Noninvasive Imaging Estimation of Myocardial Iron Repletion Following Administration of Intravenous Iron: The Myocardial-IRON Trial.

Background Intravenous ferric carboxymaltose (FCM) improves symptoms, functional capacity, and quality of life in heart failure and iron deficiency. The mechanisms underlying these effects are not fully understood. The aim of this study was to examine changes in myocardial iron content after FCM administration in patients with heart failure and iron deficiency using cardiac magnetic resonance. Methods and Results Fifty-three stable heart failure and iron deficiency patients were randomly assigned 1:1 to receive intravenous FCM or placebo in a multicenter, double-blind study. T2* and T1 mapping cardiac magnetic resonance sequences, noninvasive surrogates of intramyocardial iron, were evaluated before and 7 and 30 days after randomization using linear mixed regression analysis. Results are presented as least-square means with 95% CI. The primary end point was the change in T2* and T1 mapping at 7 and 30 days. Median age was 73 (65-78) years, with N-terminal pro-B-type natriuretic peptide, ferritin, and transferrin saturation medians of 1690 pg/mL (1010-2828), 63 ng/mL (22-114), and 15.7% (11.0-19.2), respectively. Baseline T2* and T1 mapping values did not significantly differ across treatment arms. On day 7, both T2* and T1 mapping (ms) were significantly lower in the FCM arm (36.6 [34.6-38.7] versus 40 [38-42.1], P=0.025; 1061 [1051-1072] versus 1085 [1074-1095], P=0.001, respectively). A similar reduction was found at 30 days for T2* (36.3 [34.1-38.5] versus 41.1 [38.9-43.4], P=0.003), but not for T1 mapping (1075 [1065-1085] versus 1079 [1069-1089], P=0.577). Conclusions In patients with heart failure and iron deficiency, FCM administration was associated with changes in the T2* and T1 mapping cardiac magnetic resonance sequences, indicative of myocardial iron repletion. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03398681.

Intrarenal venous flow in cardiorenal syndrome: a shining light into the darkness.

The aim of this case report is to assess the potential role of intrarenal Doppler ultrasonography as a non-invasive method to evaluate intrarenal venous flow (IRVF) in acute heart failure (AHF) and concomitant renal dysfunction. We report a case of an 81-year-old woman with valvular heart disease (previous mitral valve replacement) that presented with acutely decompensated heart failure and concomitant worsening renal function (WRF). In addition to complete physical examination, laboratory analysis, and echocardiography, IRVF was assessed at baseline and 48 h after the administration of diuretic treatment. At admission, physical examination and echocardiography revealed signs of intravascular congestion (jugular venous distension and severely dilated inferior vena cava). In addition, a significant increase in serum creatinine from 1.23 to 1.81 mg/dL was noted without signs of hypoperfusion at clinical evaluation. At baseline, intrarenal Doppler ultrasonography showed a monophasic IRVF pattern indicating a severely elevated interstitial renal pressure. After aggressive decongestion, a dynamic behaviour was found in IRVF changing from monophasic to biphasic pattern in parallel with an improvement in clinical parameters and renal function (serum creatinine changed from 1.81 to 1.44 mg/dL). In this case of a patient with AHF and WRF, IRVF changed after aggressive decongestion in agreement with clinical evolution. According to these findings, this technique could provide valuable information for identifying patients with a 'congestion kidney failure' phenotype. Further studies are needed confirming this observation and evaluating the potential role of this technique for guiding decongestive therapy in patients with AHF and WRF.

Changes in myocardial iron content following administration of intravenous iron (Myocardial-IRON): Study design.

Treatment with intravenous ferric carboxymaltose (FCM) has been shown to improve symptoms, functional capacity, and quality of life in patients with heart failure and iron deficiency. However, the underlying mechanisms for these beneficial effects remain undetermined. The aim of this study is to quantify cardiac magnetic resonance changes in myocardial iron content after administration of intravenous FCM in patients with heart failure and iron deficiency and contrast them with parameters of heart failure severity. This is a multicenter, double-blind, randomized study. Fifty patients with stable symptomatic heart failure, left ventricular ejection fraction <50%, and iron deficiency will be randomly assigned 1:1 to receive intravenous FCM or placebo. Intramyocardial iron will be evaluated by T2* and T1 mapping cardiac magnetic resonance sequences before and at 7 and 30 days after FCM. After 30 days, patients assigned to placebo will receive intravenous FCM in case of persistent iron deficiency. The main endpoint will be changes from baseline in myocardial iron content at 7 and 30 days. Secondary endpoints will include the correlation of these changes with left ventricular ejection fraction, functional capacity, quality of life, and cardiac biomarkers. The results of this study will add important knowledge about the effects of intravenous FCM on myocardial tissue and cardiac function. We hypothesize that short-term (7 and 30 days) myocardial iron content changes after intravenous FCM, evaluated by cardiac magnetic resonance, will correlate with simultaneous changes in parameters of heart failure severity. The study is registered at http://www.clinicaltrials.gov (NCT03398681).

Echocardiographic pulmonary artery pressure estimation and heart failure rehospitalization burden in patients with acute heart failure.

Pulmonary hypertension (PH) is a strong predictor of mortality in patients with heart failure (HF). However, the relationship between PH, through echocardiographic pulmonary artery pressure (PASP) estimation, and the risk of HF rehospitalizations remains unclear. METHODS: We prospectively included 2343 consecutive patients discharged for acute heart failure (AHF). PH was estimated by echocardiography through PASP determination during the index admission. Patients were categorized as follows across PASP: non-measurable, normal (≤35mmHg), mild (36-45mmHg), moderate (46-60mmHg), or severe PH (>60mmHg). Negative binomial regression method was used to evaluate the association between PASP and recurrent HF hospitalizations across preserved (HFpEF: ≥50%), mid-range (HFmrEF: 40-49%) and reduced ejection fraction (HFrEF: <40%). RESULTS: Mean age of the cohort was 72.8±11.2years, 1187 (50.5%) were women, and 1252 (53.4%) and 410 (17.5%) showed HFpEF and HFmrEF, respectively. At a median (interquartile range) follow-up of 2.3 (0.8-4.5) years, we registered 1114 (47.6%) deaths, and 1834 HF-related rehospitalizations in 943 (40.2%) patients. After multivariable adjustment, and compared to patients with normal PASP, severe PH exhibited an independent higher risk of recurrent HF admissions only in HFpEF (IRR=1.66; 95% confidence interval (CI), 1.16-2.38; p=0.005), whereas in HFmrEF patients there was a non-significant trend to higher HF readmissions (IRR: 1.73; 95% CI, 0.85-3.55; p=0.132). Severe PH was not related with recurrent hospitalizations in HFrEF (IRR: 1.19; 95% CI, 0.66-2.14; p=0.553). CONCLUSIONS: Echocardiography-derived PASP evaluated during an episode of AHF is related to HF readmission burden, particularly in those patients with HFpEF.