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BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is characterized by blunting of the positive relationship between heart rate and left ventricular (LV) contractility known as the force-frequency relationship (FFR). We have previously described that tailoring the rate-response programming of cardiac implantable electronic devices in patients with HFrEF on the basis of individual noninvasive FFR data acutely improves exercise capacity. We aimed to examine whether using FFR data to tailor heart rate response in patients with HFrEF with cardiac implantable electronic devices favorably influences exercise capacity and LV function 6 months later. METHODS: We conducted a single-center, double-blind, randomized, parallel-group trial in patients with stable symptomatic HFrEF taking optimal guideline-directed medical therapy and with a cardiac implantable electronic device (cardiac resynchronization therapy or implantable cardioverter-defibrillator). Participants were randomized on a 1:1 basis between tailored rate-response programming on the basis of individual FFR data and conventional age-guided rate-response programming. The primary outcome measure was change in walk time on a treadmill walk test. Secondary outcomes included changes in LV systolic function, peak oxygen consumption, and quality of life. RESULTS: We randomized 83 patients with a mean±SD age 74.6±8.7 years and LV ejection fraction 35.2±10.5. Mean change in exercise time at 6 months was 75.4 (95% CI, 23.4 to 127.5) seconds for FFR-guided rate-adaptive pacing and 3.1 (95% CI, -44.1 to 50.3) seconds for conventional settings (analysis of covariance; P=0.044 between groups) despite lower peak mean±SD heart rates (98.6±19.4 versus 112.0±20.3 beats per minute). FFR-guided heart rate settings had no adverse effect on LV structure or function, whereas conventional settings were associated with a reduction in LV ejection fraction. CONCLUSIONS: In this phase II study, FFR-guided rate-response programming determined using a reproducible, noninvasive method appears to improve exercise time and limit changes to LV function in people with HFrEF and cardiac implantable electronic devices. Work is ongoing to confirm our findings in a multicenter setting and on longer-term clinical outcomes. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02964650.
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Dispositivos de Terapia de Resincronización Cardíaca , Terapia de Resincronización Cardíaca , Desfibriladores Implantables , Cardioversión Eléctrica/instrumentación , Tolerancia al Ejercicio , Insuficiencia Cardíaca/terapia , Frecuencia Cardíaca , Volumen Sistólico , Función Ventricular Izquierda , Anciano , Anciano de 80 o más Años , Terapia de Resincronización Cardíaca/efectos adversos , Método Doble Ciego , Cardioversión Eléctrica/efectos adversos , Inglaterra , Femenino , Estado Funcional , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Calidad de Vida , Recuperación de la Función , Factores de Tiempo , Resultado del Tratamiento , Prueba de PasoRESUMEN
OBJECTIVE: The present study assessed agreement between resting cardiac output estimated by inert gas rebreathing (IGR) and thermodilution methods in patients with heart failure and those implanted with a left ventricular assist device (LVAD). METHODS AND RESULTS: Hemodynamic measurements were obtained in 42 patients, 22 with chronic heart failure and 20 with implanted continuous flow LVAD (34 males, aged 50 ± 11 years). Measurements were performed at rest using thermodilution and IGR methods. Cardiac output derived by thermodilution and IGR were not significantly different in LVAD (4.4 ± 0.9 L/min vs 4.7 ± 0.8 L/min, Pâ¯=â¯.27) or patients with heart failure (4.4 ± 1.4 L/min vs 4.5 ± 1.3 L/min, Pâ¯=â¯.75). There was a strong relationship between thermodilution and IGR cardiac index (râ¯=â¯0.81, Pâ¯=â¯.001) and stroke volume index (râ¯=â¯0.75, Pâ¯=â¯.001). Bland-Altman analysis showed acceptable limits of agreement for cardiac index derived by thermodilution and IGR, namely, the mean difference (lower and upper limits of agreement) for patients with heart failure -0.002 L/min/m2 (-0.65 to 0.66 L/min/m2), and -0.14 L/min/m2 (-0.78 to 0.49 L/min/m2) for patients with LVAD. CONCLUSIONS: IGR is a valid method for estimating cardiac output and should be used in clinical practice to complement the evaluation and management of chronic heart failure and patients with an LVAD.
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Insuficiencia Cardíaca , Corazón Auxiliar , Monitorización Hemodinámica , Gasto Cardíaco , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Humanos , Masculino , TermodiluciónRESUMEN
OBJECTIVES: The aim of the present study was to assess the validity and trending ability of the bioreactance method in estimating cardiac output at rest and in response to stress in advanced heart failure patients and heart transplant candidates. DESIGN: This was a prospective single-center study. SETTING: This study was conducted at the heart transplant center at the Freeman Hospital, Newcastle upon Tyne, UK. PARTICIPANTS: Eighteen patients with advanced chronic heart failure due to reduced left ventricular ejection fraction (19 ± 7%), and peak oxygen consumption 12.3 ± 3.9 mL/kg/min. INTERVENTIONS: Participants underwent right heart catheterization using the Swan-Ganz catheter. MEASUREMENTS AND MAIN RESULTS: Cardiac output was measured simultaneously using thermodilution and bioreactance at rest and during active straight leg raise test to volitional exertion. There was no significant difference in cardiac index values obtained by the thermodilution and bioreactance methods (2.26 ± 0.59 v 2.38 ± 0.50 L/min, p > 0.05) at rest and peak straight leg raise test (2.92 ± 0.77 v 3.01 ± 0.66 L/min, p > 0.05). In response to active leg raise test, thermodilution cardiac output increased by 22% and bioreactance by 21%. There was also a strong relationship between cardiac outputs from both methods at rest (râ¯=â¯0.88, p < 0.01) and peak straight leg raise test (râ¯=â¯0.92, p < 0.01). Cartesian plot analysis showed good trending ability of bioreactance compared with thermodilution (concordance rateâ¯=â¯93%) CONCLUSIONS: `Cardiac output measured by the bioreactance method is comparable to that from the thermodilution method. Bioreactance method may be used in clinical practice to assess hemodynamics and improve management of advanced heart failure patients undergoing heart transplant assessment.
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Insuficiencia Cardíaca , Trasplante de Corazón , Gasto Cardíaco , Cateterismo de Swan-Ganz , Humanos , Estudios Prospectivos , Reproducibilidad de los Resultados , Volumen Sistólico , Termodilución , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Observational studies investigating risk factors in coronavirus disease 2019 (COVID-19) have not considered the confounding effects of advanced care planning, such that a valid picture of risk for elderly, frail and multi-morbid patients is unknown. We aimed to report ceiling of care and cardiopulmonary resuscitation (CPR) decisions and their association with demographic and clinical characteristics as well as outcomes during the COVID-19 pandemic. METHODS: Retrospective, observational study conducted between 5th March and 7th May 2020 of all hospitalised patients with COVID-19. Ceiling of care and CPR decisions were documented using the Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) process. Unadjusted and multivariable regression analyses were used to determine factors associated with ceiling of care decisions and death during hospitalisation. RESULTS: A total of 485 patients were included, of whom 409 (84·3%) had a documented ceiling of care; level one for 208 (50·9%), level two for 75 (18·3%) and level three for 126 (30·8%). CPR decisions were documented for 451 (93·0%) of whom 336 (74·5%) were 'not for resuscitation'. Advanced age, frailty, White-European ethnicity, a diagnosis of any co-morbidity and receipt of cardiovascular medications were associated with ceiling of care decisions. In a multivariable model only advanced age (odds 0·89, 0·86-0·93 p < 0·001), frailty (odds 0·48, 0·38-0·60, p < 0·001) and the cumulative number of co-morbidities (odds 0·72, 0·52-1·0, p = 0·048) were independently associated. Death during hospitalisation was independently associated with age, frailty and requirement for level two or three care. CONCLUSION: Ceiling of care decisions were made for the majority of patients during the COVID-19 pandemic, broadly in line with known predictors of poor outcomes in COVID-19, but with a focus on co-morbidities suggesting ICU admission might not be a reliable end-point for observational studies where advanced care planning is routine.
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Planificación Anticipada de Atención , COVID-19/terapia , Toma de Decisiones Clínicas , Adulto , Anciano , Anciano de 80 o más Años , Reanimación Cardiopulmonar , Femenino , Humanos , Cuidados para Prolongación de la Vida , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
Cardiac resynchronization therapy (CRT) is recommended in international guidelines for patients with heart failure due to important left ventricular systolic dysfunction (or heart failure with reduced ejection fraction) and ventricular conduction tissue disease. Cardiac magnetic resonance (CMR) represents the most powerful imaging tool for dynamic assessment of the volumes and function of cardiac chambers but is rarely utilized in patients with CRT due to limitations on the device, programming and scanning. In this review, we explore the known utility of CMR in this cohort with discussion of the risks and potential benefits of scanning whilst CRT is active, including a practical strategy for conducting high quality scans safely. Our contention is that imaging in patients with CRT could be improved further by keeping resynchronization therapy active with resultant benefits on research and also patient outcomes.
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Dispositivos de Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca/terapia , Imagen por Resonancia Cinemagnética/métodos , Disfunción Ventricular Izquierda/terapia , Técnicas de Imagen Cardíaca , Terapia de Resincronización Cardíaca , Insuficiencia Cardíaca/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Medición de Riesgo , Volumen Sistólico , Disfunción Ventricular Izquierda/diagnóstico por imagenRESUMEN
OBJECTIVES: Heart rate variability (HRV) and haemodynamic response to exercise (i.e. peak cardiac power output) are strong predictors of mortality in heart failure. The present study assessed the relationship between measures of HRV and peak cardiac power output. DESIGN: In a prospective observational study of 33 patients (age 54 ± 16 years) with chronic heart failure with reduced left ventricular ejection fraction (29 ± 11%), measures of the HRV (i.e. R-R interval and standard deviation of normal R-R intervals, SDNN) were recorded in a supine position. All patients underwent maximal graded cardiopulmonary exercise testing with non-invasive (inert gas rebreathing) cardiac output assessment. Cardiac power output, expressed in watts, was calculated as the product of cardiac output and mean arterial blood pressure. RESULTS: The mean RR and SDNN were 837 ± 166 and 96 ± 29 ms, peak exercise cardiac power output 2.28 ± 0.85 watts, cardiac output 10.34 ± 3.14 L/min, mean arterial blood pressure 98 ± 14 mmHg, stroke volume 91.43 ± 40.77 mL/beat, and oxygen consumption 19.0 ± 5.6 mL/kg/min. There was a significant but only moderate relationship between the RR interval and peak exercise cardiac power output (r = 0.43, p = .013), cardiac output (r = 0.35, p = .047), and mean arterial blood pressure (r = 0.45, p = .009). The SDNN correlated with peak cardiac power output (r = 0.42, p = .016), mean arterial blood arterial (r = 0.41, p = .019), and stroke volume (r = 0.35, p = .043). CONCLUSIONS: Moderate strength of the relationship between measures of HRV and cardiac response to exercise suggests that cardiac autonomic function is not good indicator of overall function and pumping capability of the heart in chronic heart failure.
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Sistema Nervioso Autónomo/fisiopatología , Gasto Cardíaco , Tolerancia al Ejercicio , Insuficiencia Cardíaca/fisiopatología , Frecuencia Cardíaca , Corazón/inervación , Adulto , Anciano , Presión Arterial , Enfermedad Crónica , Femenino , Insuficiencia Cardíaca/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Modelos Cardiovasculares , Estudios Prospectivos , Volumen Sistólico , Factores de Tiempo , Función Ventricular IzquierdaRESUMEN
AIMS: Heart failure with reduced ejection fraction (HFrEF) induces skeletal muscle mitochondrial abnormalities that contribute to exercise limitation; however, specific mitochondrial therapeutic targets remain poorly established. This study quantified the relationship and contribution of distinct mitochondrial respiratory states to prognostic whole-body measures of exercise limitation in HFrEF. METHODS AND RESULTS: Male patients with HFrEF (n = 22) were prospectively enrolled and underwent ramp-incremental cycle ergometry cardiopulmonary exercise testing to determine exercise variables including peak pulmonary oxygen uptake (VÌO2peak ), lactate threshold (VÌO2LT ), the ventilatory equivalent for carbon dioxide (VÌE /VÌCO2LT ), peak circulatory power (CircPpeak ), and peak oxygen pulse. Pectoralis major was biopsied for assessment of in situ mitochondrial respiration. All mitochondrial states including complexes I, II, and IV and electron transport system (ETS) capacity correlated with VÌO2peak (r = 0.40-0.64; P < 0.05), VÌO2LT (r = 0.52-0.72; P < 0.05), and CircPpeak (r = 0.42-0.60; P < 0.05). Multiple regression analysis revealed that combining age, haemoglobin, and left ventricular ejection fraction with ETS capacity could explain 52% of the variability in VÌO2peak and 80% of the variability in VÌO2LT , respectively, with ETS capacity (P = 0.04) and complex I (P = 0.01) the only significant contributors in the model. CONCLUSIONS: Mitochondrial respiratory states from skeletal muscle biopsies of patients with HFrEF were independently correlated to established non-invasive prognostic cycle ergometry cardiopulmonary exercise testing indices including VÌO2peak , VÌO2LT , and CircPpeak . When combined with baseline patient characteristics, over 50% of the variability in VÌO2peak could be explained by the mitochondrial ETS capacity. These data provide optimized mitochondrial targets that may attenuate exercise limitations in HFrEF.
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Insuficiencia Cardíaca , Humanos , Masculino , Consumo de Oxígeno , Respiración , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
AIMS: In patients with chronic heart failure, QRS duration is a consistent predictor of poor outcomes. It has been suggested that for indicated patients, cardiac resynchronization therapy (CRT) could come sooner in the treatment algorithm, perhaps in parallel with the attainment of optimal guideline-directed medical therapy (GDMT). We aimed to investigate differences in left ventricular (LV) remodelling in those with narrow QRS (NQRS) compared with wide QRS (WQRS) in the absence of CRT, whether an early CRT strategy resulted in unnecessary implants and the effect of early CRT on outcomes. METHODS: Our cohort consisted of 214 consecutive patients with LV ejection fraction (LVEF) of 35% or less who underwent repeat echocardiography 1 year after enrolment. Of these, 116 patients had NQRS, and 98 had WQRS of whom 40 received CRT within 1 year and 58 did not. RESULTS: In the absence of CRT, patients with WQRS had less LV reverse remodelling compared with those with NQRS, with differences in ΔLVEF (+2 vs. +9%, Pâ<â0.001) ΔLV end-diastolic diameter (-1 vs. -2âmm, Pâ=â0.095), ΔLV end-systolic diameter (-2 vs. -4.5âmm, Pâ=â0.038), LV end-systolic volume (-12.6 vs. -25.0âml, Pâ=â0.054) and LV end-diastolic volume (-7.3 vs. -12.2âml, Pâ=â0.071). LVEF was more likely to improve by at least 10% if patients had NQRS or received CRT (Pâ=â0.08). Thirteen (24%) patients with WQRS achieved an LVEF greater than 35% in the absence of CRT; however, none achieved greater than 50%. CONCLUSION: A strictly linear approach to heart failure therapy might lead to delays to optimal treatment in those patients with the most to gain from CRT and the least to gain from GDMT.
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Electrocardiografía/métodos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Remodelación Ventricular/fisiología , Anciano , Terapia de Resincronización Cardíaca/métodos , Ecocardiografía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Volumen Sistólico/fisiología , Resultado del Tratamiento , Función Ventricular Izquierda/fisiologíaRESUMEN
Although left ventricular assist device (LVAD) improves functional capacity, on average LVAD patients are unable to achieve the aerobic capacity of normal healthy subjects or mild heart failure patients. The aim of this study was to examine if markers of right ventricular (RV) function influence maximal exercise capacity. This was a single-center prospective study that enrolled 20 consecutive HeartWare ventricular assist device patients who were admitted at the Freeman Hospital (Newcastle upon Tyne, United Kingdom) for a heart transplant assessment from August 2017 to October 2018. Mean peak oxygen consumption (Peak VO2) was 14.0 ± 5.0 ml/kg/min, and mean peak age and gender-adjusted percent predicted oxygen consumption (%VO2) was 40.0% ± 11.5%. Patients were subdivided into two groups based on the median peak VO2, so each group consisted of 10 patients (50%). Right-sided and pulmonary pressures were consistently higher in the group with poorer exercise tolerance. Patients with poor exercise tolerance (peak VO2 below the median) had higher right atrial pressures at rest (10.6 ± 6.4 vs. 4.3 mmHg ± 3.2; p = 0.02) and the increase with passive leg raising was significantly greater than those with preserved exercise tolerance (peak VO2 above the median). Patients with poor functional capacity also had greater RV dimensions (4.4 cm ± 0.5 vs. 3.7 cm ± 0.5; p = 0.02) and a higher incidence of significant tricuspid regurgitation (moderate or severe tricuspid regurgitation in five patients in the poor exercise capacity group vs. none in the preserved exercise capacity group; p = 0.03). In conclusion, echocardiographic and hemodynamic markers of RV dysfunction discriminate between preserved and nonpreserved exercise capacity in HeartWare ventricular assist device patients.
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Tolerancia al Ejercicio/fisiología , Insuficiencia Cardíaca/cirugía , Corazón Auxiliar , Disfunción Ventricular Derecha/fisiopatología , Adulto , Femenino , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
OBJECTIVE: Estimating survival can aid care planning, but the use of absolute survival projections can be challenging for patients and clinicians to contextualise. We aimed to define how heart failure and its major comorbidities contribute to loss of actuarially predicted life expectancy. METHODS: We conducted an observational cohort study of 1794 adults with stable chronic heart failure and reduced left ventricular ejection fraction, recruited from cardiology outpatient departments of four UK hospitals. Data from an 11-year maximum (5-year median) follow-up period (999 deaths) were used to define how heart failure and its major comorbidities impact on survival, relative to an age-sex matched control UK population, using a relative survival framework. RESULTS: After 10 years, mortality in the reference control population was 29%. In people with heart failure, this increased by an additional 37% (95% CI 34% to 40%), equating to an additional 2.2 years of lost life or a 2.4-fold (2.2-2.5) excess loss of life. This excess was greater in men than women (2.4 years (2.2-2.7) vs 1.6 years (1.2-2.0); p<0.001). In patients without major comorbidity, men still experienced excess loss of life, while women experienced less and were non-significantly different from the reference population (1 year (0.6-1.5) vs 0.4 years (-0.3 to 1); p<0.001). Accrual of comorbidity was associated with substantial increases in excess lost life, particularly for diabetes, chronic kidney and lung disease. CONCLUSIONS: Comorbidity accounts for the majority of lost life expectancy in people with heart failure. Women, but not men, without comorbidity experience survival close to reference controls.
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Diabetes Mellitus/epidemiología , Insuficiencia Cardíaca Sistólica , Esperanza de Vida , Enfermedades Pulmonares/epidemiología , Insuficiencia Renal Crónica/epidemiología , Anciano , Comorbilidad , Femenino , Insuficiencia Cardíaca Sistólica/diagnóstico , Insuficiencia Cardíaca Sistólica/mortalidad , Humanos , Masculino , Pronóstico , Factores Sexuales , Análisis de Supervivencia , Reino Unido/epidemiologíaRESUMEN
BACKGROUND: Long-term right ventricular (RV) pacing leads to heart failure or a decline in left ventricular (LV) function in up to a fifth of patients. We aimed to establish whether patients with focal fibrosis detected on late gadolinium enhancement cardiovascular magnetic resonance (CMR) have deterioration in LV function after RV pacing. METHODS: We recruited 84 patients with LV ejection fraction ≥40% into 2 observational CMR studies. Patients (n=34) with a dual-chamber device and preserved atrioventricular conduction underwent CMR in 2 asynchronous pacing modes (atrial asynchronous and dual-chamber asynchronous) to compare intrinsic atrioventricular conduction with forced RV pacing. Patients (n=50) with high-grade atrioventricular block underwent CMR before and 6 months after pacemaker implantation to investigate the medium-term effects of RV pacing. RESULTS: The key findings were (1) initiation of RV pacing in patients with fibrosis, compared with those without, was associated with greater immediate changes in both LV end-systolic volume index (5.3±3.5 versus 2.1±2.4 mL/m2; P<0.01) and LV ejection fraction (-5.7±3.4% versus -3.2±2.6%; P=0.02); (2) medium-term RV pacing in patients with fibrosis, compared with those without, was associated with greater changes in LV end-systolic volume index (8.0±10.4 versus -0.6±7.3 mL/m2; P=0.008) and LV ejection fraction (-12.3±7.9% versus -6.7±6.2%; P=0.012); (3) patients with fibrosis did not experience an improvement in quality of life, biomarkers, or functional class after pacemaker implantation; (4) after 6 months of RV pacing, 10 of 50 (20%) patients developed LV ejection fraction <35% and were eligible for upgrade to cardiac resynchronization according to current guidelines. All 10 patients had fibrosis on their preimplant baseline scan and were identified by >1.1 g of fibrosis with 90% sensitivity and 70% specificity. CONCLUSIONS: Fibrosis detected on CMR is associated with immediate- and medium-term deterioration in LV function following RV pacing and could be used to identify those at risk of heart failure before pacemaker implantation.
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Estimulación Cardíaca Artificial/métodos , Cardiomiopatías/terapia , Miocardio/patología , Función Ventricular Derecha/fisiología , Anciano , Cardiomiopatías/diagnóstico , Cardiomiopatías/fisiopatología , Electrocardiografía , Fibrosis/diagnóstico , Fibrosis/tratamiento farmacológico , Fibrosis/fisiopatología , Estudios de Seguimiento , Humanos , Imagen por Resonancia Cinemagnética/métodos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Background: Parents' health-seeking behaviors has changed during the COVID-19 pandemic. Providing parents with guidance in decision making might improve their confidence to seek timely advice when a child becomes ill. The aim of this study was to evaluate the "How to recognize if your child is seriously ill" leaflet on parents' confidence, health-seeking behaviors, and usefulness during the COVID-19 lockdown. Method: A nine-item survey, codesigned with parent advisors, was used to measure confidence and health-seeking behavior. Social media was used for data collection in a 6-week period (April-June 2020) during COVID-19 lockdown in the United Kingdom. Categorical data were analyzed as frequencies, and inductive content analysis was performed with the qualitative data. Results: In total, 171 parents responded. Most parents (n = 160, 93.6%) found the leaflet helpful. The leaflet increased the confidence among 116 parents (67.8%) to recognize if their child is ill, and 156 (91.2%) parents had a better understanding of when and where to seek help. Thirty-three (19.2%) parents used the leaflet, while their child was unwell during COVID-19 lockdown, and in 14 (42%) cases, the leaflet resulted in changing health-seeking behavior for that episode. Twelve of these parents decided to seek medical consultation when they had not planned to before. Content analysis revealed three categories. (1) Knowledge-parents found the leaflet an objective source to validate their concerns. (2) Usability-parents reported that the leaflet was clearly designed. (3) Decision aid-parents commented that the leaflet provided clarification around recognition of serious symptoms and when and where to seek appropriate care. Conclusions: Our leaflet provided parents with guidance on decision making and risk assessment of ill children during COVID-19 lockdown. Parents found it helpful; it increased their confidence and positively changed their health-seeking behaviors. Providing parents with targeted information to recognize serious illness in children at home could potentially foster self-care and safely maintain a reduction in pediatric emergency attendances for self-limiting illnesses.
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BACKGROUND: Hospitalization is a common adverse event in people with heart failure and reduced ejection fraction, yet is often not primarily due to decompensated heart failure (HF). We investigated the long-term prognosis following infection-related hospitalization. METHODS: We conducted a prospective observational cohort study of 711 people with heart failure and reduced ejection fraction recruited from 4 specialist HF clinics in the United Kingdom. All hospitalization episodes (n=1568) were recorded and categorized as primarily due to decompensated HF, other cardiovascular disease, infection-related, or other noncardiovascular disease. Survival was determined after the first hospitalization. RESULTS: During 2900 patient-years of follow-up, there were a total of 14 686 hospital days. At least one hospitalization occurred in 467 people (66%); 25% of first hospitalizations were primarily due to infection and these were not associated with typical signs including tachycardia and pyrexia. Compared with other categories of hospitalization, infection-related was associated with older age, lower serum albumin, higher blood neutrophil counts, and greater prevalence of chronic obstructive pulmonary disease at recruitment. Median survival after first infection-related hospitalization was 18.6 months, comparable to that after first decompensated HF hospitalization, even after age-sex adjustment. The burden of all-cause rehospitalization was comparable irrespective of the category of first hospitalization, but infection more commonly caused re-hospitalization after index infection hospitalization. CONCLUSIONS: Infection is a common driver of hospitalization in heart failure and reduced ejection fraction and often presents without classical signs. It is associated with high mortality rates, comparable to decompensated HF, and a major burden of rehospitalization caused by recurrent episodes of infection.
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Enfermedades Transmisibles/terapia , Insuficiencia Cardíaca/terapia , Hospitalización , Volumen Sistólico , Función Ventricular Izquierda , Anciano , Anciano de 80 o más Años , Enfermedades Transmisibles/mortalidad , Enfermedades Transmisibles/fisiopatología , Femenino , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Readmisión del Paciente , Pronóstico , Estudios Prospectivos , Recurrencia , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo , Reino UnidoRESUMEN
AIMS: An increasing proportion of patients with heart failure with reduced ejection fraction (HFrEF) have co-morbidities. The effect of these co-morbidities on modes of death and the effect of disease-modifying agents in multi-morbid patients is unknown. METHODS AND RESULTS: We performed a prospective cohort study of ambulatory patients with HFrEF to assess predictors of outcomes. We identified four key co-morbidities-ischaemic aetiology of heart failure, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and chronic kidney disease (CKD)-that were highly prevalent and associated with an increased risk of all-cause mortality. We used these data to explore modes of death and the utilization of disease-modifying agents in patients with and without these co-morbidities. The cohort included 1789 consecutively recruited patients who had an average age of 69.6 ± 12.5 years, and 1307 (73%) were male. Ischaemic aetiology of heart failure was the most common co-morbidity, occurring in 1061 (59%) patients; 503 (28%) patients had diabetes mellitus, 283 (16%) had COPD, and 140 (8%) had CKD stage IV/V. During mean follow-up of 3.8 ± 1.6 years, 737 (41.5%) patients died, classified as progressive heart failure (n = 227, 32%), sudden (n = 112, 16%), and non-cardiovascular deaths (n = 314, 44%). Multi-morbid patients were older (P < 0.001), more likely to be male (P < 0.001), and had higher New York Heart Association class (P < 0.001), despite having higher left ventricular (LV) ejection fraction (P = 0.001) and lower LV end-diastolic diameter (P = 0.001). Multi-morbid patients were prescribed lower doses of disease-modifying agents, especially patients with COPD who received lower doses of beta-adrenoceptor antagonists (2.7 ± 3.0 vs. 4.1 ± 3.4 mg, P < 0.001) and were less likely to be implanted with internal cardioverter defibrillators (7% vs. 13%, P < 0.001). In multivariate analysis, COPD and diabetes mellitus conferred a >2.5-fold and 1.5-fold increased risk of sudden death, whilst higher doses of beta-adrenoceptor antagonists were protective (hazard ratio per milligram 0.92, 95% confidence interval 0.86-0.98, P = 0.009). Each milligram of bisoprolol-equivalent beta-adrenoceptor antagonist was associated with 9% (P = 0.001) and 11% (P = 0.023) reduction of sudden deaths in patients with <2 and ≥2 co-morbidities, respectively. CONCLUSIONS: Higher doses of beta-adrenoceptor antagonist are associated with greater protection from sudden death, most evident in multi-morbid patients. Patients with COPD who appear to be at the highest risk of sudden death are prescribed the lowest doses and less likely to be implanted with implantable cardioverter defibrillators, which might represent a missed opportunity to optimize safe and proven therapies for these patients.
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We sought to determine hemodynamic mechanisms of exercise intolerance in a group of patients with the HeartWare ventricular assist device (VAD) compared to a group of heart failure patients. Twenty VAD and 22 heart failure patients underwent symptom-limited active straight leg raising exercise during right heart catheterization with thermodilution (TD), and upright cycling cardiopulmonary stress testing with cardiac output measurement by inert gas rebreathing (IGR) method. The TD and IGR exercise cardiac indexes were higher in VAD compared with heart failure group (both P < 0.05), although there was only a borderline increase in peak exercise oxygen consumption (VO2) (P = 0.06). Baseline and exercise right heart catheterization pressures were not significantly different between the two groups. The only significant independent predictors of peak VO2 in the heart failure group were exercise heart rate and cardiac index (both P < 0.05). In contrast, for the VAD group only, resting pulmonary arterial wedge and pulmonary arterial mean pressures were independently related to peak VO2 (both P < 0.05). Thus, in heart failure, exercise cardiac index is an important limitation to exercise capacity, and VADs increase exercise cardiac index. However, in VAD patients, this only produces limited benefits as increased pulmonary and pulmonary wedge pressures limit increases in exercise capacity.
Asunto(s)
Ejercicio Físico/fisiología , Insuficiencia Cardíaca/fisiopatología , Corazón Auxiliar , Función Ventricular Izquierda/fisiología , Adulto , Anciano , Femenino , Hemodinámica/fisiología , Humanos , Masculino , Persona de Mediana Edad , Consumo de Oxígeno/fisiologíaRESUMEN
Chronic heart failure (CHF) is a chronic, progressive disease that has detrimental consequences on a patient's quality of life (QoL). In part due to requirements for market access and licensing, the assessment of current and future treatments focuses on reducing mortality and hospitalizations. Few drugs are available principally for their symptomatic effect despite the fact that most patients' symptoms persist or worsen over time and an acceptance that the survival gains of modern therapies are mitigated by poorly controlled symptoms. Additional contributors to the failure to focus on symptoms could be the result of under-reporting of symptoms by patients and carers and a reliance on insensitive symptomatic categories in which patients frequently remain despite additional therapies. Hence, formal symptom assessment tools, such as questionnaires, can be useful prompts to encourage more fidelity and reproducibility in the assessment of symptoms. This scoping review explores for the first time the assessment options and management of common symptoms in CHF with a focus on patient-reported outcome tools. The integration of patient-reported outcomes for symptom assessment into the routine of a CHF clinic could improve the monitoring of disease progression and QoL, especially following changes in treatment or intervention with a targeted symptom approach expected to improve QoL and patient outcomes.
Asunto(s)
Insuficiencia Cardíaca , Calidad de Vida , Enfermedad Crónica , Insuficiencia Cardíaca/terapia , Humanos , Cuidados Paliativos , Reproducibilidad de los ResultadosRESUMEN
BACKGROUND: Patients with coexistent chronic heart failure (CHF) and diabetes mellitus (DM) demonstrate greater exercise limitation and worse prognosis compared with CHF patients without DM, even when corrected for cardiac dysfunction. Understanding the origins of symptoms in this subgroup may facilitate development of targeted treatments. We therefore characterized the skeletal muscle phenotype and its relationship to exercise limitation in patients with diabetic heart failure (D-HF). METHODS: In one of the largest muscle sampling studies in a CHF population, pectoralis major biopsies were taken from age-matched controls (n = 25), DM (n = 10), CHF (n = 52), and D-HF (n = 28) patients. In situ mitochondrial function and reactive oxygen species, fibre morphology, capillarity, and gene expression analyses were performed and correlated to whole-body exercise capacity. RESULTS: Mitochondrial respiration, content, coupling efficiency, and intrinsic function were lower in D-HF patients compared with other groups (P < 0.05). A unique mitochondrial complex I dysfunction was present in D-HF patients only (P < 0.05), which strongly correlated to exercise capacity (R2 = 0.64; P < 0.001). Mitochondrial impairments in D-HF corresponded to higher levels of mitochondrial reactive oxygen species (P < 0.05) and lower gene expression of anti-oxidative enzyme superoxide dismutase 2 (P < 0.05) and complex I subunit NDUFS1 (P < 0.05). D-HF was also associated with severe fibre atrophy (P < 0.05) and reduced local fibre capillarity (P < 0.05). CONCLUSIONS: Patients with D-HF develop a specific skeletal muscle pathology, characterized by mitochondrial impairments, fibre atrophy, and derangements in the capillary network that are linked to exercise intolerance. These novel preliminary data support skeletal muscle as a potential therapeutic target for treating patients with D-HF.
Asunto(s)
Complicaciones de la Diabetes/complicaciones , Insuficiencia Cardíaca/complicaciones , Músculo Esquelético/patología , Anciano , Enfermedad Crónica , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: Previous studies in heart failure with reduced ejection fraction (HFrEF) suggest that skeletal muscle mitochondrial impairments are associated with exercise intolerance in men. However, the nature of this relationship in female patients remains to be elucidated. This study aimed to determine the relationship between skeletal muscle mitochondrial impairments and exercise intolerance in male and female patients with HFrEF. METHODS: Mitochondrial respiration, enzyme activity, and gene expression were examined in pectoralis major biopsies from age-matched male (n = 45) and female (n = 11) patients with HFrEF and healthy-matched male (n = 24) and female (n = 11) controls. Mitochondrial variables were compared between sex and related to peak exercise capacity. RESULTS: Compared with sex-matched controls, complex I mitochondrial oxygen flux was 17% (P = 0.030) and 29% (P = 0.013) lower in male and female patients with HFrEF, respectively, which correlated to exercise capacity (r = 0.71; P > 0.0001). Female HFrEF patients had a 32% (P = 0.023) lower mitochondrial content compared with controls. However, after adjusting for mitochondrial content, male patients demonstrated lower complex I function by 15% (P = 0.030). Expression of key mitochondrial genes regulating organelle dynamics and maintenance (i.e. optic atrophy 1, peroxisome proliferator-activated receptor γ coactivator-1α, NADH:ubiquinone oxidoreductase core subunit S1/S3, and superoxide dismutase 2) were selectively lower in female HFrEF patients. CONCLUSIONS: These data provide novel evidence that HFrEF induces divergent sex-specific mitochondrial phenotypes in skeletal muscle that predispose towards exercise intolerance, impacting mitochondrial 'quantity' in female patients and mitochondrial 'quality' in male patients. Therapeutic strategies to improve exercise tolerance in HFrEF should consider targeting sex-specific mitochondrial abnormalities in skeletal muscle.