Same-day discharge after transvenous lead extraction: feasibility and outcomes.

AIMS: Same-day discharge (SDD) is safe for patients undergoing electrophysiology procedures. There is no existing data regarding SDD for patients undergoing transvenous lead extraction (TLE). We report our experience with SDD for patients undergoing TLE. METHODS AND RESULTS: The study group included patients undergoing TLE between February 2020 and July 2021 without an infectious indication. A modified SDD protocol for device implants/ablations was applied to TLE patients. Patient characteristics, extraction details, outcomes, and complications were reviewed. Of 239 patients undergoing TLE, 210 were excluded (94 infections and 116 did not meet SDD criteria). Of the remaining 29 patients, seven stayed due to patient preference and 22 were discharged home the same day. The SDD group had an average age of 65.9 ± 12 (47-84), 41% female, and LVEF of 52.2 ± 18% (10-80). The indication for TLE was malfunction (20), upgrade (4), advisory lead (2), and magnetic resonance imaging compatibility (1). Extractions included four implantable cardioverter-defibrillators (ICDs), 17 pacemakers (PPM), and one cardiac resynchronization therapy (CRT)-P system. The leads were 9.6 years (1.5-21.7) old, and 1.8 leads were removed per patient (1-3); the lead extraction difficulty (LED) score was 11.6 ± 7. Twenty underwent cardiovascular implantable electronic device (CIED) re-implantation (2 ICD, 3 CRT-D, 13 PPM, and 2 CRT-P). For CIED re-implants, patients sent a remote transmission the next day, and all patients received a next-day call. There were no procedure or device-related issues, morbidities, or mortalities in the 30 days after discharge. CONCLUSION: Same-day discharge after TLE for non-infectious aetiologies is safe and feasible in a select group of patients with early procedure completion who meet strict SDD criteria.

Coexisting Thyroiditis and Carditis in a Patient With Lyme Disease: Looking for a Unifying Diagnosis.

Background/Objective: Lyme disease, the most common vector-borne infection in the United States, causes multisystem inflammation. We describe a patient who presented with symptoms of Lyme disease, carditis, and thyroiditis. Case Report: A 53-year-old woman developed fatigue and dyspnea on exertion 1 month after returning from a trip to Delaware. Her electrocardiogram (ECG) showed first-degree atrioventricular (AV) block with a P-R interval up to 392 milliseconds, in the setting of elevated free thyroxine and undetectable thyroid-stimulating hormone levels. Lyme serology was positive. She was hospitalized and started on ceftriaxone. During the second day of hospitalization, AV block worsened to second-degree Mobitz type II but converted back to first-degree AV block after a few hours. Her 24-hour I-123 thyroid uptake and scan revealed markedly diminished I-123 uptake of 1.2%. On day 4, the P-R interval improved, and she was discharged on doxycycline for 3 weeks. P-R interval on ECG and repeated thyroid function tests were normal after finishing antibiotic treatment. Discussion: In our patient, known exposure to the vector, a classic rash on the chest, improvement in the symptoms, and normalization of thyroid function tests after antibiotic therapy support Lyme infection as a cause of carditis and painless, autoimmune thyroiditis. Conclusion: Our case highlights the importance of considering Lyme disease as a cause of painless, autoimmune thyroiditis, especially in patients with concurrent cardiovascular involvement.

Surface mapping demonstrates compatibility of implantable loop monitor with a continuous-flow left ventricular assist device.

Syncope in patients with continuous-flow left ventricular assist device may be associated with arrhythmia and difficult to determine without an implantable cardioverter defibrillator. We present a patient with continuous-flow left ventricular assist device, no implantable cardioverter defibrillator, and recurrent syncope. An implantable loop recorder was successfully implanted with surface mapping without noise interference.

Surface unipolar electrogram characteristics to predict site of origin of outflow tract arrhythmias using noninvasive mapping.

BACKGROUND: Noninvasive electroanatomic mapping (NIEAM) demonstrate patterns of depolarization that are useful in identifying the chamber of origin (COO) in outflow tract ventricular arrhythmias (OTVA). However, its use in predicting exact site of origin (SOO) has not yet been validated. METHODS: NIEAMs (CardioInsight, Medtronic) from 40 patients (age 62.5 ± 2.6) undergoing ablation for OTVA were reviewed for diagnostic accuracy in predicting the SOO. Earliest arrhythmia breakout and directionality of earliest instantaneous unipolar electrograms (uEGMs) on NIEAMs were evaluated subjectively by two observers for quality and amplitude. Sites with most negative earliest uEGMs on right and left ventricular outflow tracts, as well as epicardial surface were manually identified. Using NIEAM-based activation timing of the lateral mitral annulus and basal septum COO was identified for each OTVA. Predictions of SOO using NIEAMs was compared with true SOO from invasive study. NIEAMs SOO predictions were compared with subjective 12 lead electrocardiogram (ECG) review by two observers. RESULTS: Review of arrhythmia breakout and signal directionality had poor diagnostic value in predicting SOO in OTVA (50.6% and 49.4%, 56.6% and 43.4%, respectively) and underperformed compared with ECG interpretation (59.1% and 80.5%). After excluding uEGMs with poor characteristics, the uEGM with most negative amplitude at the COO was predictive of the true SOO with 96.4% sensitivity and specificity. CONCLUSION: We propose a stepwise approach when interpreting NIEAMs for OTVA where patterns of activation are evaluated first to determine the COO, followed by identification of the site with most negative amplitude instantaneous uEGM to determine SOO.

Mitochondrial MsrB2 serves as a switch and transducer for mitophagy.

Mitophagy can selectively remove damaged toxic mitochondria, protecting a cell from apoptosis. The molecular spatial-temporal mechanisms governing autophagosomal selection of reactive oxygen species (ROS)-damaged mitochondria, particularly in a platelet (no genomic DNA for transcriptional regulation), remain unclear. We now report that the mitochondrial matrix protein MsrB2 plays an important role in switching on mitophagy by reducing Parkin methionine oxidation (MetO), and transducing mitophagy through ubiquitination by Parkin and interacting with LC3. This biochemical signaling only occurs at damaged mitochondria where MsrB2 is released from the mitochondrial matrix. MsrB2 platelet-specific knockout and in vivo peptide inhibition of the MsrB2/LC3 interaction lead to reduced mitophagy and increased platelet apoptosis. Pathophysiological importance is highlighted in human subjects, where increased MsrB2 expression in diabetes mellitus leads to increased platelet mitophagy, and in platelets from Parkinson's disease patients, where reduced MsrB2 expression is associated with reduced mitophagy. Moreover, Parkin mutations at Met192 are associated with Parkinson's disease, highlighting the structural sensitivity at the Met192 position. Release of the enzyme MsrB2 from damaged mitochondria, initiating autophagosome formation, represents a novel regulatory mechanism for oxidative stress-induced mitophagy.

The Simultaneity of Coronary Artery Ectasia and Intracranial Arterial Dolichoectasia: A Rare Case Report.

In the present study, we report a case of multiple coronary artery ectasias (CAE) and multiple intracranial arterial dolichoectasias (IADEs). A 60-year-old female presented to the emergency department twice with chest pain and mild elevation of troponin and T-wave changes. Peripheral coronary angiography showed severe ectasia and stenosis of certain segments of the left main coronary artery (LMCA), left anterior descending (LAD), first obtuse marginal (OM1), distal left circumflex (LCX), and bilateral subclavian arteries. The patient was treated medically. Two weeks later, she presented with dizziness. Head computerized tomography (CT) angiography showed severe IADE involving the vertebrobasilar system, intracranial internal carotid arteries, and bilateral middle cerebral arteries. No neurovascular intervention was performed due to the complexity of the findings. CAE is an abnormal dilatation of a coronary artery segment of at least 1.5 times the size of a normal coronary artery. The slow flow phenomenon may lead to ischemia and thrombosis, which can result in acute coronary syndrome. IADE comprises a dilatation and elongation of the arteries that affects both the anterior and posterior cerebral circulation, often causing neurological complications such as ischemic stroke, intracranial hemorrhage, or compression of surrounding neural structures. We report this case due to the rarity of coexisting IADE and CAE. A rarefaction of elastic tissue of the media with degeneration of the internal elastic lamina, in addition to matrix metalloproteinase dysfunction, is a common pathological mechanism for this condition. The management of CAE and IADE is mostly conservative, essentially treating the risk factors and administering antiplatelet and anticoagulant agents. In some patients, angioplasty vs. surgical treatment may be applied.

Competitive athletes with implantable cardioverter-defibrillators-How to program? Data from the Implantable Cardioverter-Defibrillator Sports Registry.

BACKGROUND: Athletes with an implantable cardioverter-defibrillator (ICD) may require unique optimal device-based tachycardia programming. OBJECTIVE: The purpose of this study was to assess the association of tachycardia programming characteristics of ICDs with occurrence of shocks, transient loss-of-consciousness, and death among athletes. METHODS: A subanalysis of a prospective, observational, international registry of 440 athletes with ICDs followed for a median of 44 months was performed. Programming characteristics were divided into groups for rate cutoff (very high, high, or low) and detection (long-detection interval [>nominal] or nominal). Endpoints included total, appropriate, and inappropriate shocks, transient loss-of-consciousness, and mortality. RESULTS: In this cohort, 62% were programmed with high-rate cutoff and 30% with long detection. No athlete died of an arrhythmia (related or unrelated) to ICD shocks. Three patients had sustained ventricular tachycardia below programmed detection rate, presenting as palpations and/or dizziness. ICD shocks were received by 98 athletes (64 appropriate, 32 inappropriate); 2 patients received both. Programming a high-rate cutoff was associated with decreased risk of total (P = .01) and inappropriate (P = .04) shocks overall and during competition or practice. Programming long-detection intervals was associated with fewer total shocks. Single- vs dual-chamber devices and the number of zones were unrelated to risk of shock. Transient loss-of-consciousness, associated with 27 appropriate shocks, was not related to programming characteristics. CONCLUSION: High-rate cutoff and long-detection duration programming of ICDs in athletes at risk for sudden death can reduce total and inappropriate ICD shocks without affecting survival or the incidence of transient loss-of-consciousness.

Controversies Surrounding Exercise in Genetic Cardiomyopathies.

Exercise and sports are an integral part of daily life for millions of Americans, with 16% of the US population older than age 15 years engaged in sports or exercise activities (Bureau of Labor statistics). The physical and psychological benefits of exercise are well-recognized. However, high-profile cases of athletes dying suddenly on the field, often due to undiagnosed genetic cardiomyopathies, raise questions about the risks and benefits of exercise for those with cardiomyopathy.

Sudden Cardiac Death in Genetic Cardiomyopathies.

Sudden cardiac death (SCD) caused by ventricular arrhythmias is common in patients with genetic cardiomyopathies (CMs) including dilated CM, hypertrophic CM, and arrhythmogenic right ventricular CM (ARVC). Phenotypic features can identify individuals at high enough risk to warrant placement of an implantable cardioverter-defibrillator, although risk stratification schemes remain imperfect. Genetic testing is valuable for family cascade screening but with few exceptions (eg, LMNA mutations) do not identify higher risk for SCD. Although randomized trials are lacking, observational data suggest that ICDs can be beneficial. Vigorous exercise can exacerbate ARVC disease progression and increase likelihood of ventricular arrhythmias.

Ventilation-Induced Modulation of Pulse Oximeter Waveforms: A Method for the Assessment of Early Changes in Intravascular Volume During Spinal Fusion Surgery in Pediatric Patients.

BACKGROUND: Scoliosis surgery is often associated with substantial blood loss, requiring fluid resuscitation and blood transfusions. In adults, dynamic preload indices have been shown to be more reliable for guiding fluid resuscitation, but these indices have not been useful in children undergoing surgery. The aim of this study was to introduce frequency-analyzed photoplethysmogram (PPG) and arterial pressure waveform variables and to study the ability of these parameters to detect early bleeding in children during surgery. METHODS: We studied 20 children undergoing spinal fusion. Electrocardiogram, arterial pressure, finger pulse oximetry (finger PPG), and airway pressure waveforms were analyzed using time domain and frequency domain methods of analysis. Frequency domain analysis consisted of calculating the amplitude density of PPG and arterial pressure waveforms at the respiratory and cardiac frequencies using Fourier analysis. This generated 2 measurements: The first is related to slow mean arterial pressure modulation induced by ventilation (also known as DC modulation when referring to the PPG), and the second corresponds to pulse pressure modulation (AC modulation or changes in the amplitude of pulse oximeter plethysmograph when referring to the PPG). Both PPG and arterial pressure measurements were divided by their respective cardiac pulse amplitude to generate DC% and AC% (normalized values). Standard hemodynamic data were also recorded. Data at baseline and after bleeding (estimated blood loss about 9% of blood volume) were presented as median and interquartile range and compared using Wilcoxon signed-rank tests; a Bonferroni-corrected P value <0.05 was considered statistically significant. RESULTS: There were significant increases in PPG DC% (median [interquartile range] = 359% [210 to 541], P = 0.002), PPG AC% (160% [87 to 251], P = 0.003), and arterial DC% (44% [19 to 84], P = 0.012) modulations, respectively, whereas arterial AC% modulations showed nonsignificant increase (41% [1 to 85], P = 0.12). The change in PPG DC% was significantly higher than that in PPG AC%, arterial DC%, arterial AC%, and systolic blood pressure with P values of 0.008, 0.002, 0.003, and 0.002, respectively. Only systolic blood pressure showed significant changes (11% [4 to 21], P = 0.003) between bleeding phase and baseline. CONCLUSIONS: Finger PPG and arterial waveform parameters (using frequency analysis) can track changes in blood volume during the bleeding phase, suggesting the potential for a noninvasive monitor for tracking changes in blood volume in pediatric patients. PPG waveform baseline modulation (PPG DC%) was more sensitive to changes in venous blood volume when compared with respiration-induced modulation seen in the arterial pressure waveform.

Inducing mitophagy in diabetic platelets protects against severe oxidative stress.

Diabetes mellitus (DM) is a growing international concern. Considerable mortality and morbidity associated with diabetes mellitus arise predominantly from thrombotic cardiovascular events. Oxidative stress-mediated mitochondrial damage contributes significantly to enhanced thrombosis in DM A basal autophagy process has recently been described as playing an important role in normal platelet activation. We now report a substantial mitophagy induction (above basal autophagy levels) in diabetic platelets, suggesting alternative roles for autophagy in platelet pathology. Using a combination of molecular, biochemical, and imaging studies on human DM platelets, we report that platelet mitophagy induction serves as a platelet protective mechanism that responds to oxidative stress through JNK activation. By removing damaged mitochondria (mitophagy), phosphorylated p53 is reduced, preventing progression to apoptosis, and preserving platelet function. The absence of mitophagy in DM platelets results in failure to protect against oxidative stress, leading to increased thrombosis. Surprisingly, this removal of damaged mitochondria does not require contributions from transcription, as platelets lack a nucleus. The considerable energy and resources expended in "prepackaging" the complex mitophagy machinery in a short-lived normal platelet support a critical role, in anticipation of exposure to oxidative stress.

Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor.

An elevated level of von Willebrand factor (VWF) in diabetic patients is associated with increased risk of thrombotic cardiovascular events. The underlying mechanism of how VWF expression is upregulated in diabetes mellitus is poorly understood. We now report that hyperglycemia-induced repression of microRNA-24 (miR-24) increases VWF expression and secretion in diabetes mellitus. In diabetic patients and diabetic mouse models (streptozotocin/high-fat diet-induced and db/db mice), miR-24 is reduced in both tissues and plasma. Knockdown of miR-24 in mice leads to increased VWF mRNA and protein levels and enhanced platelet tethering (spontaneous thrombosis). miR-24 tightly controls VWF levels through pleiotropic effects, including direct binding to the 3' untranslated region of VWF and targeting FURIN and the histamine H1 receptor, known regulators of VWF processing and secretion in endothelial cells. We present a novel mechanism for miR-24 downregulation through hyperglycemia-induced activation of aldose reductase, reactive oxygen species, and c-Myc. These findings support a critical role for hyperglycemic repression of miR-24 in VWF-induced pathology. miR-24 represents a novel therapeutic target to prevent adverse thrombotic events in patients with diabetes mellitus.

Aldose reductase-mediated phosphorylation of p53 leads to mitochondrial dysfunction and damage in diabetic platelets.

BACKGROUND: Platelet abnormalities are well-recognized complications of diabetes mellitus. Mitochondria play a central role in platelet metabolism and activation. Mitochondrial dysfunction is evident in diabetes mellitus. The molecular pathway for hyperglycemia-induced mitochondrial dysfunction in platelets in diabetes mellitus is unknown. METHODS AND RESULTS: Using both human and humanized mouse models, we report that hyperglycemia-induced aldose reductase activation and subsequent reactive oxygen species production lead to increased p53 phosphorylation (Ser15), which promotes mitochondrial dysfunction, damage, and rupture by sequestration of the antiapoptotic protein Bcl-xL. In a glucose dose-dependent manner, severe mitochondrial damage leads to loss of mitochondrial membrane potential and platelet apoptosis (cytochrome c release, caspase 3 activation, and phosphatidylserine exposure). Although platelet hyperactivation, mitochondrial dysfunction, aldose reductase activation, reactive oxygen species production, and p53 phosphorylation are all induced by hyperglycemia, we demonstrate that platelet apoptosis and hyperactivation are 2 distinct states that depend on the severity of the hyperglycemia and mitochondrial damage. Combined, both lead to increased thrombus formation in a mouse blood stasis model. CONCLUSIONS: Aldose reductase contributes to diabetes-mediated mitochondrial dysfunction and damage through the activation of p53. The degree of mitochondrial dysfunction and damage determines whether hyperactivity (mild damage) or apoptosis (severe damage) will ensue. These signaling components provide novel therapeutic targets for thrombotic complications in diabetes mellitus.

Analysis of plethysmographic waveform changes induced by beach chair positioning under general anesthesia.

During shoulder surgery, patients typically are placed in the beach chair position. In rare cases, this positioning has resulted in devastating outcomes of postoperative cerebral ischemia (Cullen and Kirby in APSF Newsl 22(2):25-27, 2007; Munis in APSF Newsl 22(4):82-83, 2008). This study presents a method to noninvasively and continuously hemodynamically monitor patients during beach chair positioning by using the photoplethysmograph signal recorded from a commercial pulse oximeter. Twenty-nine adults undergoing shoulder surgery were monitored before and after beach chair positioning with electrocardiogram, intermittent blood pressure, end tidal carbon dioxide, and photoplethysmograph via Nellcor finger pulse oximeter. Fast Fourier transform (FFT) was used to perform frequency-domain analysis on the photoplethysmograph (PPG) signal for data segments taken 80-120 s before and after beach chair positioning. The amplitude density of respiration-associated PPG oscillations was quantified measuring the height of the FFT peak at respiratory frequency. Results were reported as (median, interquartile range) and statistical analysis was performed using Wilcoxon sign rank test. Data were also collected when vasoactive drugs phenylephrine and ephedrine were used to maintain acceptable mean arterial pressure during a case. With beach chair positioning, all subjects who did not receive vasoactive drugs showed an increase in the FFT amplitude density of respiration-associated PPG oscillations (p < 0.0001) without change in pulse-associated PPG oscillations. The PPG was more accurate at monitoring the change to beach chair position than blood pressure or heart rate. With vasoactive drugs, pulse-associated PPG oscillations decreased only with phenylephrine while respiration-associated oscillations did not change. Frequency domain analysis of the PPG signal may be a better tool than traditional noninvasive hemodynamic parameters at monitoring patients during beach chair position surgery.