Protein misfolding and clearance in the pathogenesis of a new infantile onset ataxia caused by mutations in PRDX3.

Peroxiredoxin 3 (PRDX3) encodes a mitochondrial antioxidant protein, which is essential for the control of reactive oxygen species homeostasis. So far, PRDX3 mutations are involved in mild-to-moderate progressive juvenile onset cerebellar ataxia. We aimed to unravel the molecular bases underlying the disease in an infant suffering from cerebellar ataxia that started at 19 months old and presented severe cerebellar atrophy and peripheral neuropathy early in the course of disease. By whole exome sequencing, we identified a novel homozygous mutation, PRDX3 p.D163E, which impaired the mitochondrial ROS defense system. In mouse primary cortical neurons, the exogenous expression of PRDX3 p.D163E was reduced and triggered alterations in neurite morphology and in mitochondria. Mitochondrial computational parameters showed that p.D163E led to serious mitochondrial alterations. In transfected HeLa cells expressing the mutation, mitochondria accumulation was detected by correlative light electron microscopy. Mitochondrial morphology showed severe changes, including extremely damaged outer and inner membranes with a notable cristae disorganization. Moreover, spherical structures compatible with lipid droplets were identified, which can be associated with a generalized response to stress and can be involved in the removal of unfolded proteins. In the patient's fibroblasts, PRDX3 expression was nearly absent. The biochemical analysis suggested that the mutation p.D163E would result in an unstable structure tending to form aggregates that trigger unfolded protein responses via mitochondria and endoplasmic reticulum. Altogether, our findings broaden the clinical spectrum of the recently described PRDX3-associated neurodegeneration and provide new insight into the pathological mechanisms underlying this new form of cerebellar ataxia.

Risk scores for predicting incident heart failure admission in patients with chronic coronary syndromes: Validation in a prospective, monocentric, long-term, cohort study.

BACKGROUND: Heart failure (HF) admission in chronic coronary syndrome (CCS) patients has a prognostic impact. Stratification schemes have been described for predicting this endpoint, but none of them has been externally validated. OBJECTIVES: Our aim was to develop point scores for predicting incident HF admission with data from previous studies, to perform an external validation in an independent prospective cohort and to compare their discriminative ability for this event. METHODS: Independent predictive variables of HF admission in CCS patients without baseline HF were selected from four previous prospective studies (CARE, PEACE, CORONOR and CLARIFY), generating scores based on the relative magnitude of the coefficients of Cox of each variable. Finally, the scores were validated and compared in a monocentric prospective cohort. RESULTS: The validation cohort included 1212 patients followed for up to 17 years, with 171 patients suffering at least one HF admission in the follow-up. Discriminative ability for predicting HF admission was statistically significant for all, and paired comparisons among them were all nonsignificant except for CORONOR score was superior to CLARIFY score (C-statistic 0.73, 95%CI 0.69-0.76 vs. 0.69, 95% CI 0.65-0.73; p = 0.03). CONCLUSION: All tested scores showed significant discriminative ability for predicting incident HF admission in this independent validation study. Their discriminative ability was similar, with significant differences only between the two scores with higher and lower performance.

Genetic Heterogeneity Underlying Phenotypes with Early-Onset Cerebellar Atrophy.

Cerebellar atrophy (CA) is a frequent neuroimaging finding in paediatric neurology, usually associated with cerebellar ataxia. The list of genes involved in hereditary forms of CA is continuously growing and reveals its genetic complexity. We investigated ten cases with early-onset cerebellar involvement with and without ataxia by exome sequencing or by a targeted panel with 363 genes involved in ataxia or spastic paraplegia. Novel variants were investigated by in silico or experimental approaches. Seven probands carry causative variants in well-known genes associated with CA or cerebellar hypoplasia: SETX, CACNA1G, CACNA1A, CLN6, CPLANE1, and TBCD. The remaining three cases deserve special attention; they harbour variants in MAST1, PI4KA and CLK2 genes. MAST1 is responsible for an ultrarare condition characterised by global developmental delay and cognitive decline; our index case added ataxia to the list of concomitant associated symptoms. PIK4A is mainly related to hypomyelinating leukodystrophy; our proband presented with pure spastic paraplegia and normal intellectual capacity. Finally, in a patient who suffers from mild ataxia with oculomotor apraxia, the de novo novel CLK2 c.1120T>C variant was found. The protein expression of the mutated protein was reduced, which may indicate instability that would affect its kinase activity.

Waiting times in healthcare: equal treatment for equal need?

BACKGROUND: In many universal health systems, waiting times act as a non-monetary rationing mechanism, one that should be based on clinical need rather than the ability to pay. However, there is growing evidence that among patients with similar levels of need, waiting times often differ according to socioeconomic status. The mechanisms underlying inequality in access remain unclear. METHODS: Using data for Spain, we study whether waiting times for primary and specialist care depend on patients' socioeconomic status (SES). Additionally, we make use of the continuous nature of our data to explore whether the SES-related differences in waiting times found for specialist consultations vary among different points of the waiting time distribution. RESULTS: Our results reveal the presence of a SES gradient in waiting times for specialist services explained on the basis of education, employment status and income. In addition, for primary care, we found evidence of a slightly more moderate SES gradient mostly based on employment status. Furthermore, although quantile regression estimates indicated the presence of a SES gradient within the distribution of waiting times for specialist visits, the SES differences attenuated in the context of longer waiting times in the public sector but did not disappear. CONCLUSION: Our findings suggest the principle of equal treatment for equal need, assumed to be inherent to national health systems such as the Spanish system, is not applied in practice. Determining the mechanism(s) underlying this selective barrier to healthcare is of crucial importance for policymakers, especially in the current COVID-19 health and economic crises, which could exacerbate these inequalities as increasing numbers of treatments are having to be postponed.

Mutations, Genes, and Phenotypes Related to Movement Disorders and Ataxias.

Our clinical series comprises 124 patients with movement disorders (MDs) and/or ataxia with cerebellar atrophy (CA), many of them showing signs of neurodegeneration with brain iron accumulation (NBIA). Ten NBIA genes are accepted, although isolated cases compatible with abnormal brain iron deposits are known. The patients were evaluated using standardised clinical assessments of ataxia and MDs. First, NBIA genes were analysed by Sanger sequencing and 59 patients achieved a diagnosis, including the detection of the founder mutation PANK2 p.T528M in Romani people. Then, we used a custom panel MovDisord and/or exome sequencing; 29 cases were solved with a great genetic heterogeneity (34 different mutations in 23 genes). Three patients presented brain iron deposits with Fe-sensitive MRI sequences and mutations in FBXO7, GLB1, and KIF1A, suggesting an NBIA-like phenotype. Eleven patients showed very early-onset ataxia and CA with cortical hyperintensities caused by mutations in ITPR1, KIF1A, SPTBN2, PLA2G6, PMPCA, and PRDX3. The novel variants were investigated by structural modelling, luciferase analysis, transcript/minigenes studies, or immunofluorescence assays. Our findings expand the phenotypes and the genetics of MDs and ataxias with early-onset CA and cortical hyperintensities and highlight that the abnormal brain iron accumulation or early cerebellar gliosis may resembling an NBIA phenotype.

How do policy levers shape the quality of a national health system?

Poor quality of care may have a detrimental effect on access and take-up and can become a serious barrier to the universality of health services. This consideration is of particular interest in view of the fact that health systems in many countries must address a growing public-sector deficit and respond to increasing pressures due to COVID-19 and aging population, among other factors. In line with a rapidly emerging literature, we focus on patient satisfaction as a proxy for quality of health care. Drawing on rich longitudinal and cross-sectional data for Spain and multilevel estimation techniques, we show that in addition to individual level differences, policy levers (such as public health spending and the patient-doctor ratio, in particular) exert a considerable influence on the quality of a health care system. Our results suggest that policymakers seeking to enhance the quality of care should be cautious when compromising the level of health resources, and in particular, health personnel, as a response to economic downturns in a sector that traditionally had insufficient human resources in many countries, which have become even more evident in the light of the current health crisis. Additionally, we provide evidence that the increasing reliance on the private health sector may be indicative of inefficiencies in the public system and/or the existence of features of private insurance which are deemed important by patients.

Distal hereditary motor neuropathies: Mutation spectrum and genotype-phenotype correlation.

BACKGROUND AND PURPOSE: Distal hereditary motor neuropathies (dHMNs) are a heterogeneous group of disorders characterized by degeneration of the motor component of peripheral nerves. Currently, only 15% to 32.5% of patients with dHMN are characterized genetically. Additionally, the prevalence of these genetic disorders is not well known. Recently, biallelic mutations in the sorbitol dehydrogenase gene (SORD) have been identified as a cause of dHMN, with an estimated frequency in undiagnosed cases of up to 10%. METHODS: In the present study, we included 163 patients belonging to 108 different families who were diagnosed with a dHMN and who underwent a thorough genetic screening that included next-generation sequencing and subsequent Sanger sequencing of SORD. RESULTS: Most probands were sporadic cases (62.3%), and the most frequent age of onset of symptoms was 2 to 10 years (28.8%). A genetic diagnosis was achieved in 37/108 (34.2%) families and 78/163 (47.8%) of all patients. The most frequent cause of distal hereditary motor neuropathies were mutations in HSPB1 (10.4%), GARS1 (9.8%), BICD2 (8.0%), and DNAJB2 (6.7%) genes. In addition, 3.1% of patients were found to be carriers of biallelic mutations in SORD. Mutations in another seven genes were also identified, although they were much less frequent. Eight new pathogenic mutations were detected, and 17 patients without a definite genetic diagnosis carried variants of uncertain significance. The calculated minimum prevalence of dHMN was 2.3 per 100,000 individuals. CONCLUSIONS: This study confirms the genetic heterogeneity of dHMN and that biallelic SORD mutations are a cause of dHMN in different populations.

Expanding the ß-III Spectrin-Associated Phenotypes toward Non-Progressive Congenital Ataxias with Neurodegeneration.

(1) Background: A non-progressive congenital ataxia (NPCA) phenotype caused by ß-III spectrin (SPTBN2) mutations has emerged, mimicking spinocerebellar ataxia, autosomal recessive type 14 (SCAR14). The pattern of inheritance, however, resembles that of autosomal dominant classical spinocerebellar ataxia type 5 (SCA5). (2) Methods: In-depth phenotyping of two boys studied by a customized gene panel. Candidate variants were sought by structural modeling and protein expression. An extensive review of the literature was conducted in order to better characterize the SPTBN2-associated NPCA. (3) Results: Patients exhibited an NPCA with hypotonia, developmental delay, cerebellar syndrome, and cognitive deficits. Both probands presented with progressive global cerebellar volume loss in consecutive cerebral magnetic resonance imaging studies, characterized by decreasing midsagittal vermis relative diameter measurements. Cortical hyperintensities were observed on fluid-attenuated inversion recovery (FLAIR) images, suggesting a neurodegenerative process. Each patient carried a novel de novo SPTBN2 substitution: c.193A > G (p.K65E) or c.764A > G (p.D255G). Modeling and protein expression revealed that both mutations might be deleterious. (4) Conclusions: The reported findings contribute to a better understanding of the SPTBN2-associated phenotype. The mutations may preclude proper structural organization of the actin spectrin-based membrane skeleton, which, in turn, is responsible for the underlying disease mechanism.

Limiting health-care access to undocumented immigrants: A wise option?

The number of undocumented migrants in high-income countries has increased in recent decades, imposing considerable political, fiscal, and social pressures on governments. This has fostered discussions on whether and to what extent undocumented migrants should get access to public programs and public benefits. Looking at the 2012 Spanish health reform, this is the first paper to document the impacts of a restriction on access to the health-care system for undocumented migrants on health-care utilization, health-care system perceptions, and self-reported health in a high-income country. We show that such restrictions may significantly reduce planned care for undocumented migrants and result in sharp fall in positive opinions about the health-care services still left available to them. We also exploit the heterogeneity in implementing the policy across regions and report stronger effects in regions that enforced the national ban more fully. Furthermore, in the first 3 years since the implementation of the reform, we find suggestive evidence of a worsening in self-assessed health. This study is relevant for policymakers in the developed world, especially in countries that have recently implemented initiatives aimed at reducing the health-care coverage for targeted groups, such as the United Kingdom and the United States.

Heart rate variability parameters as markers of the adaptation to a sealed environment (a hypoxic normobaric chamber) in the horse.

Simulated hypoxic normobaric devices have been used in human beings in order to enhance endurance capacity. These devices are sealed chambers where the athletes are supposed to stay for at least 6-8 hr daily. The current research assesses the changes in time-domain, spectral and non-geometrical heart rate variability (HRV) parameters in 6 horses subjected to progressive duration periods inside of a hermetically sealed chamber. It was pursued, firstly to evaluate the intensity of the stress experienced by the animals and secondly to elucidate whether the horses might require an acclimation period before implementation of hypoxic conditions. HRV parameters were monitored for 6 days: day 0 (6-hr duration; in paddocks; basal conditions), and days 1, 2, 3, 4 and 5 (1, 2, 3, 4 and 6 hr inside the chamber every day respectively). During day 1 and during the first hours of days 2 and 3, compared to day 0, horses presented increased HR and SDHR values and decreased RR interval duration. SD1 values decreased on some hours of days 2 and 3, but differences with day 0 were not found on day 1. Increased SDNN, RMSSD, SD1 and SD2 values were observed on days 4 and 5. These results showed an activation of the sympathetic activity together with an attenuation of the parasympathetic activity during the days 1 to 3. Increased parasympathetic activity was found only during the first hours of days 4 and 5. Spectral parameters experienced minor variations, with increased LFpeak and LF% during some hours of days 4 and 5. In conclusion, at least 3 days are needed to adapt the horse to a sealed environment before starting to subject the animals to hypoxic conditions. When the horses were acclimatized, however, a minor stress was detected with they spent more than 4 hr inside of the chamber.

Mutations in the MORC2 gene cause axonal Charcot-Marie-Tooth disease.

Charcot-Marie-Tooth disease (CMT) is a complex disorder with wide genetic heterogeneity. Here we present a new axonal Charcot-Marie-Tooth disease form, associated with the gene microrchidia family CW-type zinc finger 2 (MORC2). Whole-exome sequencing in a family with autosomal dominant segregation identified the novel MORC2 p.R190W change in four patients. Further mutational screening in our axonal Charcot-Marie-Tooth disease clinical series detected two additional sporadic cases, one patient who also carried the same MORC2 p.R190W mutation and another patient that harboured a MORC2 p.S25L mutation. Genetic and in silico studies strongly supported the pathogenicity of these sequence variants. The phenotype was variable and included patients with congenital or infantile onset, as well as others whose symptoms started in the second decade. The patients with early onset developed a spinal muscular atrophy-like picture, whereas in the later onset cases, the initial symptoms were cramps, distal weakness and sensory impairment. Weakness and atrophy progressed in a random and asymmetric fashion and involved limb girdle muscles, leading to a severe incapacity in adulthood. Sensory loss was always prominent and proportional to disease severity. Electrophysiological studies were consistent with an asymmetric axonal motor and sensory neuropathy, while fasciculations and myokymia were recorded rather frequently by needle electromyography. Sural nerve biopsy revealed pronounced multifocal depletion of myelinated fibres with some regenerative clusters and occasional small onion bulbs. Morc2 is expressed in both axons and Schwann cells of mouse peripheral nerve. Different roles in biological processes have been described for MORC2. As the silencing of Charcot-Marie-Tooth disease genes have been associated with DNA damage response, it is tempting to speculate that a deregulation of this pathway may be linked to the axonal degeneration observed in MORC2 neuropathy, thus adding a new pathogenic mechanism to the long list of causes of Charcot-Marie-Tooth disease.

New severity criteria for tricuspid regurgitation in a broad population of "real life" patients: Prevalence and prognostic impact.

Introduction Our objective was to determine, in "real life" patients, the prevalence of massive and torrential regurgitation among patients diagnosed with severe tricuspid regurgitation (TR), as well as its impact on long-term prognosis. Methods In a single-center retrospective study, all patients with an echocardiographic diagnosis of severe TR attended at a tertiary care hospital of an European country from January 2008 to December 2017 were recruited. Images were analysed off-line to measure the maximum vena contracta (VC) and TR was classified into three groups: severe (VC ≥ 7 mm), massive (VC 14-20 mm), and torrential (VC ≥ 21 mm). The impact of this classification on the combined event of heart failure (HF) admission and all-cause death in follow-up was investigated. Results A total of 614 patients (70 ± 13 years, 72 % women) were included. 81.4 % had severe TR, 15.8 % massive TR, and 2.8 % torrential TR. The 5-year HF-free survival  was 42 %, 43 %, and 12 % (p = 0.001), for the different subgroups of severe TR, respectively. After adjusting for baseline characteristics, TR severity was an independent predictor of survival free of the combined end-point: HR 0.91 [95 % CI 0.70-1.18] p = 0.46, for massive TR; and HR 2.5 [95 % CI 1.49-4.21] p = 0.001, for torrential TR considering severe TR as reference. Conclusions The prevalence of massive and torrential TR is not negligible among patients with severe TR in real life. The prognosis is significantly worse for patients with torrential TR measured by the maximum VC.

Clinical outcomes and mortality in patients with atrial fibrillation and recently diagnosed lung cancer in oncology outpatient settings.

INTRODUCTION: Our aim was to investigate the prevalence of atrial fibrillation (AF) and recently diagnosed lung cancer in the outpatient oncology clinic and to describe the clinical profile, management and outcomes of this population. METHODS: Among 6984 patients visited at the outpatient oncology clinics attending lung cancer patients in five university hospitals from 2017 to 2019, all consecutive subjects with recently diagnosed (<1 year) disease and AF were retrospectively selected and events in follow up were registered. RESULTS: A total of 269 patients (3.9 % of all attended, 71 ± 8 years, 91 % male) were included. Charlson, CHA2DS2-VASc and HAS-BLED indexes were 6.7 ± 2.9, 2.9 ± 1.5 y 2.5 ± 1.2, respectively. Tumour stage was I, II, III and IV in 11 %, 11 %, 33 % and 45 % of them, respectively. Anticoagulants were prescribed to 226 patients (84 %): direct anticoagulants (n = 99;44 %), low molecular weight heparins (n = 69;30 %) and vitamin K antagonists (n = 58;26 %). After 46 months of maximum follow-up, 186 patients died (69 %). Cumulative incidences of events at 3 years were 3.3 ± 1.3 % for stroke/systemic embolism (n = 7); 8.9 ± 2.2 % for thrombotic events (n = 18); 9.9 ± 2.6 % for major bleeding (n = 16), and 15.9 ± 3,0 % for cardiovascular events (n = 33). In patients with early stages of cancer (I-II), 2-year mortality was significantly higher in those with cardiovascular events or major bleeding (85 % vs 25 %, p = 0.01). CONCLUSION: Nearly 4 % or all outpatients in the oncology clinic attending lung cancer present recently diagnosed disease and AF. Major bleeding and cardiovascular event rates are high in this population, with an impact on mortality in early stages of cancer.

Health System Decentralization: Creating as Many Problems Than It Solves? Comment on "The Effects of Health Sector Fiscal Decentralisation on Availability, Accessibility, and Utilisation of Healthcare Services: A Panel Data Analysis".

This comment draws on the study by Rotulo et al about the effects of fiscal decentralization on access, utilization and availability of healthcare resources across Italian regions. We start by discussing the recent trends in health system decentralization worldwide, and then reflect on the rationale and main benefits and the key complexities and challenges of this much debated reform. We address these issues with reference to the recent experience of Italy as well as that of other comparable highly decentralized countries, most notably Spain, paying particular attention to their similarities and contrasts. We conclude that decentralization of health services poses complex challenges and trade-offs which may require careful design of equalisation mechanisms, framework regulation and efficient coordination mechanisms by central and sub central governments.

Sick and depressed? The causal impact of a diabetes diagnosis on depression.

BACKGROUND: There is sparse evidence on the impact of health information on mental health as well as on the mechanisms governing this relationship. We estimate the causal impact of health information on mental health via the effect of a diabetes diagnosis on depression. METHODS: We employ a fuzzy regression discontinuity design (RDD) exploiting the exogenous cut-off value of a biomarker used to diagnose type-2 diabetes (glycated haemoglobin, HbA1c) and information on psycometrically validated measures of diagnosed clinical depression drawn from rich administrative longitudinal individual-level data from a large municipality in Spain. This approach allows estimating the causal impact of a type-2 diabetes diagnosis on clinica ldepression. RESULTS: We find that overall a type-2 diabetes diagnosis increases the probability of becoming depressed, however this effect appears to be driven mostly by women, and in particular those who are relatively younger and obese. Results also appear to differ by changes in lifestyle induced by the diabetes diagnosis: while women who did not lose weight are more likely to develop depression, men who did lose weight present a reduced probability of being depressed. Results are robust to alternative parametric and non-parametric specifications and placebo tests. CONCLUSIONS: The study provides novel empirical evidence on the causal impact of health information on mental health, shedding light on gender-based differences in such effects and potential mechanisms through changes in lifestyle behaviours.

Improvement of left ventricular ejection fraction in patients with heart failure with reduced ejection fraction: Predictors and clinical impact.

BACKGROUND: A percentage of patients with heart failure with reduced ejection fraction (HFrEF) improve left ventricular ejection fraction (LVEF) in the evolution. This entity, defined for the first time in an international consensus as heart failure with improved ejection fraction (HFimpEF), could have a different clinical profile and prognosis than HFrEF. Our main aim was to analyze the differential clinical profile between the two entities, as well as the mid-term prognosis. MATERIAL-METHODS: Prospective study of a cohort of patients with HFrEF who had echocardiographic data at baseline and follow-up. A comparative analysis of patients who improved LVEF with those who did not was made. Clinical, echocardiographic and therapeutic variables were analyzed, and the mid-term impact in terms of mortality and hospital readmissions for HF was assessed. RESULTS: Ninety patients were analyzed. Mean age was 66.5(10.4) years, with a male predominance (72.2%). Forty five patients (50%) improved LVEF (Group-1,HFimpEF) and forty five patients (50%) sustained reduced LVEF (Group-2,HFsrEF). The mean time to LVEF improvement in Group-1 was 12.6(5.7) months. Group-1 had a more favorable clinical profile: lower prevalence of cardiovascular risk factors, higher prevalence of de novo HF (75.6% vs. 42.2%; p<0.05), lower prevalence of ischemic etiology (22.2% vs. 42.2%; p<0.05), with less basal dilatation of the left ventricle. At the end of follow-up (mean 19(1) months) Group-1 had a lower hospital readmission rate (3.1% vs. 26.7%; p<0.01), as well as lower mortality (0% vs. 24.4%; p<0.01). CONCLUSION: Patients with HFimpEF seem to have a better mid-term prognosis in terms of reduced mortality and hospital admissions. This improvement could be conditioned by the clinical profile of patients HFimpEF.

Long-Term Prognostic Impact of Sex in Patients with Chronic Coronary Syndrome: A 17-Year Prospective Cohort Study.

Background: Women and men with chronic coronary syndrome (CCS) have different clinical features and management, and studies on mid-term prognosis have reported conflicting results. Our objective was to investigate the impact of the female sex in the prognosis of the disease in the very long term. Methods and Results: We investigated differential features and very long-term prognosis in 1268 consecutive outpatients with CCS (337 [27%] women and 931 [73%] men). Women were older than men, more likely to have hypertension, diabetes, angina, and atrial fibrillation, and less likely to be exsmoker/active smoker and to have been treated with coronary revascularization (p < 0.05 for all). The prescription of statins, antiplatelets, and betablockers was similar in both groups. After up to 17 years of follow-up (median = 11 years, interquartile range = 4-15 years), cumulative incidences of acute myocardial infarction (10.2% vs. 11.8%) or stroke (11% vs. 10%) at median follow-up were similar, but the risks of major cardiovascular events (acute myocardial infarction, stroke, or cardiovascular death, 41.2% vs. 33.6%), hospital admission for heart failure (20.9% vs. 11.9%), or cardiovascular death (32.3% vs. 22.1%) were significantly higher for women (p < 0.0005), with a nonsignificant trend to higher overall mortality (45.2% vs. 39.1%, p = 0.07). However, after multivariate adjustment, all these differences disappeared. Conclusion: Although women and men with CCS presented a different clinical profile, and crude rates of major cardiovascular events, heart failure and cardiovascular death were higher in women, female sex was not an independent prognostic factor in this study with up to 17 years of follow-up.

The Worsening of Heart Failure with Reduced Ejection Fraction: The Impact of the Number of Hospital Admissions in a Cohort of Patients.

BACKGROUND: Worsening heart failure (WFH) includes heart failure (HF) hospitalisation, representing a strong predictor of mortality in patients with heart failure with reduced ejection fraction (HFrEF). However, there is little evidence analysing the impact of the number of previous HF admissions. Our main objective was to analyse the clinical profile according to the number of previous admissions for HF and its prognostic impact in the medium and long term. METHODS: A retrospective study of a cohort of patients with HFrEF, classified according to previous admissions: cohort-1 (0-1 previous admission) and cohort-2 (≥2 previous admissions). Clinical, echocardiographic and therapeutic variables were analysed, and the medium- and long-term impacts in terms of hospital readmissions and cardiovascular mortality were assessed. A total of 406 patients were analysed. RESULTS: The mean age was 67.3 ± 12.6 years, with male predominance (73.9%). Some 88.9% (361 patients) were included in cohort-1, and 45 patients (11.1%) were included in cohort-2. Cohort-2 had a higher proportion of atrial fibrillation (49.9% vs. 73.3%; p = 0.003), chronic kidney disease (36.3% vs. 82.2%; p < 0.001), and anaemia (28.8% vs. 53.3%; p = 0.001). Despite having similar baseline ventricular structural parameters, cohort-1 showed better reverse remodelling. With a median follow-up of 60 months, cohort-1 had longer survival free of hospital readmissions for HF (37.5% vs. 92%; p < 0.001) and cardiovascular mortality (26.2% vs. 71.9%; p < 0.001), with differences from the first month. CONCLUSIONS: Patients with HFrEF and ≥2 previous admissions for HF have a higher proportion of comorbidities. These patients are associated with worse reverse remodelling and worse medium- and long-term prognoses from the early stages, wherein early identification is essential for close follow-up and optimal intensive treatment.

Usefulness of transesophageal echocardiography during implantation of the CoreValve percutaneous aortic prosthesis: influence of the learning curve.

BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the usefulness of transesophageal echocardiography during the implantation of the CoreValve percutaneous aortic prosthesis and the influence of the learning curve in its indications. METHODS: From April 2008 to January 2010, 53 patients were treated for symptomatic severe aortic stenosis with a CoreValve percutaneous aortic prosthesis. Transesophageal echocardiography was performed during the procedure for two reasons: if a discrepancy between the measures of the aortic annulus arose before the implantation and to provide visualization if a complication occurred during the procedure. Patients were divided in to two groups based on the learning curve (group I:the first 25 patients, group II: all of the subsequent patients). RESULTS: Thirty-six transesophageal echocardiographies were performed on 28 patients (53%).In 15 cases the indication was to assist us in determining the proper sized prosthesis, and in the other 21 cases it was performed due to a complication during the procedure. The numbers of intraprocedure transesophageal echocardiographies were similar in both learning-curve groups, (64% in group I vs. 71% in group II, P = 0.56) but the proportion of the studies indicated by serious complications was significantly lower in the second period of the learning curve (67% in group I vs. 17% in group II, P < 0.05). CONCLUSIONS: In our experience, transesophageal echocardiography was very useful in more than one-half of the patients during the implantation of the CoreValve percutaneous aortic prosthesis. After overcoming the learning curve, its indication due to serious procedure-related complications decreased significantly.

Feasibility of bidimensional speckle-tracking echocardiography for strain analysis in consecutive patients in daily clinical practice.

PURPOSE: We aimed to analyze the feasibility of two-dimensional speckle-tracking echocardiography (2DSTE) in evaluating myocardial strain in consecutive, nonselected patients in daily clinical practice. METHODS: Strain analysis using 2DSTE was attempted in 59 consecutive patients: 24 patients with severe aortic stenosis, 28 patients with dilated cardiomyopathy, and 7 healthy controls. The analysis was done by four expert echocardiographers and one cardiology resident. RESULTS: It was possible to obtain reliable data for radial strain in 175 of 354 segments (49%), circumferential strain in 192 of 354 segments (54%), and longitudinal strain in 319 of 354 segments (90%). Experienced echocardiographers felt assessment of radial and circumferential strain was appropriate in more segments than did the cardiology resident (57% and 58% vs. 23% and 40%, respectively, P < 0.01). CONCLUSION: Longitudinal strain analysis with 2DSTE is feasible in most segments, but the radial and circumferential strain evaluation was only feasible in approximately half of the patients.