Background
Patients with atrial fibrillation (AF) and heart failure (HF) have a high risk of thromboembolism and other outcomes and anticoagulation is recommended.
Hypothesis
This study was aimed to ...explore the risk factors associated with HF worsening in patients with AF and HF taking rivaroxaban in Spain.
Methods
Multicenter, prospective, observational study that included adults with AF and chronic HF, receiving rivaroxaban ≥4 months before entering. HF worsening was defined as first hospitalization or emergency visit because of HF exacerbation.
Results
A total of 672 patients from 71 Spanish centers were recruited, of whom 658 (97.9%) were included in the safety analysis and 552 (82.1%) in the per protocol analysis. At baseline, mean age was 73.7 ± 10.9 years, 64.9% were male, CHA2DS2‐VASc was 4.1 ± 1.5, HAS‐BLED was 1.6 ± 0.9% and 51.3% had HF with preserved ejection fraction. After 24 months of follow‐up, 24.9% of patients developed HF worsening, 11.6% died, 2.9% had a thromboembolic event, 3.1% a major bleeding, 0.5% an intracranial bleeding and no patient had a fatal hemorrhage. Older age, the history of chronic obstructive pulmonary disease, the previous use of vitamin K antagonists, and restrictive or infiltrative cardiomyopathies, were independently associated with HF worsening. Only 6.9% of patients permanently discontinued rivaroxaban treatment.
Conclusions
Approximately one out of four patients with HF and AF treated with rivaroxaban developed a HF worsening episode after 2 years of follow‐up. The identification of those factors that increase the risk of HF worsening could be helpful in the comprehensive management of this population.
Multicenter, prospective, observational study that included 672 adults from 71 Spanish centers with AF and chronic HF, receiving rivaroxaban. At baseline, mean age was 73.7 ± 10.9 years, 64.9% were male, CHA2DS2‐VASc was 4.1 ± 1.5, HAS‐BLED was 1.6 ± 0.9% and 51.3% had HF with preserved ejection fraction. After 24 months of follow‐up, 24.9% of patients developed HF worsening, 11.6% died, 2.9% had a thromboembolic event, 3.1% a major bleeding, 0.5% an intracranial bleeding and no patient had a fatal hemorrhage. Older age, the history of chronic obstructive pulmonary disease, the previous use of vitamin K antagonists, and restrictive or infiltrative cardiomyopathies, were independently associated with HF worsening. Only 6.9% of patients permanently discontinued rivaroxaban treatment.
Interstitial lung disease (ILD) is a frequent manifestation of Sjögren's syndrome (SS), an autoimmune disease of salivary and lacrimal glands, and affects approximately 20% of patients. No clinical ...or serological features appear to be useful to predict its presence, severity or progression, and chest high-resolution computed tomography (CT) remains the gold standard for diagnosis. Semiquantitative CT (SQCT) based on visual assessment (Goh and Taouli scoring) can estimate ILD extent, although it is burdened by relevant intra- and interobserver variability. Quantitative chest CT (QCT) is a promising alternative modality to assess ILD severity.
To determine whether QCT assessment can identify extensive or limited lung disease in patients with SS and ILD.
This multi-center, cross-sectional and retrospective study enrolled patients with SS and a chest CT scan. SQCT assessment was carried out in a blinded and centralized manner to calculate both Goh and Taouli scores. An operator-independent analysis of all CT scans with the open-source software platform Horos was used to evaluate the QCT indices. Patients were classified according to the extent of ILD and differences in QCT index distribution were investigated with non-parametric tests.
From a total of 102 consecutive patients with SS, the prevalence of ILD was 35.3% (36/102). There was a statistically significant difference in QCT index distribution between the SS with ILD and SS without ILD groups (p<0.001). Moreover, SS-ILD patients with ILD >20% (by Goh score) had a QCT index statistically different from those with limited ILD extent (p<0.001). Finally, QCT indices showed a moderate-to-good correlation with the Goh and Taouli scores (from 0.44 to 0.65; p<0.001).
QCT indices can identify patients with SS and ILD and discriminate those with lesser or greater lung disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Curcumin (CCM) is a molecule of particular interest in health applications due to its wide spectrum of benefits for humans. However, its water-insoluble character and low bioavailability have so far ...prevented its extended use as a therapeutic agent. Incorporation of CCM in drug delivery vehicles (liposomes, vesicles, exosomes,
etc
.) is expected to contribute to increasing its bioavailability. Studies of the affinity of CCM with the components of the membrane systems of such vehicles and determination of factors that may enhance curcumin entrapment in biological membranes are of fundamental importance. To that end, here we take advantage of the nanoarchitectonic capabilities of the Langmuir technique for the construction of model cell membranes and determination of thermodynamic properties in mixed films. The obtained results may serve to: (i) provide some light on the miscibility of CCM with the components in the cell membrane and (ii) determine the optimal conditions for the fabrication of membrane systems incorporating CCM. For that, binary and ternary mixed Langmuir films of CCM, DPPC (1,2-dipalmitoyl-
sn-glycero
-3-phosphocholine) and CHOL (cholesterol) have been prepared. Whilst binary mixtures of DPPC and CCM exhibit poor miscibility and even phase segregation, CHOL has shown itself as a key element to promote the incorporation of CCM in the phospholipidic membrane containing DPPC. Both the thermodynamic studies of the ternary Langmuir films and the Atomic Force Microscopy (AFM) images of Langmuir-Blodgett films have shown that ternary mixed films with a molar fraction composition of
x
DPPC
/
x
CHOL
/
x
CCM
= 0.4/0.4/0.2 exhibit good miscibility, stability, and result in monolayers with a very homogeneous topography.
Thermodynamic studies of Langmuir model cell membranes oriented to the rational design of lipid formulations.
Alcoholic cardiomyopathy (ACM) is defined by a dilated and impaired left ventricle due to chronic excess alcohol consumption. It is largely unknown which factors determine cardiac toxicity on ...exposure to alcohol.
This study sought to evaluate the role of variation in cardiomyopathy-associated genes in the pathophysiology of ACM, and to examine the effects of alcohol intake and genotype on dilated cardiomyopathy (DCM) severity.
The authors characterized 141 ACM cases, 716 DCM cases, and 445 healthy volunteers. The authors compared the prevalence of rare, protein-altering variants in 9 genes associated with inherited DCM. They evaluated the effect of genotype and alcohol consumption on phenotype in DCM.
Variants in well-characterized DCM-causing genes were more prevalent in patients with ACM than control subjects (13.5% vs. 2.9%; p = 1.2 ×10−5), but similar between patients with ACM and DCM (19.4%; p = 0.12) and with a predominant burden of titin truncating variants (TTNtv) (9.9%). Separately, we identified an interaction between TTN genotype and excess alcohol consumption in a cohort of DCM patients not meeting ACM criteria. On multivariate analysis, DCM patients with a TTNtv who consumed excess alcohol had an 8.7% absolute reduction in ejection fraction (95% confidence interval: −2.3% to −15.1%; p < 0.007) compared with those without TTNtv and excess alcohol consumption. The presence of TTNtv did not predict phenotype, outcome, or functional recovery on treatment in ACM patients.
TTNtv represent a prevalent genetic predisposition for ACM, and are also associated with a worse left ventricular ejection fraction in DCM patients who consume alcohol above recommended levels. Familial evaluation and genetic testing should be considered in patients presenting with ACM.
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Aim
Patients with advanced heart failure (AHF) who are not candidates to advanced therapies have poor prognosis. Some trials have shown that intermittent levosimendan can reduce HF hospitalizations ...in AHF in the short term. In this real‐life registry, we describe the patterns of use, safety and factors related to the response to intermittent levosimendan infusions in AHF patients not candidates to advanced therapies.
Methods and results
Multicentre retrospective study of patients diagnosed with advanced heart failure, not HT or LVAD candidates. Patients needed to be on the optimal medical therapy according to their treating physician. Patients with de novo heart failure or who underwent any procedure that could improve prognosis were not included in the registry. Four hundred three patients were included; 77.9% needed at least one admission the year before levosimendan was first administered because of heart failure. Death rate at 1 year was 26.8% and median survival was 24.7 95% CI: 20.4–26.9 months, and 43.7% of patients fulfilled the criteria for being considered a responder lo levosimendan (no death, heart failure admission or unplanned HF visit at 1 year after first levosimendan administration). Compared with the year before there was a significant reduction in HF admissions (38.7% vs. 77.9%; P < 0.0001), unplanned HF visits (22.7% vs. 43.7%; P < 0.0001) or the combined event including deaths (56.3% vs. 81.4%; P < 0.0001) during the year after. We created a score that helps predicting the responder status at 1 year after levosimendan, resulting in a score summatory of five variables: TEER (+2), treatment with beta‐blockers (+1.5), Haemoglobin >12 g/dL (+1.5), amiodarone use (−1.5) HF visit 1 year before levosimendan (−1.5) and heart rate >70 b.p.m. (−2). Patients with a score less than −1 had a very low probability of response (21.5% free of death or HF event at 1 year) meanwhile those with a score over 1.5 had the better chance of response (68.4% free of death or HF event at 1 year). LEVO‐D score performed well in the ROC analysis.
Conclusion
In this large real‐life series of AHF patients treated with levosimendan as destination therapy, we show a significant decrease of heart failure events during the year after the first administration. The simple LEVO‐D Score could be of help when deciding about futile therapy in this population.
AbstractIntroduction and objectivesDanon disease (DD) is caused by mutations in the LAMP2 gene. It is considered a multisystemic disease characterized by hypertrophic cardiomyopathy with ...pre-excitation and extreme hypertrophy, intellectual disability, myopathy, childhood presentation, and worse prognosis in men. There are scarce data on the clinical characteristics and prognosis of DD. MethodsWe analyzed the clinical records of patients with DD from 10 Spanish hospitals.ResultsTwenty-seven patients were included (mean age, 31 ± 19 years; 78% women). Male patients showed a high prevalence of extracardiac manifestations: myopathy (80%), learning disorders (83%), and visual alterations (60%), which were uncommon findings in women (5%, 0%, and 27%, respectively). Although hypertrophic cardiomyopathy was the most common form of heart disease (61%), the mean maximum wall thickness was 15 ± 7 mm and dilated cardiomyopathy was present in 12 patients (10 women). Pre-excitation was found in only 11 patients (49%). Age at presentation was older than 20 years in 16 patients (65%). After a median follow-up of 4 years (interquartile range, 2-9), 4 men (67%) and 9 women (43%) died or required a transplant. Cardiac disease and adverse events occurred later in women (37 ± 9 vs 23 ± 16 and 36 ± 20 vs 20 ± 11 years, respectively).ConclusionsThe clinical characteristics of DD differ substantially from traditional descriptions: age at presentation of DD is older, the disease is not multisystemic in women, and pre-excitation is infrequent.
The genetic cause of hypertrophic cardiomyopathy remains unexplained in a substantial proportion of cases. Formin homology 2 domain containing 3 (FHOD3) may have a role in the pathogenesis of cardiac ...hypertrophy but has not been implicated in hypertrophic cardiomyopathy.
This study sought to investigate the relation between FHOD3 mutations and the development of hypertrophic cardiomyopathy.
FHOD3 was sequenced by massive parallel sequencing in 3,189 hypertrophic cardiomyopathy unrelated probands and 2,777 patients with no evidence of cardiomyopathy (disease control subjects). The authors evaluated protein-altering candidate variants in FHOD3 for cosegregation, clinical characteristics, and outcomes.
The authors identified 94 candidate variants in 132 probands. The variants’ frequencies were significantly higher in patients with hypertrophic cardiomyopathy (74 of 3,189 2.32%) than in disease control subjects (18 of 2,777 0.65%; p < 0.001) or in the gnomAD database (1,049 of 138,606 0.76%; p < 0.001). FHOD3 mutations cosegregated with hypertrophic cardiomyopathy in 17 families, with a combined logarithm of the odds score of 7.92, indicative of very strong segregation. One-half of the disease-causing variants were clustered in a small conserved coiled-coil domain (amino acids 622 to 655); odds ratio for hypertrophic cardiomyopathy was 21.8 versus disease control subjects (95% confidence interval: 1.3 to 37.9; p < 0.001) and 14.1 against gnomAD (95% confidence interval: 6.9 to 28.7; p < 0.001). Hypertrophic cardiomyopathy patients carrying (likely) pathogenic mutations in FHOD3 (n = 70) were diagnosed after age 30 years (mean 46.1 ± 18.7 years), and two-thirds (66%) were males. Of the patients, 82% had asymmetric septal hypertrophy (mean 18.8 ± 5 mm); left ventricular ejection fraction <50% was present in 14% and hypertrabeculation in 16%. Events were rare before age 30 years, with an annual cardiovascular death incidence of 1% during follow-up.
FHOD3 is a novel disease gene in hypertrophic cardiomyopathy, accounting for approximately 1% to 2% of cases. The phenotype and the rate of cardiovascular events are similar to those reported in unselected cohorts. The FHOD3 gene should be routinely included in hypertrophic cardiomyopathy genetic testing panels.
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The BAG3 (BLC2-associated athanogene 3) gene codes for an antiapoptotic protein located on the sarcomere Z-disc. Mutations in BAG3 are associated with dilated cardiomyopathy (DCM), but only a small ...number of cases have been reported to date, and the natural history of BAG3 cardiomyopathy is poorly understood.
This study sought to describe the phenotype and prognosis of BAG3 mutations in a large multicenter DCM cohort.
The study cohort comprised 129 individuals with a BAG3 mutation (62% males, 35.1 ± 15.0 years of age) followed at 18 European centers. Localization of BAG3 in cardiac tissue was analyzed in patients with truncating BAG3 mutations using immunohistochemistry.
At first evaluation, 57.4% of patients had DCM. After a median follow-up of 38 months (interquartile range: 7 to 95 months), 68.4% of patients had DCM and 26.1% who were initially phenotype-negative developed DCM. Disease penetrance in individuals >40 years of age was 80% at last evaluation, and there was a trend towards an earlier onset of DCM in men (age 34.6 ± 13.2 years vs. 40.7 ± 12.2 years; p = 0.053). The incidence of adverse cardiac events (death, left ventricular assist device, heart transplantation, and sustained ventricular arrhythmia) was 5.1% per year among individuals with DCM. Male sex, decreased left ventricular ejection fraction. and increased left ventricular end-diastolic diameter were associated with adverse cardiac events. Myocardial tissue from patients with a BAG3 mutation showed myofibril disarray and a relocation of BAG3 protein in the sarcomeric Z-disc.
DCM caused by mutations in BAG3 is characterized by high penetrance in carriers >40 years of age and a high risk of progressive heart failure. Male sex, decreased left ventricular ejection fraction, and enlarged left ventricular end-diastolic diameter are associated with adverse outcomes in patients with BAG3 mutations.
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Little is known about the characteristics of persons with familial hypercholesterolemia (FH) younger than 18 years, the lipid-lowering therapy used in these patients, and the lipid goals reached in ...real life. Our aim was to evaluate the achievement of low-density lipoprotein cholesterol (LDL-C) treatment goals in FH patients younger than 18 years enrolled in a large national registry.
We analyzed patients younger than 18 years enrolled in a large ongoing registry of molecularly-defined patients with FH in Spain. The attainment of guideline-recommended plasma LDL-C goals at entry and follow-up was analyzed in relation to the use of lipid-lowering therapy.
We enrolled 392 individuals younger than 18 years. Of these, 217 were molecularly-diagnosed FH patients and had a complete follow-up. The median follow-up time was 4.69 years (interquartile range, 2.48-6.38 years), 68.2% of FH patients were on statins, and 41.5% patients had LDL-C < 130mg/dL. Statin use was the only predictor of LDL-C goal attainment.
This study shows that a high proportion of FH patients younger than 18 years have high LDL-C levels and fail to achieve recommended LDL-C targets. Statin use was the only independent predictor of LDL-C goal achievement. No safety concerns were detected during follow-up. These results indicate that many FH patients are not adequately controlled and that there is still room for treatment improvement.
El estudio SAFEHEART se diseñó para analizar la situación y mejorar el conocimiento de la hipercolesterolemia familiar heterocigota (HFH) en España. Nuestro objetivo es determinar la tasa de ...incidencia de eventos cardiovasculares, el riesgo estimado de sufrir un evento y su modificación, el empleo de tratamiento hipolipemiante y la consecución de objetivos de colesterol unido a lipoproteínas de baja densidad en pacientes con HFH.
El SAFEHEART es un estudio prospectivo de cohorte, abierto, multicéntrico, de escala nacional, con seguimiento protocolizado a largo plazo en una población de HFH caracterizada molecularmente. Se analizó a los pacientes mayores de 18 años con seguimiento completo.
El análisis en este estudio se hizo con 2.648 pacientes con HFH. La mediana de seguimiento fue de 6,6 (4,8-9,7) años. La tasa de incidencia general de eventos cardiovasculares fue de 1,3 eventos/100 pacientes-año. El riesgo estimado de sufrir un evento cardiovascular a 10 años se redujo en el seguimiento, y pasó del 1,6 al 1,3% (p <0,001). En el último seguimiento, el 20,6 y el 22,2% de los pacientes en prevención primaria y secundaria consiguieron un colesterol unido a lipoproteínas de baja densidad <100 y <70 mg/dl respectivamente.
En este estudio se muestra la tasa de incidencia de eventos cardiovasculares, el riesgo estimado de sufrir un evento cardiovascular en la mayor población de pacientes con HF en España, así como su modificación, la consecución de objetivos en colesterol unido a lipoproteínas de baja densidad y su tratamiento. Aunque el riesgo cardiovascular de la HFH es elevado, un adecuado tratamiento reduce la probabilidad de sufrir un evento.
Estudio registrado en ClinicalTrials.gov (Identificador: NCT02693548).
The SAFEHEART study was designed to analyze the situation of familial heterozygous hypercholesterolemia (FHH) and improve knowledge of this disease in Spain. Our objective was to determine the incidence rate of cardiovascular events, the estimated risk of developing an event and its modification, the use of lipid-lowering treatment, and the achievement of low-density lipoprotein cholesterol targets in patients with FHH.
SAFEHEART is a prospective, open, multicenter, nationwide cohort study, with long-term protocol-based follow-up in a population of individuals with molecularly-characterized FHH. We analyzed patients older than 18 years with complete follow-up.
We included 2648 patients with FHH. The median follow-up was 6.6 (4.8-9.7) years. The overall incidence rate of cardiovascular events was 1.3 events/100 patient-years. After the follow-up, the 10-year estimated risk of developing a cardiovascular event was reduced from 1.6% to 1.3% (P <.001). In the last follow-up, 20.6% and 22.2% of the patients in primary and secondary prevention achieved low-density lipoprotein cholesterol values <100mg/dL and <70mg/dL, respectively.
This study was performed in the largest population of patients with FHH in Spain. We identified the incidence rate of cardiovascular events, the estimated risk of developing a cardiovascular event and its modification, the achievement of low-density lipoprotein cholesterol targets, and the therapeutic management in this population. Although the cardiovascular risk of FHH is high, appropriate treatment reduces the likelihood of an event.
Clinical trial registration: http://www.clinicaltrials.gov. Identifier: NCT02693548.
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