Cardiorenal syndrome (CRS) is a complex disease in which the heart and kidneys are simultaneously affected, and subsequently, the malfunction of one organ promotes the deterioration of the other. Heart failure (HF) with preserved ejection fraction (HFpEF) is the most common form of HF. The pathophysiology of CRS is not well known and several mechanisms have been proposed. An elevation of central venous pressure seems to be one of the key points to consider, among others such as an increase in intraabdominal pressure. Several diagnostic tools have been identified to establish the diagnosis of CRS in patients with HFpEF. Currently, the availability of biomarkers of renal and cardiac injury, the use of pulmonary ultrasound, the monitoring of the size of the inferior vena cava and the study of the renal venous pattern offer a new dimension in accurately diagnosing and quantifying organ damage in CRS. Beyond the symptomatic treatment of congestion, until recently specific therapeutic tools for patients with CRS and HFpEF were not available. Interestingly, the development of new drugs such as the angiotensin/neprilysin inhibitors and sodium-glucose cotransporter-2 (SGLT-2) inhibitors offer new therapeutic strategies with potential benefits in reduction of cardiorenal adverse outcomes in this population. Randomized clinical trials that focus on patients with HFpEF are currently ongoing to delineate optimal new treatments that may be able to modify their prognosis. In addition, multidisciplinary teamwork (nephrologist, cardiologist and nurse) is expected to decrease the number of visits and the rate of hospitalizations, with a subsequent patient benefit.

Heart transplantation (HT) is the gold standard therapy for advanced heart failure (ADHF), and LVADs as destination therapy are an option in non-HT candidates. Most patients with ADHF never receive HT or an LVAD, so alternative strategies are needed. Intermittent levosimendan can reduce HF hospitalizations in ADHF patients in the short term. It is uncertain whether the results of the comparison of inotropes with older-generation LVADs would have the same outcomes in the current era of ADHF patients treated with levosimendan, who are less sick but older. In this paper, we compare the use of two therapeutic strategies for end-stage HF in patients who are not candidates for HT: repetitive intermittent levosimendan vs. LVAD as destination therapy. To do so, we compare two multicenter cohorts of real-life patients from Spain: the LEVO-D registry and the REGALAD registry. In total, 715 patients coming from the two registries were found: 403 from LEVO-D and 312 from REGALAD. Non-adjusted median survival was shorter for LEVO-D patients, with the benefit for the LVADs seen only after the first year of therapy. The survival advantage for the LVAD cohort was also true after analysis of the matched cohort but, as in the non-matched analysis, the survival benefit was mainly shown after one year of follow-up. We conclude that in elderly ADHF non-HT candidates, LVAD therapy offers significantly better long-term outcomes when compared to intermittent levosimendan; thus, it should be considered in carefully selected candidates. On the other hand, in poor LVAD candidates or highly comorbid patients, intermittent inotropic support with levosimendan could be a reasonable alternative to LVAD, as 1-year outcomes are similar.

Heart transplantation (HT) is the gold standard therapy for advanced heart failure (AHF) and LVAD as destination therapy are an option in non-HT candidates. Most patients with AHF never receive a HT or a LVAD, so alternative strategies are needed. Intermittent levosimendan can reduce HF hospitalizations in AHF patients in the short term. It is uncertain whether the results of the comparison of inotropes with older generation LVAD would have the same outcomes in the current era of less sick but older, AHF treated with levosimendan patients. In this paper we compare the use of two therapeutic strategies for end-stage HF in patients not candidates for HT: Repetitive intermittent Levosimendan vs. LVAD as destination therapy. To do so we compare two multicentre cohorts of real-life patients from Spain: the LEVO-D Registry and the REGALAD registry. 715 patients coming from the 2 registries where found, 403 from the LEVO-D and 312 from the REGALAD. Non-adjusted median survival was shorter for LEVO-D patients; with the benefit for the LVAD seen only after the first year of therapy. The survival advantage for the LVAD cohort was also true after analysis of the matched cohort but, as in the non-matched analysis, the survival benefit was mainly shown after one year of follow up. We conclude that in elderly AHF non-HT-candidates, LVAD therapy offers significantly better long-term outcomes when compared to intermittent levosimendan; thus, it should be considered in carefully selected candidates. On the other hand, in poor LVAD candidates or highly comorbid patients, intermit-tent inotropic support with levosimendan could be a reasonable alternative to LVAD as 1-year outcomes are similar.