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AIMS: People with type 2 diabetes (T2D) are more likely to experience binge eating than the general population, which may interfere with their diabetes management. Guided self-help (GSH) is the recommended treatment for binge-eating disorder, but there is currently a lack of evidenced treatment for binge eating in individuals living with T2D. The aims of the current study were to adapt an existing evidence-based GSH intervention using the principles of co-design to make it available online, suitable for remote delivery to address binge eating specifically in adults living with T2D. The Working to Overcome Eating Difficulties GSH intervention comprises online GSH materials presented in seven sections delivered over 12 weeks, supported by a trained Guide. METHODS: In order to adapt the intervention, we held four collaboration workshops with three expert patients recruited from diabetes support groups, eight healthcare professionals and an expert consensus group. We used thematic analysis to make sense of the data. RESULTS AND CONCLUSIONS: The main themes included; keeping the GSH material generic, adapting Sam the central character, tailoring the dietary advice and eating diary. The length of Guidance sessions was increased to 60 min, and Guide training was focussed around working with people with diabetes.
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Transtorno da Compulsão Alimentar , Diabetes Mellitus Tipo 2 , Humanos , Adulto , Transtorno da Compulsão Alimentar/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Autocuidado/métodos , Comportamentos Relacionados com a Saúde , Grupos de Autoajuda , Resultado do TratamentoRESUMO
AIMS: To investigate the abnormalities of the coronary venous system in candidates for cardiac resynchronization therapy (CRT) and describe methods for circumventing the resulting difficulties. METHODS: From four implanting institutes, data of all CRT implants between October 2008 and October 2020 were screened for abnormal cardiac venous anatomy, defined as an anatomical variation not conforming to the accepted 'normal' anatomy. Patient demographics, procedural detail, and subsequent left ventricle (LV) lead pacing indices were collected. RESULTS: From a total of 3548 CRT implants, 15 (0.42%) patients (80% male) of 72.2 ± 10.6 years in age with an LV ejection fraction of 34 ± 10.3% were identified to have had an abnormal cardiac venous anatomy over the study period. There were 13 cases of persistent left side superior vena cava (pLSVC), five of which had coronary sinus ostium atresia (CSOA) including two with an "unroofed" coronary sinus (CS); one patient had a unique anomalous origin of the CS and one patient had an isolated CSOA. In total 14 patients (60% repeat attempt) had successful percutaneous implant under general anesthesia (46.7%) via the cephalic vein (59.1%), using the femoral approach (53.3%) for levophase venography and/or pull-through, including one case of endocardial LV implant. Pacing follow-up over 37.64 ± 37.6 months demonstrated LV lead threshold between 0.62 and 2.9 volts (pulsewidth 0.4-1.5 ms) in all cases; five patients died within 2.92 ± 1.6 years of a successful implant. CONCLUSION: CRT devices can be implanted percutaneously even in the presence of substantial abnormalities of coronary venous anatomy. Alternative routes of venous access may be required.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Veia Cava Superior Esquerda Persistente , Malformações Vasculares , Terapia de Ressincronização Cardíaca/métodos , Dispositivos de Terapia de Ressincronização Cardíaca , Drenagem , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Masculino , Veia Cava Superior/anormalidades , Veia Cava Superior/diagnóstico por imagemRESUMO
BACKGROUND: Cardiac resynchronization therapy-defibrillator (CRT-D) implantation via the cephalic vein is feasible and safe. Recent evidence has suggested a higher implantable cardioverter-defibrillator (ICD) lead failure in multi-lead defibrillator therapy via the cephalic route. We evaluated the relationship between CRT-D implantation via the cephalic and ICD lead failure. METHODS: Data was collected from three CRT-D implanting centers between October 2008 and September 2017. In total 633 patients were included. Patient and lead characteristics with ICD lead failure were recorded. Comparison of "cephalic" (ICD lead via cephalic) versus "non-cephalic" (ICD lead via non-cephalic route) cohorts was performed. Kaplan-Meier survival and a Cox-regression analysis were applied to assess variables associated with lead failure. RESULTS: The cephalic and non-cephalic cohorts were equally male (81.9% vs. 78%; p = .26), similar in age (69.7 ± 11.5 vs. 68.7 ± 11.9; p = .33) and body mass index (BMI) (27.7 ± 5.1 vs. 27.1 ± 5.7; p = .33). Most ICD leads were implanted via the cephalic vein (73.5%) and patients had a mean of 2.9 ± 0.28 leads implanted via this route. The rate of ICD lead failure was low and statistically similar between both groups (0.36%/year vs. 0.13%/year; p = .12). Female gender was more common in the lead failure cohort than non-failure (55.6% vs. 17.9%, respectively; p = .004) as was hypertension (88.9% vs. 54.2%, respectively, p = .038). On multivariate Cox-regression, female sex (p = .008; HR, 7.12 [1.7-30.2]), and BMI (p = .047; HR, 1.12 [1.001-1.24]) were significantly associated with ICD lead failure. CONCLUSION: CRT-D implantation via the cephalic route is not significantly associated with premature ICD lead failure. Female gender and BMI are predictors of lead failure.
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Terapia de Ressincronização Cardíaca , Desfibriladores Implantáveis , Insuficiência Cardíaca , Hipertensão , Dispositivos de Terapia de Ressincronização Cardíaca , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Masculino , Resultado do TratamentoRESUMO
BACKGROUND: The Sars-Cov-2 infection is a multisystem illness that can affect the cardiovascular system. Tachyarrhythmias have been reported but the prevalence of bradyarrhythmia is unclear. Cases have been described of transient high-degree atrioventricular (AV) block in COVID-19 that were managed conservatively. METHOD: A database of all patients requiring temporary or permanent pacing in two linked cardiac centers was used to compare the number of procedures required during the first year of the pandemic compared to the corresponding period a year earlier. The database was cross-referenced with a database of all patients testing positive for Sars-Cov-2 infection in both institutions to identify patients who required temporary or permanent pacing during COVID-19. RESULTS: The number of novel pacemaker implants was lower during the COVID-19 pandemic than the same period the previous year (540 vs. 629, respectively), with a similar proportion of high-degree AV block (38.3% vs. 33.2%, respectively, p = .069). Four patients with the Sars-Cov-2 infection had a pacemaker implanted for high-degree AV block, two for sinus node dysfunction. Of this cohort of six patients, two succumbed to the COVID-19 illness and one from non-COVID sepsis. Device interrogation demonstrated a sustained pacing requirement in all cases. CONCLUSION: High-degree AV block remained unaltered in prevalence during the COVID-19 pandemic. There was no evidence of transient high-degree AV block in patients with the Sars-Cov-2 infection. Our experience suggests that all clinically significant bradyarrhythmia should be treated by pacing according to usual protocols regardless of the COVID status.
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Bradicardia/epidemiologia , Bradicardia/terapia , COVID-19/complicações , Estimulação Cardíaca Artificial , Idoso , Idoso de 80 Anos ou mais , Bradicardia/etiologia , Humanos , Masculino , PrevalênciaRESUMO
BACKGROUND: Small series has shown that cardiac resynchronisation therapy (CRT) can be achieved in a majority of patients using exclusively cephalic venous access. We sought to determine whether this method is suitable for widespread use. METHODS: A group of 19 operators including 11 trainees in three pacing centres attempted to use cephalic access alone for all CRT device implants over a period of 8 years. The access route for each lead, the procedure outcome, duration, and complications were collected prospectively. Data were also collected for 105 consecutive CRT device implants performed by experienced operators not using the exclusively cephalic method. RESULTS: A new implantation of a CRT device using exclusively cephalic venous access was attempted in 1091 patients (73.6% male, aged 73 ± 12 years). Implantation was achieved using cephalic venous access alone in 801 cases (73.4%) and using a combination of cephalic and other access in a further 180 (16.5%). Cephalic access was used for 2468 of 3132 leads implanted (78.8%). Compared to a non-cephalic reference group, complications occurred less frequently (69/1091 vs 12/105; P = .0468), and there were no pneumothoraces with cephalic implants. Procedure and fluoroscopy duration were shorter (procedure duration 118 ± 45 vs 144 ± 39 minutes, P < .0001; fluoroscopy duration 15.7 ± 12.9 vs 22.8 ± 12.2 minutes, P < .0001). CONCLUSIONS: CRT devices can be implanted using cephalic access alone in a substantial majority of cases. This approach is safe and efficient.
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Veia Axilar , Dispositivos de Terapia de Ressincronização Cardíaca , Cateterismo Periférico/métodos , Competência Clínica , Idoso , Terapia de Ressincronização Cardíaca/métodos , Feminino , Humanos , Masculino , Estudos ProspectivosRESUMO
AIM: Remote follow-up (FU) of implantable cardiac defibrillators (ICDs) allows for fewer in-office visits in combination with earlier detection of relevant findings. Its implementation requires investment and reorganization of care. Providers (physicians or hospitals) are unsure about the financial impact. The primary end-point of this randomized prospective multicentre health economic trial was the total FU-related cost for providers, comparing Home Monitoring facilitated FU (HM ON) to regular in-office FU (HM OFF) during the first 2 years after ICD implantation. Also the net financial impact on providers (taking national reimbursement into account) and costs from a healthcare payer perspective were evaluated. METHODS AND RESULTS: A total of 312 patients with VVI- or DDD-ICD implants from 17 centres in six EU countries were randomised to HM ON or OFF, of which 303 were eligible for data analysis. For all contacts (in-office, calendar- or alert-triggered web-based review, discussions, calls) time-expenditure was tracked. Country-specific cost parameters were used to convert resource use into monetary values. Remote FU equipment itself was not included in the cost calculations. Given only two patients from Finland (one in each group) a monetary valuation analysis was not performed for Finland. Average age was 62.4 ± 13.1 years, 81% were male, 39% received a DDD system, and 51% had a prophylactic ICD. Resource use with HM ON was clearly different: less FU visits (3.79 ± 1.67 vs. 5.53 ± 2.32; P < 0.001) despite a small increase of unscheduled visits (0.95 ± 1.50 vs. 0.62 ± 1.25; P < 0.005), more non-office-based contacts (1.95 ± 3.29 vs. 1.01 ± 2.64; P < 0.001), more Internet sessions (11.02 ± 15.28 vs. 0.06 ± 0.31; P < 0.001) and more in-clinic discussions (1.84 ± 4.20 vs. 1.28 ± 2.92; P < 0.03), but with numerically fewer hospitalizations (0.67 ± 1.18 vs. 0.85 ± 1.43, P = 0.23) and shorter length-of-stay (6.31 ± 15.5 vs. 8.26 ± 18.6; P = 0.27), although not significant. For the whole study population, the total FU cost for providers was not different for HM ON vs. OFF [mean (95% CI): 204 (169-238) vs. 213 (182-243); range for difference (-36 to 54), NS]. From a payer perspective, FU-related costs were similar while the total cost per patient (including other physician visits, examinations, and hospitalizations) was numerically (but not significantly) lower. There was no difference in the net financial impact on providers [profit of 408 (327-489) vs. 400 (345-455); range for difference (-104 to 88), NS], but there was heterogeneity among countries, with less profit for providers in the absence of specific remote FU reimbursement (Belgium, Spain, and the Netherlands) and maintained or increased profit in cases where such reimbursement exists (Germany and UK). Quality of life (SF-36) was not different. CONCLUSION: For all the patients as a whole, FU-related costs for providers are not different for remote FU vs. purely in-office FU, despite reorganized care. However, disparity in the impact on provider budget among different countries illustrates the need for proper reimbursement to ensure effective remote FU implementation.
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Estimulação Cardíaca Artificial/economia , Serviços de Assistência Domiciliar/economia , Monitorização Ambulatorial/economia , Consulta Remota/economia , Arritmias Cardíacas/economia , Arritmias Cardíacas/terapia , Custos e Análise de Custo , Desfibriladores Implantáveis/economia , Planos de Pagamento por Serviço Prestado , Feminino , Seguimentos , Pessoal de Saúde/economia , Pessoal de Saúde/estatística & dados numéricos , Recursos em Saúde/economia , Recursos em Saúde/estatística & dados numéricos , Humanos , Assistência de Longa Duração/economia , Masculino , Pessoa de Meia-Idade , Visita a Consultório Médico/economiaRESUMO
We present a case of a 76-year-old man with ischemic cardiomyopathy. Cardiac magnetic resonance imaging demonstrated severe left ventricular (LV) impairment with possibility of scar formation. Cardiac resynchronization therapy was employed with the aid of a novel quadripolar LV lead. The quadripolar LV lead can be programmed for 10 different pacing configurations, allowing the electrophysiologist freedom to optimize the vector around scar and also avoid phrenic nerve stimulation without the requirement of LV lead repositioning.
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Dispositivos de Terapia de Ressincronização Cardíaca , Eletrodos Implantados , Ventrículos do Coração/cirurgia , Implantação de Prótese/métodos , Disfunção Ventricular Esquerda/prevenção & controle , Idoso , Cicatriz Hipertrófica/patologia , Cicatriz Hipertrófica/cirurgia , Humanos , Masculino , Resultado do Tratamento , Disfunção Ventricular Esquerda/patologia , Disfunção Ventricular Esquerda/cirurgiaRESUMO
Background: The prognostic impact of tricuspid regurgitation (TR) in acute heart failure (AHF) remains uncertain. Methods: We retrospectively assessed 418 consecutive AHF patients who underwent comprehensive echocardiographic assessment within 24 h of study recruitment. TR was quantitatively assessed with 3 guideline-directed measures: regurgitant volumes (RgVol), effective regurgitant orifice area (ERO) and vena contracta (VC) diameter. Disproportionate TR was assessed by the ratio of the VC diameter to the tricuspid annulus diameter (VC/TA) ≥ 0.24. Results: The prevalence of significant (i.e., >mild) TR differed when various standard assessment parameters were applied to quantification: RgVol 50.3% (173/344), ERO 75.6% (260/344) and VC diameter 94.6% (335/354). None were able to delineate those at excess risk of all-cause 2-year mortality using guideline-directed cut-offs of mild, moderate and severe TR. Using a cut-off of VC/TA ≥ 0.24, we identified that 36.9% (130/352) had "disproportionate" TR. Disproportionate TR was associated with an excess risk of mortality at 2 years compared to proportionate TR; HR 1.48 (95% CI 1.06−2.06 [p = 0.02]) which was not significant on multivariate assessment (p = 0.94). Conclusions: TR was not associated with outcome in AHF using guideline measures. A new assessment of "Disproportionate" TR carries a higher risk than proportionate TR but was not related to outcome based on multivariate analysis. Further research is needed to quantify TR more effectively to identify cut-offs for future guidelines and disproportionate TR may be an important part of Heart Failure 2.0.
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Aim: The severity of cardiac impairment in acute heart failure (AHF) predicts outcome, but challenges remain to identify prognostically important non-invasive parameters of cardiac function. Left ventricular ejection fraction (LVEF) is relevant, but only in those with reduced LV systolic function. We aimed to assess the standard and advanced parameters of left and right ventricular (RV) function from echocardiography in predicting long-term outcomes in AHF. Methods: A total of 418 consecutive AHF patients presenting over 12 months were prospectively recruited and underwent bedside echocardiography within 24 h of recruitment. We retrospectively assessed 8 RV and 5 LV echo parameters of the cardiac systolic function to predict 2-year mortality, using both guideline-directed and study-specific cutoffs, based on the maximum Youden indices via ROC analysis. For the RV, these were the tricuspid annular plane systolic excursion, RV fractional area change, tissue Doppler imaging (TDI) peak tricuspid annular systolic wave velocity, both peak- and end-systolic RV free wall global longitudinal strain (RV GLS) and strain rate (mean RV GLSR), RV ejection fraction (RVEF) derived from a 2D ellipsoid model and the ratio of the TAPSE to systolic pulmonary artery pressure (SPAP). For the LV, these were the LVEF, mitral regurgitant ΔP/Δt (MR dP/dt), the lateral mitral annular TDI peak systolic wave velocity, LV GLS, and the LV GLSR. Results: A total of 7/8 parameters of RV systolic function were predictive of 2-year outcome, with study cutoffs like international guidelines. A cutoff of < -1.8 s-1 mean RV GLSR was associated with worse outcome compared to > -1.8 s-1 [HR 2.13 95% CI 1.33-3.40 (p = 0.002)]. TAPSE:SPAP of > 0.027 cm/mmHg (vs. < 0.027 cm/mmHg) predicted worse outcome [HR 2.12 95% CI 1.53-2.92 (p < 0.001)]. A 3-way comparison of 2-year mortality by LVEF from the European Society of Cardiology (ESC) guideline criteria of LVEF > 50, 41-49, and < 40% was not prognostic [38.6% vs. 30.9 vs. 43.9% (p = 0.10)]. Of the 5 parameters of LV systolic function, only an MR dP/dt cutoff of < 570 mmHg was predictive of adverse outcome [HR 1.63 95% CI 1.01-2.62 (p = 0.047)]. Conclusion: With cutoffs broadly like the ESC guidelines, we identified RV dysfunction to be associated with adverse prognosis, whereas LVEF could not identify patients at risk.
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BACKGROUND: Cardiac resynchronization therapy (CRT) devices are usually implanted using subclavian vein access, which is associated with the risk of pneumothorax. We examined whether cephalic venous access is an effective alternative to subclavian access by the Seldinger technique for CRT delivery. METHODS: We retrospectively analyzed all CRT procedures performed over a 1-year period at our center with respect to the access methods, primary success rate, safety, and efficiency. RESULTS: We retrospectively analyzed 103 consecutive primary implantation procedures. The procedure was accomplished using cephalic access alone for 54 of 61 (89%) CRT implants attempted by this route. The overall success rate was 100% (61/61) with additional use of subclavian access. CRT implantation via subclavian vein access was successful in 37 of 42 (88%) (P < 0.05 vs cephalic group). The procedure duration was shorter for the cephalic group (118 ± 39 vs 147 ± 36 minutes, P < 0.0005) as were the screening times and radiation exposure (15 ± 9 vs 27 ± 18 minutes and 4.7 ± 5.8 vs 9.3 ± 9.1 Gcm(2) , both P < 0.01). In the cephalic group, procedure duration and radiation exposure diminished significantly with increasing experience of the technique. Complications occurred in two of 61 (3.3%) cases in the cephalic group and three of 42 (7.1%) in the subclavian group (P = NS). CONCLUSION: CRT devices can be implanted using cephalic access alone in a large majority of cases. This approach is safe and efficient.
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Veia Axilar/cirurgia , Dispositivos de Terapia de Ressincronização Cardíaca/efeitos adversos , Pneumotórax/etiologia , Pneumotórax/prevenção & controle , Implantação de Prótese/métodos , Idoso , Estudos de Viabilidade , Feminino , Humanos , Masculino , Implantação de Prótese/efeitos adversos , Resultado do TratamentoRESUMO
An acutely angulated coronary sinus ostium coupled with a dilated right atrium presents technical challenges for cardiac resynchronization therapy (CRT) implantation. Innovative use of a deployable left ventricle lead as an anchor to support guidewire navigation within the cardiac venous system permits optimal CRT deployment. (Level of Difficulty: Advanced.).
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Objectives: To assess the prevalence and impact of mitral regurgitation (MR) on survival in patients presenting to hospital in acute heart failure (AHF) using traditional echocardiographic assessment alongside more novel indices of proportionality. Background: It remains unclear if the severity of MR plays a significant role in determining outcomes in AHF. There is also uncertainty as to the clinical relevance of indexing MR to left ventricular volumes. This concept of disproportionality has not been assessed in AHF. Methods: A total of 418 consecutive patients presenting in AHF over 12 months were recruited and followed up for 2 years. MR was quantitatively assessed within 24 h of recruitment. Standard proximal isovelocity surface area (PISA) and a novel proportionality index of effective regurgitant orifice/left ventricular end-diastolic volume (ERO/LVEDV) >0.14 mm2/ml were used to identify severe and disproportionate MR. Results: Every patient had MR. About 331/418 (78.9%) patients were quantifiable by PISA. About 165/418 (39.5%) patients displayed significant MR. A larger cohort displayed disproportionate MR defined by either a proportionality index using ERO/LVEDV > 0.14 mm2/ml or regurgitant volumes/LVEDV > 0.2 [217/331 (65.6%) and 222/345 (64.3%), respectively]. The LVEDV was enlarged in significant MR-129.5 ± 58.95 vs. 100.0 ± 49.91 ml in mild, [p < 0.0001], but remained within the normal range. Significant MR was associated with a greater mortality at 2 years {44.2 vs. 34.8% in mild MR [hazard ratio (HR) 1.39; 95% CI: 1.01-1.92, p = 0.04]}, which persisted with adjustment for comorbid conditions (HR; 1.43; 95% CI: 1.04-1.97, p = 0.03). Disproportionate MR defined by ERO/LVEDV >0.14 mm2/ml was also associated with worse outcome [42.4 vs. 28.3% (HR 1.62; 95% CI 1.12-2.34, p = 0.01)]. Conclusions: MR was a universal feature in AHF and determines outcome in significant cases. Furthermore, disproportionate MR, defined either by effective regurgitant orifice (ERO) or volumetrically, is associated with a worse prognosis despite the absence of adverse left ventricular (LV) remodeling. These findings outline the importance of adjusting acute volume overload to LV volumes and call for a review of the current standards of MR assessment. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02728739, identifier NCT02728739.
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INTRODUCTION: Atypical chest pain is frequently an aetiological conundrum, and missing a diagnosis of underlying cardiac disease can have detrimental consequences. The investigation of this may rule out cardiac disease but often provides no clear answers to the underlying pathology. CASE PRESENTATION: An 80-year-old man with a background of bilateral inguinal hernia repairs but no cardiac disease presented to his general practitioner with intermittent chest pain of approximately 15 min duration, felt inside his chest under his right nipple. His episodes of chest discomfort had increased in frequency, occurring both at rest and upon exertion. He was seen by the cardiology team at his local hospital and reassured following normal coronary angiography and outpatient echocardiography. The pain persisted, so cardiac magnetic resonance imaging (MRI) was arranged to exclude the underlying myocardial disease. This demonstrated a mass within the right ventricular free wall, which MRI was unable to characterize. Follow-up cardiac computed tomography showed this to be a metallic object within the right ventricular wall, but despite thorough examination of his medical and social history, there remains no obvious explanation to its aetiology other than potentially due to clip migration from his hernia repair. DISCUSSION: Metallic foreign bodies within the myocardium are described in case reports but almost entirely in the setting of intentional self-injury. There is no previous case evidence of migration of distal surgical clips to the heart, but there appears to be no other clear aetiology for this gentleman's pathology, thus representing a novel description of iatrogenic injury.
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Aneurisma Aórtico , Seio Aórtico , Taquicardia Ventricular , Aneurisma Aórtico/complicações , Aneurisma Aórtico/diagnóstico por imagem , Aneurisma Aórtico/cirurgia , Arritmias Cardíacas , Humanos , Seio Aórtico/diagnóstico por imagem , Taquicardia Ventricular/diagnóstico por imagem , Taquicardia Ventricular/etiologiaRESUMO
BACKGROUND: We have described the use of femoral access followed by pull through of the lead to a pectoral position to circumvent difficulty in implanting a left ventricular (LV) lead by standard methods. OBJECTIVE: The purpose of this study was to establish the effect of femoral implantation and pull through on the overall rate of success in percutaneous implantation of LV leads. METHODS: We collected data prospectively in all attempts at LV lead implantation from the time that we envisioned the femoral pull-through approach. RESULTS: In the 6 years to September 30, 2014, our group attempted to implant a new LV lead in 736 patients, including 16 who previously had failed attempts by other groups. A standard superior approach was successful in 726 of 731 patients (99.3%) in whom it was attempted. In 5 patients (0.7%), we failed to deliver a lead from a superior approach; in 5 of 16 patients, with previous failed attemtps (31%), we judged that those attempts had been exhaustive. In all 10 cases, LV lead placement was achieved from a femoral approach, with the procedure time being 186 ± 65 minutes. In the first case attempted, the pull through failed; the lead was tunneled to the pectoral generator. In 1 case, the coronary sinus was found to be occluded at the ostium: a transseptal approach was used with the subsequent pull through. No complication occurred. At 22.3 ± 18.5 months after the implantation, all systems implanted by a femoral approach continued to function. CONCLUSION: Used as an adjunct to standard methods, the femoral access and pull through method allows percutaneous LV lead placement in virtually all cases.
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Terapia de Ressincronização Cardíaca/métodos , Cateterismo Periférico/métodos , Veia Femoral/cirurgia , Implantação de Prótese/métodos , Idoso , Dispositivos de Terapia de Ressincronização Cardíaca , Feminino , Insuficiência Cardíaca/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Estudos Prospectivos , Reino UnidoRESUMO
BACKGROUND: A respiratory cycle for nitric oxide (NO) would involve the formation of vasoactive metabolites between NO and hemoglobin during pulmonary oxygenation. We investigated the role of these metabolites in hypoxic tissue in vitro and in vivo in healthy subjects and patients with congestive heart failure (CHF). METHODS AND RESULTS: We investigated the capacity for red blood cells (RBCs) to dilate preconstricted aortic rings under various O2 tensions. RBCs induced cyclic guanylyl monophosphate-dependent vasorelaxation during hypoxia (35+/-4% at 1% O2, 4.7+/-1.6% at 95% O2; P<0.05). RBC-induced relaxations during hypoxia correlated with S-nitrosohemoglobin (SNO-Hb) (R2=0.88) but not iron nitrosylhemoglobin (HbFeNO) content. Relaxation responses for RBCs were compared with S-nitrosoglutathione across a range of O2 tensions. The fold increases in relaxation evoked by RBCs were significantly greater at 1% and 2% O2 compared with relaxations induced at 95% (P<0.05), consistent with an allosteric mechanism of hypoxic vasodilation. We also measured transpulmonary gradients of NO metabolites in healthy control subjects and in patients with CHF. In CHF patients but not control subjects, levels of SNO-Hb increase from 0.00293+/-0.00089 to 0.00585+/-0.00137 mol NO/mol hemoglobin tetramer (P=0.005), whereas HbFeNO decreases from 0.00361+/-0.00109 to 0.00081+/-0.00040 mol NO/mol hemoglobin tetramer (P=0.03) as hemoglobin is oxygenated in the pulmonary circulation. These metabolite gradients correlated with the hemoglobin O2 saturation gradient (P<0.05) and inversely with cardiac index (P<0.05) for both CHF patients and control subjects. CONCLUSIONS: We confirm that RBC-bound NO mediates hypoxic vasodilation in vitro. Transpulmonary gradients of hemoglobin-bound NO are evident in CHF patients and are inversely dependent on cardiac index. Hemoglobin may transport and release NO bioactivity to areas of tissue hypoxia or during increased peripheral oxygen extraction via an allosteric mechanism.