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BACKGROUND AND AIMS: Transcatheter pulmonary valve implantation (TPVI) is indicated to treat right-ventricular outflow tract (RVOT) dysfunction related to congenital heart disease (CHD). Outcomes of TPVI with the SAPIEN 3 valve that are insufficiently documented were investigated in the EUROPULMS3 registry of SAPIEN 3-TPVI. METHODS: Patient-related, procedural, and follow-up outcome data were retrospectively assessed in this observational cohort from 35 centres in 15 countries. RESULTS: Data for 840 consecutive patients treated in 2014-2021 at a median age of 29.2 (19.0-41.6) years were obtained. The most common diagnosis was conotruncal defect (70.5%), with a native or patched RVOT in 50.7% of all patients. Valve sizes were 20, 23, 26, and 29â mm in 0.4%, 25.5%, 32.1%, and 42.0% of patients, respectively. Valve implantation was successful in 98.5% [95% confidence interval (CI), 97.4%-99.2%] of patients. Median follow-up was 20.3 (7.1-38.4) months. Eight patients experienced infective endocarditis; 11 required pulmonary valve replacement, with a lower incidence for larger valves (P = .009), and four experienced pulmonary valve thrombosis, including one who died and three who recovered with anticoagulation. Cumulative incidences (95%CI) 1, 3, and 6 years after TPVI were as follows: infective endocarditis, 0.5% (0.0%-1.0%), 0.9% (0.2%-1.6%), and 3.8% (0.0%-8.4%); pulmonary valve replacement, 0.4% (0.0%-0.8%), 1.3% (0.2%-2.4%), and 8.0% (1.2%-14.8%); and pulmonary valve thrombosis, 0.4% (0.0%-0.9%), 0.7% (0.0%-1.3%), and 0.7% (0.0%-1.3%), respectively. CONCLUSIONS: Outcomes of SAPIEN 3 TPVI were favourable in patients with CHD, half of whom had native or patched RVOTs.
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Endocardite Bacteriana , Endocardite , Cardiopatias Congênitas , Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Insuficiência da Valva Pulmonar , Valva Pulmonar , Trombose , Adulto , Humanos , Cateterismo Cardíaco/efeitos adversos , Endocardite/epidemiologia , Endocardite Bacteriana/complicações , Cardiopatias Congênitas/complicações , Próteses Valvulares Cardíacas/efeitos adversos , Implante de Prótese de Valva Cardíaca/efeitos adversos , Desenho de Prótese , Valva Pulmonar/cirurgia , Insuficiência da Valva Pulmonar/epidemiologia , Insuficiência da Valva Pulmonar/cirurgia , Sistema de Registros , Estudos Retrospectivos , Trombose/etiologia , Resultado do TratamentoRESUMO
AIMS: Evidence for CRT in adults with congenital heart disease (ACHD) and chronic heart failure is limited, with recommendations for its use extrapolated from the population with structurally normal hearts. This retrospective observational study investigates the efficacy of CRT in this heterogenous group, discussing factors predicting response to CRT. METHODS: Twenty-seven patients with structural ACHD who underwent CRT insertion or upgrade at a tertiary center in the United Kingdom were retrospectively studied. The primary outcome measure was clinical response to CRT, defined as improvement of NYHA class and/or improvement in systemic ventricular ejection fraction by one category. Secondary outcomes included change in QRS duration and adverse events. RESULTS: Thirty-seven percent of patients had a systemic right ventricle (sRV). RBBB was the commonest baseline QRS morphology (40.7%) despite this being an unfavorable characteristic for CRT. Overall, positive response to CRT was demonstrated in 18 patients (66.7%). NYHA class improved in 55.5% following CRT (p = .001) and 40.7% showed improvement in systemic ventricular ejection fraction (p = .118). There were no baseline characteristics that predicted response to CRT, and electrocardiographic measures such as QRS shortening post-CRT was not associated with positive response. Good response rates (60.0%) were demonstrated in those with sRV. CONCLUSION: CRT is efficacious in structural ACHD including in those who do not meet conventional criteria. Extrapolation of recommendations from adults with structurally normal hearts may be inappropriate. Future research should focus on improving patient selection for CRT, for example using techniques to better quantify mechanical dysynchrony and intra-procedural electrical activation mapping in these complex patients.
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Terapia de Ressincronização Cardíaca , Cardiopatias Congênitas , Insuficiência Cardíaca , Humanos , Adulto , Estudos Retrospectivos , Resultado do Tratamento , Insuficiência Cardíaca/terapia , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/terapia , Doença CrônicaRESUMO
AIMS: In patients with an extra-cardiac Fontan circulation, there is no direct access to the heart. The insertion of a permanent pacemaker requires surgery to insert epicardial pacing wires. We present the implantation of a permanent endocardial pacing lead from the superior vena cava (SVC) into the atrium via direct passage from the right pulmonary artery (RPA). METHODS AND RESULTS: A permanent pacing lead was passed directly from the SVC to the RPA and then into the atrial mass. Direct passage from the RPA (attached directly to the right SVC) into the atrial mass was achieved using a trans-septal puncture needle. CONCLUSION: This novel technique is an alternative to epicardial pacing in patients with an extra-cardiac Fontan circulation, thus avoiding the need for surgical intervention. It may also be applied to gain access to the atrial mass for arrhythmia ablation therapy.
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Arritmias Cardíacas/terapia , Cateterismo Cardíaco , Estimulação Cardíaca Artificial/métodos , Técnica de Fontan , Artéria Pulmonar , Veia Cava Superior , Adulto , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/fisiopatologia , Septos Cardíacos , Humanos , Masculino , Marca-Passo Artificial , Flebografia/métodos , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia , Punções , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Veia Cava Superior/diagnóstico por imagem , Veia Cava Superior/cirurgiaRESUMO
Neuroendocrine tumours (NETs) are rare but once metastasised, can lead to the release of vasoactive substances into the systemic circulation, and the classical features of carcinoid syndrome (CS) such as flushing and diarrhoea. A consequence of CS is carcinoid heart disease (CHD) which primarily affects the right-sided heart valves and can eventually lead to right heart failure. In this cohort, tricuspid and/or pulmonary valve replacement provides symptomatic relief. A patent foramen ovale (PFO) in patients with CHD can lead to the shunting of oxygen deficient blood to the systemic circulation causing hypoxaemia and reduced exercise tolerance. Additionally, the haemodynamic changes caused by regurgitant right-sided heart valves can increase the patency of a PFO allowing the passage of vasoactive substances to the systemic circulation thereby affecting the left-sided heart valves. We present data on the incidence of PFO in patients referred for surgery at our centre, in which the standard approach is to close the defect at time of cardiothoracic surgery. In addition, we present a series of four cases that highlight how the option of percutaneous PFO closure prior to open valve surgery may reduce haemodynamic instability and open a window of opportunity to enhance preoperative status. Percutaneous PFO closure then acts as a bridge to definitive cardiothoracic surgery, although there are risks in such an approach.
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Doença Cardíaca Carcinoide , Forame Oval Patente , Humanos , Forame Oval Patente/complicações , Forame Oval Patente/cirurgia , Doença Cardíaca Carcinoide/complicações , Doença Cardíaca Carcinoide/cirurgia , Doença Cardíaca Carcinoide/epidemiologiaRESUMO
Pre-conditioning is an exciting physiological phenomenon that, despite great efforts, has so far resisted translation to mainstream clinical medicine. Many potential triggers (e.g., ischemia of the organ in question or a remote organ, many different drugs) have been investigated, but recent work has implicated activation of mitochondrial aldehyde dehydrogenase (ALDH2) as central to the process. A genetic polymorphism, known as ALDH2*2, is common worldwide (present in up to 40% of Han Chinese people) and produces a functionally different enzyme. The authors used a variety of protocols in the human ischemic forearm model, in participants with both enzyme types, to assess cytoprotection with low-dose sodium nitrite and attempt to further elucidate the role of ALDH2.
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Retinal artery occlusion in an otherwise healthy, young patient is rare. In this context it is important to consider patent foramen ovale as a differential. Early referral to a cardiology specialist for diagnosis and treatment is important for preventing further ocular and non-ocular events.
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BACKGROUND: Nitrite exhibits hypoxia-dependent vasodilator properties, selectively dilating capacitance vessels in healthy subjects. Unlike organic nitrates, it seems not to be subject to the development of tolerance. Currently, therapeutic options for decompensated heart failure (HF) are limited. We hypothesized that by preferentially dilating systemic capacitance and pulmonary resistance vessels although only marginally dilating resistance vessels, sodium nitrite (NaNO2) infusion would increase cardiac output but reduce systemic arterial blood pressure only modestly. We therefore undertook a first-in-human HF proof of concept/safety study, evaluating the hemodynamic effects of short-term NaNO2 infusion. METHODS AND RESULTS: Twenty-five patients with severe chronic HF were recruited. Eight received short-term (5 minutes) intravenous NaNO2 at 10 µg/kg/min and 17 received 50 µg/kg/min with measurement of cardiac hemodynamics. During infusion of 50 µg/kg/min, left ventricular stroke volume increased (from 43.22±21.5 to 51.84±23.6 mL; P=0.003), with marked falls in pulmonary vascular resistance (by 29%; P=0.03) and right atrial pressure (by 40%; P=0.007), but with only modest falls in mean arterial blood pressure (by 4 mm Hg; P=0.004). The increase in stroke volume correlated with the increase in estimated trans-septal gradient (=pulmonary capillary wedge pressure-right atrial pressure; r=0.67; P=0.003), suggesting relief of diastolic ventricular interaction as a contributory mechanism. Directionally similar effects were observed for the above hemodynamic parameters with 10 µg/kg/min; this was significant only for stroke volume, not for other parameters. CONCLUSIONS: This first-in-human HF efficacy/safety study demonstrates an attractive profile during short-term systemic NaNO2 infusion that may be beneficial in decompensated HF and warrants further evaluation with longer infusion regimens.
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Circulação Coronária/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Hemodinâmica/efeitos dos fármacos , Circulação Pulmonar/efeitos dos fármacos , Nitrito de Sódio/administração & dosagem , Vasodilatadores/administração & dosagem , Adulto , Pressão Arterial/efeitos dos fármacos , Débito Cardíaco/efeitos dos fármacos , Doença Crônica , Esquema de Medicação , Inglaterra , Feminino , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/fisiopatologia , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Nitrito de Sódio/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Resistência Vascular/efeitos dos fármacos , Vasodilatação/efeitos dos fármacos , Vasodilatadores/efeitos adversosRESUMO
BACKGROUND AND PURPOSE: Hypoxic conditions favour the reduction of nitrite to nitric oxide (NO) to elicit vasodilatation, but the mechanism(s) responsible for bioconversion remains ill defined. In the present study, we assess the role of aldehyde dehydrogenase 2 (ALDH2) in nitrite bioactivation under normoxia and hypoxia in the rat and human vasculature. EXPERIMENTAL APPROACH: The role of ALDH2 in vascular responses to nitrite was studied using rat thoracic aorta and gluteal subcutaneous fat resistance vessels from patients with heart failure (HF; 16 patients) in vitro and by measurement of changes in forearm blood flow (FBF) during intra-arterial nitrite infusion (21 patients) in vivo. Specifically, we investigated the effects of (i) ALDH2 inhibition by cyanamide or propionaldehyde and the (ii) tolerance-independent inactivation of ALDH2 by glyceryl trinitrate (GTN) on the vasodilator activity of nitrite. In each setting, nitrite effects were measured via evaluation of the concentration-response relationship under normoxic and hypoxic conditions in the absence or presence of ALDH2 inhibitors. KEY RESULTS: Both in rat aorta and human resistance vessels, dilatation to nitrite was diminished following ALDH2 inhibition, in particular under hypoxia. In humans there was a non-significant trend towards attenuation of nitrite-mediated increases in FBF. CONCLUSIONS AND IMPLICATIONS: In human and rat vascular tissue in vitro, hypoxic nitrite-mediated vasodilatation involves ALDH2. In patients with HFâ in vivo, the role of this enzyme in nitrite bioactivation is at the most, modest, suggesting the involvement of other more important mechanisms.
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Aldeído Desidrogenase/fisiologia , Artérias/fisiologia , Hipóxia/fisiopatologia , Proteínas Mitocondriais/fisiologia , Nitritos/farmacologia , Vasodilatadores/farmacologia , Idoso , Aldeído Desidrogenase/antagonistas & inibidores , Aldeído-Desidrogenase Mitocondrial , Aldeídos/farmacologia , Animais , Artérias/efeitos dos fármacos , Cianamida/farmacologia , Feminino , Antebraço/irrigação sanguínea , Insuficiência Cardíaca/fisiopatologia , Humanos , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Proteínas Mitocondriais/antagonistas & inibidores , Doadores de Óxido Nítrico/farmacologia , Nitroglicerina/farmacologia , Ratos Sprague-Dawley , Fluxo Sanguíneo Regional/efeitos dos fármacos , Espermina/análogos & derivados , Espermina/farmacologia , Vasodilatação/fisiologiaRESUMO
BACKGROUND AND PURPOSE: Nitrite (NO2â») has recently been shown to represent a potential source of NO, in particular under hypoxic conditions. The aim of the current study was to compare the haemodynamic effects of NO2â» in healthy volunteers and patients with stable congestive heart failure (CHF). EXPERIMENTAL APPROACH: The acute haemodynamic effects of brachial artery infusion of NO2â» (0.31 to 7.8 µmol·min⻹) was assessed in normal subjects (n = 20) and CHF patients (n = 21). KEY RESULTS: NO2â» infusion was well tolerated in all subjects. Forearm blood flow (FBF) increased markedly in CHF patients at NO2â» infusion rates which induced no changes in normal subjects (ANOVA: F = 5.5; P = 0.02). Unstressed venous volume (UVV) increased even with the lowest NO2â» infusion rate in all subjects (indicating venodilation), with CHF patients being relatively hyporesponsive compared with normal subjects (ANOVA: F = 6.2; P = 0.01). There were no differences in venous blood pH or oxygen concentration between groups or during NO2â» infusion. Venous plasma NO2â» concentrations were lower in CHF patients at baseline, and rose substantially less with NO2â» infusion, without incremental oxidative generation of nitrate, consistent with accelerated clearance in these patients. Plasma protein-bound NO concentrations were lower in CHF patients than normal subjects at baseline. This difference was attenuated during NO2â» infusion. Prolonged NO2â» exposure in vivo did not induce oxidative stress, nor did it induce tolerance in vitro. CONCLUSIONS AND IMPLICATIONS: The findings of arterial hyper-responsiveness to infused NO2â» in CHF patients, with evidence of accelerated transvascular NO2â» clearance (presumably with concomitant NO release) suggests that NO2â» effects may be accentuated in such patients. These findings provide a stimulus for the clinical exploration of NO2â» as a therapeutic modality in CHF.
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Insuficiência Cardíaca/fisiopatologia , Nitrito de Sódio/farmacocinética , Vasodilatadores/farmacocinética , Sistema Vasomotor/efeitos dos fármacos , Idoso , Artéria Braquial , Estudos de Coortes , Tolerância a Medicamentos , Feminino , Antebraço , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Hemodinâmica/efeitos dos fármacos , Humanos , Técnicas In Vitro , Infusões Intra-Arteriais , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Óxido Nítrico/administração & dosagem , Óxido Nítrico/análogos & derivados , Óxido Nítrico/metabolismo , Óxido Nítrico/farmacocinética , Nitroglicerina/administração & dosagem , Nitroglicerina/metabolismo , Nitroglicerina/farmacocinética , Nitroglicerina/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Veia Safena/efeitos dos fármacos , Veia Safena/fisiopatologia , Nitrito de Sódio/administração & dosagem , Nitrito de Sódio/metabolismo , Nitrito de Sódio/farmacologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/administração & dosagem , Vasodilatadores/metabolismo , Vasodilatadores/farmacologia , Sistema Vasomotor/fisiopatologiaRESUMO
AIMS: This work investigates the role of myoglobin in mediating the vascular relaxation induced by nitrite. Nitrite, previously considered an inert by-product of nitric oxide metabolism, is now believed to play an important role in several areas of pharmacology and physiology. Myoglobin can act as a nitrite reductase in the heart, where it is plentiful, but it is present at a far lower level in vascular smooth muscle-indeed, its existence in the vessel wall is controversial. Haem proteins have been postulated to be important in nitrite-induced vasodilation, but the specific role of myoglobin is unknown. The current study was designed to confirm the presence of myoglobin in murine aortic tissue and to test the hypothesis that vascular wall myoglobin is important for nitrite-induced vasodilation. METHODS AND RESULTS: Aortic rings from wild-type and myoglobin knockout mice were challenged with nitrite, before and after exposure to the haem-protein inhibitor carbon monoxide (CO). CO inhibited vasodilation in wild-type rings but not in myoglobin-deficient rings. Restitution of myoglobin using a genetically modified adenovirus both increased vasodilation to nitrite and reinstated the wild-type pattern of response to CO. CONCLUSION: Myoglobin is present in the murine vasculature and contributes significantly to nitrite-induced vasodilation.