Cause of Death in Heart Failure Based on Etiology: Long-Term Cohort Study of All-Cause and Cardiovascular Mortality.

We assessed differences in long-term all-cause and cardiovascular (CV) mortality in heart failure (HF) outpatients based on the etiology of HF. Consecutive patients admitted to the HF Clinic from August 2001 to September 2019 (N = 2587) were considered for inclusion. HF etiology was divided into ischemic heart disease (IHD), dilated cardiomyopathy (DCM), hypertensive heart disease, alcoholic cardiomyopathy, drug-induced cardiomyopathy (DICM), valvular heart disease, and hypertrophic cardiomyopathy. All-cause death and CV death were the primary end points. Among 2387 patients included in the analysis (mean age 66.5 ± 12.5 years, 71.3% men), 1317 deaths were recorded (731 from CV cause) over a maximum follow-up of 18 years (median 4.1 years, interquartile range (IQR) 2-7.8). Considering IHD as the reference, only DCM had a lower risk of all-cause death (adjusted hazard ratio (aHR) 0.68, 95% confidence interval (CI) 0.56-0.83, p < 0.001), and only DICM had a higher risk of all-cause death (aHR 1.47, 95% CI 1.02-2.11, p = 0.04). However, almost all etiologies had a significantly lower risk of CV death than IHD. Among the studied HF etiologies, DCM and DICM have the lowest and highest risk of all-cause death, respectively, whereas IHD has the highest adjusted risk of CV death.

Mortality trends in an ambulatory multidisciplinary heart failure unit from 2001 to 2018.

To assess mortality trends at 1 and 3 years from 2001 to 2018 in a real-life cohort of HF outpatients from different etiologies with depressed and preserved LVEF. A total of 2368 consecutive patients with HF (mean age 66.4 ± 12.9 years, 71% men, 15.4% with preserved LVEF) admitted to a HF clinic from August 2001 to September 2018 were included in the study. Patients were divided into five quintiles (Q) according to the period of admission. Trends for all-cause and cardiovascular mortality from Q1 to Q5 were assessed by linear regression. Patients with LVEF < 50% had a progressive decrease in the rates of all-cause and cardiovascular death at 1 year (12.1% in Q1 to 6.5% in Q5, p = 0.003; and 8.4% in Q1 to 3.8% in Q5, p = 0.007, respectively) and 3 years (30.5% in Q1 to 17.0% in Q5, p = 0.003; and 23.9% in Q1 to 9.8% in Q5, p = 0.003, respectively). These trends remained significant after adjusting for clinical characteristics and risk. No significant trend in mortality was observed in patients with LVEF ≥ 50%. In a cohort of real-life ambulatory patients with HF, mortality progressively declined in patients with LVEF < 50%, but the same trend was not observed in patients with preserved LVEF.

Trends in modes of death in heart failure over the last two decades: less sudden death but cancer deaths on the rise.

AIMS: Better management of heart failure (HF) over the past two decades has improved survival, mainly by reducing the incidence of death due to cardiovascular (CV) causes. Deaths due to non-CV causes, particularly cancer, may be increasing. This study explored the modes of death of consecutive patients who attended a HF clinic over 17 years. METHODS AND RESULTS: A total of 935 deaths were ascertained from 2002 to 2018 among 1876 patients (mean age 65.8 ± 12.5 years, 75% men, left ventricular ejection fraction < 50%) admitted to our HF clinic. Median follow-up was 4.2 years [1.9-7.8]. Mode of death was curated from patient health records and verified by the Catalan and Spanish health system databases. Trends for every mode of death were assessed by polynomial regression. Two trends were observed: a significant reduction in sudden death (P = 0.03) without changes in HF progression as mode of death (P = 0.26), and a significant increase in non-CV modes of death (P < 0.001). Non-CV deaths accounted for 17.4% of deaths in 2002 and 65.8% of deaths in 2018. A total 138 deaths were due to cancer (37% of non-CV deaths). A significant trend was observed towards a progressive increase in cancer deaths over time (P = 0.002). The main mode of cancer mortality was lung cancer. CONCLUSIONS: The modes of death in HF have shifted over the last two decades. Patients with HF die less due to sudden death and more due to non-CV causes, mainly cancer. Whether HF triggers cancer, or cancer develops in HF survivors, deserves further insight.

A bio-clinical approach for prediction of sudden cardiac death in outpatients with heart failure: The ST2-SCD score.

BACKGROUND: Sudden cardiac death (SCD) is one of the main modes of death in heart failure (HF) patients and its prediction remains a real challenge. Our aim was to assess the incidence of SCD at 5 years HF contemporary managed outpatients, and to find a simple prediction model for SCD. METHODS: SCD was considered any unexpected death, witnessed or not, occurring in a previously stable patient with no evidence of worsening HF or any other cause of death. A competing risk strategy was adopted using the Fine-Gray method of Cox regressions analyses that considered other causes of death as the competing event. RESULTS: The derivation cohort included 744 consecutive outpatients (72% men, age 67.9 ±â€¯12.2 years, left ventricular ejection fraction [LVEF] 36% ±â€¯14). During follow-up, 312 deaths occurred, 40 SCDs (5.4%). Age, haemoglobin, eGFR, HF duration, high-sensitivity troponin T, NTproBNP, and ST2 were associated with SCD in univariate analyses; HF duration (p = 0.006), eGFR (p < 0.001), LVEF <45% (p = 0.03), and ST2 (p = 0.006) remained in multivariable analysis. A predictive score (ST2-SCD) including dichotomous variables (ST2 > 45, LVEF <45%, HF duration >3 years, eGFR < 55, age ≥ 60 years and male sex) provided a Harrell's C-statistic of 0.82 (0.76-0.89)), reaching 0.87 (0.80-0.95) in the validation cohort (n = 149). CONCLUSIONS: In contemporary managed HF, SCD occurred in 5.4% of outpatients, accounting for 12.8% of all deaths at 5 years. Of the 3 studied biomarkers, only ST2 remained independently associated with SCD. A model containing age, sex, ST2, eGFR, LVEF, and HF duration reasonably predicted 5-years risk of SCD.

Cinética de la hemoglobina y pronóstico a largo plazo en insuficiencia cardiaca / Hemoglobin kinetics and long-term prognosis in heart failure

Introducción y objetivos: La influencia de la cinética de la hemoglobina en la insuficiencia cardiaca no se ha establecido por completo. Métodos: Se determinó la hemoglobina en la primera visita y a los 6 meses. La anemia se definió según los criterios de la Organización Mundial de la Salud (hemoglobina < 13 g/dl los varones y < 12 g/dl las mujeres). Según los valores de hemoglobina, se estableció una clasificación de los pacientes como sin anemia (ambas determinaciones normales), con anemia transitoria (anemia en la primera visita, pero no a los 6 meses), con anemia de nueva aparición (inicialmente sin anemia, pero con anemia a los 6 meses) o con anemia permanente (anemia en ambas determinaciones). Resultados: Se incluyó en el estudio a 1.173 pacientes consecutivos (el 71,9% varones; media de edad, 66,8 ± 12,2 años). Se consideró sin anemia a 476 pacientes (40,6%), con anemia transitoria a 170 (14,5%), con anemia de nueva aparición a 147 (12,5%) y con anemia persistente a 380 (32,4%). Durante un seguimiento de 3,7 ± 2,8 años después de la visita realizada a los 6 meses, fallecieron 494 pacientes. En los análisis multivariables generales, la anemia (p < 0,001) y el tipo de anemia (p < 0,001) continuaron siendo factores independientes predictivos de mortalidad por cualquier causa. En comparación con los pacientes sin anemia, aquellos con anemia persistente (hazard ratio [HR] = 1,62; intervalo de confianza del 95% [IC95%], 1,30-2,03; p < 0,001) o con anemia de nueva aparición (HR = 1,39; IC95%, 1,04-1,87; p = 0,03) presentaron más mortalidad, e incluso los pacientes con anemia transitoria mostraron una tendencia similar, aunque sin alcanzar significación estadística (HR = 1,31; IC95%, 0,97-1,77; p = 0,075). Conclusiones: La anemia —en especial la persistente y la de nueva aparición y, en menor medida, la anemia transitoria— tiene efectos nocivos en la insuficiencia cardiaca (AU)

Introduction and objectives: The influence of hemoglobin kinetics on outcomes in heart failure has been incompletely established. Methods: Hemoglobin was determined at the first visit and at 6 months. Anemia was defined according to World Health Organization criteria (hemoglobin < 13 g/dL for men and hemoglobin < 12 g/dL for women). Patients were classified relative to their hemoglobin values as nonanemic (both measurements normal), transiently anemic (anemic at the first visit but not at 6 months), newly anemic (nonanemic initially but anemic at 6 months), or permanently anemic (anemic in both measurements). Results: A total of 1173 consecutive patients (71.9% men, mean age 66.8 ± 12.2 years) were included in the study. In all, 476 patients (40.6%) were considered nonanemic, 170 (14.5%) had transient anemia, 147 (12.5%) developed new-onset anemia, and 380 (32.4%) were persistently anemic. During a follow-up of 3.7 ± 2.8 years after the 6-month visit, 494 patients died. On comprehensive multivariable analyses, anemia (P < .001) and the type of anemia (P< .001) remained as independent predictors of all-cause mortality. Compared with patients without anemia, patients with persistent anemia (hazard ratio [HR] = 1.62; 95% confidence interval [95%CI], 1.30-2.03; P < .001) and new-onset anemia (HR = 1.39; 95%CI, 1.04-1.87, P= .03) had higher mortality, and even transient anemia showed a similar trend, although without reaching statistical significance (HR = 1.31; 95%CI, 0.97-1.77, P = .075). Conclusions: Anemia, especially persistent and of new-onset, and to a lesser degree, transient anemia, is deleterious in heart failure (AU)

Hemoglobin Kinetics and Long-term Prognosis in Heart Failure.

INTRODUCTION AND OBJECTIVES: The influence of hemoglobin kinetics on outcomes in heart failure has been incompletely established. METHODS: Hemoglobin was determined at the first visit and at 6 months. Anemia was defined according to World Health Organization criteria (hemoglobin < 13g/dL for men and hemoglobin < 12g/dL for women). Patients were classified relative to their hemoglobin values as nonanemic (both measurements normal), transiently anemic (anemic at the first visit but not at 6 months), newly anemic (nonanemic initially but anemic at 6 months), or permanently anemic (anemic in both measurements). RESULTS: A total of 1173 consecutive patients (71.9% men, mean age 66.8±12.2 years) were included in the study. In all, 476 patients (40.6%) were considered nonanemic, 170 (14.5%) had transient anemia, 147 (12.5%) developed new-onset anemia, and 380 (32.4%) were persistently anemic. During a follow-up of 3.7±2.8 years after the 6-month visit, 494 patients died. On comprehensive multivariable analyses, anemia (P < .001) and the type of anemia (P < .001) remained as independent predictors of all-cause mortality. Compared with patients without anemia, patients with persistent anemia (hazard ratio [HR] = 1.62; 95% confidence interval [95%CI], 1.30-2.03; P < .001) and new-onset anemia (HR = 1.39; 95%CI, 1.04-1.87, P = .03) had higher mortality, and even transient anemia showed a similar trend, although without reaching statistical significance (HR = 1.31; 95%CI, 0.97-1.77, P = .075). CONCLUSIONS: Anemia, especially persistent and of new-onset, and to a lesser degree, transient anemia, is deleterious in heart failure.

Weight Loss in Obese Patients With Heart Failure.

BACKGROUND: In heart failure (HF), weight loss (WL) has been associated with an adverse prognosis whereas obesity has been linked to lower mortality (the obesity paradox). The impact of WL in obese patients with HF is incompletely understood. Our objective was to explore the prevalence of WL and its impact on long-term mortality, with an emphasis on obese patients, in a cohort of patients with chronic HF. METHODS AND RESULTS: Weight at first visit and the 1-year follow-up and vital status after 3 years were assessed in 1000 consecutive ambulatory, chronic HF patients (72.7% men; mean age 65.8±12.1 years). Significant WL was defined as a loss of ≥5% weight between baseline and 1 year. Obesity was defined as body mass index ≥30 kg/m(2) (N=272). Of the 1000 patients included, 170 experienced significant WL during the first year of follow-up. Mortality was significantly higher in patients with significant WL (27.6% versus 15.3%, P<0.001). In univariable Cox regression analysis, patients with significant WL had 2-fold higher mortality (hazard ratio 1.95 [95% CI 1.39-2.72], P<0.001). In multivariable analysis, adjusting for age, sex, body mass index, New York Heart Association functional class, left ventricular ejection fraction, HF duration, ischemic etiology, diabetes, and treatment, significant WL remained independently associated with higher mortality (hazard ratio 1.89 [95% CI 1.32-2.68], P<0.001). Among obese patients with HF, significant WL was associated with an even more ominous prognosis (adjusted hazard ratio for death of 2.38 [95% CI 1.31-4.32], P=0.004) than that observed in nonobese patients (adjusted hazard ratio 1.83 [95% CI 1.16-2.89], P=0.01). CONCLUSIONS: Weight loss ≥5% in patients with chronic HF was associated with high long-term mortality, particularly among obese patients with HF.

Early intensive treatment improves outcomes in patients with glomerular hyperfiltration and type 2 diabetes / El tratamiento intensivo precoz mejora los resultados en pacientes con hiperfiltración glomerular y diabetes tipo 2

Background and objective: Approximately 24-40% of patients with type 2 diabetes mellitus (T2DM) develop kidney damage. Our objective was to evaluate the long-term evolution of renal function using isotopic determination of GFR and urinary albumin excretion (UAE) in patients with T2DM undergoing intensive treatment for renal and cardiovascular risk factors. Patients and methods: This was a single-center, prospective study of 201 patients with T2DM and UAE who initiated intensive treatment. They were followed for 17.2 ± 6.5 years. Patients were divided into three groups, according to renal function: 167(85.6%) had stable renal function, 16(8.2%) had creatinine levels that doubled and 12(6.2%) began renal replacement therapy (RRT). We performed periodic isotopic determinations of GFR using 125I-iothalamate. Results: There were significant differences between the three groups with respect to age, duration of T2DM at baseline, years of follow-up in the study and systolic blood pressure, serum creatinine, isotopic GFR, and UAE at baseline. Renal function evolution slopes were −1.55 mL/min/1.73 m2/year in patients with stable creatinine, −2.49 mL/min/1.73 m2/year in those with doubled creatinine, and −8.16 mL/min/1.73 m2/year in those requiring RRT. We also found that differences in renal events were determined by delayed initiation of intensive treatment. Conclusion: Patients with glomerular hyperfiltration who were undergoing treatment with renin angiotensin aldosterone system blockers exhibited a better evolution in renal function, possibly because these patients initiated intensive treatment earlier. Although diabetic nephropathy is associated with classic risk factors, early initiation of intensive treatment should be a priority in order to prevent worsening renal function (AU)

Antecedentes y objetivo: Aproximadamente el 24-40% de los pacientes con diabetes mellitus tipo 2 (DM2) desarrollan daño renal. Nuestro objetivo fue evaluar la evolución a largo plazo de la función renal mediante la determinación isotópica del filtrado glomerular (FG) y la excreción urinaria de albúmina (EUA) en pacientes con DM2 en tratamiento intensivo de los factores de riesgo renal y cardiovascular. Pacientes y métodos: Estudio prospectivo unicéntrico de 201 pacientes con DM2 y EUA que iniciaron un tratamiento intensivo. El seguimiento fue de 17,2 ± 6,5 años. Los pacientes fueron divididos en 3 grupos según la función renal al final: 167 (85,6%) tenían función renal estable, 16 (8,2%) doblaron la creatinina y 12 (6,2%) requirieron tratamiento renal sustitutivo (TRS). Se realizaron determinaciones isotópicas periódicas del FG usando 125I-iotalamato. Resultados: Hay diferencias significativas entre los 3 grupos respecto a la edad, los años de duración de la DM2 al inicio, los años de seguimiento, la presión arterial sistólica, la creatinina sérica, el FG isotópico y la EUA basal. Las pendientes de evolución de la función renal fueron: −1,55 ml/min/1,73 m2/año en pacientes estables, −2,49 ml/min/1,73 m2/año en los que doblaron la creatinina y −8,16 ml/min/1,73 m2/año en los que requirieron TRS. Además, esta diferente evolución de la función renal venía determinada por el inicio tardío del tratamiento intensivo. Conclusión: Los pacientes con hiperfiltración glomerular en tratamiento con bloqueadores del sistema renina-angiotensina-aldosterona mostraron una mejor evolución de la función renal, posiblemente debido a que estos pacientes iniciaron tratamiento intensivo antes. Aunque la nefropatía diabética se asocia a factores de riesgo clásicos, el tratamiento intensivo precoz debe ser una prioridad con el fin de prevenir el deterioro de la función renal (AU)

Early intensive treatment improves outcomes in patients with glomerular hyperfiltration and type 2 diabetes.

BACKGROUND AND OBJECTIVE: Approximately 24-40% of patients with type 2 diabetes mellitus (T2DM) develop kidney damage. Our objective was to evaluate the long-term evolution of renal function using isotopic determination of GFR and urinary albumin excretion (UAE) in patients with T2DM undergoing intensive treatment for renal and cardiovascular risk factors. PATIENTS AND METHODS: This was a single-center, prospective study of 201 patients with T2DM and UAE who initiated intensive treatment. They were followed for 17.2±6.5 years. Patients were divided into three groups, according to renal function: 167(85.6%) had stable renal function, 16(8.2%) had creatinine levels that doubled and 12(6.2%) began renal replacement therapy (RRT). We performed periodic isotopic determinations of GFR using (125)I-iothalamate. RESULTS: There were significant differences between the three groups with respect to age, duration of T2DM at baseline, years of follow-up in the study and systolic blood pressure, serum creatinine, isotopic GFR, and UAE at baseline. Renal function evolution slopes were -1.55mL/min/1.73m(2)/year in patients with stable creatinine, -2.49mL/min/1.73m(2)/year in those with doubled creatinine, and -8.16mL/min/1.73m(2)/year in those requiring RRT. We also found that differences in renal events were determined by delayed initiation of intensive treatment. CONCLUSION: Patients with glomerular hyperfiltration who were undergoing treatment with renin angiotensin aldosterone system blockers exhibited a better evolution in renal function, possibly because these patients initiated intensive treatment earlier. Although diabetic nephropathy is associated with classic risk factors, early initiation of intensive treatment should be a priority in order to prevent worsening renal function.

Poor histological lesions in IgA nephropathy may be reflected in blood and urine peptide profiling.

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide, leading to renal failure in 15% to 40% of cases. IgAN is diagnosed by renal biopsy, an invasive method that is not risk-free. We used blood and urine peptide profiles as a noninvasive method of linking IgAN-associated changes with histological lesions by Oxford classification. METHODS: We prospectively studied 19 patients with biopsy-proven IgAN and 14 healthy subjects from 2006 to 2009, excluding subjects with crescentic glomerulonephritis and collecting clinical and biochemical data at the time of diagnosis and during follow-up (24 months). Histological lesions were evaluated by Oxford classification. Proteomic analysis was performed by combining magnetic bead (MB) technology and mass spectrometry (MALDI-TOF MS) to obtain peptide profiles. Doubling of serum creatinine was considered a variable of poor renal prognosis. RESULTS: We identified 55 peptides-13 in serum, 26 in plasma, and 16 in urine-that differentiated IgAN patients from healthy subjects. A significant association was noted between serum/plasma and urine peptides and histological findings-ie, tubulointerstitial damage, segmental glomerulosclerosis, and endocapillary injury. CONCLUSIONS: In patients with IgAN, the use of noninvasive approaches, such as blood and urine proteomics, can provide valuable information beyond that of standard diagnostic techniques, allowing us to identify blood and urine peptide profiles that are associated with poor histological lesions in IgAN patients.