Oral Sodium to Preserve Renal Efficiency in Acute Heart Failure: A Randomized, Placebo-Controlled, Double-Blind Study.

BACKGROUND: Evidence for modulating the sodium chloride (NaCl) intake of patients hospitalized with acute heart failure (AHF) is inconclusive. Salt restriction may not benefit; hypertonic saline may aid diuresis. OBJECTIVE: To compare the safety and efficacy of oral NaCl during intravenous (IV) diuretic therapy in renal function and weight. METHODS: Seventy hospitalized patients with AHF who were being treated with IV furosemide infusion consented to receive, randomly, 2 grams of oral NaCl or placebo 3 times a day in a double-blind manner during diuresis. Treatment efficacy (bivariate primary endpoints of change in serum creatinine levels and change in weight) was measured at 96 hours, and adverse safety events were tracked for 90 days. RESULTS: Sixty-five patients (34 NaCl, 31 placebo) were included for analysis after 5 withdrew. A median of 13 grams of NaCl was given compared to placebo. At 96 hours, there was no significant difference between treatment groups with respect to the primary endpoint (P = 0.33); however, the trial was underpowered, and there was greater than expected standard deviation in weight change. The mean change in creatinine levels and weight was 0.15 ± 0.44 mg/dL and 4.6 ± 4.2 kg in the placebo group compared with 0.04 ± 0.40 mg/dL and 4.0 ± 4.3 kg in the NaCl group (P = 0.30 and 0.57, respectively). Across efficacy and safety endpoints, we observed no significant difference between the 2 groups other than changes in serum sodium levels (-2.6 ± 2.7 in the placebo group and -0.3 ± 3.3 mEq/L in the NaCl group; P < 0.001) and in serum blood urea nitrogen levels (11 ± 15 in the placebo group; 3.1 ± 13 mEq/L in the NaCl group; P = 0.025). CONCLUSIONS: In this single-center study, liberal vs restrictive oral sodium chloride intake strategies did not impact the safety and efficacy of intravenous diuretic therapy in patients with AHF. (ClinicalTrials.gov registration NCT04334668.).

Novel Strategies to Improve Prescription of Guideline-Directed Medical Therapy in Heart Failure.

Purpose of review: To examine the emerging data for novel strategies being studied to improve use and dose titration of guideline-directed medical therapy (GDMT) for patients with heart failure (HF). Recent findings: There is mounting evidence to employ novel multi-pronged strategies to address HF implementation gaps. Summary: Despite high-level randomized evidence and clear national society recommendations, a large gap persists in use and dose titration of guideline-directed medical therapy (GDMT) in patients with heart failure (HF). Accelerating the safe implementation of GDMT has proven to reduce the morbidity and mortality associated with HF but remains an ongoing challenge for patients, clinicians, and health systems. In this review, we examine the emerging data for novel strategies to improve the use of GDMT including the use of multidisciplinary team-based approaches, nontraditional patient encounters, patient messaging/engagement, remote patient monitoring, and electronic health record (EHR)-based clinical alerts. While societal guidelines and implementation studies have focused on heart failure with reduced ejection fraction (HFrEF), expanding indications and evidence for the use of sodium glucose cotransporter2 (SGLT2i) will necessitate implementation efforts across the LVEF spectrum.

Captopril Versus Hydralazine-Isosorbide Dinitrate Vasodilator Protocols in Patients With Acute Decompensated Heart Failure Transitioning From Sodium Nitroprusside.

BACKGROUND: The role of oral vasodilators in the management of acute decompensated heart failure (ADHF) is not clearly defined. We evaluated the use of captopril vs hydralazine-isosorbide dinitrate (H-ISDN) in the transition from sodium nitroprusside (SNP) in patients with ADHF. METHODS AND RESULTS: A retrospective chart review was performed of 369 consecutive adult patients in the intensive care unit with ADHF and reduced ejection fraction, who received either a captopril or an H-ISDN protocol to transition from SNP. Captopril patients were matched 1:2 to H-ISDN patients, based on serum creatinine and race (Black vs non-Black). Baseline demographics, serum chemistry and use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs) were similar in both groups. Time to SNP discontinuation (46.9 vs 40.4 hours, P = 0.11) and length of hospital stay (9.86 vs 7.99 days, P = 0.064) were similar in both groups. Length of hospital stay in the intensive care unit was statistically shorter in the H-ISDN group (4.11 vs 3.96 days, P = 0.038). Fewer H-ISDN protocol patients were discharged on ACEis/ARBs (82.9 % vs 69.9%, P = 0.003) despite similar kidney function at time of discharge (serum creatinine 1.1 vs 1.2, P = 0.113). No difference was observed in rates of readmission (40.7% vs 50%, P = 0.09) or mortality (16.3% vs 17.5 %, P = 0.77) at 1 year postdischarge. CONCLUSION: Similar inpatient and 1-year outcomes were observed between patients using H-ISDN vs ACEi when transitioning from SNP, even though fewer H-ISDN protocol patients were discharged taking ACEis/ARBs despite similar kidney function.

The growing dilemma of legalized cannabis and heart transplantation.

This in-depth review discusses cannabis as it relates to heart transplantation and the growing dilemma of legalization around the world creating disparities in transplant candidacy. One will learn about two of the most common cannabinoids: Δ9-tetrahydrocannabinol (THC) and cannabidiol (CBD). These cannabinoids are metabolized by cytochrome P-450 and P glycoprotein, which are essential for the metabolism of drugs for transplantation, such as calcineurin inhibitors. Addiction, withdrawal, and cannabis use disorder will be reviewed as well as hyperemesis syndrome. Maintaining adequate immunosuppression will depend on a variety of factors, including drug-drug interactions, pharmacokinetics of cannabinoids and chronicity of cannabis usage. These drug interactions are further confounded by varying concentrations of cannabis products available at medical dispensaries. One will also learn about the outcomes of transplant recipients using cannabis such as graft failure and the risk of infections. Although more research is needed to establish transplant guidelines, the available data is concerning and fairness in organ distribution should not vary by transplant program or institution.

Acute Hemodynamic Effects of Sacubitril-Valsartan In Heart Failure Patients Receiving Intravenous Vasodilator and Inotropic Therapy.

BACKGROUND: Prior study has demonstrated that transitioning patients in acutely decompensated heart failure with a low cardiac output directly from intravenous (i.v.) vasoactive (ie, vasodilators or inotropes) drugs to sacubitril-valsartan (S/V) can be done safely with tolerance to the 1-month follow-up. Here, we further characterize the hemodynamic impact of S/V after patients have been optimized on vasoactive therapy. METHODS AND RESULTS: In a single-center, retrospective analysis, 25 patients with cardiac index of less than 2.2 L/min/m2 were admitted to the cardiac intensive care unit and newly initiated on angiotensin receptor-neprilysin inhibitor therapy with the guidance of invasive hemodynamic monitoring. Hemodynamic data were gathered and compared upon cardiac intensive care unit admission, after optimization with i.v. vasoactive therapy, and after S/V initiation and weaning off i.v. THERAPY: All patients who tolerated S/V (n = 20) were weaned off vasoactive medications before transfer out of cardiac intensive care unit. Patients maintained their significant improvement in cardiac index and reduction in SVR/PVR on transition from i.v. inotropic and vasodilator therapy to oral S/V. There was an increase in pulmonary artery pulsatility index with S/V therapy compared with the i.v. vasoactive phase of care. CONCLUSIONS: Patients in the cardiac intensive care unit can be successfully bridged from vasoactive i.v. therapy to oral S/V with sustained improvement in cardiac index garnered from vasoactive agents. We also observed improvement in the pulmonary artery pulsatility index and maintenance of left and right ventricular unloading with S/V. These encouraging findings merit further prospective study.

The Impact of Pharmacist-Based Services Across the Spectrum of Outpatient Heart Failure Therapy.

PURPOSE OF REVIEW: A multidisciplinary approach is vital to reduce mortality and hospitalizations in patients with heart failure. As members of the multidisciplinary team, pharmacists are uniquely positioned to care for patients across the spectrum of heart failure. This comprehensive review explores the different facets in which pharmacists can be utilized to impact the care for patients with heart failure, including those with cardiac transplant and left ventricular assist devices (LVADs), in the outpatient setting. RECENT FINDINGS: Pharmacists can see heart failure patients in a variety of settings to reduce drug therapy-related issues, increase use of guideline-directed medical therapy (GDMT), and reduce hospitalizations. Although there is limited data available, pharmacists have also been described in aiding the therapeutic drug monitoring of warfarin for patients with LVADs and immunosuppression agents in the transplant population. Through collaborative practice agreements, pharmacists can provide progressive services such as titration of GDMT and lab monitoring, in addition to medication reconciliation, education, and review for potential drug-related problems. Pharmacists can increase access to patient care by providing services through distance-visits, shared medical appointments, and home visits.

Evaluation of bleeding in patients receiving direct oral anticoagulants.

Direct oral anticoagulants (DOACs) are recognized by evidence-based treatment guidelines as the first-line option for the treatment of venous thromboembolism and prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. As use of these anticoagulants has become favored over the past several years, reported bleeding-related adverse drug events with these agents has increased. In randomized clinical trials, all DOACs have a reduced risk for intracranial hemorrhage, while major and other bleeding results have varied among the agents compared to vitamin K antagonists. We have reviewed the bleeding incidence and severity from randomized and real-world data in patients receiving DOACs in an effort to provide the clinician with a critical review of bleeding and offer practical considerations for avoiding adverse events with these anticoagulants.

Heparin Versus Bivalirudin Monotherapy in the Setting of Primary Percutaneous Coronary Intervention for Patients With ST-Segment Elevation Myocardial Infarction.

OBJECTIVE: To evaluate direct comparisons of bivalirudin versus unfractionated heparin (UFH) as anticoagulants during ST-segment elevation myocardial infarction (STEMI) in patients undergoing primary percutaneous coronary intervention (PPCI). DATA SOURCES: Relevant information was identified through a search of MEDLINE (1966-September 2015), International Pharmaceutical Abstracts (1960-September 2015), and Cochrane Databases (publications archived until September 2015) using the terms bivalirudin, unfractionated heparin, ST-segment elevation myocardial infarction, and primary percutaneous coronary intervention. STUDY SELECTION AND DATA EXTRACTION: English-language randomized controlled trials and meta-analyses were eligible for inclusion for data review of STEMI where PPCI was performed. DATA SYNTHESIS: Either bivalirudin or UFH is recommended in the setting of STEMI where PPCI is to be performed. Bivalirudin is touted for its predictable pharmacokinetics, effects on thrombin-mediated platelet inhibition, and favorable outcomes with regard to adverse bleeding profiles, whereas UFH, the gold standard anticoagulant during PPCI, remains a viable treatment strategy. Only recently have direct comparisons of UFH and bivalirudin during PPCI become available. The evidence available is complicated by variances in use of glycoprotein IIb/IIIa inhibitors (GPIs), P2Y12 inhibitors, access sites, and anticoagulant dosing strategies. We provide a review of contemporary trials and advancements in this area. CONCLUSIONS: When compared to UFH with limited use of GPI, available evidence demonstrates that bivalirudin reduces bleeding at the expense of increasing risk for acute stent thrombosis. Further randomized studies are needed to determine the potential benefits of a post-PCI infusion of bivalirudin to reduce the risk for acute stent thrombosis, long-term follow-up beyond 30 days, and mortality.