Mattia Arrigo

Current management of patients with severe acute peripartum cardiomyopathy: practical guidance from the Heart Failure Association of the European Society of Cardiology Study Group on peripartum cardiomyopathy

Johann Bauersachs1,†,*, Mattia Arrigo2,3,†, Denise Hilfiker-Kleiner1, Christian Veltmann1, Andrew J.S. Coats4, Maria G. Crespo-Leiro5, Rudolf A. De Boer6, Peter van der Meer6, Christoph Maack7, Frederic Mouquet8, Mark C. Petrie9, Massimo F. Piepoli10, Vera Regitz-Zagrosek11, Maria Schaufelberger12, Petar Seferovic13, Luigi Tavazzi14, Frank Ruschitzka3, Alexandre Mebazaa15, and Karen Sliwa16 1Department of Cardiology and Angiology, Medical School Hannover, Hannover, Germany; 2Department of Cardiology, AP-HP, Lariboisière University Hospital, Paris, France; 3Department of Cardiology, University Heart Center, University Hospital Zurich, Zurich, Switzerland; 4Monash-Warwick Alliance, Monash University, Australia, and University of Warwick, UK; 5Cardiology Service, Complexo Hospitalario Universitario A Coruña, La Coruña, Spain; 6Department of Cardiology, University Medical Center Groningen, Groningen, The Netherlands; 7Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg, Germany; 8Department of Cardiology, Polyclinique du Bois, Lille, France; 9Department of Cardiology, Golden Jubilee National Hospital and Glasgow University, Glasgow, UK; 10Department of Cardiology, Guglielmo da Saliceto Hospital, Piacenza, Italy; 11Institute of Gender in Medicine, Charité Universitaetsmedizin Berlin, and German Center for Cardiovascular Research, Berlin, Germany; 12Section of Acute and Cardiovascular Medicine, Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Sahlgrenska University Hospital/Östra, Gothenburg, Sweden; 13University Medical Center, Belgrade, Serbia; 14Maria Cecilia Hospital, Gruppo Villa Maria Care and Research, Ettore Sansavini Health Science Foundation, Cotignola, Italy; 15Department of Anesthesiology and Critical Care Medicine, AP-HP, Saint Louis Lariboisière University Hospitals, Paris, France; and 16Hatter Institute for Cardiovascular Research in Africa & IDM, Inter-Cape Heart Group, Medical Research Council South Africa, Department of Medicine, University of Cape Town, Cape Town, South Africa

Management of Atrial Fibrillation in Critically Ill Patients

Atrial fibrillation (AF) is common in ICU patients and is associated with a two- to fivefold increase in mortality. This paper provides a reappraisal of the management of AF with a special focus on critically ill patients with haemodynamic instability. AF can cause hypotension and heart failure with subsequent organ dysfunction. The underlying mechanisms are the loss of atrial contraction and the high ventricular rate. In unstable patients, sinus rhythm must be rapidly restored by synchronised electrical cardioversion (ECV). If pharmacological treatment is indicated, clinicians can choose between the rate control and the rhythm control strategy. The optimal substance should be selected depending on its potential adverse effects. A beta-1 antagonist with a very short half-life (e.g., esmolol) is an advantage for ICU patients because the effect of beta-blockade on cardiovascular stability is unpredictable in those patients. Amiodarone is commonly used in the ICU setting but has potentially severe cardiac and noncardiac side effects. Digoxin controls the ventricular response at rest, but its benefit decreases in the presence of adrenergic stress. Vernakalant converts new-onset AF to sinus rhythm in approximately 50% of patients, but data on its efficacy and safety in critically ill patients are lacking.

Understanding the differences among inotropes

Inotropes are indicated to restore cardiac output (CO) in the presence of signs of tissue hypoperfusion despite optimization of volume status, oxygenation and haematocrit level. Inotropes, especially catecholamines, cannot be widely used as they are associated with numerous and frequent shortand long-term adverse events. However, despite clear indications by the most prominent international societies of intensive care and cardiology to restrict their use, the current use of catecholamines is very frequent [1]. The 2012 European Society of Cardiology (ESC) Heart Failure Guidelines and the 2014 European Society of Intensive Care Medicine (ESICM) Consensus on shock recommend that ‘‘inotropic agents should be added when the altered cardiac function is accompanied by a low or inadequate CO and signs of tissue hypoperfusion persist after preload optimization’’ (Level 2; QoE low) [2]. Furthermore, the 2014 ESICM Consensus on shock indicated that evaluation of CO and cardiac function, by any means, becomes crucial when deciding on whether inotropic agents have a place in the therapy of a given patient and in evaluating the haemodynamic impact of those therapeutic interventions [2]. We provide a brief overview on current and future inotropic agents with a special focus on the pharmacological and clinical characteristics of the different classes (Table 1). The ‘‘ideal’’ inotropic agent should improve stroke volume without increasing myocardial oxygen consumption or causing arrhythmias, should ameliorate diastolic function and upstream congestion, should have a short half-life so as to be easily titratable and should have positive effects on long-term outcome. The ‘‘ideal’’ agent has not yet been found.

Acutely decompensated heart failure with preserved and reduced ejection fraction present with comparable haemodynamic congestion

Congestion is a central feature of acute heart failure (HF) and its assessment is important for clinical decisions (e.g. tailoring decongestive treatments). It remains uncertain whether patients with acute HF with preserved ejection fraction (HFpEF) are comparably congested as in acute HF with reduced EF (HFrEF). This study assessed congestion, right ventricular (RV) and renal dysfunction in acute HFpEF, HFrEF and non‐cardiac dyspnoea.

Bromocriptine for the treatment of peripartum cardiomyopathy: welcome on BOARD

Peripartum cardiomyopathy (PPCM), according to the actual definition proposed by the Study Group on PPCM of the Heart Failure Association of the European Society of Cardiology (ESC), is an idiopathic cardiomyopathy frequently presenting with left ventricular (LV) systolic dysfunction (LV ejection fraction <45%) towards the end of pregnancy or in the months following delivery in the absence of other causes. The most common clinical presentation consists of acute heart failure (AHF) occurring in the first weeks after delivery. The worldwide burden of PPCM is estimated based on singlecentre case series from Haiti, South Africa, and the USA showing incidences ranging from 1:3000 to 1:100 pregnancies. Women of African origin display a significantly higher risk of developing PPCM. The clinical outcome of women with PPCM seems to vary across the world, probably because of differences in ethnic and social factors and access to AHF treatment, but also due to heterogeneity in the inclusion criteria in the studies. Accordingly, reported mortality rates may vary from <5% up to 50%. Moreover, despite the fact that several publications reported rapid recovery of LV function (within 6 months after diagnosis) in the majority of patients, other studies reported delayed LV recovery in a significant proportion of patients. Notably, Afro-American women showed lower rates of recovery and worse prognosis compared with Caucasians. New insights into the epidemiology and outcome of PPCM from the EURObservational Research Programme of the ESC may, however, suggest comparable outcome between European and non-European regions. The management of women presenting with AHF due to PPCM remains very challenging. The initial treatment depends on the time point of onset and the ability to have a diagnosis. Women presenting with PPCM during pregnancy require joint cardiac and obstetric care, because therapeutic interventions need always to consider the health of both the mother and the foetus. Women presenting after delivery can generally be treated according to the ESC Guidelines for heart failure. Very recently, the Study Group on PPCM of the Heart Failure Association of the ESC published a practical guidance paper on the management of acute PPCM patients. The treatment of post-partal AHF due to PPCM consist—similarly to other forms of AHF—of (i) decongestive treatment via vasorelaxing agents, diuretics, and non-invasive ventilation to improve symptoms and reduce organ dysfunction; (ii) neuro-humoral inhibition via oral heart failure therapies (e.g. beta-blockers, ACE inhibitors, and mineralocorticoid receptor antagonists) to improve LV recovery and outcome; and (iii) in selected patients, device therapy to reduce symptoms and improve outcome. Ideally, a specific pathophysiologydirected therapy should complete the treatment: for that purpose, knowledge of mechanisms involved in disease onset is required. The paper by Hilfiker-Kleiner et al. in this issue of the journal confirmed that PPCM should be treated with bromocriptine as specific aetiological therapy for PPCM. In recent years, multiple mechanisms, in addition to general cardiovascular risk and pregnancy-related factors, have been described as having a role in the aetiology of PPCM, albeit that the exact pathophysiology remains poorly understood. A ‘double-hit’ model of angiogenic imbalance in the heart during the peripartal period has been proposed, combining systemic antiangiogenic signals during late pregnancy and host susceptibility through insufficient local proangiogenic defences in the heart. Evidence of dysregulated plasma levels of proand antiangiogenic factors supports early diagnosis of PPCM. Angiogenic imbalance can further be triggered by oxidative stress activating cathepsin D, a protease responsible for the cleavage of the nursing hormone prolactin into the angiostatic and proapoptotic 16 kDa subfragment. In a previous mouse model, suppression of prolactin production prevented the onset of PPCM. Bromocriptine, a substance used for many years to stop lactation in post-partum women by suppressing prolactin production, was evaluated as adjunctive treatment of PPCM in a proof-of-concept clinical

Disappointing success of electrical cardioversion for new-onset atrial fibrillation in cardiosurgical ICU patients

Objectives: To assess the success of electrical cardioversion for the treatment of new-onset atrial fibrillation in critically ill patients and to evaluate the stability of sinus rhythm in responders during the subsequent 24 hours. Design: Retrospective study. Setting: Twelve-bed cardiosurgical ICU at a university hospital. Patients: Seventy-two consecutive patients with postoperative new-onset atrial fibrillation (< 7 d of duration) treated by electrical cardioversion. Interventions: Electrical cardioversion using synchronized biphasic shocks. Measurements and Main Results: During 144 electrical cardioversions, 209 shocks were delivered to 72 patients. Maximal energy (200 J) was used in 85% of shocks. Electrical cardioversion immediately restored sinus rhythm in 102 sessions (71%). Pretreatment with amiodarone did not increase the success rates. During the follow-up, the percentages of sinus rhythm decreased from 43% after 1 hour to 23% after 24 hours. However, at ICU discharge, 54 patients (75%) were in sinus rhythm. Of the 54 patients in sinus rhythm, only 18 (33%) converted to sinus rhythm after repeated cardioversions, whereas the remaining 36 (66%) did so spontaneously or with amiodarone. Conclusions: Biphasic electrical cardioversion in cardiosurgical ICU patients was immediately successful in restoring sinus rhythm in 71% of sessions. However, early relapse of atrial fibrillation was common in the 24-hour follow-up. At ICU discharge, the majority of patients were in sinus rhythm, but the efficacy of repetitive electrical cardioversion in restoring sinus rhythm was disappointing.

Soluble CD146 Is a Novel Marker of Systemic Congestion in Heart Failure Patients: An Experimental Mechanistic and Transcardiac Clinical Study.

BACKGROUND Soluble CD146 (sCD146), is an endothelial marker with similar diagnostic power as natriuretic peptides in decompensated heart failure (HF). While natriuretic peptides are released by the failing heart, sCD146 may be released by veins in response to stretch induced by systemic congestion in HF. This study investigated the source, effects of vascular stress on release and prognostic properties of sCD146 in HF. METHODS In a peripheral venous stress study, plasma concentrations of sCD146 and N-terminal probrain natriuretic-peptide (NT-proBNP) were measured in 44 HF patients at baseline and after 90 min of unilateral forearm venous congestion. In addition, sCD146 and NT-proBNP were measured in peripheral vein (PV) and coronary sinus (CS) blood samples of 137 HF patients and the transcardiac gradient was calculated. Those patients were followed for major adverse cardiovascular events (MACE) during 2 years. RESULTS The induction of venous stress was associated with a pronounced increase in circulating concentrations of sCD146 in the congested arm (+60 μg/L) compared to the control arm (+16 μg/L, P = 0.025), while no difference in NT-proBNP concentrations was seen. In contrast to positive transcardiac gradient for NT-proBNP, median sCD146 concentrations were lower in CS than in PV (396 vs 434, P < 0.001), indicating a predominantly extracardiac source of sCD146. Finally, increased PV concentrations of sCD146 were associated with higher risk of MACE at 2 years. CONCLUSIONS Soluble CD146 is released from the peripheral vasculature in response to venous stretch and may reflect systemic congestion in chronic HF patients.

The heart regulates the endocrine response to heart failure: cardiac contribution to circulating neprilysin

Aims Heart failure (HF) is accompanied by major neuroendocrine changes including the activation of the natriuretic peptide (NP) pathway. Using the unique model of patients undergoing implantation of the CARMAT total artificial heart and investigating regional differences in soluble neprilysin (sNEP) in patients with reduced or preserved systolic function, we studied the regulation of the NP pathway in HF. Methods and results Venous blood samples from two patients undergoing replacement of the failing ventricles with a total artificial heart were collected before implantation and weekly thereafter until post-operative week 6. The ventricular removal was associated with an immediate drop in circulating NPs, a nearly total disappearance of circulating glycosylated proBNP and furin activity and a marked decrease in sNEP. From post-operative week 1 onwards, NP concentrations remained overall unchanged. In contrast, partial recoveries in glycosylated proBNP, furin activity, and sNEP were observed. Furthermore, while in patients with preserved systolic function (n = 6), sNEP concentrations in the coronary sinus and systemic vessels were similar (all P > 0.05), in patients with reduced left-ventricular systolic function, sNEP concentration, and activity were ∼three-fold higher in coronary sinus compared to systemic vessels (n = 21, all P < 0.0001), while the trans-pulmonary gradient was neutral (n = 5, P = 1.0). Conclusion The heart plays a pivotal role as a regulator of the endocrine response in systolic dysfunction, not only by directly releasing NPs but also by contributing to circulating sNEP, which in turn determines the bioavailability of other numerous vasoactive peptides.

Plasma Levels of Soluble CD146 Reflect the Severity of Pulmonary Congestion Better Than Brain Natriuretic Peptide in Acute Coronary Syndrome

Background Acute heart failure negatively affects short-term outcomes of patients with acute coronary syndrome (ACS). Therefore, reliable and non-invasive assessment of pulmonary congestion is needed to select patients requiring more intensive monitoring and therapy. Since plasma levels of natriuretic peptides are influenced by myocardial ischemia, they might not reliably reflect congestion in the context of ACS. The novel endothelial biomarker, soluble CD146 (sCD146), presents discriminative power for detecting the cardiac origin of acute dyspnea similar to that of natriuretic peptides and is associated with systemic congestion. We evaluated the performance of sCD146 for the assessment of pulmonary congestion in the early phase of ACS. Methods One thousand twenty-one consecutive patients with ACS were prospectively enrolled. Plasma levels of sCD146, brain natriuretic peptide (BNP), and high-sensitive troponin T were measured within 24 hr after the onset of chest pain. Pulmonary congestion on chest radiography was determined and classified in three groups according to the degree of congestion. Results Nine hundred twenty-seven patients with ACS were analyzed. Ninety-two (10%) patients showed signs of pulmonary edema on chest radiography. Plasma levels of sCD146 reflected the radiological severity of pulmonary congestion. Higher plasma levels of sCD146 were associated with the worse degree of pulmonary congestion. In contrast to BNP, sCD146 levels were not affected by the level of troponin T. Conclusions The novel endothelial biomarker, sCD146, correlates with radiological severity of pulmonary congestion in the early phase of ACS and, in contrast to BNP, is not affected by the amount of myocardial cell necrosis.

East Asia may have a better 1-year survival following an acute heart failure episode compared with Europe: results from an international observational cohort: East Asia may have a better 1-year survival following an acute heart failure episode compared with Europe: results from an international observational

Acute heart failure (AHF) is a major health problem worldwide and trials to assess novel therapies are increasingly global, as a means to reduce costs, expedite timelines, provide broad applicability, and satisfy regulatory authorities.The significant geographic differences in patient characteristics, outcomes, and treatment effect may affect trial results and raise important questions about generalizability of the results to a broader population.