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AIMS: Left ventricular assist devices (LVADs) are increasingly implanted in patients with advanced heart failure. Currently, LVAD care is predominantly concentrated at specialized tertiary care hospitals. The increasing workload and logistical burden for implanting centers poses significant challenges to access to care for individual patients in remote areas. An emerging approach to LVAD patient management is the use of a shared care model (SCM), which allows implanting centers to collaborate with local non-implanting hospitals. This scoping review explores and synthesizes the current scientific evidence on the use of an SCM in LVAD care management. METHODS: Eligible studies were identified in EMBASE, Pubmed MEDLINE, Web of Science, Cochrane, and Google Scholar. The PRISMA-ScR method was used to systematically synthesize findings. RESULTS: Of the 950 records screened, five articles met the inclusion criteria. Four review articles focused on the proposed benefits and challenges of using an SCM. Main benefits included improved patient satisfaction and continuity of care. Important challenges were initial education of non-implanting center staff and maintaining competency. One prospective study showed that absence of LVAD-specific care was associated with impaired survival and higher rates of pump thrombosis and LVAD-related infections. CONCLUSIONS: The use of an SCM is a promising approach in the long-term management of LVAD patients. However, sufficient evidence about the impact of an SCM on patients and the healthcare system is currently lacking. Standardized protocols based on prospective studies are needed to develop safe and effective shared care for LVAD patients.
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The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell-based immune therapies including chimeric antigen receptor T lymphocyte (CAR-T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune-related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune-related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI-related myocarditis with cardiogenic shock to more common complications including less severe ICI-related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non-inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR-T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus.
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OBJECTIVE: Heart failure (HF) pathophysiology in patients with obesity may be distinct. To study these features, we identified obesity-related biomarkers from 4210 circulating proteins in patients with HF with reduced ejection fraction (HFrEF) and examined associations of these proteins with HF prognosis and biological mechanisms. METHODS: In 373 patients with trimonthly blood sampling during a median follow-up of 2.1 (25th-75th percentile: 1.1-2.6) years, we applied an aptamer-based multiplex approach measuring 4210 proteins in baseline samples and the last two samples before study end. Associations between obesity (BMI > 30 kg/m2) and baseline protein levels were analyzed. Subsequently, associations of serially measured obesity-related proteins with biological mechanisms and the primary endpoint (PEP; composite of cardiovascular mortality, HF hospitalization, left ventricular assist device implantation, and heart transplantation) were examined. RESULTS: Obesity was identified in 26% (96/373) of patients. A total of 30% (112/373) experienced a PEP (with obesity: 26% [25/96] vs. without obesity: 31% [87/277]). A total of 141/4210 proteins were linked to obesity, reflecting mechanisms of neuron projection development, cell adhesion, and muscle cell migration. A total of 50/141 proteins were associated with the PEP, of which 12 proteins related to atherosclerosis or hypertrophy provided prognostic information beyond clinical characteristics, N-terminal pro-B-type natriuretic peptide, and high-sensitivity troponin T. CONCLUSIONS: Patients with HFrEF and obesity show distinct proteomic profiles compared to patients with HFrEF without obesity. Obesity-related proteins are independently associated with HF outcome. These proteins carry potential to improve management of obesity-related HF and could be leads for future research.
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AIM: Senescence is a major risk factor for heart failure (HF), and insulin-like growth factor-binding protein-7 (IGFBP7) has been identified as an important senescence-inducing factor. The aim of this study was to examine the value of baseline and repeat IGFBP7 measurements in predicting future HF among community-dwelling Dutch adults from the Prevention of Renal and Vascular End-stage Disease (PREVEND) study. METHODS AND RESULTS: Individuals without prevalent HF who attended PREVEND visits 2 and 4 median of 5.1 years apart (25th-75th percentile, 4.9-5.2) with measurements of IGFBP7 were included. We used Cox proportional hazards models to investigate the association between IGFBP7 and HF incidence. A total of 6125 participants attending visit 2 (mean ± standard deviation [SD] age 53.1 ± 12.2 years; 3151 [51.4%] men) were followed for a median of 8.4 (7.8-8.9) years, and 194 participants (3.2%) developed incident HF. Median baseline IGFBP7 concentration was 87.0 (75.1-97.3) ng/ml, and baseline IGFBP7 levels were significantly associated with risk for incident HF (HF risk factors adjusted hazard ratio [HR] per 1 SD change in log-transformed IGFBP7: 1.22, 95% confidence interval [CI] 1.03-1.46). Baseline IGFBP7 was also significantly associated with incident HF in individuals with N-terminal pro-B-type natriuretic peptide <125 ng/L. Among 3879 participants attending both visits 2 and 4 (mean ± SD age 57.5 ± 11.3 years; 1952 [50.3%] men), 93 individuals developed HF (after visit 4) during a median follow-up of 3.2 (2.8-3.9) years. Median increase in IGFBP7 concentration between visits was 0.68 (-7.09 to 8.36) ng/ml, and changes in IGFBP7 levels were significantly associated with risk for incident HF (HF risk factors adjusted HR per 1 SD change in log-transformed IGFBP7: 1.68, 95% CI 1.19-2.36). CONCLUSIONS: Both baseline as well as repeat IGFBP7 measurements provide information about the risk of developing HF.
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AIMS: The primary aim was to evaluate the effect of dapagliflozin according to QRS duration across the spectrum of left ventricular ejection fraction (LVEF), given that prolongation of QRS duration is associated with less favourable ventricular remodelling with pharmacological therapy and worse outcomes. METHODS AND RESULTS: A pooled analysis of the DAPA-HF and DELIVER trials, excluding patients with a paced rhythm and cardiac resynchronization therapy. Overall, 4008 patients had heart failure (HF) with reduced ejection fraction (HFrEF), and 5816 had HF with mildly reduced/preserved ejection fraction (HFmrEF/HFpEF). QRS duration was <120 ms in 7039 patients (71.7%), 120-149 ms in 1725 (17.6%), and ≥150 ms in 1060 patients (10.8%). The median follow-up time was 23 months. The rate of the primary composite outcome of cardiovascular death or worsening HF was 9.2 (95% confidence interval [CI] 8.7-9.7), 14.3 (13.0-15.7), and 15.9 (14.1-17.9) per 100 patient-years in the <120, 120-149, and ≥150 ms groups, respectively. This gradient in event rates was observed both in HFrEF and HFmrEF/HFpEF. Dapagliflozin, compared with placebo, reduced the risk of the primary outcome consistently across the QRS duration subgroups (hazard ratio [95% CI] 0.75 [0.67-0.85], 0.79 [0.65-0.96], and 0.89 [0.70-1.13] in the <120, 120-149, and ≥150 ms groups, respectively; p for interaction = 0.28). The effect of dapagliflozin on the primary outcome was consistent across the QRS duration regardless of HF phenotype that is, HFrEF or HFmrEF/HFpEF. CONCLUSIONS: Prolongation of QRS duration is associated with worse outcomes irrespective of HF phenotype. Dapagliflozin reduced the risk of the primary outcome, regardless of QRS duration, in DAPA-HF and DELIVER.
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BACKGROUND: Half of patients with heart failure with preserved ejection fraction (HFpEF) remain undiagnosed by resting evaluation alone. Therefore, exercise testing is proposed. The diastolic stress test (DST), however, has limited sensitivity. We aimed to determine the clinical significance of adding the mean pulmonary artery pressure over cardiac output (mPAP/CO) slope to the DST in suspected HFpEF. METHODS AND RESULTS: In this prospective cohort study, consecutive patients (n=1936) with suspected HFpEF underwent exercise echocardiography with simultaneous respiratory gas analysis. These patients were stratified by exercise E over e' (exE/e') and mPAP/CO slope, and peak oxygen uptake, natriuretic peptides (NT-proBNP [N-terminal pro-B-type natriuretic peptide]), and score-based HFpEF likelihood were compared. Twenty-two percent of patients (n=428) had exE/e'<15 despite a mPAP/CO slope>3 mm Hg/L per min, 24% (n=464) had a positive DST (exE/e'≥15), and 54% (n=1044) had a normal DST and slope. Percentage of predicted oxygen uptake was similar in the group with exE/e'<15 but high mPAP/CO slope and the positive DST group (-2% [-5% to +1%]), yet worse than in those with normal DST and slope (-12% [-14% to -9%]). Patients with exE/e'<15 but a high slope had NT-proBNP levels and H2FPEF (heavy, hypertensive, atrial fibrillation, pulmonary hypertension, elder; filling pressure) scores intermediate to the positive DST group and the group with both a normal DST and slope. CONCLUSIONS: Twenty-two percent of patients with suspected HFpEF presented with a mPAP/CO slope>3 mm Hg/L per min despite a negative DST. These patients had HFpEF characteristics and a peak oxygen uptake as low as patients with a positive DST. Therefore, an elevated mPAP/CO slope might indicate HFpEF irrespective of the DST result.
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Prueba de Esfuerzo , Insuficiencia Cardíaca , Hipertensión Pulmonar , Volumen Sistólico , Humanos , Femenino , Masculino , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/sangre , Volumen Sistólico/fisiología , Anciano , Estudios Prospectivos , Persona de Mediana Edad , Hipertensión Pulmonar/fisiopatología , Hipertensión Pulmonar/diagnóstico , Prueba de Esfuerzo/métodos , Ecocardiografía de Estrés , Fragmentos de Péptidos/sangre , Péptido Natriurético Encefálico/sangre , Diástole , Función Ventricular Izquierda/fisiología , Gasto Cardíaco/fisiología , Valor Predictivo de las Pruebas , Consumo de Oxígeno , Relevancia ClínicaAsunto(s)
Biomarcadores , Insuficiencia Cardíaca , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Humanos , Insuficiencia Cardíaca/inmunología , Biomarcadores/sangre , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/sangre , Animales , Vacunas , Senescencia CelularRESUMEN
AIMS: Heart failure (HF), a global pandemic affecting millions of individuals, calls for adequate predictive guidance for improved therapy. Congestion, a key factor in HF-related hospitalizations, further underscores the need for timely interventions. Proactive monitoring of intracardiac pressures, guided by pulmonary artery (PA) pressure, offers opportunities for efficient early-stage intervention, since haemodynamic congestion precedes clinical symptoms. METHODS: The BioMEMS study, a substudy of the MONITOR-HF trial, proposes a multifaceted approach integrating blood biobank data with traditional and novel HF parameters. Two additional blood samples from 340 active participants in the MONITOR-HF trial were collected at baseline, 3-, 6-, and 12-month visits and stored for the BioMEMS biobank. The main aims are to identify the relationship between temporal biomarker patterns and PA pressures derived from the CardioMEMS-HF system, and to identify the biomarker profile(s) associated with the risk of HF events and cardiovascular death. CONCLUSION: Since the prognostic value of single baseline measurements of biomarkers like N-terminal pro-B-type natriuretic peptide is limited, with the BioMEMS study we advocate a dynamic, serial approach to better capture HF progression. We will substantiate this by relating repeated biomarker measurements to PA pressures. This design rationale presents a comprehensive review on cardiac biomarkers in HF, and aims to contribute valuable insights into personalized HF therapy and patient risk assessment, advancing our ability to address the evolving nature of HF effectively.
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BACKGROUND: Cardiovascular disease (CVD) and cancer are the two leading causes of death worldwide. Given their high prevalence, it is important to understand the disease burden of cancer mortality in CVD patients. OBJECTIVE: We aimed to evaluate whether patients with incident CVD have a higher risk of malignancy-related mortality, compared to the general population without CVD. METHODS: We performed a national population-based cohort study selecting patients with incident CVD in the Netherlands between 01 April 2000 and 31 December 2005. A reference cohort was selected from the Dutch population using age, sex and ethnicity. Mortality follow-up data were evaluated after data linkage of national registries from Statistics Netherlands until 31 December 2020. RESULTS: A total of 2,240,879 individuals were selected with a mean follow-up of 12 years (range 0.4-21.0), of which 738,666 patients with incident CVD with a mean age of 71 ± 15 years. Malignancy mortality per 1000 person years was 84 for the reference group and 118 for patients with CVD, with the highest rate of 258 in patients with heart failure. Patients with CVD had a higher malignancy mortality risk, compared to the reference group: HR 1.35 (95%CI 1.33-1.36). Highest risks were observed in patients with venous diseases (HR 2.27, 95%CI 2.17-2.36) and peripheral artery disease (HR 1.87, 95%CI 1.84-2.01). CONCLUSION: Results show that CVD predisposes to a higher cancer mortality rate. Of all CVD subtypes, HF patients have the highest cancer mortality rate and the hazards were highest in patients with venous diseases and peripheral artery disease.
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AIMS: Electronic health records (EHR) linked to Digital Imaging and Communications in Medicine (DICOM), biological specimens, and deep learning (DL) algorithms could potentially improve patient care through automated case detection and surveillance. We hypothesized that by applying keyword searches to routinely stored EHR, in conjunction with AI-powered automated reading of DICOM echocardiography images and analysing biomarkers from routinely stored plasma samples, we were able to identify heart failure (HF) patients. METHODS AND RESULTS: We used EHR data between 1993 and 2021 from Tayside and Fife (~20% of the Scottish population). We implemented a keyword search strategy complemented by filtering based on International Classification of Diseases (ICD) codes and prescription data to EHR data set. We then applied DL for the automated interpretation of echocardiographic DICOM images. These methods were then integrated with the analysis of routinely stored plasma samples to identify and categorize patients into HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), and controls without HF. The final diagnosis was verified through a manual review of medical records, measured natriuretic peptides in stored blood samples, and by comparing clinical outcomes among groups. In our study, we selected the patient cohort through an algorithmic workflow. This process started with 60 850 EHR data and resulted in a final cohort of 578 patients, divided into 186 controls, 236 with HFpEF, and 156 with HFrEF, after excluding individuals with mismatched data or significant valvular heart disease. The analysis of baseline characteristics revealed that compared with controls, patients with HFrEF and HFpEF were generally older, had higher BMI, and showed a greater prevalence of co-morbidities such as diabetes, COPD, and CKD. Echocardiographic analysis, enhanced by DL, provided high coverage, and detailed insights into cardiac function, showing significant differences in parameters such as left ventricular diameter, ejection fraction, and myocardial strain among the groups. Clinical outcomes highlighted a higher risk of hospitalization and mortality for HF patients compared with controls, with particularly elevated risk ratios for both HFrEF and HFpEF groups. The concordance between the algorithmic selection of patients and manual validation demonstrated high accuracy, supporting the effectiveness of our approach in identifying and classifying HF subtypes, which could significantly impact future HF diagnosis and management strategies. CONCLUSIONS: Our study highlights the feasibility of combining keyword searches in EHR, DL automated echocardiographic interpretation, and biobank resources to identify HF subtypes.
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AIMS: Although much is known about the usefulness of heart failure (HF)-specific instruments for assessing patient well-being, less is known about the value of generic instruments for the measurement of health-related quality of life (HRQL) in HF. The aim of this study was to assess the relationship between the EuroQol 5-dimension 5-level (EQ-5D-5L) visual analogue scale (VAS) and index scores, clinical characteristics, and outcomes in patients with HF and the effect of dapagliflozin on these scores. METHODS AND RESULTS: We performed a patient-level pooled analysis of the DAPA-HF and DELIVER trials, which investigated the effectiveness and safety of dapagliflozin in patients with HF and reduced ejection fraction (HFrEF) and mildly reduced/preserved ejection fraction (HFmrEF/HFpEF), respectively. Patients reporting higher (better) EQ-5D-5L VAS and index scores had a lower prevalence of comorbidities, including atrial fibrillation and hypertension, than patients with a worse score. They were also more likely to have better investigator-reported (New York Heart Association class) and patient-self-reported (Kansas City Cardiomyopathy Questionnaire) health status and lower median N-terminal pro-B-type natriuretic peptide levels. Compared to patients with the lowest scores (Q1), those with higher EQ-5D-5L VAS scores had better outcomes: the hazard ratio for the composite of cardiovascular death or worsening HF was 0.81 (95% confidence interval 0.72-0.91) in Q2, 0.74 (0.65-0.84) in Q3, and 0.62 (0.54-0.72) in Q4. The risk of each component of the composite outcome, and all-cause death, was also lower in patients with better scores. Similar findings were observed for the index score. Treatment with dapagliflozin improved both EQ-5D-5L VAS and index scores across the range of ejection fraction. CONCLUSIONS: Both higher (better) EQ-5D-5L VAS and index scores were associated with better outcomes. Dapagliflozin treatment improved EQ-5D-5L VAS and index scores, irrespective of ejection fraction.
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Compuestos de Bencidrilo , Glucósidos , Insuficiencia Cardíaca , Calidad de Vida , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Masculino , Volumen Sistólico/fisiología , Femenino , Glucósidos/uso terapéutico , Compuestos de Bencidrilo/uso terapéutico , Anciano , Encuestas y Cuestionarios , Persona de Mediana Edad , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéuticoRESUMEN
AIMS: Type 2 diabetes (T2D) and heart failure (HF) frequently coexist, but whether clinical outcomes and treatment effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) vary in relation to background glucose-lowering therapy (GLT) in this population is uncertain. METHODS AND RESULTS: DELIVER randomized patients with HF and left ventricular ejection fraction (LVEF) >40% to dapagliflozin or placebo. The primary outcome was a composite of worsening HF (HF hospitalization or urgent HF visit) or cardiovascular death. In this pre-specified analysis of participants with T2D, treatment effects were assessed by number and class of background GLT(s). Of 3150 participants with T2D at baseline, 22.9% were on no GLT, 36.5% were treated with 1 GLT, and 40.6% with ≥2 GLTs. During follow-up (median: 2.3 years), treatment benefits of dapagliflozin (vs. placebo) on the primary outcome were consistent irrespective of the number of background GLTs (0 GLTs: hazard ratio [HR] 0.71, 95% confidence interval [CI] 0.50-1.00; 1 GLT: HR 1.04, 95% CI 0.80-1.34; ≥2 GLTs: HR 0.71, 95% CI 0.56-0.90; pinteraction = 0.59). Similar findings were observed among participants with (HR 0.73, 95% CI 0.59-0.92) and without background metformin use (HR 0.89, 95% CI 0.72-1.11; pinteraction = 0.22) and in participants with (HR 0.89, 95% CI 0.69-1.16) and without background insulin use (HR 0.78, 95% CI 0.65-0.95; pinteraction = 0.45). Dapagliflozin was well-tolerated irrespective of the number of background GLTs. CONCLUSIONS: Dapagliflozin safely and consistently improved clinical outcomes among individuals with T2D and HF with LVEF >40% irrespective of the number and class of background GLTs, and the benefits were not influenced by concomitant metformin or insulin use. These data bolster contemporary guidelines supporting first-line SGLT2i among individuals with T2D and HF, irrespective of background GLT.
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Compuestos de Bencidrilo , Diabetes Mellitus Tipo 2 , Glucósidos , Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Volumen Sistólico , Humanos , Compuestos de Bencidrilo/uso terapéutico , Glucósidos/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Volumen Sistólico/fisiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Anciano , Resultado del Tratamiento , Método Doble Ciego , Glucemia/metabolismo , Glucemia/efectos de los fármacos , Hipoglucemiantes/uso terapéuticoRESUMEN
AIMS: Remote haemodynamic monitoring with an implantable pulmonary artery (PA) sensor has been shown to reduce heart failure (HF) hospitalizations and improve quality of life. Cost-effectiveness analyses studying the value of remote haemodynamic monitoring in a European healthcare system with a contemporary standard care group are lacking. METHODS AND RESULTS: A Markov model was developed to estimate the cost-effectiveness of PA-guided therapy compared to the standard of care based upon patient-level data of the MONITOR-HF trial performed in the Netherlands in patients with chronic HF (New York Heart Association class III and at least one previous HF hospitalization). Cost-effectiveness was measured as the incremental cost per quality-adjusted life year (QALY) gained from the Dutch societal perspective with a lifetime horizon which encompasses a wide variety of costs including costs of hospitalizations, monitoring time, telephone contacts, laboratory assessments, and drug changes in both treatment groups. In the base-case analysis, PA-guided therapy increased costs compared to standard of care by 12 121. The QALYs per patient for PA-guided therapy and standard of care was 4.07 and 3.481, respectively, reflecting a gain of 0.58 QALYs. The resulting incremental cost-effectiveness ratio was 20 753 per QALY, which is below the Dutch willingness-to-pay threshold of 50 000 per QALY gained for HF. CONCLUSIONS: The current cost-effectiveness study suggests that remote haemodynamic monitoring with PA-guided therapy on top of standard care is likely to be cost-effective for patients with symptomatic moderate-to-severe HF in the Netherlands.
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Análisis Costo-Beneficio , Insuficiencia Cardíaca , Monitorización Hemodinámica , Arteria Pulmonar , Años de Vida Ajustados por Calidad de Vida , Humanos , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/terapia , Países Bajos , Monitorización Hemodinámica/métodos , Masculino , Femenino , Arteria Pulmonar/fisiopatología , Anciano , Cadenas de Markov , Calidad de Vida , Persona de Mediana Edad , Enfermedad CrónicaRESUMEN
BACKGROUND: Patients recently hospitalized for heart failure (HF) are at a higher risk of adverse clinical outcomes, but they may experience a greater absolute and relative benefit from effective therapies than individuals who are considered more "stable." OBJECTIVES: The authors examined the effects of dapagliflozin according to the timing of prior HF hospitalization in a patient-level pooled analysis of DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) and DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients with Preserved Ejection Fraction Heart Failure). METHODS: A total of 11,007 patients were randomized in DAPA-HF and DELIVER. The primary outcome was the composite of worsening HF or cardiovascular death. RESULTS: In total, 12.4% were hospitalized for HF within 3 months of randomization, 14.2% between 3 and 12 months, and 16.8% more than 1 year before randomization, whereas 56.5% had not been hospitalized. The risk of the primary endpoint was inversely associated with time from prior HF hospitalization, and patients with a recent HF hospitalization had the highest risk. Compared with placebo, dapagliflozin reduced the risk of the primary outcome across HF hospitalization category (0-3 months, HR: 0.66 [95% CI: 0.55-0.81]; 3-12 months, HR: 0.73 [95% CI: 0.59-0.90]; >1 year, HR: 0.91 [95% CI: 0.74-1.12]; and no prior hospitalization, HR: 0.83 [95% CI: 0.73-0.94]; Pinteraction = 0.09). The number of patients needed to treat with dapagliflozin to prevent 1 event over the median follow-up of 22 months was 13, 20, 23, and 28, respectively. The beneficial effect was consistent across the range of LVEF regardless of HF hospitalization category. CONCLUSIONS: The relative benefits of dapagliflozin were consistent across the range of LVEF regardless of the timing of the most recent HF hospitalization with a greater absolute benefit in patients with recent hospitalization.
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AIMS: Recently, a genetic variant-specific prediction model for phospholamban (PLN) p.(Arg14del)-positive individuals was developed to predict individual major ventricular arrhythmia (VA) risk to support decision-making for primary prevention implantable cardioverter defibrillator (ICD) implantation. This model predicts major VA risk from baseline data, but iterative evaluation of major VA risk may be warranted considering that the risk factors for major VA are progressive. Our aim is to evaluate the diagnostic performance of the PLN p.(Arg14del) risk model at 3-year follow-up. METHODS AND RESULTS: We performed a landmark analysis 3 years after presentation and selected only patients with no prior major VA. Data were collected of 268 PLN p.(Arg14del)-positive subjects, aged 43.5 ± 16.3 years, 38.9% male. After the 3 years landmark, subjects had a mean follow-up of 4.0 years (± 3.5 years) and 28 (10%) subjects experienced major VA with an annual event rate of 2.6% [95% confidence interval (CI) 1.6-3.6], defined as sustained VA, appropriate ICD intervention, or (aborted) sudden cardiac death. The PLN p.(Arg14del) risk score yielded good discrimination in the 3 years landmark cohort with a C-statistic of 0.83 (95% CI 0.79-0.87) and calibration slope of 0.97. CONCLUSION: The PLN p.(Arg14del) risk model has sustained good model performance up to 3 years follow-up in PLN p.(Arg14del)-positive subjects with no history of major VA. It may therefore be used to support decision-making for primary prevention ICD implantation not merely at presentation but also up to at least 3 years of follow-up.
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Arritmias Cardíacas , Desfibriladores Implantables , Femenino , Humanos , Masculino , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/genética , Arritmias Cardíacas/terapia , Proteínas de Unión al Calcio/genética , Muerte Súbita Cardíaca/etiología , Muerte Súbita Cardíaca/prevención & control , Reproducibilidad de los Resultados , Factores de Riesgo , Adulto , Persona de Mediana EdadRESUMEN
Heart failure (HF) patients have a significantly higher risk of new-onset cancer and cancer-associated mortality, compared to subjects free of HF. While both the prevention and treatment of new-onset HF in patients with cancer have been investigated extensively, less is known about the prevention and treatment of new-onset cancer in patients with HF, and whether and how guideline-directed medical therapy (GDMT) for HF should be modified when cancer is diagnosed in HF patients. The purpose of this review is to elaborate and discuss the effects of pillar HF pharmacotherapies, as well as digoxin and diuretics on cancer, and to identify areas for further research and novel therapeutic strategies. To this end, in this review, (i) proposed effects and mechanisms of action of guideline-directed HF drugs on cancer derived from pre-clinical data will be described, (ii) the evidence from both observational studies and randomized controlled trials on the effects of guideline-directed medical therapy on cancer incidence and cancer-related outcomes, as synthetized by meta-analyses will be reviewed, and (iii) considerations for future pre-clinical and clinical investigations will be provided.
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Insuficiencia Cardíaca , Neoplasias , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Neoplasias/epidemiologíaRESUMEN
AIM: To assess the cost-effectiveness of dapagliflozin in addition to usual care, compared with usual care alone, in a large population of patients with heart failure (HF), spanning the full range of left ventricular ejection fraction (LVEF). METHODS AND RESULTS: Patient-level data were pooled from HF trials (DAPA-HF, DELIVER) to generate a population including HF with reduced, mildly reduced and preserved LVEF, to increase statistical power and enable exploration of interactions among LVEF, renal function and N-terminal pro-B-type natriuretic peptide levels, as they are relevant determinants of health status in this population. Survival and HF recurrent event risk equations were derived and applied to a lifetime horizon Markov model with health states defined by Kansas City Cardiomyopathy Questionnaire total symptom score quartiles; costs and utilities were in the UK setting. The base case incremental cost-effectiveness ratio (ICER) was £6470 per quality-adjusted life year (QALY) gained, well below the UK willingness-to-pay (WTP) threshold of £20 000/QALY gained. In interaction sensitivity analyses, the highest ICER was observed for elderly patients with preserved LVEF (£16 624/QALY gained), and ranged to a region of dominance (increased QALYs, decreased costs) for patients with poorer renal function and reduced/mildly reduced LVEF. Results across the patient characteristic interaction plane were mostly between £5000 and £10 000/QALY gained. CONCLUSIONS: Dapagliflozin plus usual care, versus usual care alone, yielded results well below the WTP threshold for the UK across a heterogeneous population of patients with HF including the full spectrum of LVEF, and is likely a cost-effective intervention.
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Compuestos de Bencidrilo , Análisis Costo-Beneficio , Glucósidos , Insuficiencia Cardíaca , Años de Vida Ajustados por Calidad de Vida , Volumen Sistólico , Humanos , Compuestos de Bencidrilo/uso terapéutico , Compuestos de Bencidrilo/economía , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Insuficiencia Cardíaca/economía , Volumen Sistólico/fisiología , Glucósidos/uso terapéutico , Glucósidos/economía , Masculino , Femenino , Anciano , Persona de Mediana Edad , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Inhibidores del Cotransportador de Sodio-Glucosa 2/economíaRESUMEN
AIMS: Patients with heart failure (HF) and history of myocardial infarction (MI) face a higher risk of disease progression and clinical events. Whether sodium-glucose cotransporter 2 inhibitors may modify clinical trajectory in such individuals remains incompletely understood. METHODS AND RESULTS: The DAPA-HF and DELIVER trials compared dapagliflozin with placebo in patients with symptomatic HF with left ventricular ejection fraction (LVEF) ≤40% and > 40%, respectively. In this pooled participant-level analysis, we assessed efficacy and safety outcomes by history of MI. The primary outcome in both trials was the composite of cardiovascular death or worsening HF. Of the total of 11 007 patients, 3731 (34%) had a previous MI and were at higher risk of the primary outcome across the spectrum of LVEF in covariate-adjusted models (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.02-1.24). Dapagliflozin reduced the risk of the primary outcome to a similar extent in patients with (HR 0.83, 95% CI 0.72-0.96) and without previous MI (HR 0.76, 95% CI 0.68-0.85; pinteraction = 0.36), with consistent benefits on key secondary outcomes as well. Serious adverse events did not occur more frequently with dapagliflozin, irrespective of previous MI. CONCLUSION: History of MI confers increased risks of adverse cardiovascular outcomes in patients with HF across the LVEF spectrum, even among those with preserved ejection fraction. Dapagliflozin consistently and safely reduces the risk of cardiovascular death or worsening HF, regardless of previous MI.
Asunto(s)
Compuestos de Bencidrilo , Glucósidos , Insuficiencia Cardíaca , Infarto del Miocardio , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Volumen Sistólico , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/fisiopatología , Glucósidos/uso terapéutico , Glucósidos/administración & dosificación , Compuestos de Bencidrilo/uso terapéutico , Infarto del Miocardio/tratamiento farmacológico , Masculino , Femenino , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Volumen Sistólico/fisiología , Anciano , Persona de Mediana Edad , Resultado del Tratamiento , Progresión de la Enfermedad , Función Ventricular Izquierda/fisiología , Función Ventricular Izquierda/efectos de los fármacos , Método Doble CiegoRESUMEN
Background: A single albuminuria measurement is reported to be an independent predictor of cancer risk. Whether change in albuminuria is also independently associated with cancer is not known. Methods: We included 64 303 subjects of the Stockholm CREAtinine Measurements (SCREAM) project without a history of cancer and with at least two urine albumin-creatinine ratio (ACR) tests up to 2 years apart. Albuminuria changes were quantified by the fold-change in ACR over 2 years, and stratified into the absence of clinically elevated albuminuria (i.e. never), albuminuria that remained constant, and albuminuria that increased or decreased. The primary outcome was overall cancer incidence. Secondary outcomes were site-specific cancer incidences. Results: During a median follow-up of 3.7 (interquartile range 3.6-3.7) years, 5126 subjects developed de novo cancer. After multivariable adjustment including baseline estimated glomerular filtration rate and baseline ACR, subjects with increasing ACR over 2 years had a 19% (hazard ratio 1.19; 95% confidence interval 1.08-1.31) higher risk of overall cancer compared with those who never had clinically elevated ACR. No association with cancer risk was seen in the groups with decreasing or constant ACR. Regarding site-specific cancer risks, subjects with increasing ACR or constant ACR had a higher risk of developing urinary tract and lung cancer. No other associations between 2-year ACR changes and site-specific cancers were found. Conclusions: Increases in albuminuria over a 2-year period are associated with a higher risk of developing overall, urinary tract and lung cancer, independent of baseline kidney function and albuminuria. These data add important weight to the link that exists between albuminuria and cancer incidence.