Impact of diversified grazing systems on milk production, nutrient use and enteric methane emissions in dual-purpose cows.

This study evaluated three continuous grazing systems: Brachiaria Brizantha, Clitoria ternatea and naturalized pastures, complemented with commercial concentrate and C. ternatea silage on milk yield, nutrient use and enteric methane (CH4) emissions. Nine multiparous cows of local Zebu breeds, with an average weight of 448 ± 87 kg, were used. The chemical composition of the food was determined. Live weight, milk production, and quality were assessed. Furthermore, serum urea, urea nitrogen, creatinine and glucose in blood were monitored, and nitrogen use efficiency were calculated. Enteric methane (CH4) emissions were estimated using Tier-2 methodology. A 3 × 3 latin square experimental design was applied. The grazing systems of B. brizantha and C. ternatea had the greater live weights of 465.8 and 453.3 kg/cow, although the latter is similar to naturalized pasture. Milk production and quality were not affected by grazing system, with the exception of the non-fat solids, where the C. ternatea system was lower (102.2 g/kg) than the other grazing systems. The crude protein and N intake, and N excretion in feces and urine were lower in naturalized pasture systems (1139.0 g/day). N outputs in milk was high in the C. ternatea system (56.3 g/cow/day). The naturalized pastures systems showed the better feed use efficiency (25.7%) compared to others. Serum urea and blood urea nitrogen were greater in B. brizantha followed by C. ternatea. Enteric CH4 emissions were indifferent among grazing systems when expressed as a percentage of greenhouse gases (7.1%). In conclusion, the grazing C. ternatea supplemented with commercial concentrate and C. ternatea silage maintains milk production and quality, reduced cow/day emissions (by 2.5%) and lowered energy losses as methane.

Monocyte-to-High-Density Lipoprotein Ratio Is Associated with Systemic Inflammation, Insulin Resistance, and Coronary Subclinical Atherosclerosis in Psoriasis: Results from 2 Observational Cohorts.

Systemic inflammation or insulin resistance drive atherosclerosis. However, they are difficult to capture for assessing cardiovascular risk in clinical settings. The monocyte-to-high-density lipoprotein ratio (MHR) is an accessible biomarker that integrates inflammatory and metabolic information and has been associated with poorer cardiovascular outcomes. Our aim was to evaluate the association of MHR with the presence of subclinical atherosclerosis in patients with psoriasis. The study involved a European and an American cohort including 405 patients with the disease. Subclinical atherosclerosis was assessed by coronary computed tomography angiography. First, MHR correlated with insulin resistance through homeostatic model assessment for insulin resistance, with high-sensitivity CRP and with 18F-fluorodeoxyglucose uptake in spleen, liver, and bone marrow by positron emission tomography/computed tomography. MHR was associated with both the presence of coronary plaques >50% of the artery lumen and noncalcified coronary burden, beyond traditional cardiovascular risk factors (P < .05). In a noncalcified coronary burden prediction model accounting for cardiovascular risk factors, statins, and biologic treatment, MHR added value (area under the curve base model = 0.72 vs area under the curve base model plus MHR = 0.76, P = .04) within the American cohort. These results suggests that MHR may detect patients with psoriasis who have subclinical burden of cardiovascular disease and warrant more aggressive measures to reduce lifetime adverse cardiovascular outcomes.

Association of the Complement System with Subclinical Atherosclerosis in Psoriasis: Findings from an Observational Cohort Study.

Psoriasis is a chronic and inflammatory disease that affects the skin and joints and is associated with multiple comorbidities and cardiovascular risk factors. Consequently, patients with psoriasis have an increased risk of cardiovascular diseases such as atherosclerosis, a chronic pathology that shares common inflammatory and immune-response mechanisms with psoriasis, including vascular inflammation and complement activation. To better understand the relationship between atherosclerosis and psoriasis, a proteomics study followed by a bioinformatics analysis was carried out, with a subsequent validation step using ELISA and western blotting. When the plasma from patients with psoriasis alone was compared with that from patients with psoriasis and atherosclerosis, 31 proteins of interest related to the complement system and oxygen transport were identified. After the validation phase, 11 proteins appeared to define the presence of subclinical atherosclerosis in patients with psoriasis, indicating the importance of complement cascades in the development of atherosclerotic plaques in individuals with psoriasis. These results are a step forward in understanding the pathological pathways implicated in the cardiovascular risk associated with this population, which may represent an interesting starting point for developing predictive tools that improve the follow-up of these patients and design more effective therapies.

Effect of Pelagic Sargassum on In Vitro Dry Matter and Organic Matter Degradation, Gas Production, and Protozoa Population.

This study determined the effect of pelagic Sargassum on in vitro dry matter and organic matter degradation, total gas production (TGP), and protozoa population. The treatments were different levels of Sargassum inclusion on a basal substrate (Stargrass hay; Cynodon nlemfuensis) as follows: T0 (control treatment based on Stargrass hay), T10 (90% Stargrass hay + 10% Sargassum), T20 (80% Stargrass hay + 20% Sargassum), and T30 (70% Stargrass hay + 30% Sargassum). Ruminal fermentation kinetics and protozoa population were determined during 72 h of in vitro incubations. Compared to control, dry matter degradability at 48 and 72 h and organic matter degradability at 24 and 48 h were higher in Sargassum treatments. TGP was lower with T20 at 48 h. The total population of protozoa and the concentration of Entodinium spp. were lower at T20 at 48 h and T30 at 72 h. Cl, S, Ca, K, and Zn (103, 5.97, 88.73, 285.70 g/kg, and 15,900 mg/kg) were high in Sargassum, reaching twice or even nine times higher than the contents in Stargrass (11.37, 1.60, 43.53, 87.73 g/kg, and 866.67 mg/kg). Overall, up to 30% pelagic Sargassum could be included in hay-based substrates from tropical grasses without negative effects on in vitro dry matter and organic matter degradability.

Early Detection and Progression of Subclinical Atherosclerosis in Psoriasis (EDSAP): protocol for an observational, single-centre, prospective cohort study.

INTRODUCTION: Life expectancy of patients with psoriasis is reduced by 4-5 years due to cardiovascular disease with an increased risk of myocardial infarction at an earlier age compared with the general population. This increased risk is independent of traditional cardiovascular risk factors and higher in moderate-to-severe forms of psoriasis. Inflammation may play a key role in the development of atherosclerosis in these patients. METHODS AND ANALYSIS: A prospective cohort study, Early Detection and Progression of Subclinical Atherosclerosis in Psoriasis (EDSAP), was initiated in January 2020 to investigate the presence and progression of subclinical atherosclerosis in patients with psoriasis. 120 patients aged 30-65 years and eligible for biological treatment have been recruited at Hospital Ramón y Cajal in Madrid, Spain. Patients undergo a baseline visit, and 1-year follow-up visit after starting biological therapy. Each visit includes: assessment of cardiovascular risk factors, screening for subclinical atherosclerosis by two-dimensional/three-dimensional ultrasound of carotid and femoral arteries, cardiac CT of coronary arteries and blood sampling. All baseline visits were completed by December 2022, and the remaining follow-up visits will be concluded by the end of 2023. The EDSAP study aims to identify new molecular and imaging markers associated with the presence of atherosclerosis and its progression in a chronic inflammatory state such as psoriasis. This has the potential to: (1) help improve primary cardiovascular prevention strategies in these patients; (2) understand the effect of biological drugs on the cardiovascular system; and (3) serve as a model for understanding atherosclerosis in other chronic inflammatory diseases. ETHICS AND DISSEMINATION: The study protocol has been approved by the Institutional Review Board of the Hospital Ramón y Cajal in Madrid. We will present our findings at national and international congresses, and peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05858099.

Cardiovascular and renal health: Preeclampsia as a risk marker.

BACKGROUND: Cardiovascular (CVD) and chronic kidney disease (CKD) in women have unique risk factors related to hormonal status and obstetric history that must be taken into account. Pregnancy complications, such as preeclampsia (PE), can reveal a subclinical predisposition for the development of future disease that may help identify women who could benefit from early CVD and CKD prevention strategies. MATERIALS AND METHODS: Review of PE and its association with future development of CVD and CKD. RESULTS: Multiple studies have established an association between PE and the development of ischemic heart disease, chronic hypertension, peripheral vascular disease, stroke and CKD. It has not been sufficiently clarified if this relation is a causal one or if it is mediated by common risk factors. Nevertheless, the presence of endothelial dysfunction and thrombotic microangiopathy during pregnancies complicated with PE makes us believe that PE may leave a long-term imprint. Early identification of women who have had a pregnancy complicated by PE becomes a window of opportunity to improve women's health through adequate follow-up and targeted preventive actions. Oxidative stress biomarkers and vascular ultrasound may play a key role in the early detection of this arterial damage. CONCLUSIONS: The implementation of preventive multidisciplinary targeted strategies can help slow down CVD and CKD's natural history in women at risk through lifestyle modifications and adequate blood pressure control. Therefore, we propose a series of recommendations to guide the prediction and prevention of CVD and CKD throughout life of women with a history of PE.

Heart Failure in the Elderly: the Role of Biological and Sociocultural Aspects Related to Sex.

PURPOSE OF REVIEW: Heart failure (HF) entails poor prognosis, with high morbidity and mortality burden, particularly in elderly patients. Notably, important sex differences have been described between men and women with HF. In this regard, some biological and sociocultural aspects related to sex may play a key role in the different development and prognosis of HF in elderly men and women. RECENT FINDINGS: Important differences between men and women with HF, especially in the elderly population, have been specifically addressed in recent studies. Consequently, specific differences in biological and sociocultural aspects have been found to associate differences in pathophysiology, baseline clinical profile, and prognosis according to sex. Moreover, differences in comorbidities and frailty and other geriatric conditions, frequent in elderly population with HF, have also been described. Biological and sociocultural differences related to sex are key in the different clinical presentation and prognosis of heart failure in elderly women. Further studies will be required to better understand some other underlying reasons that may differently impact prognosis in elderly patients with HF.

Differences in clinical outcomes, health care resource utilization and costs in heart failure patients according to left ventricular ejection fraction.

INTRODUCTION AND OBJECTIVES: The impact of left ventricular ejection fraction (LVEF) on health care resource utilization (HCRU) and cost in heart failure (HF) patients is not well known. We aimed to compare outcomes, HCRUs and costs according to LVEF groups. METHODS: Retrospective, observational study of all patients with an emergency department (ED) visit or admission to a tertiary hospital in Spain 2018 with a primary HF diagnosis. We excluded patients with newly diagnosed heart failure. One-year clinical outcomes, costs and HCRUs were compared according to LVEF (reduced [HFrEF], mildly reduced [HFmrEF], and preserved [HFpEF]). RESULTS: Among 1287 patients with a primary diagnosis of HF in the ED, 365 (28.4%) were discharged to home (ED group), and 919 (71.4%) were hospitalized (hospital group [HG]). In total, 190 patients (14.7%) had HFrEF, 146 (11.4%) HFmrEF, and 951 (73.9%) HFpEF. The mean age was 80.1±10.7 years; 57.1% were female. The median [interquartile range] of costs per patient/y was €1889 [259-6269] in the ED group and €5008 [2747-9589] in the HG (P <.001). Hospitalization rates were higher in patients with HFrEF in the ED group. The median costs of HFrEF per patient/y were higher in patients in both groups: €4763 [2076-17 155] vs €3900 [590-8013] for HFmrEF vs €3812 [259-5486] for HFpEF in the ED group, and €6321 [3335-796] vs €6170 [3189-10484] vs €4636 [2609-8977], respectively, in the hospital group (all P <.001). This difference was driven by the more frequent admission to intensive care units, and greater use of diagnostic and therapeutic tests among HFrEF patients. CONCLUSIONS: In HF, LVEF significantly impacts costs and HCRU. Costs were higher in patients with HFrEF, especially those requiring hospitalization, than in those with HFpEF.

Comparison of mathematical models to estimate live weight from heart girth in growing Pelibuey sheep / Comparación de modelos matemáticos para estimar el peso vivo mediante el perímetro torácico en ovinos Pelibuey en crecimiento / Comparação de modelos matemáticos para estimar o peso vivo por meio do perímetro torácico em ovinos Pelibuey em crescimento

Abstract Background: Assessment of animal growth based on live weight (LW) in traditional sheep production systems is limited by the high cost of purchase and maintenance of livestock scales. Objective: To develop and evaluate equations for LW prediction using heart girth (HG) in growing Pelibuey sheep. Methods: A dataset (n=415) of clinically healthy male Pelibuey sheep from two months to one year of age, with an average LW of 25.96 ± 10.25 kg and HG of 68.31 ± 10.53 cm, were used. Three equations were evaluated: LW (kg) = −37.70 + 0.93 × HG (Eq. 1); LW (kg) = −1.74 + 0.19 × HG + 0.008 × HG2 (Eq. 2); and LW (kg) = 0.003 × HG2.68 (Eq. 3). Results: The correlation coefficient between LW and HG was r = 0.94 (p<0.001). The three equations showed a high concordance correlation coefficient (CCCs≥0.97). However, the random error was the main component of the mean square partition of the prediction error (≥82.78%) only for Eqs. 1 and 2. The test for parameter identity (intercept=0; slope=1) was accepted only for Eq. 2 (p>0.05). On the other hand, for Eqs. 1 and 3 the intercept was different from zero and the slope was different from one (p<0.05). Conclusion: The second-degree equation accurately and precisely estimated body weight of growing Pelibuey sheep using the HG as a sole predictor variable.

Resumen Antecedentes : Debido a las condiciones de los sistemas tradicionales de producción ovina, la evaluación del crecimiento animal en función del peso vivo (PV) está limitada por el alto costo de la báscula ganadera y su mantenimiento. Objetivo: Desarrollar y evaluar ecuaciones para predecir el peso corporal utilizando el perímetro torácico (PT) en ovinos Pelibuey en crecimiento. Métodos : Se utilizó un conjunto de datos (n=415) de ovinos Pelibuey machos clínicamente sanos, de dos meses a un año de edad y peso promedio de 25,96 ± 10,25 kg y PT de 68,31 ± 10,53 cm. Se evaluaron tres ecuaciones: PV (kg) = −37,70 + 0,93 × PT (Ec. 1), PV (kg) = −1,74 + 0,19 × PT + 0,008 × PT2 (Ec. 2) y PV (kg) = 0,003 × PT2,68 (Ec. 3). Resultados: El coeficiente de correlación entre PV y PT fue r=0,94 (p<0,001). Las tres ecuaciones mostraron alto coeficiente de correlación de concordancia (CCCs≥0,97). Sin embargo, el error aleatorio fue el componente principal de la partición cuadrática media del error de predicción (≥82,78%) solo para las Ecs. 1 y 2. Sin embargo, la prueba de identidad de parámetros (intersección = 0; pendiente = 1) solo se aceptó para la ecuación 2 (p>0,05). Por otro lado, el intercepto fue diferente de cero y la pendiente fue diferente de uno (p<0.05) para las Ecs. 1 y 3. Conclusión: La ecuación de segundo grado estima con exactitud y precisión el peso corporal de ovinos Pelibuey en crecimiento utilizando la PT como única variable predictora.

Resumo Antecedentes: Devido às condições dos sistemas tradicionais de produção de ovinos, a avaliação do crescimento animal com base no peso corporal (PV) é limitada pelo alto custo da balança pecuária, bem como pela manutenção sofisticada necessária. Objetivo: Desenvolver e avaliar equações para predizer o PV usando o perímetro torácico (PT) em ovinos Pelibuey em crescimento. Métodos: Um conjunto de dados (n=415) de ovinos Pelibuey machos clinicamente saudáveis de dois meses a um ano de idade, com peso médio de 25,96 ± 10,25 kg e PT de 68,31 ± 10,53 cm foi utilizado para o desenvolvimento das equações. Três equações foram avaliadas: PV (kg) = -37,70 + 0,93 × PT (Eq. 1), PV (kg) = -1,74 + 0,19 × PT + 0,008 × PT2 (Eq. 2) e PV (kg) = 0,003 × PT2,68 (Eq. 3). Resultados: O coeficiente de correlação entre PV e PT foi r = 0,94 (P < 0,001). As três equações apresentaram alto coeficiente de correlação e concordância (CCCs≥0,97). No entanto, o erro aleatório foi o principal componente da partição do quadrado médio do erro de predição (≥82,78%) apenas para as Eqs. 1 e 2. No entanto, o teste de identidade dos parâmetros (intercepto = 0; inclinação = 1) foi aceito apenas para a Eq. 2 (p>0,05). Por outro lado, para a Eq. 1 e 3, o intercepto foi diferente de zero e a inclinação foi diferente de um (p<0,05). Conclusões: A equação de segundo grau estima com precisão e acurácia o peso corporal de ovinos Pelibuey em crescimento usando o PT como única variável preditora.

Outcome of moderate-severe tricuspid regurgitation after pulmonary endarterectomy or balloon pulmonary angioplasty.

INTRODUCTION AND OBJECTIVES: The management of persistent moderate-severe tricuspid regurgitation (TR) in patients with chronic thromboembolic pulmonary hypertension after treatment with pulmonary endarterectomy (PEA) or balloon pulmonary angioplasty (BPA) is not well defined. This study aimed to analyze the progression and predictors of significant persistent postintervention TR and its prognostic impact. METHODS: This single-center observational study included 72 patients undergoing PEA and 20 who completed a BPA program with a previous diagnosis of chronic thromboembolic pulmonary hypertension and moderate-to-severe TR. RESULTS: The postintervention prevalence of moderate-to-severe TR was 29%, with no difference between the PEA- or BPA-treated groups (30.6% vs 25% P=.78). Compared with patients with absent-mild postprocedure TR, those with persistent TR had higher mean pulmonary arterial pressure (40.2±1.9 vs 28.5±1.3mmHg P <.001), pulmonary vascular resistance (472 [347-710] vs 282 [196-408] dyn.s/cm5; P <.001), and right atrial area (23.0 [21-31] vs 16.0 [14.0-20.0] P <.001). The variables independently associated with persistent TR were pulmonary vascular resistance> 400 dyn.s/cm5 and postprocedure right atrial area> 22cm2. No preintervention predictors were identified. The variables associated with increased 3-year mortality were residual TR and mean pulmonary arterial pressure> 30mmHg. CONCLUSIONS: Residual moderate-to-severe TR following PEA-PBA was associated with persistently high afterload and unfavorable postintervention right chamber remodeling. Moderate-to-severe TR and residual pulmonary hypertension were associated with a worse 3-year prognosis.

Diabetes mellitus and aortic stenosis head to head: toward personalized medicine in patients with both pathologies.

Diabetes mellitus (DM) and calcific aortic stenosis (CAS) are common morbidities in the elderly, which are both chronic, progressive and often concomitant diseases. Several studies revealed that DM increases the risk of developing severe CAS, yet clear information about the relationship between both these diseases and the influence of DM on the progression of CAS is currently lacking. To evaluate the effect of DM on aortic valves and on the process of calcification, and to achieve better patient management in daily clinical practice, we analysed calcified and noncalcified valve tissue from patients with severe CAS, with or without DM. A proteomic strategy using isobaric tags was adopted and the plasma concentrations of nine proteins were studied using 3 orthogonal methods and in a separate cell model. The differentially expressed proteins identified are implicated in biological processes like endopeptidase activity, lipid metabolism, coagulation, and fibrinolysis. The results obtained provide evidence that DM provokes changes in the proteome of aortic valves, affecting valve calcification. This finding may help enhance our understanding of the pathogenesis of CAS and how DM affects the evolution of this condition, an important step in identifying targets to personalize the treatment of these patients.

From Double-Chambered Right Ventricle to Double-Chambered Left Ventricle: Unusual Evolution of a Ventricular Septal Defect.

We present the first imaging registry of the progressive isolation of an apical chamber of the right ventricle caused by the hypertrophy of the moderator band generated from the hemodynamic effect of a ventricular septal defect, leaving the apex of the right ventricle as an accessory chamber of the left ventricle. (Level of Difficulty: Advanced.).

Prioritization of Candidate Biomarkers for Degenerative Aortic Stenosis through a Systems Biology-Based In-Silico Approach.

Degenerative aortic stenosis is the most common valve disease in the elderly and is usually confirmed at an advanced stage when the only treatment is surgery. This work is focused on the study of previously defined biomarkers through systems biology and artificial neuronal networks to understand their potential role within aortic stenosis. The goal was generating a molecular panel of biomarkers to ensure an accurate diagnosis, risk stratification, and follow-up of aortic stenosis patients. We used in silico studies to combine and re-analyze the results of our previous studies and, with information from multiple databases, established a mathematical model. After this, we prioritized two proteins related to endoplasmic reticulum stress, thrombospondin-1 and endoplasmin, which have not been previously validated as markers for aortic stenosis, and analyzed them in a cell model and in plasma from human subjects. Large-scale bioinformatics tools allow us to extract the most significant results after using high throughput analytical techniques. Our results could help to prevent the development of aortic stenosis and open the possibility of a future strategy based on more specific therapies.

Residual Feed Intake and Rumen Metabolism in Growing Pelibuey Sheep.

This study was carried out to evaluate the residual feed intake (RFI), volatile fatty acid (VFA) production and enteric methane (CH4) from growing Pelibuey sheep. In this case, 12 non-castrated Pelibuey with an initial average live weight (LW) of 21.17 ± 3.87 kg and an age of 3 months, were housed in individual pens and fed a basal diet with 16% of crude protein and 11 MJ ME for 45 days. Dry matter intake (DMI) was measured and the daily weight gain (DWG) was calculated using a linear regression between the LW and experimental period. Mean metabolic live weight (LW0.75) was calculated. RFI was determined by linear regression with DWG and LW0.75 as independent variables. Lambs were classified as low, medium, and high RFI. Feed efficiency was determined as DWG/DMI. For determining rumen pH, ammonia nitrogen concentration NH3-N), and VFA, ruminal fluid was obtained using an esophageal probe on day 40. Feed intake of low RFI lambs was approximately 16% lower (p < 0.05) while growth rate was not significantly different. Their average energy loss, expressed as CH4 production per kilogram of metabolic weight, was 17% lower (p < 0.05).

Early detection of anthracycline- and trastuzumab-induced cardiotoxicity: value and optimal timing of serum biomarkers and echocardiographic parameters.

AIMS: To evaluate echocardiographic and biomarker changes during chemotherapy, assess their ability to early detect and predict cardiotoxicity and to define the best time for their evaluation. METHODS AND RESULTS: Seventy-two women with breast cancer (52 ± 9.8 years) treated with anthracyclines (26 also with trastuzumab), were evaluated for 14 months (6 echocardiograms/12 laboratory tests). We analysed: high-sensitivity cardiac troponin T, NT-proBNP, global longitudinal strain (GLS), left ventricle end-systolic volume (LVESV), left ventricle end-diastolic volume (LVEDV), and left ventricular ejection fraction (LVEF). Cardiotoxicity was defined as a reduction in LVEF>10% compared with baseline with LVEF<53%. High-sensitivity troponin T levels rose gradually reaching a maximum peak at 96 ± 13 days after starting chemotherapy (P < 0.001) and 62.5% of patients presented increased values during treatment. NT-proBNP augmented after each anthracycline cycle (mean pre-cycle levels of 72 ± 68 pg/mL and post-cycle levels of 260 ± 187 pg/mL; P < 0.0001). Cardiotoxicity was detected in 9.7% of patients (mean onset at 5.2 months). In the group with cardiotoxicity, the LVESV was higher compared with those without cardiotoxicity (40 mL vs. 29.5 mL; P = 0.045) at 1 month post-anthracycline treatment and the decline in GLS was more pronounced (-17.6% vs. -21.4%; P = 0.03). Trastuzumab did not alter serum biomarkers, but it was associated with an increase in LVESV and LVEDV (P < 0.05). While baseline LVEF was an independent predictor of later cardiotoxicity (P = 0.039), LVESV and GLS resulted to be early detectors of cardiotoxicity [odds ratio = 1.12 (1.02-1.24), odds ratio = 0.66 (0.44-0.92), P < 0.05] at 1 month post-anthracycline treatment. Neither high-sensitivity troponin T nor NT-proBNP was capable of predicting subsequent cardiotoxicity. CONCLUSIONS: One month after completion of anthracycline treatment is the optimal time to detect cardiotoxicity by means of imaging parameters (LVESV and GSL) and to determine maximal troponin rise. Baseline LVEF was a predictor of later cardiotoxicity. Trastuzumab therapy does not affect troponin values hence imaging techniques are recommended to detect trastuzumab-induced cardiotoxicity.

The anti-aging factor Klotho protects against acquired long QT syndrome induced by uremia and promoted by fibroblast growth factor 23.

BACKGROUND: Chronic kidney disease (CKD) is associated with increased propensity for arrhythmias. In this context, ventricular repolarization alterations have been shown to predispose to fatal arrhythmias and sudden cardiac death. Between mineral bone disturbances in CKD patients, increased fibroblast growth factor (FGF) 23 and decreased Klotho are emerging as important effectors of cardiovascular disease. However, the relationship between imbalanced FGF23-Klotho axis and the development of cardiac arrhythmias in CKD remains unknown. METHODS: We carried out a translational approach to study the relationship between the FGF23-Klotho signaling axis and acquired long QT syndrome in CKD-associated uremia. FGF23 levels and cardiac repolarization dynamics were analyzed in patients with dialysis-dependent CKD and in uremic mouse models of 5/6 nephrectomy (Nfx) and Klotho deficiency (hypomorphism), which show very high systemic FGF23 levels. RESULTS: Patients in the top quartile of FGF23 levels had a higher occurrence of very long QT intervals (> 490 ms) than peers in the lowest quartile. Experimentally, FGF23 induced QT prolongation in healthy mice. Similarly, alterations in cardiac repolarization and QT prolongation were observed in Nfx mice and in Klotho hypomorphic mice. QT prolongation in Nfx mice was explained by a significant decrease in the fast transient outward potassium (K+) current (Itof), caused by the downregulation of K+ channel 4.2 subunit (Kv4.2) expression. Kv4.2 expression was also significantly reduced in ventricular cardiomyocytes exposed to FGF23. Enhancing Klotho availability prevented both long QT prolongation and reduced Itof current. Likewise, administration of recombinant Klotho blocked the downregulation of Kv4.2 expression in Nfx mice and in FGF23-exposed cardiomyocytes. CONCLUSION: The FGF23-Klotho axis emerges as a new therapeutic target to prevent acquired long QT syndrome in uremia by minimizing the predisposition to potentially fatal ventricular arrhythmias and sudden cardiac death in patients with CKD.

Subclinical Liver Disease Is Associated with Subclinical Atherosclerosis in Psoriasis: Results from Two Observational Studies.

Psoriasis is associated with a higher risk of liver diseases. We investigated the impact of hepatic steatosis (European cohort) and hepatic inflammation (United States cohort) on subclinical atherosclerosis. In the European cohort (n = 76 psoriasis participants and 76 controls), nonalcoholic fatty liver disease, assessed by the sonographic hepatorenal index, was more prevalent in psoriasis than in controls (61% vs. 45%; P = 0.04). Participants with psoriasis with nonalcoholic fatty liver disease had a higher prevalence of subclinical atherosclerosis (ultrasonographic presence of plaque in femoral or carotid arteries) than participants with psoriasis without nonalcoholic fatty liver disease (61% vs. 23%; P = 0.006) and controls with nonalcoholic fatty liver disease (61% vs. 32%; P < 0.05). Sonographic hepatorenal index was a determinant of subclinical atherosclerosis in psoriasis (OR = 3.5; P = 0.01). In the United States cohort (n = 162 participants with psoriasis who underwent positron emission tomography and coronary computed tomography angiography), those with high hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake had higher noncalcified (1.3 [0.49 mm2] vs. 1.0 [0.40 mm2]), fibrofatty (0.23 [0.15 mm2] vs. 0.11 [0.087 mm2]), and lipid-rich necrotic core (4.3 [2.3 mm2] vs. 3.0 [1.7 mm2]) coronary burden (all P < 0.001). Hepatic 2-[fluorine-18]fluoro-2-deoxy-D-glucose uptake associated with noncalcified (ß = 0.28; P < 0.001), fibrofatty (ß = 0.49; P < 0.001), and lipid-rich necrotic core (ß = 0.28; P = 0.003) burden. These results show the downstream cardiovascular effects of subclinical liver disease in psoriasis.

Mitral valve prolapse morphofunctional features by cardiovascular magnetic resonance: more than just a valvular disease.

INTRODUCTION: Mitral valve (MV) prolapse (MVP) is a primary valvular abnormality. We hypothesized that additionally there are concomitant abnormalities of the left ventricle (LV) and MV apparatus in this entity even in the absence of significant mitral regurgitation (MR). OBJECTIVE: To characterize MV and LV anatomic and functional features in MVP with preserved LV ejection fraction, with and without significant MR, using cardiovascular magnetic resonance (CMR). METHODS: Consecutive MVP patients (n = 80, mean 52 years, 37% males) with preserved LV ejection fraction, and 44 controls (46 years, 52% males) by CMR were included, as well as 13 additional patients with "borderline" MVP. From cine images we quantified LV volumes, MV and LV anatomic measurements (including angle between diastolic and systolic annular planes, annular displacement, and basal inferolateral hypertrophy) and, using feature tracking, longitudinal and circumferential peak systolic strains. RESULTS: Significant MR was found in 46 (56%) MVP patients. Compared with controls, MVP patients had LV enlargement, basal inferolateral hypertrophy, higher posterior annular excursion, and reduced shortening of the papillary muscles. LV basal strains were significantly increased, particularly in several basal segments. These differences remained significant in patients without significant MR, and many persisted in "borderline" MVP. CONCLUSIONS: In patients with MVP and preserved LV ejection fraction there is LV dilatation, basal inferolateral hypertrophy, exaggerated posterior annular displacement and increased basal deformation, even in the absence of significant MR or overt MVP. These findings suggest that MVP is a disease not only of the MV but also of the adjacent myocardium.

Diabetes Mellitus and Its Implications in Aortic Stenosis Patients.

Aortic stenosis (AS) and diabetes mellitus (DM) are both progressive diseases that if left untreated, result in significant morbidity and mortality. Several studies revealed that the prevalence of DM is substantially higher in patients with AS and, thus, the progression from mild to severe AS is greater in those patients with DM. DM and common comorbidities associated with both diseases, DM and AS, increase patient management complexity and make aortic valve replacement the only effective treatment. For that reason, a better understanding of the pathogenesis underlying both these diseases and the relationships between them is necessary to design more appropriate preventive and therapeutic approaches. In this review, we provided an overview of the main aspects of the relationship between AS and DM, including common comorbidities and risk factors. We also discuss the established treatments/therapies in patients with AS and DM.