Published data have shown potential advantages of levosimendan in the management of acute decompensated heart failure and advanced heart failure when standard medical therapies threaten hemodynamics and organ perfusion are unable to alleviate clinical symptoms. Levosimendan distinguishes itself from other catecholaminergic inotropes by its three mechanisms of action: positive inotropy, vasodilation, and cardioprotection. In addition, its pharmacokinetics allow for a longer duration of action from the metabolite OR1896 allowing for further cardiovascular therapeutic effects for several days, even after discontinuation of the parent drug.

Portopulmonary hypertension (POPH) is seen in 5-8% of orthotopic liver transplantation (OLT) candidates and has significant implications for clinical outcomes. POPH is characterized by vasoconstriction and remodeling of the pulmonary vasculature. It is exacerbated by the hyperdynamic circulation that is common in advanced liver disease. Screening all OLT candidates with transthoracic echocardiography to assess pulmonary pressures and right ventricular function is crucial, as clinical symptoms alone are not reliable. Any significant right ventricular dysfunction or dilatation along with an elevation in estimated pulmonary pressures usually triggers further investigation with right heart catheterization. The mainstays of therapy of POPH are vasodilators that are used in pulmonary arterial hypertension. They include monotherapy or combination therapy with prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors/guanylate cyclase stimulator. Limited evidence from smaller studies and case series suggests that a timely diagnosis of POPH and the early initiation of treatment improve patient outcomes, whether or not OLT is ultimately undertaken. Given the historically high perioperative mortality rate of more than 35%, POPH remains a contraindication to OLT unless it is treated and responsive to vasodilator therapy. We review the current literature and International Liver Transplant Society practice guidelines (2016) for the latest in understanding POPH, its pathogenesis, diagnosis, modern pharmacological treatment, indications, and contraindications for OLT, as well as perioperative management.

Peripartum cardiomyopathy is a rare and a severe form of heart failure that affects women during pregnancy or shortly after delivery. Risk factors include advanced age, race, multiparity, multifetal pregnancy, socioeconomic disparity, and medical comorbidities including systemic hypertension, diabetes, asthma, and anemia. Peripartum cardiomyopathy is associated with increased morbidity and mortality, as well as a detrimental long-term impact on quality of life. Its etiology is not clear, although it is thought to be a combined effect of a hyperdynamic fluid state associated with pregnancy, hormonal changes unique to gestation, and a genetic predisposition. There is no current expert consensus on an optimal treatment regimen. This article will provide a comprehensive review and update on this important disease state.

Pulmonary hypertension in left heart disease (PH-LHD) commonly complicates prolonged heart failure (HF). When advanced, the PH becomes fixed or out of proportion and is associated with increased morbidity and mortality in patients undergoing orthotopic heart transplant (OHT). To date, the only recommended treatment of out of proportion PH is the treatment of the underlying HF by reducing the pulmonary capillary wedge pressure (PCWP) with medications and often along with use of mechanical circulatory support. Medical therapies typically used in the treatment of World Health Organization (WHO) group 1 pulmonary arterial hypertension (PAH) have been employed off-label in the setting of PH-LHD with varying efficacy and often negative outcomes. We will discuss the current standard of care including treating HF and use of mechanical circulatory support. In addition, we will review the studies published to date assessing the efficacy and safety of PAH medications in patients with PH-LHD being considered for OHT.

Background: To describe baseline characteristics and outcomes in the largest known registry of advanced heart failure (HF) patients receiving continuous outpatient intravenous inotrope therapy. Studies evaluating the use of outpatient inotropes for palliation or as a bridge to advanced therapies were performed before current guideline directed medical and device therapy (GDMDT). There are limited data on the modern experience using outpatient inotrope (OI) therapy. Study Question: We aimed to study current use and outcomes of OI. Study Design: Retrospective database analysis. Measures and Outcomes: From 2015 to 2017, 1540 advanced HF patients in a largess nationwide registry received OI with either milrinone or dobutamine. Baseline characteristics of 1149 patients data were retrospectively reviewed. Unadjusted Kaplan–Meier survival estimates censored at the time of transplant or mechanical circulatory support were reported. Results: Of 1149 patients, more patients were treated with milrinone than dobutamine (64.6% vs. 35.4%). Regardless of the indication for OI, estimated 1 and 2-years survival was 61.8% and 41.6%, respectively. Milrinone use was associated with a greater 1-year survival than dobutamine (70.7% vs. 46.2%, P < 0.0001). The superiority of milrinone over dobutamine extended to all indications for OI, including bridge to transplant (85.9% vs. 71.3%, P < 0.0001), bridge to mechanical support (91.4% vs. 71%, P = 0.001), and palliation (73.6% vs. 63.3%, P < 0.001). After adjusting for indication, age, gender and weight, milrinone was associated with lower mortality than dobutamine (HR 0.50, 95% CI 0.39–0.64, P < 0.0001). Conclusions: In the largest dataset of HF patients receiving OI, survival on OI for palliation in the current era of GDMDT is significantly higher than previously reported. Compared with dobutamine, milrinone was associated with improved survival in all cohorts.

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The need for noninvasive biomarkers for diagnostic, prognostic, and therapeutic purposes is increasingly being recognized in the field of heart transplantation. MicroRNAs are a class of novel biomarkers that control gene expression and influence cellular functions, including differentiation, proliferation, and functional regulation of the immune system. They can be detected in the serum, plasma, and urine and may serve as early noninvasive biomarkers for various disease processes. Despite significant advances in heart transplantation, challenges remain in the short and long term with early graft injury and dysfunction, both cellular and antibody-mediated rejection, infections of varying types and severity, and cardiac allograft vasculopathy, which require an interventional approach for diagnosis and management. In this article, we review the current knowledge on the role of microRNAs in heart transplantation and its related complications and discuss their potential impact in future strategies to manage heart transplantation.

Mineralocorticoid receptor antagonists (MRAs) are known to have a proven mortality benefit in heart failure with reduced ejection fraction (HFrEF) without kidney disease. As patients with end-stage renal disease (ESRD) requiring either peritoneal dialysis or hemodialysis were excluded in clinical trials of HFrEF, the data are scant on the appropriate use of MRAs in this population. The unknown efficacy, along with concerns of adverse effects such as hyperkalemia, has limited the willingness of clinicians to consider using MRAs in these patients. However, it is unclear whether the risk of hyperkalemia is present if a patient is oliguric or anuric. Current guidelines recommend against the use of MRAs in patients with chronic kidney disease, but do not address the use of MRAs in patients requiring dialysis. This article will review the epidemiology of heart failure in ESRD, the pathophysiological derangements of the renin–angiotensin–aldosterone system in patients with kidney disease, and the results from case series and trials of the use of MRAs in ESRD with HFrEF. Although limited to several small trials using MRAs in peritoneal and hemodialysis patients with or without HFrEF, the current literature appears to show the potential for clinical benefits with little risk.