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INTRODUCTION: Ventricular tachycardia storm or electrical storm (ES) is a common complication following left ventricular assist device (LVAD) implantation. The factors contributing to ES and outcomes are less studied. The study aimed to determine the factors associated with ES and the probability of survival in patients undergoing LVAD in three tertiary centers over a span of 15 years. METHODS: We performed a retrospective cohort study on all patients who underwent LVAD implantation at the Mayo Clinic (Rochester, Phoenix, and Jacksonville) from January 1, 2006 to December 31, 2020. ES was defined as ≥3 episodes of sustained ventricular tachycardia over a period of 24 h with no identifiable reversible cause. Detailed chart reviews of the electronic health records within the Mayo Clinic and outside medical records were performed. RESULTS: A total of 883 patients who underwent LVAD implantation were included in our study. ES occurred in 7% (n = 61) of patients with a median of 13 days (interquartile range [IQR]: 5-297 days) following surgery. We found 57% of patients (n = 35) developed ES within 30 days, while 43% (n = 26) patients developed ES at a median of 545 (IQR 152-1032) days after surgery. Following ES, 26% of patients died within 1 year. Patients with ES had a significant association with a history of ventricular arrhythmias and implantable cardioverter defibrillator (ICD) shocks before the procedure. ES was significantly associated with reduced survival compared to patients without ES (hazards ratio [HR]: 1.92, 95% CI: 1.39-2.64, p < .001). CONCLUSION: Following LVAD implantation, the rate of ES was 7% with majority of ES occurring within 30 days of LVAD. Risk factors for ES included pre-implant history of ventricular arrhythmias and ICD shock. ES was significantly associated with reduced survival compared to patients without ES.
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Insuficiência Cardíaca , Coração Auxiliar , Implantação de Prótese , Taquicardia Ventricular , Função Ventricular Esquerda , Humanos , Feminino , Estudos Retrospectivos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Taquicardia Ventricular/mortalidade , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/etiologia , Resultado do Tratamento , Idoso , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Implantação de Prótese/efeitos adversos , Implantação de Prótese/instrumentação , Implantação de Prótese/mortalidade , Medição de Risco , Potenciais de Ação , Frequência Cardíaca , AdultoRESUMO
BACKGROUND: The real-world data on the safety profile of transvenous lead extraction (TLE) for infected cardiac implantable electronic devices (CIED) among elderly patients is not well-established. This study aimed to evaluate the hospital outcomes between patients of different age groups who underwent TLE for infected CIED. METHOD: Using the Nationwide Readmissions Database, our study included patients aged ≥18 years who underwent TLE for infected CIED between 2017 and 2020. We divided the patients into four groups: Group A. Young (<50 years), Group B. Young intermediate (50-69 years old), Group C. Older intermediate (70-79 years old), and Group D. Octogenarian (≥80 years old). We then analyzed the in-hospital outcome and 30-day readmission between these age groups. RESULTS: A total of 10,928 patients who were admitted for TLE of infected CIED were included in this study: 982 (9.0%) patients in group A, 4,234 (38.7%) patients in group B, 3,204 (29.3%) patients in group C and 2,508 (23.0%) of patients in group D. Our study demonstrated that the risk of early mortality increased with older age (Group B vs. Group A: OR: 1.92, 95% CI: 1.19-3.09, p < .01; Group C vs. Group A: OR: 2.47, 95% CI: 1.51-4.04, p < .01; Group D vs. Group A: OR: 2.82, 95% CI: 1.69-4.72, p < .01). The risk of non-home discharge also increased in elderly groups (Group B vs. Group A: OR: 1.89; 95% CI: 1.52-2.36; p < .01; Group C vs. Group A: OR: 2.82; 95% CI 2.24-3.56; p < .01; Group D vs. Group A: OR: 4.16; 95% CI: 3.28-5.28; p < .01). There was no significant difference in hospitalization length and 30-day readmission between different age groups. Apart from a higher rate of open heart surgery in group A, the procedural complications were comparable between these age groups. CONCLUSION: Elderly patients had worse in-hospital outcomes in early mortality and non-home discharge following the TLE for infected CIED. There was no significant difference between elderly and non-elderly groups in prolonged hospital stay and 30-day readmission. Elderly patients did not have a higher risk of procedural complications.
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Desfibriladores Implantáveis , Marca-Passo Artificial , Idoso , Idoso de 80 Anos ou mais , Humanos , Adolescente , Adulto , Pessoa de Meia-Idade , Desfibriladores Implantáveis/efeitos adversos , Marca-Passo Artificial/efeitos adversos , Remoção de Dispositivo/efeitos adversos , Fatores de Risco , Hospitais , Resultado do Tratamento , Estudos RetrospectivosRESUMO
BACKGROUND: Long-term outcomes of sterile lead management strategies of lead abandonment (LA) or transvenous lead extraction (TLE) remain unclear. METHODS: We performed a retrospective study of a population residing in southeastern Minnesota with follow-up at the Mayo Clinic and its health systems. Patients who underwent LA or TLE of sterile leads from January 1, 2000, to January 1, 2011, and had follow-up for at least 10 years or until their death were included. RESULTS: A total of 172 patients were included in the study with 153 patients who underwent LA and 19 who underwent TLE for sterile leads. Indications for subsequent lead extraction arose in 9.1% (n = 14) of patients with initial LA and 5.3% (n = 1) in patients with initial TLE, after an average of 7 years. Moreover, 28.6% of patients in the LA cohort who required subsequent extraction did not proceed with the extraction, and among those who proceeded, 60% had clinical success and 40% had a clinical failure. Subsequent device upgrades or revisions were performed in 18.3% of patients in the LA group and 31.6% in the TLE group, with no significant differences in procedural challenges (5.2% vs. 5.3%). There was no difference in 10-year survival probability among the LA group and the TLE group (p = .64). CONCLUSION: An initial lead abandonment strategy was associated with more complicated subsequent extraction procedures compared to patients with an initial transvenous lead extraction strategy. However, there was no difference in 10-year survival probability between both lead management approaches.
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Remoção de Dispositivo , Humanos , Masculino , Feminino , Estudos Retrospectivos , Idoso , Minnesota/epidemiologia , Desfibriladores Implantáveis , Marca-Passo Artificial , Resultado do Tratamento , Pessoa de Meia-Idade , Eletrodos ImplantadosRESUMO
AIMS: The MicraTM transcatheter pacing system (TPS) (Medtronic) is the only leadless pacemaker that promotes atrioventricular (AV) synchrony via accelerometer-based atrial sensing. Data regarding the real-world experience with this novel system are scarce. We sought to characterize patients undergoing MicraTM -AV implants, describe percentage AV synchrony achieved, and analyze the causes for suboptimal AV synchrony. METHODS: In this retrospective cohort study, electronic medical records from 56 consecutive patients undergoing MicraTM -AV implants at the Mayo Clinic sites in Minnesota, Florida, and Arizona with a minimum follow-up of 3 months were reviewed. Demographic data, comorbidities, echocardiographic data, and clinical outcomes were compared among patients with and without atrial synchronous ventricular pacing (AsVP) ≥ 70%. RESULTS: Sixty-five percent of patients achieved AsVP ≥ 70%. Patients with adequate AsVP had smaller body mass indices, a lower proportion of congestive heart failure, and prior cardiac surgery. Echocardiographic parameters and procedural characteristics were similar across the two groups. Active device troubleshooting was associated with higher AsVP. The likely reasons for low AsVP were small A4-wave amplitude, high ventricular pacing burden, and inadequate device reprogramming. Importantly, in patients with low AsVP, subjective clinical worsening was not noted during follow-up. CONCLUSION: With the increasing popularity of leadless pacemakers, it is paramount for device implanting teams to be familiar with common predictors of AV synchrony and troubleshooting with MicraTM -AV devices.
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Marca-Passo Artificial , Estimulação Cardíaca Artificial/efeitos adversos , Ecocardiografia , Átrios do Coração , Ventrículos do Coração , Humanos , Marca-Passo Artificial/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A 73-year old male developed syncope during a bicycle race. Exercise stress testing demonstrated non-sustained ventricular tachycardia (NSVT) and ischemic changes. Coronary angiography revealed a 99% occluded right coronary artery which was stented; repeat stress testing demonstrated normal perfusion and NSVT. An electrophysiology study demonstrated left posterior fascicular ventricular tachycardia, which was ablated at two lower turnaround points. NSVT was observed during subsequent stress testing, prompting a repeat electrophysiology study. The inferoseptum and inferior wall were extensively ablated, along with a posteromedial papillary muscle premature ventricular complex. With no further demonstrable NSVT, the patient was cleared to return to competition.
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Ablação por Cateter , Doença da Artéria Coronariana , Taquicardia Ventricular , Idoso , Atletas , Doença da Artéria Coronariana/complicações , Eletrocardiografia , Humanos , Masculino , Músculos Papilares , Taquicardia Ventricular/complicações , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/cirurgiaRESUMO
Magnetic resonance imaging (MRI) is a valuable imaging modality for the assessment of both cardiac and non-cardiac structures. With a growing population of patients with cardiovascular implantable electronic devices (CIEDs), 50%-75% of these patients will need an MRI. MRI-conditional CIEDs have demonstrated safety of MRI scanning with such devices, yet non-conditional devices such as hybrid CIEDs which have generator and lead brand mismatch may pose a safety risk. In this retrospective study, we examined the outcomes of patients with hybrid CIEDs undergoing MRI compared to those patients with non-hybrid CIEDs. A total of 349 patients were included, of which 24 patients (7%) had hybrid CIEDs. The primary endpoint was the safety of MRI for patients with hybrid CIEDs as compared to those with non-hybrid devices, measured by the rate of adverse events, including death, lead or generator failure needing immediate replacement, loss of capture, new onset arrhythmia, or power-on reset. Secondary endpoints consisted of pre- and post-MRI changes of decreased P-wave or R-wave sensing by ≥50%, changes in pacing lead impedance by ≥50 ohms, increase in pacing thresholds by ≥ 0.5 V at 0.4 ms, and decreasing battery voltage of ≥ 0.04 V. The primary endpoint of any adverse reaction was present in 1 (4.2%) patient with a hybrid device, and consistent of atrial tachyarrhythmia, and in 10 (3.1%) patients with a non-hybrid device, and consisted of self-limited atrial and non-sustained ventricular arrhythmias; this was not statistically significant. No significant differences were found in the secondary endpoints. This study demonstrates that MRI in patients with hybrid CIEDs does not result in increased patient risk or significant device changes when compared to those patients who underwent MRI with non-hybrid CIEDs.
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Desfibriladores Implantáveis , Marca-Passo Artificial , Eletrônica , Humanos , Imageamento por Ressonância Magnética/métodos , Estudos RetrospectivosRESUMO
BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (S-ICD) has a larger generator and its implantation involves more dissection and tunneling compared to traditional transvenous defibrillator system. Liposomal bupivacaine, an extended-release bupivacaine with 72 h of duration has been used for postoperative pain management in patients undergoing S-ICD implantation. Our aim was to compare postoperative pain and opioid prescription patterns among patients undergoing S-ICD implantation who received intraprocedural liposomal bupivacaine and those who did not. METHODS: We performed a retrospective analysis of all patients who underwent subcutaneous ICD implantation from January 1, 2013 to March 30, 2018 at the Mayo Clinic in Rochester, Minnesota. Patients were categorized into those who received liposomal bupivacaine and those who did not. Data on inpatient pain score, outpatient opioid prescription rates at discharge, and doses based on oral morphine equivalents (OME) were collected. RESULTS: A total of 104 patients underwent S-ICD implantation. Intraprocedural liposomal bupivacaine was used in 69% of patients. Patients who received intraprocedural liposomal bupivacaine had similar mean inpatient pain scores (2.9 vs. 2.9, p = .786). There was also no difference in the rate of inpatient opioid administration (79.2% vs. 87.5%, p = .4139), outpatient opioid prescription (23.6% vs. 12.5%, p = .29), or mean OME (41.7-mg vs. 16.6-mg, p = .188) when comparing patients those who received intraprocedural liposomal bupivacaine and those who did not. CONCLUSION: Intraprocedural liposomal bupivacaine administration was not associated with any significant impact on postoperative pain scores, inpatient opioid administration, and outpatient opioid prescription rates or OME amounts at discharge.
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Analgésicos Opioides/uso terapêutico , Anestésicos Locais/uso terapêutico , Bupivacaína/uso terapêutico , Desfibriladores Implantáveis , Manejo da Dor/métodos , Dor Pós-Operatória/prevenção & controle , Adulto , Preparações de Ação Retardada , Feminino , Humanos , Lipossomos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos RetrospectivosRESUMO
There are two different prion conformations: (1) the cellular natural (PrPC) and (2) the scrapie (PrPSc), an infectious form that tends to aggregate under specific conditions. PrPC and PrPSc are widely different regarding secondary and tertiary structures. PrPSc contains more and longer ß-strands compared to PrPC. The lack of solved PrPSc structures precludes a proper understanding of the mechanisms related to the transition between cellular and scrapie forms, as well as the aggregation process. In order to investigate the conformational transition between PrPC and PrPSc, we applied MDeNM (molecular dynamics with excited normal modes), an enhanced sampling simulation technique that has been recently developed to probe large structural changes. These simulations yielded new structural rearrangements of the cellular prion that would have been difficult to obtain with standard MD simulations. We observed an increase in ß-sheet formation under low pH (≤ 4) and upon oligomerization, whose relevance was discussed on the basis of the energy landscape theory for protein folding. The characterization of intermediate structures corresponding to transition states allowed us to propose a conversion model from the cellular to the scrapie prion, which possibly ignites the fibril formation. This model can assist the design of new drugs to prevent neurological disorders related to the prion aggregation mechanism.
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Simulação de Dinâmica Molecular , Proteínas PrPC/química , Proteínas PrPSc/química , Agregados Proteicos , Humanos , Concentração de Íons de Hidrogênio , Conformação Proteica em Folha beta , Dobramento de ProteínaRESUMO
Aims: To evaluate coronary sinus single-site (CSSS) left ventricular pacing in adult patients with normal left ventricular ejection fraction (LVEF) when traditional right ventricular lead implantation is not feasible or is contraindicated. Methods and results: We performed a retrospective analysis of 23 patients with tricuspid valve surgery/disease who received a CSSS ventricular pacing lead to avoid crossing the tricuspid valve. Two matched control populations were obtained from patients receiving (i) conventional right ventricular single-site (RVSS) leads and (ii) coronary sinus leads for cardiac resynchronization therapy (CSCRT). Main outcomes of interest were lead stability, electrical lead parameters and change in LVEF during long-term follow-up. Successful CSSS pacing was accomplished in all 23 patients without any procedural complications. During the 5.3 ± 2.8-year follow-up 22/23 (95.7%) leads were functional with stable pacing and sensing parameters, and 1/23 (4.3%) was extracted for unrelated reasons. Compared to CSSS leads, the lead revision/abandonment was similar with RVSS leads (Hazard ratio (HR) 0.87, 95% confidence interval (CI) 0.03, 22.0), but was higher with CSCRT leads (HR 7.41, 95% CI 1.30, 139.0). There was no difference in change in LVEF between CSSS and RVSS groups (-2.4 ± 11.0 vs. 1.5 ± 12.8, P = 0.76), but LVEF improved in CSCRT group (11.2 ± 16.5%, P = 0.002). Fluoroscopy times were longer during implantation of CSSS compared to RVSS leads (25.6 ± 24.6 min vs. 12.3 ± 18.6 min, P = 0.049). Conclusion: In patients with normal LVEF, single-site ventricular pacing via the coronary sinus is a feasible, safe and reliable alternative to right ventricular pacing.
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Fibrilação Atrial/terapia , Estimulação Cardíaca Artificial/métodos , Seio Coronário/fisiopatologia , Bloqueio Cardíaco/terapia , Insuficiência Cardíaca/terapia , Doenças das Valvas Cardíacas/complicações , Valva Tricúspide/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Estimulação Cardíaca Artificial/efeitos adversos , Estudos de Viabilidade , Feminino , Bloqueio Cardíaco/complicações , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/fisiopatologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Doenças das Valvas Cardíacas/diagnóstico , Doenças das Valvas Cardíacas/fisiopatologia , Doenças das Valvas Cardíacas/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Volume Sistólico , Fatores de Tempo , Resultado do Tratamento , Valva Tricúspide/cirurgia , Função Ventricular Esquerda , Função Ventricular DireitaRESUMO
Thioredoxins are multifunctional oxidoreductase proteins implicated in the antioxidant cellular apparatus and oxidative stress. They are involved in several pathologies and are promising anticancer targets. Identification of noncatalytic binding sites is of great interest for designing new allosteric inhibitors of thioredoxin. In a recent work, we predicted normal mode motions of human thioredoxin 1 and identified two major putative hydrophobic binding sites. In this work we investigated noncovalent interactions of human thioredoxin 1 with three phenotiazinic drugs acting as prooxidant compounds by using molecular docking and circular dichroism spectrometry to probe ligand binding into the previously predicted allosteric hydrophobic pockets. Our in silico and CD spectrometry experiments suggested one preferred allosteric binding site involving helix 3 and adopting the best druggable conformation identified by NMA. The CD spectra showed binding of thioridazine into thioredoxin 1 and suggested partial helix unfolding, which most probably concerns helix 3. Taken together, these data support the strategy to design thioredoxin inhibitors targeting a druggable allosteric binding site.
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Sítio Alostérico , Fenotiazinas/farmacologia , Tiorredoxinas/metabolismo , Humanos , Interações Hidrofóbicas e Hidrofílicas , Simulação de Acoplamento Molecular , Fenotiazinas/química , Ligação Proteica , Tiorredoxinas/químicaRESUMO
BACKGROUND: Transvenous lead removal (TLR) is associated with increased mortality and morbidity. This study sought to evaluate the impact of TLR on in-hospital mortality and outcomes in patients with and without CIED infection. METHODS: From January 1, 2017, to December 31, 2020, we utilized the nationally representative, all-payer, Nationwide Readmissions Database to assess patients who underwent TLR. We categorized TLR as indicated for infection, if the patient had a diagnosis of bacteremia, sepsis, or endocarditis during the initial admission. Conversely, if none of these conditions were present, TLR was considered sterile. The impact of infective vs sterile indications of TLR on mortality and major adverse events was studied. RESULTS: Out of the total 25,144 patients who underwent TLR, 14,030 (55.8%) received TLR based on sterile indications, while 11,114 (44.2%) received TLR due to device infection, with 40.5% having systemic infection and 59.5% having isolated pocket infection. TLR due to infective indications was associated with a significant in-hospital mortality (5.59% vs 1.13%; OR = 5.16; 95% CI 4.33-6.16; p < 0.001). Moreover, when compared with sterile indications, TLR performed due to device infection was associated with a considerable risk of thromboembolic events including pulmonary embolism and stroke (OR = 3.80; 95% CI 3.23-4.47, p < 0.001). However, there was no significant difference in the conversion to open heart surgery (1.72% vs. 1.47%, p < 0.111), and infection was not an independent predictor of cardiac (OR = 1.12; 95% CI 0.97-1.29) or vascular complications (OR = 1.12; 95% CI 0.73-1.72) between the two groups. CONCLUSION: Higher in-hospital mortality and rates of thromboembolic events associated with TLR resulting from infective indications may warrant further pursuing this diagnosis in patients.
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BACKGROUND: Patients with ventricular tachycardia (VT) who require VT ablation are at high risk for readmission. This study aimed to identify the causes and outcomes of 30-day readmission after VT ablation and to analyze the predictors of recurrent VT that required rehospitalization. METHODS: Using the Nationwide Readmission Database, our study included patients aged ≥ 18 years who underwent VT catheter ablation between 2017 and 2020. Based on the International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM), we identified the causes of 30-day readmission by organ systems and analyzed their outcomes. Additional analysis was performed to determine the independent predictors of 30-day readmission for recurrent VT. RESULTS: Of the 4228 patients who underwent VT ablation, 14.2% were readmitted within 30 days of the procedure. The most common cause of readmission was cardiac events (73.6%). Among the cardiac-related readmissions, recurrent VT (47.7%) and congestive heart failure (CHF) (12.9%) were the most common etiologies. Among the readmissions, patients readmitted for CHF had the highest rate of readmission mortality (9.2%). Of the patients readmitted within 30 days of the procedure, 278 patients (6.8%) were readmitted for recurrent VT. Via multivariable analysis, CHF (OR: 1.97; 95% CI: 1.12-3.47; P = 0.02) and non-elective index admissions (OR: 1.63; 95% CI: 1.04-2.55; P = 0.03) were identified as the independent predictors predictive of 30-day readmissions for recurrent VT. CONCLUSIONS: Recurrent VT was the most common cause of readmission after the VT ablation procedure, and CHF and non-elective index admissions were the significant predictors of these early readmissions. Readmission due to CHF had the highest mortality rate during readmission.
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Ablação por Cateter , Insuficiência Cardíaca , Taquicardia Ventricular , Humanos , Readmissão do Paciente , Resultado do Tratamento , Hospitalização , Insuficiência Cardíaca/complicações , Ablação por Cateter/métodosRESUMO
Aims: Cardiac amyloidosis (CA) is common in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Cardiac amyloidosis has poor outcomes, and its assessment in all TAVR patients is costly and challenging. Electrocardiogram (ECG) artificial intelligence (AI) algorithms that screen for CA may be useful to identify at-risk patients. Methods and results: In this retrospective analysis of our institutional National Cardiovascular Disease Registry (NCDR)-TAVR database, patients undergoing TAVR between January 2012 and December 2018 were included. Pre-TAVR CA probability was analysed by an ECG AI predictive model, with >50% risk defined as high probability for CA. Univariable and propensity score covariate adjustment analyses using Cox regression were performed to compare clinical outcomes between patients with high CA probability vs. those with low probability at 1-year follow-up after TAVR. Of 1426 patients who underwent TAVR (mean age 81.0 ± 8.5 years, 57.6% male), 349 (24.4%) had high CA probability on pre-procedure ECG. Only 17 (1.2%) had a clinical diagnosis of CA. After multivariable adjustment, high probability of CA by ECG AI algorithm was significantly associated with increased all-cause mortality [hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.01-1.96, P = 0.046] and higher rates of major adverse cardiovascular events (transient ischaemic attack (TIA)/stroke, myocardial infarction, and heart failure hospitalizations] (HR 1.36, 95% CI 1.01-1.82, P = 0.041), driven primarily by heart failure hospitalizations (HR 1.58, 95% CI 1.13-2.20, P = 0.008) at 1-year follow-up. There were no significant differences in TIA/stroke or myocardial infarction. Conclusion: Artificial intelligence applied to pre-TAVR ECGs identifies a subgroup at higher risk of clinical events. These targeted patients may benefit from further diagnostic evaluation for CA.
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The Thioredoxin (Trx) system plays important roles in several diseases (e.g. cancer, viral infections, cardiovascular and neurodegenerative diseases). Therefore, there is a therapeutic interest in the design of modulators of this system. In this work, we used normal mode analysis to identify putative binding site regions for Human Trx1 that arise from global motions. We identified three possible inhibitor's binding regions that corroborate previous experimental findings. We show that intrinsic motions of the protein are related to the exposure of hydrophobic regions and non-active site cysteines that could constitute new binding sites for inhibitors.
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Tiorredoxinas/química , Regulação Alostérica , Domínio Catalítico , Descoberta de Drogas , Humanos , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Estrutura Secundária de Proteína , Bibliotecas de Moléculas Pequenas , Propriedades de Superfície , Termodinâmica , Tiorredoxinas/antagonistas & inibidoresRESUMO
BACKGROUND: Recent in-vitro observations suggest that left ventricular (LV) contraction is powered by 'stretch activation', an intrinsic mechanism by which the stretching of an activated cardiomyocyte causes delayed force redevelopment. We hypothesized that mechanical dyssynchrony is related to prolonged early systolic stretch that delays the timing of peak segmental shortening. METHODS AND RESULTS: The time intervals from R wave to segmental longitudinal stretch in early systole (Tstretch) and peak shortening (Tpeak) and the respective standard deviations (σTstretch and σTpeak) were measured by speckle-tracking echocardiography in 57 patients undergoing cardiac resynchronization therapy (CRT). The percentage of time spent in shortening, normalized to Tpeak duration [corrected ΔT=(Tpeak-Tstretch)/Tpeak] correlated with LV reverse remodeling (reduction in end-systolic volume ≥ 15%). Of the 57 patients, 40 (70.2%) demonstrated LV reverse remodeling at an average follow-up of 263 ± 125 days after CRT. At baseline, Tstretch and σTstretch correlated with Tpeak and σTpeak, respectively. Though there was no difference in Tstretch, Tpeak, σTstretch and σTpeak between responders and non-responders, corrected ΔT in the mid-lateral and mid-septal segments was shorter in the responders (P<0.05 for both) and the average of the 2 independently predicted LV reverse remodeling (area under the curve: 0.77, P=0.001). CONCLUSIONS: Mapping LV segmental shortening in relation to early systolic stretch may aid dyssynchrony assessment in patients undergoing CRT.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Função Ventricular Esquerda , Remodelação Ventricular , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/terapia , Ventrículos do Coração , Humanos , Masculino , Pessoa de Meia-Idade , Sístole , Fatores de TempoRESUMO
Ecdysteroid signal transduction is a key process in insect development and therefore an important target for insecticide development. We employed an in vitro cell-based reporter bioassay for the screening of potential ecdysone receptor (EcR) agonistic and antagonistic compounds. Natural ecdysteroids were assayed with ecdysteroid-responsive cell line cultures that were transiently transfected with the reporter plasmid ERE-b.act.luc. We used the dipteran Schneider S2 cells of Drosophila melanogaster and the lepidopteran Bm5 cells of Bombyx mori, representing important pest insects in medicine and agriculture. Measurements showed an EcR agonistic activity only for cyasterone both in S2 (EC50=3.3µM) and Bm5 cells (EC50=5.3µM), which was low compared to that of the commercial dibenzoylhydrazine-based insecticide tebufenozide (EC50=0.71µM and 0.00089µM, respectively). Interestingly, a strong antagonistic activity was found for castasterone in S2 cells with an IC50 of 0.039µM; in Bm5 cells this effect only became visible at much higher concentrations (IC50=18µM). To gain more insight in the EcR interaction, three-dimensional modeling of dipteran and lepidopteran EcR-LBD was performed. In conclusion, we showed that the EcR cell-based reporter bioassay tested here is a useful and practical tool for the screening of candidate EcR agonists and antagonists. The docking experiments as well as the normal mode analysis provided evidence that the antagonist activity of castasterone may be through direct binding with the receptor with specific changes in protein flexibility. The search for new ecdysteroid-like compounds may be particularly relevant for dipterans because the activity of dibenzoylhydrazines appears to be correlated with an extension of the EcR-LBD binding pocket that is prominent in lepidopteran receptors but less so in the modeled dipteran structure.
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Ecdisteroides/metabolismo , Lepidópteros/metabolismo , Receptores de Esteroides/metabolismo , Animais , Linhagem Celular , Dípteros , Ligação Proteica , Transdução de SinaisRESUMO
Background: Real-world clinical data on the adverse events related to the use of cryoballoon catheter for pulmonary vein isolation remains limited. Objective: To report and describe the adverse events related to the use of Artic Front cryoballoon catheters (Arctic Front, Arctic Front Advance, and Arctic Front Advance Pro) reported in the Food and Drug Administration's (FDA) Manufacturers and User Defined Experience (MAUDE) database. Methods: We reviewed all the adverse events reported to the FDA MAUDE database over a 10.7-year study period from January 01, 2011 to September 31, 2021. All events were independently reviewed by two physicians. Results: During the study period, a total of 320 procedural-related adverse events reported in the MAUDE database were identified. The most common adverse event was transient or persistent phrenic nerve palsy (PNP), accounting for 48% of all events. This was followed by cardiac perforation (15%), pulmonary vein stenosis (8%), transient ischemic attack or stroke (6%), vascular injury (4%), transient or persistent ST-elevation myocardial infarction (3%), hemoptysis (2%), pericarditis (2%), and esophageal ulcer or fistula (1%). There were six reported intra-procedural death events as a result of cardiac perforation. Conclusion: The two most common procedural adverse events associated with cryoballoon ablation were PNP and cardiac perforation. All cases of procedural mortality were due to cardiac perforation.
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The outcomes of leadless pacemaker (LP) implantation after transvenous lead removal (TLR) of infected cardiac implantable electronic devices (CIEDs) are not well-established. This study sought to describe the outcomes of LP implantation after TLR of infected CIED. We conducted a literature search using PubMed and Embase for a combination of terms including LP implantation, transvenous lead extraction, TLR, transvenous lead explant, infected CIED, infected pacemaker, and infected implantable cardioverter defibrillator. The inclusion criterion was LP implantation after TLR of infected CIED. The exclusion criterion was TLR for noninfectious reasons. Study end points included procedural complications and LP infection during follow-up. Of 132 publications reviewed, 13 studies with a total of 253 patients (74 ± 14 years of age, 174 [69%] males) were included. The most common indication of the initial device implantations was a high-degree atrioventricular block (n = 100 of 253, 39.5%). Of the 253 patients included, 105 patients (41.5%) underwent concomitant LP implantation during the TLR procedure, and 36 patients (14.2%) had temporary transvenous pacing as a bridge from TLR to LP implantation. Of the 148 patients with data on the type of CIED infection, 56.8% had systemic CIED infection and 43.2% had isolated pocket infection. Staphylococcus aureus was the most common causative organism in 33% of the reported patients. The LP was implanted an average of 5.4 ± 10.7 days after TLR of infected CIED. During the LP implantation, 1 patient (0.4%) had unsuccessful implantation because of an intraprocedural complication requiring sternotomy. After LP implantation, 2 patients (0.8%) developed groin hematoma, 2 patients (0.8%) developed femoral arteriovenous fistula, and 1 patient (0.4%) developed pericardial effusion requiring pericardiocentesis. During a mean follow-up of 11.3 ± 10.6 months, 3 patients (1.2%) developed pacemaker syndrome, 1 patient (0.4%) developed acute on chronic heart failure exacerbation, and only 1 patient (0.4%) developed LP-related infection requiring LP retrieval. This study suggests that LP implant is feasible and safe after removal of infected CIED with cumulative adverse events at 4% and a reinfection rate of 0.4%. Large prospective studies are needed to better evaluate the best timing of LP implantation after TLR of an infected CIED.
Assuntos
Desfibriladores Implantáveis , Marca-Passo Artificial , Infecções Relacionadas à Prótese , Masculino , Humanos , Feminino , Resultado do Tratamento , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/terapia , Infecções Relacionadas à Prótese/etiologia , Remoção de Dispositivo/efeitos adversos , Marca-Passo Artificial/efeitos adversos , Desfibriladores Implantáveis/efeitos adversos , Estudos RetrospectivosRESUMO
Primary cardiac sarcoma is a rare type of intracardiac mass. This report describes a patient with atrial flutter who had a new right atrial mass incidentally discovered on transesophageal echocardiography. A thrombus was suspected based on radiographic appearance, but there was minimal change with anticoagulation. The mass was resected and found to be an undifferentiated pleomorphic cardiac sarcoma, an uncommon sub-type within the already rare category of primary cardiac neoplasms. This report highlights the importance of considering primary malignancy and thoroughly correlating radiographic and clinical evidence during the diagnostic workup of patients with intracardiac masses.
Assuntos
Fibrilação Atrial , Flutter Atrial , Neoplasias Cardíacas , Sarcoma , Humanos , Ecocardiografia Transesofagiana , Neoplasias Cardíacas/complicações , Neoplasias Cardíacas/diagnóstico , Neoplasias Cardíacas/cirurgia , Sarcoma/complicações , Sarcoma/diagnóstico , Sarcoma/cirurgia , Átrios do Coração/diagnóstico por imagemRESUMO
BACKGROUND: Recognition of the causes of early mortality after ventricular tachycardia (VT) ablation in patients with reduced left ventricular ejection fraction (LVEF) is an essential step toward improving postprocedural outcomes. OBJECTIVES: This study sought to determine the causes of early mortality (≤30 days) after VT ablation in patients with reduced LVEF and to understand further the circumstances surrounding death after the procedure. METHODS: We performed a retrospective analysis of all patients undergoing VT ablation in patients with reduced LVEF from January 1, 2013, to November 10, 2021, at the Mayo Clinic (Rochester, Phoenix, and Jacksonville). Causes of death were identified through a detailed chart review of the electronic health record within the Mayo Clinic system and outside records. RESULTS: A total of 503 patients (mean age 63 ± 13 years, 11.2% women) with ejection fraction <50% were included in the study. The 30-day all-cause mortality rate was 5.0% (n = 25), and the mortality rate due to a procedural complication was 0.4%. Among all 30-day deaths, recurrent VT was the most common primary cause of death (44.0%). This was followed by decompensated heart failure (28.0%), procedure-related death (8.0%), cerebrovascular accident (4.0%), and infection (4.0%). Most patients (91.0%) who died from VT had VT recurrence within 3 days of the ablation. The average PAINESD score among early mortality was 20 ± 4, and 92.0% of these patients (n = 23) had a score >15. Significant predictors of early mortality included nonischemic cardiomyopathy, lower LVEF, electrical storm, and ventricular fibrillation. CONCLUSIONS: The overall early mortality (≤30 days) rate after catheter ablation of VT in patients with reduced LVEF was 5.0%, but the death rate directly due to a procedural complication was only 0.4%. The most common cause of death was recurrent VT, followed by heart failure. Further research into ablation strategies is vital to improving the safety, efficacy, and durability of VT ablation.