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Importance: Sudden death and cardiac arrest frequently occur without explanation, even after a thorough clinical evaluation. Calcium release deficiency syndrome (CRDS), a life-threatening genetic arrhythmia syndrome, is undetectable with standard testing and leads to unexplained cardiac arrest. Objective: To explore the cardiac repolarization response on an electrocardiogram after brief tachycardia and a pause as a clinical diagnostic test for CRDS. Design, Setting, and Participants: An international, multicenter, case-control study including individual cases of CRDS, 3 patient control groups (individuals with suspected supraventricular tachycardia; survivors of unexplained cardiac arrest [UCA]; and individuals with genotype-positive catecholaminergic polymorphic ventricular tachycardia [CPVT]), and genetic mouse models (CRDS, wild type, and CPVT were used to define the cellular mechanism) conducted at 10 centers in 7 countries. Patient tracings were recorded between June 2005 and December 2023, and the analyses were performed from April 2023 to December 2023. Intervention: Brief tachycardia and a subsequent pause (either spontaneous or mediated through cardiac pacing). Main Outcomes and Measures: Change in QT interval and change in T-wave amplitude (defined as the difference between their absolute values on the postpause sinus beat and the last beat prior to tachycardia). Results: Among 10 case patients with CRDS, 45 control patients with suspected supraventricular tachycardia, 10 control patients who experienced UCA, and 3 control patients with genotype-positive CPVT, the median change in T-wave amplitude on the postpause sinus beat (after brief ventricular tachycardia at ≥150 beats/min) was higher in patients with CRDS (P < .001). The smallest change in T-wave amplitude was 0.250 mV for a CRDS case patient compared with the largest change in T-wave amplitude of 0.160 mV for a control patient, indicating 100% discrimination. Although the median change in QT interval was longer in CRDS cases (P = .002), an overlap between the cases and controls was present. The genetic mouse models recapitulated the findings observed in humans and suggested the repolarization response was secondary to a pathologically large systolic release of calcium from the sarcoplasmic reticulum. Conclusions and Relevance: There is a unique repolarization response on an electrocardiogram after provocation with brief tachycardia and a subsequent pause in CRDS cases and mouse models, which is absent from the controls. If these findings are confirmed in larger studies, this easy to perform maneuver may serve as an effective clinical diagnostic test for CRDS and become an important part of the evaluation of cardiac arrest.
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Eletrocardiografia , Humanos , Camundongos , Estudos de Casos e Controles , Masculino , Animais , Feminino , Adulto , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/fisiopatologia , Taquicardia Ventricular/etiologia , Parada Cardíaca/etiologia , Parada Cardíaca/diagnóstico , Cálcio/metabolismo , Cálcio/sangue , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/fisiopatologia , Taquicardia Supraventricular/etiologia , Pessoa de Meia-Idade , Modelos Animais de Doenças , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Adolescente , Adulto Jovem , Canal de Liberação de Cálcio do Receptor de Rianodina/genéticaRESUMO
Cardiac arrhythmias are associated with significant morbidity, mortality and poor quality of life. Cardiovascular magnetic resonance (CMR) imaging, with its unsurpassed capability of non-invasive tissue characterisation, high accuracy, and reproducibility of measurements, plays an integral role in determining the underlying aetiology of cardiac arrhytmias. CMR can reliably diagnose previous myocardial infarction, non-ischemic cardiomyopathy, characterise congenital heart disease and valvular pathologies, and also detect the underlying substrate concealed on conventional investigations in a significant proportion of patients with arrhythmias. Determining the underlying substrate of arrhythmia is of paramount importance for treatment planning and prognosis. However, CMR imaging in patients with irregular heart rates can be problematic. Understanding the different ways to overcome the limitations of CMR in arrhythmia is essential for providing high-quality imaging, comprehensive information, and definitive answers in this diverse group of patients.
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BACKGROUND: The rate of left ventricular (LV) lead displacement after cardiac resynchronization therapy (CRT) remains high despite improvements in lead technology. In 2017, a novel quadripolar lead with active fixation technology became available in the UK. METHODS: This was a retrospective, observational study analyzing device complications in 476 consecutive patients undergoing successful first-time implantation of a CRT device at a tertiary center from 2017 to 2020. RESULTS: Both active (n = 135) and passive fixation (n = 341) quadripolar leads had similar success rates for implantation (99.3% vs. 98.8%, p = 1.00), although the pacing threshold (0.89 [0.60-1.25] vs. 1.00 [0.70-1.60] V, p = .01) and lead impedance (632 [552-794] vs. 730 [636-862] Ohms, p < .0001) were significantly lower for the active fixation lead. Patients receiving an active fixation lead had a reduced incidence of lead displacement at 6 months (0.74% vs. 4.69%, p = .036). There was no significant difference in the rate of right atrial (RA) and right ventricular (RV) lead displacement between the two groups (RA: 1.48% vs. 1.17%, p = .68; RV: 2.22% vs. 1.76%, p = .72). Reprogramming the LV lead after displacement was unsuccessful in most cases (successful reprogramming: Active fix = 0/1, Passive fix = 1/16) therefore nearly all patients required a repeat procedure. As a result, the rate of intervention within 6 months for lead displacement was significantly lower when patients were implanted with the active fixation lead (0.74% vs. 4.40%, p = .049). CONCLUSION: The novel active fixation lead in our study has a lower incidence of lead displacement and re-intervention compared to conventional quadripolar leads for CRT.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Terapia de Ressincronização Cardíaca/efeitos adversos , Terapia de Ressincronização Cardíaca/métodos , Dispositivos de Terapia de Ressincronização Cardíaca , Eletrodos Implantados/efeitos adversos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/terapia , Humanos , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Paravalvular leak (PVL) occurs in 5% to 17% of patients following surgical valve replacement. Percutaneous device closure represents an alternative to repeat surgery. METHODS: All UK and Ireland centers undertaking percutaneous PVL closure submitted data to the UK PVL Registry. Data were analyzed for association with death and major adverse cardiovascular events (MACE) at follow-up. RESULTS: Three hundred eight PVL closure procedures were attempted in 259 patients in 20 centers (2004-2015). Patient age was 67±13 years; 28% were female. The main indications for closure were heart failure (80%) and hemolysis (16%). Devices were successfully implanted in 91% of patients, via radial (7%), femoral arterial (52%), femoral venous (33%), and apical (7%) approaches. Nineteen percent of patients required repeat procedures. The target valve was mitral (44%), aortic (48%), both (2%), pulmonic (0.4%), or transcatheter aortic valve replacement (5%). Preprocedural leak was severe (61%), moderate (34%), or mild (5.7%) and was multiple in 37%. PVL improved postprocedure (P<0.001) and was none (33.3%), mild (41.4%), moderate (18.6%), or severe (6.7%) at last follow-up. Mean New York Heart Association class improved from 2.7±0.8 preprocedure to 1.6±0.8 (P<0.001) after a median follow-up of 110 (7-452) days. Hospital mortality was 2.9% (elective), 6.8% (in-hospital urgent), and 50% (emergency) (P<0.001). MACE during follow-up included death (16%), valve surgery (6%), late device embolization (0.4%), and new hemolysis requiring transfusion (1.6%). Mitral PVL was associated with higher MACE (hazard ratio [HR], 1.83; P=0.011). Factors independently associated with death were the degree of persisting leak (HR, 2.87; P=0.037), New York Heart Association class (HR, 2.00; P=0.015) at follow-up and baseline creatinine (HR, 8.19; P=0.001). The only factor independently associated with MACE was the degree of persisting leak at follow-up (HR, 3.01; P=0.002). CONCLUSION: Percutaneous closure of PVL is an effective procedure that improves PVL severity and symptoms. Severity of persisting leak at follow-up is independently associated with both MACE and death. Percutaneous closure should be considered as an alternative to repeat surgery.
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Implante de Prótese de Valva Cardíaca , Próteses Valvulares Cardíacas , Valva Mitral/cirurgia , Complicações Pós-Operatórias/etiologia , Falha de Prótese/efeitos adversos , Substituição da Valva Aórtica Transcateter , Adulto , Idoso , Idoso de 80 Anos ou mais , Cateterismo Cardíaco/métodos , Feminino , Insuficiência Cardíaca/etiologia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Implante de Prótese de Valva Cardíaca/métodos , Humanos , Irlanda , Masculino , Pessoa de Meia-Idade , Reoperação/métodos , Substituição da Valva Aórtica Transcateter/métodos , Reino UnidoRESUMO
The National Institute for Health and Care Excellence (NICE) CG95 clinical guideline on chest pain of recent onset was published in 2010. There is debate over whether the proposed strategy improves patient care and its implications on service costs. Following a six-month pilot, 472 consecutive patient records were audited for pre-test probability of significant coronary artery disease, investigations performed and outcomes. Low- and moderate-risk patients had an unexpectedly low rate of coronary disease and revascularisation. Computerised tomography coronary angiography (CTCA) and stress echocardiography performed similarly, though the latter was more resource intensive. High-/very high-risk patients frequently required revascularisation and greater than 10% of each group had prognostically significant disease, going against the recommendation that very high risk patients do not undergo angiography. There were frequent protocol deviations and training clinic staff in the new approach was challenging. In conclusion, implementing NICE CG95 is feasible but presents challenges. Staff require training to follow the protocol consistently. Functional testing had no benefits over anatomical testing with CTCA, which may allow cost savings in some departments.
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Dor no Peito/diagnóstico , Fidelidade a Diretrizes/estatística & dados numéricos , Hospitais Gerais/normas , Adulto , Idoso , Doença da Artéria Coronariana , Ecocardiografia sob Estresse , Feminino , Indicadores Básicos de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Reino Unido/epidemiologiaRESUMO
AIMS: The trials upon which recommendations for the use of cardiac resynchronization therapy (CRT) in heart failure used optimal medical therapy (OMT) before sodium-glucose co-transporter 2 inhibitors (SGLT2i). Moreover, the SGLT2i heart failure trials included only a small proportion of participants with CRT, and therefore, it remains uncertain whether SGLT2i should be considered part of OMT prior to CRT. METHODS AND RESULTS: We compared electrocardiogram (ECG) and echocardiographic responses to CRT as well as hospitalization and mortality rates in consecutive patients undergoing implantation at a large tertiary centre between January 2019 to June 2022 with and without SGLT2i treatment. Three hundred seventy-four participants were included aged 74.0 ± 11.5 years (mean ± standard deviation), with a left ventricular ejection fraction (LVEF) of 31.8 ± 9.9% and QRS duration of 161 ± 29 ms. The majority had non-ischaemic cardiomyopathy (58%) and were in NYHA Class II/III (83.6%). These characteristics were similar between patients with (n = 66) and without (n = 308) prior SGLT2i treatment. Both groups demonstrated similar evidence of response to CRT in terms of QRS duration shortening, and improvements in LVEF, left ventricular end-diastolic inner-dimension (LVIDd) and diastolic function (E/A and e/e'). While there was no difference in rates of hospitalization (for heart failure or overall), mortality was significantly lower in patients treated with SGLT2i compared with those who were not (6.5 vs. 16.6%, P = 0.049). CONCLUSIONS: We observed an improvement in mortality in patients undergoing CRT prescribed SGLT2i compared with those not prescribed SGLT2i, despite similar degrees of reverse remodelling. The authors recommend starting SGLT2i prior to CRT implantation, where it does not delay implantation.
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Terapia de Ressincronização Cardíaca , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Masculino , Feminino , Terapia de Ressincronização Cardíaca/métodos , Idoso , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Resultado do Tratamento , Volume Sistólico/fisiologia , Estudos Retrospectivos , Função Ventricular Esquerda/fisiologia , Ecocardiografia , Eletrocardiografia , Seguimentos , Taxa de Sobrevida/tendênciasRESUMO
Mitochondrial aldehyde dehydrogenase-2 (ALDH-2) is involved in preconditioning pathways, but its role in remote ischaemic preconditioning (rIPC) is unknown. We investigated its role in animal and human models of rIPC. (i) In a rabbit model of myocardial infarction, rIPC alone reduced infarct size [69 ± 5.8 % (n = 11) to 40 ± 6.5 % (n = 12), P = 0.019]. However, rIPC protection was lost after pre-treatment with the ALDH-2 inhibitor cyanamide (62 ± 7.6 % controls, n = 10, versus 61 ± 6.9 % rIPC after cyanamide, n = 10, P > 0.05). (ii) In a forearm plethysmography model of endothelial ischaemia-reperfusion injury, 24 individuals of Asian ethnic origin underwent combined rIPC and ischaemia-reperfusion (IR). 11 had wild-type (WT) enzyme and 13 carried the Glu504Lys (ALDH2*2) polymorphism (rendering ALDH-2 functionally inactive). In WT individuals, rIPC protected against impairment of response to acetylcholine (P = 0.9), but rIPC failed to protect carriers of Glu504Lys polymorphism (P = 0.004). (iii) In a second model of endothelial IR injury, 12 individuals participated in a double-blind placebo-controlled crossover study, receiving the ALDH-2 inhibitor disulfiram 600 mg od or placebo for 48 h prior to assessment of flow-mediated dilation (FMD) before and after combined rIPC and IR. With placebo, rIPC was effective with no difference in FMD before and after IR (6.18 ± 1.03 % and 4.76 ± 0.93 % P = 0.1), but disulfiram inhibited rIPC with a reduction in FMD after IR (7.87 ± 1.27 % and 3.05 ± 0.53 %, P = 0.001). This study demonstrates that ALDH-2 is involved in the rIPC pathway in three distinct rabbit and human models. This has potential implications for future clinical studies of remote conditioning.
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Aldeído Desidrogenase/antagonistas & inibidores , Cianamida/farmacologia , Dissulfiram/farmacologia , Inibidores Enzimáticos/farmacologia , Antebraço/irrigação sanguínea , Membro Posterior/irrigação sanguínea , Precondicionamento Isquêmico/métodos , Infarto do Miocárdio/prevenção & controle , Miocárdio/enzimologia , Traumatismo por Reperfusão/prevenção & controle , Aldeído Desidrogenase/genética , Aldeído Desidrogenase/metabolismo , Aldeído-Desidrogenase Mitocondrial , Análise de Variância , Animais , Estudos Cross-Over , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Método Duplo-Cego , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/enzimologia , Endotélio Vascular/fisiopatologia , Genótipo , Humanos , Modelos Lineares , Mutação , Infarto do Miocárdio/enzimologia , Infarto do Miocárdio/patologia , Traumatismo por Reperfusão Miocárdica/enzimologia , Traumatismo por Reperfusão Miocárdica/patologia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Miocárdio/patologia , Fenótipo , Pletismografia , Coelhos , Fluxo Sanguíneo Regional/efeitos dos fármacos , Traumatismo por Reperfusão/enzimologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Fatores de Tempo , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
Background Idiopathic ventricular fibrillation (VF) is a diagnosis of exclusion following normal cardiac investigations. We sought to determine if exercise-induced changes in electrical substrate could distinguish patient groups with various ventricular arrhythmic pathophysiological conditions and identify patients susceptible to VF. Methods and Results Computed tomography and exercise testing in patients wearing a 252-electrode vest were combined to determine ventricular conduction stability between rest and peak exercise, as previously described. Using ventricular conduction stability, conduction heterogeneity in idiopathic VF survivors (n=14) was compared with those surviving VF during acute ischemia with preserved ventricular function following full revascularization (n=10), patients with benign ventricular ectopy (n=11), and patients with normal hearts, no arrhythmic history, and negative Ajmaline challenge during Brugada family screening (Brugada syndrome relatives; n=11). Activation patterns in normal subjects (Brugada syndrome relatives) are preserved following exercise, with mean ventricular conduction stability of 99.2±0.9%. Increased heterogeneity of activation occurred in the idiopathic VF survivors (ventricular conduction stability: 96.9±2.3%) compared with the other groups combined (versus 98.8±1.6%; P=0.001). All groups demonstrated periodic variation in activation heterogeneity (frequency, 0.3-1 Hz), but magnitude was greater in idiopathic VF survivors than Brugada syndrome relatives or patients with ventricular ectopy (7.6±4.1%, 2.9±2.9%, and 2.8±1.2%, respectively). The cause of this periodicity is unknown and was not replicable by introducing exercise-induced noise at comparable frequencies. Conclusions In normal subjects, ventricular activation patterns change little with exercise. In contrast, patients with susceptibility to VF experience activation heterogeneity following exercise that requires further investigation as a testable manifestation of underlying myocardial abnormalities otherwise silent during routine testing.
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Síndrome de Brugada , Complexos Ventriculares Prematuros , Humanos , Síndrome de Brugada/complicações , Síndrome de Brugada/diagnóstico , Sistema de Condução Cardíaco , Complexos Ventriculares Prematuros/etiologia , Complexos Ventriculares Prematuros/complicações , Eletrocardiografia , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/etiologia , SobreviventesRESUMO
BACKGROUND: A novel familial arrhythmia syndrome, cardiac ryanodine receptor (RyR2) calcium release deficiency syndrome (CRDS), has recently been described. We evaluated a large and well characterized family to assess provocation testing, risk factor stratification and response to therapy in CRDS. METHODS: We present a family with multiple unheralded sudden cardiac deaths and aborted cardiac arrests, primarily in children and young adults, with no clear phenotype on standard clinical testing. RESULTS: Genetic analysis, including whole genome sequencing, firmly established that a missense mutation in RYR2, Ala4142Thr, was the underlying cause of disease in the family. Functional study of the variant in a cell model showed RyR2 loss-of-function, indicating that the family was affected by CRDS. EPS (Electrophysiological Study) was undertaken in 9 subjects known to carry the mutation, including a survivor of aborted sudden cardiac death, and the effects of flecainide alone and in combination with metoprolol were tested. There was a clear gradation in inducibility of nonsustained and sustained ventricular arrhythmia between subjects at EPS, with the survivor of aborted sudden cardiac death being the most inducible subject. Administration of flecainide substantially reduced arrhythmia inducibility in this subject and abolished arrhythmia in all others. Finally, the effects of additional metoprolol were tested; it increased inducibility in 4/9 subjects. CONCLUSIONS: The Ala4142Thr mutation of RYR2 causes the novel heritable arrhythmia syndrome CRDS, which is characterized by familial sudden death in the absence of prior symptoms or a recognizable phenotype on ambulatory monitoring or exercise stress testing. We increase the experience of a specific EPS protocol in human subjects and show that it is helpful in establishing the clinical status of gene carriers, with potential utility for risk stratification. Our data provide evidence that flecainide is protective in human subjects with CRDS, consistent with the effect previously shown in a mouse model.
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Canalopatias , Canal de Liberação de Cálcio do Receptor de Rianodina/metabolismo , Taquicardia Ventricular , Animais , Arritmias Cardíacas/complicações , Cálcio/metabolismo , Morte Súbita Cardíaca/etiologia , Flecainida , Humanos , Metoprolol , Camundongos , Canal de Liberação de Cálcio do Receptor de Rianodina/genética , Taquicardia Ventricular/genéticaRESUMO
Heart failure is a syndrome of huge and growing importance worldwide. It is widely accepted that the energy status of the myocardium in heart failure is impaired, irrespective of etiology. Agents which modify cardiac substrate utilisation have the potential to ameliorate this energy deficiency by increasing cardiac mechanical efficiency. This may represent a new therapeutic paradigm in heart failure. In this review we discuss existing and new agents that alter cardiac substrate use and summarise the data on clinical efficacy.
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Metabolismo Energético/efeitos dos fármacos , Insuficiência Cardíaca/tratamento farmacológico , Miocárdio/metabolismo , Animais , Metabolismo dos Carboidratos/efeitos dos fármacos , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Humanos , Modelos Biológicos , Miocárdio/patologia , Oxirredução/efeitos dos fármacosAssuntos
Mapeamento Potencial de Superfície Corporal/métodos , Serviços Médicos de Emergência/métodos , Bloqueio Cardíaco/diagnóstico , Bloqueio Cardíaco/prevenção & controle , Sistema de Condução Cardíaco/anormalidades , Veia Cava Inferior/anormalidades , Diagnóstico Diferencial , Sistema de Condução Cardíaco/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Veia Cava Inferior/patologiaRESUMO
With the growing popularity of water-based sports, cases of swimming-induced pulmonary edema (SIPE) are becoming increasingly recognized. SIPE, a potentially life-threatening condition, is an acute cause of breathlessness in athletes. It has been described frequently in scuba divers, swimmers, and triathletes and is characterized by symptoms and signs of pulmonary edema following water immersion. It is important to recognize that athletes' symptoms can present with a spectrum of severity from mild breathlessness to severe dyspnea, hemoptysis, and hypoxia. In most cases, there is rapid resolution of symptoms within 48 hours of exiting the water. Recent advances in the understanding of the pathophysiology of SIPE, particularly regarding exaggerated pulmonary vascular pressures, have begun to explain this elusive condition more clearly and to distinguish its predisposing factors. It is essential that event organizers and athletes are aware of SIPE. Prompt recognition is required not only to prevent drowning, but also to implement appropriate medical management and subsequent advice regarding return to swimming and the risk of recurrence. This manuscript provides a current perspective on SIPE regarding the incidence rate, the current understanding of the pathophysiology, clinical presentation, medical management, recurrence rates, and advice on return to sport.
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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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OBJECTIVES: The objective of this study was to evaluate the cost-effectiveness of quadripolar versus bipolar cardiac resynchronization defibrillator therapy systems. BACKGROUND: Quadripolar left ventricular (LV) leads for cardiac resynchronization therapy reduce phrenic nerve stimulation (PNS) and are associated with reduced mortality compared with bipolar leads. METHODS: A total of 606 patients received implants at 3 UK centers (319 Q, 287 B), between 2009 and 2014; mean follow-up was 879 days. Rehospitalization episodes were costed at National Health Service national tariff rates, and EQ-5D utility values were applied to heart failure admissions, acute coronary syndrome events, and mortality data, which were used to estimate quality-adjusted life-year differences over 5 years. RESULTS: Groups were matched with regard to age and sex. Patients with quadripolar implants had a lower rate of hospitalization than those with bipolar implants (42.6% vs. 55.4%; p = 0.002). This was primarily driven by fewer hospital readmissions for heart failure (51 [16%] vs. 75 [26.1%], respectively, for quadripolar vs. bipolar implants; p = 0.003) and generator replacements (9 [2.8%] vs. 19 [6.6%], respectively; p = 0.03). Hospitalization for suspected acute coronary syndrome, arrhythmia, device explantation, and lead revisions were similar. This lower health-care utilization cost translated into a cumulative 5-year cost saving for patients with quadripolar systems where the acquisition cost was <£932 (US $1,398) compared with bipolar systems. Probabilistic sensitivity analysis results mirrored the deterministic calculations. For the average additional price of £1,200 (US $1,800) over a bipolar system, the incremental cost-effective ratio was £3,692 per quality-adjusted life-year gained (US $5,538), far below the usual willingness-to-pay threshold of £20,000 (US $30,000). CONCLUSIONS: In a UK health-care 5-year time horizon, the additional purchase price of quadripolar cardiac resynchronization defibrillator therapy systems is largely offset by lower subsequent event costs up to 5 years after implantation, which makes this technology highly cost-effective compared with bipolar systems.
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Dispositivos de Terapia de Ressincronização Cardíaca/economia , Desfibriladores Implantáveis/economia , Síndrome Coronariana Aguda/economia , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Idoso , Arritmias Cardíacas/economia , Arritmias Cardíacas/mortalidade , Arritmias Cardíacas/terapia , Estimulação Cardíaca Artificial/economia , Estimulação Cardíaca Artificial/mortalidade , Terapia de Ressincronização Cardíaca/economia , Terapia de Ressincronização Cardíaca/mortalidade , Análise Custo-Benefício , Feminino , Insuficiência Cardíaca/economia , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/terapia , Hospitalização/economia , Humanos , Masculino , Desenho de Prótese , Anos de Vida Ajustados por Qualidade de Vida , Sistema de Registros , Reino Unido/epidemiologiaRESUMO
Evidence indicates that anatomical and physiological phenotypes of hypertrophic cardiomyopathy (HCM) stem from genetically mediated, inefficient cardiomyocyte energy utilization, and subsequent cellular energy depletion. However, HCM often presents clinically with normal left ventricular (LV) systolic function or hyperkinesia. If energy inefficiency is a feature of HCM, why is it not manifest as resting LV systolic dysfunction? In this Perspectives article, we focus on an idiosyncratic form of reversible systolic dysfunction provoked by LV obstruction that we have previously termed the 'lobster claw abnormality' - a mid-systolic drop in LV Doppler ejection velocities. In obstructive HCM, this drop explains the mid-systolic closure of the aortic valve, the bifid aortic pressure trace, and why patients cannot increase stroke volume with exercise. This phenomenon is characteristic of a broader phenomenon in HCM that we have termed dynamic systolic dysfunction. It underlies the development of apical aneurysms, and rare occurrence of cardiogenic shock after obstruction. We posit that dynamic systolic dysfunction is a manifestation of inefficient cardiomyocyte energy utilization. Systolic dysfunction is clinically inapparent at rest; however, it becomes overt through the mechanism of afterload mismatch when LV outflow obstruction is imposed. Energetic insufficiency is also present in nonobstructive HCM. This paradigm might suggest novel therapies. Other pathways that might be central to HCM, such as myofilament Ca2+ hypersensitivity, and enhanced late Na+ current, are discussed.
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Cardiomiopatia Hipertrófica/fisiopatologia , Metabolismo Energético , Miócitos Cardíacos/metabolismo , Disfunção Ventricular Esquerda/fisiopatologia , Cardiomiopatia Hipertrófica/tratamento farmacológico , Cardiomiopatia Hipertrófica/metabolismo , Diástole , Humanos , Volume Sistólico , Sístole , Taquicardia/fisiopatologiaRESUMO
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.
Assuntos
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
A 43-year-old woman having significant risk factors for ischaemic heart disease was admitted with an acute coronary syndrome (ACS). Coronary angiography revealed a non-flow limiting lesion in her right coronary artery with the rest of her arteries unremarkable. Risk stratification of the culprit lesion in the right coronary artery through intravascular ultrasound virtual histology demonstrated that the rupture plaque had less than 5% necrotic core with low vulnerability indices. This important finding suggested that the re-rupture risk was low so aggressive pharmacological treatment that can influence the plaque characteristics was instigated in preference to mechanical plaque sealing with a coronary stent. At a year of follow-up the patient was well and had no further events.