ICD-10 codes. Subgroup analysis was conducted between heart failure patients with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). Results: Among 65,649 patients with acute heart failure, 4595 (7%) patients were found to have OSA. The patients with OSA were more likely to be male, older in age and had a higher burden of comorbidities. No significant differences were observed in mortality between heart failure patients with and without OSA. In HFrEF patients, OSA was associated with longer hospital stays (6.45 days vs. 5.79 days, p < 0.001), higher rates of acute kidney injury (AKI) (adjusted odds ratio 1.28, 95% CI: 1.07–1.54, p = 0.007), and atrial fibrillation (adjusted odds ratio 1.35, 95% CI: 1.13–1.61, p = 0.001). In HFpEF patients, an association between OSA and AF was observed (adjusted odds ratio 1.20, 95% CI: 1.01–1.42, p = 0.03). Conclusions: OSA is associated with poor in-hospital outcomes in patients admitted with acute heart failure. HFrEF subgroup is especially vulnerable, with OSA leading to a significant increase in healthcare utilization and complication rates in these patients. This nationwide study underscores the importance of timely identification and treatment of OSA in heart failure to alleviate healthcare burdens and improve patient outcomes. Full article

Sodium glucose cotransporter-2 inhibitors (SGLT2i), originally developed for type II diabetes mellitus, have recently been approved for the treatment of heart failure in both diabetic and non-diabetic patients due to their significant cardiovascular benefits. Beyond their established role in diabetes and heart failure management, current research is exploring the potential applications of SGLT2 inhibitors in the field of cardio-oncology. This interest is driven by dual possible benefits: cardioprotection against the adverse effects of antitumor therapies and inherent antitumor properties. Patients affected by cancer often face the challenge of managing cardiovascular toxicity induced by antineoplastic treatments. SGLT2 inhibitors have shown promise in mitigating toxicities, thereby enhancing the cardiovascular health of these patients. Additionally, emerging evidence suggests that SGLT2 inhibitors may possess direct antitumor effects, further contributing to their therapeutic potential in oncology. This review aims to provide a comprehensive overview of the molecular mechanisms through which SGLT2 inhibitors exert their cardioprotective and antitumor effects. Furthermore, we will examine the current body of evidence supporting the use of these inhibitors in a cardio-oncology setting. Full article

Six patients in our clinical program who were diagnosed with high burden (>10%) premature ventricular contractions (PVCs) and concomitant significant upper GI disease with no other significant cardiac history demonstrated a significant reduction in the burden of PVCs following surgical or procedural interventions of the upper GI tract (68.34% reduction, p = 0.024). Furthermore, in all cases, the origin of the PVCs was from the base of the right ventricular outflow tract (RVOT). This is the first report in the literature that we are aware of that makes the unique association that we propose a dual mechanism of action of the upper GI and vagally mediated PVCs and through direct, anatomical extrinsic triggering of the right ventricular outflow tract (RVOT) of the heart. These are very preliminary findings that warrant larger clinical and mechanistic studies that if confirmed, may define a new physiologic subset of PVCs for which we propose a new term, “E-PVCs”. Full article

(1) Background: Arrhythmias, or irregular heart rhythms, are a prevalent cardiovascular condition and are diagnosed using electrocardiogram (ECG) signals. Advances in deep learning have enabled automated analysis of these signals. However, the effectiveness of deep learning models depends greatly on the quality of signal preprocessing. This study evaluated the impact of different windowing techniques applied to Fourier transform-preprocessed ECG signals on the classification accuracy of deep learning models. (2) Methods: We applied three windowing techniques—Hamming, Hann, and Blackman—to transform ECG signals into the frequency domain. A one-dimensional convolutional neural network was employed to classify the ECG signals into five arrhythmia categories based on features extracted from each windowed signal. (3) Results: The Blackman window yielded the highest classification accuracy, with improved signal-to-noise ratio and reduced spectral leakage compared to the Hamming and Hann windows. (4) Conclusions: The choice of windowing technique significantly influences the effectiveness of deep learning models in ECG classification. Future studies should explore additional preprocessing methods and their clinical applications. Full article

Introduction: Whether the association between atrial fibrillation (AF) and ischemic stroke (IS) outcomes differs by IS treatment type is unknown. We hypothesize that patients with IS who have AF will have a worse NIH Stroke Scale (NIHSS) and 90-day modified Rankin Scale (mRS) score than non-AF, with differences by IS treatment type. Methods: Patients with, and without AF admitted to Johns Hopkins (2020–2023) with confirmed IS and complete covariates were eligible for inclusion. Consecutive patients either received acute IS treatment (intravenous tissue plasminogen activator (IVtPA), mechanical thrombectomy (MT), or both) or did not receive treatment (2:1 ratio). Multivariable regression models were used to determine the association between AF and discharge NIHSS, or 90-day mRS, separately, with interaction terms for IS treatment type as appropriate. Results: Among 353 IS patients (mean age 69 years, 52.1% female, 54.7% Black), 62 received IVtPA only, 66 received IVtPA then MT, 108 received MT only, and 117 were not treated. Patients with AF (N = 152) were, on average, 11 years older and had more comorbidities than non-AF. AF was associated with higher odds of an NIHSS > 5, even after adjusting for demographics and comorbidities (OR 2.09, 95% CI 1.29–3.40). AF increased the odds of a worse 90-day mRS (Ordinal OR 1.65, 95% CI 1.03–2.64). The association between AF and NIHSS differed by whether MT was received (p-interaction 0.037), but not by IVtPA (p-interaction 0.105). AF and 90-day mRS differed by whether MT was received (p-interaction 0.020), but not by IVtPA (p-interaction 0.139). Patients with AF who did not receive MT had a worse NIHSS (OR 4.24, 95% CI 1.38–13.00) and 90-day mRS (OR 2.79, 95% CI 1.30–1.97) compared to non-AF. The individual effect estimates were not significant for those treated with MT when comparing AF to non-AF. Conclusions: The association between AF (vs non-AF) and both NIHSS and 90-day mRS differed by whether MT was received, but not by IVtPA. Patients with AF who did not receive MT had more severe strokes and worse outcomes than non-AF. These findings suggest that while AF is typically linked to more severe strokes, not receiving MT when eligible is particularly detrimental. Receipt of IVtPA did not appear to make a difference, possibly due to treatment contraindications and delays among those with AF. Full article

Background: Cavotricuspid isthmus (CTI)-dependent atrial flutter (AFL) is the most common atrial macro-reentrant tachycardia, characterized by a typical ECG pattern (type I ECG). Often, tachycardia terminates before it can be confirmed by an electrophysiological study (EPS), necessitating CTI ablation in sinus rhythm (SR). This study aims to compare the success rate of CTI ablation in patients with type I ECG during SR versus ongoing CTI-dependent AFL, focusing on arrhythmia recurrence. Methods: We screened patients at Ulm University Heart Center from January 2010 to November 2020 with type I ECG who underwent CTI ablation. Patients were divided into two groups: those whose tachycardia terminated before EPS and underwent ablation in SR, and those with ongoing CTI-dependent AFL during EPS. CTI ablation was deemed complete when a bidirectional conductance block was achieved, confirmed after 30 min. Results: A total of 230 patients were included, all showing typical AFL in ECG recordings. Of these, 67 patients underwent ablation in SR, while 163 were ablated during ongoing AFL. The median follow-up time was 2.7 years. Recurrence of CTI-dependent AFL occurred in 8.3% of patients: 4.5% in the SR ablation group and 9.8% in the ongoing AFL group. Kaplan–Meier estimation showed similar efficacy for both methods regarding arrhythmia recurrence (log-rank p = 0.07). Conclusions: Our decade-long study indicates that CTI ablation during SR is as effective as ablation during ongoing CTI-dependent AFL in achieving long-term freedom from arrhythmia. This research supports the efficacy of both techniques in clinical settings, validating a widely practiced approach. Full article

A 67-year-old man started treatment due to frequent asymptomatic premature ventricular complexes (PVCs) accidentally being registered during a preventive examination by a specialist, because of which he was referred to cardiologist. During the initial 24-hour (h) ECG monitoring, 4.5% PVCs and one episode of asymptomatic non-sustained ventricular tachycardia (NSVT) with three PVCs in row, at a frequency of 150 beats per minute (bpm), were detected. After the introduction of beta blockers into therapy, a lower number of PVCs, without NSVT, were recorded in the control 24 h Holter ECG, while transthoracic echocardiography (TTE) showed normal left ventricular (LV) systolic function without cardiomyopathy. So, an exercise test was indicated, and it was interrupted in the third minute at 120 beats per minute (bpm) due to fatigue and pain in the hips, without malignant arrhythmias, angina or dyspneic complaints. During the rest period, a significant inferolateral depression of the ST junction was observed, which recovered in the ninth minute. Immediately after the ECG monitoring stopped, the patient lost consciousness; his pulse was not palpable, but breathing was audible, so cardiac massage was started. After he had regained consciousness, the ECG showed alternating sinus and junctional rhythm with the lowest frequency of 33 bpm, which was accompanied by marked hypotension (80/50 mmHg). The patient was immediately hospitalized; coronary angiography and repeated TTE were completely normal, while continuous ECG monitoring did not confirm malignant rhythm disorders or asystole. It was concluded that it was vasovagal syncope (VVS), most likely caused by the Bezold–Jarisch reflex (BJR). Full article

Background: Even though beta-blockers had been used as a first-line therapy for hypertension, since the late 1960s, the Eighth Joint National Committee, JNC 8, decided to recommend them no longer. This decision was based on relatively weak evidence from previous studies, which found that first-line beta-blockers were less effective in reducing stroke and heart failure, the main outcomes of hypertension. Despite the general perception, the most common events caused by hypertension are death and MI, not stroke or heart failure. Therefore, this study aimed to clarify beta-blocker efficacy by incorporating the data from all relevant beta-blocker trials, using the composite outcome of major cardiovascular events. Method: A search was conducted on MEDLINE, PubMed, Embase, and the Cochrane Library, restricted to published, peer-reviewed, human, meta-analysis, and controlled clinical trials. The term words used were “beta-blockers or adrenergic beta antagonists”, “hypertension”, and “death or coronary heart disease or stroke or congestive heart failure or myocardial infarction”. For this research, we selected six randomized controlled trials, and three meta-analyses were also chosen. Results: The results showed that beta-blockers were as effective as other first-line medications in younger hypertensive patients. On the other hand, in the patients aged above 60, the results were mixed. Beta-blockers were more effective than diuretics, but inferior to angiotensin receptor blockers. Also, beta-blockers were as safe and effective as angiotensin-converting enzyme inhibitors in reducing coronary heart disease, myocardial infarction, heart failure, and sudden death. However, beta-blockers were inferior to calcium channel blockers in reducing strokes. Conclusions: Beta-blockers were found to be the most effective in many aspects except for strokes. Further studies are needed to assess beta-blockers’ effectiveness in treating primary hypertension. Full article

Introduction: The problem can be stated as over three billion choices to improve 14 disease states with nine optimization goals (some of the optimization goals are diametrically opposed) to improve dyspnea, shortness of breath, fatigability, exercise intolerance, edema, swelling, fluid retention, and arrhythmias. The goal is to increase the Left Ventricular Outflow Integral, reduce mitral regurgitation, increase longitudinal conduction velocities, and restore synchrony of the septum to the ventricle that needs it the most. The paper is organized in the following sections: (I) Spectrum of Cardiac Disease and Desired Pacing Outcomes; (II) Echo Evaluation of Disease Processes; (III) Pacing Goals in the Spectrum of Disease; (IV) Remodeling—Mathematical Model; (V) Method of Optimization of the Pacing Devices. Conclusions: Pacing trials provided the basic justification for an additional pacing lead but fell short in optimizing individual patients. The physician needs to recognize the spectrum of disease and use the protocol to improve the quality of life of the individual patient. A method to accomplish this task for the spectrum of cardiac disease is presented. Full article

Recent advancements in disease modeling for myocardial infarction (MI) and coronary artery disease (CAD) have significantly enhanced our understanding of cardiovascular pathology and therapeutic development. This review comprehensively reviews the integration of in vivo and in vitro approaches to better model and study these conditions. We specifically focus on cutting-edge in vitro techniques, such as cardiac organoids, engineered heart tissues, and patient-derived induced pluripotent stem cells (iPSCs), which allow for detailed exploration of cellular and molecular mechanisms involved in MI and CAD. These models provide insights into ischemic injury, myocardial remodeling, and the effects of potential therapeutic interventions at a cellular level. In parallel, we discuss advances in the in vivo models, including genetically modified mice and large animal models, which offer valuable information on disease progression, cardiac function, and response to treatments within a more complex physiological context. By bridging these in vivo and in vitro approaches, researchers can gain a more comprehensive understanding of disease mechanisms, validate experimental findings, and accelerate the development of effective therapies. This review highlights recent progress, identifies current limitations, and proposes strategies for future research to enhance the translation of model-based discoveries into clinical practice for MI and CAD. Full article

Background: With the growing trends in recreational marijuana use, our study aims at analyzing the association between acute coronary syndromes (ACS) and ventricular fibrillation (Vfib) and cannabis use disorder in young adults (18–45). Methods: Young adult hospitalizations (18–45 years) with documented ACS/ventricular fibrillation and documented cannabis use were identified from the National Inpatient Sample (2019). Primary outcomes included prevalence and odds of ACS/ventricular fibrillation with cannabis use disorder. Patient factors that held significant association with adverse cardiovascular events in young cannabis users were studied. Propensity scoring and neighbor matching were used to compare resource utilization and in-hospital outcomes in the study population. Results: Among young patients (18–45) admitted for ACS, documented cannabis use disorder (CUD) had a statistically significant association with an odds ratio of 2.29 (2.48–3.04) after adjusting for age, sex, race, household income, smoking, cocaine use, uncontrolled hypertension, diabetes and hyperlipidemia. Documented CUD had a significant association with ventricular fibrillation in the population with an odds ratio of 2.29 (1.51–3.49) after adjusting for the above-mentioned factors. Among admissions with documented CUD, patient factors that held significant association with admitting diagnosis of ACS/Vfib were: black race (OR: 1.73), uncontrolled hypertension (OR: 4.08) and diabetes (OR: 2.45). Propensity-matched cohorts with documented CUD and ACS had significantly higher mean length of hospital stay 3.28 (2.98–3.53) days when compared to the cohort without documented CUD, 2.69 (2.32–2.82) days. The mean of total hospital charges was higher in the cohort with documented CUD at $92,390.64 (92,240.31–92,445.76) compared to $90,886.44 (89,932.21–91,042.56) in the cohort without cannabis use disorder. Conclusions: Documented diagnosis of cannabis use disorder had statistically significant association with admission diagnosis of ACS/Vfib even after accounting for confounders. A documented race as black and co-existing diagnosis of uncontrolled hypertension and diabetes had a significant association with admission diagnosis of ACS in the population with documented cannabis use disorder. Propensity-matched cohorts with cannabis use disorder with the main admitting diagnosis of ACS/Vfib were associated with a higher mean length of hospital stay and a higher mean of total charges compared to the matched cohorts without documented cannabis use disorder. Full article

Atherosclerosis is an inflammatory disease wherein neutrophils play a key role in plaque evolution. We observed that neutrophil CD11b was associated with a higher necrotic core volume in coronary plaques. Since platelets modulate neutrophil function, we explored the influence of neutrophil–platelet conjugates on the cytokine-modulated neutrophil complex CD11b/CD18 and CCR5 receptor expression. In 55 patients [68.53 ± 7.95 years old (mean ± SD); 71% male], neutrophil positivity for CD11b, CD18 and CCR5 was expressed as Relative Fluorescence Intensity (RFI) and taken as a dependent variable. Cytokines and chemokines were assessed by ELISA. Following log-10-based logarithmic transformation, they were used as independent variables in Model 1 of multiple regression together with Body Mass Index and albumin. Model 1 was expanded with the RFI of neutrophil CD41a+ (model 2). The RFI of neutrophil CD41a+ correlated positively and significantly with CD11b, CD18, and CCR5. In Model 2, CCR5 correlated positively only with the RFI of neutrophil CD41a+. Albumin maintained its positive effect on CD11b in both models. These observations indicate the complexity of neutrophil phenotypic modulation in stable CAD. Despite limitations, these findings suggest there is a role played by neutrophil–platelet interaction on the neutrophil cytokine-modulated expression of adhesive and chemotactic receptors. Full article