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1.
J Cardiovasc Electrophysiol ; 34(3): 652-661, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36640431

RESUMO

INTRODUCTION: Substrate-based ablation for ventricular tachycardia (VT) using Ripple map (RM) is an effective treatment strategy for patients with ischemic cardiomyopathy but has yet to be evaluated in patients with nonischemic cardiomyopathy (NICMO). The aim of this study is to determine the feasibility and effectiveness of an RM-based ablation for NICMO patients. METHODS AND RESULTS: This was a single-center, retrospective study including all NICMO patients undergoing VT ablation at St Vincent Hospital between January 1, 2018 and January 12, 2019. Retrospective RM analysis was performed on those that had a substrate-based ablation to identify the location and number of Ripple channels as well as their proximity to ablation lesions. Thirty-three patients met the inclusion criteria and had a median age of 65 (58, 73.5) with 15.2% of the population being female, and were followed for a median duration of 451 (217.5, 586.5) days. Of these patients, 23 (69.7%) had a substrate-based ablation with a median procedural duration of 196.4 (186.8, 339) min, 1946 (517, 2750) points collected per map, and 277 (141, 554) points were within the scar. Two (8.6%) procedural complications occurred, and 7 (30.4%) patients had VT recurrence during follow-up. RM analysis revealed an average of two Ripple channels and the patients without VT recurrence had ablation performed closer to the Ripple channels: 0 (0, 4.7) versus 14.3 (0, 23.5) cm; p = .02. CONCLUSION: An RM-based substrate ablation can be performed in NICMO patients and ablation within Ripple channels is a predictor of VT freedom.


Assuntos
Cardiomiopatias , Ablação por Cateter , Isquemia Miocárdica , Taquicardia Ventricular , Humanos , Feminino , Lactente , Masculino , Estudos Retrospectivos , Arritmias Cardíacas/cirurgia , Isquemia Miocárdica/complicações , Resultado do Tratamento , Ablação por Cateter/efeitos adversos
2.
Europace ; 25(2): 756-761, 2023 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-36106617

RESUMO

AIMS: Multiple re-entry circuits may operate simultaneously in the atria in the form of dual loop re-entry using a common isthmus, or multiple re-entrant loops without a common isthmus. When two or more re-entrant circuits coexist, ablation of an individual isthmus may lead to a seamless transition (without significant changes in surface electrocardiogram, coronary sinus activation or tachycardia cycle length) to a second rhythm, and the isthmus block can go unnoticed. METHODS AND RESULTS: We hypothesize and subsequently illustrate in three patient cases, methods to rapidly identify a transition in the rhythm and isthmus block using local electrogram changes at the ablation site. CONCLUSION: Local activation sequence changes, electrogram timing, and the behaviour of pre-existing double potentials can reveal isthmus block promptly when rhythm transitions occur during ablation of multiloop re-entry tachycardias.


Assuntos
Flutter Atrial , Ablação por Cateter , Humanos , Flutter Atrial/diagnóstico , Flutter Atrial/cirurgia , Arritmias Cardíacas , Átrios do Coração , Eletrocardiografia , Ablação por Cateter/métodos
3.
Ann Noninvasive Electrocardiol ; 28(5): e13073, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37515396

RESUMO

BACKGROUND: The use of a Left Ventricular Assist Device (LVAD) in patients with advanced heart failure refractory to optimal medical management has progressed steadily over the past two decades. Data have demonstrated reduced LVAD efficacy, worse clinical outcome, and higher mortality for patients who experience significant ventricular tachyarrhythmia (VTA). We hypothesize that a novel prophylactic intra-operative VTA ablation protocol at the time of LVAD implantation may reduce the recurrent VTA and adverse events postimplant. METHODS: We designed a prospective, multicenter, open-label, randomized-controlled clinical trial enrolling 100 patients who are LVAD candidates with a history of VTA in the previous 5 years. Enrolled patients will be randomized in a 1:1 fashion to intra-operative VTA ablation (n = 50) versus conventional medical management (n = 50) with LVAD implant. Arrhythmia outcomes data will be captured by an implantable cardioverter defibrillator (ICD) to monitor VTA events, with a uniform ICD programming protocol. Patients will be followed prospectively over a mean of 18 months (with a minimum of 9 months) after LVAD implantation to evaluate recurrent VTA, adverse events, and procedural outcomes. Secondary endpoints include right heart function/hemodynamics, healthcare utilization, and quality of life. CONCLUSION: The primary aim of this first-ever randomized trial is to assess the efficacy of intra-operative ablation during LVAD surgery in reducing VTA recurrence and improving clinical outcomes for patients with a history of VTA.


Assuntos
Desfibriladores Implantáveis , Insuficiência Cardíaca , Coração Auxiliar , Taquicardia Ventricular , Humanos , Coração Auxiliar/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Fatores de Risco , Eletrocardiografia , Arritmias Cardíacas , Taquicardia Ventricular/etiologia , Resultado do Tratamento
4.
Circulation ; 141(21): e823-e831, 2020 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-32228309

RESUMO

Coronavirus disease 2019 (COVID-19) is a global pandemic that is wreaking havoc on the health and economy of much of human civilization. Electrophysiologists have been impacted personally and professionally by this global catastrophe. In this joint article from representatives of the Heart Rhythm Society, the American College of Cardiology, and the American Heart Association, we identify the potential risks of exposure to patients, allied healthcare staff, industry representatives, and hospital administrators. We also describe the impact of COVID-19 on cardiac arrhythmias and methods of triage based on acuity and patient comorbidities. We provide guidance for managing invasive and noninvasive electrophysiology procedures, clinic visits, and cardiac device interrogations. In addition, we discuss resource conservation and the role of telemedicine in remote patient care along with management strategies for affected patients.


Assuntos
Arritmias Cardíacas/etiologia , Betacoronavirus , Infecções por Coronavirus/epidemiologia , Eletrocardiografia , Pandemias , Pneumonia Viral/epidemiologia , Guias de Prática Clínica como Assunto , American Heart Association , Arritmias Cardíacas/terapia , COVID-19 , Cardiologia , Reanimação Cardiopulmonar , Infecções por Coronavirus/complicações , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/fisiopatologia , Humanos , Pneumonia Viral/complicações , Pneumonia Viral/diagnóstico , Pneumonia Viral/fisiopatologia , SARS-CoV-2 , Sociedades Médicas , Telemedicina , Triagem , Estados Unidos
5.
J Cardiovasc Electrophysiol ; 32(2): 325-332, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33270311

RESUMO

INTRODUCTION: Elevated left atrial pressure (LAP) during catheter ablation of atrial fibrillation (AF) is associated with an increased risk of AF recurrence, but it is unknown if this correlates with heart failure (HF). The objective of the study was to determine if elevated LAP after AF ablation correlates with HF events. METHODS: Prospective, single-center, cohort study measuring LAP and right atrial pressure (RAP) during AF ablation in 100 patients. The primary endpoint was clinical HF within 30 days of ablation. The secondary outcome was AF-free HF. RESULTS: One hundred patients (63% male, mean age 64.5) were enrolled and 20% had clinical HF within 30 days. Bivariate correlates included mitral valve (MV) disease, persistent AF, class III antiarrhythmics, LAP, and recurrent AF. Multivariate analysis revealed class III antiarrhythmics were protective (odds ratio [OR]: 0.24 [0.1-0.5], p = .04), while MV disease (OR: 8.7 [3.3-23], p = .03) and loop diuretics (OR: 4.8 [2.6-9.1], p = .01) were hazardous. AF-free HF occurred in 9% of patients and correlated with higher LAP and RAP, and chronic kidney disease. CONCLUSION: Patients with HF after AF ablation had higher LAP. MV disease, diuretic use, and class III antiarrhythmics also correlated to HF. These present opportunities to target future interventions to reduce a common complication of AF ablation.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Insuficiência Cardíaca , Hipertensão , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/cirurgia , Ablação por Cateter/efeitos adversos , Estudos de Coortes , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Resultado do Tratamento
6.
Europace ; 23(4): 634-639, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33176356

RESUMO

AIMS: The response to premature atrial complexes (PACs) during tachycardia has been shown to differentiate atrioventricular nodal re-entrant tachycardia (AVNRT) from focal junctional tachycardia (JT). His refractory PAC (HrPACs) perturbing the next His (resetting with fusion) is diagnostic of AVNRT and such a late PAC fusing with the native beat cannot reset the focal source of JT. Early PAC advancing the immediate His with continuation of tachycardia suggests JT but can also occur in AVNRT due to simultaneous conduction through the AV nodal fast and slow pathways [two-for-one response (TFOR)]. The objective of this study was to evaluate the incidence and mechanism of TFOR after early premature atrial complexes (ePACs) during AVNRT and to differentiate it from the known response to ePACs during JT. METHODS AND RESULTS: Typical AVNRT cases were diagnosed using standard criteria. We evaluated the responses to scanning PACs delivered during tachycardia in 100 patients undergoing AV node slow pathway modification for AVNRT. The responses to HrPACs and ePACs delivered from coronary sinus os or high right atrium were retrospectively reviewed. In 10 patients, ePACs advanced the immediate His with continuation of tachycardia. In all 10 cases, HrPACs advanced the next His, confirming AVNRT as the mechanism, and indicating a TFOR. CONCLUSION: A TFOR can occur in a small number of patients during AVNRT and is therefore not diagnostic of JT. However, HrPACs always perturbed the next His in these cases, confirming the diagnosis of AVNRT and allowing for differentiation from JT.


Assuntos
Complexos Atriais Prematuros , Ablação por Cateter , Taquicardia por Reentrada no Nó Atrioventricular , Complexos Atriais Prematuros/diagnóstico , Nó Atrioventricular/cirurgia , Eletrocardiografia , Frequência Cardíaca , Humanos , Estudos Retrospectivos , Taquicardia por Reentrada no Nó Atrioventricular/diagnóstico , Taquicardia por Reentrada no Nó Atrioventricular/cirurgia
7.
BMC Health Serv Res ; 21(1): 1189, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34727944

RESUMO

BACKGROUND: First investigated in the 1990s, medication therapy management (MTM) is an evidence-based practice offered by pharmacists to ensure a patient's medication regimen is individualized to include the safest and most effective medications. MTM has been shown to a) improve quality of patient care, b) reduces health care costs, and c) lead to fewer medication-related adverse effects. However, there has been limited testing of evidence-based, a-priori implementation strategies that support MTM implementation on a large scale. METHODS: The study has two objectives assessed at the organizational and individual level: 1) to determine the adoption, feasibility, acceptability and appropriateness of a multi-faceted implementation strategy to support the MTM pilot program in Tennessee; and 2) to report on the contextual factors associated with program implementation based on the Consolidated Framework for Implementation Research (CFIR). The overall design of the study was a hybrid type 2 effectiveness-implementation study reporting outcomes of Tennessee state Medicaid's (TennCare) MTM Pilot program. This paper presents early stage implementation outcomes (e.g., adoption, feasibility, acceptability, appropriateness) and explores implementation barriers and facilitators using the CFIR. The study was assessed at the (a) organizational and (b) individual level. A mixed-methods approach was used including surveys, claims data, and semi-structured interviews. Interview data underwent initial, rapid qualitative analysis to provide real time feedback to TennCare leadership on project barriers and facilitators. RESULTS: The total reach of the program from July 2018 through June 2020 was 2033 MTM sessions provided by 17 Medicaid credentialed pharmacists. Preliminary findings suggest participants agreed that MTM was acceptable (µ = 16.22, SD = 0.28), appropriate (µ = 15.33, SD = 0.03), and feasible (µ = 14.72, SD = 0.46). Each of the scales had an excellent level of internal (> 0.70) consistency (feasibility, α = 0.91; acceptability, α = 0.96; appropriateness, α = 0.98;). Eight program participants were interviewed and were mapped to the following CFIR constructs: Process, Characteristics of Individuals, Intervention Characteristics, and Inner Setting. Rapid data analysis of the contextual inquiry allowed TennCare to alter initial implementation strategies during project rollout. CONCLUSION: The early stage implementation of a multi-faceted implementation strategy to support delivery of Tennessee Medicaid's MTM program was found to be well accepted and appropriate across multiple stakeholders including providers, administrators, and pharmacists. However, as the early stage of implementation progressed, barriers related to relative priority, characteristics of the intervention (e.g., complexity), and workflow impeded adoption. Programmatic changes to the MTM Pilot based on early stage contextual analysis and implementation outcomes had a positive impact on adoption.


Assuntos
Serviços Comunitários de Farmácia , Conduta do Tratamento Medicamentoso , Humanos , Medicaid , Farmacêuticos , Tennessee , Estados Unidos
8.
World J Urol ; 38(7): 1607-1613, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31444604

RESUMO

PURPOSE: Video assessment is an emerging tool for understanding surgical technique. Patient outcomes after robot-assisted radical prostatectomy (RARP) may be linked to technical aspects of the procedure. In an effort to refine surgical approaches and improve outcomes, we sought to understand technical variation for the key steps of RARP in a surgical collaborative. METHODS: The Michigan Urological Surgery Improvement Collaborative (MUSIC) is a statewide quality improvement collaborative with the aim of improving prostate cancer care. MUSIC surgeons were invited to submit representative complete videos of nerve-sparing RARP for blinded analysis. We also analyzed peri-operative outcomes from these surgeons in the registry. RESULTS: Surgical video data from 20 unique surgeons identified many variations in technique and time to complete different steps. Common to all surgeons was a transperitoneal approach and a running urethrovesical anastomosis. Prior to anastomosis, 25% surgeons undertook a posterior reconstruction and 30% employed urethral suspension. 65% surgeons approached the seminal vesicle anteriorly. For control of the dorsal vein complex, suture ligation was used in 60%, and vascular stapler was 15%. The majority (80%) of surgeons employed clips for managing pedicles. In examining patient outcomes for surgeons, peri-operative outcomes were not correlated with surgeon's operative time; however, surgeons with an EBL > 400 ml had significant difference among the five different techniques employed. CONCLUSIONS: Despite the worldwide popularity of RARP, the operation is still far from standardized. Correlating variation in technique with clinical outcomes may help provide objective data to support best practices with the goal to improve patient outcomes.


Assuntos
Prostatectomia/métodos , Prostatectomia/normas , Neoplasias da Próstata/cirurgia , Melhoria de Qualidade , Procedimentos Cirúrgicos Robóticos , Gravação em Vídeo , Humanos , Masculino , Michigan , Resultado do Tratamento
9.
Pacing Clin Electrophysiol ; 43(2): 217-222, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31808167

RESUMO

BACKGROUND: Technical advances have improved the safety of cardiac implantable electronic device (CIED) insertion, but periprocedural complications persist. Despite ultrasound (US) guidance for vascular access being feasible and exhibiting shorter fluoroscopy times, it is not widely adopted for insertion of CIEDs. Thus, we studied the use of US for CIED insertion to (1) quantify the success rate of venous cannulation, (2) identify predictors of failed cannulation, and (3) quantify the rate of complications using US guidance. METHODS: We studied 166 consecutive patients who underwent US-guided CIED implantation. Anatomic parameters of the axillary vein were measured. The primary outcome was success (group 1) or failure (group 2) to obtain vascular access utilizing US guidance. Secondary outcomes included pneumothorax and hematoma. RESULTS: Successful US-guided cannulation occurred in 154 of 166 patients (93%). No patient had a pneumothorax. Hematoma occurred in 1 of 166 patients (0.01%). Group 2 exhibited higher male proportion at 11 of 12 (92%) compared with 94 of 154 (61%) in group 1 (P = .03), increased vein depth at 3.84 versus 2.85 cm (P = .003), more right-sided implants (P = .03), higher weight at 104.6 versus 85.3 kg (P = .017), higher body mass index at 35.6 versus 29.2 kg/m2 (P = .049), and higher body surface area at 2.24 versus 1.99 m2 (P = .013). Other parameters were statistically nonsignificant. In multivariate analysis, vein depth remained significantly associated with failure. CONCLUSION: Using US guidance for CIED implantation is successful in the vast majority (93%) of patients. Rare cases of unsuccessful cannulation were associated with right-sided implants and increased venous depth.


Assuntos
Desfibriladores Implantáveis , Implantação de Prótese/métodos , Ultrassonografia de Intervenção , Idoso , Axila/irrigação sanguínea , Feminino , Hematoma/epidemiologia , Humanos , Masculino , Pneumotórax/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
10.
J Cardiovasc Electrophysiol ; 29(12): 1635-1640, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30192033

RESUMO

BACKGROUND: Electrophysiology study (EPS) is an important part of the diagnosis and workup for supraventricular tachycardia (SVT). Provocative medications are used to induce arrhythmias, when they are not inducible at baseline. The most common medication is the ß1-specific agonist, isoproterenol, but recent price increases have resulted in a shift toward the nonspecific agonist, epinephrine. OBJECTIVE: We hypothesize that isoproterenol is a better induction agent for SVT during EPS than epinephrine. METHODS: We created a retrospective cohort of 131 patients, who underwent EPS and required medication infusion with either isoproterenol or epinephrine for SVT induction. The primary outcome was arrhythmia induction. RESULTS: Successful induction was achieved in 71% of isoproterenol cases and 53% of epinephrine cases (P = 0.020). Isoproterenol was significantly better than epinephrine for SVT induction during EPS (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.14-4.85; P = 0.021). There was no difference in baseline variables or complications between the two groups. Other variables associated with successful arrhythmia induction included a longer procedure duration and atrioventricular nodal re-entry tachycardia as the clinical arrhythmia. In a multivariable model, isoproterenol remained significantly associated with successful induction (OR, 2.57; 95% CI, 1.002-6.59; P = 0.05). CONCLUSIONS: Isoproterenol was significantly better than epinephrine for SVT arrhythmia induction. However, epinephrine was safe and successfully induced arrhythmias in the majority of patients who received it. Furthermore, when atropine was added in epinephrine-refractory cases, in a post hoc analysis there was no difference in arrhythmia induction between medications. Cost savings could thus be significant without compromising safety.


Assuntos
Agonistas Adrenérgicos beta/efeitos adversos , Técnicas Eletrofisiológicas Cardíacas/métodos , Epinefrina/efeitos adversos , Isoproterenol/efeitos adversos , Taquicardia Supraventricular/induzido quimicamente , Taquicardia Supraventricular/fisiopatologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
11.
J Cardiovasc Electrophysiol ; 29(3): 477-481, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29364552

RESUMO

A 25-year-old man with severe nonischemic dilated cardiomyopathy underwent subcutaneous implantable cardioverter defibrillator (S-ICD) implant and subsequently underwent HeartWare ventricular assist device (HVAD) placement. Postoperative interrogation revealed both primary and secondary S-ICD vectors inappropriately regarded sinus rhythm as "noise," and the alternate vector significantly undersensed sinus rhythm. The S-ICD was reinterrogated using high-resolution capture to visually confirm EMI with a dominant frequency in both the primary and secondary vectors of 46.67 Hz that fell within the S-ICD operational range of 9-60 Hz. The 46.67 Hz frequency correlated with the HVAD operational speed of 2,800 RPM. The HVAD pump speed was increased from 2,800 to 3,000 RPM, resulting in a dominant frequency of 50 Hz. The notch filter is nonprogrammable in S-ICDs. However, the built-in filter is 50 Hz for countries in European time zones as opposed to 60 Hz in US time zones due to differences in the anticipated noise from electrical sources within each continent. Thus, the S-ICD time zone was reprogrammed from EST to GMT, which reduced the notch filter from 60  to 50 Hz, resulting in S-ICD successfully eliminating EMI when the patient was in a supine position. The EMI interference was still intermittently present in the upright patient position. This case demonstrates the utility of high-resolution electrogram capture to identify the source and frequency of EMI in S-ICD and offers a potential avenue to troubleshoot dominant frequency oversensing by changing the device time zone.


Assuntos
Cardiomiopatia Dilatada/terapia , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Campos Eletromagnéticos , Coração Auxiliar , Falha de Prótese , Disfunção Ventricular Esquerda/terapia , Função Ventricular Esquerda , Adulto , Cardiomiopatia Dilatada/diagnóstico , Cardiomiopatia Dilatada/fisiopatologia , Técnicas Eletrofisiológicas Cardíacas , Humanos , Masculino , Posicionamento do Paciente/métodos , Desenho de Prótese , Decúbito Dorsal , Resultado do Tratamento , Disfunção Ventricular Esquerda/diagnóstico , Disfunção Ventricular Esquerda/fisiopatologia
13.
Heart Rhythm ; 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38942104

RESUMO

The complexity of cardiac electrophysiology procedures has increased significantly over the past three decades. Anesthesia requirements of these procedures can be different based on patient- and procedure-specific factors. This manuscript outlines various anesthesia strategies for cardiac implantable electronic devices and electrophysiology procedures including pre-procedural, procedural and post-procedural management. A team-based approach with collaboration between cardiac electrophysiologists and anesthesiologists is required with careful pre-procedural and intra-procedural planning. Given the recent advances in electrophysiology, there is a need for specialized cardiac electrophysiology anesthesia care to improve the efficacy and safety of the procedures.

14.
Heart Rhythm ; 2024 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-38768839

RESUMO

BACKGROUND: The safety and long-term efficacy of radiofrequency (RF) catheter ablation (CA) of paroxysmal atrial fibrillation (PAF) has been well established. Contemporary techniques to optimize ablation delivery, reduce fluoroscopy use, and improve clinical outcomes have been developed. OBJECTIVE: The purpose of this study was to assess the contemporary real-world practice approach and short and long-term outcomes of RF CA for PAF through a prospective multicenter registry. METHODS: Using the REAL-AF (Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal and Persistent Atrial Fibrillation; ClincalTrials.gov Identifier: NCT04088071) Registry, patients undergoing RF CA to treat PAF across 42 high-volume institutions and 79 experienced operators were evaluated. The procedures were performed using zero or reduced fluoroscopy, contact force sensing catheters, wide area circumferential ablation, and ablation index as a guide with a target of 380-420 for posterior and 500-550 for anterior lesions. The primary efficacy outcome was freedom from all-atrial arrhythmia recurrence at 12 months. RESULTS: A total of 2470 patients undergoing CA from January 2018 to December 2022 were included. Mean age was 65.2 ±11.14 years, and 44% were female. Most procedures were performed without fluoroscopy (71.5%), with average procedural and total RF times of 95.4 ± 41.7 minutes and 22.1±11.8 minutes, respectively. At 1-year follow-up, freedom from all-atrial arrhythmias was 81.6% with 89.7% of these patients off antiarrhythmic drugs. No significant difference was identified comparing pulmonary vein isolation vs pulmonary vein isolation plus ablation approaches. The complication rate was 1.9%. CONCLUSION: Refinement of RF CA to treat PAF using contemporary tools, standardized protocols, and electrophysiology laboratory workflows resulted in excellent short- and long-term clinical outcomes.

15.
Small ; 9(16): 2774-83, 2013 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-23468416

RESUMO

In the past decades, numerous types of nanomedicines have been developed for the efficient and safe delivery of nucleic acid-based drugs for cancer therapy. Given that the destination sites for nucleic acid-based drugs are inside cancer cells, delivery systems need to be both targeted and shielded in order to overcome the extracellular and intracellular barriers. One of the major obstacles that has hindered the translation of nanotechnology-based gene-delivery systems into the clinic has been the complexity of the design and assembly processes, resulting in non-uniform nanocarriers with unpredictable surface properties and efficiencies. Consequently, no product has reached the clinic yet. In order to address this shortcoming, a multifunctional targeted biopolymer is genetically engineered in one step, eliminating the need for multiple chemical conjugations. Then, by systematic modulation of the ratios of the targeted recombinant vector to PEGylated peptides of different sizes, a library of targeted-shielded viral-mimetic nanoparticles (VMNs) with diverse surface properties are assembled. Through the use of physicochemical and biological assays, targeted-shielded VMNs with remarkably high transfection efficiencies (>95%) are screened. In addition, the batch-to-batch variability of the assembled targeted-shielded VMNs in terms of uniformity and efficiency is examined and, in both cases, the coefficient of variation is calculated to be below 20%, indicating a highly reproducible and uniform system. These results provide design parameters for engineering uniform, targeted-shielded VMNs with very high cell transfection rates that exhibit the important characteristics for in vivo translation. These design parameters and principles could be used to tailor-make and assemble targeted-shielded VMNs that could deliver any nucleic acid payload to any mammalian cell type.


Assuntos
Nanopartículas/química , Nanotecnologia/métodos , Vírus , Animais
18.
JACC Clin Electrophysiol ; 9(7 Pt 2): 1060-1066, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37086227

RESUMO

BACKGROUND: Pericarditis is common after radiofrequency ablation for atrial fibrillation (AF). OBJECTIVES: Study investigators hypothesized an empirical post-AF ablation treatment protocol with colchicine may reduce the incidence and severity of pericarditis. PAPERS (Post-Ablation PEricarditis Reduction Study) aimed to quantify the risks and benefits associated with prophylactic use of colchicine to prevent pericarditis following AF ablation. METHODS: PAPERS is a multicenter, prospective, randomized controlled study. Patients were randomized on the day of the procedure to receive no postprocedure prophylaxis (group A; standard of care arm) or colchicine 0.6 mg orally twice daily for 7 days starting immediately post-procedure (group B; study arm). All participants underwent a follow-up survey at 14 days postoperatively. The primary endpoint was the development of clinical pericarditis within 2 weeks following ablation. Secondary outcomes included the incidence of pericarditis by ablation type and medical therapy. RESULTS: Among 139 patients enrolled, 66 were randomized to standard of care (group A), and 73 patients were randomized to the colchicine arm (group B). The primary outcome of clinical pericarditis was reached in 7 of 66 (10.6%) patients in group A and in 7 of 73 (9.6%) patients in group B (P = 0.84). The rate of gastrointestinal discomfort was 10 of 66 (15%) in group A and 34 of 73 (47%) in group B (P < 0.001). There was an increased incidence of pericarditis in patients who underwent cavotricuspid isthmus ablation (17 of 50; 34%) in addition to pulmonary vein isolation (6 of 69; 8.7%; P = 0.001). CONCLUSIONS: Prophylactic colchicine therapy initiated after the ablation procedure in patients with AF did not affect the incidence of post-ablation pericarditis and was associated with an increased incidence of gastrointestinal side effects.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Pericardite , Humanos , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/etiologia , Colchicina/efeitos adversos , Estudos Prospectivos , Resultado do Tratamento , Recidiva Local de Neoplasia/etiologia , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Pericardite/epidemiologia , Pericardite/prevenção & controle , Pericardite/complicações
19.
J Interv Card Electrophysiol ; 64(2): 437-442, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34415475

RESUMO

PURPOSE: Atrial fibrillation (AF) ablation is a common procedure to reduce cardiovascular morbidity but is limited by recurrence. The objective of this study was to determine if post-ablation acute surface P wave morphology and other electrocardiographic parameters correlate with AF recurrence. METHODS: The Avoiding Bladder Catheters During AF ablation (ABCD-AF) trial was a randomized, prospective trial in 160 subjects undergoing AF ablation. The present study examined correlation between AF recurrence in follow-up and acute post-ablation electrocardiographic P wave parameters. RESULTS: Median follow-up was 255 (188, 306) days. The ABCD-AF cohort had a mean age of 62.7 ± 12.8 with 32.1% being females. Rate of recurrent AF was 35.8%, with a median time to AF of 135 (109, 182) days. There was no baseline demographic associated with AF recurrence. There was more AF recurrence in those with longer follow-up (p = 0.001). Lead 2 PR interval, lead 2 P wave duration/PR (Pdur/PR), lead V1 PR interval, and lead V1 Pdur/PR were all significantly associated with recurrent AF (p = 0.03, 0.02, 0.01, 0.01). Longer PR and shorter Pdur/PR predicted AF recurrence. In a multivariable model, lead V1 Pdur/PR provided the best predictor of AF recurrence, with an odds ratio of 0.018 (p = 0.016) per standard deviation change. CONCLUSIONS: Shorter P wave duration combined with longer AV node delay, as measured by proportion of the PR that the P wave occupies, was the best predictor of AF recurrence post-ablation.


Assuntos
Fibrilação Atrial , Ablação por Cateter , Idoso , Fibrilação Atrial/cirurgia , Ablação por Cateter/métodos , Eletrocardiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Resultado do Tratamento
20.
JACC Case Rep ; 4(10): 621-625, 2022 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-35615219

RESUMO

We present a case of persistent dual AV node conduction during AV node reentry tachycardia as a new clinical manifestation of 2-for-1 AV node conduction. The interpretation of the complex physiology ponders the possibility of an accessory pathway mediated atrioventricular reentry existing with more ventricular than atrial events.

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