Hospitalizaciones y eventos por insuficiencia cardiaca sistólica y diastólica en España entre 2016 y 2019. Un estudio de base poblacional / Hospital admissions and outcomes for systolic and diastolic heart failure in Spain between 2016 and 2019: A population-based study

Antecedentes y objetivos: En España carecemos de datos poblacionales de hospitalizaciones por insuficiencia cardiaca (IC) según sea sistólica o diastólica. Analizamos las diferencias clínicas, en mortalidad intrahospitalaria y reingresos de causa cardiovascular a los 30 días entre ambos tipos. Métodos: Estudio observacional retrospectivo de pacientes dados de alta con el diagnóstico principal de IC de los hospitales del Sistema Nacional de Salud entre 2016 y 2019, distinguiendo entre IC sistólica y diastólica. La fuente de datos fue el conjunto mínimo básico de datos del Ministerio de Sanidad. Se calcularon las razones de mortalidad intrahospitalaria y de reingreso a los 30 días estandarizadas por riesgo usando sendos modelos de regresión logística multinivel de ajuste de riesgo. Resultados: Se seleccionaron 190.200 episodios de IC. De ellos, 163.727 (86,1%) fueron por IC diastólica y se caracterizaron por presentar mayor edad, mayor proporción de mujeres, de diabetes y de insuficiencia renal que los de IC sistólica. Según los modelos de ajuste de riesgo la IC diastólica, frente a la sistólica, se comportó como un factor protector de mortalidad intrahospitalaria (odds ratio [OR]: 0,79; intervalo de confianza del 95% [IC 95%]: 0,75-0,83; p<0,001) y de reingreso de causa cardiovascular a los 30 días (OR: 0,93; IC 95%: 0,88-0,97; p0,002). Conclusiones: En España, entre 2016 y 2019, los episodios de hospitalización por IC fueron mayoritariamente por IC diastólica. Según los modelos de ajuste de riesgo la IC diastólica, con respecto a la sistólica, fue un factor protector de mortalidad intrahospitalaria y de reingreso de causa cardiovascular a los 30 días.(AU)

Background and purpose: In Spain there is a lack of population data that specifically compare hospitalization for systolic and diastolic heart failure (HF). We assessed clinical characteristics, in-hospital mortality and 30-day cardiovascular readmission rates differentiating by HF type. Methods: We conducted a retrospective observational study of patients discharged with the principal diagnosis of HF from The National Health System’ acute hospital during 2016-2019, distinguishing between systolic and diastolic HF. The source of the data was the Minimum Basic Data Set. The risk-standardized in-hospital mortality ratio and risk-standardized 30-day cardiovascular readmission ratio were calculated using multilevel risk adjustment models. Results: The 190,200 episodes of HF were selected. Of these, 163,727 (86.1%) were classified as diastolic HF and were characterized by older age, higher proportion of women, diabetes mellitus, dementia and renal failure than those with systolic HF. In the multilevel risk adjustment models, diastolic HF was a protective factor for both in-hospital mortality (odds ratio [OR]: 0.79; 95% confidence interval [CI]: 0.75-0.83; P<.001) and 30-day cardiovascular readmission versus systolic HF (OR: 0.93; 95% CI: 0.88-0.97; P=.002). Conclusions: In Spain, between 2016 and 2019, hospitalization episodes for HF were mostly due to diastolic HF. According to the multilevel risk adjustment models, diastolic HF compared to systolic HF was a protective factor for both in-hospital mortality and 30-day cardiovascular readmission.(AU)

Myofilament dysfunction in diastolic heart failure.

Diastolic heart failure (DHF), in which impaired ventricular filling leads to typical heart failure symptoms, represents over 50% of all heart failure cases and is linked with risk factors, including metabolic syndrome, hypertension, diabetes, and aging. A substantial proportion of patients with this disorder maintain normal left ventricular systolic function, as assessed by ejection fraction. Despite the high prevalence of DHF, no effective therapeutic agents are available to treat this condition, partially because the molecular mechanisms of diastolic dysfunction remain poorly understood. As such, by focusing on the underlying molecular and cellular processes contributing to DHF can yield new insights that can represent an exciting new avenue and propose a novel therapeutic approach for DHF treatment. This review discusses new developments from basic and clinical/translational research to highlight current knowledge gaps, help define molecular determinants of diastolic dysfunction, and clarify new targets for treatment.

Prevalence of respiratory failure and use of mechanical ventilation in heart failure patients undergoing left atrial appendage occlusion device implantation.

BACKGROUND: We sought to evaluate respiratory complications in heart failure patients undergoing left atrial appendage occlusion (LAAO) for stroke prevention in atrial fibrillation. METHODS: Adult admissions (>18 years) undergoing LAAO during 2016-2020 were identified from the National Inpatient Sample. Heart failure (HF) was stratified into systolic (SHF) and diastolic heart failure (DHF) and were compared to those without HF. Outcomes of interested included acute respiratory failure, use of non-invasive and invasive mechanical ventilation, and in-hospital mortality. RESULTS: Of 74,440 admissions for atrial fibrillation undergoing LAAO, SHF and DHF were noted in 8335 (11.2%) and 10,925 (14.7%), respectively. The SHF cohort was predominantly male (78%) whereas DHF cohort were female (53%). Compared to those without HF, presence of SHF (2.3% vs. 0.6%; adjusted odds ratio [OR] 1.61 [95% confidence interval {CI} 1.10-2.36]; p = 0.01) and DHF (2.8% vs. 0.6%; adjusted OR 2.20 [95% CI 1.58-3.06]; p < 0.001) were associated with higher rates of acute respiratory failure. SHF (1.7% vs. 0.6%; adjusted OR 1.70 [95% CI 1.07-2.71]; p = 0.02) group but not DHF (1.2% vs. 0.6%; adjusted OR 1.21 [95% CI 0.78-1.89]; p = 0.39) was associated with higher rates of non-invasive ventilation, whereas the DHF group (0.9% vs. 0.2%; adjusted OR 1.91 [95% CI 1.08-3.34]; p = 0.02) but not SHF (0.8% vs. 0.2%; adjusted OR 1.54 [95% CI 0.83-2.84]; p = 0.17) was associated with higher rates of invasive mechanical ventilation use. In-hospital mortality was comparable between cohorts. CONCLUSION: Compared to those without HF, atrial fibrillation admissions with HF undergoing LAAO had higher rates of acute respiratory failure and mechanical ventilation rates without differences in in-hospital mortality.

Effect of different types of aerobic training on peak VO2 and ejection fraction for diastolic heart failure patients; a comparative randomized control trial.

BACKGROUND: Heart failure is described by a lack of confirmed efficient therapies and exercise intolerance. Engagement in physical activity decreases the possibility of adverse cardiovascular consequences involving heart failure. THE PURPOSE OF THE STUDY: Determine the effect of different types of aerobic training on peak VO2 and ejection fraction in diastolic heart failure patients. SUBJECT AND METHODS: The study was designed as a randomized control trail. Forty-eight eligible male patients with diastolic heart failure, aged between 50 and 65 years old, enrolled in this study. They were picked up from Police hospital outpatient clinic and were assigned to 2 equal groups in numbers. The first group (A) received aerobic exercise for the upper limb in the form of arm ergometer exercises, while the second group (B) received aerobic exercise for the lower limb in the form of cycling. Training duration for both groups was 3 sessions/week for 12 weeks. Peak VO2, and ejection fraction of both groups were measured and compared pre- and post-treatment. RESULTS: There was no significant difference (p > 0.05) in the ejection fraction between groups post-treatment. However, a significant increase (p < 0.001) was observed in the peak VO2 of group B when compared to group A post-treatment. CONCLUSION: There is no effect of different types of aerobic training on ejection fraction in diastolic heart failure patients, but lower limb exercise is more effective than upper limb exercise in improving peak VO2 in diastolic heart failure patients. Therefore, the current study recommended the use of lower limb exercise over upper limb exercise in training diastolic heart failure patients. CLINICAL TRIAL REGISTRATION: The study was registered in ClinicalTrial.gov as a clinical trial ID (NCT05637125).

Serum anion gap is associated with mortality in intensive care unit patients with diastolic heart failure.

Serum anion gap (AG) is closely related to mortality in critically ill patients with several diseases. We aimed to determine the relationship between serum AG levels and 28-day intensive care unit (ICU) mortality in patients with diastolic heart failure (DHF). This cohort study enrolled critically ill patients with DHF from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Serum AG levels were calculated using the traditional and albumin-adjusted methods. Multivariate Cox proportional hazards regression and restricted cubic spline curves were used to determine the correlation between serum AG levels and 28-day ICU mortality. We used receiver operating characteristic (ROC) curves and area under the curve (AUC) to compare the ability of traditional and albumin-adjusted AG to predict mortality. Overall, 3290 patients were included. Multivariate analysis showed an association of high levels of traditional (hazard ratio [HR], 1.48; 95% confidence interval [CI], 1.1-1.98, p = 0.009) and albumin-adjusted AG (HR, 1.36; 95% CI, 1.02-1.79, p = 0.033) with higher risk of 28-day ICU mortality. Restricted cubic spline curves indicated a linear relationship between AG level and 28-day ICU mortality. Comparison of the ROC curves revealed that albumin-adjusted AG had a greater ability to predict 28-day ICU mortality compared with traditional AG (AUCs of 0.569 [95% CI, 0.536-0.601] and 0.619 [95% CI, 0.588-0.649], respectively). In ICU patients with DHF, higher levels of traditional and albumin-adjusted AG were associated with higher 28-day ICU mortality. Albumin-adjusted AG exhibited greater predictive ability for mortality compared with traditional AG.

Carboximaltosa férrica en pacientes con insuficiencia cardíaca con fracción de eyección reducida y deficiencia de hierro previo cirugía cardiovascular / Ferric carboxymaltose in patients with heart failure with reduced exercise fraction and iron deficiency before cardiovascular surgery

ÁREA DESCRIPTIVA DEL PROBLEMA DE SALUD: Definición: La anemia y la ferropenia son dos importantes comorbilidades comunes en pacientes con Insuficiencia Cardíaca (IC) y se asocian a un mal estado clínico y a peores resultados a corto y largo plazo; la anemia y la ferropenia son de hecho, medidores de pobre pronóstico en pacientes con IC, corregir estas comorbilidades sería una diana terapéutica atractiva y novedosa para mejorar los resultados. La anemia se asocia de forma independiente con la gravedad de la IC y la mortalidad, y la deficiencia de hierro parece asociarse de forma exclusiva con una menor capacidad de ejercicio. La deficiencia de hierro suele definirse como un nivel de ferritina <100 µg /L o un nivel de 100 a 300 µg/L, si la saturación de transferrina es <20%. Se ha demostrado que la repleción intravenosa de hierro mejora la capacidad de ejercicio y la calidad de vida. Principales manifestaciones clínicas: la identificación de los síntomas es un paso clave en el diagnóstico; estos incluyen aquellos relacionados a la sobrecarga hídrica (disnea, ortopnea, edema, dolor por la congestión hepática, y discomfort abdominal asociado a la distensión por la ascitis) y aquellos secundarios a la reducción del gasto cardíaco (debilidad, fatiga) que se pronuncian más con el ejercicio.(2) En cuanto a la anemia, definida como la reducción de 1 o más componentes de la línea roja celular (concentración de hemoglobina, hematocrito, o conteo de glóbulos rojos) una concentración baja de hemoglobina o bajo hematocrito son los parámetros ampliamente usados para el diagnóstico, con los siguientes rangos. METODOLOGÍA: Se realizó una búsqueda en las principales bases de datos bibliográficas Pubmed Carboximaltosa férrica; Insuficiencia cardiaca; Deficiencia de hierro; Hierro Sacarosa; Anemia; cirugía cardiovascular. Se filtra la búsqueda a Estudios Clínicos fase 111, controlados randomizados, Revisiones Sistemáticas, Meta-análisis, Guías de Práctica Clínica, además se limitó la búsqueda estudios en humanos. También se realiza búsqueda manual en otras bases de datos bibliográficas (Cochrane, NIH, TRIP 0ATABASE), en buscadores genéricos de internet, agencias de evaluación de tecnologías sanitarias y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas, meta-análisis, estudios clínicos aleatorizados y controlados, guías de práctica clínica, evaluaciones de tecnología sanitaria, evaluaciones económicas y políticas de cobertura de otros sistemas de salud. CONCLUSIONES. Eficacia: Carboximaltosa Férrica es un medicamento propuesto para el tratamiento de pacientes con anemia por déficit de hierro, en quienes no se puede corregir esta afección con hierro oral, o se necesita hacerlo de una manera rápida; La evaluación de este efecto se ha hecho a través de ensayos clínicos controlados y aleatorizados. Estos estudios sugieren que el uso de carboximaltosa férrica puede ser eficaz para corregir la anemia secundaria por déficit de hierro, pero es importante recalcar que los estudios pivotales están hechos comparando su uso con placebo; la utilización se asocia con mejoría en la calidad de vida de estos pacientes y menos tiempo de estancia hospitalaria; sin embargo, estos mismos informes refieren que no hay disminución en la probabilidad de muerte en general para estos pacientes; es muy importante mencionar que a pesar de que la carboximaltosa férrica al momento está siendo muy estudiada para el uso de pacientes con déficit de hierro e insuficiencia cardíaca, los preparados como Hierro Sacarosa también han sido estudiados en esta patología , y faltan más investigaciones donde se comparen estos dos preparados para obtener mayor evidencia sobre el beneficio de usar uno sobre el otro; además, también hay una gran falta de estudios específicos sobre la población preoperatoria que se someterá a cirugía cardiovascular; si bien es cierto se hace un especial énfasis acerca de la importancia de identificar y corregir la anemia preoperatoria, las guías clínicas actualizadas y revisiones de la literatura no especifican a la carboximaltosa férrica como medicamento de primera línea en el manejo de los pacientes sometidos a cirugía cardiovascular. También, es de hacer notar que la mayoría de investigaciones se han realizado en poblaciones específicas que no pueden ser generalizados a otras poblaciones, así como hay heterogeneidad en los parámetros estudiados entre ellos como los valores de hemoglobina en cada estudio siendo un dato importante para esta revisión. Seguridad: De acuerdo a la revisión realizada se puede concluir que la administración de Carboximaltosa férrica es segura; La reacción adversa reportada con mayor frecuencia fue náuseas (que se produce en el 3,2% de los sujetos), seguida por reacciones en el lugar de inyección/perfusión, hipofosfatemia, cefalea, rubefacción, mareos e hipertensión. Las reacciones en el lugar de inyección/perfusión se componen de varias reacciónes adversas que de forma individual son poco frecuentes o raras. La más grave es la reacción anafiláctica (rara); se han notificado muertes con su uso; los estudios también demuestran que ambas terapias presentan reacciones similares, siendo las más comunes los trastornos de hipersensibilidad, gastrointestinales y desequilibrios hidroelectrolíticos. Aunque es cierto que la literatura describe un ligero aumento en la frecuencia de estas reacciones con Hierro Sacarosa, también se menciona que la mayoría de ellas son rápidamente reversibles y no ponen en peligro la vida de los pacientes. Costo: Para el ISSS, el uso de Carboximaltosa Férrica en pacientes con Insuficiencia Cardíaca y anemia podría considerarse una opción rentable a largo plazo. Dado que se requiere una única aplicación y menos personal y espacio hospitalario, el costo de adquisición se puede recuperar a través de la reducción de recursos de salud utilizados y la ocupación de camas hospitalarias. Aunque al comparar el costo de adquisición de este medicamento con Hierro Sacarosa, un medicamento ya disponible en la institución, se observa que, a pesar de que se necesitan dosis mayores de Hierro Sacarosa para lograr el mismo efecto, el costo total de estas dosis no supera la aplicación individual de Carboximaltosa Férrica. Conveniencia: A pesar de lo antes mencionado sobre el beneficio del uso de carboximaltosa de hierro, en pacientes con déficit de hierro e insuficiencia cardíaca; La mayoría de documentos mencionan que el hierro intravenoso podría controlar los niveles de hemoglobina en los pacientes sometidos a cirugía electiva, no está clara la repercusión del hierro intravenoso sobre los resultados (transfusiones sanguíneas, riesgo de infecciones, o supervivencia en general). En la institución se cuenta con Hierro Sacarosa, un preparado endovenoso que también se utiliza para la corrección de la anemia por déficit de hierro; las ventajas que se presentan de la carboximaltosa férrica a este preparado se centran en menor número de dosis y menor estancia hospitalaria, que se traducen en menor uso de recursos y menor tiempo cama hospitalaria; sin embargo, no hay estudios que prueben el beneficio en una rápida corrección de hemoglobina utilizando carboximaltosa férrica sobre hierro sacarosa, por lo que no es posible concluir que sea más conveniente su uso en pacientes preoperatorios que necesiten un rápido restablecimiento de estos valores.

Outpatient Worsening Among Patients With Mildly Reduced and Preserved Ejection Fraction Heart Failure in the DELIVER Trial.

BACKGROUND: Hospitalization is recognized as a sentinel event in the disease trajectory of patients with heart failure (HF), but not all patients experiencing clinical decompensation are ultimately hospitalized. Outpatient intensification of diuretics is common in response to symptoms of worsening HF, yet its prognostic and clinical relevance, specifically for patients with HF with mildly reduced or preserved ejection fraction, is uncertain. METHODS: In this prespecified analysis of the DELIVER trial (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure), we assessed the association between various nonfatal worsening HF events (those requiring hospitalization, urgent outpatient visits requiring intravenous HF therapies, and outpatient oral diuretic intensification) and rates of subsequent mortality. We further examined the treatment effect of dapagliflozin on an expanded composite end point of cardiovascular death, HF hospitalization, urgent HF visit, or outpatient oral diuretic intensification. RESULTS: In DELIVER, 4532 (72%) patients experienced no worsening HF event, whereas 789 (13%) had outpatient oral diuretic intensification, 86 (1%) required an urgent HF visit, 585 (9%) had an HF hospitalization, and 271 (4%) died of cardiovascular causes as a first presentation. Patients with a first presentation manifesting as outpatient oral diuretic intensification experienced rates of subsequent mortality that were higher (10 [8-12] per 100 patient-years) than those without a worsening HF event (4 [3-4] per 100 patient-years) but similar to rates of subsequent death after an urgent HF visit (10 [6-18] per 100 patient-years). Patients with an HF hospitalization as a first presentation of worsening HF had the highest rates of subsequent death (35 [31-40] per 100 patient-years). The addition of outpatient diuretic intensification to the adjudicated DELIVER primary end point (cardiovascular death, HF hospitalization, or urgent HF visit) increased the overall number of patients experiencing an event from 1122 to 1731 (a 54% increase). Dapagliflozin reduced the need for outpatient diuretic intensification alone (hazard ratio, 0.72 [95% CI, 0.64-0.82]) and when analyzed as a part of an expanded composite end point of worsening HF or cardiovascular death (hazard ratio, 0.76 [95% CI, 0.69-0.84]). CONCLUSIONS: In patients with HF with mildly reduced or preserved ejection fraction, worsening HF requiring oral diuretic intensification in ambulatory care was frequent, adversely prognostic, and significantly reduced by dapagliflozin. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03619213.

Systolic Heart Failure is Associated with Higher Mortality Among Patients Undergoing Transcatheter Aortic Valve Replacement: A Nationwide Analysis.

Heart failure (HF) is prevalent among patients with aortic stenosis and presents a poor prognosis. In order to better portray outcomes for HF patients undergoing transcatheter aortic valve replacement (TAVR), we evaluated clinical outcomes in patients with systolic vs diastolic heart failure who underwent TAVR in a large nationwide database. We searched the National Inpatient Sample (NIS) for hospitalized adult patients who underwent TAVR with coexisting history of systolic (SHF) or diastolic heart failure (DHF) as a secondary diagnosis using the ICD-10 codes. The primary outcome was in-hospital mortality, with secondary outcomes of cardiac arrest (CA), cardiogenic shock (CS), respiratory failure (RF), Non-ST elevation myocardial infarction (NSTEMI), acute kidney injury (AKI), use of cardiac and respiratory assist device, and health care utilization defined as length of stay, average hospital cost (AHC) and patient charge (APC). Both univariate and multivariate logistic, generalized linear, and Poisson regression analyses were used to evaluate and test the outcomes. A P-value of <0.05 was significant. A total of 106,815 patients were admitted to acute care hospitals for TAVR, and 73% had a secondary diagnosis of heart failure (41% had SHF and 59% DHF). SHF group were older (mean age of 78.9 years [SD ± 8.9] vs 79.9 years [SD ± 8.3]) with more males (61.8% vs 48.2%) and white predominant (whites [85.9% vs 87.9%]). Compared to DHF, SHF had higher inpatient mortality (1.75% vs 1.14%, P = 0.003), CA (1.31% vs 0.81%, P = 0.01), NSTEMI (2.52% vs 1.0%, P = 0.001), RF (10.87% vs 8.01%, P = 0.001), and CS (3.94% vs 1.14%, P = 0.001). In addition, SHF had greater LOS (5.1 days vs. .3.9, P = 0.0001) & AHC ($52,901 vs $48,070, P = 0.0001). HF is common among patients admitted for TAVR. SHF had worse CV outcomes, greater use of hospital resources, and higher acute care hospital mortality compared to those with DHF.

Association of Hypoalbuminemia With Clinical Outcomes in Patients Admitted With Acute Heart Failure.

Albumin is a protein produced by the liver essential for maintaining blood volume and regulating fluid balance. Hypoalbuminemia is characterized by low levels of albumin in the blood. It is also a marker of malnutrition-inflammatory syndrome. Several studies have demonstrated its prognostic role in patients with chronic heart failure; however, data regarding hypoalbuminemia in acute heart failure admissions are scarce. This study aims to analyze the relationship between hypoalbuminemia and heart failure. We used a retrospective cohort study surveying data from the 2016-2018 combined National Inpatient Sample (NIS) database. Adult hospitalizations for heart failure patients were identified using the ICD-10 codes, stratified into cohorts with and without hypoalbuminemia. Primary outcomes were (1) in-patient mortality, (2) length of stay, and total hospital charge. We also reclassified the HF admissions with hypoalbuminemia to those with systolic or diastolic heart failure to compare any differences in mortality and other in-patient complications. Multivariate linear and logistic regression were used to adjust for confounders and to analyze the outcomes. There were 1,365,529 adult hospitalizations for Congestive Heart Failure (CHF), and among them 1,205,990 (88 %) had secondary diagnoses of hypoalbuminemia. Patients with comorbid hypoalbuminemia were, on average, 8 years older (P < 0.001), predominantly white race, and males (P-value <0.001). HF hospitalizations with hypoalbuminemia had double in-hospital mortality than those without (4.8% vs 2.7%, P < 0.001). However, there was no difference in mortality between patients with Systolic heart failure and Diastolic heart failure with concomitant low albumin levels (from 4.9 % vs 4.7%, P 0.13). We found that patients admitted with HF and concomitant Hypoalbuminemia (HA) had nearly twice the odds of in-patient mortality than those with normal albumin levels. The Length of Stay (LOS) was higher between comparison groups. THC remained statistically indifferent in patients regardless of albumin levels but was greater in hypoalbuminemic patients with Systolic heart failure than Diastolic heart failure ones.

Sodium-glucose cotransporter 2 inhibitors vs. sitagliptin in heart failure and type 2 diabetes: an observational cohort study.

AIMS: The effectiveness of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with heart failure (HF) in routine clinical practice is not extensively studied. This study aimed to evaluate the comparative effectiveness of SGLT2i vs. sitagliptin in older adults with HF and type 2 diabetes and to investigate whether there were any differences between agents within the SGLT2i class or for reduced and preserved ejection fraction. METHODS AND RESULTS: Using Medicare claims data (April 2013 to December 2019), 16 253 SGLT2i initiators vs. 43 352 initiators of sitagliptin aged ≥65 years with type 2 diabetes and HF were included. The primary outcome was a composite of all-cause mortality, hospitalization for HF or urgent visit requiring intravenous diuretics; secondary outcomes included its individual components. Propensity score fine stratification weighted Cox regression was used to adjust for 100 pre-exposure characteristics. Mean age was 74 years; 49.8% were women. Initiation of SGLT2i vs. sitagliptin was associated with a lower risk of the primary composite outcome [adjusted hazard ratio (HR) 0.72; 95% confidence interval 0.67-0.77]. The adjusted HRs were 0.70 (0.63-0.78) for all-cause mortality, 0.64 (0.58-0.70) for hospitalization for HF, and 0.77 (0.69-0.86) for urgent visit requiring intravenous diuretics. Similar associations with the primary composite outcome were observed for all three agents within the SGLT2i class, for reduced and preserved ejection fraction, and subgroups based on demographics, comorbidities, and other HF treatments. Bias-calibrated HRs for the primary endpoint using negative and positive control outcomes ranged between 0.81 and 0.89, suggesting that the observed benefit could not be fully explained by residual confounding. CONCLUSION: In routine US clinical practice, SGLT2i demonstrated robust clinical effectiveness in older adults with HF and type 2 diabetes compared with sitagliptin, with no evidence of heterogeneity across the SGLT2i class or across ejection fraction.

Dapagliflozin in Heart Failure With Mildly Reduced or Preserved Ejection Fraction According to Polypharmacy Status.

BACKGROUND: Patients with heart failure (HF) have a high burden of multimorbidity, often necessitating numerous medications. There may be clinical concern about introducing another medication, especially among individuals with polypharmacy. OBJECTIVES: This study examined the efficacy and safety of addition of dapagliflozin according to the number of concomitant medications in HF with mildly reduced or preserved ejection fraction. METHODS: In this post hoc analysis of the DELIVER (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure) trial, 6,263 participants with symptomatic HF with left ventricular ejection fraction >40% were randomized to dapagliflozin or placebo. Baseline medication use (including vitamins and supplements) was collected. Efficacy and safety outcomes were assessed by medication use categories ("nonpolypharmacy": <5 medications; "polypharmacy": 5 to 9 medications; and "hyperpolypharmacy": ≥10 medications) and continuously. The primary outcome was worsening HF or cardiovascular death. RESULTS: Overall, 3,795 (60.6%) patients met polypharmacy and 1,886 (30.1%) met hyperpolypharmacy criteria. Higher numbers of medications were strongly associated with higher comorbidity burden and increased rates of the primary outcome. Compared with placebo, dapagliflozin similarly reduced the risk of the primary outcome irrespective of polypharmacy status (nonpolypharmacy HR: 0.88 [95% CI: 0.58-1.34]; polypharmacy HR: 0.88 [95% CI: 0.75-1.03]; hyperpolypharmacy HR: 0.73 [95% CI: 0.60-0.88]; Pinteraction = 0.30). Similarly, benefits with dapagliflozin were consistent across the spectrum of total medication use (Pinteraction = 0.06). Although adverse events increased with higher number of medications, they were not more frequent with dapagliflozin, regardless of polypharmacy status. CONCLUSIONS: In the DELIVER trial, dapagliflozin safely reduced worsening HF or cardiovascular death across a broad range of baseline medication use, including among individuals with polypharmacy (Dapagliflozin Evaluation to Improve the Lives of Patients With Preserved Ejection Fraction Heart Failure [DELIVER]; NCT03619213).

Depressed myocardial cross-bridge cycling kinetics in a female guinea pig model of diastolic heart failure.

Cardiac hypertrophy is associated with diastolic heart failure (DHF), a syndrome in which systolic function is preserved but cardiac filling dynamics are depressed. The molecular mechanisms underlying DHF and the potential role of altered cross-bridge cycling are poorly understood. Accordingly, chronic pressure overload was induced by surgically banding the thoracic ascending aorta (AOB) in ∼400 g female Dunkin Hartley guinea pigs (AOB); Sham-operated age-matched animals served as controls. Guinea pigs were chosen to avoid the confounding impacts of altered myosin heavy chain (MHC) isoform expression seen in other small rodent models. In vivo cardiac function was assessed by echocardiography; cardiac hypertrophy was confirmed by morphometric analysis. AOB resulted in left ventricle (LV) hypertrophy and compromised diastolic function with normal systolic function. Biochemical analysis revealed exclusive expression of ß-MHC isoform in both sham control and AOB LVs. Myofilament function was assessed in skinned multicellular preparations, skinned single myocyte fragments, and single myofibrils prepared from frozen (liquid N2) LVs. The rates of force-dependent ATP consumption (tension-cost) and force redevelopment (Ktr), as well as myofibril relaxation time (Timelin) were significantly blunted in AOB, indicating reduced cross-bridge cycling kinetics. Maximum Ca2+ activated force development was significantly reduced in AOB myocytes, while no change in myofilament Ca2+ sensitivity was observed. Our results indicate blunted cross-bridge cycle in a ß-MHC small animal DHF model. Reduced cross-bridge cycling kinetics may contribute, at least in part, to the development of DHF in larger mammals, including humans.

[Diastolic heart failure: 20 years later. Сurrent issues of pathoge-nesis, diagnosis and treatment of heart failure with preserved LVEF].

Relevant aspects of the pathogenesis, diagnosis, And treatment of heart failure with preserved LV EFThis review analyzes results of studies of the recent decade that focus on epidemiology, mechanisms of development, diagnostic methods, and treatments of heart failure with preserved ejection fraction (HFpEF). As expected, the prevalence of HFpEF continues to increase due to the growing contribution of comorbidities to the structure of causes for chronic heart failure (CHF), such as arterial hypertension with left ventricular hypertrophy, obesity, chronic kidney disease, as well as due to ageing of the population and decreased contributions of ischemic heart disease and myocardial infarction. Concomitant diseases are a source of low-intensity microvascular inflammation, which is currently assigned a role of a trigger mechanism eventually provoking energy deficiency, disorders of cardiomyocyte relaxation, and diffuse myocardial fibrosis. Both these processes lead to increased heart muscle rigidity and abnormally high left ventricular filling pressure (LVFP). High LVFP is associated with the development of pulmonary venous congestion and impairment of alveolar blood oxygenation, which form the clinical picture of HFpEF. Detecting high LVEF with tissue Doppler echocardiography by the E / e' value became the instrumental basis for the HFpEF diagnostics. Recognition of inflammation and fibrosis as the key pathogenetic factors marked the main vector of modern therapy for HFpEF (anti-inflammatory and antifibrotic). The best implementation of this vector became possible with the advent of drugs from the class of angiotensin receptor and neprilysin inhibitors (ARNI), sodium-glucose cotransporter type 2 (SGLT2) inhibitors, and aldosterone antagonists. However, the efficacy of such treatments is evident only with the LV EF <60-65% while at higher values, the efficacy substantially decreases. This limitation may result from the heterogenous nature of the disease and requires more advanced methods for verification of HFpEF clinical phenotypes. Among such methods, transcriptomic, metabolomic, and proteomic approaches are considered. With the use of capabilities of the "machine learning" and the artificial intelligence, these approaches can become a new frontier in research to represent an important step towards personalized medicine for patients with HFpEF.

Bendopneia é um sinal semiológico associado a baixa reserva diastólica em pacientes insuficiência cardíaca com fração de ejeção preservada / Bendopnea is a semiological sign associated with low diastolic reserve in heart failure patients with preserved ejection fraction

INTRODUÇÃO: A Insuficiência Cardíaca com Fração de Ejeção Preservada (ICFEP) é uma condição prevalente na população geral, cujo diagnóstico pode ser desafiador. Atualmente, há uma escassez de dados sobre quais aspectos do exame clínico são mais relevantes para o diagnóstico. MÉTODOS: Foram avaliados pacientes com suspeita de ICFEP em um ambulatório de hospital terciário de Cardiologia. A bendopneia foi explorada por um operador experiente através da ântero-flexão do tórax do paciente em posição sentada por tempo>30s. Casos com elevação da frequência respiratória com sensação de dispneia foram considerados positivos. Em caso de dúvida um segundo examinador era consultado. Casos duvidosos foram considerados negativos. A reserva diastólica foi acessada utilizando a ecocardiografia com Doppler tissular para acessar os valores de e' lateral em condições de repouso e durante um teste de pré-carga provocado pela elevação passiva de membros inferiores. Ademais, realizou-se cálculo do escore H2FPEF para diagnóstico de ICFEP. Estes grupos foram comparados através das diferenças das médias do escore H2FPEF estimada pelo teste t não pareado com nível de significância (a) de 95%. Finalmente, realizou-se regressão linear para comparação dos beta-coeficientes (b) da variação do e lateral repouso e durante a elevação de membros inferiores. Desta forma, o valor do b coeficiente será diretamente proporcional à reserva diastólica. RESULTADOS: Obteve-se 305 pacientes, dos quais 149 com bendopneia presente ao exame físico. O grupo sem bendopneia apresentou um H2FPEF de 2.7(±0.16), enquanto com pacientes com dispneia apresentaram um escore de 3.8(±0.16). Essa diferença entre os grupos apresentou significância estatística(p<0,001) (Figura 1). O teste de reserva diastólica foi realizado em 92 pacientes. O grupo sem bendopneia apresentou b=0.77(IC 95%:0.64;0.89), enquanto aqueles com bendopneia apresentaram um valor mais baixo de reserva diastólica com b=0.53 (IC 95%:0.32;0.74) (Figura 2). CONCLUSÕES: A bendopneia é um sinal semiológico útil para diagnóstico de ICFEP e está associado a baixa reserva diastólica.

Avaliação de setup para teste de elevação de pós-carga em pacientes com insuficiência cardíaca com fração de ejeção preservada: um estudo experimental / Evaluation of afterload elevation test setup in heart failure patients with preserved ejection fraction: an experimental study

INTRODUÇÃO: A Insuficiência Cardíaca com Fração de Ejeção Preservada (ICFEP) é uma doença de alta prevalência e de difícil diagnóstico devido ao fato que parte dos pacientes apresenta alterações apenas quando submetidos a determinadas condições de estresse hemodinâmico como elevação da pré-carga e da pós-carga do ventrículo esquerdo. OBJETIVOS: Avaliar a efetividade de um setup para elevação da pós-carga em pacientes com ICFEP. MÉTODOS: Realizou-se medida da pressão arterial sistólica (PAS), pressão arterial diastólica (PAD) e frequência cardíaca (FC) em repouso no membro superior direito com o paciente em decúbito supino seguindo as diretrizes da Sociedade Brasileira de Cardiologia. Em seguida, realizou-se um teste de elevação de pós-carga através da contração isométrica da mão esquerda com 60% da força máxima com um dinamômetro combinada com compressão pneumática de ambos os membros inferiores 20 mmHg acima da pressão sistólica utilizando dois esfigmomanômetros. Uma nova medida da pressão e frequência cardíaca foi realizada após 30s de início da manobra. Para comparação das métricas entre repouso e estresse, utilizou-se o teste-t pareado com intervalo de confiança de 95%. RESULTADOS: A população do estudo foi de 37 pacientes: 17 controles e 20 com ICFEP. A idade foi 58 ± 15 anos e 19 (51%) eram do sexo feminino. Houve diferença significativa para PAS: 128,2 ± 17,7 mmHg e 146,7 ± 19,9 mmHg (p<0,001) e FC 66 ± 11 bpm x 77 ± 14 bpm (p<0,001) repouso e estresse, respectivamente (Figura 1). CONCLUSÃO: O setup utilizado foi efetivo em elevar a pós-carga na população estudada. Os dados desta pesquisa têm grande potencial de aplicação para protocolos alternativos ao exercício padrão em cicloergômetro como teste provocativo para diagnóstico de ICFEP. Palavras-chaves: Insuficiência cardíaca com fração de ejeção preservada, Aumento de pós-carga, Teste de Estresse.

Teste de caminhada para caracterização de intolerância ao esforço de indivíduos com insuficiência cardíaca com fração de ejeção preservada: um estudo observacional / Walk test for characterization of exercise intolerance in individuals with heart failure with preserved ejection fraction: an observational study

INTRODUÇÃO: A Insuficiência Cardíaca com Fração de Ejeção Preservada (ICFEP) é uma condição clínica caracterizada por intolerância ao esforço e, nesse contexto, ferramentas que possam mensurar objetivamente este sintoma podem ser de grande valor na prática clínica. A abordagem diagnóstica atual da ICFEP requer aplicação de escores. O escore europeu HFA-PEFF, considera domínios morfológico, funcional e de peptídeos natriuréticos. Cada domínio tem um critério maior, que vale 2 pontos, e um critério menor, que vale 1 ponto. Se o total do escore for ≥ 5 pontos, o paciente tem diagnóstico de ICFEP. O teste de caminhada de seis minutos (TC6min) é uma ferramenta capaz de avaliar objetivamente a capacidade funcional traduzindo a habilidade dos pacientes em realizar tarefas cotidianas. OBJETIVOS: Avaliar a capacidade funcional de uma população de indivíduos em investigação para ICFEP. MÉTODOS: Trata-se de um estudo observacional transversal realizado em uma população de indivíduos com suspeita de ICFEP de um centro terciário de cardiologia. Foram incluídos sujeitos que realizaram o TC6min e categorizados de acordo com a probabilidade de ICFEP pelo escore HFA-PEFF. A normalidade dos dados foi avaliada pelo teste Shapiro-Wilk e a comparação entre os grupos foi realizada por meio do teste de Kruskal-Wallis. O nível de confiança adotado foi de 95%. Realizou-se ainda modelos de regressão linear univariado e multivariado. RESULTADOS: A amostra foi 105 indivíduos com idade de 59,5 ± 12,0 anos, 64% sexo feminino, IMC=31(5,8) Kg/m². A probabilidade de ICFEP foi baixa em 32 indivíduos, intermediária em 46; e alta em 27. A distância percorrida no TC6min foi de 416(±90) m. Para indivíduos com baixa probabilidade a distância percorrida foi de 472(±72) m, probabilidade intermediária de 406(±73) m e com alta probabilidade 356(±96) m. A diferença na distância percorrida entres os grupos com alta e baixa probabilidade de ICFEP foi estatisticamente significativa (P<0,05). Em um modelo de regressão multivariada, o efeito se manteve quando ajustado para idade, sexo e IMC. CONCLUSÃO: O presente estudo sugere que indivíduos com alta probabilidade de ICFEP classificados pelo escore HFA-PEF percorreram distâncias menores no TC6min quando comparados a indivíduos sem ICFEP (baixa probabilidade). Estes achados demonstram o valor clínico do TC6min na avaliação de indivíduos com suspeita de ICFEP. Palavras chaves: Insuficiência Cardíaca com Fração de Ejeção Preservada, Teste de Caminhada de Seis Minutos, Capacidade Funcional.

Associação entre ângulo de fase e o SCORE HFA-PEFF de pacientes com ICFEP / Association between phase angle and HFA-PEFF SCORE in patients with HFpEF

INTRODUÇÃO: A insuficiência cardíaca com fração de ejeção preservada (ICFEp), já é responsável por mais da metade de todas as internações hospitalares por insuficiência cardíaca (IC). Pesquisas mostram que na população geral com idade >60 anos, 4,9% são diagnosticados com ICFEP e espera-se um aumento à medida que as pessoas vivem mais e a obesidade e diabetes tornam-se mais comuns. Heart Failure Association (HFA) da European Society of Cardiology (ESC) publicou uma recomendação para o diagnóstico da insuficiência cardíaca com fração de ejeção preservada ICFEp, trata-se do score (HFA-PEFF).A utilização de índices prognósticos no paciente com IC permite uma avaliação quanto à gravidade e ao impacto da doença na sobrevida do seu portador, além do monitoramento adequado da evolução clínica do mesmo. Nesse contexto, o exame de bioimpedância elétrica (BIA) vem sendo adotado para a avaliação de prognóstico. A partir da BIA obtém-se o ângulo de fase (AF), que expressa o equilíbrio entre os espaços intra e extracelulares, e tem sido relacionado com o sucesso, sobrevivência e evolução da doença, possibilitando não só monitorar a resposta do paciente ao tratamento em curso, mas reprogramar o cuidado prestado com a possibilidade de modificar o prognóstico. OBJETIVO: Verificar associação entre o AF a classificação dos pacientes com ICFEp, de acordo com o score HFA-PEFF. MÉTODO: Estudo transversal com 132 pacientes que foram avaliados e classificados através do score HFA-PEFF em baixa, intermediária ou alta probabilidade de ICFEp. Foram obtidos dados antropométricos e realizaram o exame de BIA para avaliação do AF. RESULTADOS: A média etária dos avaliados foi de 63±12 anos, sendo 65,15% (n= 86) do sexo feminino. Segundo a probabilidade de ICFEP pelo score HFA-PEFF, foram classificados em Baixa (n=39), Intermediário (n=57) e Alta (n=36). Em relação ao AF, houve associação entre pacientes com alta probabilidade de ICFEP e AF significativamente menores do que aqueles com probabilidades baixa e intermediária. CONCLUSÃO: O menor AF verificado foi encontrado nos pacientes com alta probabilidade de ICFEP segundo o score HFA-PEFF, sugerindo como um potencial marcador prognóstico na evolução da ICFEp.

La disfunción diastólica es un predictor independiente de eventos cardiovasculares tras un fracaso renal agudo / Diastolic dysfunction is an independent predictor for cardiovascular events after an acute kidney injury

Antecedente y objetivo: El desarrollo de un fracaso renal agudo (FRA) condiciona complicaciones a corto, medio y largo plazo. El objetivo de nuestro estudio fue analizar el impacto de las alteraciones cardiacas en el pronóstico cardiovascular de pacientes que presentan un episodio de FRA. Materiales y métodos: Realizamos un estudio observacional de cohortes retrospectivo incluyendo a todos los pacientes con FRA en 2013 y 2014. Basalmente recogimos variables epidemiológicas, comorbilidades y parámetros ecocardiográficos. Seguimos a los pacientes tras el ingreso durante una media de 49 ± 28 meses, recogiendo la incidencia de eventos cardiovasculares (ECV) y los factores asociados a los mismos. Resultados: Se incluyeron 1.255 pacientes (55% varones, edad 75 ± 13 años). De los 676 (54%) pacientes que disponían de un ecocardiograma previo, el 46% tenían hipertrofia de ventrículo izquierdo, el 38% hipertensión pulmonar, el 38% disfunción diastólica y el 22% disfunción sistólica. Tras la hospitalización por FRA, 484 (39%) tuvieron un ECV. Los factores asociados a presentar un ECV fueron el sexo (varón), la edad, diabetes mellitus, hipertensión arterial, dislipidemia, cardiopatía isquémica, insuficiencia cardiaca, fibrilación auricular, neoplasia previa y enfermedad renal crónica (y el filtrado glomerular estimado basal y tras el FRA). El análisis de supervivencia demostró que todos los parámetros ecocardiográficos se asociaban a ECV. Un modelo de regresión de Cox ajustado demostró que la edad (HR 1,017), la diabetes mellitus (HR 1,576) y la disfunción diastólica (HR 1,358) eran predictores independientes de ECV. Conclusiones: La disfunción diastólica es un predictor independiente de ECV a largo plazo tras un episodio hospitalario de FRA. (AU)

Background and aim: Acute kidney injury (AKI) conditions several short- and long-term complications. The aim of the present study was to analyse the impact of cardiac function and structure in the cardiovascular prognosis after an in-hospital AKI episode. Materials and methods: This is an observational retrospective cohorts study including all in-hospital AKI episoes in 2013 and 2014 in our centre. At baseline, epidemiological values, comorbidities and echocardiography parameters were collected. During a follow-up of 49 ± 28 months, cardiovascular events (CVEs) were collected, and associated factors were analysed. Results: 1255 patients were included (55% male, age 75 ± 13 years). Of the 676 (54%) that had a previous echocardiogram, 46% had left ventricular hypertrophy, 38% pulmonary hypertension, 38% diastolic dysfunction and 22% systolic dysfunction. During the follow-up, 484 (39%) developed a CVE. Associated factors to CVE were male sex, age, diabetes mellitus, hypertension, dyslipidemia, coronary heart disease, heart failure, atrial fibrillation, neoplasia and chronic kidney disease (also, glomerular filtration rate at baseline and after the AKI episode). Survival curves demonstrated that all the echocardiographic parameters were associated to CVE. An adjusted Cox regression model showed that age (HR 1.017), diabetes (HR 1.576) and diastolic dysfunction (HR 1.358) were independent predictors for CVE. Conclusion: Diastolic dysfunction is an independent predictor for long-term CVEs after an in-hospital AKI episode. (AU)

QRS Fragmentation in Preserved Ejection Fraction Heart Failure: Functional Insights, Pathological Correlates, and Prognosis.

Background Fragmented QRS (fQRS) morphology as a surrogate marker of the possible presence of myocardial scarring has been shown to confer a higher risk in patients with reduced ejection fraction heart failure. We aimed to investigate the pathophysiological correlates and prognostic implications of fQRS in patients with heart failure with preserved ejection fraction (HFpEF). Methods and Results We consecutively studied 960 patients with HFpEF (76.4±12.7 years, men: 37.2%). fQRS was assessed using a body surface ECG during hospitalization. QRS morphology was available and classified into 3 categories among 960 subjects with HFpEF as non-fQRS, inferior fQRS, and anterior/lateral fQRS groups. Despite comparable clinical features in most baseline demographics among the 3 fQRS categories, anterior/lateral fQRS showed significantly higher B-type natriuretic peptide/troponin levels (both P<0.001), with both the inferior and anterior/lateral fQRS HFpEF groups demonstrating a higher degree of unfavorable cardiac remodeling, greater extent of myocardial perfusion defect, and slower coronary flow phenomenon (all P<0.05). Patients with anterior/lateral fQRS HFpEF exhibited significantly altered cardiac structure/function and more impaired diastolic indices (all P<0.05). During a median of 657 days follow-up, the presence of anterior/lateral fQRS conferred a doubled HF re-admission risk (adjusted hazard ratio 1.90, P<0.001), with both inferior and anterior/lateral fQRS having a higher risk of cardiovascular and all-cause death (all P<0.05) by using Cox regression models. Conclusions The presence of fQRS in HFpEF was associated with more extensive myocardial perfusion defects and worsened mechanics, which possibly denotes a more severe involvement of cardiac damage. Early recognition in such patients with HFpEF likely benefits from targeted therapeutic interventions.