The association between GRACE score at admission for myocardial infarction and the incidence of sudden cardiac arrests in long-term follow-up - the MADDEC study.

Background. Sudden cardiac arrest (SCA), often also leading to sudden cardiac death (SCD), is a common complication in coronary artery disease. Despite the effort there is a lack of applicable prediction tools to identify those at high risk. We tested the association between the validated GRACE score and the incidence of SCA after myocardial infarction. Material and methods. A retrospective analysis of 1,985 patients treated for myocardial infarction (MI) between January 1st 2015 and December 31st 2018 and followed until the 31st of December of 2021. The main exposure variable was patients' GRACE score at the point of admission and main outcome variable was incident SCA after hospitalization. Their association was analyzed by subdistribution hazard (SDH) model analysis. The secondary endpoints included SCA in patients with no indication to implantable cardioverter-defibrillator (ICD) device and incident SCD. Results. A total of 1985 patients were treated for MI. Mean GRACE score at baseline was 118.7 (SD 32.0). During a median follow-up time of 5.3 years (IQR 3.8-6.1 years) 78 SCA events and 52 SCDs occurred. In unadjusted analyses one SD increase in GRACE score associated with over 50% higher risk of SCA (SDH 1.55, 95% CI 1.29-1.85, p < 0.0001) and over 40% higher risk for SCD (1.42, 1.12-1.79, p = 0.0033). The associations between SCA and GRACE remained statistically significant even with patients without indication for ICD device (1.57, 1.30-1.90, p < 0.0001) as well as when adjusting with patients LVEF and omitting the age from the GRACE score to better represent the severity of the cardiac event. The association of GRACE and SCD turned statistically insignificant when adjusting with LVEF. Conclusions. GRACE score measured at admission for MI associates with long-term risk for SCA.

What is already known about this subject?Nearly 50% of cardiac mortality is caused by sudden cardiac death, often due to sudden cardiac arrest.Despite the effort, there is a lack of applicable prediction tools to identify those at high risk.What does this study add?This study shows that GRACE score measured at the point of admission for myocardial infarction can be used to evaluate patients' risk for sudden cardiac arrest in a long-term follow-up.How might this impact on clinical practice?Based on our findings, the GRACE score at the point of admission could significantly affect the patients' need for an ICD device after hospitalization for MI and should be considered as a contributing factor when evaluating the patients' follow-up care.

Chronic intermittent hypoxia-induced cardiovascular and renal dysfunction: from adaptation to maladaptation.

Chronic intermittent hypoxia (CIH) is the dominant pathological feature of human obstructive sleep apnoea (OSA), which is highly prevalent and associated with cardiovascular and renal diseases. CIH causes hypertension, centred on sympathetic nervous overactivity, which persists following removal of the CIH stimulus. Molecular mechanisms contributing to CIH-induced hypertension have been carefully delineated. However, there is a dearth of knowledge on the efficacy of interventions to ameliorate high blood pressure in established disease. CIH causes endothelial dysfunction, aberrant structural remodelling of vessels and accelerates atherosclerotic processes. Pro-inflammatory and pro-oxidant pathways converge on disrupted nitric oxide signalling driving vascular dysfunction. In addition, CIH has adverse effects on the myocardium, manifesting atrial fibrillation, and cardiac remodelling progressing to contractile dysfunction. Sympatho-vagal imbalance, oxidative stress, inflammation, dysregulated HIF-1α transcriptional responses and resultant pro-apoptotic ER stress, calcium dysregulation, and mitochondrial dysfunction conspire to drive myocardial injury and failure. CIH elaborates direct and indirect effects in the kidney that initially contribute to the development of hypertension and later to chronic kidney disease. CIH-induced morphological damage of the kidney is dependent on TLR4/NF-κB/NLRP3/caspase-1 inflammasome activation and associated pyroptosis. Emerging potential therapies related to the gut-kidney axis and blockade of aryl hydrocarbon receptors (AhR) are promising. Cardiorenal outcomes in response to intermittent hypoxia present along a continuum from adaptation to maladaptation and are dependent on the intensity and duration of exposure to intermittent hypoxia. This heterogeneity of OSA is relevant to therapeutic treatment options and we argue the need for better stratification of OSA phenotypes.

Transvenous versus subcutaneous implantable cardioverter defibrillators in young cardiac arrest survivors.

Secondary prevention implantable cardioverter defibrillators (ICDs) are indicated in young patients presenting with aborted sudden cardiac death (SCD) because of ventricular arrhythmias. Transvenous-ICDs (TV-ICDs) are effective, established therapies supported by evidence. The significant morbidity associated with transvenous leads led to the development of the newer subcutaneous-ICD (S-ICD). This review discusses the clinical considerations when selecting an ICD for the young patient presenting with out-of-hospital cardiac arrest. The major benefits of TV-ICDs are their ability to pace (antitachycardia pacing [ATP], bradycardia support and cardiac resynchronisation therapy [CRT]) and the robust evidence base supporting their use. Other benefits include a longer battery life. Significant complications associated with transvenous leads include pneumothorax and tamponade during insertion and infection and lead failure in the long term. Comparatively, S-ICDs, by virtue of having no intravascular leads, prevent these complications. S-ICDs have been associated with a higher incidence of inappropriate shocks. Patients with an indication for bradycardia pacing, CRT or ATP (documented ventricular tachycardia) are seen as unsuitable for a S-ICD. If venous access is unsuitable or undesirable, S-ICDs should be considered given the patient is appropriately screened. There is a need for further randomised controlled trials to directly compare the two devices. TV-ICDs are an effective therapy for preventing SCD limited by significant lead-related complications. S-ICDs are an important development hindered largely by an inability to pace. Young patients stand to gain the most from a S-ICD as the cumulative risk of lead-related complications is high. A clinical framework to aid decision-making is presented.

RyR2 disease mutations at the C-terminal domain intersubunit interface alter closed-state stability and channel activation.

Ryanodine receptors (RyRs) are ion channels that mediate the release of Ca2+ from the sarcoplasmic reticulum/endoplasmic reticulum, mutations of which are implicated in a number of human diseases. The adjacent C-terminal domains (CTDs) of cardiac RyR (RyR2) interact with each other to form a ring-like tetrameric structure with the intersubunit interface undergoing dynamic changes during channel gating. This mobile CTD intersubunit interface harbors many disease-associated mutations. However, the mechanisms of action of these mutations and the role of CTD in channel function are not well understood. Here, we assessed the impact of CTD disease-associated mutations P4902S, P4902L, E4950K, and G4955E on Ca2+- and caffeine-mediated activation of RyR2. The G4955E mutation dramatically increased both the Ca2+-independent basal activity and Ca2+-dependent activation of [3H]ryanodine binding to RyR2. The P4902S and E4950K mutations also increased Ca2+ activation but had no effect on the basal activity of RyR2. All four disease mutations increased caffeine-mediated activation of RyR2 and reduced the threshold for activation and termination of spontaneous Ca2+ release. G4955D dramatically increased the basal activity of RyR2, whereas G4955K mutation markedly suppressed channel activity. Similarly, substitution of P4902 with a negatively charged residue (P4902D), but not a positively charged residue (P4902K), also dramatically increased the basal activity of RyR2. These data suggest that electrostatic interactions are involved in stabilizing the CTD intersubunit interface and that the G4955E disease mutation disrupts this interface, and thus the stability of the closed state. Our studies shed new insights into the mechanisms of action of RyR2 CTD disease mutations.

Stroke-Heart Syndrome: Incidence and Clinical Outcomes of Cardiac Complications Following Stroke.

BACKGROUND: The risk of major adverse cardiovascular events is substantially increased following a stroke. Although exercise-based cardiac rehabilitation has been shown to improve prognosis following cardiac events, it is not part of routine care for people following a stroke. We, therefore, investigated the association between cardiac rehabilitation and major adverse cardiovascular events for people following a stroke. Following a stroke, individuals have an increased risk of new-onset cardiovascular complications. However, the incidence and long-term clinical consequence of newly diagnosed cardiovascular complications following a stroke is unclear. The aim of the present study was to investigate the incidence and long-term clinical outcomes of newly diagnosed cardiovascular complications following incident ischemic stroke. METHODS: A retrospective cohort study was conducted using anonymized electronic medical records from 53 participating health care organizations. Patients with incident ischemic stroke aged ≥18 years with 5 years of follow-up were included. Patients who were diagnosed with new-onset cardiovascular complications (heart failure, severe ventricular arrhythmia, atrial fibrillation, ischemic heart disease, Takotsubo syndrome) within 4-weeks (exposure) of incident ischemic stroke were 1:1 propensity score-matched (age, sex, ethnicity, comorbidities, cardiovascular care) with ischemic stroke patients who were not diagnosed with a new-onset cardiovascular complication (control). Logistic regression models produced odds ratios (OR) with 95% CIs for 5-year incidence of all-cause mortality, recurrent stroke, hospitalization, and acute myocardial infarction. RESULTS: Of 365 383 patients with stroke with 5-year follow-up: 11.1% developed acute coronary syndrome; 8.8% atrial fibrillation/flutter; 6.4% heart failure; 1.2% severe ventricular arrythmias; and 0.1% Takotsubo syndrome within 4 weeks of incident ischemic stroke. Following propensity score matching, odds of 5-year all-cause mortality were significantly higher in stroke patients with acute coronary syndrome (odds ratio, 1.49 [95% CI, 1.44-1.54]), atrial fibrillation/flutter (1.45 [1.40-1.50]), heart failure (1.83 [1.76-1.91]), and severe ventricular arrhythmias (2.08 [1.90-2.29]), compared with matched controls. Odds of 5-year rehospitalization and acute myocardial infarction were also significantly higher for patients with stroke diagnosed with new-onset cardiovascular complications. Takotsubo syndrome was associated with significantly higher odds of 5-year composite major adverse cardiovascular events (1.89 [1.29-2.77]). Atrial fibrillation/flutter was the only new-onset cardiac complication associated with significantly higher odds of recurrent ischemic stroke at 5 years (1.10 [1.07-1.14]). CONCLUSIONS: New-onset cardiovascular complications diagnosed following an ischemic stroke are very common and associate with significantly worse 5-year prognosis in terms of major adverse cardiovascular events. People with stroke and newly diagnosed cardiovascular complications had >50% prevalence of recurrent stroke at 5 years.

Bruton's tyrosine kinase Inhibitors and Cardiotoxicity: More Than Just Atrial Fibrillation.

PURPOSE OF REVIEW: The purpose of this review is to summarize the epidemiology, mechanisms, and management of cardiovascular complications of Bruton's Tyrosine Kinase inhibitors (BTKIs). RECENT FINDINGS: Ibrutinib increases the risk of atrial fibrillation, bleeding, and hypertension compared with non-BTKI therapies. The evidence to support an association between ibrutinib and other cardiovascular complications including ventricular tachyarrhythmias or cardiomyopathy is limited. Ibrutinib metabolism can be inhibited by some medications used to treat cardiovascular complications. The cardiovascular effects of more selective BTKIs, such as acalabrutinib, remain to be determined. Future research should address the mechanisms underlying the cardiovascular complications of BTKIs and how best to manage them. The risks and benefits of more selective BTKIs as compared with ibrutinib require further evaluation.

Acute interaction between human epicardial adipose tissue and human atrial myocardium induces arrhythmic susceptibility.

Epicardial adipose tissue (EAT) deposition has a strong clinical association with atrial arrhythmias; however, whether a direct functional interaction exists between EAT and the myocardium to induce atrial arrhythmias is unknown. Therefore, we aimed to determine whether human EAT can be an acute trigger for arrhythmias in human atrial myocardium. Human trabeculae were obtained from right atrial appendages of patients who have had cardiac surgery (n = 89). The propensity of spontaneous contractions (SCs) in the trabeculae (proxy for arrhythmias) was determined under physiological conditions and during known triggers of SCs (high Ca2+, ß-adrenergic stimulation). To determine whether EAT could trigger SCs, trabeculae were exposed to superfusate of fresh human EAT, and medium of 24 h-cultured human EAT treated with ß1/2 (isoproterenol) or ß3 (BRL37344) adrenergic agonists. Without exposure to EAT, high Ca2+ and ß1/2-adrenergic stimulation acutely triggered SCs in, respectively, 47% and 55% of the trabeculae that previously were not spontaneously active. Acute ß3-adrenergic stimulation did not trigger SCs. Exposure of trabeculae to either superfusate of fresh human EAT or untreated medium of 24 h-cultured human EAT did not induce SCs; however, specific ß3-adrenergic stimulation of EAT did trigger SCs in the trabeculae, either when applied to fresh (31%) or cultured (50%) EAT. Additionally, fresh EAT increased trabecular contraction and relaxation, whereas media of cultured EAT only increased function when treated with the ß3-adrenergic agonist. An acute functional interaction between human EAT and human atrial myocardium exists that increases the propensity for atrial arrhythmias, which depends on ß3-adrenergic rather than ß1/2-adrenergic stimulation of EAT.

Bolus potassium in frustrated ventricular fibrillation storm.

BACKGROUND: Ventricular fibrillation (VF) is a well-known ominous complication of ischemic heart disease. While firmly structured algorithms have been developed for its management, yet its mortality rate remains high. CASE PRESENTATION: This is a case report of a 46-year-old gentleman who was a victim of recurrent cardiac arrest in the ward while awaiting coronary artery bypass grafting (CABG) surgery. Emergency CABG was performed, intraoperatively he experienced recurrent VF which was reverted by direct current cardioversion-Defibrillation. He was sent to the Cardiac Surgery Intensive Care Unit (CSICU) with an open chest on extracorporeal membrane oxygenation (ECMO) support and an intra-aortic balloon pump. Postoperatively in CSICU he still experienced malignant ventricular arrhythmia with dropping of ejection fraction to less than 10%. The last few episodes of VF were lengthy, lasting more than an hour (while on ECMO support) with the failure of various antiarrhythmic medications to abort them. Eventually, a decision was made to give him 20 mmol boluses of potassium chloride (KCl) intravenously aiming at introducing a state of asystole, but the rhythm changed to sinus rhythm. CONCLUSIONS: This report highlighted the fact that optimum management of VF is still lacking and necessitates more studies. The appropriate effective dose of potassium replacement during VF might need to be reconsidered in patients with persistent VF.

Assessment of the risk of QT-interval prolongation associated with potential drug-drug interactions in patients admitted to Intensive Care Units.

OBJECTIVES: To evaluate the relationship between drug interactions and QT-interval prolongation in patients admitted to a general intensive care unit (ICU). METHODS: This study was approved by the Institutional Review Board and written informed consent was obtained from all patients. From May 2015 to July 2016, all patients over 18 years-old admitted to the ICU for more than 24 h and in whom the QT-interval on the ECG could be read were prospectively included in this observational, cross-sectional study. All medications administered in the 24 h prior to admission were recorded and the QT-interval was measured upon ICU admission and corrected with Bazzet's formula (QTc). Drug-drug interactions involving drugs potentially associated with QTc prolongation (DDIQT) were searched and QTc increase associated with pharmacokinetic (PK-DDIQT) and pharmacodynamic (PD-DDIQT) interactions was assessed with multiple regression adjusted by patient varibles. RESULTS: The study population consisted of 283 patients, 54.4% males, mean age 57.6 ±â€¯16.7 years-old. Forty five (15.9%) patients presented 65 DDIQT with predominance of pharmacodynamic (66.1%). The risk of DDIQT prescription increased with lower systolic blood pressure, in hypokalemia, in non-diabetics and with the number of medications. PK-DDIQT alone did not affect the QTc interval (7.75 ms, 95%CI: -22.4 to 37.9 ms, p = 0.61), but PD-DDIQT increased QTc by 28.4 ms (95%CI: 9.67 to 47.4 ms, p = 0.003). Most PD-DDIQT involved metoclopramide with ondansetron or amiodarone, and ondansetron with ciprofloxacin. CONCLUSIONS: In patients exposed to drugs associated with prolonged QTc in the 24 h prior to ICU admission, pharmacodynamic DDIQT are associated with increased risk of QTc prolongation.

Seizure secondary to cardiac arrythmias.

BACKGROUND: The relationship between seizure activity and arrhythmias is not well established. Sinus tachycardia is commonly seen post seizure. Bradyarrythmias leading to seizure activity is rarely reported in the literature thus far. CASE PRESENTATION: A 62-year-old lady presented with nocturnal seizures and was subsequently started on oral anti-convulsant with no relief of her symptoms. Further investigations led to outpatient ambulatory ECGs which showed marked sinus bradycardia prior to seizure activity and post seizure atrial fibrillation with fast ventricular rate. The patient was commenced on oral anticoagulant and beta blocker for ventricular rate control in view of atrial fibrillation. A backup dual chamber permanent pacemaker was implanted to treat the bradycardia. The patient became seizure free since the implantation of permanent pacemaker. CONCLUSION: This case stresses the importance of investigating and treating cardiac arrhythmias underlying seizure activity.

The Unseen Side of Feline Hypertrophic Cardiomyopathy: Diagnostic and Prognostic Utility of Electrocardiography and Holter Monitoring.

Hypertrophic cardiomyopathy (HCM) is a common heart disease in cats, characterized by regional or diffuse hypertrophy of the left ventricular walls, with an uncertain etiology and heterogenous natural history. Several types of rhythm disturbances are often associated with the disease. This study conducts a comprehensive review of the current literature, in order to evaluate the diagnostic and prognostic effectiveness of electrocardiography and Holter monitoring in the management of feline hypertrophic cardiomyopathy. The main subjects of discussion will include general information about HCM and its connection to arrhythmias. We will explore the rhythm disturbances documented in the current literature on Holter monitoring, as well as the techniques used for Holter monitoring. Additionally, the review will cover classical electrocardiography (ECG) and its diagnostic utility. Prognostic indicators and anti-arrhythmic therapy will also be discussed in detail. The findings highlight the importance of understanding arrhythmias in feline HCM for accurate diagnosis, risk assessment, and therapeutic intervention. ECG and Holter monitoring may offer valuable insights into managing feline HCM.

Nose-to-Heart Approach: Unveiling an Alternative Route of Acute Treatment.

Intranasal (IN) administration has emerged as a novel approach for rapid systemic absorption, with potential applicability in the management of acute cardiovascular events. This review explores the evolution of IN cardiovascular pharmacotherapy, emphasizing its potential in achieving systemic effects and bypassing the first-pass metabolism associated with oral administration. The extensive vascularization of nasal mucosa and a porous endothelial basement membrane facilitate efficient drug absorption into the bloodstream. The IN route ensures a critical swift onset of action, which allows self-administration in at-home settings. For instance, etripamil nasal spray, a first-in-class formulation, exemplifies the therapeutic potential of this approach in the treatment of spontaneous supraventricular tachycardia. The review critically assesses studies on IN formulations for angina, acute myocardial infarction, hypertensive episodes, and cardiac arrhythmias. Preclinical evaluations of beta-blockers, calcium-channel blockers, and antianginal drugs demonstrate the feasibility of IN administration for acute cardiovascular events. A small number of clinical trials have revealed promising results, emphasizing the superiority of IN drug delivery over oral administration in terms of bioavailability and onset of action. Unambiguously, the limited clinical trials and patient enrollment pose challenges in generalizing experimental outcomes. However, the nose-to-heart approach has clinical potential.

Arrhythmias: Its Occurrence, Risk Factors, Therapy, and Prognosis in Acute Coronary Syndrome.

BACKGROUND: Patients with acute coronary syndrome may lead to various metabolic and electrophysiological changes that induce both asymptomatic and symptomatic life-threatening arrhythmias, which increases morbidity and mortality. METHODS: This observational retrospective study was conducted at Manmohan Cardiothoracic Vascular and Transplant Center, Institute of Medicine, Maharajgunj, Kathmandu, Nepal. Three hundred ninety-five patients with a diagnosis of acute coronary syndrome were enrolled in the study. RESULTS: A total of 395 patients were included in the study with a mean age of patients 61.29± 13.5 years and with male predominance. A total number of 115 cases of arrhythmia were recorded among which the most common were atrioventricular block (10%), reperfusion arrhythmia (9.6%) followed by ventricular premature complex (8%), atrial fibrillation/flutter (6%), and ventricular tachycardia/fibrillation (5%). There was a significant difference in the incidence of arrhythmia in acute coronary syndrome group. STEMI (39.7%), NSTEMI 26(20.8%) and unstable angina11(14.8%) respectively (p=<0.001). Reperfusion arrhythmia was present in 89.47% of STEMI and 10.4 % of NSTEMI/ unstable angina and was statistically significant (p-value <0.001). A total of three patients (0.7%) needed permanent pacemaker insertion in the acute coronary syndrome group. All of these patients were STEMI which was 1.5% of total STEMI, two in inferior wall STEMI (2.6%) and 1 in anterior wall STEMI (0.8%). The total in-hospital mortality was 20 (5.06%), 17(8.6%) among STEMI and 3(2.4%) among NSTEMI, and none in unstable angina (P =<0.001). Pulmonary edema (12.9%) was the most common in-hospital outcome followed by cardiac arrest (7.6%). CONCLUSIONS: Arrhythmia in acute coronary syndrome is a common problem and may lead to structural and functional impairment of myocardial function.

A perspective on Notch signalling in progression and arrhythmogenesis in familial hypertrophic and dilated cardiomyopathies.

In this perspective, we discussed emerging data indicating a role for Notch signalling in inherited disorders of the heart failure with focus on hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) linked to variants of genes encoding mutant proteins of the sarcomere. We recently reported an upregulation of elements in the Notch signalling cascade in cardiomyocytes derived from human inducible pluripotent stem cells expressing a TNNT2 variant encoding cardiac troponin T (cTnT-I79N+/-), which induces hypertrophy, remodelling, abnormalities in excitation-contraction coupling and electrical instabilities (Shafaattalab S et al. 2021 Front. Cell Dev. Biol. 9, 787581. (doi:10.3389/fcell.2021.787581)). Our search of the literature revealed the novelty of this finding and stimulated us to discuss potential connections between the Notch signalling pathway and familial cardiomyopathies. Our considerations focused on the potential role of these interactions in arrhythmias, microvascular ischaemia, and fibrosis. This finding underscored a need to consider the role of Notch signalling in familial cardiomyopathies which are trigged by sarcomere mutations engaging mechano-signalling pathways for which there is evidence of a role for Notch signalling with crosstalk with Hippo signalling. Our discussion included a role for both cardiac myocytes and non-cardiac myocytes in progression of HCM and DCM. This article is part of the theme issue 'The heartbeat: its molecular basis and physiological mechanisms'.

Fluoroless Catheter Ablation of Left Ventricular Summit Arrhythmias: A Step-by-Step Approach.

Prolonged use of fluoroscopy during catheter ablation (CA) of arrhythmias is associated with a significant exposure to ionizing radiation and risk of orthopedic injuries given the need for heavy protective equipment. CA of ventricular arrhythmias (VAs) arising from the left ventricular (LV) summit is challenging, requiring a vast knowledge of the intricate cardiac anatomy of this area and careful imaging delineation of the different anatomical structures, which is frequently performed using fluoroscopic guidance. Certain techniques, including pericardial mapping and ablation, use of intracoronary wires, and mapping and ablation inside the coronary venous system have been proposed, further prolonging fluoroscopy time. Fluoroless CA procedures are feasible with currently available technology and appear to have similar safety and efficacy outcomes compared with conventional techniques. To successfully perform fluoroless CA of LV summit arrhythmias, it is important to be fully acquainted with intracardiac echocardiography (ICE) imaging and electroanatomic mapping (EAM). We will describe our approach to perform fluoroless CA in LV summit VAs.

A Patient with Epilepsy Presenting for a Dental Hygiene Visit.

All dentists should be trained in the diagnosis and management of seizures in a dental chair. Although epilepsy is a common etiological factor, there are other medical situations whereby seizures are manifested. Once a seizure is suspected and other causes of altered consciousness or involuntary motor movements are ruled out, proper management should commence immediately. The first step in management is to immediately remove/stop all provocative factors, like bright flashing lights, drill sounds, and such. Benzodiazepines remain as the first-line treatment for patients with continued seizures before activating emergency medical services.

Anticoagulant Treatment Adherence and Persistence in German Patients with Atrial Fibrillation.

INTRODUCTION: Treatment adherence and persistence impact the effectiveness of edoxaban for the prevention of thromboembolism in patients with atrial fibrillation (AF). The objective of this analysis was to assess adherence and persistence of edoxaban vs. other non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs). METHODS: Utilizing a German claims database, adults with AF with the first pharmacy claim identified for edoxaban, apixaban, dabigatran, rivaroxaban, or VKAs from January 2013 to December 2017 were included in a propensity score-matched analysis. The first pharmacy claim was the index claim. Adherence (i.e., proportion of days covered [PDC]) and persistence (proportion of patients who continued therapy) were compared between edoxaban and other therapies. Patients receiving once-daily (QD) vs. twice-daily (BID) NOAC were also analyzed. RESULTS: Overall, 21,038 patients were included (1236 edoxaban, 6053 apixaban, 1306 dabigatran, 7013 rivaroxaban, and 5430 VKA). After matching, baseline characteristics were well balanced across cohorts. Adherence was significantly higher for edoxaban vs. apixaban, dabigatran, and VKAs (all P < 0.0001). Significantly more edoxaban patients continued therapy vs. rivaroxaban (P = 0.0153), dabigatran (P < 0.0001), and VKAs (P < 0.0001). Time to discontinuation was significantly longer for edoxaban vs. dabigatran, rivaroxaban, and VKAs (all P < 0.0001). More patients receiving NOACs QD had a PDC ≥ 0.8 compared with those receiving NOACs BID (65.3 vs. 49.6%, respectively; P < 0.05); persistence rates were comparable between QD and BID groups. CONCLUSIONS: Patients with AF receiving edoxaban had significantly higher adherence and persistence compared with those receiving VKAs. This trend was also seen in NOAC QD regimens vs. NOAC BID regimens for adherence. These results provide insight into how adherence and persistence may contribute to the effectiveness of edoxaban for stroke prevention in patients with AF in Germany.

Cfdp1 Is Essential for Cardiac Development and Function.

Cardiovascular diseases (CVDs) are the prevalent cause of mortality worldwide. A combination of environmental and genetic effectors modulates the risk of developing them. Thus, it is vital to identify candidate genes and elucidate their role in the manifestation of the disease. Large-scale human studies have revealed the implication of Craniofacial Development Protein 1 (CFDP1) in Coronary Artery Disease (CAD). CFDP1 belongs to the evolutionary conserved Bucentaur (BCNT) family, and to date, its function and mechanism of action in Cardiovascular Development are still unclear. We utilized zebrafish to investigate the role of cfdp1 in the developing heart due to the high genomic homology, similarity in heart physiology, and ease of experimental manipulations. We showed that cfdp1 was expressed during development, and we tested two morpholinos and generated a cfdp1 mutant line. The cfdp1-/- embryos developed arrhythmic hearts and exhibited defective cardiac performance, which led to a lethal phenotype. Findings from both knockdown and knockout experiments showed that abrogation of cfdp1 leads to downregulation of Wnt signaling in embryonic hearts during valve development but without affecting Notch activation in this process. The cfdp1 zebrafish mutant line provides a valuable tool for unveiling the novel mechanism of regulating cardiac physiology and function. cfdp1 is essential for cardiac development, a previously unreported phenotype most likely due to early lethality in mice. The detected phenotype of bradycardia and arrhythmias is an observation with potential clinical relevance for humans carrying heterozygous CFDP1 mutations and their risk of developing CAD.

The Integration of Artificial Intelligence Into Patient Care: A Case of Atrial Fibrillation Caught by a Smartwatch.

Artificial intelligence (AI) offers a wide range of applications in clinical practice, and new technologies are rapidly evolving the healthcare industry and enhancing outcomes. Smartwatches represent the most popular type of wearable AI device that can assist people in detecting cardiac arrhythmias via constant monitoring of heart activity. Numerous advantages result from integrating AI into healthcare systems, including improved patient care, lower rates of medical errors, better treatment recommendations, and more accurate diagnosis of diseases. However, doubts still remain regarding the adoption of AI into patient care due to the challenges it poses. In this paper, we report a case of atrial fibrillation (AF) in a young patient that was detected by his smartwatch. We also highlight some of the benefits and challenges of AI applications in healthcare.