Anemia and iron deficiency are important and common comorbidities that often coexist in patients with heart failure. Both conditions, together or independently, are associated with poor clinical ...status and worse outcomes. Whether anemia and iron deficiency are just markers of heart failure severity or whether they mediate heart failure progression and outcomes and therefore should be treated is not entirely clear. Treatment of anemia in patients with heart failure with erythropoiesis-stimulating agents has been evaluated intensively during the past several years. Unfortunately, these agents did not improve outcomes but were associated with a higher risk of adverse events. Iron deficiency in patients with heart failure can be absolute, when total body iron is decreased, or functional, when total body iron is normal or increased but is inadequate to meet the needs of target tissues because of sequestration in the storage pool. Whereas iron replacement is appropriate in patients with anemia resulting from absolute iron deficiency, it has been unclear whether and how absolute or functional iron deficiency should be treated in nonanemic patients with heart failure. Recently, small studies found that administration of intravenous iron in patients with heart failure and absolute or functional iron deficiency with or without anemia improves symptoms and exercise capacity, but long-term outcomes and safety data are not yet available. In this review, we discuss the causes and pathogenesis of and treatment options for anemia and iron deficiency in patients with heart failure.
Anemia is a common comorbidity in patients with heart failure and is associated with worse long-term outcomes. Although the cause of anemia in heart failure is unclear, the weight of evidence ...suggests that renal dysfunction, along with neurohormonal and proinflammatory cytokine activation in heart failure, favors the development of anemia of chronic disease, with defective iron utilization, inappropriate erythropoietin production, and depressed bone marrow function. Similarly, the mechanisms by which anemia worsens heart failure outcomes are unknown but may be related to increased myocardial workload. If anemia is a mediator and not just a marker of poor outcomes, correcting anemia could become an important and novel therapeutic target to improve long-term outcomes in such patients. Indeed, several small-sized studies have shown the beneficial effects of empirically treating anemia in heart failure patients with recombinant erythropoietin and intravenous iron. However, the ideal threshold at which therapy should be initiated and the extent of correction considered safe and desirable in the individual patient with heart failure need to be known. These issues become more important because of increasing safety concerns that recombinant erythropoietin therapy for treating anemia may be associated with adverse cardiovascular outcomes in patients with chronic kidney disease and may worsen cancer in patients receiving chemotherapy to treat various types of cancer. Therefore, further prospectively designed studies are required to address some of these questions. Fortunately, 2 large mortality morbidity trials, TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) in patients with chronic kidney disease and RED-HF (Reduction of Events with Darbepoetin alfa in Heart Failure) in heart failure patients, are in progress and are likely to provide definitive answers.
Comorbidities are common in patients with heart failure (HF) and complicate treatment and outcomes. We identified patterns of multimorbidity in Asian patients with HF and their association with ...patients' quality of life (QoL) and health outcomes.
We used data on 6,480 patients with chronic HF (1,204 with preserved ejection fraction) enrolled between 1 October 2012 and 6 October 2016 in the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry. The ASIAN-HF registry is a prospective cohort study, with patients prospectively enrolled from in- and outpatient clinics from 11 Asian regions (Hong Kong, Taiwan, China, Japan, Korea, India, Malaysia, Thailand, Singapore, Indonesia, and Philippines). Latent class analysis was used to identify patterns of multimorbidity. The primary outcome was defined as a composite of all-cause mortality or HF hospitalization within 1 year. To assess differences in QoL, we used the Kansas City Cardiomyopathy Questionnaire. We identified 5 distinct multimorbidity groups: elderly/atrial fibrillation (AF) (N = 1,048; oldest, more AF), metabolic (N = 1,129; obesity, diabetes, hypertension), young (N = 1,759; youngest, low comorbidity rates, non-ischemic etiology), ischemic (N = 1,261; ischemic etiology), and lean diabetic (N = 1,283; diabetic, hypertensive, low prevalence of obesity, high prevalence of chronic kidney disease). Patients in the lean diabetic group had the worst QoL, more severe signs and symptoms of HF, and the highest rate of the primary combined outcome within 1 year (29% versus 11% in the young group) (p for all <0.001). Adjusting for confounders (demographics, New York Heart Association class, and medication) the lean diabetic (hazard ratio HR 1.79, 95% CI 1.46-2.22), elderly/AF (HR 1.57, 95% CI 1.26-1.96), ischemic (HR 1.51, 95% CI 1.22-1.88), and metabolic (HR 1.28, 95% CI 1.02-1.60) groups had higher rates of the primary combined outcome compared to the young group. Potential limitations include site selection and participation bias.
Among Asian patients with HF, comorbidities naturally clustered in 5 distinct patterns, each differentially impacting patients' QoL and health outcomes. These data underscore the importance of studying multimorbidity in HF and the need for more comprehensive approaches in phenotyping patients with HF and multimorbidity.
ClinicalTrials.gov NCT01633398.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The cardiorenal syndrome has recently been defined as "disorders of the heart and kidney whereby acute or chronic dysfunction in one organ may induce acute or chronic dysfunction of the other." The ...syndrome is extremely common and independently associated with poor clinical outcomes. However, no pharmacological therapy has been shown to improve its outcomes. Unfortunately, the mechanisms that initiate the development of renal dysfunction in heart failure are still debated. This review tries to clarify some of the misunderstanding regarding the principle hemodynamic factors that drive the kidneys to retain salt and water.
Prognostic Value of Changes in N-Terminal Pro-Brain Natriuretic Peptide in Val-HeFT (Valsartan Heart Failure Trial) Serge Masson, Roberto Latini, Inder S. Anand, Simona Barlera, Laura Angelici, ...Tarcisio Vago, Gianni Tognoni, Jay N. Cohn, for the Val-HeFT Investigators We assessed the prognostic value of repeated determinations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in a large population of patients with stable and chronic heart failure (HF). A single determination of NT-proBNP showed a higher prognostic discrimination during the course of a strict clinical monitoring period than continuous changes of concentrations. Categorical changes across a threshold value predicted outcome independently of a single determination. Serial determinations of NT-proBNP and classification into few categories of changes may be a superior strategy for risk stratification of patients with chronic and stable HF, and may offer an aid in monitoring these patients.
Abstract
Aims
Concern about hypotension often leads to withholding of beneficial therapy in patients with heart failure and reduced ejection fraction (HFrEF). We evaluated the efficacy and safety of ...dapagliflozin, which lowers systolic blood pressure (SBP),according to baseline SBP in Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).
Methods and results
Key inclusion criteria were: New York Heart Association Class II−IV, left ventricular ejection fraction ≤ 40%, elevated N-terminal pro-B-type natriuretic peptide level, and SBP ≥95 mmHg. The primary outcome was a composite of worsening heart failure or cardiovascular death. The efficacy and safety of dapagliflozin were examined using SBP as both a categorical and continuous variable. A total of 1205 patients had a baseline SBP <110 mmHg; 981 ≥ 110 < 120; 1149 ≥ 120 < 130; and 1409 ≥ 130 mmHg. The placebo-corrected reduction in SBP from baseline to 2 weeks with dapagliflozin was −2.54 (−3.33 to −1.76) mmHg (P < 0.001), with a smaller between-treatment difference in patients in the lowest compared to highest SBP category. Patients in the lowest SBP category had a much higher rate (per 100 person-years) of the primary outcome 20.6, 95% confidence interval (95% CI) 17.6–24.2 than those in the highest SBP category (13.8, 11.7–16.4). The benefit and safety of dapagliflozin was consistent across the range of SBP; hazard ratio (95% CI) in each SBP group, lowest to highest: 0.76 (0.60–0.97), 0.76 (0.57–1.02), 0.81 (0.61–1.08), and 0.67 (0.51–0.87), P interaction = 0.78. Study drug discontinuation did not differ between dapagliflozin and placebo across the SBP categories examined.
Conclusion
Dapagliflozin had a small effect on SBP in patients with HFrEF and was superior to placebo in improving outcomes, and well tolerated, across the range of SBP included in DAPA-HF.
Clinical Trial Registration:
ClinicalTrials.gov NCT03036124.
Graphical Abstract
BACKGROUND—Impairment in left ventricular systolic function has been described in heart failure (HF) with preserved ejection fraction (HFpEF), but its prognostic relevance is not known. We determined ...whether left ventricular longitudinal strain (LS) is predictive of cardiovascular outcomes in HFpEF beyond clinical and conventional echocardiographic measures.
METHODS AND RESULTS—LS was assessed by 2-dimensional speckle-tracking echocardiography at baseline in 447 patients with HFpEF enrolled in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) trial. At a median follow-up of 2.6 years (interquartile range, 1.5–3.9 years), 115 patients experienced the primary composite outcome of cardiovascular death, HF hospitalization, or aborted cardiac arrest. Impaired LS, defined as an absolute LS <15.8%, was present in 52% of patients and was predictive of the composite outcome (adjusted hazard ratio, 2.14; 95% confidence interval, 1.26–3.66; P=0.005), cardiovascular death alone (adjusted hazard ratio, 3.20; 95% confidence interval, 1.44–7.12; P=0.004), and HF hospitalization alone (adjusted hazard ratio, 2.23; 95% confidence interval, 1.16–4.28; P=0.016) after adjustment for clinical and conventional echocardiographic variables. LS was the strongest echocardiographic predictor of the composite outcome. Exploratory analysis in a subset of 131 patients with follow-up LS assessed after 12 to 18 months demonstrated a trend toward improvement in LS associated with spironolactone in patients enrolled in the Americas but not in Russia or Georgia.
CONCLUSIONS—Impaired left ventricular systolic function is a powerful predictor of HF hospitalization, cardiovascular death, or aborted cardiac arrest in HFpEF independent of clinical predictors. Impaired LS represents a novel imaging biomarker to identify patients with HFpEF at particularly high risk for cardiovascular morbidity and mortality.
CLINICAL TRIAL REGISTRATION—URLhttp://www.clinicaltrials.gov. Unique identifierNCT00094302.
Abstract Objective ANTHEM-HF evaluated a novel autonomic regulation therapy (ART) via either left or right vagus nerve stimulation (VNS) in patients with heart failure (HF) and reduced ejection ...fraction (HFrEF). Methods and Results Sixty subjects (New York Heart Association NYHA functional class II–III, left ventricular ejection fraction (LVEF) ≤40%, left ventricular end-diastolic diameter ≥50 mm to <80 mm) receiving optimal pharmacologic therapy were randomized at 10 sites. VNS systems were randomly implanted on the left (n = 31) or right (n = 29) side. All patients were successfully implanted and 59 were titrated over 10 weeks to a well tolerated stimulation intensity. One patient died 3 days after an embolic stroke that occurred during implantation. Common device-related adverse events after VNS titration were transient mild dysphonia, cough, and oropharyngeal pain, which were similar for left- and right-side VNS. After 6 months of ART, the adjusted left-right differences in LVEF, left ventricular end-systolic volume (LVESV), and left ventricular end-systolic diameter (LVESD) were 0.2% (95% CI -4.4 to 4.7), 3.7 mL (95% CI -7.0 to 14.4), and 1.3 mm (95% CI -0.9 to 3.6), respectively. In the combined population, absolute LVEF improved by 4.5% (95% CI 2.4–6.6), LVESV improved by -4.1 mL (95% CI -9.0 to 0.8), and LVESD improved by -1.7 mm (95% CI -2.8 to -0.7). Heart rate variability improved by 17 ms (95% CI 6.5–28) with minimal left-right difference. Six-minute walk distance improved an average of 56 m (95% CI 37–75); however, improvement was greater for right-side ART (77 m 95% CI 49-105). NYHA functional class improved in 77% of patients (baseline to 6 months). Conclusions Chronic open-loop ART via left- or right-side VNS is feasible and well tolerated in HFrEF patients. Safety and efficacy measures are encouraging and warrant further study.
Aims
Uncertainties remain on the biological and prognostic significance and therapeutic implications of loss in body weight (W‐LOSS) in chronic heart failure (HF) patients. We assessed whether W‐LOSS ...added additional prognostic value to classical clinical risk factors in two separate and large cohorts of patients with chronic HF. The factors associated with W‐LOSS were studied.
Methods and results
W‐LOSS and estimated plasma volume changes were measured serially in the GISSI‐HF (n = 6820) and Val‐HeFT trials (n = 4892). In both studies, experiencing at least one episode of ≥5% W‐LOSS during the first year of follow‐up was considered a sign of wasting. In GISSI‐HF, self‐reported unintentional W‐LOSS ≥2 kg between two consecutive clinical visits within 1 year was also considered a sign of wasting. W‐LOSS occurred in 16.4% and 15.7% of the patients enrolled in GISSI‐HF and Val‐HeFT, respectively (unintentional ≥2 kg W‐LOSS occurred in 18.9% in GISSI‐HF). In multivariable analyses adjusting for a number of baseline covariates as well as for plasma volume changes, W‐LOSS was found to be independently associated with mortality and adverse cardiovascular and non‐cardiovascular outcomes, with a significant net reclassification improvement (cfNRI) and an increase in integrated discrimination improvement (IDI). W‐LOSS was independently associated with several features representing the severity of HF, including baseline NT‐proBNP and high sensitivity C‐reactive protein (hsCRP) in Val‐HeFT.
Conclusions
W‐LOSS was a frequent finding in the GISSI‐HF and Val‐HeFT trials, associated with multiple patient features, and added additional prognostic information beyond clinical variables of HF severity, including estimated plasma volume changes.
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