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Background New-generation self-expanding transcatheter aortic heart valves (THV) were designed to overcome technical constraints of their preceding generations. We sought to compare the efficacy and safety of the self-expanding ACURATE neo2 (Neo2) versus Evolut PRO (PRO) devices. Methods Seven hundred nine patients undergoing transfemoral transcatheter aortic valve implantation (TAVI) with either Neo2 (n = 496) or PRO (n = 213) were included. Propensity score matching (PSM) was performed to account for differences in baseline characteristics. In-hospital and 30-day clinical outcomes were evaluated according to Valve Academic Research Consortium-3 criteria. Results Baseline characteristics were comparable between both groups after PSM (Neo2: n = 155, Evolut Pro: n = 155). Technical success rates were high in both groups (Neo2: 94.8% vs PRO: 97.4%; p = 0.239). Need for permanent pacemaker implantation was less frequent with Neo2 compared with PRO (7.5% vs 20.6%; p = 0.002), whereas major vascular complications were more frequent with Neo2 (Neo2: 11.6% vs PRO: 4.5%; p = 0.022). Intended valve performance at discharge was high in both groups without relevant differences among groups (Neo2: 97.4% vs. 95.3%; p = 0.328). Conclusions Short-term outcomes after TAVI using latest-generation self-expanding THV were excellent, with overall low rates of adverse events. However, Neo2 was associated with lower pacemaker rates and reduced the prevalence of moderate–severe paravalvular leakage. Transprosthetic gradients after TAVI were higher with Neo2 compared with PRO. Graphical abstract

Peripartum cardiomyopathy (PPCM) is a rare but potentially life-threatening heart disease, with onset in the last month of pregnancy or in the first months after delivery in previously heart-healthy women. PPCM patients typically present with heart failure due to left ventricular (LV) dysfunction with an LV ejection fraction (EF) 45 %. In the last years clinical and experimental studies contributed to a better understanding of the pathophysiology and the clinical course of PPCM. In the context of oxidative stress, the nursing hormone prolactin is cleaved into a smaller antiangiogenic and proapoptotic 16k Da form, leading to myocardial dysfunction. In an animal model this can be prevented by treatment with the dopamine agonist bromocriptine, which suppresses prolactin release. This therapeutic approach was confirmed in several clinical studies. Therefore, the current guidelines recommend a treatment consisting of a heart failure treatment according to current guidelines in combination with the dopamine agonist bromocriptine. If the diagnosis is made early and the treatment is started immediately, the prognosis is good compared to other forms of cardiomyopathies, as LV function recovers in most cases.In the acute phase the severity of heart failure differs among PPCM patients. Some patients present with mild forms, whereas some PPCM patients display severely reduced LV function and cardiogenic shock. Especially the latter cases are still challenging, as treatment with β1-adrenergic receptor agonists is associated with progression of heart failure and a worse cardiac outcome. Therefore, patients with cardiogenic shock complicating PPCM should be treated in centers experienced in mechanical circulatory support in combination with bromocriptine treatment.

Peripartum cardiomyopathy (PPCM) is a rare heart disease, occurring in previously heart-healthy women during the last month of pregnancy or the first months after delivery due to left ventricular (LV) systolic dysfunction. A common pathomechanistic pathway of PPCM includes increased oxidative stress and the subsequent generation of a cleaved prolactin fragment (16 kDa PRL), which promotes the onset of heart failure (HF) in a microRNA (miR)-146a-dependent manner. Inhibition of prolactin secretion with the dopamine D2 receptor (D2R) agonist bromocriptine combined with standard HF therapy supports cardiac recovery. This study examined whether treatment with the more selective D2R agonist cabergoline prevents HF development in an experimental PPCM mouse model and might be used as an alternative treatment regime for PPCM.Postpartum (PP) female PPCM-prone mice with a cardiomyocyte restricted STAT3-deficiency (αMHC-CreIn the experimental PPCM mouse model, the selective D2R agonist cabergoline prevents the onset of postpartum HF similar to bromocriptine. In PPCM patients, cabergoline treatment was safe and effective as all patients fully recovered. Cabergoline might serve as a promising alternative to bromocriptine. However, these findings are based on experimental data and a small case series and thus have to be interpreted with caution and should be validated in a larger clinical trial.

Background: Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure (HF), presenting with left ventricular (LV) systolic dysfunction either at the end of pregnancy or in the months following delivery. In rare cases, PPCM leads to severe impairment of LV function, refractory cardiogenic shock or advanced HF. LV assist devices (LVAD) have been shown to be a feasible treatment option in advanced HF. However, little is known about long-term outcomes and prognosis of PPCM patients undergoing LVAD implantation. Methods: A retrospective analysis of data from PPCM patients undergoing LVAD implantation in two tertiary centers with respect to long-term outcomes was performed. Results: Twelve patients of median age 30 (18–39) years were included. Eight patients were experiencing cardiogenic shock (INTERMACS 1) at implantation. Seven patients were implanted within 1 month of their PPCM diagnosis. Median duration of LVAD support was 19 (2–92) months with median follow up of 67 (18–136) months (100% complete). In-hospital and 1-year mortality were 0% and 8.3%, respectively. Two patients died on LVAD support, four patients were successfully bridged to transplantation, two patients are still on LVAD, and four were successfully weaned due to sufficient LV recovery (one died after LV function deteriorated again). Conclusion: LVAD treatment of decompensated end-stage PPCM is feasible. Early LVAD provision led to hemodynamic stabilization in our cohort and facilitated safe LV recovery in one third of these young female patients.

Modern treatment strategies have improved prognosis and survival of patients with malignant diseases. The key components of tumor treatment are conventional chemotherapy, radiotherapy, targeted therapies, and immunotherapy. Cardiovascular side-effects may occur in the early phase of tumor therapy or even decades later. Therefore, knowledge and awareness of acute and long-lasting cardiac side effects of anti-cancer therapies are essential. Cardiotoxicity impairs quality of life and overall survival. The new cardiologic subspecialty ‘cardio-oncology’ deals with the different cardiovascular problems arising from tumor treatment and the relationship between cancer and heart diseases. Early detection and treatment of cardiotoxicity is of crucial importance. A detailed cardiac assessment of patients prior to administration of cardiotoxic agents, during and after treatment should be performed in all patients. The current review focusses on acute and long-term cardiotoxic side effects of classical cytotoxic and selected modern drug treatments such as immune checkpoint inhibitors and discusses strategies for the diagnosis of treatment-related adverse cardiovascular effects in cancer patients.

Background Over the past decades the use of assisted reproduction technology (ART) increased worldwide. ARTs are associated with an elevated risk for cardiovascular complications. However, a potential relation between subfertility/ARTs and the heart disease peripartum cardiomyopathy (PPCM) has not been systematically analyzed yet. Methods A retrospective cohort study was carried out, including n = 111 PPCM patients from the German PPCM registry. Data from PPCM patients were compared to those from postpartum women in the German general population. Results The prevalence of reported subfertility was high among PPCM patients (30%; 33/111). Most of the subfertile PPCM patients (55%; 18/33) obtained vitro fertilizations (IVF) or intracytoplasmic sperm injections (ICSI). PPCM patients were older (p p p p p n = 15 subfertile PPCM patients revealed that 33% (5/15) carried pathogenic or likely pathogenic gene variants associated with cardiomyopathies and/or cancer predisposition syndrome. Conclusions Subfertility occurred frequently among PPCM patients and was associated with increased age, hormonal disorders, higher twin pregnancy rate and high prevalence of pathogenic gene variants suggesting a causal relationship between subfertility and PPCM. Although this study found no evidence that the ART treatment per se increases the risk for PPCM or the risk for an adverse outcome, women with subfertility should be closely monitored for signs of peripartum heart failure. Graphical abstract

As a result of better treatment options for malignant cancer, the cardiovascular side effects of such therapies have increasingly come into focus in recent years. The new cardiological subspecialty of oncocardiology is developing strategies to prevent and/or detect those effects early in order to treat them in a timely and adequate manner. The diagnosis of cardiotoxic effects is based mainly on imaging and specific biomarkers. Echocardiography has become the main imaging technique due to its wide availability. In addition to quantitative determination of left ventricular function using two-dimensional methods, three-dimensional methods offer better precision and less variability in the detection of cardiac dysfunction. Furthermore, the analysis of the global longitudinal strain (GLS) reveals even subtle changes in left ventricular function and thus detects very early damage before left ventricular ejection fraction drops. Various biomarkers have been tested recently for their potential to detect cardiotoxicity. Cardiac troponins are currently the best investigated biomarkers and certainly have the highest impact. Due to contradicting results, the importance of natriuretic peptides has not yet been conclusively clarified. Results for myeloperoxidase are promising, as are the results for circulating microRNAs, which still mainly derive from experimental data. In this context, further studies still need to show the value of these in everyday clinical practice.

Background To test the effects of guided endurance training on work ability in middle-aged female hospital workers of various occupations. Methods We randomized 265 healthy, sedentary, middle-aged women (45–65 years) to an endurance training group (EG 210 min/week) or a wait-list control group (CG). At baseline and at 6-month follow-up, we assessed work ability (Work Ability Index [WAI]), physical activity (Freiburger activity questionnaire) and peak oxygen uptake (VO2peak) by cardiopulmonary exercise testing. To examine the influence of baseline work ability, participants were divided into poor-moderate (WAI 1, 7–36 points, n = 83), good (WAI 2, 37–43 points, n = 136) and excellent (WAI 3, 44–49 points, n = 46) WAI subgroups. Results Cardiorespiratory fitness improved significantly after 6 months in the EG but not in the CG. The WAI total score increased significantly in the EG (38.3 ± 5.0 to 39.8 ± 4.9 points) but not in the CG (39.4 ± 4.7 to 39.3 ± 4.9 points), with a significant difference between groups (p p Conclusions A 6-month guided exercise training intervention significantly increases cardiorespiratory fitness with concomitant improvements in work ability in middle-aged previously sedentary hospital employees. Women with low baseline work ability seem to particularly benefit from the intervention, which implies that similar interventions may be particularly beneficial for this group of individuals. Trial registration German Clinical Trails Register Identifier: DRKS00005159. Registered 25 September 2013.

Ischaemic stroke and systemic embolism are the major potentially preventable complications of atrial fibrillation (AF) leading to severe morbidity and mortality. Anticoagulation using vitamin K antagonists (VKA) or non-vitamin K oral anticoagulants (NOACs) is mandatory for stroke prevention in AF. Following approval of the four NOACs dabigatran, rivaroxaban, apixaban, and edoxaban, the use of VKA is declining steadily. Increasing age with thresholds of 65 and 75 years is a strong risk factor when determining annual stroke risk in AF patients. Current recommendations such as the “2016 Guidelines for the management of atrial fibrillation” of the European Society of Cardiology and the “2019 AHA/ACC/HRS Focused Update” by the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society strengthen the importance of anticoagulation and detection of bleeding risks, of which older age is an important one. While patients aged ≥ 75 years are usually underrepresented in randomised clinical trials, they represent almost 40% of the trial populations in the large NOAC approval studies. Therefore, a sufficient amount of data is available to assess the efficacy and safety for this patient cohort in that specific indication. In this article, the evidence for stroke prevention in AF using either VKA or NOACs is summarised with a special focus on efficacy compared to bleeding risk in patients aged ≥ 75 years. Specifically, we used a model of increased weighing of intracranial bleeding to illustrate the potential benefit of NOACs over VKA in the elderly population. In brief, there are at least two tested strategies with apixaban and edoxaban which even confer an additional clinical net benefit compared with VKA. Furthermore, elderly subgroups of trials for combined antithrombotic treatment following percutaneous coronary interventions in anticoagulated patients are analysed.

AIMS Low cardiac iron levels promote heart failure in experimental models. While cardiac iron concentration (CI) is decreased in patients with advanced heart failure with reduced ejection fraction (HFrEF), CI has never been measured in non-advanced HFrEF. We measured CI in left ventricular (LV) endomyocardial biopsies (EMB) from patients with non-advanced HFrEF and explored CI association with systemic iron status and disease severity. METHODS AND RESULTS We enrolled 80 consecutive patients with non-ischaemic HFrEF with New York Heart Association class II or III symptoms and a median (interquartile range) LV ejection fraction of 25 (18-33)%. CI was 304 (262-373) μg/g dry tissue. CI was not related to immunohistological findings or the presence of cardiotropic viral genomes in EMBs and was not related to biomarkers of systemic iron status or anaemia. Patients with CI in the lowest quartile (CIQ1 ) had lower body mass indices and more often presented with heart failure histories longer than 6 months than patients in the upper three quartiles (CIQ2-4 ). CIQ1 patients had higher serum N-terminal pro-B-type natriuretic peptide levels than CIQ2-4 patients [3566 (1513-6412) vs. 1542 (526-2811) ng/L; P = 0.005]. CIQ1 patients also had greater LV end-diastolic (P = 0.001) and end-systolic diameter indices (P = 0.003) and higher LV end-diastolic pressures (P = 0.046) than CIQ2-4 patients. CONCLUSION Low CI is associated with greater disease severity in patients with non-advanced non-ischaemic HFrEF. CI is unrelated to systemic iron homeostasis. The prognostic and therapeutic implications of CI measurements in EMBs should be further explored.

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.

Background Dialysis patients are at increased risk of HF. However, diagnostic utility of NT-proBNP as a biomarker is decreased in patients on dialysis. GDF-15 and cNEP are biomarkers of distinct mechanisms that may contribute to HF pathophysiology in such cohorts. The aim of this study was to determine whether growth differentiation factor-15 (GDF-15) and circulating neprilysin (cNEP) improve the diagnosis of congestive heart failure (HF) in patients on dialysis. Methods and results We compared circulating concentrations of NT-proBNP, GDF-15, and cNEP along with cNEP activity in patients on chronic dialysis without (n = 80) and with HF (n = 73), as diagnosed by clinical parameters and post-dialysis echocardiography. We used correlation, linear and logistic regression as well as receiver operating characteristic (ROC) analyses. Compared to controls, patients with HF had higher median values of NT-proBNP (16,216 [interquartile range, IQR = 27739] vs. 2883 [5866] pg/mL, p p = 0.014), but not cNEP (315 [107] vs. 318 [124] pg/mL, p = 0.818). Median cNEP activity was significantly lower in HF vs. controls (0.189 [0.223] vs. 0.257 [0.166] nmol/mL/min, p p Conclusion We present novel comparative data on physiologically distinct circulating biomarkers for HF in patients on dialysis. cNEP activity but not concentration and GDF-15 provided incremental diagnostic information over clinical covariates and NT-proBNP and may aid in diagnosing HF in dialysis patients. Graphic abstract

Aims Peripartum cardiomyopathy (PPCM) establishes late in pregnancy or in the first postpartum months. Many patients recover well within the first year, but long-term outcome studies on morbidity and mortality are rare. Here, we present 5-year follow-up data of a German PPCM cohort. Methods and results Five-year follow-up data were available for 66 PPCM patients (mean age 34 ± 5 years) with a mean left ventricular ejection fraction (LVEF) of 26 ± 9% at diagnosis. Ninety-eight percent initially received standard heart failure therapy (beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, and/or mineralocorticoid receptor antagonists), and 86% were additionally treated with dopamine D2 receptor agonists (mainly bromocriptine) and anticoagulation. After 1 year, mean LVEF had improved to 50 ± 11% (n = 48) and further increased to 54 ± 7% at 5-year follow-up with 72% of patients having achieved full cardiac recovery (LVEF >50%). At 5-year follow-up, only three patients (5%) displayed no recovery, of whom one had died. However, 20% had arterial hypertension and 17% arrhythmias, including paroxysmal supraventricular tachycardia, ventricular tachycardia, or ventricular fibrillation. Moreover, 70% were still on at least one heart failure drug. Subsequent pregnancy occurred in 16 patients with two abortions and 14 uneventful pregnancies. Mean LVEF was 55 ± 7% at 5-year follow-up in these patients. Conclusion Our PPCM collective treated with standard therapy for heart failure, dopamine D2 receptor agonists, and anticoagulation displays a high and stable long-term recovery rate with low mortality at 5-year follow-up. However, long-term use of cardiovascular medication, persisting or de novo hypertension and arrhythmias were frequent.

Atrial fibrillation (AF) is the most common arrhythmia in adults but its impact on allogeneic stem cell transplantation (SCT) is not well characterized. We studied AF manifestation during the hospital stay for allogeneic SCT, referred to as AF in hospital (AFiH), and analyzed the incidence of, risk factors for, and clinical impact of AFiH on intensive care unit (ICU)-/hospital-/ and overall survival (OS), relapse-free survival (RFS), nonrelapse mortality (NRM), and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS). This retrospective matched cohort study comprised 553 consecutive SCT recipients at Hannover Medical School between January 2013 and October 2019. Patients with AFiH were compared with a non-AFiH control cohort matched for Hematopoietic Stem Cell-Specific Comorbidity Index (HCT-CI), European Group for Blood and Marrow Transplantation (EBMT) risk score, disease, conditioning regimen and availability of molecular genetic data for patients with myeloid diseases. AFiH occurred in 46 patients (8%) at a median of 2 days (interquartile range, 0 to 8 days) after SCT. Patient history of AF and elevated NT-proBNP and high-sensitivity troponin T levels, but not conventional echocardiographic parameters, were predictive for AFiH. AFiH occurred more often in patients with mutations in DNMT3A, TET2, and ASXL1 genes related to clonal hematopoiesis compared with patients with wild-type alleles, with the greatest impact from DMT3A mutations. ICU admission was significantly higher in the AFiH cohort (46% versus 7%), without significant differences in ICU or post-ICU hospital survival (62% versus 40% and 52% versus 40%, respectively). The main cause of death was sepsis. In terms of long-term outcomes, the incidences of relapse and grade II-IV acute GVHD did not differ significantly between the AFiH and the non-AFiH groups; however, OS was significantly shorter in the AFiH group (1 year OS, 39% versus 65%), owing to late noncardiac NRM (1 year NRM, 49% versus 27%). Although the underlying cellular and molecular mechanisms remain to be characterized in further detail, these data clearly demonstrate the impact of inpatient AF manifestation/AFiH on long-term outcomes of SCT recipients.

Background Subclinical atrial fibrillation (AF) is the underlying cause in a relevant part of patients with embolic stroke of unknown source (ESUS). This pilot study aims to identify novel echocardiographic parameters predicting AF subsequently detected in patients originally hospitalized with ESUS. Methods and results Patients with acute ischemic stroke [baseline diagnosis of ESUS (n = 69), stroke of macro- or microvascular cause (n = 16/25), stroke caused by AF (n = 5)] and controls with paroxysmal AF without acute ischemic stroke (n = 22) as well as healthy controls of young and old age (n = 21/17) in sinus rhythm were included (overall n = 175). Echocardiography was performed in all participants. Prolonged Holter-ECG-monitoring was performed in all stroke patients. In the overall cohort, septal total atrial conduction time (sPA-TDI), left atrial (LA) volume index to tissue Doppler velocity (LAVI/a`) and second negative peak strain rate during LA contraction (SRa), representing echocardiographic parameters of LA remodelling and function, were statistically significant different in patients with and without AF and predictive for subclinical AF (multivariate regression analysis: sPA-TDI: HR 1.06 [1.04–1.08], p

Open in a separate window During the last 20 years, the prognosis for heart failure (HF) with reduced ejection fraction has steadily improved due to advances in drug treatment and the consistent implementation of guideline-recommended evidence-based drug therapy. Nevertheless, the morbidity and mortality rates of patients with HF can still be improved. The prevalence of HF is high and continues to increase steadily. Thus, timely and efficient drug treatment plays a central role in improving the quality of life and prognosis for patients with HF. Current therapeutic concepts combine inhibition of the renin–angiotensin–aldosterone system with blockage of the sympathetic system. New therapeutic approaches such as selective heart rate reduction, attenuation of the degradation of natriuretic peptides by neutral endopeptidase inhibition and treatment of comorbidities (e.g. iron deficiency, diabetes mellitus, hyperkalaemia) have led to a further improvement in the survival, time-out-of hospital and quality of life of affected patients. The goal of this article was to give an overview of the current standard drug therapy for HF and the value of new therapeutic approaches implemented in recent years.

Background: Left ventricular assist devices (LVAD) are increasingly used in patients with end stage heart failure. The HeartAssist 5 and aVAD LVADs offer telemetric monitoring capabilities. Here we report our initial single centre experience with the largest telemonitoring cohort of LVAD patients. Methods: Eleven patients (9 males) received a telemonitoring-capable LVAD and were included in our telemonitoring cohort. Waveforms and alarm data were obtained from the telemonitoring system and hospital records were reviewed for clinical data. Results: Mean age at LVAD implantation was 59±5.1 years (mean ± standard deviation). Seven patients had non-ischemic cardiomyopathy and 4 patients had ischemic cardiomyopathy. Median LVEF at implant was 16% (IQR, 15–20%). The total follow-up time was 2,438 patient-days. A total of 6,216 alarm messages were generated in 11 patients. Most common were low flow alarms due to hypovolemia, followed by low flow alarms because of suspected pump thrombosis. One patient died during follow-up, one received a cardiac transplant and one had the LVAD explanted because of pump thrombosis. Pump thrombosis was suspected in 5 patients with 8 episodes of sudden flow decreases and laboratory signs of haemolysis. Conclusions: Real-time telemonitoring of LVAD pump flow, motor speed and power consumption is a promising tool in the follow-up of LVAD recipients. Trending pump flow over hours or days can assist in the early detection of complications, especially flow reductions due to hypovolemia and LVAD thrombosis. Further studies are warranted to delineate the impact of remote monitoring on patients’ prognosis.

Background The Heartmate 3 (HM3) is a Conformitee Europeenne mark–approved left ventricular (LV) assist device (LVAD) with fully magnetically levitated rotor and features consisting of a wide range operational speeds, wide flow paths, and artificial pulse. We performed a hemodynamic-echocardiographic speed optimization evaluation in HM3-implanted patients to achieve optimal LV- and right ventricular (RV) shape. Methods and Results Sixteen HM3 patients underwent pump speed ramp tests with right heart catheterization. Three-dimensional echocardiographic (3DE) LV and RV datasets (Philips) were acquired, and volumetric (Tomtec) and shape (custom software) analyses were performed (LV: sphericity, conicity; RV: septal and free-wall curvatures). Data were recorded at up to 13 speed settings. Speed changes were in 100-rpm steps, starting at 4600 rpm and ramping up to 6200 rpm. 3DE was feasible in 50% of the patients. Mean original speed was 5306 ± 148 rpm. LV end-diastolic (ED) diameter (−0.15 ± 0.09 cm/100 rpm) and volumes (ED: 269 ± 109 mL to 175 ± 90 mL; end-systolic [ES]: 234 ± 111 mL to 146 ± 81 mL) progressively decreased as the shape became less spherical and more conical; RV volumes initially remained stable, but at higher speeds increased (ED: from 148 ± 64 mL to 181 ± 92 mL; ES: 113 ± 63 mL to 130 ± 69 mL). On average, the RV septum became less convex (bulging toward the LV) at the highest speeds. Conclusions LV and RV shape changes were noted in HM3-supported patients. Although a LV volumetric decrease and shape improvement was consistently noted, RV volumes grew in response to increase in speed above a certain point. A next concern would be whether understanding of morphologic and function changes in LV and RV during LVAD speed change assessed with the use of 3DE helps to optimize LVAD speed settings and improve clinical outcomes.

Introduction Angiotensin-converting enzyme 2 (ACE2) is a key enzyme of the renin-angiotensin system (RAS) that has been implicated in the pathogenesis of acute respiratory distress syndrome (ARDS). Enhancing ACE2 activity using GSK2586881, a recombinant form of human ACE2, could be beneficial in diseases such as ARDS but may blunt the hypoxic pulmonary vasoconstriction (HPV) response and potentially impact systemic and tissue oxygenation. This study aimed to evaluate the effect of GSK2586881 0.8 mg/kg on HPV response in healthy adult volunteers during exercise under hypoxic conditions. Methods In this phase I, randomised, double-blind (sponsor open) study, GSK2586881 or placebo was administered as a single intravenous (IV) dose in a two-period crossover design. Treatment periods were separated by a washout period of 3–14 days. The primary endpoint was change from baseline in pulmonary artery systolic pressure (PASP) measured by echocardiography. Secondary endpoints included RAS peptides and oxygen saturation. Results Seventeen adults aged 18–40 years were randomised to treatment. There were no clinically relevant differences (defined as a reduction of ≥ 5 mmHg) in change from baseline in PASP between GSK2586881 and placebo. GSK2586881 was well tolerated, with no serious adverse events, no worsening of hypoxaemia and no evidence of immunogenicity. The study was terminated early after review of the data, which showed that the predefined success criteria had not been met. Following GSK2586881 administration, levels of the RAS peptide angiotensin II decreased while angiotensin (1-7) increased, as expected, indicating that GSK2586881 was pharmacologically active. Conclusions A single IV dose of GSK2586881 0.8 mg/kg was well tolerated but did not impact the acute HPV response in healthy volunteers. Supplementary Information The online version contains supplementary material available at 10.1007/s41030-021-00164-7.

Background: Worse outcomes in women compared to men undergoing left ventricular assist device (LVAD) implantation remain an underestimated problem in heart failure (HF) patients. With device miniaturization, less-invasive LVAD implantation techniques have gained relevance, but their impact on outcomes in women is unknown. This study investigates sex-related differences in patients undergoing LVAD implantation through less-invasive procedures. Methods: This retrospective single-center cohort study included patients who underwent isolated LVAD implantation between 2011 and 2018 through less-invasive techniques. Propensity score matching (PSM) was utilized to balance preoperative heterogeneity. Primary endpoint was two-year survival, and secondary endpoints included long-term survival, surgical outcomes and postoperative adverse events. Results: Baseline analysis of 191 patients (females 18.3%) showed differences in terms of age [female (median, 52; IQR, 47–61); male (median, 58.5; IQR, 49–66); P=0.005], underlying diagnosis (P

Background Chronic congestive heart failure is a common condition that, if untreated, markedly impairs the quality of life and is associated with a high risk of recurrent hospitalization and death. Methods This review is based on articles retrieved by a selective search in PubMed, as well as on relevant guidelines. Results Evidence-based treatment options are available only for congestive heart failure with a low ejection fraction. Pharma - cotherapy is based on neurohumoral inhibition of the renin-angiotensin-aldosterone system and the adrenergic system. The prognosis of patients with this condition has been further improved recently through the introduction of combined angiotensin receptor antagonists and neprilysin inhibitors. Modern implantable devices are a further component of treatment. Implantable defibrillators and special pacemakers for cardiac resynchronization are well established; the utility of alternative devices (baroreflex modulation or cardiac contractility modulation) needs to be investigated in further studies. It was recently shown that the catheter-based treatment of secondary mitral regurgitation with a MitraClip improves the outcome of selected patients. Conclusion The treatment of chronic systolic heart failure as recommended in the relevant guidelines, with drugs and implanted devices if indicated, can significantly improve the clinical outcome.

BackgroundTo test the effects of guided endurance training on work ability in middle-aged female hospital workers of various occupations. Methods We randomized 265 healthy, sedentary, middle-aged women (45-65 years) to an endurance training group (EG 210 min/week) or a wait-list control group (CG). At baseline and at 6-month follow-up, we assessed work ability (Work Ability Index [WAI]), physical activity (Freiburger activity questionnaire) and peak oxygen uptake (VO2peak) by cardiopulmonary exercise testing. To examine the influence of baseline work ability, participants were divided into poor-moderate (WAI 1, 7-36 points, n=83), good (WAI 2, 37-43 points, n=136) and excellent (WAI 3, 44-49 points, n=46) WAI subgroups.ResultsCardiorespiratory fitness improved significantly after 6 months in the EG but not in the CG. The WAI total score increased significantly in the EG (38.3±5.0 to 39.8±4.9 points) but not in the CG (39.4±4.7 to 39.3±4.9 points), with a significant difference between groups (pConclusionsA 6-month guided exercise training intervention significantly increases cardiorespiratory fitness with concomitant improvements in work ability in middle-aged previously sedentary hospital employees. Women with low baseline work ability seem to particularly benefit from the intervention, which implies that similar interventions may be particularly beneficial for this group of individuals.

Aims: Peripartum cardiomyopathy (PPCM) is a heart disease affecting women during the last month of pregnancy or in the first months after delivery. The impact of the disease on mental health is largely unknown. Methods and results: Major mental disorders were assessed by a structured clinical interview in 40 patients with a confirmed PPCM diagnosis, and the data were compared with published prevalence in postpartum women. Circulating biomarkers associated with mental health, such as kynurenine, serotonin, and microRNA (miR)‐30e, were evaluated in PPCM and compared with matched healthy pregnancy‐matched postpartum controls (PP‐Ctrl). Major mental disorders were diagnosed in 65% (26/40) of the PPCM cohort. The prevalence for major depressive disorders was 4‐fold, for post‐traumatic stress disorder 14‐fold, and for panic disorder 6‐fold higher in PPCM patients compared with postpartum women without a PPCM diagnosis. Compared with PP‐Ctrl, PPCM patients displayed elevated levels of serum kynurenine (P < 0.01), reduced levels of serum serotonin (P < 0.05), and elevated levels of plasma miR‐30e (P < 0.05). Conclusions: The majority of PPCM patients in the present cohort displayed mental disorders with a higher prevalence of major depressive disorders, post‐traumatic stress disorder (PTBS), and panic disorder, compared with postpartum women without a PPCM diagnosis. This higher prevalence was associated with an impaired tryptophan metabolism and elevated levels of the depression‐associated miR‐30e, suggesting a potential predisposition for mental disorders at the time of PPCM diagnosis. Consequently, physicians should be aware of the increased risk for mental disorders in PPCM patients, and psychiatric assessment should be included in the diagnosis and management of PPCM patients.

Chronic end-stage heart failure (CHF) is a major healthcare problem with rapidly growing incidences in Europe and the United States (1). With decreasing cardiac transplant rates worldwide, alternative treatment methods become increasingly important.

Summary Background Pulmonary hyperinflation in chronic obstructive pulmonary disease (COPD) is associated with reduced biventricular end-diastolic volumes and increased morbidity and mortality. The combination of a long-acting β agonist (LABA) and a muscarinic antagonist (LAMA) is more effective in reducing hyperinflation than LABA–inhaled corticosteroid combination therapy but whether dual bronchodilation improves cardiac function is unknown. Methods We did a double-blind, randomised, two-period crossover, placebo-controlled, single-centre study (CLAIM) at the Fraunhofer Institute of Toxicology and Experimental Medicine (Hannover, Germany), a specialty clinic. Eligible participants were patients aged at least 40 years with COPD, pulmonary hyperinflation (defined by a baseline residual volume >135% of predicted), a smoking history of at least ten pack-years, and airflow limitation (FEV 1 1 : forced vital capacity Findings Between May 18, 2015, and April 20, 2017, we randomly assigned 62 eligible participants to treatment; 30 to indacaterol–glycopyrronium followed by placebo and 32 to placebo followed by indacaterol–glycopyrronium. The 62 randomly assigned patients were included in the intent-to-treat analysis. There were two protocol violations and therefore 60 were included in the per-protocol analysis. 57 patients completed both treatment periods. After indacaterol–glycopyrronium treatment, left-ventricular end-diastolic volume increased from a mean 55·46 mL/m 2 (SD 15·89) at baseline to a least-squares (LS) mean of 61·76 mL/m 2 (95% CI 57·68–65·84), compared with a change from 56·42 mL/m 2 at baseline (13·54) to 56·53 mL/m 2 (52·43–60·62) after placebo (LS means treatment difference 5·23 mL/m 2 [95% CI 3·22 to 7·25; p Interpretation This is the first study to analyse the effect of LABA–LAMA combination therapy on cardiac function in patients with COPD and lung hyperinflation. Dual bronchodilation with indacaterol–glycopyrronium significantly improved cardiac function as measured by left-ventricular end-diastolic volume. The results are important because of the known association of cardiovascular impairment with COPD, and support the early use of dual bronchodilation in patients with COPD who show signs of pulmonary hyperinflation. Funding Novartis Pharma GmbH.

ZusammenfassungDie chronische Herzinsuffizienz nimmt aufgrund einer veränderten Altersstruktur der Bevölkerung, aber auch einer verbesserten medizinischen (Akut-)Versorgung kardiovaskulärer Erkrankungen an Inzidenz und Prävalenz zu. Unbehandelt hat sie eine schlechte Prognose – (rezidivierende) Hospitalisierungen stellen ein zunehmendes gesundheitsökonomisches Problem dar. Fortschritte in der Therapie der Patienten durch moderne Substanzen und konsequente Umsetzung der Therapieempfehlungen können die Prognose der Betroffenen deutlich verbessern. Neben der Etablierung der Mineralokortikoid-Rezeptor-Antagonisten bereits in milderen Stadien der systolischen Herzinsuffizienz und der Therapie mit dem If-Kanal-Blocker Ivabradin verspricht insbesondere der neue Angiotensin-Rezeptor-/Neprilysin-Inhibitor Sacubitril/Valsartan eine Verbesserung der Prognose. Daneben rücken zunehmend Diagnostik und Therapie prognosemodifizierender Komorbiditäten weiter in den Fokus. Die im Sommer 2016 vorgestellten aktualisierten Leitlinien der Europäischen Gesellschaft für Kardiologie (ESC) fassen den aktuellen Stand der Evidenz zusammen und geben Empfehlungen zur zeitgemäßen Therapie der Herzinsuffizienz.

Aims Subsequent pregnancies (SSPs) in patients with peripartum cardiomyopathy (PPCM) have a high risk of heart failure relapse. We report on outcome of SSPs in PPCM patients in Germany, Scotland, and South Africa. Methods and results Among 34 PPCM patients with a SSP, pregnancy ended prematurely in four patients while it was full-term in 30. Overall relapse rate [left ventricular ejection fraction, LVEF

Statins are the most widely prescribed drugs to reduce serum low density lipoprotein cholesterol (LDL-C) by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase. LDL-C reduction is associated with a decreased risk of atherosclerotic cardiovascular disease (ASCVD), including cardiovascular disease (CVD) and stroke. Statins reduce LDL-C by 30 to 40%, and the combination with other lipid-lowering agents such as ezetimibe leads to a further reduction by 20 to 25%. However, even the combination of these two agents might not be sufficient in high risk patients to require aggressive LDL-C reduction. Therefore, starting from observations on individuals with loss-of-function in proprotein convertase subtilisin/kexin type 9 (PCSK9), which was associated with lower LDL-C levels and CVD rates, monoclonal antibodies (mAbs) against PCSK9 were developed. To date, two mAbs, alirocumab and evolocumab, have received approval by the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA). In the present review we give an overview about pathophysiological and clinical aspects as well as evidence for these drugs with respect to cerebrovascular events.