Auftreten potentiell lebensbedrohlicher ventrikulärer Arryhthmien nach ICD-Implantation bei Patienten mit bioptisch gesicherter Myokarditis

Einleitung: Das klinische Bild einer viralen Myokarditis reicht von inapperenten bis hin zu akut-fulminanten Krankheitsverläufen, die in der Folge völlig ausheilen oder chronisch-progredient bis zum Vollbild einer dilatativen Kardiomyopathie (DCM) voranschreiten können. Lebensbedrohliche Arrhythmien, wie z.B. ventrikuläre Tachykardien als auch eine hochgradig eingeschränkte linksventrikuläre Pumpfunktion können den Verlauf komplizieren, so dass eine Implantation eines „Implanted Cardioverter Defibrillators“ (ICD) zur Primär- und Sekundärprophylaxe eines plötzlichen Herztodes notwendig werden kann. Bisher liegen keine ausreichenden Daten über das Auftreten von lebensbedrohlichen Herzrhythmusstörungen bei Patienten mit Myokarditis im Langzeitverlauf vor. Die vorliegende Studie untersucht daher die Notwendigkeit einer ICD-Implantation sowie das Auftreten von therapiebedürftigen ventrikulären Arrhythmien nach ICD-Implantation bei Patienten mit Herzmuskelentzündung. Methodik und Ergebnisse: Zwischen 2000-2016 wurden 191 Patienten (mittleres Alter 43±13 Jahren, 71% männlich, linksventrikuläre Ejektionsfraktion 33±15%) mit den klinischen Kriterien für das Vorliegen einer viralen Myokarditis prospektiv über einen Zeitraum von 6,9 (4,1-13) Jahre nachverfolgt. Bei allen Patienten wurde eine Endomyokardbiopsie (EMB) zur Diagnosestellung durchgeführt. Als primärer Endpunkt der Studie wurde die Notwendigkeit einer primärprophylaktischen oder sekundärprophylaktischen ICD-Implantation definiert. Das Auftreten von ventrikulären Arrhythmien, die durch den ICD terminiert werden mussten, und das Eintreten eines kardialen Todes sowie die Notwendigkeit einer Herztransplantation stellten die sekundären Studienendpunkte dar. Entsprechend den Ergebnissen der EMB zeigte sich bei 96 Patienten (50,3%) eine chronische Myokarditis, bei 10 Patienten (5,2%) eine akute Myokarditis und bei 85 Patienten (44,5%) eine DCM. Eine ICD-Implantation erfolgte bei 58 der Erkrankten (30,4%) 4,4 (0,5-47,2) Monate nach EMB. Patienten mit chronischer Myokarditis erhielten 3,8 (1,6-35,3) Monate nach EMB einen ICD zur Primärprophylaxe und damit signifikant früher als Patienten mit einer DCM (27 (2-50,4) Monate nach EMB; p=0,045). Bei 29 der 58 ICD-Patienten (50%) wurden therapiebedürftige ventrikuläre Arrhythmien im Verlauf nachgewiesen. Dabei trat die erste Arrhythmie 13,7 (2,3-37) Monate nach EMB auf. Die Inzidenz ventrikulärer Arrhythmien betrug bei Patienten mit einer bioptisch nachgewiesenen myokardialen Entzündungsreaktion 59% und war gegenüber Patienten mit einer DCM (41%) nicht signifikant erhöht. Innerhalb des ersten Jahres nach EMB wurden therapiebedürftige ventrikuläre Arrhythmien nur bei Patienten mit nachgewiesener myokardialer Inflammation verzeichnet. Insgesamt traten in den ersten 12 Monaten nach EMB 38 lebensbedrohliche ventrikuläre Arrhythmien bei 7 Patienten mit Myokarditis (12,1%, n=58) auf, die durch den ICD terminiert werden mussten. Patienten mit DCM blieben in dieser Zeit frei von ventrikulären Arrhythmien (p=0,019). Die erste therapiebedürftige ventrikuläre Arrhythmie wurde bei Patienten mit DCM nach 19 Monaten detektiert. Schlussfolgerung: Etwa ein Drittel der eingeschlossenen Patienten entwickelten die Indikation zur primär- oder sekundärprophylaktischen ICD-Implantation im Studienverlauf. Der Nachweis einer chronischen myokardialen Inflammation ging mit der Notwendigkeit einer signifikant früheren primärprophylaktischen ICD-Implantation einher. Im ersten Jahr nach EMB traten behandlungsbedürftige ventrikuläre Arrhythmien ausschließlich bei Patienten mit bioptisch gesicherter Myokarditis auf. Die myokardiale Entzündungsreaktion muss daher als richtungsweisender prognostischer Parameter für das frühzeitige Einsetzen von ventrikulären Arrhythmien diskutiert werden.Introduction: Viral myocarditis may appear as a clinically inapparent or as an acute-fulminant disease from which patients completely recover or which progresses chronically, eventually leading to DCM. At any time of the disease, life-threatening ventricular arrhythmias and severe impairment of left ventricular function can occur, subsequently requiring a primary or secondary ICD-implantation to prevent patients from sudden cardiac death. Studies on the occurrence of life-threatening ventricular arrhythmias during long-term follow-up in patients with myocarditis have not been conducted yet. Therefore, this study investigates the need of ICD-implantation and occurrence of ventricular arrhythmias requiring termination through the ICD in these patients. Methods and Results: Between 2000-2016 one hundred and ninety-one patients (age 43±13 years, 71% male, left ventricular ejection fraction 33±15%) with clinically suspected myocarditis were prospectively enrolled for 6.9 (4.1-13) years. All patients underwent EMB at the beginning of the study. The primary endpoint of the study was defined as ICD-implantation for either primary or secondary prevention. Occurrence of ventricular arrhythmias requiring ICD-therapy after ICD-implantation and cardiac death or heart transplantation during follow-up were defined as secondary endpoints. Workup of EMB revealed chronic myocarditis in 55.5% (n=96), acute myocarditis in 5.2% (n=10) and DCM in 50.3% (n=85) of the patients. ICD-Implantation was performed in 58 patients (30.4%) after 4.4 (0.5-47.2) months. Patients with chronic myocarditis received an ICD for primary prevention after 3.8 (1.6-35.3) months after EMB, which was significantly earlier than patients with DCM (27 (2-50.4) months after EMB; p=0.045). Ventricular arrhythmias requiring ICD-therapy were reported in 29 patients (50%; n=58) after 13.7 (2.2-37) months. There was no statistically relevant difference in incidence of ventricular arrhythmias in patients with myocardial inflammation (59%) and patients with DCM (41%). During the first year after EMB, ventricular arrhythmias requiring ICD-therapy were only documented in patients with detection of myocardial inflammation. In total, 38 arrhythmic events had to be terminated by the ICD in 7 patients with myocarditis (12.1%; n=58) during the first 12 months after EMB. In contrast, patients with DCM did not experience any arrhythmic episode within the first year after EMB (p=0,019). The first ventricular arrhythmia in patients with DCM occurred 19 months after EMB. Conclusion: Nearly one third of all patients enrolled in the study needed an ICD for primary or secondary prevention during follow-up. Patients with chronic myocarditis received an ICD for primary prevention earlier than patients with DCM. Within the first year after EMB, ventricular arrhythmias requiring ICD-termination were detected in patients with biopsy-proven myocarditis only. As a consequence, myocardial inflammation must be discussed as a crucial prognostic marker for early occurrence of ventricular arrhythmias

Inducibility of atrial fibrillation after catheter ablation predicts recurrences of atrial fibrillation: a meta-analysis

Background Pulmonary vein isolation (PVI) is a component of standard care for patients with symptomatic atrial fibrillation (AF). Procedural inducibility of AF following PVI has been suggested as predictor of AF recurrence but is discussed controversially. This meta-analysis aimed at evaluating the relevance of electrophysiological inducibility of AF following PVI for future AF recurrences. Methods A literature search of MEDLINE and Web of Science was performed until April 2020. Prospective trials of PVI in patients with AF and post-procedural atrial stimulation to test for inducibility of AF as well as adequate follow-up for AF recurrence (defined as AF >10 s to >10 min at follow-up) were included. Odds ratios (ORs) were analyzed using random-effects models. Results A total of 11 trials with 1544 patients (follow-up 7–39 months, age 56 ± 6 years, predominantly male 74 ± 6%) were included. Inducibility of AF post-PVI was predictive for AF recurrence during follow-up (OR 2.08; 95% CI 1.25 to 3.46). Prediction for AF recurrence at follow-up was better for patients with paroxysmal AF (OR 4.06; 95% CI 1.39 to 11.91), stimulation in the CS (OR 2.82, 95% CI 1.17 to 6.79). A trend towards higher ORs was seen without the use of isoproterenol (OR 2.43; 95% CI 1.17 to 5.07), as well as few stimulations during induction and a short definition of AF in meta-regression analyses. Conclusions Electrophysiological inducibility of AF following PVI was predictive for future recurrence of AF, in particular in patients with paroxysmal AF, stimulation in only CS and no use of isoproterenol

Heart-Focused Anxiety, General Anxiety, Depression and Health-Related Quality of Life in Patients with Atrial Fibrillation Undergoing Pulmonary Vein Isolation

(1) Background: Atrial fibrillation (AF) is associated with anxiety, depression, and chronic stress, and vice versa. The purpose of this study was to evaluate potential effects of pulmonary vein isolation (PVI) on psychological factors. (2) Methods: Psychological assessment was performed before PVI as well as after six months. (3) Results: A total of 118 patients [age 64 ± 9 years, 69% male, left ventricular ejection fraction 57 ± 8%, 56% paroxysmal AF] undergoing PVI were included. After PVI, significant improvements were observed in the mean total heart-focused anxiety (HFA) score, as well as in the Cardiac Anxiety Questionnaire (CAQ) sub-scores: HFA attention, HFA fear, and HFA avoidance scores. Subgroup analyses showed an association of improvement with freedom of documented AF recurrence. Mean scores of general anxiety and depression evaluated by the Hospital Anxiety and Depression Scale (HADS) decreased significantly after PVI in all subgroups regardless of AF recurrence. Further, both physical and mental composite scores of the Short Form Health Survey (SF-12) increased significantly from baseline. (4) Conclusions: PVI results in a significant reduction in HFA. Improvements in general anxiety and depressive symptoms did not seem to be related only to rhythm control per se. Therefore, CAQ may represent a more specific evaluation tool as HADS in patients with AF

Timely and individualized heart failure management: need for implementation into the new guidelines

Due to remarkable improvements in heart failure (HF) management over the last 30 years, a significant reduction in mortality and hospitalization rates in HF patients with reduced ejection fraction (HFrEF) has been observed. Currently, the optimization of guideline-directed chronic HF therapy remains the mainstay to further improve outcomes for patients with HFrEF to reduce mortality and HF hospitalization. This includes established device therapies, such as implantable defibrillators and cardiac resynchronization therapies, which improved patients' symptoms and prognosis. Over the last 10 years, new HF drugs have merged targeting various pathways, such as those that simultaneously suppress the renin–angiotensin–aldosterone system and the breakdown of endogenous natriuretic peptides (e.g., sacubitril/valsartan), and those that inhibit the If channel and, thus, reduce heart rate (e.g., ivabradine). Furthermore, the treatment of patient comorbidities (e.g., iron deficiency) has shown to improve functional capacity and to reduce hospitalization rates, when added to standard therapy. More recently, other potential treatment mechanisms have been explored, such as the sodium/glucose co-transporter inhibitors, the guanylate cyclase stimulators and the cardiac myosin activators. In this review, we summarize the novel developments in HFrEF pharmacological and device therapy and discuss their implementation strategies into practice to further improve outcomes

Renal denervation reduces atrial remodeling in hypertensive rats with metabolic syndrome

Atrial fibrillation (AF) is highly prevalent in hypertensive patients with metabolic syndrome and is related to inflammation and activation of the sympathoadrenergic system. The multi-ligand Receptor-for-Advanced-Glycation-End-products (RAGE) activates inflammation-associated tissue remodeling and is regulated by the sympathetic nervous system. Its counterpart, soluble RAGE (sRAGE), serves as anti-inflammatory decoy receptor with protective properties. We investigated the effect of sympathetic modulation by renal denervation (RDN) on atrial remodeling, RAGE/sRAGE and RAGE ligands in metabolic syndrome. RDN was performed in spontaneously hypertensive obese rats (SHRob) with metabolic syndrome compared with lean spontaneously hypertensive rats (SHR) and with normotensive non-obese control rats. Blood pressure and heart rate were measured by telemetry. The animals were killed 12 weeks after RDN. Left atrial (LA) and right atrial (RA) remodeling was assessed by histological analysis and collagen types. Sympathetic innervation was measured by tyrosine hydroxylase staining of atrial nerve fibers, RAGE/sRAGE, RAGE ligands, cytokine expressions and inflammatory infiltrates were analyzed by Western blot and immunofluorescence staining. LA sympathetic nerve fiber density was higher in SHRob (+44%) versus controls and reduced after RDN (-64% versus SHRob). RAGE was increased (+718%) and sRAGE decreased (− 62%) in SHRob as compared with controls. RDN reduced RAGE expression (− 61% versus SHRob), significantly increased sRAGE levels (+162%) and induced a significant decrease in RAGE ligand levels in SHRob (− 57% CML and − 51% HMGB1) with reduced pro-inflammatory NFkB activation (− 96%), IL-6 production (− 55%) and reduced inflammatory infiltrates. This led to a reduction in atrial fibrosis (− 33%), collagen type I content (− 72%), accompanied by reduced LA myocyte hypertrophy (− 21%). Transfection experiments on H9C2 cardiomyoblasts demonstrated that RAGE is directly involved in fibrosis formation by influencing cellular production of collagen type I. In conclusion, suppression of renal sympathetic nerve activity by RDN prevents atrial remodeling in metabolic syndrome by reducing atrial sympathetic innervation and by modulating RAGE/sRAGE balance and reducing pro-inflammatory and pro-fibrotic RAGE ligands, which provides a potential therapeutic mechanism to reduce the development of AF

Therapeutic approaches in heart failure with preserved ejection fraction: past, present, and future

In contrast to the wealth of proven therapies for heart failure with reduced ejection fraction (HFrEF), therapeutic efforts in the past have failed to improve outcomes in heart failure with preserved ejection fraction (HFpEF). Moreover, to this day, diagnosis of HFpEF remains controversial. However, there is growing appreciation that HFpEF represents a heterogeneous syndrome with various phenotypes and comorbidities which are hardly to differentiate solely by LVEF and might benefit from individually tailored approaches. These hypotheses are supported by the recently presented PARAGON-HF trial. Although treatment with LCZ696 did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among HFpEF patients, subanalyses suggest beneficial effects in female patients and those with an LVEF between 45 and 57%. In the future, prospective randomized trials should focus on dedicated, well-defined subgroups based on various information such as clinical characteristics, biomarker levels, and imaging modalities. These could clarify the role of LCZ696 in selected individuals. Furthermore, sodium-glucose cotransporter-2 inhibitors have just proven efficient in HFrEF patients and are currently also studied in large prospective clinical trials enrolling HFpEF patients. In addition, several novel disease-modifying drugs that pursue different strategies such as targeting cardiac inflammation and fibrosis have delivered preliminary optimistic results and are subject of further research. Moreover, innovative device therapies may enhance management of HFpEF, but need prospective adequately powered clinical trials to confirm safety and efficacy regarding clinical outcomes. This review highlights the past, present, and future therapeutic approaches in HFpEF

Therapeutic approaches in heart failure with preserved ejection fraction: past, present, and future

In contrast to the wealth of proven therapies for heart failure with reduced ejection fraction (HFrEF), therapeutic efforts in the past have failed to improve outcomes in heart failure with preserved ejection fraction (HFpEF). Moreover, to this day, diagnosis of HFpEF remains controversial. However, there is growing appreciation that HFpEF represents a heterogeneous syndrome with various phenotypes and comorbidities which are hardly to differentiate solely by LVEF and might benefit from individually tailored approaches. These hypotheses are supported by the recently presented PARAGON-HF trial. Although treatment with LCZ696 did not result in a significantly lower rate of total hospitalizations for heart failure and death from cardiovascular causes among HFpEF patients, subanalyses suggest beneficial effects in female patients and those with an LVEF between 45 and 57%. In the future, prospective randomized trials should focus on dedicated, well-defined subgroups based on various information such as clinical characteristics, biomarker levels, and imaging modalities. These could clarify the role of LCZ696 in selected individuals. Furthermore, sodium-glucose cotransporter-2 inhibitors have just proven efficient in HFrEF patients and are currently also studied in large prospective clinical trials enrolling HFpEF patients. In addition, several novel disease-modifying drugs that pursue different strategies such as targeting cardiac inflammation and fibrosis have delivered preliminary optimistic results and are subject of further research. Moreover, innovative device therapies may enhance management of HFpEF, but need prospective adequately powered clinical trials to confirm safety and efficacy regarding clinical outcomes. This review highlights the past, present, and future therapeutic approaches in HFpEF

Understanding Quality of Life in Patients With Acute Leukemia, a Global Survey

Purpose: The Acute Leukemia Advocates Network (ALAN) sought to determine which factors are most associated with poor quality of life (QoL) in patients with acute leukemia and to determine key issues and unmet needs through administration of an online survey distributed worldwide via partner patient organizations. Methods: ALAN developed a questionnaire informed by literature review and based extensively on the hematological malignancy-specific patient-reported outcomes (HM-PRO) measure to assess the impact of acute leukemia on QoL and its relationships with patients’ demographics, disease state, disease impact, and support from health care professionals. Univariate and multivariable statistical analysis was used to investigate relationships between HM-PRO scores and the other factors. Results: Of 552 respondents from 42 countries, 332 had acute myeloid leukemia, 139 had acute lymphoblastic leukemia, and 81 had acute promyelocytic leukemia (survey data collected in 2019). Younger age, female gender, and lower income were all significantly negatively associated with QoL. Weak or moderate correlations were observed between overall support, management, and impact of treatment and diagnosis of acute leukemia. Feeling isolated and having reduced ability to carry out physical or enjoyable activities were the most important individual factors, while the best predictors for QoL impact were age, gender, and income (model r-squared = 0.16, complete case n = 449). Conclusions: Findings indicated key factors, particularly age, gender, and socioeconomic state, that clinicians responsible for the care of patients with acute leukemia should be aware of when designing support strategies. The importance of social functioning in relation to patient QoL also should be included in considerations

Less loop diuretic use in patients on sacubitril/valsartan undergoing remote pulmonary artery pressure monitoring

Aims Control of pulmonary pressures monitored remotely reduced heart failure hospitalizations mainly by lowering filling pressures through the use of loop diuretics. Sacubitril/valsartan improves heart failure outcomes and increases the kidney sensitivity for diuretics. We explored whether sacubitril/valsartan is associated with less utilization of loop diuretics in patients guided with haemodynamic monitoring in the CardioMEMS European Monitoring Study for Heart Failure (MEMS-HF). Methods and results The MEMS-HF population (n = 239) was separated by the use of sacubitril/valsartan (n = 68) or no use of it (n = 164). Utilization of diuretics and their doses was prespecified in the protocol and was monitored in both groups. Multivariable regression, ANCOVA, and a generalized linear model were used to fit baseline covariates with furosemide equivalents and changes for 12 months. MEMS-HF participants (n = 239) were grouped in sacubitril/valsartan users [n = 68, 64 ± 11 years, left ventricular ejection fraction (LVEF) 25 ± 9%, cardiac index (CI) 1.89 ± 0.4 L/min/m2] vs. non-users (n = 164, 70 ± 10 years, LVEF 36 ± 16%, CI 2.11 ± 0.58 L/min/m2, P = 0.0002, P < 0.0001, and P = 0.0015, respectively). In contrast, mean pulmonary artery pressure (PAP) values were comparable between groups (29 ± 11 vs. 31 ± 11 mmHg, P = 0.127). Utilization of loop diuretics was lower in patients taking sacubitril/valsartan compared with those without (P = 0.01). Significant predictor of loop diuretic use was a history of renal failure (P = 0.005) but not age (P = 0.091). After subjects were stratified by sacubitril/valsartan or other diuretic use, PAP was nominally, but not significantly lower in sacubitril/valsartan-treated patients (baseline: P = 0.52; 6 months: P = 0.07; 12 months: P = 0.53), while there was no difference in outcome or PAP changes. This difference was observed despite lower CI (P = 0.0015). Comparable changes were not observed for other non-loop diuretics (P = 0.21). Conclusions In patients whose treatment was guided by remote PAP monitoring, concomitant use of sacubitril/valsartan was associated with reduced utilization of loop diuretics, which could potentially be relevant for outcomes

Neues zur Diagnostik und Therapie der Herzinsuffizienz

The incidence and prevalence of heart failure are increasing worldwide. Despite numerous scientific and clinical innovations the mortality and morbidity rates in heart failure patients remain high, so that guideline-conform diagnostics and treatment are of decisive importance. Cardiac decompensation is one of the leading reasons for hospital admissions in Germany. Thus, the treatment of patients with heart failure represents a substantial challenge for the German healthcare system. This article highlights the latest scientific knowledge on acute and chronic heart failure from the years 2018-2020