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1.
Pacing Clin Electrophysiol ; 42(12): 1558-1565, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31589336

RESUMO

BACKGROUND: A number of patients with neurally mediated syncope (NMS) have isolated QRS complexes of very low voltage (≤0.3 mV) in the frontal plane leads on the 12-lead electrocardiogram (ECG). HYPOTHESIS: The aim of this study was to assess the importance of QRS voltage in predicting response to tilt-table testing (TTT) in patients with suspected NMS. METHODS: We included 216 patients (age: 49 ± 20 years, 103 men) with suspected NMS who had either a positive or negative response to TTT (n = 91 TTT+, and n = 125 TTT-). The QRS voltage was measured in mV on 12-lead ECGs performed within 3 days of the TTT. The lowest QRS voltage (QRSmin), as well as the voltage in each of the 12 leads was also determined. RESULTS: Very low voltage (QRSmin  ≤ 0.3 mV) in the frontal leads was significantly more prevalent in the TTT+ group than in the TTT- group (74 vs 22%, respectively; P  < .001). Patients in the TTT+ group had significantly lower QRSmin when compared to patients in the TTT- group. QRSmin predicted a positive tilt-table test in a multivariate model that also included patient gender, height, history of presyncope, QRS duration, and left ventricular end-diastolic diameter indexed to height. ROC analysis showed that QRSmin of ≥0.3 mV discriminated between TTT+ and TTT- patients with a sensitivity of 78% and specificity of 68%. CONCLUSION: Isolated very low QRS voltage in the frontal leads predicts a positive response to TTT in patients with suspected NMS.


Assuntos
Sistema de Condução Cardíaco/fisiopatologia , Síncope Vasovagal/fisiopatologia , Teste da Mesa Inclinada , Eletrocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade
2.
J Acoust Soc Am ; 143(4): EL285, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29716304

RESUMO

The echolocation signals of most beaked whale species are still unknown. In fact, out of the 22 species comprising the family Ziphiidae, only the echolocation pulses for 7 species have been clearly described. This study describes two distinct beaked whale echolocation signals recorded in the Cook Strait region using passive acoustic technology. These signals differ from previously described Ziphiid species clicks. A description of the time-frequency characteristics of the two signals is provided. Understanding the characteristics of these signals is necessary to correctly identify species from their echolocation signals and enables future monitoring of beaked whales using passive acoustics techniques.


Assuntos
Acústica , Ecolocação/fisiologia , Vocalização Animal/fisiologia , Baleias/fisiologia , Animais , Nova Zelândia , Especificidade da Espécie , Fatores de Tempo , Baleias/classificação
3.
J Acoust Soc Am ; 142(3): EL281, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28964046

RESUMO

Geotechnical site investigations prior to marine construction typically involve shallow, small-core drilling and standard penetration testing (SPT), during which a small tube is hammered into the ground at the bottom of the borehole. Drilling (120 kW, 83 mm diameter drillbit, 1500 rpm, 16-17 m drill depth in sand and mudstone) and SPT (50 mm diameter test tube, 15 mm wall thickness, 100 kg hammer, 1 m drop height) by a jack-up rig in 7-13 m of water were recorded with a drifting hydrophone at 10-50 m range. Source levels were 142-145 dB re 1 µPa rms @ 1 m (30-2000 Hz) for drilling and 151-160 dB re 1 µPa2s @ 1 m (20-24 000 Hz) for SPT.

4.
Antimicrob Agents Chemother ; 59(4): 2439-42, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25605364

RESUMO

Preliminary enthusiasm over the encouraging spectrum and in vitro activities of siderophore conjugates, such as MB-1, was recently tempered by unexpected variability in in vivo efficacy. The need for these conjugates to compete for iron with endogenously produced siderophores has exposed a significant liability for this novel antibacterial strategy. Here, we have exploited dependence on efflux for siderophore secretion in Pseudomonas aeruginosa and provide evidence that efflux inhibition may circumvent this in vivo-relevant resistance liability.


Assuntos
Antibacterianos/farmacologia , Monobactamas/farmacologia , Piridonas/farmacologia , Sideróforos/farmacologia , Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Testes de Sensibilidade Microbiana , Mutação , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/enzimologia , Reserpina/farmacologia
5.
Sleep Breath ; 19(1): 407-10, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24809294

RESUMO

BACKGROUND: The relationship between obstructive sleep apnea (OSA) and increased risk for atrial fibrillation (AF) has been well established in previous studies. The relationship between OSA and silent AF is unknown. We hypothesized that patients with OSA but no known history of AF are at an increased risk for the arrhythmia and may be detectable by prolonged electrocardiogram (ECG) monitoring. In this study, we examined whether 7 days of extended cardiac monitoring with an ECG event recorder is an effective screening tool to detect intermittent, silent AF in patients with severe OSA. METHODS: The study was a prospective observational study. Randomly chosen patients with newly diagnosed severe OSA, apnea-hypopnea index (AHI) ≥ 30, were included. Demographic, medical history, and sleep data were collected. Patients with a history of AF or symptoms of palpitations were excluded from participating. Seven consecutive days of ambulatory ECG event recording (with Model ER920W, eCardio, Houston, TX) were performed prior to the initiation of CPAP treatment. RESULTS: A total of 20 subjects, with a BMI of 38.8 ± 12.2, successfully completed the study. The mean age group was 52.6 ± 12.6 years and mean AHI 63.5 ± 29.2. The majority of subjects (70 %) had no abnormal cardiac rhythms detected. AF lasting for 7 s was seen in one subject, and paroxysmal atrial tachycardia lasting for 3.6 s was seen in another. Clinically relevant AF was not detected in any of the subjects. CONCLUSION: In patients with severe OSA without a known history of AF, 7 days of extended cardiac monitoring with an ECG event recorder did not detect clinically meaningful, silent AF.


Assuntos
Fibrilação Atrial/diagnóstico , Eletrocardiografia Ambulatorial , Apneia Obstrutiva do Sono/diagnóstico , Adulto , Idoso , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polissonografia , Estudos Prospectivos , Fatores de Risco
6.
Antimicrob Agents Chemother ; 57(9): 4197-207, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23774440

RESUMO

Multidrug resistance in Gram-negative bacteria has become so threatening to human health that new antibacterial platforms are desperately needed to combat these deadly infections. The concept of siderophore conjugation, which facilitates compound uptake across the outer membrane by hijacking bacterial iron acquisition systems, has received significant attention in recent years. While standard in vitro MIC and resistance frequency methods demonstrate that these compounds are potent, broad-spectrum antibacterial agents whose activity should not be threatened by unacceptably high spontaneous resistance rates, recapitulation of these results in animal models can prove unreliable, partially because of the differences in iron availability in these different methods. Here, we describe the characterization of MB-1, a novel siderophore-conjugated monobactam that demonstrates excellent in vitro activity against Pseudomonas aeruginosa when tested using standard assay conditions. Unfortunately, the in vitro findings did not correlate with the in vivo results we obtained, as multiple strains were not effectively treated by MB-1 despite having low MICs. To address this, we also describe the development of new in vitro assays that were predictive of efficacy in mouse models, and we provide evidence that competition with native siderophores could contribute to the recalcitrance of some P. aeruginosa isolates in vivo.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Monobactamas/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Piridonas/farmacologia , Sideróforos/farmacologia , Adaptação Fisiológica/efeitos dos fármacos , Adaptação Fisiológica/genética , Animais , Antibacterianos/química , Bioensaio , Farmacorresistência Bacteriana/genética , Feminino , Ferro/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Testes de Sensibilidade Microbiana , Monobactamas/química , Mutagênese Sítio-Dirigida , Oligopeptídeos/genética , Oligopeptídeos/metabolismo , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/crescimento & desenvolvimento , Piridonas/química , Sideróforos/genética , Sideróforos/metabolismo , Falha de Tratamento
7.
Ann Noninvasive Electrocardiol ; 18(4): 336-43, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23879273

RESUMO

BACKGROUND: The ventriculophasic response (VR) refers to shortening of sinus cycle length during heart block when a QRS complex is interposed between 2 P waves. Our purpose was to analyze its relationship to respiratory sinus arrhythmia (SA) and to compare VR in relation to paced versus intrinsic QRS complexes. METHODS: Patients with advanced heart block had their pacer devices temporarily programmed to ventricular inhibited mode at 30 ppm. In 35 subjects, we analyzed VR and SA before, during and after 3 cycles of deep breathing. In 16 other patients we compared VR in the presence of paced versus narrower intrinsic QRS complexes. RESULTS: The magnitude of P-P interval shortening surrounding QRS complexes during inspiration correlated with SA (r = 0.36, P = 0.03). The prevalence of VR increased from 37% at baseline to 77% of subjects during deep breathing (P = 0.02). The mean P-P interval shortening was greater surrounding intrinsic QRS complexes than paced QRS complexes (3.6 ± 3.6% vs. 1.4 ± 1.1%, P = 0.02). The prevalence of VR increased from 25% during paced rhythm to 56% when intrinsic complexes were present. CONCLUSION: VR, like SA, increases with deep breathing and likely reflects intact parasympathetic nervous system function. Its increase in the presence of narrower beats suggests it may reflect ventricular synchrony.


Assuntos
Arritmia Sinusal/diagnóstico , Estimulação Cardíaca Artificial/métodos , Desfibriladores Implantáveis , Eletrocardiografia , Bloqueio Cardíaco/terapia , Disfunção Ventricular Esquerda/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Arritmia Sinusal/mortalidade , Arritmia Sinusal/terapia , Estudos de Coortes , Comorbidade , Feminino , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/mortalidade , Humanos , Masculino , Sistema Nervoso Parassimpático/fisiopatologia , Prognóstico , Estudos Prospectivos , Tempo de Reação , Medição de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Resultado do Tratamento , Disfunção Ventricular Esquerda/mortalidade , Disfunção Ventricular Esquerda/fisiopatologia
8.
Ann Noninvasive Electrocardiol ; 18(1): 21-8, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23347023

RESUMO

BACKGROUND: The 2009 "AHA/ACCF/HRS Recommendations for Standardization and Interpretation of the Electrocardiogram" state that left ventricular hypertrophy (LVH) criteria that include R-wave amplitude in leads I and aVL are not likely reliable in the presence of left anterior fascicular block (LAFB). This statement was referenced to three relatively small studies. The present study reexamines the utility of selected electrocardiographic (ECG) criteria for LVH in the presence of LAFB. METHODS: We identified 185 ECG tracings with LAFB from patients in whom echocardiogram had been performed within 30 days of the ECG. These ECGs were evaluated for the presence of selected LVH criteria: (1) Sokolow index (R-wave-aVL > 11 mm); (2) Cornell criteria (R-wave-aVL + S-wave-V3 > 28 mm in men (>20 mm in women); (3) Gertsch criterion (S-wave-III + (R + S) maximal precordial >30 mm); and (4) Bozzi criterion (SV1 or SV2 + (RV6 + SV6) > 25 mm). The "gold standard" for LVH was left ventricular mass index on echocardiogram. RESULTS: Although the aVL-based LVH criteria demonstrated lower sensitivity (45-68%) and a trend toward higher specificity (67-81%) compared to non-aVL-based criteria, the four studied criteria demonstrated similar diagnostic accuracy. CONCLUSIONS: In the presence of LAFB, the aVL-based Sokolow index and Cornell criteria, which were excluded from 2009 multisociety ECG guidelines, identify LVH with similar diagnostic accuracy as the non-aVL-based criteria that were included. Moreover, they are easier to calculate and are included in some of the computer-assisted ECG interpretation software presently in use. Their exclusion from the 2009 guidelines was unnecessary.


Assuntos
Eletrocardiografia , Hipertrofia Ventricular Esquerda/diagnóstico , Guias de Prática Clínica como Assunto , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Ecocardiografia , Feminino , Humanos , Hipertrofia Ventricular Esquerda/fisiopatologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Processamento de Sinais Assistido por Computador
9.
J Acoust Soc Am ; 133(6): EL465-70, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23742441

RESUMO

Underwater acoustic recordings of six Floating Production Storage and Offloading (FPSO) vessels moored off Western Australia are presented. Monopole source spectra were computed for use in environmental impact assessments of underwater noise. Given that operations on the FPSOs varied over the period of recording, and were sometimes unknown, the authors present a statistical approach to noise level estimation. No significant or consistent aspect dependence was found for the six FPSOs. Noise levels did not scale with FPSO size or power. The 5th, 50th (median), and 95th percentile source levels (broadband, 20 to 2500 Hz) were 188, 181, and 173 dB re 1 µPa @ 1 m, respectively.

10.
ACS Biomater Sci Eng ; 9(9): 5163-5175, 2023 09 11.
Artigo em Inglês | MEDLINE | ID: mdl-37647169

RESUMO

Chronic stress can lead to prolonged adrenal gland secretion of cortisol, resulting in human ailments such as anxiety, post-traumatic stress disorder, metabolic syndrome, diabetes, immunosuppression, and cardiomyopathy. Real time monitoring of chronic increases in cortisol and intervening therapies to minimize the physiological effects of stress would be beneficial to prevent these endocrine related illnesses. Gut microbiota have shown the ability to secrete, respond, and even regulate endocrine hormones. One such microbe, Clostridium scindens, responds transcriptionally to cortisol. We engineered these cortisol responsive genetic elements from C. scindens into an enteric probiotic, E. coli Nissle 1917, to drive the expression of a fluorescent reporter allowing for the designing, testing, and building of a robust and physiologically relevant novel cortisol probiotic sensor. This smart probiotic was further engineered to be more sensitive and to respond to elevated cortisol by expressing tryptophan decarboxylase, thereby bestowing the ability to generate tryptamine and serotonin. Here we show that upon cortisol treatment the smart probiotic produces measurable amounts of tryptamine. Accumulated levels of these neuromodulators should improve mood, anxiety, and depression and drive down cortisol levels. Importantly, this work can serve as a model for the engineering of a sense-and-respond probiotic to modulate the gut-brain axis.


Assuntos
Escherichia coli , Hidrocortisona , Humanos , Engenharia
11.
Sch Psychol ; 38(4): 199-214, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37053426

RESUMO

Oral language and early literacy skills are theorized to provide the foundation for reading acquisition. To understand these relations, methods are needed that depict dynamic skill development in the context of reading acquisition. We modeled contributions of school-entry skills and early skill trajectories to later reading with 105 5-year-old children beginning primary school and formal literacy instruction in New Zealand. Children were assessed at school-entry (Preschool Early Literacy Indicators), followed every fourth school week over their first 6 months of school (five probes of First Sound Fluency, Letter Sound Fluency, and New Zealand Word Identification Fluency: Year 1), and after 1 year of school (researcher-administered and school-used indices of literacy-related skills and reading progress). Modified latent change score (mLCS) modeling was used to describe skill development from repeated progress-monitoring data. Ordinal regression and structural equation modeling (path analyses) indicated skills at school-entry and early learning trajectories, indexed by mLCS, predicted children's early literacy progress. Results have implications for research and screening in beginning reading, supporting school-entry screening and progress monitoring of early literacy skills in beginning reading acquisition. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Alfabetização , Leitura , Humanos , Pré-Escolar , Instituições Acadêmicas , Nova Zelândia
12.
Antimicrob Agents Chemother ; 56(12): 6334-42, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23027195

RESUMO

The incidence of hospital-acquired infections with multidrug-resistant (MDR) Gram-negative pathogens is increasing at an alarming rate. Equally alarming is the overall lack of efficacious therapeutic options for clinicians, which is due primarily to the acquisition and development of various antibiotic resistance mechanisms that render these drugs ineffective. Among these mechanisms is the reduced permeability of the outer membrane, which prevents many marketed antibiotics from traversing this barrier. To circumvent this, recent drug discovery efforts have focused on conjugating a siderophore moiety to a pharmacologically active compound that has been designed to hijack the bacterial siderophore transport system and trick cells into importing the active drug by recognizing it as a nutritionally beneficial compound. MC-1, a novel siderophore-conjugated ß-lactam that promotes its own uptake into bacteria, has exquisite activity against many Gram-negative pathogens. While the inclusion of the siderophore was originally designed to facilitate outer membrane penetration into Gram-negative cells, here we show that this structural moiety also renders other clinically relevant antibiotic resistance mechanisms unable to affect MC-1 efficacy. Resistance frequency determinations and subsequent characterization of first-step resistant mutants identified PiuA, a TonB-dependent outer membrane siderophore receptor, as the primary means of MC-1 entry into Pseudomonas aeruginosa. While the MICs of these mutants were increased 32-fold relative to the parental strain in vitro, we show that this resistance phenotype is not relevant in vivo, as alternative siderophore-mediated uptake mechanisms compensated for the loss of PiuA under iron-limiting conditions.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/fisiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/genética , beta-Lactamas/farmacologia , Animais , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Western Blotting , Clonagem Molecular , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana/genética , Farmacorresistência Bacteriana Múltipla/genética , Escherichia coli/genética , Biblioteca Gênica , Camundongos , Porinas/genética , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/genética , Sepse/tratamento farmacológico , Sepse/microbiologia , Sideróforos , beta-Lactamases/biossíntese , beta-Lactamases/genética
13.
R Soc Open Sci ; 8(3): 201503, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33959320

RESUMO

Baleen whales reliably produce stereotyped vocalizations, enabling their spatio-temporal distributions to be inferred from acoustic detections. Soundscape analysis provides an integrated approach whereby vocal species, such as baleen whales, are sampled holistically with other acoustic contributors to their environment. Acoustic elements that occur concurrently in space, time and/or frequency can indicate overlaps between free-ranging species and potential stressors. Such information can inform risk assessment framework models. Here, we demonstrate the utility of soundscape monitoring in central New Zealand, an area of high cetacean diversity where potential threats are poorly understood. Pygmy blue whale calls were abundant in the South Taranaki Bight (STB) throughout recording periods and were also detected near Kaikoura during autumn. Humpback, Antarctic blue and Antarctic minke whales were detected in winter and spring, during migration. Wind, rain, tidal and wave activity increased ambient sound levels in both deep- and shallow-water environments across a broad range of frequencies, including those used by baleen whales, and sound from shipping, seismic surveys and earthquakes overlapped in time, space and frequency with whale calls. The results highlight the feasibility of soundscape analysis to quantify and understand potential stressors to free-ranging species, which is essential for conservation and management decisions.

14.
Front Med (Lausanne) ; 8: 749732, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34589507

RESUMO

In response to the COVID-19 pandemic, immediate and scalable testing solutions are needed to direct return to full capacity planning in the general public and across the Department of Defense (DoD). To fully understand the extent to which a population has been affected by COVID-19, active monitoring approaches require an estimation of overall seroprevalence in addition to accurate, affordable, and rapid tests to detect current SARS-CoV-2 infection. In this study, researchers in the Air Force Research Laboratory's 711th Human Performance Wing, Airman Systems Directorate evaluated the performance of various testing methods for the detection of SARS-CoV-2 antibodies and viral RNA in asymptomatic adults working at Wright-Patterson Air Force Base and the surrounding area during the period of 23 July 2020-23 Oct 2020. Altogether, there was a seroprevalance of 3.09% and an active infection rate of 0.5% (determined via the testing of saliva samples) amongst individuals tested, both of which were comparable to local and national averages at the time. This work also presents technical and non-technical assessments of various testing strategies as compared to the gold standard approaches (e.g., lateral flow assays vs. ELISA and RT-LAMP vs. RT-PCR) in order to explore orthogonal supply chains and fieldability. Exploration and validation of multiple testing strategies will allow the DoD and other workforces to make informed responses to COVID-19 and future pandemics.

15.
Heart Rhythm ; 16(12): 1862-1869, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31201963

RESUMO

BACKGROUND: The study was prompted by our observation that some patients with neurally mediated syncope (NMS) have an isolated QRS complex, of very low voltage (≤0.3 mV cutoff), in 1 of the frontal leads on the 12-lead electrocardiogram. OBJECTIVE: To prospectively evaluate whether the presence of isolated very low voltage (VLV) predicts recurrence of NMS. METHODS: We included 205 patients (aged 50 ± 17 years) with a median of 3 syncopal episodes. Tilt testing was performed in all patients and was positive in 87 (42%). The patients were followed for a median of 14 months. RESULTS: VLV in frontal leads was present in 92 patients (45%). During the follow-up period 60 patients experienced recurrence of syncope. The actuarial total syncope recurrence rate at 1 year was 32% (95% confidence interval [CI 23%-44%) in patients with isolated VLV in frontal plane leads, and 14% (95% CI 8%-24%) in patients without VLV (log-rank test P < .0001). The significant relationship between the presence of isolated VLV in the frontal leads and syncope recurrence was retained in Cox multivariate analysis that included the history of presyncope and syncope as well as the left ventricular end-diastolic diameter. The presence of isolated VLV in frontal leads was associated with a 3-fold increase of the risk of recurrent syncope. CONCLUSIONS: Isolated very low QRS voltage in the frontal leads predicts recurrence of NMS independent of clinical factors that predict recurrence of syncope in such patients. This phenomenon may help generate new diagnostic tools and insights into the pathogenesis of NMS.


Assuntos
Eletrocardiografia/métodos , Síncope Vasovagal , Correlação de Dados , Ecocardiografia/métodos , Feminino , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Valor Preditivo dos Testes , Prognóstico , Recidiva , Síncope Vasovagal/diagnóstico , Síncope Vasovagal/fisiopatologia
16.
J Am Coll Cardiol ; 72(6): 636-645, 2018 08 07.
Artigo em Inglês | MEDLINE | ID: mdl-30071993

RESUMO

BACKGROUND: Ventricular tachycardia (VT) and ventricular fibrillation (VF) remain a challenging problem in patients with implantable cardioverter-defibrillators (ICDs). OBJECTIVES: This study aimed to determine whether ranolazine administration decreases the likelihood of VT, VF, or death in patients with an ICD. METHODS: This was double-blind, placebo-controlled clinical trial in which high-risk ICD patients with ischemic or nonischemic cardiomyopathy were randomized to 1,000 mg ranolazine twice a day or placebo. The primary endpoint was VT or VF requiring appropriate ICD therapy or death, whichever occurred first. Pre-specified secondary endpoints included ICD shock for VT, VF, or death and recurrent VT or VF requiring ICD therapy. RESULTS: Among 1,012 ICD patients (510 randomized to ranolazine and 502 to placebo) the mean age was 64 ± 10 years and 18% were women. During 28 ± 16 months of follow-up there were 372 (37%) patients with primary endpoint, 270 (27%) patients with VT or VF, and 148 (15%) deaths. The blinded study drug was discontinued in 199 (39.6%) patients receiving placebo and in 253 (49.6%) patients receiving ranolazine (p = 0.001). The hazard ratio for ranolazine versus placebo was 0.84 (95% confidence interval: 0.67 to 1.05; p = 0.117) for VT, VF, or death. In a pre-specified secondary analysis, patients randomized to ranolazine had a marginally significant lower risk of ICD therapies for recurrent VT or VF (hazard ratio: 0.70; 95% confidence interval: 0.51 to 0.96; p = 0.028). There were no other significant treatment effects in other pre-specified secondary analyses, which included individual components of the primary endpoint, inappropriate shocks, cardiac hospitalizations, and quality of life. CONCLUSIONS: In high-risk ICD patients, treatment with ranolazine did not significantly reduce the incidence of the first VT or VF, or death. However, the study was underpowered to detect a difference in the primary endpoint. In prespecified secondary endpoint analyses, ranolazine administration was associated with a significant reduction in recurrent VT or VF requiring ICD therapy without evidence for increased mortality. (Ranolazine Implantable Cardioverter-Defibrillator Trial [RAID]; NCT01215253).


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Desfibriladores Implantáveis/tendências , Ranolazina/uso terapêutico , Taquicardia Ventricular/prevenção & controle , Fibrilação Ventricular/prevenção & controle , Idoso , Desfibriladores Implantáveis/efeitos adversos , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Taquicardia Ventricular/epidemiologia , Taquicardia Ventricular/fisiopatologia , Fibrilação Ventricular/epidemiologia , Fibrilação Ventricular/fisiopatologia
17.
Am J Cardiol ; 100(10): 1561-5, 2007 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-17996520

RESUMO

Standard coronary venous angiography (SCVA) provides a static, fixed projection of the coronary venous (CV) tree. High-speed rotational coronary venous angiography (RCVA) is a novel method of mapping CV anatomy using dynamic, multiangle visualization. The purpose of this study was to assess the value of RCVA during cardiac resynchronization therapy. Digitally acquired rotational CV angiograms from 49 patients (mean age 69 +/- 11 years) who underwent left ventricular lead implantation were analyzed. RCVA, which uses rapid isocentric rotation over a 110 degrees arc, acquiring 120 frames/angiogram, was compared with SCVA, defined as 2 static orthogonal views: right anterior oblique 45 degrees and left anterior oblique 45 degrees . RCVA demonstrated that the posterior vein-to-coronary sinus (CS) angle and the left marginal vein-to-CS angle were misclassified in 5 and 11 patients, respectively, using SCVA. RCVA identified a greater number of second-order tributaries with diameters >1.5 mm than SCVA. The CV branch selected for lead placement was initially identified in 100% of patients using RCVA but in only 74% of patients using SCVA. RCVA showed that the best angiographic view for visualizing the CS and its tributaries differed significantly among different areas of the CV tree and among patients. The area of the CV tree that showed less variability was the CS ostium, which had a fairly constant relation with the spine in shallow right anterior oblique and left anterior oblique projections. In conclusion, RCVA provided a more precise map of CV anatomy and the spatial relation of venous branches. It allowed the identification of fluoroscopic views that could facilitate cannulation of the CS. The final x-ray view displaying the appropriate CV branch for left ventricular lead implantation was often different from the conventional left anterior oblique and right anterior oblique views. RCVA identified the target branch for lead implantation more often than SCVA.


Assuntos
Estimulação Cardíaca Artificial/métodos , Angiografia Coronária/métodos , Radiografia Intervencionista , Idoso , Vasos Coronários/anatomia & histologia , Feminino , Insuficiência Cardíaca/terapia , Ventrículos do Coração , Humanos , Masculino , Interpretação de Imagem Radiográfica Assistida por Computador
18.
J Cardiovasc Electrophysiol ; 18(5): 512-7, 2007 May.
Artigo em Inglês | MEDLINE | ID: mdl-17428273

RESUMO

INTRODUCTION: While implantable defibrillator shocks save lives, shock can lead to ventricular arrhythmias. However, the mechanism of shock-related proarrhythmia remains unclear. We evaluated the impact of ICD shock on repolarization instability, a factor associated with ventricular arrhythmogenesis. METHODS AND RESULTS: Sixty-five patients with ICDs underwent ambulatory ECG monitoring during defibrillation testing 3 months postimplant. TWA was analyzed continuously in the time domain during baseline, sedated, and post-shock states. RR, QRS, and QT intervals and catecholamines were also measured continuously. Adequate pre- and post-shock Holter data were recorded in 55 patients, 48 male, mean 64 +/- 12 years, 50 with coronary disease, 48 with prior spontaneous or induced arrhythmia. TWA significantly increased after shock, from 9.6 +/- 0.5 to 11.9 +/- 0.6 microV, as did QRS duration, epinephrine, and norepinephrine levels, compared with sedated and baseline states. RR intervals decreased minimally. TWA changes with shock were not associated with RR or QRS duration changes, but were associated with changes in epinephrine. CONCLUSIONS: ICD shock, even in the sedated state, increases repolarization instability as measured by TWA, an effect mediated in part by sympathetic stimulation. This association between shock and TWA may have important mechanistic and clinical implications for optimization of defibrillation therapy.


Assuntos
Desfibriladores Implantáveis/efeitos adversos , Cardioversão Elétrica/efeitos adversos , Eletrocardiografia Ambulatorial , Insuficiência Cardíaca/prevenção & controle , Medição de Risco/métodos , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fibrilação Ventricular/prevenção & controle
19.
Heart Rhythm ; 4(3): 268-73, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17341385

RESUMO

BACKGROUND: Anger can precipitate ventricular arrhythmias in patients with implantable cardioverter-defibrillators (ICDs). Determining electrophysiologic characteristics of anger-triggered arrhythmias may help elucidate the mechanisms that link emotion and arrhythmia. OBJECTIVES: We sought to compare the morphology and initiation pattern between ventricular arrhythmias that are triggered by anger and those that are not. METHODS: At the time of shock, patients with ICDs recorded levels of defined mood states preceding the shock in a diary. Stored intracardiac electrograms (EGMs) were retrieved and analyzed in relation to corresponding mood states. The EGMs from 56 appropriate shocks in 24 patients (18 male, mean age 66 years, 74% with coronary artery disease) were reviewed and analyzed for morphology, mechanism of initiation (sudden onset vs. premature ventricular contraction [PVC]), pause dependence, and other characteristics. RESULTS: Polymorphic ventricular tachycardia was more common in anger-triggered events, occurring in three (37.5%) of eight anger-triggered events compared with five (10.4%) of 48 of non-anger-triggered events (P <.05). Anger-triggered events were more likely to have PVC initiation, occurring in eight (100%) of eight, compared with 30 (68%) of 44 of non-anger-triggered events (P <.05). More anger-triggered events were pause dependent: five (62.5%) of eight versus seven (15%) of 37 non-anger-related events (P <.01). No difference in response to initial therapy was observed in anger-triggered arrhythmias. CONCLUSION: Ventricular arrhythmias occurring in the setting of anger are more likely pause dependent and polymorphic. This suggests that in predisposed populations anger may create an arrhythmogenic substrate susceptible to more disorganized rhythms, a possible mechanism linking emotion and sudden death.


Assuntos
Ira , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/psicologia , Eletrocardiografia , Afeto , Idoso , Arritmias Cardíacas/terapia , Estudos Cross-Over , Desfibriladores Implantáveis , Feminino , Seguimentos , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Recidiva , Projetos de Pesquisa , Taquicardia Ventricular/fisiopatologia , Fibrilação Ventricular/fisiopatologia , Complexos Ventriculares Prematuros/fisiopatologia
20.
Heart Rhythm ; 4(9): 1155-62, 2007 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-17765613

RESUMO

BACKGROUND: Imaging the coronary venous (CV) tree to delineate the coronary sinus and its tributaries can facilitate electrophysiological procedures, such as cardiac resynchronization therapy (CRT) and catheter ablation. Venography also allows visualization of the left atrial (LA) veins, which may be a potential conduit for ablative or pacing strategies given their proximity to foci that can trigger atrial fibrillation. OBJECTIVE: The aim of this study was to provide a detailed description of CV anatomy using rotational venography in patients undergoing CRT. METHODS: Coronary sinus (CS) size and the presence, size, and angulation of its tributaries were determined from the analysis of rotational CV angiograms from 51 patients (age 68 +/- 11 years; n = 12 women) undergoing CRT. RESULTS: The CS, posterior veins, and lateral veins were identified in 100%, 76%, and 91% of patients. Lateral veins were less prevalent in patients with a history of lateral myocardial infarction than in patients without such a history (33% vs. 96%; P = .014). The diameters of the CS and its tributaries were fairly variable (7.3-18.9 mm for CS, 1.3-10.5 mm for CS tributaries). The CS was larger in men than in women and in cases of ischemic than in cases of nonischemic cardiomyopathy (all P <.05). The vein of Marshall, the most constant LA vein, was identified in 37 patients; its diameter is 1.7 +/- 0.5 mm, and its takeoff angle is 154 degrees +/- 15 degrees , making the vein potentially accessible for cannulation. CONCLUSIONS: Differences in CV anatomy that are related to either gender or coronary artery disease could have important practical implications during the left ventricular lead implantation. The anatomical features of the vein of Marshall make it a feasible potential conduit for epicardial LA pacing.


Assuntos
Estimulação Cardíaca Artificial , Angiografia Coronária/métodos , Doença da Artéria Coronariana/patologia , Vasos Coronários/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Pesos e Medidas Corporais , Doença da Artéria Coronariana/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Flebografia/métodos , Fatores Sexuais , Método Simples-Cego , Estatísticas não Paramétricas
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