Necroptosis blockade prevents lung injury in severe influenza.

Severe influenza A virus (IAV) infections can result in hyper-inflammation, lung injury and acute respiratory distress syndrome1-5 (ARDS), for which there are no effective pharmacological therapies. Necroptosis is an attractive entry point for therapeutic intervention in ARDS and related inflammatory conditions because it drives pathogenic lung inflammation and lethality during severe IAV infection6-8 and can potentially be targeted by receptor interacting protein kinase 3 (RIPK3) inhibitors. Here we show that a newly developed RIPK3 inhibitor, UH15-38, potently and selectively blocked IAV-triggered necroptosis in alveolar epithelial cells in vivo. UH15-38 ameliorated lung inflammation and prevented mortality following infection with laboratory-adapted and pandemic strains of IAV, without compromising antiviral adaptive immune responses or impeding viral clearance. UH15-38 displayed robust therapeutic efficacy even when administered late in the course of infection, suggesting that RIPK3 blockade may provide clinical benefit in patients with IAV-driven ARDS and other hyper-inflammatory pathologies.

Pelleting and particle size reduction of corn increase net energy and digestibility of fiber, protein, and fat in corn-soybean meal diets fed to group-housed pigs.

BACKGROUND: Reduction of the particle size of corn increases energy digestibility and concentrations of digestible and metabolizable energy. Pelleting may also reduce particle size of grain, but it is not known if there are interactions between particle size reduction and pelleting. The objective of this experiment was to test the hypothesis that particle size reduction and pelleting, separately or in combination, increase N balance, apparent total tract digestibility (ATTD) of fiber and fat, and net energy (NE) in corn-soybean meal diets fed to group-housed pigs. METHODS: Six corn-soybean meal-based diets were used in a 3 × 2 factorial design with 3 particle sizes of corn (i.e., 700, 500, or 300 µm) and 2 diet forms (i.e., meal or pelleted). Pigs were allowed ad libitum access to feed and water. Twenty-four castrated male pigs (initial weight: 29.52 kg; standard diviation: 1.40) were allotted to the 6 diets using a 6 × 6 Latin square design with 6 calorimeter chambers (i.e., 4 pigs/chamber) and 6 periods. Oxygen consumption and CO2 and CH4 productions were measured during fed and fasting states and fecal and urine samples were collected. RESULTS: Regardless of particle size of corn, the ATTD of gross energy (GE), N, and acid-hydrolyzed ether extract (AEE), and the concentration of NE were greater (P < 0.05) in pelleted diets than in meal diets. Regardless of diet form, the ATTD of GE, N, and AEE, and the concentration of NE were increased (linear; P < 0.05) by reducing the particle size of corn, but the increase was greater in meal diets than in pelleted diets (interaction; P < 0.05). CONCLUSIONS: Both pelleting and reduction of corn particle size increased nutrient digestibility and NE, but increases were greater in meal diets than in pelleted diets.

Cardioverter-defibrillator reduces mortality risk in eligible ischemic and non-ischemic cardiomyopathy patients: Sub-analysis of the multi-center Improve SCA study.

BACKGROUND & OBJECTIVE: Despite the burden of sudden cardiac arrest (SCA) worldwide, implantable cardioverter-defibrillators (ICDs) are underutilized, particularly in Asia, Latin America, Eastern Europe, the Middle East, and Africa. The Improve SCA trial demonstrated that primary prevention (PP) patients in these regions benefit from an ICD or a cardiac resynchronization therapy defibrillator (CRT-D). We aimed to compare the rate of device therapy and mortality among ischemic and non-ischemic cardiomyopathy (ICM and NICM) PP patients who met guideline indications for ICD therapy and had an ICD/CRT-D implanted. METHODS: Improve SCA was a prospective, non-randomized, non-blinded multicenter trial that enrolled patients from the above-mentioned regions. All-cause mortality and device therapy were examined by cardiomyopathy (ICM vs NICM) and implantation status. Cox proportional hazards methods were used, adjusting for factors affecting mortality risk. RESULTS: Of 1848 PP NICM patients, 1007 (54.5%) received ICD/CRT-D, while 303 of 581 (52.1%) PP ICM patients received an ICD/CRT-D. The all-cause mortality rate at 3 years for NICM patients with and without an ICD/CRT-D was 13.1% and 18.3%, respectively (HR 0.51, 95% CI 0.38-0.68, p < 0.001). Similarly, all-cause mortality at 3 years in ICM patients was 13.8% in those with a device and 19.9% in those without an ICD/CRT-D (HR 0.54, 95% CI 0.33-.0.88, p = 0.011). The time to first device therapy, time to first shock, and time to first antitachycardia pacing (ATP) therapy were not significantly different between groups (p ≥ 0.263). CONCLUSIONS: In this large data set of patients with a guideline-based PP ICD indication, defibrillator device implantation conferred a significant mortality benefit in both NICM and ICM patients. The rate of appropriate device therapy was also similar in both groups. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02099721.

Caspase-8 and FADD prevent spontaneous ZBP1 expression and necroptosis.

The absence of Caspase-8 or its adapter, Fas-associated death domain (FADD), results in activation of receptor interacting protein kinase-3 (RIPK3)- and mixed-lineage kinase-like (MLKL)-dependent necroptosis in vivo. Here, we show that spontaneous activation of RIPK3, phosphorylation of MLKL, and necroptosis in Caspase-8- or FADD-deficient cells was dependent on the nucleic acid sensor, Z-DNA binding protein-1 (ZBP1). We genetically engineered a mouse model by a single insertion of FLAG tag onto the N terminus of endogenous MLKL (MlklFLAG/FLAG), creating an inactive form of MLKL that permits monitoring of phosphorylated MLKL without activating necroptotic cell death. Casp8-/-MlklFLAG/FLAG mice were viable and displayed phosphorylated MLKL in a variety of tissues, together with dramatically increased expression of ZBP1 compared to Casp8+/+ mice. Studies in vitro revealed an increased expression of ZBP1 in cells lacking FADD or Caspase-8, which was suppressed by reconstitution of Caspase-8 or FADD. Ablation of ZBP1 in Casp8-/-MlklFLAG/FLAG mice suppressed spontaneous MLKL phosphorylation in vivo. ZBP1 expression and downstream activation of RIPK3 and MLKL in cells lacking Caspase-8 or FADD relied on a positive feedback mechanism requiring the nucleic acid sensors cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), and TBK1 signaling pathways. Our study identifies a molecular mechanism whereby Caspase-8 and FADD suppress spontaneous necroptotic cell death.

Localization of a TORC1-eIF4F translation complex during CD8+ T cell activation drives divergent cell fate.

Activated CD8+ T lymphocytes differentiate into heterogeneous subsets. Using super-resolution imaging, we found that prior to the first division, dynein-dependent vesicular transport polarized active TORC1 toward the microtubule-organizing center (MTOC) at the proximal pole. This active TORC1 was physically associated with active eIF4F, required for the translation of c-myc mRNA. As a consequence, c-myc-translating polysomes polarized toward the cellular pole proximal to the immune synapse, resulting in localized c-myc translation. Upon division, the TORC1-eIF4A complex preferentially sorted to the proximal daughter cell, facilitating asymmetric c-Myc synthesis. Transient disruption of eIF4A activity at first division skewed long-term cell fate trajectories to memory-like function. Using a genetic barcoding approach, we found that first-division sister cells often displayed differences in transcriptional profiles that largely correlated with c-Myc and TORC1 target genes. Our findings provide mechanistic insights as to how distinct T cell fate trajectories can be established during the first division.

Extracellular Vesicle-Based Hybrid Systems for Advanced Drug Delivery.

The continuous technological advancement of nanomedicine has enabled the development of novel vehicles for the effective delivery of therapeutic substances. Synthetic drug delivery systems are nano-sized carriers made from various materials that can be designed to deliver therapeutic cargoes to cells or tissues. However, rapid clearance by the immune system and the poor targeting profile of synthetic drug delivery systems are examples of the pressing obstacles faced in nanomedicine, which have directed the field toward the development of alternative strategies. Extracellular vesicles (EVs) are nanoscale particles enclosed by a protein-rich lipid bilayer; they are released by cells and are considered to be important mediators of intercellular communication. Owing to their natural composition, EVs have been suggested to exhibit good biocompatibility and to possess homing properties to specific cell types. Combining EVs with synthetic nanoparticles by defined hybridization steps gives rise to a novel potential drug delivery tool, i.e., EV-based hybrid systems. These novel therapeutic vehicles exhibit potential advantageous features as compared to synthetic drug delivery systems such as enhanced cellular uptake and cargo delivery, immuno-evasive properties, capability of crossing biological barriers, and tissue targeting profile. Here, we provide an overview of the various strategies practiced to produce EV-based hybrid systems and elucidate those advantageous features obtained by synthetic drug delivery systems upon hybridization with EVs.

Cost-Effectiveness Analysis of Implantable Cardioverter Defibrillator Therapy for Primary Prevention Patients with Additional Risk Factors in Brazil

Abstract Background: Implantable cardiac defibrillators (ICDs) therapy for primary prevention (PP) of sudden cardiac arrest (SCA) is well-established but underutilized globally. The Improve SCA study has identified a cohort of patients called 1.5 primary prevention (1.5PP), based on PP patients with the presence of documented risk factors: non-sustained ventricular tachycardia, frequent premature ventricular contractions, left ventricular ejection fraction < 25%, and pre-syncope or syncope. Objective: This study evaluated the cost-effectiveness of ICD therapy compared to no ICD among 1.5PP patients in the Brazilian public healthcare system. Methods: Modified inputs to a published Markov model were applied to compare costs and outcomes of ICD therapy to no ICD therapy from the Brazilian payer's perspective. Mortality and utility estimates were obtained from the IMPROVE SCA trial. Additional effectiveness inputs were sourced from the literature. Cost inputs were obtained from the Brazilian Unified Health System and the Ministry of Health. Costs were discounted at 4.7%; quality-adjusted life years (QALYs) were discounted at 1.45%. This study applied a willingness-to-pay (WTP) value of three times Brazil's gross domestic product (GDP) in 2017, R$105,723 (Brazilian Real). Results: The total discounted lifetime costs for ICD therapy were R$100,920 compared to R$43,866 for no ICD therapy. Total discounted QALYs for ICD therapy and no ICD therapy were 9.85 and 7.15, respectively. The incremental cost effectiveness ratio was R$21,156 per QALY and less than the R$105,723 WTP threshold. Results from sensitivity analyses were consistent with base case results. Conclusions: ICD therapy compared to no ICD therapy is cost-effective in the 1.5PP population in Brazil. (Int J Cardiovasc Sci. 2021; [online].ahead print, PP.0-0)

Control of lysosomal-mediated cell death by the pH-dependent calcium channel RECS1.

Programmed cell death is regulated by the balance between activating and inhibitory signals. Here, we have identified RECS1 (responsive to centrifugal force and shear stress 1) [also known as TMBIM1 (transmembrane BAX inhibitor motif containing 1)] as a proapoptotic member of the TMBIM family. In contrast to other proteins of the TMBIM family, RECS1 expression induces cell death through the canonical mitochondrial apoptosis pathway. Unbiased screening indicated that RECS1 sensitizes cells to lysosomal perturbations. RECS1 localizes to lysosomes, where it regulates their acidification and calcium content, triggering lysosomal membrane permeabilization. Structural modeling and electrophysiological studies indicated that RECS1 is a pH-regulated calcium channel, an activity that is essential to trigger cell death. RECS1 also sensitizes whole animals to stress in vivo in Drosophila melanogaster and zebrafish models. Our results unveil an unanticipated function for RECS1 as a proapoptotic component of the TMBIM family that ignites cell death programs at lysosomes.

The mortality analysis of primary prevention patients receiving a cardiac resynchronization defibrillator (CRT-D) or implantable cardioverter-defibrillator (ICD) according to guideline indications in the improve SCA study.

BACKGROUND: In primary prevention (PP) patients the utilization of implantable cardioverter-defibrillators (ICD) and cardiac resynchronization therapy-defibrillators (CRT-D) remains low in many geographies, despite the proven mortality benefit. PURPOSE: The objective of this analysis was to examine the mortality benefit in PP patients by guideline-indicated device type: ICD and CRT-D. METHODS: Improve sudden cardiac arrest was a prospective, nonrandomized, nonblinded multicenter trial that enrolled patients from regions where ICD utilization is low. PP patient's CRT-D or ICD eligibility was based upon the 2008 ACC/AHA/HRS and 2006 ESC guidelines. Mortality was assessed according to guideline-indicated device type comparing implanted and nonimplanted patients. Cox proportional hazards methods were used, adjusting for known factors affecting mortality risk. RESULTS: Among 2618 PP patients followed for a mean of 20.8 ± 10.8 months, 1073 were indicated for a CRT-D, and 1545 were indicated for an ICD. PP CRT-D-indicated patients who received CRT-D therapy had a 58% risk reduction in mortality compared with those without implant (adjusted hazard ratio [HR]: 0.42, 95% confidence interval [CI]: 0.28-0.61, p < .0001). PP patients with an ICD indication had a 43% risk reduction in mortality with an ICD implant compared with no implant (adjusted HR: 0.57, 95% CI: 0.41-0.81, p = .002). CONCLUSIONS: This analysis confirms the mortality benefit of adherence to guideline-indicated implantable defibrillation therapy for PP patients in geographies where ICD therapy was underutilized. These results affirm that medical practice should follow clinical guidelines when choosing therapy for PP patients who meet the respective defibrillator device implant indication.

Growth performance and carcass quality are not different between pigs fed diets containing cold-fermented low-oil DDGS and pigs fed conventional DDGS, but pelleting improves gain to feed ratio regardless of source of DDGS.

The objective of this study was to test the hypothesis that growth performance and carcass characteristics of pigs fed diets containing cold-fermented, low oil distillers dried grains with solubles (DDGS) is not different from that of pigs fed diets containing conventional DDGS regardless of the physical form of the diets. A total of 160 barrows and gilts were used. There were 4 diets, 10 pens per diet, and 4 pigs per pen. Pigs were weaned at 21 d of age and fed a common phase 1 diet that did not contain DDGS during the initial 7 d post-weaning. Pigs were then allotted to the four diets that were arranged in a 2 × 2 factorial design with two sources of DDGS (cold-fermented and conventional DDGS) and two diet forms (meal and pellets). Pigs were fed phase 2 diets from day 7 to 21 and phase 3 diets from day 21 to 43 post-weaning. All diets were based on corn and soybean meal, but phase 2 diets also contained 15% DDGS and phase 3 diets contained 30% DDGS. From day 43, pigs were fed grower diets for 38 d, early finisher diets for 38 d, and late finisher diets for 18 d and these diets also contained 30% DDGS. Feed was provided on an ad libitum basis and daily feed allotments were recorded. Pigs were weighed at the beginning of each phase and at the conclusion of the experiment. On the last day of the experiment, the pig in each pen with a body weight that was closest to the pen average was slaughtered and carcass measurements were determined. Combined results for the two nursery phases indicated that feeding meal diets instead of pelleted diets increased (P < 0.001) average daily feed intake and decreased (P < 0.05) gain to feed ratio (G:F). However, no differences between the two sources of DDGS were observed for the overall growth performance of weanling pigs. For the entire growing-finishing period, the source of DDGS did not affect growth performance, but pigs fed meal diets had reduced (P < 0.001) G:F compared with pigs fed the pelleted diets. There were no differences between the two sources of DDGS for carcass characteristics. Back fat was greater (P < 0.05) for pigs fed pelleted diets than for pigs fed meal diets. In conclusion, no differences in growth performance or carcass characteristics between pigs fed cold-fermented DDGS and pigs fed conventional DDGS were observed. However, pigs fed pelleted diets had greater G:F and greater back fat than pigs fed meal diets.

Malnutrition According to GLIM Criteria Is Associated with Mortality and Hospitalizations in Rehabilitation Patients with Stable Chronic Obstructive Pulmonary Disease.

Malnutrition has a negative impact on patients with chronic pulmonary obstructive disease (COPD). The purpose of this study was to assess the prevalence of malnutrition, defined by the Global Leadership Initiative for Malnutrition (GLIM), in stable COPD patients referred to pulmonary rehabilitation, and to explore potential associations of malnutrition according to GLIM, and its components, with increased risk of mortality and hospitalizations in 2 years. In a post-hoc analysis of a prospective cohort of 200 rehabilitation patients with stable COPD, main outcome variables were hospital admissions, length of stay, and mortality during a 2-year follow-up. Covariates were malnutrition according to GLIM and its phenotypic criteria: unintentional weight loss, low body mass index (BMI), and low fat-free mass (FFM). Univariate and multivariate analysis were performed using logistic and proportional hazard Cox regression. Malnutrition according to GLIM showed 45% prevalence and was associated with increased mortality risk. Low age-related BMI and FFM were independently associated with mortality, which persisted after adjustment for age and lung function. Malnutrition and low BMI were also associated with increased risk of hospitalization. Malnutrition according to GLIM criteria was highly prevalent in rehabilitation patients with COPD and was associated with nearly 3 times greater mortality and hospitalization risk.

Comparison of cost-effectiveness of implantable cardioverter defibrillator therapy in patients for primary prevention in Latin America: an analysis using the Improve SCA study.

OBJECTIVE: The mortality benefit of implantable cardioverter defibrillators (ICDs) for primary prevention (PP) of sudden cardiac arrest (SCA) has been well-established, but ICD therapy remains globally underutilized. The results of the Improve SCA study showed a 49% relative risk reduction in all-cause mortality among ICD patients with 1.5 primary prevention (1.5PP) characteristics (patients with one or more risk factors, p < 0.0001). We evaluated the cost-effectiveness of ICD compared to no ICD therapy among patients with 1.5PP characteristics in three Latin American countries and analyzed the factors involved in cost-effectiveness. METHODS: We used a published Markov model that compares costs and outcomes of ICD to no ICD therapy from local payers' perspective and included country-specific and disease-specific inputs from the Improve SCA study and current literature. We used WHO-recommended willingness-to-pay (WTP) thresholds to assess cost-effectiveness and compared model outcomes between countries. RESULTS: Incremental costs per QALY (quality-adjusted life year) saved by ICD compared to no ICD therapy are Colombian Pesos COP$46,729,026 in Colombia, Mexican Pesos MXN$246,016 in Mexico, and Uruguayan Pesos UYU$1,213,614 in Uruguay in the base case scenario; all three figures are between 1-3-times GDP per capita for each country. One-way and probabilistic sensitivity analyses confirm the base case scenario results. Non-cardiac accumulated deaths are lower in Mexico, resulting in a comparatively increased cost-effective ICD therapy. LIMITATIONS: The Improve SCA study was not randomized, so clinical results could be biased; however, measures were taken to reduce this bias. Costs and benefits were modelled beyond the timeline of direct observation in the Improve SCA study. CONCLUSIONS: ICD therapy is cost-effective in Mexico and Uruguay and potentially cost-effective in Colombia for a 1.5PP population. Variability in ICER estimates by country can be explained by differences in non-cardiac deaths and cost inputs.

Deficient muscle regeneration potential in sarcopenic COPD patients: Role of satellite cells.

Sarcopenia is a major comorbidity in chronic obstructive pulmonary (COPD). Whether deficient muscle repair mechanisms and regeneration exist in the vastus lateralis (VL) of sarcopenic COPD remains debatable. In the VL of control subjects and severe COPD patients with/without sarcopenia, satellite cells (SCs) were identified (immunofluorescence, specific antibodies, anti-Pax-7, and anti-Myf-5): activated (Pax-7+/Myf-5+), quiescent/regenerative potential (Pax-7+/Myf-5-), and total SCs, nuclear activation (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling [TUNEL]), and muscle fiber type (morphometry and slow- and fast-twitch, and hybrid fibers), muscle damage (hematoxylin-eosin staining), muscle regeneration markers (Pax-7, Myf-5, myogenin, and MyoD), and myostatin levels were identified. Compared to controls, in VL of sarcopenic COPD patients, myostatin content, activated SCs, hybrid fiber proportions, TUNEL-positive cells, internal nuclei, and muscle damage significantly increased, while quadriceps muscle strength, numbers of Pax-7+/Myf-5- and slow- and fast-twitch, and hybrid myofiber areas decreased. In the VL of sarcopenic and nonsarcopenic patients, TUNEL-positive cells were greater, whereas muscle regeneration marker expression was lower than in controls. In VL of severe COPD patients regardless of the sarcopenia level, the muscle regeneration process is triggered as identified by SC activation and increased internal nuclei. Nonetheless, a lower regenerative potential along with significant alterations in muscle phenotype and damage, and increased myostatin were prominently seen in sarcopenic COPD.

Digestibility of amino acids, but not fiber, fat, or energy, is greater in cold-fermented, low-oil distillers dried grains with solubles (DDGS) compared with conventional DDGS fed to growing pigs.

Two experiments were conducted to test the hypothesis that the digestibility of gross energy (GE) and nutrients, and concentrations of digestible energy (DE) and metabolizable energy (ME) in two sources of distillers dried grains with solubles (DDGS) are not different despite different concentrations of fat in the two sources. Cold-fermented DDGS (6.82% fat) and a conventional DDGS (9.54% fat) were used. In experiment 1, 12 growing barrows (initial body weight = 55.2 ± 3.6 kg) that had a T-cannula installed in the distal ileum were allotted to one of three diets and two periods. Two diets contained either cold-fermented or conventional DDGS as the sole source of crude protein (CP) and amino acids (AA). The third diet was an N-free diet that was used to determine the basal endogenous losses of AA from the pigs. Each experimental period lasted 7 d and ileal digesta were collected on days 6 and 7 of each period. Results demonstrated that values for the standardized ileal digestibility (SID) of CP and most AA were greater (P < 0.05) or tended to be greater (P < 0.10) in cold-fermented than in conventional DDGS. In experiment 2, 24 barrows (initial body weight = 17.3 ± 1.3 kg) were randomly allotted to three diets with 8 replicate pigs per diet. A corn-based basal diet and two diets containing corn and either cold-fermented DDGS or conventional DDGS were formulated. Pigs were housed individually in metabolism crates and feces and urine were collected separately for 5 d after 7 d of adaptation. The apparent total tract digestibility (ATTD) of neutral detergent fiber (NDF), acid detergent fiber (ADF), and acid-hydrolyzed ether extract (AEE) was greater (P < 0.01) in conventional DDGS than in cold-fermented DDGS, but there was no difference in ATTD of GE between the two sources of DDGS. However, conventional DDGS contained more (P < 0.001) DE and ME than cold-fermented DDGS because of greater GE. In conclusion, the SID of AA was greater in cold-fermented DDGS than in the conventional DDGS that was evaluated in this experiment, but the ATTD of NDF, ADF, and AEE, and ME were greater in conventional DDGS than in cold-fermented DDGS.

Necroptosis restricts influenza A virus as a stand-alone cell death mechanism.

Influenza A virus (IAV) activates ZBP1-initiated RIPK3-dependent parallel pathways of necroptosis and apoptosis in infected cells. Although mice deficient in both pathways fail to control IAV and succumb to lethal respiratory infection, RIPK3-mediated apoptosis by itself can limit IAV, without need for necroptosis. However, whether necroptosis, conventionally considered a fail-safe cell death mechanism to apoptosis, can restrict IAV-or indeed any virus-in the absence of apoptosis is not known. Here, we use mice selectively deficient in IAV-activated apoptosis to show that necroptosis drives robust antiviral immune responses and promotes effective virus clearance from infected lungs when apoptosis is absent. We also demonstrate that apoptosis and necroptosis are mutually exclusive fates in IAV-infected cells. Thus, necroptosis is an independent, "stand-alone" cell death mechanism that fully compensates for the absence of apoptosis in antiviral host defense.

Evaluación del impacto de la terapia de resincronización cardiaca en pacientes de Latinoamérica / Evaluation of the impact of cardiac resynchronisation on patients Latin America

Resumen Objetivo: medir el impacto de la terapia de resincronización cardiaca en términos de variables ecocardiográficas en pacientes de países latinoamericanos. Método: se realizó un estudio prospectivo, multicéntrico, intervencionista, en el que los pacientes elegibles fueron llevados, por primera vez, a implante de un dispositivo de resincronización cardiaca. El objetivo primario fue valorar los cambios del tamaño y la función del ventrículo izquierdo por medio de un ecocardiograma previo al implante del dispositivo y en el sexto mes. Los objetivos secundarios evaluados fueron hospitalizaciones, cambios en la clase funcional, mortalidad, calidad de vida y un score compuesto clínico basado en estos factores de evaluación global del paciente. Resultados: para cumplir el objetivo primario se analizaron datos de 75 sujetos. La edad promedio fue de 63,7 años; 21.3% fueron mujeres y 30.7% tuvieron cardiopatía isquémica. Al sexto mes de seguimiento las mediciones de volumen de fin de diástole y sístole del ventrículo izquierdo disminuyeron en promedio 37.6 ml y 37.8 ml, respectivamente. La fracción de eyección del ventrículo izquierdo en promedio se incrementó un 11%. El puntaje compuesto clínico mostró mejoría en el 86.4% de los pacientes en el sexto mes postimplante del resincronizador. Conclusiones: se observó remodelado inverso del ventrículo izquierdo y mejoría en el estado clínico de los pacientes con insuficiencia cardiaca y disfunción sistólica del ventrículo izquierdo que recibieron terapia de resincronización cardiaca en el ámbito de la práctica clínica de rutina.

Abstract Objective: To measure the impact of cardiac resynchronisation therapy in terms of cardiac ultrasound variables in patients from Latin-American countries. Method: A prospective, multicentre, interventionist study was conducted, in which the eligible patients were those that had a cardiac resynchronisation device implanted for the first time. The primary objective was to assess the changes in size and left ventricular function by means of a cardiac ultrasound carried out prior to implanting the device and in the sixth month. The secondary objectives evaluated were hospital admissions, change in functional class, mortality, quality of life, and an overall assessment of the patient using a combined clinical score based on these factors. Results: A total of 75 subjects were analysed in order to complete the primary objective. The mean age was 63.7 years; 21.3% were female, and 30.7% had ischaemic heart disease. At the sixth month, the left ventricular end-diastolic and systolic volume decreased by a mean of 37.6 ml and 37.8 ml, respectively. The left ventricular ejection fraction increased by a mean of 11%. The combined clinical score showed an improvement in 86.4% of the patients in the sixth month after the implantation of the synchronisation device. Conclusions: A reverse remodelling of the left ventricle was observed, as well as an improvement in the clinical stage of patients with heart failure and left ventricular systolic dysfunction that received cardiac resynchronisation treatment in the setting of routine clinical practice.