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Introduction: There is a lack of consensus on the definition of response to cardiac resynchronization therapy (CRT), and it is not clear which response criteria have most influence on cardiac event-free survival. Objectives: To assess the predictive value of various response criteria in patients undergoing CRT and the agreement between them. Methods: We performed a secondary analysis of the BETTER-HF trial. Patient response was classified at six months after CRT according to eleven criteria used in previous trials. The predictive value of response criteria for survival free from mortality, cardiac transplantation and heart failure hospitalization was assessed by Cox regression analysis. Agreement between the different response criteria was assessed using Cohen's kappa (κ). Results: A total of 115 patients were followed for a mean of 25 months. During follow-up, 15 deaths occurred (13%) and 29 patients had at least one adverse cardiac event (25%). Only five of the eleven response criteria were predictors of event-free survival. The most powerful isolated clinical and echocardiographic predictors were a reduction of ≥1 NYHA functional class (HR 0.39 for responders; 95% CI 0.18-0.83, p=0.014) and an increase of at least 15% in left ventricular ejection fraction (HR 0.43, 95% CI 0.20-0.90, p=0.024), respectively. Agreement between the different response criteria was poor. Conclusions: Most currently used response criteria do not predict clinical outcomes and have poor agreement. It is essential to establish a consensus on the definition of CRT response in order to standardize studies. Resumo: Introdução: Não existe consenso na definição de respondedor à ressincronização cardíaca (TRC), e desconhece-se qual o critério de resposta que poderá ter maior influência na sobrevida livre de eventos cardíacos. Objectivos: Avaliar o valor preditivo de vários critérios de resposta em doentes submetidos à TRC, e analisar a concordância entre eles. Métodos: Subanálise do ensaio BETTER-HF. Os doentes foram classificados aos seis meses após TRC em respondedores, de acordo com onze critérios utilizados na literatura. O valor preditivo dos diferentes critérios de resposta para uma sobrevida livre de morte, transplante cardíaco e hospitalização por insuficiência cardíaca foi avaliado usando a regressão de Cox. A concordância entre os diferentes critérios foi avaliada usando o coeficiente k de Cohen. Resultados: 115 doentes foram seguidos durante um período médio de 25 meses. Durante o follow-up ocorreram 15 mortes (13%) e 29 doentes tiveram, pelo menos, um evento cardíaco adverso (25%). Apenas cinco dos onze critérios de resposta foram preditores de sobrevida livre de eventos. Os preditores clínicos e ecocardiográficos isolados mais poderosos foram a redução de, pelo menos, uma classe funcional de NYHA (HR 0,39; IC 95% 0,18-0,83, p=0,014) e um aumento de, pelo menos, 15% na fração de ejeção ventricular esquerda (FEVE) (HR 0,43; IC 95% 0,20-0,90, p=0,024), respetivamente. A concordância entre os diferentes critérios de resposta foi fraca. Conclusão: A maioria dos critérios de resposta utilizados não prevê outcomes clínicos e têm fraca concordância. É essencial criar um consenso na definição de resposta à TRC de forma a uniformizar os estudos. Keywords: Cardiac resynchronization therapy, Heart failure, Predictors of events, Response criteria, Palavras-chave: Terapia de ressincronização cardíaca, Insuficiência cardíaca, Preditores de eventos, Critérios de resposta

Background Optimally treated patients with coarctation of the aorta remain at risk for late vascular dysfunction. The effect of treatment modality on vascular function is unknown. The LOVE‐COARCT (Long‐term Outcomes and Vascular Evaluation After Successful Coarctation of the Aorta Treatment) study was done to compare vascular function in patients with coarctation of the aorta treated with surgery, balloon dilation (BD), or stent implantation. Methods and Results In treated coarctation of the aorta patients without residual coarctation, we prospectively compared aortic stiffness by applanation tonometry and cardiac magnetic resonance; endothelial function by endothelial pulse amplitude testing; blood pressure (BP) phenotype by office BP, ambulatory BP monitoring, and BP response to exercise; left ventricular mass by cardiac magnetic resonance; and blood biomarkers of endothelial function, inflammation, vascular wall function, and extracellular matrix. Participants included 75 patients treated with surgery (n=28), BD (n=23), or stent (n=24). Groups had similar age at enrollment, coarctation of the aorta severity, residual gradient, and metabolic profile, but differed by age at treatment. Prevalence of systemic hypertension, aortic stiffness, endothelial function, and left ventricular mass were similar among treatment groups. However, BD patients had more‐distensible ascending aortas, lower peak systolic BP during exercise, less impairment in diurnal BP variation, and lower inflammatory biomarkers. Results were unchanged after adjustment for potential confounders, including age at treatment. Conclusions In our cohort of patients without residual coarctation, treatment modality was not associated with major vascular outcomes, even though there were some favorable vascular characteristics in the BD patients. Although this suggests that choice of treatment modality should continue to be driven by likelihood of achieving a good anatomical result, more long‐term studies are required to assess the clinical significance of the more‐optimal results of secondary markers of vascular function in BD patients. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03262753.

Objectives . Evaluate the effects of a 6-month High Intensity Interval Training (HIIT) program on (1) functional capacity and health-related quality of life, (2) multiple blood biomarkers, (3) echocardiographic parameters, and (4) exercise performance, in patients in cardiac resynchronization therapy (CRT) stratified by the presence of atrial fibrillation (AF), targeting the following questions: (1) Does CRT provide similar benefits in patients in AF and sinus rhythm (SR)?; and (2) Does HIIT provides similar benefits in patients in AF and SR? Design. Estimates were available at baseline and 6 months after CRT implantation in 37 patients with heart failure. Patients were randomized after CRT to a 24-week HIIT group or to a usual care group (CON). In this sub-analysis, HIIT (AF = 7; SR = 11) and CON (AF = 9; SR = 10) were stratified by the presence of AF. Results. Patients in AF benefitted to a lesser degree from CRT in functional status than patients in SR (23.8-46.0%). However, HIIT induced superior improvements in patients in AF compared to CON (23.9-61.0%). Decreases in TNF-α (8.5-42.9%), BNP (15.3-34.6%) and left ventricular mass (9.6-26.2%) were only observed in patients in SR, whereas increases in peak oxygen uptake were only observed in patients in AF (19.5-23.2%). HIIT improved exercise capacity (8.8-59.4%) in patients in SR. Conclusions. Patients in AF or SR undergoing CRT demonstrated distinct benefits from device implantation and from HIIT as an adjunctive therapeutic strategy. This suggests that both mainstay and adjunctive therapeutics may need to be managed differently in patients in AF and SR.

Background: Coarctation of the aorta (CoA) can be treated using surgery, balloon angioplasty, or stent implantation. Although short-term results are excellent with all three treatment modalities, long-term cardiovascular (CV) morbidity and mortality remain high, likely due to persistently abnormal vascular function. The effects of treatment modality on long-term vascular function remain uncharacterized. The goal of this study is to assess vascular function in this patient population for comparison among the treatment modalities., Methods: We will prospectively assess vascular Afunction in large and small arteries fusing multiple noninvasive modalities and compare the results among the three groups of CoA patients previously treated using surgery, balloon angioplasty, or stent implantation after frequency matching for confounding variables. A comprehensive vascular function assessment protocol has been created to be used in 7 centers. Our primary outcome is arterial stiffness measured by arterial tonometry. Inclusion and exclusion criteria have been carefully established after consideration of several potential confounders. Sample size has been calculated for the primary outcome variable., Conclusion: Treatment modalities for CoA may have distinct impact on large and small arterial vascular function. The results of this study will help identify the treatment modality that is associated with the most optimal level of vascular function, which, in the long term, may reduce CV risk., Competing Interests: There are no conflicts of interest.

Agricultural nutrient balances have been receiving increasing attention in both historical and nutrient management research. The main objectives of this study were to further develop balance methodologies and to carry out a comprehensive assessment of the functioning and nutrient cycling of 1950s agroecosystems in Portugal. Additionally, the main implications for the history of agriculture in Portugal were discussed from the standpoint of soil fertility. We used a mass balance approach that comprises virtually all nitrogen (N), phosphorus (P) and potassium (K) inputs and outputs from cropland topsoil for average conditions in the period 1951-56. We found a consistent deficit in N, both for nationwide (-2.1 kg.ha -1 .yr -1 ) and arable crops (-1.6 kg.ha -1 .yr -1 ) estimates, that was rectified in the turn to the 1960 decade. P and K were, in contrast, accumulating in the soil (4.2-4.6 kg.ha -1 .yr -1 and 1.0-3.0 kg.ha -1 .yr -1 , respectively). We observed that the 1950s is the very moment of inflection from an agriculture fertilized predominantly through reused N in biomass (livestock excretions plus marine, plant and human waste sources) to one where chemical fertilizers prevailed. It is suggested that N deficiency played an important role in this transition.