Long-term effects of iron deficiency in patients with heart failure with or without anemia: the RAID-HF follow-up study.

INTRODUCTION: Iron deficiency (ID) has been recognized as a relevant comorbidity in heart failure with reduced ejection fraction (HFrEF); however, study data have shown that diagnostic and therapeutic efforts on ID are primarily performed in patients with anemia. METHODS: The RAID-HF registry investigated consecutive patients with ID and HFrEF in 11 heart centers in Germany and Switzerland. The present analysis focuses on 1-year follow-up data in patients with versus without anemia. RESULTS: In 505 patients with HFrEF and ID and 418 patients with HFrEF without ID 1-year follow-up was performed. Patients with ID had a higher long-term mortality compared to those without ID (19.5% vs. 13.7%, p = 0.02) and reported a lower quality of life. Only a minority of patients with ID (9.3%) received iron supplementation during long-term course, just 4.7% intravenously. Anemia was associated with an elevated mortality whereas ID versus no ID did not predict mortality in anemic patients (log-rank p = 0.78). However, in patients without anemia ID versus no ID predicted mortality (log-rank p = 0.002). In the adjusted analysis a significant interaction remained, with ID being a significant predictor of 1-year mortality in patients without anemia (HR 2.15, 95% CI 1.12-3.78), but not in anemic patients (HR 0.99, 95% CI 0.65-1.49). CONCLUSIONS: RAID-HF demonstrates the impact of ID on long-term mortality and quality of life in patients with HFrEF and reveals an underuse of iron supplementation in current clinical practice. Particularly in patients without anemia the diagnosis of ID is of clinical relevance to identify patients at higher mortality risk.

Quality of vitamin K antagonist oral anticoagulation in 322 patients with atrial fibrillation - real-life data from a survey in Eastern Switzerland.

AIM OF THE STUDY: To better appreciate the role of the non-vitamin K oral anticoagulants (NOACs) for patients with non-valvular atrial fibrillation in Switzerland we aimed to assess the quality of vitamin K antagonist (VKA) anticoagulation in daily practice. METHODS: In a cross-sectional study, clinically stable patients on VKA treatment for non-valvular atrial fibrillation for at least 6 months, documentation of international normalised ratio (INR) values for at least 3 months and with at least two INR values were included. The percentage of INR values within the therapeutic range of 2.0 to 3.0 and the time in therapeutic range (TTR; Rosendaal method) and predictors for these measures of VKA anticoagulation quality were assessed. RESULTS: We studied 332 patients (62% male, mean age 74 ± 9 years) with median (interquartile range) CHA2DS2Vasc and HAS-BLED scores of 4 (3-5) and 3 (2-4) points. The median number of INR values per patient was 8 (5-14), and the average interval between INR measurements was 20 (13-27) days. The percentage of INR values between 2.0 and 3.0 was 67% (50-83%). The median TTR was 69% (51-89%), and TTR ≥65% was found in 202 (61%) patients. Independent predictors of ≥80% INR values between 2.0 and 3.0 included a longer interval between INR measurements and the non-use of spironolactone. The non-use of amiodarone and spironolactone and a longer interval between INR measurements were the only independent predictors of a TTR ≥65%. CONCLUSIONS: The quality of VKA anticoagulation in Switzerland is highly variable. Importantly, only 60% of patients achieve a TTR ≥65%, which is currently considered to be the minimal acceptable TTR required for VKA therapy. There are few clinical predictors of a good VKA anticoagulation quality. These data may represent a novel basis for decision making regarding the choice of anticoagulation for atrial fibrillation in Switzerland.

Pulmonary hypertension associated with left-sided heart disease.

Pulmonary hypertension associated with left-sided heart disease (PH-LHD) is the most common type of pulmonary hypertension. In patients with left-sided heart disease, the presence of pulmonary hypertension is typically a marker of more advanced disease, more severe symptoms, and worse prognosis. In contrast to pulmonary arterial hypertension, PH-LHD is characterised by an elevated pulmonary artery wedge pressure (postcapillary pulmonary hypertension) without or with an additional precapillary component (isolated postcapillary versus combined postcapillary and precapillary pulmonary hypertension). Transthoracic echocardiography is the primary nonin-vasive imaging tool to estimate the probability of pulmonary hypertension and to establish a working diagnosis on the mechanism of pulmonary hyperten-sion. However, right heart catheterisation is always required if significant pulmonary hypertension is sus-pected and exact knowledge of the haemodynamic constellation is necessary. The haemodynamic con-stellation (mean pulmonary artery pressure, mean pulmonary artery wedge pressure, left ventricular end-diastolic pressure) in combination with clinical infor-mation and imaging findings (mainly echocardiog-raphy, coronary angiography and cardiac magnetic resonance imaging) will usually allow the exact mech-anism underlying PH-LHD to be defined, which is a prerequisite for appropriate treatment. The general principle for the management of PH-LHD is to treat the underlying left-sided heart disease in an optimal man-ner using drugs and/or interventional or surgical ther-apy. There is currently no established indication for pulmonary arterial hypertension-specific therapies in PH-LHD, and specific therapies may even cause harm in patients with PH-LHD.

Usefulness of Iron Deficiency Correction in Management of Patients With Heart Failure [from the Registry Analysis of Iron Deficiency-Heart Failure (RAID-HF) Registry].

Iron deficiency (ID) has been identified as an important co-morbidity in patients with heart failure (HF). Intravenous iron therapy reduced symptoms and rehospitalizations of iron-deficient patients with HF in randomized trials. The present multicenter study investigated the "real-world" management of iron status in patients with HF. Consecutive patients with HF and ejection fraction ≤40% were recruited and analyzed from December 2010 to October 2015 by 11 centers in Germany and Switzerland. Of 1,484 patients with HF, iron status was determined in only 923 patients (62.2%), despite participation of the centers in a registry focusing on ID and despite guideline recommendation to determine iron status. In patients with determined iron status, a prevalence of 54.7% (505 patients) for ID was observed. Iron therapy was performed in only 8.5% of the iron-deficient patients with HF; 2.6% were treated with intravenous iron therapy. The patients with iron therapy were characterized by a high rate of symptomatic HF and anemia. In conclusion, despite strong evidence of beneficial effects of iron therapy on symptoms and rehospitalizations, diagnostic and therapeutic efforts on ID in HF are low in the actual clinical practice, and the awareness to diagnose and treat ID in HF should be strongly enforced.

Frequency and predictors of hyperkalemia in patients ≥60 years of age with heart failure undergoing intense medical therapy.

Hyperkalemia is a concern in heart failure (HF), especially in older patients with co-morbidities. Previous studies addressing this issue have focused mainly on younger patients. This study was aimed at determining the frequency and predictors of hyperkalemia in older patients with HF undergoing intense medical therapy. Frequency and predictors of hyperkalemia were defined in patients (n = 566) participating in the Trial of Intensified versus Standard Medical Therapy in Elderly Patients with Congestive Heart Failure, in which patients ≥60 years of age were randomized to a standard versus an intensified N-terminal brain natriuretic peptide-guided HF therapy. During an 18-month follow-up 76 patients (13.4%) had hyperkalemia (≥5.5 mmol/L) and 28 (4.9%) had severe hyperkalemia (≥6.0 mmol/L). Higher baseline serum potassium (odds ratio [OR] 2.92 per mmol/L), baseline creatinine (OR 1.11 per 10 µmol/L), gout (OR 2.56), New York Heart Association (NYHA) class (compared to NYHA class II, IV OR 3.08), higher dosage of spironolactone at baseline (OR 1.20 per 12.5 mg/day), and higher dose changes of spironolactone (compared to no dose change: 12.5 mg, OR 1.45; 25 mg, OR 2.52; >25 mg, OR 3.24) were independent predictors for development of hyperkalemia (p <0.05 for all comparisons). In conclusion, hyperkalemia is common in patients ≥60 years of age with HF undergoing intense medical therapy. Risk is increased in patients treated with spironolactone, in addition to patient-specific risk factors such as chronic kidney disease, higher serum potassium, advanced NYHA class, and gout. Careful surveillance of serum potassium and cautious use of spironolactone in patients at risk may help to decrease the incidence of potentially hazardous complications caused by hyperkalemia.

Impact of the exercise mode on heart rate recovery after maximal exercise.

Heart rate recovery 1 min after exercise termination (HRR-1) is a prognostic predictor. However, the influence of the exercise mode on HRR-1 is incompletely characterised. Twenty-nine young and healthy subjects and 16 elderly patients with chronic heart failure underwent cardiopulmonary exercise testing using cycle ergometer and treadmill ramp protocols in random order. HRR-1 and heart rate recovery 2 and 3 min after exercise (HRR-2, HRR-3) during active recovery and peak oxygen consumption (peak VO(2)) were measured. In both healthy subjects (32 +/- 14 vs. 27 +/- 10 bpm) and HF patients (19 +/- 8 vs. 14 +/- 9 bpm), HRR-1 was faster after cycle exercise (p = 0.029; p for between group difference 0.94). In contrast, HRR-2 and HRR-3 were similar after both tests in both groups. Peak VO(2) was lower during cycle as compared to treadmill exercise in both groups. In conclusion, in both healthy subjects and HF patients, HRR-1 depends on the mode of exercise as peak VO(2) does.

Cardiopulmonary exercise testing in mild heart failure: impact of the mode of exercise on established prognostic predictors.

OBJECTIVES: In patients with heart failure (HF), peak oxygen consumption (peak VO(2)), the relationship between minute ventilation and carbon dioxide production (VE/VCO(2) slope) and heart rate recovery (HRR) are established prognostic predictors. However, treadmill exercise has been shown to elicit higher peak VO(2) values than bicycle exercise. We sought to assess whether the VE/VCO(2) slope and HRR in HF also depend on the exercise mode. METHODS: Twenty-one patients with mild HF on chronic beta-blocker therapy underwent treadmill and bicycle cardiopulmonary exercise testing for measurement of peak VO(2) and the VE/VCO(2) slope. In patients with sinus rhythm (n = 16), HRR at 1 (HRR-1) and 2 min (HRR-2) after exercise termination was assessed. RESULTS: Peak VO(2) was higher during treadmill as compared with bicycle testing (21.7 +/- 4.6 vs. 19.6 +/- 3.4 ml/kg/min; p = 0.006). HRR-1 tended to be slower (15 bpm, interquartile range 8-19, vs. 18 bpm, interquartile range 11-22; p = 0.16), and HRR-2 was significantly slower after treadmill exercise (26 bpm, interquartile range 20-39, vs. 31 bpm, interquartile range 22-41; p = 0.04). In contrast, VE/VCO(2) slope values did not differ between the test modes (32.9 +/- 5.5 vs. 32.3 +/- 5.0; p = 0.56). CONCLUSIONS: In contrast to peak VO(2) and HRR, the VE/VCO(2) slope is not affected by the exercise mode in patients with mild HF.

Relevance of short-term variation of B-type natriuretic peptide in patients with clinically stable heart failure.

BACKGROUND: In patients with clinically stable chronic heart failure, circulating B-type natriuretic peptide (BNP) levels may exhibit considerable variation over a period of a few days. The aim of this study was to evaluate the clinical impact of this phenomenon. METHODS: In 23 patients with clinically stable mild-to-moderate systolic heart failure [median (interquartile range) 72 (64-77) years, left ventricular ejection fraction 30 (27-40)%] and a history of previous hospitalization for heart failure, BNP was measured at two time points [T1 and T2, interval 5 (3-7) days] for calculation of the absolute change in BNP concentrations between T1 and T2 (DeltaBNP; irrespective of whether there was a decrease or increase). Follow-up for rehospitalization was 436 (407-458) days. RESULTS: In the group overall, DeltaBNP was 26 (9-116) pg/ml [19 (10-28)% of the value at T1]. During follow-up, 8/23 (35%) patients were rehospitalized. BNP concentrations at T1 [340 (187-533) vs. 210 (108-606) pg/ml; P = 0.33] and T2 [328 (125-491) vs. 259 (89-536) pg/ml; P = 0.51] were similar in patients who were rehospitalized and those who were not; however, DeltaBNP was higher in patients requiring rehospitalization [98 (36-186) vs. 19 (6-93) pg/ml; P = 0.04]. Patients with DeltaBNP <26 pg/ml had a longer rehospitalization-free survival than those with DeltaBNP > or = 26 pg/ml (log rank P = 0.02). Sensitivity and specificity of DeltaBNP > or = 26 pg/ml for the prediction of rehospitalization were 88% and 67% respectively. CONCLUSIONS: In this small study among patients with clinically stable heart failure, higher DeltaBNP over a period of a few days was associated with a higher likelihood of rehospitalization during follow-up.