Efficacy of Intravenous Furosemide Versus a Novel, pH-Neutral Furosemide Formulation Administered Subcutaneously in Outpatients With Worsening Heart Failure.

OBJECTIVES: This study sought to determine the efficacy and safety of a novel, pH-neutral formulation of furosemide administered subcutaneously (SC) for treatment of acute decompensated heart failure (HF). BACKGROUND: Congestion requiring intravenous (IV) administration of a diuretic agent is the main reason patients with HF present for acute medical care. METHODS: Outpatients presenting with decompensated HF were randomized to receive a single SC or IV dose of furosemide. Primary outcome was 6-h urine output, and secondary outcomes were weight change, natriuresis, and adverse events. RESULTS: Forty-one patients were randomized: 19 were treated with IV (mean dose: 123 ± 47 mg) and 21 with SC furosemide (fixed dose of 80 mg over 5 h). The 6-h urine output in the IV group was not significantly different from that in the SC furosemide group (median IV: 1,425 ml; interquartile range [IQR]: 1,075 to 1,950 ml; vs. median SC: 1,350 ml; IQR: 900 to 1,900 ml; p = 0.84). Additionally, mean weight loss was not significantly different (-1.5 ± 1.1 kg in the IV group vs. -1.5 ± 1.2 kg in the SC group; p = 0.95). Hourly urine output was significantly higher in the IV group at hour 2 (425 ml in the IV group vs. 250 ml in the SC group; p = 0.02) and higher in the SC group at hour 6 (125 ml, IV group vs. 325 ml, SC group; p = 0.005). Natriuresis was higher in the SC group (IV: 7.3 ± 35.3 mEq/l vs. SC: 32.8 ± 43.6 mEq/l; p = 0.05). There was no worsening renal function, ototoxicity, or skin irritation with either formulation. Thirty-day hospitalization rates were similar. CONCLUSIONS: In this phase II trial, we did not identify significant differences between urine output obtained with pH-neutral furosemide administered SC and that obtained by IV. This method of decongestion may allow treatment at home and reduced HF resources and warrants further investigation. (Sub-Q Versus IV Furosemide in Acute Heart Failure; NCT02579057).

Genetic testing improves identification of transthyretin amyloid (ATTR) subtype in cardiac amyloidosis.

Amyloidosis is a group of conditions characterized by the accumulation of amyloid deposits in various tissues. Among these disorders, ATTR amyloidosis occurs either with or without a TTR pathogenic variant. Treatment for amyloidosis depends on the subtype, which is often identified through a tissue biopsy followed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Genetic testing may be done to confirm these results for patients with ATTR amyloidosis; however, the necessity of genetic testing after LC-MS/MS has not been evaluated. A retrospective review identified 153 patients diagnosed with biopsy-proven ATTR amyloidosis, and 56 of these patients underwent both genetic testing and LC-MS/MS. LC-MS/MS and proteomics correctly reported the mutant peptide and heterozygosity in 47/56 (84%) cases. It failed to identify two individuals who were homozygous for the ATTRV122I mutation and failed to detect the following mutations in six other individuals: ATTRA19D, ATTRF44L, ATTRT60A, ATTRI68L and ATTRV122I. Therefore, LC-MS/MS is not sufficient to rule out a pathogenic mutation in cases of ATTR amyloid, and genetic testing should be performed in most cases of ATTR amyloidosis. Correct recognition of hereditary ATTR amyloidosis is important for estimating prognosis, proper familial counselling and guiding use of therapies, such as liver transplantation.

Baseline Characteristics Predict the Presence of Amyloid on Endomyocardial Biopsy.

BACKGROUND: Recent studies have suggested a high prevalence of cardiac amyloidosis (CAm) in heart failure (HF) patients. CAm might be underdiagnosed owing to low clinical suspicion. METHODS AND RESULTS: We performed retrospective analysis of 259 patients with HF and ejection fraction (EF) ≥50% referred for endomyocardial biopsy. Seventy-three (28%) had CAm. Multivariable independent predictors of CAm were identified. Over a mean follow-up of 2.6 ± 3.3 years, CAm patients had worse survival than those without (1.5 y vs 6.3 y; log rank P < .0001). CONCLUSIONS: Clinicians should be suspicious of CAm in patients with EF 50%-75%, >50 years of age, BMI <30 kg/m2, peripheral neuropathy, Sokolow-Lyon index ≤15 mm, and septal wall thickness ≥1.4 cm.

Nutritional Interventions in Heart Failure: A Systematic Review of the Literature.

BACKGROUND: Heart failure (HF) is a major health care burden and there is a growing need to develop strategies to maintain health and sustain quality of life in persons with HF. The purpose of this review is to critically appraise the components of nutrition interventions and to establish an evidence base for future advances in HF nutrition research and practice. METHODS AND RESULTS: Cinahl, Pubmed, and Embase were searched to identify articles published from 2005 to 2015. A total of 17 randomized controlled trials were included in this review. Results were divided into 2 categories of nutrition-related interventions: (1) educational and (2) prescriptive. Educational interventions improved patient outcomes such as adherence to dietary restriction in urine sodium levels and self-reported diet recall. Educational and prescriptive interventions resulted in decreased readmission rates and patient deterioration. Adherence measurement was subjective in many studies. Evidence showed that a normal-sodium diet and 1-liter fluid restriction along with high diuretic dosing enhanced B-type natriuretic peptide, aldosterone, tumor necrosis factor α, and interleukin-6 markers. CONCLUSIONS: Educational nutrition interventions positively affect patient clinical outcomes. Although clinical practice guidelines support a low-sodium diet and fluid restriction, research findings have revealed that a low-sodium diet may be harmful. Future research should examine the role of macronutrients, food quality, and energy balance in HF nutrition.