Multimorbidity in patients with acute heart failure across world regions and country income levels (REPORT-HF): a prospective, multicentre, global cohort study.

BACKGROUND: Multimorbidity (two or more comorbidities) is common among patients with acute heart failure, but comprehensive global information on its prevalence and clinical consequences across different world regions and income levels is scarce. This study aimed to investigate the prevalence of multimorbidity and its effect on pharmacotherapy and prognosis in participants of the REPORT-HF study. METHODS: REPORT-HF was a prospective, multicentre, global cohort study that enrolled adults (aged ≥18 years) admitted to hospital with a primary diagnosis of acute heart failure from 358 hospitals in 44 countries on six continents. Patients who currently or recently participated in a clinical treatment trial were excluded. Follow-up data were collected at 1-year post-discharge. The primary outcome was 1-year post-discharge mortality. All patients in the REPORT-HF cohort with full data on comorbidities were eligible for the present study. We stratified patients according to the number of comorbidities, and countries by world region and country income level. We used one-way ANOVA, χ2 test, or Mann-Whitney U test for comparisons between groups, as applicable, and Cox regression to analyse the association between multimorbidity and 1-year mortality. FINDINGS: Between July 23, 2014, and March 24, 2017, 18 553 patients were included in the REPORT-HF study. Of these, 18 528 patients had full data on comorbidities, of whom 11 360 (61%) were men and 7168 (39%) were women. Prevalence rates of multimorbidity were lowest in southeast Asia (72%) and highest in North America (92%). Fewer patients from lower-middle-income countries had multimorbidity than patients from high-income countries (73% vs 85%, p<0·0001). With increasing comorbidity burden, patients received fewer guideline-directed heart failure medications, yet more drugs potentially causing or worsening heart failure. Having more comorbidities was associated with worse outcomes: 1-year mortality increased from 13% (no comorbidities) to 26% (five or more comorbidities). This finding was independent of common baseline risk factors, including age and sex. The population-attributable fraction of multimorbidity for mortality was higher in high-income countries than in upper-middle-income or lower-middle-income countries (for patients with five or more comorbidities: 61% vs 27% and 31%, respectively). INTERPRETATION: Multimorbidity is highly prevalent among patients with acute heart failure across world regions, especially in high-income countries, and is associated with higher mortality, less prescription of guideline-directed heart failure pharmacotherapy, and increased use of potentially harmful medications. FUNDING: Novartis Pharma. TRANSLATIONS: For the Arabic, French, German, Hindi, Mandarin, Russian and Spanish translations of the abstract see Supplementary Materials section.

Global Variations According to Sex in Patients Hospitalized for Heart Failure in the REPORT-HF Registry.

BACKGROUND: Previous reports suggest that risk factors, management, and outcomes of acute heart failure (AHF) may differ by sex, but they rarely extended analysis to low- and middle-income countries. OBJECTIVES: In this study, the authors sought to analyze sex differences in treatment and outcomes in patients hospitalized for AHF in 44 countries. METHODS: The authors investigated differences between men and women in treatment and outcomes in 18,553 patients hospitalized for AHF in 44 countries in the REPORT-HF (Registry to Assess Medical Practice With Longitudinal Observation for the Treatment of Heart Failure) registry stratified by country income level, income disparity, and world region. The primary outcome was 1-year all-cause mortality. RESULTS: Women (n = 7,181) were older than men (n = 11,372), were more likely to have heart failure with preserved left ventricular ejection fraction, had more comorbid conditions except for coronary artery disease, and had more severe signs and symptoms at admission. Coronary angiography, cardiac stress tests, and coronary revascularization were less frequently performed in women than in men. Women with AHF and reduced left ventricular ejection fraction were less likely to receive an implanted device, regardless of region or country income level. Women were more likely to receive treatments that could worsen HF than men (18% vs 13%; P < 0.0001). In countries with low-income disparity, women had better 1-year survival than men. This advantage was lost in countries with greater income disparity (Pinteraction < 0.001). CONCLUSIONS: Women were less likely to have diagnostic testing or receive guideline-directed care than men. A survival advantage for women was observed only in countries with low income disparity, suggesting that equity of HF care between sexes remains an unmet goal worldwide.

Hospitalization for acute heart failure during non-working hours impacts on long-term mortality: the REPORT-HF registry.

AIMS: Hospital admission during nighttime and off hours may affect the outcome of patients with various cardiovascular conditions due to suboptimal resources and personnel availability, but data for acute heart failure remain controversial. Therefore, we studied outcomes of acute heart failure patients according to their time of admission from the global International Registry to assess medical practice with lOngitudinal obseRvation for Treatment of Heart Failure. METHODS AND RESULTS: Overall, 18 553 acute heart failure patients were divided according to time of admission into 'morning' (7:00-14:59), 'evening' (15:00-22:59), and 'night' (23:00-06:59) shift groups. Patients were also dichotomized to admission during 'working hours' (9:00-16:59 during standard working days) and 'non-working hours' (any other time). Clinical characteristics, treatments, and outcomes were compared across groups. The hospital length of stay was longer for morning (odds ratio: 1.08; 95% confidence interval: 1.06-1.10, P < 0.001) and evening shift (odds ratio: 1.10; 95% confidence interval: 1.07-1.12, P < 0.001) as compared with night shift. The length of stay was also longer for working vs. non-working hours (odds ratio: 1.03; 95% confidence interval: 1.02-1.05, P < 0.001). There were no significant differences in in-hospital mortality among the groups. Admission during working hours, compared with non-working hours, was associated with significantly lower mortality at 1 year (hazard ratio: 0.88; 95% confidence interval: 0.80-0.96, P = 0.003). CONCLUSIONS: Acute heart failure patients admitted during the night shift and non-working hours had shorter length of stay but similar in-hospital mortality. However, patients admitted during non-working hours were at a higher risk for 1 year mortality. These findings may have implications for the health policies and heart failure trials.

Impact of left ventricular ejection fraction phenotypes on healthcare resource utilization in hospitalized heart failure: a secondary analysis of REPORT-HF.

AIM: Evidence on healthcare resource utilization (HCRU) for hospitalized patients with heart failure (HF) and reduced (HFrEF), mildly reduced (HFmrEF) and preserved (HFpEF) ejection fraction is limited. METHODS AND RESULTS: We analysed HCRU in relation to left ventricular ejection fraction (LVEF) phenotypes, clinical features and in-hospital and 12-month outcomes in 16 943 patients hospitalized for HF in a worldwide registry. HFrEF was more prevalent (53%) than HFmrEF (17%) or HFpEF (30%). Patients with HFmrEF and HFpEF were older, more often women, with milder symptoms and more comorbidities, but differences were not pronounced. HCRU was high in all three groups; two or more in- and out-of-hospital services were required by 51%, 49% and 52% of patients with HFrEF, HFmrEF and HFpEF, respectively, and intensive care unit by 41%, 41% and 37%, respectively. Hospitalization length was similar (median, 8 days). Discharge prescription of neurohormonal inhibitors was <80% for each agent in HFrEF and only slightly lower in HFmrEF and HFpEF (74% and 67%, respectively, for beta-blockers). Compared to HFrEF, 12-month all-cause and cardiovascular mortality were lower for HFmrEF (adjusted hazard ratios 0.78 [95% confidence interval 0.59-0.71] and 0.80 [0.70-0.92]) and HFpEF (0.64 [0.59-0.87] and 0.63 [0.56-0.71]); 12-month HF hospitalization was also lower for HFpEF and HFmrEF (21% and 20% vs. 25% for HFrEF). In-hospital mortality, 12-month non-cardiovascular mortality and 12-month all-cause hospitalization were similar among groups. CONCLUSIONS: In patients hospitalized for HF, overall HCRU was similarly high across LVEF spectrum, reflecting the subtle clinical differences among LVEF phenotypes during hospitalization. Discharge prescription of neurohormonal inhibitors was suboptimal in HFrEF and lower but significant in patients with HFpEF and HFmrEF, who had better long-term cardiovascular outcomes than HFrEF, but similar risk for non-cardiovascular events.

Association of time-to-intravenous furosemide with mortality in acute heart failure: data from REPORT-HF.

AIM: Acute heart failure can be a life-threatening medical condition. Delaying administration of intravenous furosemide (time-to-diuretics) has been postulated to increase mortality, but prior reports have been inconclusive. We aimed to evaluate the association between time-to-diuretics and mortality in the international REPORT-HF registry. METHODS AND RESULTS: We assessed the association of time-to-diuretics within the first 24 h with in-hospital and 30-day post-discharge mortality in 15 078 patients from seven world regions in the REPORT-HF registry. We further tested for effect modification by baseline mortality risk (ADHERE risk score), left ventricular ejection fraction (LVEF) and region. The median time-to-diuretics was 67 (25th-75th percentiles 17-190) min. Women, patients with more signs and symptoms of heart failure, and patients from Eastern Europe or Southeast Asia had shorter time-to-diuretics. There was no significant association between time-to-diuretics and in-hospital mortality (p > 0.1). The 30-day mortality risk increased linearly with longer time-to-diuretics (administered between hospital arrival and 8 h post-hospital arrival) (p = 0.016). This increase was more significant in patients with a higher ADHERE risk score (pinteraction  = 0.008), and not modified by LVEF or geographic region (pinteraction > 0.1 for both). CONCLUSION: In REPORT-HF, longer time-to-diuretics was not associated with higher in-hospital mortality. However, we did found an association with increased 30-day mortality, particularly in high-risk patients, and irrespective of LVEF or geographic region. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02595814.

Efficacy of empagliflozin in heart failure with preserved versus mid-range ejection fraction: a pre-specified analysis of EMPEROR-Preserved.

The EMPEROR-Preserved trial showed that the sodium-glucose co-transporter 2 inhibitor empagliflozin significantly reduces the risk of cardiovascular death or hospitalization for heart failure (HHF) in heart failure patients with left ventricular ejection fraction (LVEF) > 40%. Here, we report the results of a pre-specified analysis that separately evaluates these patients stratified by LVEF: preserved (≥ 50%) (n = 4,005; 66.9%) or mid-range (41-49%). In patients with LVEF ≥ 50%, empagliflozin reduced the risk of cardiovascular death or HHF (the primary endpoint) by 17% versus placebo (hazard ratio (HR) 0.83; 95% confidence interval (CI): 0.71-0.98, P = 0.024). For the key secondary endpoint, the HR for total HHF was 0.83 (95%CI: 0.66-1.04, P = 0.11). For patients with an LVEF of 41-49%, the HR for empagliflozin versus placebo was 0.71 (95%CI: 0.57-0.88, P = 0.002) for the primary outcome (Pinteraction = 0.27), and 0.57 (95%CI: 0.42-0.79, P < 0.001) for total HHF (Pinteraction = 0.06). These results, together with those from the EMPEROR-Reduced trial in patients with LVEF < 40%, support the use of empagliflozin across the full spectrum of LVEF in heart failure.

Global disparities in prescription of guideline-recommended drugs for heart failure with reduced ejection fraction.

BACKGROUND: Heart failure (HF) is a global challenge, with lower- and middle-income countries (LMICs) carrying a large share of the burden. Treatment for HF with reduced ejection fraction (HFrEF) improves survival but is often underused. Economic factors might have an important effect on the use of medicines. METHODS AND RESULTS: This analysis assessed prescription rates and doses of renin-angiotensin system (RAS) inhibitors, ß-blockers, and mineralocorticoid receptor antagonists at discharge and 6-month follow-up in 8669 patients with HFrEF (1458 from low-, 3363 from middle-, and 3848 from high-income countries) hospitalized for acute HF in 44 countries in the prospective REPORT-HF study. We investigated determinants of guideline-recommended treatments and their association with 1-year mortality, correcting for treatment indication bias.Only 37% of patients at discharge and 34% of survivors at 6 months were on all three medication classes, with lower proportions in LMICs than high-income countries (19 vs. 41% at discharge and 15 vs. 37% at 6 months). Women and patients without health insurance, or from LMICs, or without a scheduled medical follow-up within 6 months of discharge were least likely to be on guideline-recommended medical therapy at target doses, independent of confounders. Being on ≥50% of guideline-recommended doses of RAS inhibitors, and ß-blockers were independently associated with better 1-year survival, regardless of country income level. CONCLUSION: Patients with HFrEF in LMICs are less likely to receive guideline-recommended drugs at target doses. Improved access to medications and medical care could reduce international disparities in outcome.

Quality of life assessed 6 months after hospitalisation for acute heart failure: an analysis from REPORT-HF (international REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure).

AIMS: Recovery of well-being after hospitalisation for acute heart failure (AHF) is a measure of the success of interventions and the quality of care but has rarely been quantified. Accordingly, we measured health status after discharge in an international registry (REPORT-HF) of AHF. METHODS AND RESULTS: The analysis included 4606 patients with AHF who survived to hospital discharge, had known vital status at 6 months, and were enrolled in the United States of America, Russian Federation, or Western Europe, where the Kansas City Cardiomyopathy Questionnaire (KCCQ) was administered. Median age was 69 years (quartiles 59-78), 40% were women, and 34% had a left ventricular ejection fraction (LVEF) <40%, and 12% patients died by 6 months. Of 2475 patients with a follow-up KCCQ, 28% were 'alive and well' (KCCQ >75), while 43% had poor health status (KCCQ ≤50). Being 'alive and well' was associated with new-onset AHF, LVEF <40%, younger age, higher baseline KCCQ, country, and race. Associations were similar for increasing health status, with the exception of country and addition of comorbidities. CONCLUSION: In this international global registry, health status recovery after AHF hospitalisation was highly variable. Those with the best health status at 6 months were younger, had new-onset heart failure, and higher baseline KCCQ; nearly one-third of survivors were 'alive and well'. Investigating reasons for changes in KCCQ after hospitalisation might identify new therapeutic targets to improve patient-centred outcomes.

Regional differences in precipitating factors of hospitalization for acute heart failure: insights from the REPORT-HF registry.

AIMS: Few prior studies have investigated differences in precipitants leading to hospitalizations for acute heart failure (AHF) in a cohort with global representation. METHODS AND RESULTS: We analysed the prevalence of precipitants and their association with outcomes in 18 553 patients hospitalized for AHF in REPORT-HF (prospective international REgistry to assess medical Practice with lOngitudinal obseRvation for Treatment of Heart Failure) according to left ventricular ejection fraction subtype (reduced [HFrEF] and preserved ejection fraction [HFpEF]) and presentation (new-onset vs. decompensated chronic heart failure [DCHF]). Patients were enrolled from 358 centres in 44 countries stratified according to Latin America, North America, Western Europe, Eastern Europe, Eastern Mediterranean and Africa, Southeast Asia, and Western Pacific. Precipitants were pre-with mutually exclusive categories and selected according to the local investigator's discretion. Outcomes included in-hospital and 1-year mortality. The median age was 67 (interquartile range 57-77) years, and 39% were women. Acute coronary syndrome (ACS) was the most common precipitant in patients with new-onset heart failure in all regions except for North America and Western Europe, where uncontrolled hypertension and arrhythmia, respectively, were the most common precipitants, independent of confounders. In patients with DCHF, non-adherence to diet/medication was the most common precipitant regardless of region. Uncontrolled hypertension was a more likely precipitant in HFpEF, non-adherence to diet/medication, and ACS were more likely precipitants in HFrEF. Patients admitted due to worsening renal function had the worst in-hospital (5%) and 1-year post-discharge (30%) mortality rates, regardless of region, heart failure subtype and admission type (pinteraction >0.05 for all). CONCLUSION: Data on global differences in precipitants for AHF highlight potential regional differences in targets for preventing hospitalization for AHF and identifying those at highest risk for early mortality.

A global perspective of racial differences and outcomes in patients presenting with acute heart failure.

Important racial differences in characteristics, treatment, and outcomes of patients with acute heart failure (AHF) have been described. The objective of this analysis of the International Registry to assess medical Practice with longitudinal observation for Treatment of Heart Failure (REPORT-HF) registry was to investigate racial differences in patients with AHF according to country income level.

Aggressive Afterload Lowering to Improve the Right Ventricle: A New Target for Medical Therapy in Pulmonary Arterial Hypertension?

Despite numerous therapeutic advances in pulmonary arterial hypertension, patients continue to suffer high morbidity and mortality, particularly considering a median age of 50 years. This article explores whether early, robust reduction of right ventricular afterload would facilitate substantial improvement in right ventricular function and thus whether afterload reduction should be a treatment goal for pulmonary arterial hypertension. The earliest clinical studies of prostanoid treatment in pulmonary arterial hypertension demonstrated an important link between lowering mean pulmonary arterial pressure (or pulmonary vascular resistance) and improved survival. Subsequent studies of oral monotherapy or sequential combination therapy demonstrated smaller reductions in mean pulmonary arterial pressure and pulmonary vascular resistance. More recently, retrospective reports of initial aggressive prostanoid treatment or initial combination oral and parenteral therapy have shown marked afterload reduction along with significant improvements in right ventricular function. Some data suggest that reaching threshold levels for pressure or resistance (components of right ventricular afterload) may be key to interrupting the self-perpetuating injury of pulmonary vascular disease in pulmonary arterial hypertension and could translate into improved long-term clinical outcomes. Based on these clues, the authors postulate that improved clinical outcomes might be achieved by targeting significant afterload reduction with initial oral combination therapy and early parenteral prostanoids.

El impacto de CoViD-19 en la hipertensión arterial pulmonar

La enfermedad por coronavirus 2019 (CoViD-19) está causada por el virus del síndrome respiratorio agudo severo por coronavirus 2 (SARS-CoV-2), siendo particularmente perjudicial para los pacientes con enfermedad cardiovascular subyacente, y provocando una causa de morbilidad y mortalidad significativas en todo el mundo. Este virus lleva a una neumopatía, al tiempo que causa lesiones agudas de miocardio y daño crónico al sistema cardiovascular. Como consecuencia del daño del parénquima pulmonar y de la circulación pulmonar alterada, puede desarrollarse hipertensión pulmonar (HP), con su respectiva consecuencia. La fisiopatología de este tipo de HP es compleja y multifactorial, considerándose factores potenciales para las alteraciones de la circulación pulmonar. En estudios recientes, la prevalencia evidenciada de HP en pacientes con CoViD-19 es de alrededor del 12%, pero su evolución aún no está clara. La pandemia de CoViD-19 ha tenido un impacto significativo en todos los aspectos de la HP, desde el diagnóstico y manejo hasta la observación de un mayor riesgo de muerte en pacientes con hipertensión arterial pulmonar (HAP). En una encuesta de 77 centros de atención médica integral de HAP, la incidencia de infección por CoViD-19 fue de 2,1 casos por cada 1000 pacientes con HAP, similar a la incidencia de infección por CoViD-19 en la población general. Si bien, esta pandemia ha alterado el estándar de atención médica de rutina y de manejo agudo, particularmente, en aquellos pacientes con HAP, los riesgos asociados con CoViD-19 son significativos, presentándose nuevos desafíos en el cuidado de pacientes con HP. Dado que los pacientes con HAP han demostrado tener peores resultados en el ámbito de esta pandemia, es esencial trabajar de manera proactiva para disminuir el riesgo de infección por CoViD-19, mientras se continúa brindando un alto nivel de atención médica. El impacto de CoViD-19 en la prestación de atención médica y en la sociedad en general requirió que se establecieran nuevos protocolos para el tratamiento de HAP para disminuir el riesgo de exposición o transmisión de CoViD-19. De manera similar, ha habido una disminución en las pruebas de pacientes estables. Actualmente, la forma en que brindamos la atención médica se evidencia en un aumento de las visitas de telemedicina, una menor exposición a los entornos de atención médica para los pacientes y los profesionales de la salud, ayudando a nuestra necesidad continua de brindar servicios a los pacientes dentro del entorno de CoViD-19 y adaptándonos a una forma diferente de interactuar, ampliando nuestra comprensión de la mejor manera de cuidar a nuestros pacientes.

Coronavirus disease 2019 (CoViD-19) causes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), being particularly harmful for patients with underlying cardiovascular disease, and causing a cause of significant morbidity and mortality throughout the world. This virus leads to lung disease, while causing acute myocardial injury and chronic damage to the cardiovascular system. As a consequence of the damage to the lung parenchyma and altered pulmonary circulation, pulmonary hypertension (PH) can develop, with its respective consequence. The pathophysiology of this type of PH is complex and multifactorial, considering potential factors for alterations in pulmonary circulation. In recent studies, the evidenced prevalence of PH in patients with CoViD-19 is around 12%, but its evolution is not yet clear. The CoViD-19 pandemic has had a significant impact on all aspects of PH, from diagnosis and management to observing an increased risk of death in patients with pulmonary arterial hypertension (PAH). In a survey of 77 comprehensive PAH healthcare centers, the incidence of CoViD-19 infection was 2.1 cases per 1,000 PAH patients, similar to the incidence of CoViD-19 infection in the general population. Although this pandemic has altered the standard of routine medical care and acute management, particularly in those patients with PAH, the risks associated with CoViD-19 are significant, presenting new challenges in the care of patients with PH. Since PAH patients have been shown to have worse outcomes in the setting of this pandemic, it is essential to work proactively to decrease the risk of CoViD-19 infection, while continuing to provide a high level of medical care. The impact of CoViD-19 on the provision of health care and on society in general required that new protocols be established for the treatment of PAH to reduce the risk of exposure or transmission of CoViD-19. Similarly, there has been a decline in stable patient testing. Currently, the way we provide healthcare is evidenced by an increase in telemedicine visits, less exposure to healthcare settings for patients and healthcare professionals, aiding our continued need to provide services to patients. patients within the CoViD-19 environment and adapting to a different way of interacting, broadening our understanding of the best way to care for our patients

A doença coronavírus 2019 (CoViD-19) causa síndrome respiratória aguda grave coronavírus 2 (SARS-CoV-2), sendo particularmente prejudicial para pacientes com doença cardiovascular subjacente e causando uma importante morbidade e mortalidade em todo o mundo. Este vírus leva à doença pulmonar, enquanto causa lesão aguda do miocárdio e dano crônico ao sistema cardiovascular. Como consequência do dano ao parênquima pulmonar e da circulação pulmonar alterada, pode ocorrer hipertensão pulmonar (HP), com suas respectivas consequências. A fisiopatologia desse tipo de HP é complexa e multifatorial, considerando fatores potenciais para alterações da circulação pulmonar. Em estudos recentes, a prevalência de HP evidenciada em pacientes com CoViD-19 gira em torno de 12%, mas sua evolução ainda não está clara. A pandemia CoViD-19 teve um impacto significativo em todos os aspectos da HP, desde o diagnóstico e tratamento até a observação de um risco aumentado de morte em pacientes com hipertensão arterial pulmonar (HAP). Em uma pesquisa com 77 centros de saúde com HAP abrangentes, a incidência de infecção por CoViD-19 foi de 2,1 casos por 1.000 pacientes com HAP, semelhante à incidência de infecção por CoViD-19 na população em geral. Embora essa pandemia tenha alterado o padrão de cuidados médicos de rotina e tratamento agudo, particularmente em pacientes com HAP, os riscos associados ao CoViD-19 são significativos, apresentando novos desafios no cuidado de pacientes com HP. Como os pacientes com HAP demonstraram ter resultados piores no cenário dessa pandemia, é essencial trabalhar proativamente para diminuir o risco de infecção por CoViD-19, enquanto continua a fornecer um alto nível de cuidados médicos. O impacto do CoViD-19 na prestação de cuidados de saúde e na sociedade em geral exigiu o estabelecimento de novos protocolos para o tratamento da HAP para reduzir o risco de exposição ou transmissão do CoViD-19. Da mesma forma, houve um declínio nos testes de pacientes estáveis. Atualmente, a forma como prestamos serviços de saúde é evidenciada por um aumento nas visitas de telemedicina, menos exposição aos ambientes de saúde para pacientes e profissionais de saúde, auxiliando nossa necessidade contínua de fornecer serviços aos pacientes. Pacientes dentro do ambiente CoViD-19 e adaptando-se de uma maneira diferente de interagir, ampliando nosso entendimento sobre a melhor forma de cuidar de nossos pacientes.

Rol de los péptidos natriuréticos en insuficiencia cardíaca: El fino equilibrio entre la medicina de precisión y la optimización de los recursos

La insuficiencia cardíaca constituye la fase final de la mayoría de las patologías cardiovasculares. Si bien el interrogatorio, el conocimiento de los antecedentes personales y familiares del paciente, sumados al examen físico detallado, contribuyen en sobremanera al diagnóstico; muchas veces el diagnóstico diferencial del síndrome de insuficiencia cardíaca no nos permite diferenciar entre los cuadros compensados de aquellos portadores de insuficiencia cardíaca en las primeras fases de la descompensación o nos llevan a la duda entre diagnósticos diferenciales. La falta de disponibilidad de camas de hospitalización, problemas de cobertura médica o incluso problemas sociales o psicológicos, obligan muchas veces a la determinación de altas precoces con el riesgo presente de descompensaciones e internaciones reiteradas. Evitar descompensaciones frecuentes es el trabajo silencioso que debe realizar el médico para tratar de detectar precozmente con la finalidad de enlentecer o detener el progreso de la enfermedad cardiovascular, evitando estudios e internaciones costosas. Entre el armamento necesario para cumplir con esta finalidad se encuentra el dosaje de péptidos natriuréticos. La presente revisión trata de resumir los datos disponibles que valoran el control de los niveles de péptidos natriuréticos en nuestra asistencia de los pacientes con insuficiencia cardíaca.

Heart failure constitutes the final stage of most cardiovascular diseases. Although the questioning, the knowledge of the patient s personal and family history, added to the detailed physical examination, greatly contribute to the diagnosis; Many times the differential diagnosis of heart failure syndrome does not allow us to differentiate between the compensated conditions of those with heart failure in the early stages of decompensation or leads us to doubt between differential diagnoses. The lack of availability of hospital beds, problems of medical coverage or even social or psychological problems, often force the determination of early discharges with the present risk of decompensation and repeated hospitalizations. Avoiding frequent decompensations is the silent work that the physician must do to try to detect it early in order to slow down or stop the progress of cardiovascular disease, avoiding expensive studies and hospitalizations. Among the weapons necessary to fulfill this purpose is the dosage of natriuretic peptides. This review attempts to summarize the available data that assess the control of natriuretic peptide levels in our care of patients with heart failure.

A insuficiência cardíaca constitui o estágio final da maioria das doenças cardiovasculares. Apesar do questionamento, o conhecimento da história pessoal e familiar do paciente, somado ao exame físico detalhado, contribuem muito para o diagnóstico; Muitas vezes, o diagnóstico diferencial da síndrome da insuficiência cardíaca não nos permite diferenciar as condições compensadas dos portadores de insuficiência cardíaca nos estágios iniciais de descompensação ou nos leva à dúvida entre os diagnósticos diferenciais. A falta de disponibilidade de leitos hospitalares, problemas de cobertura médica ou mesmo problemas sociais ou psicológicos, muitas vezes obrigam à determinação de altas precoces com o risco atual de descompensação e hospitalizações repetidas. Evitar descompensações frequentes é o trabalho silencioso que o médico deve fazer para tentar detectá-la precocemente, a fim de retardar ou interromper o progresso das doenças cardiovasculares, evitando estudos e internações dispendiosas. Entre as armas necessárias para cumprir esse propósito está a dosagem de peptídeos natriuréticos. Esta revisão tenta resumir os dados disponíveis que avaliam o controle dos níveis de peptídeo natriurético em nosso tratamento de pacientes com insuficiência cardíaca.

Empagliflozin in Heart Failure with a Preserved Ejection Fraction.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors reduce the risk of hospitalization for heart failure in patients with heart failure and a reduced ejection fraction, but their effects in patients with heart failure and a preserved ejection fraction are uncertain. METHODS: In this double-blind trial, we randomly assigned 5988 patients with class II-IV heart failure and an ejection fraction of more than 40% to receive empagliflozin (10 mg once daily) or placebo, in addition to usual therapy. The primary outcome was a composite of cardiovascular death or hospitalization for heart failure. RESULTS: Over a median of 26.2 months, a primary outcome event occurred in 415 of 2997 patients (13.8%) in the empagliflozin group and in 511 of 2991 patients (17.1%) in the placebo group (hazard ratio, 0.79; 95% confidence interval [CI], 0.69 to 0.90; P<0.001). This effect was mainly related to a lower risk of hospitalization for heart failure in the empagliflozin group. The effects of empagliflozin appeared consistent in patients with or without diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (407 with empagliflozin and 541 with placebo; hazard ratio, 0.73; 95% CI, 0.61 to 0.88; P<0.001). Uncomplicated genital and urinary tract infections and hypotension were reported more frequently with empagliflozin. CONCLUSIONS: Empagliflozin reduced the combined risk of cardiovascular death or hospitalization for heart failure in patients with heart failure and a preserved ejection fraction, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Preserved ClinicalTrials.gov number, NCT03057951).

[Relevance of right ventricle in the clinical management of pulmonary arterial hypertension]. / Manejo clínico de la hipertensión arterial pulmonar. Relevancia del ventrículo derecho.

Pulmonary arterial hypertension (PAH) requires structured processes of diagnosis and risk stratification, being the function of the right ventricle (RV) a hallmark prognosis determinant. The main therapeutic goals in PAH are to improve and try to revert RV dysfunction and maintaining a low risk. Currently, there are multiple treatments with different mechanisms of action, the combination of which in double or triple therapy has shown improved results compared to monotherapy. Recent clinical evidence shows the importance of early incorporation of parenteral prostanoids to the scheme, improving RV function and survival. In this review, we discuss the role of the RV function in the diagnosis, prognosis, and follow-up of PAH. We recommend the systematic and standardised evaluation of the RV as well as the early initiation of combined treatment in cases of intermediatehigh risk to try to reach and keep the patient with PAH at a low risk and / or avoid the progression of PAH.

La hipertensión arterial pulmonar (HAP) requiere procesos estructurados de diagnóstico y estratificación de riesgo, siendo la función del ventrículo derecho (VD) un marcador pronóstico central. Los principales objetivos terapéuticos en la HAP son mejorar y/o intentar revertir la disfunción del VD y mantener condición de bajo riesgo. Actualmente existen múltiples fármacos con diferentes mecanismos de acción cuya combinación en doble o triple terapia ha mostrado mejores resultados que la monoterapia. Evidencia actual demuestra la importancia de incorporar tempranamente prostanoides parenterales al esquema, mejorando la funcionalidad del VD y la supervivencia. En esta revisión se refleja el papel de la función del VD en el diagnóstico, pronóstico y seguimiento de la HAP. Se recomienda la evaluación sistemática y estandarizada del VD, así como el inicio temprano de tratamiento combinado en riesgo intermedio-alto para obtener las metas de alcanzar y mantener un riesgo bajo y/o evitar la progresión de la HAP.

Manejo clínico de la hipertensión arterial pulmonar. Relevancia del ventrículo derecho / Relevance of right ventricle in the clinical management of pulmonary arterial hypertension

Resumen La hipertensión arterial pulmonar (HAP) requiere procesos estructurados de diagnóstico y estratificación de riesgo, siendo la función del ventrículo derecho (VD) un marcador pronóstico central. Los principales objetivos terapéuticos en la HAP son mejorar y/o intentar revertir la disfunción del VD y mantener condición de bajo riesgo. Actualmente existen múltiples fármacos con diferentes mecanismos de acción cuya combinación en doble o triple terapia ha mostrado mejores resultados que la monoterapia. Evidencia actual demuestra la importancia de incorporar tempranamente prostanoides parenterales al esquema, mejorando la funcionalidad del VD y la supervivencia. En esta revisión se refleja el papel de la función del VD en el diagnós tico, pronóstico y seguimiento de la HAP. Se recomienda la evaluación sistemática y estandarizada del VD, así como el inicio temprano de tratamiento combinado en riesgo intermedio-alto para obtener las metas de alcanzar y mantener un riesgo bajo y/o evitar la progresión de la HAP.

Abstract Pulmonary arterial hypertension (PAH) requires structured processes of diagnosis and risk stratifica tion, being the function of the right ventricle (RV) a hallmark prognosis determinant. The main therapeutic goals in PAH are to improve and try to revert RV dysfunction and maintaining a low risk. Currently, there are multiple treatments with different mechanisms of action, the combination of which in double or triple therapy has shown improved results compared to monotherapy. Recent clinical evidence shows the importance of early incorpora tion of parenteral prostanoids to the scheme, improving RV function and survival. In this review, we discuss the role of the RV function in the diagnosis, prognosis, and follow-up of PAH. We recommend the systematic and standardised evaluation of the RV as well as the early initiation of combined treatment in cases of intermediate-high risk to try to reach and keep the patient with PAH at a low risk and / or avoid the progression of PAH.

Global Differences in Burden and Treatment of Ischemic Heart Disease in Acute Heart Failure: REPORT-HF.

OBJECTIVES: The primary aim of the current study was to investigate global differences in prevalence, association with outcome, and treatment of ischemic heart disease (IHD) in patients with acute heart failure (AHF) in the REPORT-HF (International Registry to Assess Medical Practice With Longitudinal Observation for Treatment of Heart Failure) registry. BACKGROUND: Data on IHD in patients with AHF are primarily from Western Europe and North America. Little is known about global differences in treatment and prognosis of patients with IHD and AHF. METHODS: A total of 18,539 patients with AHF were prospectively enrolled from 44 countries and 365 centers in the REPORT-HF registry. Patients with a history of coronary artery disease, an ischemic event causing admission for AHF, or coronary revascularization were classified as IHD. Clinical characteristics, treatment, and outcomes of patients with and without IHD were explored. RESULTS: Compared with 8,766 (47%) patients without IHD, 9,773 (53%) patients with IHD were older, more likely to have a left ventricular ejection fraction <40% (heart failure with reduced ejection fraction [HFrEF]), and reported more comorbidities. IHD was more common in lower income compared with high-income countries (61% vs. 48%). Patients with IHD from countries with low health care expenditure per capita or without health insurance less likely underwent coronary revascularization or used anticoagulants at discharge. IHD was independently associated with worse cardiovascular death (hazard ratio: 1.21; 95% confidence interval: 1.09 to 1.35). The association between IHD and cardiovascular death was stronger in HFrEF compared with heart failure with preserved ejection fraction (pinteraction <0.001). CONCLUSIONS: In this large global contemporary cohort of patients with AHF, IHD was more common in low-income countries and conveyed worse 1-year mortality, especially in HFrEF. Patients in regions with the greatest burden of IHD were less likely to receive coronary revascularization and treatment for IHD.

Manifestaciones pulmonares y sistémicas de la hipertensión arterial pulmonar: Un enfoque panvascular

La hipertensión arterial pulmonar (HAP) es una grave enfermedad cuyo resultado final de la interacción entre el tono vascular y la alteración progresiva de la remodelación de las arterias pulmonares provoca insuficiencia cardíaca derecha y muerte. El remodelado vascular pulmonar es la alteración estructural clave en la hipertensión pulmonar. Este proceso implica cambios en la íntima, media, adventicia y espacio perivascular, a menudo con la interacción de células inflamatorias. Los mecanismos fisiopatológicos de la HAP abarcan una serie de modificaciones vasculares que producen un aumento de la resistencia vascular pulmonar. Las modificaciones vasculares que se producen en la HAP incluyen: la vasoconstricción, la proliferación del músculo liso, la inflamación, la apoptosis endotelial, la proliferación endotelial resistente a la apoptosis, la fibrosis, la trombosis in-situ, y finalmente, las lesiones plexiformes. Hasta hace poco, la HAP se consideraba una enfermedad restringida a la circulación pulmonar. Sin embargo, existe una creciente evidencia de que los pacientes con HAP también exhiben disfunción vascular sistémica, como lo demuestra la alteración de la dilatación mediada por el flujo de la arteria braquial, el flujo sanguíneo cerebral anormal, la miopatía esquelética y la enfermedad renal intrínseca. Los datos recientes apoyan un vínculo con los eventos genéticos y moleculares detrás de la patogénesis de la HAP. Esta revisión sirve de introducción a los principales hallazgos sistémicos en la HAP y la evidencia que apoya un vínculo común con la fisiopatología de la HAP. Sobre la base de la evidencia disponible, proponemos un paradigma en el que las anomalías metabólicas, la lesión genética y la disfunción vascular sistémica contribuyen a las manifestaciones sistémicas de la HAP. Este concepto no sólo abre interesantes posibilidades de investigación, sino que también anima a considerar las manifestaciones extrapulmonares en el tratamiento de los pacientes con HAP, pues la disfunción vascular sistémica contribuiría a las manifestaciones sistémicas de la HAP.

Pulmonary arterial hypertension (PAH) is a serious disease whose end result of the interaction between vascular tone and the progressive alteration of the remodeling of the pulmonary arteries causes right heart failure and death. Pulmonary vascular remodeling is the key structural alteration in pulmonary hypertension. This process involves changes in the intima, media, adventitia, and perivascular space, often with the interaction of inflammatory cells. The pathophysiological mechanisms of PAH include a series of vascular modifications that produce an increase in pulmonary vascular resistance. Vascular modifications that occur in PAH include: vasoconstriction, proliferation of smooth muscle, inflammation, Endothelial apoptosis, apoptosis-resistant endothelial proliferation, fibrosis, in-situ thrombosis, and finally, plexiform lesions. Until recently, PAH was considered a disease restricted to the pulmonary circulation. However, there is growing evidence that patients with PAH also exhibit systemic vascular dysfunction, as evidenced by impaired brachial artery flow-mediated dilation, abnormal cerebral blood flow, skeletal myopathy, and intrinsic kidney disease. Recent data support a link to the genetic and molecular events behind the pathogenesis of PAH. This review serves as an introduction to the main systemic findings in PAH and the evidence supporting a common link with the pathophysiology of PAH. Based on the available evidence, we propose a paradigm in which metabolic abnormalities, genetic injury, and systemic vascular dysfunction contribute to the systemic manifestations of PAH. This concept not only opens up interesting research possibilities, but also encourages consideration of extrapulmonary manifestations in the treatment of patients with PAH, since systemic vascular dysfunction would contribute to the systemic manifestations of PAH.

A hipertensão arterial pulmonar (HAP) é uma doença grave cujo resultado final da interação entre o tônus vascular e a alteração progressiva da remodelação das artérias pulmonares causa insuficiência cardíaca direita e morte. A remodelação vascular pulmonar é a principal alteração estrutural na hipertensão pulmonar. Esse processo envolve mudanças na íntima, média, adventícia e espaço perivascular, muitas vezes com a interação de células inflamatórias. Os mecanismos fisiopatológicos da HAP incluem uma série de modificações vasculares que produzem um aumento na resistência vascular pulmonar. As modificações vasculares que ocorrem na HAP incluem: vasoconstrição, proliferação do músculo liso, inflamação, apoptose endotelial, proliferação endotelial resistente à apoptose, fibrose, trombose in situ e, finalmente, lesões plexiformes. Até recentemente, a HAP era considerada uma doença restrita à circulação pulmonar. No entanto, há evidências crescentes de que os pacientes com HAP também apresentam disfunção vascular sistêmica, conforme evidenciado pela dilatação prejudicada mediada pelo fluxo da artéria braquial, fluxo sanguíneo cerebral anormal, miopatia esquelética e doença renal intrínseca. Dados recentes suportam uma ligação com os eventos genéticos e moleculares por trás da patogênese da HAP. Esta revisão serve como uma introdução aos principais achados sistêmicos em HAP e as evidências que apoiam uma ligação comum com a fisiopatologia da HAP. Com base nas evidências disponíveis, propomos um paradigma em que anormalidades metabólicas, lesão genética e disfunção vascular sistêmica contribuem para as manifestações sistêmicas da HAP. Esse conceito não apenas abre possibilidades interessantes de pesquisa, mas também incentiva a consideração das manifestações extrapulmonares no tratamento de pacientes com HAP, uma vez que a disfunção vascular sistêmica contribuiria para as manifestações sistêmicas da HAP.

Effect of Empagliflozin on Cardiovascular and Renal Outcomes in Patients With Heart Failure by Baseline Diabetes Status: Results From the EMPEROR-Reduced Trial.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors improve outcomes in patients with heart failure with reduced ejection fraction, but additional information is needed about whether glycemic status influences the magnitude of their benefits on heart failure and renal events. METHODS: Patients with Class II-IV heart failure and a left ventricular ejection fraction ≤40% were randomized to receive empagliflozin (10 mg daily) or placebo in addition to recommended therapy. We prespecified a comparison of the effect of empagliflozin in patients with and without diabetes. RESULTS: Of the 3730 patients enrolled, 1856 (50%) had diabetes, 1268 (34%) had prediabetes (hemoglobin A1c [HbA1c] 5.7-6.4%), and 606 (16%) had normoglycemia (HbA1c <5.7%). The risks of the primary outcome (cardiovascular death or hospitalization for heart failure), total hospitalizations for heart failure, and adverse renal outcomes were higher in patients with diabetes, but were similar between patients with prediabetes and normoglycemia. Empagliflozin reduced the risk of the primary outcome in patients with and without diabetes (hazard ratio, 0.72 [95% CI, 0.60-0.87] and 0.78 [95% CI, 0.64-0.97], respectively, P-interaction=0.57). Patients with and without diabetes also did not differ with respect to the effect of empagliflozin on total hospitalizations for heart failure, on the decline in estimated glomerular filtration rate over time, and on the risk of serious adverse renal outcomes. Among these end points, the effects of the drug did not differ in patients with prediabetes or normoglycemia. When analyzed as a continuous variable, baseline HbA1c did not significantly modify the benefits of empagliflozin on the primary outcome (P-interaction=0.40). Empagliflozin did not lower HbA1c in patients with prediabetes or normoglycemia and was not associated with increased risk of hypoglycemia. CONCLUSIONS: In EMPEROR-Reduced (Empagliflozin Outcome Trial in Patients With Chronic Heart Failure With Reduced Ejection Fraction), empagliflozin significantly improved cardiovascular and renal outcomes in patients with heart failure and a reduced ejection fraction, independent of baseline diabetes status and across the continuum of HbA1c. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03057977.