Levosimendan in Acute and Advanced Heart Failure: an Expert Perspective on Posology and Therapeutic Application.

Levosimendan, a calcium sensitizer and potassium channel-opener, is widely appreciated by many specialist heart failure practitioners for its effects on systemic and pulmonary hemodynamics and for the relief of symptoms of acute heart failure. The drug's impact on mortality in large randomized controlled trials has been inconsistent or inconclusive but, in contrast to conventional inotropes, there have been no indications of worsened survival and some signals of improved heart failure-related quality of life. For this reason, levosimendan has been proposed as a safer inodilator option than traditional agents in settings, such as advanced heart failure. Positive effects of levosimendan on renal function have also been described. At the HEART FAILURE 2018 congress of the Heart Failure Association of the European Society of Cardiology, safe and effective use levosimendan in acute and advanced heart failure was examined in a series of expert tutorials. The proceedings of those tutorials are summarized in this review, with special reference to advanced heart failure and heart failure with concomitant renal dysfunction. Meta-analysis of clinical trials data is supportive of a renal-protective effect of levosimendan, while physiological observations suggest that this effect is exerted at least in part via organ-specific effects that may include selective vasodilation of glomerular afferent arterioles and increased renal blood flow, with no compromise of renal oxygenation. These lines of evidence require further investigation and their clinical significance needs to be evaluated in specifically designed prospective trials.

Repetitive use of levosimendan for treatment of chronic advanced heart failure: clinical evidence, practical considerations, and perspectives: an expert panel consensus.

BACKGROUND: The intravenous inodilator levosimendan was developed for the treatment of patients with acutely decompensated heart failure. In the last decade scientific and clinical interest has arisen for its repetitive or intermittent use in patients with advanced chronic, but not necessarily acutely decompensated, heart failure. Recent studies have suggested long-lasting favourable effects of levosimendan when administered repetitively, in terms of haemodynamic parameters, neurohormonal and inflammatory markers, and clinical outcomes. The existing data, however, requires further exploration to allow for definitive conclusions on the safety and clinical efficacy of repetitive use of levosimendan. METHODS AND RESULTS: A panel of 30 experts from 15 countries convened to review and discuss the existing data, and agreed on the patient groups that can be considered to potentially benefit from intermittent treatment with levosimendan. The panel gave recommendations regarding patient dosing and monitoring, derived from the available evidence and from clinical experience. CONCLUSIONS: The current data suggest that in selected patients and support out-of-hospital care, intermittent/repetitive levosimendan can be used in advanced heart failure to maintain patient stability. Further studies are needed to focus on morbidity and mortality outcomes, dosing intervals, and patient monitoring. Recommendations for the design of further clinical studies are made.

Congo red-positive cardiac kappa-AL amyloidosis in plasmacytoma -- case report and review of the literature.

We report on a 51-year-old female patient who was diagnosed in 2001 as suffering from plasmacytoma. The patient had had complaints of bilateral carpal tunnel syndrome in 1999, treated by a simple dissection without performing histological examination. Congestive heart failure had gradually developed since that time. In 2001 echocardiography revealed a pronounced thickening of the left ventricular wall with systolic and diastolic dysfunction. A kappa-light chain M component and kappa-light chain-restricted bone marrow plasmacytosis were detected. Amyloid deposits staining positive in the kappa-light chain-restriction analysis were observed in a gastric biopsy. Taking into consideration all these findings, a plasmacytoma-associated systemic AL amyloidosis was diagnosed. Cyclophosphamide/prednisolone chemotherapy regimen led to complete haematological remission. Cardiac transplantation, combined with autologous peripheral blood stem cell graft, was considered as the next therapeutic step, but the patient died while on the waiting list for transplantation. Autopsy detected a highly hypertrophic myocardium with narrowed heart cavities. Microscopic examination revealed dense, pink, acellular, Congo red-staining and kappa-immunoperoxidase-positive AL amyloid masses splitting the cardiomyocytes. The present case is remarkable as it demonstrates that carpal tunnel syndrome and congestive heart failure could be symptoms of plasma cell dyscrasia-associated amyloidoses.

[Rational cardiologic diagnosis after cerebral ischemic event]. / Rationelle kardiologische Diagnostik nach zerebralem ischämischen Ereignis.

Stroke continues to be a serious socioeconomic problem in the industrialized countries. The three disease processes responsible for most ischemic cerebrovascular events (CVE) are large-vessel and small-vessel atherothrombotic disease and, in up to 20-30% of cases, cardiac embolism. Data from the literature show that life expectancy after CVE is mainly dependent on the coexistence of cardiac disease. It is the responsibility of the cardiologist to exclude or identify the source of cardiac embolism and to initiate adequate treatment for the prevention of recurrences, as well as to diagnose, and treat any concomitant cardiac disease which may be present. We propose a cost-effective algorithmic approach to help the cardiologist in the diagnosis and treatment of patients with transient ischemic attacks and ischemic stroke.