Circulating soluble fibroblast activation protein (FAP) levels are independent of cardiac and extra-cardiac FAP expression determined by targeted molecular imaging in patients with myocardial FAP activation.

INTRODUCTION: Tissue Fibroblast Activation Protein alpha (FAP) is overexpressed in various types of acute and chronic cardiovascular disease. A soluble form of FAP has been detected in human plasma, and low circulating FAP concentrations are associated with increased risk of death in patients with acute coronary syndrome. However, little is known about the regulation and release of FAP from fibroblasts, and whether circulating FAP concentration is associated with tissue FAP expression. This study characterizes the release of FAP in human cardiac fibroblasts (CF) and analyzes the association of circulating FAP concentrations with in vivo tissue FAP expression in patients with acute (ST-segment elevation myocardial infarction, STEMI) and chronic (severe aortic stenosis, AS) myocardial FAP expression. METHODS AND RESULTS: FAP was released from CF in a time- and concentration-dependent manner. FAP concentration was higher in supernatant of TGFß-stimulated CF, and correlated with cellular FAP concentration. Inhibition of metallo- and serine-proteases diminished FAP release in vitro. Median FAP concentrations of patients with acute (77 ng/mL) and chronic (75 ng/mL, p = 0.50 vs. STEMI) myocardial FAP expression did not correlate with myocardial nor extra-myocardial nor total FAP volume (P ≥ 0.61 in all cases) measured by whole-body FAP-targeted positron emission tomography. CONCLUSION: We describe a time- and concentration dependent, protease-mediated release of FAP from cardiac fibroblasts. Circulating FAP concentrations were not associated with increased in vivo tissue FAP expression determined by molecular imaging in patients with both chronic and acute myocardial FAP expression. These data suggest that circulating FAP and tissue FAP expression provide complementary, non-interchangeable information.

Cardiac amyloidosis-interdisciplinary approach to diagnosis and therapy.

The vast majority of cardiac amyloidosis (CA) cases are caused by light chain (AL) or transthyretin (ATTR) amyloidosis. The latter is divided into hereditary (ATTRv) and wild-type forms (ATTRwt). The incidence of ATTRwt amyloidosis has significantly increased, particularly due to the improved diagnosis of cardiac manifestations, with relevant proportions in patient populations with heart failure (HF) and preserved ejection fraction (HFpEF). Cardiac amyloidosis should be suspected in HF with indicative clinical scenarios/"red flags" with typical signs of CA in echocardiography. Further noninvasive imaging (cardiovascular magnetic resonance imaging, scintigraphy) and specific laboratory diagnostics are important for the diagnosis and typing of CA into the underlying main forms of ATTR and AL amyloidosis. The histopathologic analysis of an endomyocardial biopsy is necessary if noninvasive diagnostic methods do not enable reliable typing of CA. This is crucial for initiating specific therapy. Therapy of HF in CA is largely limited to the use of diuretics in the absence of evidence on the benefit of classic HF therapy with neurohormonal modulators. Innovative therapies have been developed for amyloidosis with improvement in organ protection, prognosis, and quality of life. These include specific cytoreductive therapies for monoclonal light-chain disease in AL amyloidosis and pharmacologic stabilization or inhibition of transthyretin expression in ATTR amyloidosis. Since the CA underlying amyloidosis is a systemic disease also affecting other organ systems, close interdisciplinary cooperation is crucial for rapid and effective diagnosis and therapy.

Diagnosis and treatment of cardiac amyloidosis: position statement of the German Cardiac Society (DGK).

Systemic forms of amyloidosis affecting the heart are mostly light-chain (AL) and transthyretin (ATTR) amyloidoses. The latter is caused by deposition of misfolded transthyretin, either in wild-type (ATTRwt) or mutant (ATTRv) conformation. For diagnostics, specific serum biomarkers and modern non-invasive imaging techniques, such as cardiovascular magnetic resonance imaging (CMR) and scintigraphic methods, are available today. These imaging techniques do not only complement conventional echocardiography, but also allow for accurate assessment of the extent of cardiac involvement, in addition to diagnosing cardiac amyloidosis. Endomyocardial biopsy still plays a major role in the histopathological diagnosis and subtyping of cardiac amyloidosis. The main objective of the diagnostic algorithm outlined in this position statement is to detect cardiac amyloidosis as reliably and early as possible, to accurately determine its extent, and to reliably identify the underlying subtype of amyloidosis, thereby enabling subsequent targeted treatment.

[Short version of the 2nd edition of the German-Austrian S3 guidelines "Cardiogenic shock complicating myocardial infarction-Diagnosis, monitoring and treatment"]. / Kurzversion der 2. Auflage der deutsch-österreichischen S3-Leitlinie "Infarkt-bedingter Kardiogener Schock ­ Diagnose, Monitoring und Therapie".

BACKGROUND: The present guidelines ( http://leitlinien.net ) focus exclusively on cardiogenic shock due to myocardial infarction (infarction-related cardiogenic shock, ICS). The cardiological/cardiac surgical and the intensive care medicine strategies dealt with in these guidelines are essential to the successful treatment and survival of patients with ICS; however, both European and American guidelines on myocardial infarction and heart failure and also position papers on cardiogenic shock focused mainly on cardiological aspects. METHODS: Evidence on the diagnosis, monitoring and treatment of ICS was collected and recommendations compiled in a nominal group process by delegates of the German Cardiac Society (DGK), the German Society for Medical Intensive Care Medicine and Emergency Medicine (DGIIN), the German Society for Thoracic and Cardiovascular Surgery (DGTHG), the German Society for Anaesthesiology and Intensive Care Medicine (DGAI), the Austrian Society for Internal and General Intensive Care Medicine (ÖGIAIM), the Austrian Cardiology Society (ÖKG), the German Society for Prevention and Rehabilitation of Cardiovascular Diseases (DGPR) and the German Interdisciplinary Association for Intensive Care and Emergency Medicine (DIVI), under the auspices of the Working Group of the Association of Medical Scientific Societies in Germany (AWMF). If only poor evidence on ICS was available, general study results on intensive care patients were inspected and presented in order to enable analogue conclusions. RESULTS: A total of 95 recommendations, including 2 statements were compiled and based on these 7 algorithms with defined instructions on the course of treatment.

Dilated cardiomyopathies and non-compaction cardiomyopathy.

Dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy and one of the most common causes of heart failure. It is characterized by left or biventricular dilation and a reduced systolic function. The causes are manifold and range from myocarditis to alcohol and other toxins, to rheumatological, endocrinological, and metabolic diseases. Peripartum cardiomyopathy is a special form that occurs at the end of or shortly after pregnancy. Genetic mutations can be detected in approximately 30-50% of DCM patients. Owing to the growing possibilities of genetic diagnostics, increasingly more triggering variants and hereditary mechanisms emerge. This is particularly important with regard to risk stratification for patients with variants with an increased risk of arrhythmias. Patient prognosis is determined by the occurrence of heart failure and arrhythmias. In addition to the treatment of the underlying disease or the elimination of triggering harmful toxins, therapy consists in guideline-directed heart failure treatment including drug and device therapy.

Left heart function in COPD : Impact of lung deflation.

Chronic obstructive pulmonary disease (COPD) primarily affects the lungs; however, cardiovascular conditions are among the most common extrapulmonary comorbidities. Besides shared risk factors such as cigarette smoking, pathophysiological connections between the lung and the heart have been identified as mediators of reduced cardiac output. Recent research has focused on hyperinflation of the lung as a pulmonary cause for heart dysfunction. Hyperinflation is a typical lung abnormality seen in COPD; it is characterized by increased residual volume, intrathoracic gas volume, and total lung capacity while vital capacity is decreased. The degree of hyperinflation with airway obstruction is inversely related to left ventricular filling, stroke volume, and cardiac output. The underlying mechanisms are assumed to be compression of the pulmonary veins and thus reduced preload of the left heart as well as decreased pulmonary microvascular blood flow due to compression of the pulmonary vasculature. Treatment with a dual bronchodilator antagonizes this detrimental lung-heart unbalance effectively: Pulmonary blood flow, left ventricular end-diastolic volume, and stroke volume increase in COPD patients without cardiac abnormalities. Similar effects, yet less pronounced, were reported with single bronchodilator therapy. Future work needs to investigate whether these promising findings can be reproduced in COPD patients with cardiovascular diseases.

[Oral anticoagulation and antiplatelet therapy in patients with atrial fibrillation after coronary interventions]. / Orale Antikoagulation und antithrombozytäre Therapie bei Patienten mit Vorhofflimmern nach Koronarintervention.

Dual antiplatelet therapy (DAPT) is the cornerstone of maintenance medication following elective percutaneous coronary intervention and also after acute coronary syndrome (ST-elevation myocardial infarction, non-ST-elevation myocardial infarction, unstable angina pectoris); however, DAPT is not sufficient for stroke prevention in atrial fibrillation (SPAF). For SPAF, oral anticoagulation (OAC) with vitamin K antagonists (VKA) or non-vitamin K-dependent anticoagulants (NOAC) is required. If a patient who is receiving anticoagulants for SPAF, requires a coronary intervention, triple therapy consisting of OAC plus DAPT is given, at least for a limited time following the procedure. This article reviews the current data from studies testing strategies with NOACs plus one or two antiplatelet substances in comparison to triple therapy with VKA.

Multimodal Elimination for Intoxication with a Lethal Dose of Organic Mercury.

We here report on a case of massive organic mercury intoxication in a 40-year-old man that resulted in progressive multiorgan failure. We treated the patient intravenously and enterally with the chelating agent (RS)-2,3-bis(sulfanyl) propane-1-sulfonic acid (DMPS) in addition to hemodialysis. The patient was treated for 6 weeks and could successfully be weaned from mechanical ventilation and hemodialysis. He awoke and was sent to rehabilitation, but unfortunately died 7 months later from refractory status epilepticus. Autopsy revealed severe brain atrophy consistent with organ damage from massive mercury intoxication. The present case illustrates that bimodal DMPS application is sufficient for detoxification from lethal mercury levels, with an associated chance for weaning of organ support and survival to discharge. The case further reminds us of intoxication as a cause of multiorgan dysfunction. We propose to immediately initiate combined parenteral and enteral detoxification in cases of methyl mercury intoxication, especially in cases of high doses.

Key inflammatory mechanisms underlying heart failure.

Inflammation plays a central role in the development of heart failure, especially in heart failure with preserved ejection fraction (HFpEF). Furthermore, the inflammatory response enables the induction of regenerative processes following acute myocardial injury. Recent studies in humans and animals have greatly advanced our understanding of the underlying mechanisms behind these adaptations. Importantly, inflammation can have both beneficial and detrimental effects, dependent on its extent, localization, and duration. Therefore, modulation of cardiac inflammation has been suggested as an attractive target for the treatment of heart failure, which has been investigated in numerous clinical trials. This review discusses key inflammatory mechanisms contributing to the pathogenesis of heart failure and their potential impact as therapeutic targets.

The prognostic significance of the 12-lead ECG in peripartum cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is an important cause of pregnancy-associated heart failure, which appears in previously healthy women towards the end of pregnancy or within five months following delivery. Although the ECG is widely used in clinical practice, its prognostic value has not been established in PPCM. METHODS: We analysed 12-lead ECGs of patients with PPCM, taken at index presentation and follow-up visits at 6 and 12 months. Poor outcome was determined by the composite endpoint of death, readmission, NYHA functional class III/IV or left ventricular ejection fraction (LVEF) of ≤35% at follow-up. RESULTS: This cohort of 66 patients had a median age of 28.59 (IQR 25.43-32.19). The median LVEF at presentation (33%, IQR 25-40) improved significantly at follow-up (LVEF 49%, IQR 38-55, P < 0.001 at 6 months; 52% IQR 38-57, P = 0.001 at 12 months). Poor outcome occurred in 27.91% at 6 months and 41.18% at 1 year. Whereas sinus tachycardia at baseline was an independent predictor of poor outcome at 12 months (OR 6.56, 95% CI 1.17-20.41, P = 0.030), sinus arrhythmia was associated with event free survival (log rank P = 0.013). T wave inversion was associated with an LVEF ≤35% at presentation (P = 0.038), but did not predict poor outcome. A prolonged QTc interval at presentation (found in almost half of the cohort) was an independent predictor of poor outcome at 6 months (OR 6.34, 95% CI 1.06-37.80, P = 0.043). CONCLUSION(S): A prolonged QTc and sinus tachycardia at baseline were independent predictors of poor outcome in PPCM at 6 months and 1 year respectively.

[Update of the ESC guidelines 2018 on cardiovascular diseases during pregnancy : Most important facts]. / Update 2018 der ESC-Leitlinie zu kardiovaskulären Erkrankungen in der Schwangerschaft : Die wichtigsten Fakten.

Heart diseases are the most common cause of maternal death during pregnancy in Western countries. The current ESC guidelines 2018 for the management of cardiovascular diseases during pregnancy is a guide for any physician facing the challenge of caring for pregnant women with cardiovascular diseases. Among the new concepts compared to 2011, are recommendations to classify maternal risk due to the modified World Health Organization (mWHO) classification, introduction of the pregnancy heart team, guidance on assisted reproductive therapy, specific recommendations on anticoagulation for low-dose and high-dose requirements of vitamin K antagonists and the potential use of bromocriptine in peripartum cardiomyopathy. The Food and Drug Administration (FDA) categories A-D and X should no longer be used. Therefore, the table of drugs was completed with detailed information from animal and human studies on maternal and fetal risks. The new findings on specific heart diseases are presented in detail in the respective chapters.

[Recommendations for extracorporeal cardiopulmonary resuscitation (eCPR) : Consensus statement of DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI and GRC]. / Empfehlungen zur extrakorporalen kardiopulmonalen Reanimation (eCPR) : Konsensuspapier der DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI und GRC.

Extracorporeal cardiopulmonary resuscitation (eCPR) may be considered as a rescue attempt for highly selected patients with refractory cardiac arrest and potentially reversible etiology. Currently there are no randomized, controlled studies on eCPR, and valid predictors of benefit and outcome which might guide the indication for eCPR are lacking. Currently selection criteria and procedures differ across hospitals and standardized algorithms are lacking. Based on expert opinion, the present consensus statement provides a proposal for a standardized treatment algorithm for eCPR.

[Recommendations for extracorporeal cardiopulmonary resuscitation (eCPR) : Consensus statement of DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI and GRC]. / Empfehlungen zur extrakorporalen kardiopulmonalen Reanimation (eCPR) : Konsensuspapier der DGIIN, DGK, DGTHG, DGfK, DGNI, DGAI, DIVI und GRC.

Extracorporeal cardiopulmonary resuscitation (eCPR) may be considered as a rescue attempt for highly selected patients with refractory cardiac arrest and potentially reversible etiology. Currently there are no randomized, controlled studies on eCPR, and valid predictors of benefit and outcome which might guide the indication for eCPR are lacking. Currently selection criteria and procedures differ across hospitals and standardized algorithms are lacking. Based on expert opinion, the present consensus statement provides a proposal for a standardized treatment algorithm for eCPR.

Current drug therapy for heart failure with reduced ejection fraction.

The prevalence of heart failure has been steadily increasing during the past few years, with a further increase predicted in the years to come. Without treatment, the syndrome of heart failure has a very poor prognosis. Advances in drug treatments and the consequent implementation of a guideline-recommended drug therapy have significantly improved the prognosis in heart failure with reduced ejection fraction (HFrEF). Besides angiotensin-converting enzyme (ACE) inhibitors (ACEi) or angiotensin receptor blockers, beta-blockers and diuretics treatment with mineralocorticoid receptor antagonists and ivabradine have become standard in the therapy of symptomatic patients with HFrEF. Recently, the impact of the adequate dosage of ACEi and beta-blockers was emphasized again. Angiotensin receptor-neprilysin inhibition is an auspicious new therapeutic approach and is predicted to play a crucial role in heart failure treatment in the coming years. The role of cardiac glycosides in the modern era of heart failure therapy is the focus of a current randomized controlled trial. Last but not least, potassium binders such as the new substance patiromer might help in overcoming the problem of hyperkalemia, which frequently limits the dosing of vital heart failure drugs. These advances offer optimism for further improvements in the prognosis and quality of life of HFrEF patients.

Peripartum cardiomyopathy.

Peripartum cardiomyopathy (PPCM) is a rare and potentially life-threatening disease that occurs toward the end of pregnancy or in the months following delivery in previously heart-healthy women. The incidence varies widely depending on geographical region and ethnic background, with an estimated number of 1 in 1000-1500 pregnancies in Germany. The course of the disease ranges from mild forms with minor symptoms to severe forms with acute heart failure and cardiogenic shock. The understanding of the etiology of PPCM has evolved in recent years. An oxidative stress-mediated cleaved 16-kDa fragment of the nursing hormone prolactin is thought to damage endothelial cells and cardiomyocytes. Bromocriptine, a dopamine-receptor agonist, effectively blocks prolactin release from the pituitary gland. In addition to standard heart failure therapy, this disease-specific treatment reduces morbidity and mortality in PPCM patients. This review summarizes the current knowledge on PPCM and the disease-specific treatment options.

Drug treatment of heart failure in the elderly.

The prevalence of heart failure increases with age. Changes in the age distribution and growing life expectancy will lead to a further rise. However, data concerning drug treatment of heart failure especially in the elderly are scarce. Subgroup analyses of the heart failure trials suggest that drug therapy in older patients should follow the recommendations in the current guidelines. In doing so, several common comorbidities in these patients (e. g., impaired renal function) have to be considered and may have an influence on the therapy (e. g., drug dose, choice of active pharmaceutical ingredient, etc.). Especially in old, multimorbid patients, possible interaction of drugs might play a substantial role. In many cases the main goal of the therapy, especially in the very elderly, is to improve symptoms and quality of life.