Aging-Related Protein Alterations in the Brain.

Aging is an intrinsic aspect of an organism's life cycle and is characterized by progressive physiological decline and increased susceptibility to mortality. Many age-associated disorders, including neurological disorders, are most commonly linked with the aging process, such as Alzheimer's disease (AD). This review aims to provide a comprehensive overview of the effects of aging and AD on the molecular pathways and levels of different proteins in the brain, including metalloproteins, neurotrophic factors, amyloid proteins, and tau proteins. AD is caused by the aggregation of amyloid proteins in the brain. Factors such as metal ions, protein ligands, and the oligomerization state of amyloid precursor protein significantly influence the proteolytic processing of amyloid-ß protein precursor (AßPP). Tau, a disordered cytosolic protein, serves as the principal microtubule-associated protein in mature neurons. AD patients exhibit decreased levels of nerve growth factor within their nervous systems and cerebrospinal fluid. Furthermore, a significant increase in brain-derived neurotrophic factor resulting from the neuroprotective effect of glial cell line-derived neurotrophic factor suggests that the synergistic action of these proteins plays a role in inhibiting neuronal degeneration and atrophy. The mechanism through which Aß and AßPP govern Cu2+ transport and their influence on Cu2+ and other metal ion pools requires elucidation in future studies. A comprehensive understanding of the influence of aging and AD on molecular pathways and varying protein levels may hold the potential for the development of novel diagnostic and therapeutic methods for the treatment of AD.

Sensitivity and Specificity of Wearables for Atrial Fibrillation in Elderly Populations: A Systematic Review.

PURPOSE OF REVIEW: This study aims to evaluate the sensitivity and specificity of wearable devices for AF detection in older adults, as well as examine the incidence of AF across various studies, contextual factors impacting AF detection, and safety and adverse events associated with wearable use. RECENT FINDINGS: A systematic search of three databases identified 30 studies on wearables for AF detection in older adults, encompassing 111,798 participants. Both PPG-based and single-lead electrocardiography-based wearables show scalable potential for screening and managing AF. The results of this systematic review demonstrate that wearable devices, such as smartwatches, can effectively identify arrhythmias like AF in older adults, with scalable potential in PPG-based and single-lead electrocardiography-based wearables. As wearable technologies continue to gain prominence in healthcare, it is crucial to understand their challenges and incorporate them as preventative and monitoring tools for AF detection in elderly populations to improve patient care and prevention techniques.

Limitations of Unipolar Signals in Guiding Successful Outflow Tract Premature Ventricular Contraction Ablation.

BACKGROUND: Unipolar electrograms (UniEGMs) are commonly used to annotate earliest local activation of focal arrhythmias. However, their utility in guiding premature ventricular contractions (PVCs) ablation may be limited when the PVC source is less superficial. OBJECTIVES: The authors sought to compare bipolar electrograms (BiEGMs) vs UniEGMs in guiding successful ablation of right ventricular outflow tract (RVOT) vs intramural outflow tract (OT) PVCs. The authors hypothesized that: 1) earliest bipolar local activation time (LATBi) would better guide mapping and ablation, vs UniEGM dV/dt (LATUni) or QS morphology; and 2) LAT differences using bipolar vs unipolar EGMs (ΔLATBi-Uni) would be greater for intramural OT than RVOT PVCs. METHODS: Consecutive patients undergoing successful PVC ablation 2017 to2020 requiring only RVOT or RVOT+left ventricular OT (RVOT+LVOT) ablation were retrospectively analyzed. BiEGMs and UniEGMs at successful ablation sites were compared. RESULTS: Of 70 patients, 50 required RVOT-only, and 20 required RVOT+LVOT ablation for acute and long-term PVC suppression. Mean ΔLATBi-Uni was lower for RVOT vs RVOT+LVOT groups (9.3 ± 6.4 ms vs 17.4 ± 9.9 ms; P < 0.01). QS UniEGM was seen in 78% of RVOT, compared with 53% of RVOT+LVOT patients (P < 0.016). RVOT+LVOT sites most frequently included the posteroseptal RVOT and adjacent LVOT (73%), and 43% lacked a QS unipolar EGM. ΔLATBi-Uni ≥15 ms best distinguished sites in which RVOT-only vs RVOT+LVOT ablation achieved acute PVC suppression (area under the curve: 0.77). CONCLUSIONS: Earliest BiEGM activation guides successful ablation of OT PVCs better than UniEGM-guided analysis, especially when an intramural PVC source is present.

Safety and efficacy of left atrial appendage closure using an epicardial suture snaring device: Systematic review and current status.

INTRODUCTION: The LARIAT epicardial suture snaring device has been fraught with technical challenges and procedural complications. Over time, technique modification and improved operator experience have helped overcome many of these challenges. METHODS AND RESULTS: Studies reporting left atrial appendage epicardial closure over a 12-year period from 2009 to 2020 were evaluated. The primary efficacy outcome evaluated was left atrial appendage closure with residual flow ≤1 mm. Safety outcomes evaluated were periprocedural and long term complications after device placement. Nine studies consisting of 1430 patients were included in this analysis, of which 1386 (97%) underwent successful device placement. The mean age was 69.3 years, with a mean CHADS2 -VASC score of 3.78. Primary efficacy end point was achieved in 95.8% patients immediately after device placement, and in 92.8% patients on long term follow-up. Early procedural complications consisted of pericardial effusion 5.6%, cardiac perforation 2.7%, pericarditis 2.6%, and need for open heart surgery 1.5%. Long term complications consisted of all-cause mortality 2.3%, stroke 1.5%, and left atrial appendage thrombus 2.3%. Reduced complications were noted using micropuncture needles (2.20% vs. 10.14%; p < .0001), a longer duration pericardial drainage, and use of anti-inflammatory medications (1.58% vs. 8.4%). Oral anticoagulation use decreased from 44.7% to 22.9% post device implantation, and to 8.5% on last clinical follow up. CONCLUSIONS: The LARIAT device is effective in epicardial closure of the left atrial appendage. Improvement in device techniques such as use of micropuncture needle, prophylactic colchicine, and maintenance of a pericardial drain have helped improve safety over time.

Catastrophic Cardiac Complications of Takayasu's Arteritis.

Takayasu's arteritis (TA) causes inflammation and necrosis of vessel walls, leading to aneurysm formation, extensive coronary damage and valvular abnormalities. We review a case of recurrent coronary, aortic and mitral valve involvement in a patient with TA and discuss the various treatment options available for such patients.

Pacemaker Implantation in Patient With Persistent Left Superior Vena Cava and Absent Right Superior Vena Cava.

Persistent left superior vena cava (LSVC) is an asymptomatic congenital heart disease. It is usually found incidentally on imaging, during central line placements or while undergoing electrophysiological procedures. We present a case of a 91-year-old female who initially presented with seizures and was diagnosed with tachy-brady syndrome. She was planned to undergo dual-chamber permanent pacemaker placement. However, during the procedure, she was incidentally found to have an LSVC without a right superior vena cava. Due to challenging anatomy, her pacemaker was changed to a single-chamber atrial lead pacemaker. This case highlights the clinical implications of this unusual structural anomaly, technical difficulties that arise alongside and solutions on how to overcome these issues in the context of pacemaker implantation.

Ventricular Septal Aneurysm Mimicking Right Ventricular Outflow Tract Mass in a Patient With Ventricular Septal Defect.

A 50-year-old man presented with an episode of chest pain. Cardiac magnetic resonance revealed the presence of a large ventricular septal aneurysm partially closing a perimembranous ventricular septal defect, prolapsing into the right ventricular outflow tract, and mimicking a mass. We illustrate the diagnostic approach and management of such ventricular septal aneurysms. (Level of Difficulty: Advanced.).

Large Coronary Arteries Mean No Chance of a Heart Attack, Right? An Acute Myocardial Infarction in the Setting of Holding Anticoagulation for a Routine Colonoscopy.

Coronary artery ectasia (CAE) is an uncommon pathology, which is sometimes incidentally found on left heart catheterization (LHC). CAE is occasionally treated with systemic anticoagulation to prevent thrombosis or progression of the clot in the coronary arteries. We present a 63-year-old male with known CAE on warfarin who presented to the hospital with myocardial infarction after a routine colonoscopy for which anticoagulation was held. His myocardial infarction was attributed to a likely coronary thromboembolic event. This case highlights the need for consideration of bridging anticoagulation therapy before and after procedures in patients with CAE to prevent adverse coronary events.

Atrial fibrillation in hypertrophic cardiomyopathy: prevalence, clinical impact, and management.

Hypertrophic cardiomyopathy (HCM) is the most common hereditary cardiomyopathy characterized by left ventricular hypertrophy and spectrum of clinical manifestation. Atrial fibrillation (AF) is a common sustained arrhythmia in HCM patients and is primarily related to left atrial dilatation and remodeling. There are several clinical, electrocardiographic (ECG), and echocardiographic (ECHO) features that have been associated with development of AF in HCM patients; strongest predictors are left atrial size, age, and heart failure class. AF can lead to progressive functional decline, worsening heart failure and increased risk for systemic thromboembolism. The management of AF in HCM patient focuses on symptom alleviation (managed with rate and/or rhythm control methods) and prevention of complications such as thromboembolism (prevented with anticoagulation). Finally, recent evidence suggests that early rhythm control strategy may result in more favorable short- and long-term outcomes.

Takotsubo Cardiomyopathy Presenting with Sinoatrial Disease: A Rare Presentation.

Takotsubo cardiomyopathy (TCM), or apical ballooning syndrome, is a distinct nonischemic cardiomyopathy mimicking acute coronary syndrome. A 76-year-old female presented with ST elevation in the inferior lead and a troponin level of 0.81 ng/dL. An immediate coronary angiography showed non-obstructive coronary artery disease. A subsequent ventriculogram and echocardiogram showed anteroapical and distal inferior wall hypokinesis suggestive of TCM. Despite therapy with beta blocker, she was observed to have two significant sinus pauses, one eight-second, and a second 29-second pause. An urgent transvenous pacemaker was put in place and later followed by a permanent pacemaker. The patient was discharged on carvedilol and losartan. Although other arrhythmias such as complete heart block, torsades, and ventricular arrhythmias have been commonly reported, the association of TCM with recurrent sinus arrest has rarely been reported in the literature. The occurrence observed in this case implies that patients with TCM should be monitored closely for arrhythmias, and, if such a condition is identified, planning for permanent pacemaker implantation should be started early enough to avoid recurrent life-threatening episodes.

The Disappearing Murmur: Systolic Anterior Motion of the Mitral Valve Leaflet in a Non-hypertrophic Cardiomyopathy Patient.

Systolic anterior motion (SAM) of the mitral valve is a well-known phenomenon associated with left ventricular outflow tract obstruction and hemodynamic compromise. This finding may occur in patients with or without hypertrophic cardiomyopathy. In this report, a patient with no prior medical history presented to the hospital with left-sided chest pain and high-risk echocardiogram (ECG) findings. Left heart catheterization with coronary angiography was negative for coronary artery disease. His initial examination was significant for a systolic murmur due to the underlying SAM, as demonstrated by transthoracic echocardiogram. During his hospitalization, he developed acute heart failure syndrome as a result of dynamic outflow tract obstruction. He was treated with fluid resuscitation with a resolution of his hemodynamic compromise. On a follow-up examination, there was no murmur and SAM was no longer present on echocardiogram. This case demonstrates the importance of recognizing the clinical manifestations of SAM as well as its role in maintaining an appropriate hemodynamic status.

Syncopal Episodes of Arrhythmogenic Right Ventricular Cardiomyopathy in a Patient with Pre-existing Seizure Disorder.

Arrhythmogenic right ventricular cardiomyopathy (ARVC), is a heritable condition that is an important, and under-recognized cause of sudden cardiac death. Microscopically, it is represented by fibrofatty replacement of myocardium involving the right ventricular inflow area, apex, and infundibulum. Common clinical manifestations of ARVC include palpitations, syncope, chest pain, dyspnea, and sudden cardiac death. This is a case of a 25-year-old male with a history of thalassemia, and tonic-clonic seizure status post head trauma with cystic encephalomalacia in left parietal lobe who described recurrent syncope. He was followed by neurology and maintained only on Lamotrigine. Episodes occurred within the span of four weeks and were without prodrome, lasting only a few seconds. On evaluation, blood pressure was 123/69 mmHg. Neurologic exam was grossly normal. Heart was regular rate and rhythm without gallops, murmur, or rub. An EKG showed normal sinus rhythm with an incomplete right bundle branch block and Epsilon waves in leads V1 and V2 without evidence of Brugada syndrome. The patient was admitted and had a 24-hour electroencephalogram that showed no seizure activity. A 2D Echo showed normal left ventricular function and no valvular disease. Eventual cardiac magnetic resonance imaging (MRI) showed small focal outpouchings of the right ventricular free wall. A diagnosis of ARVC was achieved, and the patient underwent electrophysiology (EP) study and successful implantation of a dual-chamber cardioverter defibrillator.

Ten Lifestyle Modification Approaches to Treat Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia affecting three million people in the United States (US). Across different races in the US, the incidence of other races was comparable to that of Caucasian population. This points towards the importance of certain lifestyle modifications that can help prevent and treat this disorder. This article discusses 10 such factors. Smoking has been linked to AF, with almost 36% risk reduction if quit. Hypertension has 56% increased risk of atrial fibrillation in which the role of lifestyle changes is well known. Similarly, alcohol-induced atrial fibrillation has 10% increased risk of atrial fibrillation. On the other hand, several case reports document red bull as the cause of atrial fibrillation. Moreover, the risk of atrial fibrillation is four times higher in patients with obstructive sleep apnea (OSA) independent of other confounding variables. Additionally, it has been shown that acute sleep deprivation increases AF risk by 3.36 times. Furthermore, diabetes mellitus and obesity also contribute greatly to atrial fibrillation. This risk has been shown to be around 40% more with diabetes. Diet itself has an impact: numerous studies have shown Mediterranean diet to reduce the risk of AF and cerebrovascular accident in addition to olive oil, fruits and vegetables. Even emotions are important with 85% less AF on 'happy days'. Needless to mention, yoga has been well demonstrated to have almost 24% reduction in AF. Similarly, physical activity in all forms is beneficial. In summary, lifestyle modifications reduce the incidence of AF, induce more AF remission and also produce successful ablation outcomes.

Cardiovascular Risk of Nonsteroidal Anti-Inflammatory Drugs: An Under-Recognized Public Health Issue.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are drugs with analgesic, anti-inflammatory, and antipyretic activity. Their effect is achieved by the reduction in synthesis of prostanoids. Inhibition of prostanoids is responsible for a substantial risk of adverse effects. The risk of side effects affecting the gastrointestinal tract and kidneys has long been known. The possibilities of blood pressure elevation and the development of congestive heart failure are also widely recognized. Increased incidence of acute myocardial infarction in clinical trials with rofecoxib drew attention to the potential cardiotoxicity of selective cyclooxygenase-2 inhibitors, and similarly, concerns have been raised regarding the cardiovascular safety of non-selective NSAIDs. The safety of NSAIDs with regards to cardiovascular events has been studied in recent years in a large number of retrospective and prospective clinical studies and meta-analyses. The results indicate that cardiotoxicity is a class effect, but the magnitude of the risk is widely variable between individual NSAID drugs. This article aims to summarize the available data on the risk of adverse cardiovascular events with NSAIDs, the clinical impact of these events and possible underlying mechanisms.

A Reversible Cause of Complete Heart Block Causing Chest Pain and Syncope.

Vasospastic angina (VSA), also known as variant or Prinzmetal's angina, is a relatively uncommon cause of retrosternal chest pain with transient ST segment elevation, mainly due to vasospasm in the coronary arteries. This is a case of 37-year-old female who presented with chest pain and syncope. Her initial workup, including echocardiogram, was negative. Subsequently, she was sent home with an event monitor. During the next two weeks, she continued to have recurrent episodes of similar chest pains and presented to her cardiology appointment with a heart rate of 45 bpm and blood pressure of 100/60 mmHg and was taken to hospital emergency department. Event monitor review showed intermittent complete heart block. In the hospital, the electrocardiogram (EKG) showed complete heart block and inferior lead ST elevations concomitantly with the chest pains. Although suspicious for vasospastic angina, coronary artery disease had to be ruled out for which patient underwent coronary angiography without evidence of significant obstructive disease. Immediately thereafter, the patient underwent permanent pacemaker placement without recurrence of syncopal episodes. This case signifies complete heart block as one of the rare complications of vasospastic angina which otherwise can also lead to symptoms such as dizziness, shortness of breath, syncope, cardiac arrest, and sudden cardiac death.