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Literature describing recovery of left ventricular (LV) function post sacubitril/valsartan treatment and the optimal management of heart failure (HF) patients receiving sacubitril/valsartan remain sparse.We recruited 437 consecutive chronic HF patients with baseline left ventricular ejection fraction (LVEF) less than 40%, who were treated with sacubitril/valsartan. All patients underwent routine echocardiographic measurement.During treatment period, recovery of LVEF to 50% or greater was observed in 77 (17.6%) patients. After multivariate analysis, recovery of LV dysfunction was associated with non-ischemic etiology of HF, smaller baseline LV end-diastolic diameter (LVEDD), and higher initial dosage of sacubitril/valsartan. Compared to those without recovery of LV dysfunction, death from cardiovascular causes or first unplanned hospitalization for HF (CVD/HFH) were significantly lower in patients with LVEF recovery [11.7% vs. 24.4%, hazard ratio (HR) 0.42, p = 0.014]. Among patients with recovery of LVEF, 51 patients continued to receive the same dosage of sacubitril/valsartan had higher LVEF and were less likely to have deterioration of LVEF than the other 26 patients who received either tapering dose of sacubitril/valsartan or switching from sacubitril/valsartan to renin-angiotensin-system blockers (LVEF 56.4 ± 5.3% vs. 45.0 ± 12.8%, p 0.001; ΔLVEF 1.2 ± 5.1% vs. -9.3 ± 12.0%, p 0.001). CVD/HFH occurred more frequently in the taper group than the maintenance group (23.1% vs. 5.9%, HR 0.22, p = 0.035).Non-ischemic etiology of HF, smaller baseline LVEDD, and higher initial dosage of sacubitril/valsartan could predict better recovery of LV function. Among patients with functional recovery, tapering sacubitril/valsartan dose was associated with deterioration of recovered heart function and had less favorable prognosis during follow-up.

Aims We collected the different prescription patterns of diabetes medications in a cohort of patients with heart failure with reduced ejection fraction (HFrEF) and analysed the impact of different prescription patterns on clinical outcomes. Methods and results Consecutive diabetic patients with HFrEF from a heart failure referral centre were retrospectively analysed between 2015 and 2016. Exclusion criteria include being lost to follow‐up, not receiving diabetes medications, and having severe renal impairment with a glomerular filtration rate < 30 mL/min/1.73 m2. Prescription of diabetes medications and the respective clinical outcomes were collected between 2016 and 2018. Among 381 patients (mean age, 64.8 ± 12.8 years; 71.9% male; mean left ventricular ejection fraction, 27.6 ± 7.0%; mean body mass index, 26.1 ± 4.7 kg/m2), the prescription rates of sodium‐glucose co‐transporter 2 inhibitor (SGLT2i) increased from 10.3% in 2016 to 17.6% in 2017 and 26.5% in 2018 (P < 0.001); the prescription rates of metformin, sulfonylurea, insulin, and dipeptidyl peptidase‐4 inhibitors did not change significantly over time. The prescription rates of metformin and SGLT2i were significantly higher in patients managed by cardiologists than non‐cardiologists (in 2018, 71.1% vs. 44.2% for metformin, 45.4% vs. 9.9% for SGLT2i, both P < 0.001). During the study period, annualized event rates of cardiovascular death or first unplanned HF hospitalization were 19.0 per 100 patient‐years. After a multivariate analysis, prescriptions of metformin {odds ratio (OR): 0.49 [95% confidence interval (CI) 0.27–0.51], P < 0.001} and SGLT2i [OR: 0.52 (95% CI 0.28–0.98), P = 0.042] were independently associated with lower annualized event rates of cardiovascular death or unplanned HF hospitalization. Conclusions Prescription patterns of diabetes medications in diabetics with HFrEF were diverse among different specialists. Prescriptions of metformin and SGLT2i were associated with favourable clinical outcomes. Our finding indicates the importance of awareness of beneficial effect of different classes of diabetes medications and collaboration between specialists in the management of diabetic HFrEF patients.

Background Angiotensin receptor and neprilysin inhibition (ARNI) has been shown to reduce cardiovascular mortality by 20% as compared with enalapril in a randomized controlled trial. However, there is a paucity of real-world data on the effects of ARNI in heart failure patients with reduced ejection fraction (HFrEF), especially those with concurrent renal impairment or hypotension. Methods Between 2016 and 2017, we recruited 466 HFrEF patients treated with sacubitril/valsartan (Group A) and 466 patients managed with standard HF treatment without ARNI (Group B) in a HF referral center. Baseline characteristics and clinical outcomes were collected between both groups. Results Baseline characteristics were comparable between the two groups. During a follow-up period of 15 months, death from cardiovascular causes or first unplanned hospitalization for HF occurred in 100 patients in Group A (21.5%) and 144 in Group B (30.9%, hazard ratio 0.66; 95% CI 0.51–0.85; p = 0.001). The incidences of deaths from any causes, cardiovascular death, sudden death, and HF re-hospitalization were all significantly lower in Group A than Group B patients. Among patients with different chronic kidney disease stages and normotensive patients, treatment with sacubitril/valsartan showed more favorable outcomes than treatment with standard HF care without ARNI. However, in patients with baseline systolic blood pressure lower than 100 mmHg, there were no significant differences of outcomes in both groups. Among Group A patients, escalation of sacubitril/valsartan was associated with better outcomes. Conclusions Our study demonstrated the effectiveness of sacubitril/valsartan on HFrEF patients in real world practice, including those with advanced renal impairment.

Objective: The soluble guanylate cyclase stimulator riociguat is approved for the treatment of adult patients with pulmonary arterial hypertension (PAH) and inoperable or persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH) following Phase 3 randomized trials. The EXPosurE Registry RiociguaT in patients with pulmonary hypertension (EXPERT) study was designed to monitor the long-term safety of riociguat in clinical practice. Methods: EXPERT was an international, multicenter, prospective, uncontrolled, non-interventional cohort study of patients treated with riociguat. Patients were followed for at least 1 year and up to 4 years from enrollment or until 30 days after stopping riociguat treatment. Primary safety outcomes were adverse events (AEs) and serious adverse events (SAEs) coded using Medical Dictionary for Regulatory Activities preferred terms and System Organ Classes version 21.0, collected during routine clinic visits and collated via case report forms. Results: In total, 956 patients with CTEPH were included in the analysis. The most common AEs in these patients were peripheral edema/edema (11.7%), dizziness (7.5%), right ventricular (RV)/cardiac failure (7.7%), and pneumonia (5.0%). The most common SAEs were RV/cardiac failure (7.4%), pneumonia (4.1%), dyspnea (3.6%), and syncope (2.5%). Exposure-adjusted rates of hemoptysis/pulmonary hemorrhage and hypotension were low and comparable to those in the long-term extension study of riociguat (Chronic Thromboembolic Pulmonary Hypertension Soluble Guanylate Cyclase–Stimulator Trial [CHEST-2]). Conclusion: Data from EXPERT show that in patients with CTEPH, the safety of riociguat in routine practice was consistent with the known safety profile of the drug, and no new safety concerns were identified. © 2020 The Authors Eli Lilly and Company; Pfizer; Bayer; GlaxoSmithKline; Merck; Actelion Pharmaceuticals; Meso Scale Diagnostics; United Therapeutics Corporation; Novartis Pharma; Merck Sharp and Dohme; GlaxoSmithKline Australia; Deutsche Forschungsgemeinschaft; Grupo Ferrer Internacional, S.A The EXPERT registry was funded by Bayer AG (Berlin, Germany) and Merck Sharp & Dohme Corp., a subsidiary of Merck & Co. Inc., Kenilworth, NJ, USA. The authors acknowledge the database administration by Torsten Tille, Dresden, and the project administration of Mrs Romy Hoppenz and Mrs Linda Kottke at GWT-TUD GmbH, Dresden. Medical writing services provided by Richard Murphy PhD of Adelphi Communications Ltd, Macclesfield, UK were funded by Bayer AG in accordance with Good Publication Practice (GPP3) guidelines. The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof Marius M. Hoeper reports personal fees from Bayer AG, during the conduct of the study; personal fees from Actelion, personal fees from Acceleron, personal fees from MSD, personal fees from Jansen, personal fees from Pfizer, outside the submitted work. Dr Hans Klose reports speaker and consultancy fees from Actelion, Bayer AG, GSK, Novartis, Pfizer, and United Therapeutics and research support from Actelion, Bayer AG, GSK, Pfizer, and MSD. Dr Michael Halank reports personal fees and non-financial support from Actelion, AstraZeneca, Bayer AG, Berlin-Chemie, GSK, OMT, MSD, and Novartis. Dr George Giannakoulas reports speaker and consultancy fees from Actelion, Bayer, ELPEN Pharmaceuticals, GSK, Pfizer, Lilly, and United Therapeutics, and research support from GSK, ELPEN Pharmaceuticals, and Galenica. Dr Henning Gall has received honoraria and/or other support from Actelion, AstraZeneca, Bayer, BMS, GSK, Janssen-Cilag, Lilly, MSD, Novartis, OMT, Pfizer, and United Therapeutics. Dr Pavel Jansa reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Prof Ekkehard Grünig reports research grants and speaker honoraria/consultancy fees from Actelion and Bayer/MSD, research grants from GSK, United Therapeutics, Bellerophon, OMT GmbH, Pfizer, Reata, and Novartis, and speaker honoraria from Bial, Medscape, and OrPha Swiss GmbH. Prof David Pittrow reports personal fees from Actelion, Bayer AG, Aspen, Boehringer Ingelheim, Sanofi, Biogen, Shire, and MSD outside the submitted work. Silvia Ulrich reports research grants and personal fees from Actelion, Bayer, MSD, and Orpha Swiss. Tobias J. Lange has received personal fees from Actelion, MSD, Pfizer, and OMT orphan. Dr Iraklis Tsangaris reports speaker and consultancy fees from Actelion, Bayer AG, ELPEN, GSK, MSD, Pfizer, and United Therapeutics. Stephan Rosenkranz reports remunerations for lectures and/or consultancy from Abbott, Actelion, Arena, Bayer, Ferrer, GSK, MSD, Novartis, Pfizer, and United Therapeutics; and research support to his institution from Actelion, Bayer, Novartis, Pfizer, and United Therapeutics. Repke J. Snijder reports grants from Pfizer and Actelion Pharmaceuticals. Prof Iveta Šimková reports consultancy and speaker fees from MSD, AOP Orphan, and Actelion. Dr Marc Humbert reports grants and personal fees from Bayer and GSK, and personal fees from Actelion, Merck, and United Therapeutics. Marion Delcroix has received investigator, speaker, consultant, and steering committee member fees from Actelion, Bayer AG, Bellerophon, Eli Lilly, GlaxoSmithKline, MSD, Pfizer, and Reata, and research grants from Actelion. Joan A. Barberà reports receipt of honoraria for consultation or speaker fees from Actelion and Merck; and research support through his institution from Actelion, Merck, GlaxoSmithKline, and Ferrer. Joanna Pepke-Zaba reports research grants and speaker honoraria/consultancy fees from Actelion, Bayer/MSD, and GSK. Jean-Luc Vachiéry reports ongoing consultancies to Actelion, Sonnivie, Arena Pharma, Bial Portela, and Respira Therapeutics, past consultancies to AstraZeneca, BayerShering, CardioMEMS, GlaxoSmithKline, Pfizer, Merck, and United Therapeutics, and current membership of an advisory board or similar group for Actelion and GlaxoSmithKline. Jean-Luc Vachiéry's institution receives funding from Actelion Pharmaceuticals for performing clinical studies. Regina Steringer-Mascherbauer, Jens Klotsche, and Miguel-Angel Gomez Sanchez have no conflicts of interest relevant to the EXPERT study. Hossein-Ardeschir Ghofrani reports personal fees for advisory board work, and payment for lectures including service on speaker bureaus, from Actelion, Bayer, GSK, Novartis, and Pfizer; consultancy fees from Actelion, Bayer, Bellerophon Pulse Technologies, GSK, MSD, Novartis, and Pfizer; and grants from Deutsche Forschungsgemeinschaft (DFG). Pilar Escribano Subias reports personal fees from Actelion, Bayer AG, GlaxoSmithKline, and Merck Sharp & Dohme, and grants from Actelion, Bayer AG, GlaxoSmithKline, and Ferrer, outside the submitted work. Gérald Simonneau reports personal fees and non-financial support from Actelion, personal fees and non-financial support from Bayer, personal fees and non-financial support from MSD, outside the submitted work. Douglas S. Helmersen reports industry-sponsored research with Bayer AG, United Therapeutics, and Gilead Sciences, Inc., and advisory board/speaker fees from Bayer AG and Actelion. David Langleben reports honoraria, consultation fees, research support, and/or travel expenses from Actelion, Arena, Bayer AG, Northern Therapeutics, PhaseBio, Acceleron, Janssen, and United Therapeutics. Anco Boonstra reports consultancy fees from Pfizer BV and hospitality from Teva Nederland. Lisa M. Mielniczuk reports speaker fees and honoraria from Bayer AG, and speaker fees, consultancy fees, and travel fees from Actelion. Evgenia Williams and Christian Meier are employees of Bayer AG.

The prognostic significance and the optimal treatment strategy for patients with atrial fibrillation (AF) and heart failure (HF) remain controversial.We extracted data from a large prospective national database involving Taiwanese patients with AF who were hospitalized for acute HF with reduced ejection fraction. Baseline characteristics, AF types, medications, and 1-year outcomes of the patients were analyzed.At baseline, 393 (26%) patients had AF, including 117 (29.8%) patients with paroxysmal AF (PAF) and 276 (70.2%) with nonparoxysmal AF (N-PAF). Patients with PAF were more likely to have ischemic cardiomyopathy (47.3% vs 29.7%, p = 0.021), chronic kidney disease (46.2% vs 29.0%, p = 0.001), and higher CHA2DS2-VASc score (4.0 vs 3.6, p = 0.033) compared with patients with N-PAF; however, patients with N-PAF had larger left atrial diameter (50.5 vs 47.3 mm, p = 0.004) than patients with PAF. Patients with PAF were more likely to receive treatment with amiodarone (31.6% vs 13.8%, p0.001) and antiplatelet agents (54.1% vs 42.5%, p = 0.041) but less likely to receive treatment with renin-angiotensin system blockers (52.3% vs 64.9%, p = 0.021) and anticoagulants (33.3% vs 50%, p = 0.003) compared with patients with N-PAF at discharge. The 1-year mortality (26.2% vs 16.5%, p = 0.024) and non-HF-related death rates (13.1% vs 5%, p = 0.005) were significantly higher in patients with PAF, whereas HF and arrhythmic death rates were similar in both groups (13.1% vs 11.5%).Among patients with HF complicated with AF, those with PAF were more likely to receive antiarrhythmic agents, less likely to receive guideline-recommended therapy, but developed worse 1-year outcome compared with patients with N-PAF. These findings further emphasize the importance of optimal guideline-recommended medical therapy in patients with HF.

INTRODUCTION Rhodiola, a popular plant in Tibet, has been proven to decrease arrhythmia. The aim of this study was to elucidate the molecular mechanism and electrophysiological properties of rhodiola in the suppression of atrial fibrillation. METHODS This study consisted of 3 groups as follows: Group 1: normal control rabbits (n = 5); Group 2: rabbits with heart failure (HF) created by coronary ligation and who received 2 weeks of water orally as a placebo (n = 5); and Group 3: rabbits with HF who received 2 weeks of a rhodiola 270 mg/kg/day treatment orally (n = 5). The monophasic action potential, histology, and real-time polymerase chain reaction (RT-PCR) analysis of ionic channels and PI3K/AKT/eNOS were examined. RESULTS Compared with the HF group, attenuated atrial fibrosis (35.4 ± 17.4% vs. 16.9 ± 8.4%, P = 0.05) and improved left ventricular (LV) ejection fraction (51.6 ± 3.4% vs. 68.0 ± 0.5%, P = 0.001) were observed in the rhodiola group. The rhodiola group had a shorter ERP (85.3 ± 6.8 vs. 94.3 ± 1.2, P = 0.002), APD90 (89.3 ± 1.5 vs. 112.7 ± 0.7, P < 0.001) in the left atrium (LA), and decreased AF inducibility (0.90 ± 0.04 vs. 0.42 ± 0.04, P < 0.001) compared with the HF group. The mRNA expressions of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, and SERCA2a in the HF LA were up-regulated after rhodiola treatment. The rhodiola-treated HF LA demonstrated higher mRNA expression of PI3K-AKT compared with the HF group. CONCLUSIONS Rhodiola reversed LA electrical remodeling, attenuated atrial fibrosis and suppressed AF in rabbits with HF. The beneficial electrophysiological effect of rhodiola may be related to upregulation of Kv1.4, Kv1.5, Kv4.3, KvLQT1, Cav1.2, SERCA2a, and activation of PI3K/AKT signaling.

Background Myocardial infarction increases the risk of heart failure ( HF ) and atrial fibrillation. Renal denervation ( RDN ) might suppress the development of atrial remodeling. This study aimed to elucidate the molecular mechanism of RDN in the suppression of atrial fibrillation in a HF model after myocardial infarction. Methods and Results HF rabbits were created 4 weeks after coronary ligation. Rabbits were classified into 3 groups: normal control (n=10), HF (n=10), and HF ‐ RDN (n=6). Surgical and chemical RDN were approached through midabdominal incisions in HF ‐ RDN . Left anterior descending coronary artery in HF and HF ‐ RDN was ligated to create myocardial infarction. After electrophysiological study, the rabbits were euthanized and the left atrial appendage was harvested for real‐time polymerase chain reaction analysis and Trichrome stain. Left atrial dimension and left ventricular mass were smaller in HF ‐ RDN by echocardiography compared with HF . Attenuated atrial fibrosis and tyrosine hydroxylase levels were observed in HF ‐ RDN compared with HF . The mRNA expressions of Cav1.2, Nav1.5, Kir2.1, Kv LQT 1, phosphoinositide 3‐kinase, AKT , and endothelial nitric oxide synthase in HF ‐ RDN were significantly higher compared with HF . The effective refractory period and action potential duration of HF ‐ RDN were significantly shorter compared with HF . Decreased atrial fibrillation inducibility was noted in HF ‐ RDN compared with HF (50% versus 100%, P Conclusions RDN reversed atrial electrical and structural remodeling, and suppressed the atrial fibrillation inducibility in an ischemic HF model. The beneficial effect of RDN may be related to prevention of the downregulation of the phosphoinositide 3‐kinase/ AKT /endothelial nitric oxide synthase signaling pathway.

Background Baseline fasting plasma glucose (FPG) level predicts the onset of type 2 diabetes mellitus (DM). Other predictors have been less investigated. This study aimed to investigate non-glucose predictors together with FPG for future onset of type 2 DM in fresh essential hypertensives. Methods Consecutive nondiabetic patients with newly diagnosed essential hypertension were prospectively evaluated for diurnal blood pressure (BP) change by ambulatory BP monitoring, vascular endothelial function by plethysmography, and biomarkers by blood biochemistry. They were then given guideline-based treatment and followed-up regularly for more than 5 years. Results During a mean follow-up period of 5.9 years, 6 of the 106 study patients developed DM. Baseline FPG, alanine aminotransferase (ALT) level, and day-night difference in diastolic BP were related to future onset of DM. FPG > 5.8 mmol/L ( p = 0.034) and ALT > 31 U/L ( p = 0.048) independently and day-night difference in diastolic BP £ 2.9% potentially predicted new-onset DM ( p = 0.089). Simultaneously having at least 2 of the indicators mentioned above at baseline is predictive of new-onset DM. Parameters of reactive hyperemia by plethysmography were not relevant. Conclusion In addition to FPG, baseline serum ALT level independently and diurnal diastolic BP changes potentially predicted future onset of type 2 DM in newly diagnosed hypertensives. Both glucose and non-glucose indicators could be examined together for early risk stratification of future DM.

Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by premature platelet destruction mediated by autoantibodies. We report a 71-year-old ITP patient with concomitant acute coronary syndrome. Cardiac catheterization was performed through the right radial artery and premedicated with immunoglobulin. Left anterior descending artery was stented, followed by clopidogrel treatment for 7 weeks without major bleeding complication. The patient has been observed for 2 years without clinical restenosis. We suggest that stent implantation is a safe treatment in this special condition. Treatment should be individualized, but it is still a challenge to balance bleeding and thrombosis complication.

Tremor-induced electrocardiographic artifacts could be misdiagnosed as ventricular tachycardia (VT). However, there has been no electrocardiographic algorithm effectively differentiating pseudo-VT. In this study, we used 3 electrocardiographic "signs": "Sinus" sign, "Spike" sign, and "Notch" sign, and created an electrocardiographic algorithm. The algorithm was prospectively tested in 98 electrocardiographs (37 tremor-induced pseudo-VT and 61 true VT) Thirty-six out of 37 (97.3%) tremor-induced pseudo-VTs could be accurately diagnosed. In conclusion, this is the first study to systemically analyze the tremor-induced pseudo-VT. Our new electrocardiographic algorithm provides a useful tool for a rapid and accurate diagnosis.

Aims The efficacy and stability of the atrial electrode sensing function is essential for maintaining atrioventricular (AV) synchrony. This study aimed to explore the long-term reliability and causes of the long-term sensing failure of VDD systems. Methods and results We enrolled all the patients with complete or high-degree AV block who received VDD pacemakers between August 1994 to January 2006 and who were followed up for more than 12 months. The interrogation parameters, including the atrial potentials (APs) and AV-synchrony ratio were acquired immediately post-implantation and at 3–6 month intervals thereafter. An inappropriate atrial sensing efficacy was defined as an AV-synchrony ratio of

Although moderate exercise can benefit health, acute and vigorous exercise may have the opposite effect. Strenuous exercise can induce alterations in the physiology and viability of circulating leucocytes, which have a causal relationship with exercise-induced immune distress.To investigate the use of mitochondrial transmembrane potential (MTP), a functional marker of the energy and viability status of leucocytes, for monitoring the immunomodulating effects of short-term, high-intensity exercise.12 healthy volunteers with a mean Vo(2)max of 70.4 ml/kg/min carried out 3 consecutive days of high-intensity exercise (85% of Vo(2)max for 30 min every day). Blood samples were collected at multiple time points immediately before and after each exercise session and at 24 and 72 h after the completion of exercise. Leucocyte MTP, apoptosis and circulatory inflammation markers were measured by flow cytometry and enzyme-linked immunosorbent assays.MTP of peripheral blood leucocytes had declined immediately after the first exercise session and remained subnormal 24 h later. It did not normalise until 72 h after exercise. The sequential changes in MTP were consistent among the three leucocyte subpopulations (polymorphonuclear neutrophils, lymphocytes and monocytes) and were significant (p0.05). Leucocytes displayed a gradual and incremental change in their propensity for apoptosis during and after exercise. Similarly, plasma concentrations of tumour necrosis factor-alpha and soluble Fas ligand were raised during the exercise sessions and had not normalised by 72 h after the completion of exercise. Correlation between changes in leucocyte MTP and plasma concentrations of tumour necrosis factor-alpha and soluble Fas ligand was variable, but significant for polymorphonuclear neutrophils and lymphocytes (p0.05).Short-term, high-intensity exercise can lead to a significant and prolonged dysfunction of the mitochondrial energy status of peripheral blood leucocytes, which is accompanied by an increased propensity for apoptosis and raised pro-inflammatory mediators. These results support the immunosuppressive effects of excessive exercise and suggest that MTP is a useful marker of these effects.

In a 44-year-old woman admitted due to exertional anginasymptoms, diagnostic coronary angiography (Fig. 1) demon-strated an enlarged right coronary artery with profuse septalcollaterals communicating with the left anterior decendingand left circumflex arteries, and finally draining into the pul-monary artery (PA) via the left main coronary artery (LMCA).Multislice computed tomography (Fig. 2) showed an anoma-lous connection between the LMCA and the PA, further con-firming the diagnosis of Bland-White-Garland syndrome. Thepatient later received bypass surgery and the orifice of LMCAwas repaired with an equine pericardial patch from inside ofthe main PA. Finally, the patient recovered uneventfully.