A systematic review on the effectiveness of robot-assisted minimally invasive gastrectomy.

BACKGROUND: Robot-assisted minimally invasive gastrectomy (RAMIG) is increasingly used as a surgical approach for gastric cancer. This study assessed the effectiveness of RAMIG and studied which stages of the IDEAL-framework (1 = Idea, 2A = Development, 2B = Exploration, 3 = Assessment, 4 = Long-term follow-up) were followed. METHODS: The Cochrane Library, Embase, Pubmed, and Web of Science were searched for studies on RAMIG up to January 2023. Data collection included the IDEAL-stage, demographics, number of participants, and study design. For randomized controlled trials (RCTs) and long-term studies, data on intra-, postoperative, and oncologic outcomes, survival, and costs of RAMIG were collected and summarized. RESULTS: Of the 114 included studies, none reported the IDEAL-stage. After full-text reading, 18 (16%) studies were considered IDEAL-2A, 75 (66%) IDEAL-2B, 4 (4%) IDEAL-3, and 17 (15%) IDEAL-4. The IDEAL-stages were followed sequentially (2A-4), with IDEAL-2A studies still ongoing. IDEAL-3 RCTs showed lower overall complications (8.5-9.2% RAMIG versus 17.6-19.3% laparoscopic total/subtotal gastrectomy), equal 30-day mortality (0%), and equal length of hospital stay for RAMIG (mean 5.7-8.5 days RAMIG versus 6.4-8.2 days open/laparoscopic total/subtotal gastrectomy). Lymph node yield was similar across techniques, but RAMIG incurred significantly higher costs than laparoscopic total/subtotal gastrectomy ($13,423-15,262 versus $10,165-10,945). IDEAL-4 studies showed similar or improved overall/disease-free survival for RAMIG. CONCLUSION: During worldwide RAMIG implementation, the IDEAL-framework was followed in sequential order. IDEAL-3 and 4 long-term studies showed that RAMIG is similar or even better to conventional surgery in terms of hospital stay, lymph node yield, and overall/disease-free survival. In addition, RAMIG showed reduced postoperative complication rates, despite higher costs.

Longitudinal Changes in Circulating Ketone Body Levels in Patients With Acute Heart Failure: A Post Hoc Analysis of the EMPA-Response-AHF Trial.

BACKGROUND: Ketone bodies are endogenous fuels produced by the liver under conditions of metabolic or neurohormonal stress. Circulating ketone bodies are increased in patients with chronic heart failure (HF), yet little is known about the effect of acute HF on ketosis. We tested the hypothesis that ketogenesis is increased in patients with acute decompensated HF. METHODS AND RESULTS: This was a post hoc analysis of 79 patients with acute HF included in the EMPA-RESPONSE-AHF trial, which compared sodium-dependent glucose-cotransporter protein 2 inhibitor treatment with empagliflozin for 30 days with placebo in patients with acute HF [NCT03200860]. Plasma concentrations of ketone bodies acetone, ß-hydroxybutyrate, and acetoacetate were measured at baseline and 5 different timepoints. Changes in ketone bodies over time were monitored using repeated measures analysis of variance. In the total cohort, median total ketone body concentration was 251 µmol/L (interquartile range, 178-377 µmol/L) at baseline, which gradually decreased to 202 µmol/L (interquartile range, 156-240 µmol/L) at day 30 (P = .041). Acetone decreased from 60 µmol/L (interquartile range, 34-94 µmol/L) at baseline to 30 µmol/L (interquartile range, 21-42 µmol/L) ( P < .001), whereas ß-hydroxybutyrate and acetoacetate remained stable over time. Higher acetone concentrations were correlated with higher N-terminal pro brain natriuretic peptide levels (r = 0.234; P = .039). Circulating ketone bodies did not differ between patients treated with empagliflozin or placebo throughout the study period. A higher acetone concentration at baseline was univariately associated with a greater risk of the composite end point, including in-hospital worsening HF, HF rehospitalizations, and all-cause mortality after 30 days. However, after adjustment for age and sex, acetone did not remain an independent predictor for the combined end point. CONCLUSIONS: Circulating ketone body concentrations, and acetone in particular, were significantly higher during an episode of acute decompensated HF compared with after stabilization. Treatment with empagliflozin did not affect ketone body concentrations in patients with acute HF.

Search for Λ[over ¯]-Λ Baryon-Number-Violating Oscillations in the Decay J/ψ→pK

We report on the first search for Λ[over ¯]-Λ oscillations in the decay J/ψ→pK^{-}Λ[over ¯]+c.c. by analyzing 1.31×10^{9} J/ψ events accumulated with the BESIII detector at the BEPCII collider. The J/ψ events are produced using e^{+}e^{-} collisions at a center of mass energy sqrt[s]=3.097 GeV. No evidence for hyperon oscillations is observed. The upper limit for the oscillation rate of Λ[over ¯] to Λ hyperons is determined to be P(Λ)=[B(J/ψ→pK^{-}Λ+c.c.)/B(J/ψ→pK^{-}Λ[over ¯]+c.c.)]<4.4×10^{-6} corresponding to an oscillation parameter δm_{ΛΛ[over ¯]} of less than 3.8×10^{-18} GeV at the 90% confidence level.

Deep learning-based recognition of key anatomical structures during robot-assisted minimally invasive esophagectomy.

OBJECTIVE: To develop a deep learning algorithm for anatomy recognition in thoracoscopic video frames from robot-assisted minimally invasive esophagectomy (RAMIE) procedures using deep learning. BACKGROUND: RAMIE is a complex operation with substantial perioperative morbidity and a considerable learning curve. Automatic anatomy recognition may improve surgical orientation and recognition of anatomical structures and might contribute to reducing morbidity or learning curves. Studies regarding anatomy recognition in complex surgical procedures are currently lacking. METHODS: Eighty-three videos of consecutive RAMIE procedures between 2018 and 2022 were retrospectively collected at University Medical Center Utrecht. A surgical PhD candidate and an expert surgeon annotated the azygos vein and vena cava, aorta, and right lung on 1050 thoracoscopic frames. 850 frames were used for training of a convolutional neural network (CNN) to segment the anatomical structures. The remaining 200 frames of the dataset were used for testing the CNN. The Dice and 95% Hausdorff distance (95HD) were calculated to assess algorithm accuracy. RESULTS: The median Dice of the algorithm was 0.79 (IQR = 0.20) for segmentation of the azygos vein and/or vena cava. A median Dice coefficient of 0.74 (IQR = 0.86) and 0.89 (IQR = 0.30) were obtained for segmentation of the aorta and lung, respectively. Inference time was 0.026 s (39 Hz). The prediction of the deep learning algorithm was compared with the expert surgeon annotations, showing an accuracy measured in median Dice of 0.70 (IQR = 0.19), 0.88 (IQR = 0.07), and 0.90 (0.10) for the vena cava and/or azygos vein, aorta, and lung, respectively. CONCLUSION: This study shows that deep learning-based semantic segmentation has potential for anatomy recognition in RAMIE video frames. The inference time of the algorithm facilitated real-time anatomy recognition. Clinical applicability should be assessed in prospective clinical studies.

Measurement of the Cross Section for e

Based on electron-positron collision data collected with the BESIII detector operating at the Beijing Electron-Positron Collider II storage rings, the value of R≡σ(e^{+}e^{-}→hadrons)/σ(e^{+}e^{-}→µ^{+}µ^{-}) is measured at 14 center-of-mass energies from 2.2324 to 3.6710 GeV. The resulting uncertainties are less than 3.0% and are dominated by systematic uncertainties.

First Measurement of Polarizations in the Decay D

Using a data sample corresponding to an integrated luminosity of 2.93 fb^{-1} collected at a center-of-mass energy sqrt[s]=3.773 GeV by the BESIII detector, the decay D^{0}→ωϕ is observed for the first time. The branching fraction is measured to be (6.48±0.96±0.40)×10^{-4} with a significance of 6.3σ, where the first and second uncertainties are statistical and systematic, respectively. An angular analysis reveals that the ϕ and ω mesons from the D^{0}→ωϕ decay are transversely polarized. The 95% confidence level upper limit on longitudinal polarization fraction is set to be less than 0.24, which is inconsistent with current theoretical expectations and challenges our understanding of the underlying dynamics in charm meson decays.

Observation of J/ψ Electromagnetic Dalitz Decays to X(1835), X(2120), and X(2370).

Using a sample of about 10^{10} J/ψ events collected at a center-of-mass energy sqrt[s]=3.097 GeV with the BESIII detector, the electromagnetic Dalitz decays J/ψ→e^{+}e^{-}π^{+}π^{-}η^{'}, with η^{'}→γπ^{+}π^{-} and η^{'}→π^{+}π^{-}η, have been studied. The decay J/ψ→e^{+}e^{-}X(1835) is observed with a significance of 15σ, and also an e^{+}e^{-} invariant-mass dependent transition form factor of J/ψ→e^{+}e^{-}X(1835) is presented for the first time. The intermediate states X(2120) and X(2370) are also observed in the π^{+}π^{-}η^{'} invariant-mass spectrum with significances of 5.3σ and 7.3σ. The corresponding product branching fractions for J/ψ→e^{+}e^{-}X, X→π^{+}π^{-}η^{'} [X=X(1835), X(2120), and X(2370)] are reported.

Observation of the Singly Cabibbo Suppressed Decay Λ_{c}

The singly Cabibbo-suppressed decay Λ_{c}^{+}→nπ^{+} is observed for the first time with a statistical significance of 7.3σ by using 3.9 fb^{-1} of e^{+}e^{-} collision data collected at center-of-mass energies between 4.612 and 4.699 GeV with the BESIII detector at BEPCII. The branching fraction of Λ_{c}^{+}→nπ^{+} is measured to be (6.6±1.2_{stat}±0.4_{syst})×10^{-4}. By taking the upper limit of branching fractions of Λ_{c}^{+}→pπ^{0} from the Belle experiment, the ratio of branching fractions between Λ_{c}^{+}→nπ^{+} and Λ_{c}^{+}→pπ^{0} is calculated to be larger than 7.2 at the 90% confidence level, which disagrees with most predictions of the available phenomenological models. In addition, the branching fractions of the Cabibbo-favored decays Λ_{c}^{+}→Λπ^{+} and Λ_{c}^{+}→Σ^{0}π^{+} are measured to be (1.31±0.08_{stat}±0.05_{syst})×10^{-2} and (1.22±0.08_{stat}±0.07_{syst})×10^{-2}, respectively, which are consistent with previous results.

Computer-aided anatomy recognition in intrathoracic and -abdominal surgery: a systematic review.

BACKGROUND: Minimally invasive surgery is complex and associated with substantial learning curves. Computer-aided anatomy recognition, such as artificial intelligence-based algorithms, may improve anatomical orientation, prevent tissue injury, and improve learning curves. The study objective was to provide a comprehensive overview of current literature on the accuracy of anatomy recognition algorithms in intrathoracic and -abdominal surgery. METHODS: This systematic review is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. Pubmed, Embase, and IEEE Xplore were searched for original studies up until January 2022 on computer-aided anatomy recognition, without requiring intraoperative imaging or calibration equipment. Extracted features included surgical procedure, study population and design, algorithm type, pre-training methods, pre- and post-processing methods, data augmentation, anatomy annotation, training data, testing data, model validation strategy, goal of the algorithm, target anatomical structure, accuracy, and inference time. RESULTS: After full-text screening, 23 out of 7124 articles were included. Included studies showed a wide diversity, with six possible recognition tasks in 15 different surgical procedures, and 14 different accuracy measures used. Risk of bias in the included studies was high, especially regarding patient selection and annotation of the reference standard. Dice and intersection over union (IoU) scores of the algorithms ranged from 0.50 to 0.98 and from 74 to 98%, respectively, for various anatomy recognition tasks. High-accuracy algorithms were typically trained using larger datasets annotated by expert surgeons and focused on less-complex anatomy. Some of the high-accuracy algorithms were developed using pre-training and data augmentation. CONCLUSIONS: The accuracy of included anatomy recognition algorithms varied substantially, ranging from moderate to good. Solid comparison between algorithms was complicated by the wide variety of applied methodology, target anatomical structures, and reported accuracy measures. Computer-aided intraoperative anatomy recognition is an upcoming research discipline, but still at its infancy. Larger datasets and methodological guidelines are required to improve accuracy and clinical applicability in future research. TRIAL REGISTRATION: PROSPERO registration number: CRD42021264226.

Diagnostic role of echocardiography for patients with heart failure symptoms and preserved left ventricular ejection fraction.

The syndrome heart failure with preserved ejection fraction (HFpEF) represents patients with different comorbidities and specific etiologies, but with a key and common alteration: an elevation in left ventricular (LV) filling pressure or pulmonary capillary wedge pressure (PCWP). Expert consensuses, society guidelines, and diagnostic scores have been stated to diagnose HFpEF syndrome based mainly on the determination of elevated LV filling pressure or PCWP by transthoracic echocardiography (TTE). Echocardiographic parameters such as early (E) and late diastolic mitral inflow velocity (mitral E/A ratio), septal and lateral mitral annular early diastolic velocity (E'), ratio of the early diastolic mitral inflow and annular velocity (E/E'-ratio), maximal left atrial volume index (LAVImax), and tricuspid regurgitation peak velocity (VTR) constitute the pivotal parameters for determining elevated LV filling pressure or PCWP in patients with suspected HFpEF symptoms. Notwithstanding this, taking into consideration the heterogeneity of patients with HFpEF symptoms, the term "HFpEF" should be considered as a syndrome rather than an entity since HFpEF results from different pathological entities that should and can be characterized by echocardiography and multimodality imaging. Comprehensive TTE might help diagnose specific diseases and etiologies by characterization of specific cardiac phenotypes.

Immune checkpoint inhibitor-associated myocarditis : Case reports and a review of the literature.

Immune checkpoint inhibitors (ICIs) are increasingly recognised to effectuate long-lasting therapeutic responses in solid tumours. However, ICI therapy can also result in various immune-related adverse events, such as ICI-associated myocarditis, a rare but serious complication. The clinical spectrum is wide and includes asymptomatic patients and patients with fulminant heart failure, making it challenging to diagnose this condition. Furthermore, the optimal diagnostic algorithm and treatment of ICI-associated myocarditis is unknown. In this review, we describe two cases on both ends of the spectrum and discuss the challenges in recognising, diagnosing and treating ICI-associated myocarditis.

Rationale and design of the PHOspholamban RElated CArdiomyopathy intervention STudy (i-PHORECAST).

BACKGROUND: The p.Arg14del (c.40_42delAGA) phospholamban (PLN) pathogenic variant is a founder mutation that causes dilated cardiomyopathy (DCM) and arrhythmogenic cardiomyopathy (ACM). Carriers are at increased risk of malignant ventricular arrhythmias and heart failure, which has been ascribed to cardiac fibrosis. Importantly, cardiac fibrosis appears to be an early feature of the disease, occurring in many presymptomatic carriers before the onset of overt disease. As with most monogenic cardiomyopathies, no evidence-based treatment is available for presymptomatic carriers. AIMS: The PHOspholamban RElated CArdiomyopathy intervention STudy (iPHORECAST) is designed to demonstrate that pre-emptive treatment of presymptomatic PLN p.Arg14del carriers using eplerenone, a mineralocorticoid receptor antagonist with established antifibrotic effects, can reduce disease progression and postpone the onset of overt disease. METHODS: iPHORECAST has a multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) design. Presymptomatic PLN p.Arg14del carriers are randomised to receive either 50 mg eplerenone once daily or no treatment. The primary endpoint of the study is a multiparametric assessment of disease progression including cardiac magnetic resonance parameters (left and right ventricular volumes, systolic function and fibrosis), electrocardiographic parameters (QRS voltage, ventricular ectopy), signs and/or symptoms related to DCM and ACM, and cardiovascular death. The follow-up duration is set at 3 years. BASELINE RESULTS: A total of 84 presymptomatic PLN p.Arg14del carriers (n = 42 per group) were included. By design, at baseline, all participants were in New York Heart Association (NHYA) class I and had a left ventricular ejection fraction > 45% and < 2500 ventricular premature contractions during 24-hour Holter monitoring. There were no statistically significant differences between the two groups in any of the baseline characteristics. The study is currently well underway, with the last participants expected to finish in 2021. CONCLUSION: iPHORECAST is a multicentre, prospective randomised controlled trial designed to address whether pre-emptive treatment of PLN p.Arg14del carriers with eplerenone can prevent or delay the onset of cardiomyopathy. iPHORECAST has been registered in the clinicaltrials.gov-register (number: NCT01857856).

Observation of D

Using 2.93 fb^{-1} of e^{+}e^{-} collision data taken with the BESIII detector at a center-of-mass energy of 3.773 GeV, the observation of the D^{0}→K_{1}(1270)^{-}e^{+}ν_{e} semileptonic decay is presented. The statistical significance of the decay D^{0}→K_{1}(1270)^{-}e^{+}ν_{e} is greater than 10σ. The branching fraction of D^{0}→K_{1}(1270)^{-}e^{+}ν_{e} is measured to be (1.09±0.13_{-0.16}^{+0.09}±0.12)×10^{-3}. Here, the first uncertainty is statistical, the second is systematic, and the third originates from the assumed branching fraction of K_{1}(1270)^{-}→K^{-}π^{+}π^{-}. The fraction of longitudinal polarization in D^{0}→K_{1}(1270)^{-}e^{+}ν_{e} is determined for the first time to be 0.50±0.19_{stat}±0.08_{syst}.

First Measurement of the Absolute Branching Fraction of Λ→pµ

The absolute branching fraction of Λ→pµ^{-}ν[over ¯]_{µ} is reported for the first time based on an e^{+}e^{-} annihilation sample of 10×10^{9} J/ψ events collected with the BESIII detector at sqrt[s]=3.097 GeV. The branching fraction is determined to be B(Λ→pµ^{-}ν[over ¯]_{µ})=[1.48±0.21(stat)±0.08(syst)]×10^{-4}, which is improved by about 30% in precision over the previous indirect measurements. Combining this result with the world average of B(Λ→pe^{-}ν[over ¯]_{e}), we obtain the ratio {[Γ(Λ→pµ^{-}ν[over ¯]_{µ})]/[Γ(Λ→pe^{-}ν[over ¯]_{e})]} to be 0.178±0.028, which agrees with the standard model prediction assuming lepton flavor universality. The asymmetry of the branching fractions of Λ→pµ^{-}ν[over ¯]_{µ} and Λ[over ¯]→p[over ¯]µ^{+}ν_{µ} is also determined, and no evidence for CP violation is found.

Direct Measurement of the Branching Fractions B(ψ(3686)→J/ψX) and B(ψ(3770)→J/ψX), and Observation of the State R(3760) in e

We report a measurement of the observed cross sections of e^{+}e^{-}→J/ψX based on 3.21 fb^{-1} of data accumulated at energies from 3.645 to 3.891 GeV with the BESIII detector operated at the BEPCII collider. In analysis of the cross sections, we measured the decay branching fractions of B(ψ(3686)→J/ψX)=(64.4±0.6±1.6)% and B(ψ(3770)→J/ψX)=(0.5±0.2±0.1)% for the first time. The energy-dependent line shape of these cross sections cannot be well described by two Breit-Wigner (BW) amplitudes of the expected decays ψ(3686)→J/ψX and ψ(3770)→J/ψX. Instead, it can be better described with one more BW amplitude of the decay R(3760)→J/ψX. Under this assumption, we extracted the R(3760) mass M_{R(3760)}=3766.2±3.8±0.4 MeV/c^{2} , total width Γ_{R(3760)}^{tot}=22.2±5.9±1.4 MeV, and product of leptonic width and decay branching fraction Γ_{R(3760)}^{ee}B[R(3760)→J/ψX]=(79.4±85.5±11.7) eV. The significance of the R(3760) is 5.3σ. The first uncertainties of these measured quantities are from fits to the cross sections and second systematic.

Measurement of the Absolute Branching Fraction of D_{s}

Using a dataset of 6.32 fb^{-1} of e^{+}e^{-} annihilation data collected with the BESIII detector at center-of-mass energies between 4178 and 4226 MeV, we have measured the absolute branching fraction of the leptonic decay D_{s}^{+}→τ^{+}ν_{τ} via τ^{+}→e^{+}ν_{e}ν[over ¯]_{τ}, and find B_{D_{s}^{+}→τ^{+}ν_{τ}}=(5.27±0.10±0.12)×10^{-2}, where the first uncertainty is statistical and the second is systematic. The precision is improved by a factor of 2 compared to the previous best measurement. Combining with f_{D_{s}^{+}} from lattice quantum chromodynamics calculations or the |V_{cs}| from the CKMfitter group, we extract |V_{cs}|=0.978±0.009±0.012 and f_{D_{s}^{+}}=(251.1±2.4±3.0) MeV, respectively. Combining our result with the world averages of B_{D_{s}^{+}→τ^{+}ν_{τ}} and B_{D_{s}^{+}→µ^{+}ν_{µ}}, we obtain the ratio of the branching fractions B_{D_{s}^{+}→τ^{+}ν_{τ}}/B_{D_{s}^{+}→µ^{+}ν_{µ}}=9.72±0.37, which is consistent with the standard model prediction of lepton flavor universality.

Observation of a Near-Threshold Structure in the K

We report a study of the processes of e^{+}e^{-}→K^{+}D_{s}^{-}D^{*0} and K^{+}D_{s}^{*-}D^{0} based on e^{+}e^{-} annihilation samples collected with the BESIII detector operating at BEPCII at five center-of-mass energies ranging from 4.628 to 4.698 GeV with a total integrated luminosity of 3.7 fb^{-1}. An excess of events over the known contributions of the conventional charmed mesons is observed near the D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0} mass thresholds in the K^{+} recoil-mass spectrum for events collected at sqrt[s]=4.681 GeV. The structure matches a mass-dependent-width Breit-Wigner line shape, whose pole mass and width are determined as (3982.5_{-2.6}^{+1.8}±2.1) MeV/c^{2} and (12.8_{-4.4}^{+5.3}±3.0) MeV, respectively. The first uncertainties are statistical and the second are systematic. The significance of the resonance hypothesis is estimated to be 5.3 σ over the contributions only from the conventional charmed mesons. This is the first candidate for a charged hidden-charm tetraquark with strangeness, decaying into D_{s}^{-}D^{*0} and D_{s}^{*-}D^{0}. However, the properties of the excess need further exploration with more statistics.

Model-Independent Determination of the Spin of the Ω

We present an analysis of the process ψ(3686)→Ω^{-}Ω[over ¯]^{+} (Ω^{-}→K^{-}Λ, Ω[over ¯]^{+}→K^{+}Λ[over ¯], Λ→pπ^{-}, Λ[over ¯]→p[over ¯]π^{+}) based on a dataset of 448×10^{6} ψ(3686) decays collected with the BESIII detector at the BEPCII electron-positron collider. The helicity amplitudes for the process ψ(3686)→Ω^{-}Ω[over ¯]^{+} and the decay parameters of the subsequent decay Ω^{-}→K^{-}Λ (Ω[over ¯]^{+}→K^{+}Λ[over ¯]) are measured for the first time by a fit to the angular distribution of the complete decay chain, and the spin of the Ω^{-} is determined to be 3/2 for the first time since its discovery more than 50 years ago.

Improvement in left ventricular ejection fraction after pharmacological up-titration in new-onset heart failure with reduced ejection fraction.

OBJECTIVE: Recent studies have reported suboptimal up-titration of heart failure (HF) therapies in patients with heart failure and a reduced ejection fraction (HFrEF). Here, we report on the achieved doses after nurse-led up-titration, reasons for not achieving the target dose, subsequent changes in left ventricular ejection fraction (LVEF), and mortality. METHODS: From 2012 to 2018, 378 HFrEF patients with a recent (< 3 months) diagnosis of HF were referred to a specialised HF-nurse led clinic for protocolised up-titration of guideline-directed medical therapy (GDMT). The achieved doses of GDMT at 9 months were recorded, as well as reasons for not achieving the optimal dose in all patients. Echocardiography was performed at baseline and after up-titration in 278 patients. RESULTS: Of 345 HFrEF patients with a follow-up visit after 9 months, 69% reached ≥ 50% of the recommended dose of renin-angiotensin-system (RAS) inhibitors, 73% reached ≥ 50% of the recommended dose of beta-blockers and 77% reached ≥ 50% of the recommended dose of mineralocorticoid receptor antagonists. The main reasons for not reaching the target dose were hypotension (RAS inhibitors and beta-blockers), bradycardia (beta-blockers) and renal dysfunction (RAS inhibitors). During a median follow-up of 9 months, mean LVEF increased from 27.6% at baseline to 38.8% at follow-up. Each 5% increase in LVEF was associated with an adjusted hazard ratio of 0.84 (0.75-0.94, p = 0.002) for mortality and 0.85 (0.78-0.94, p = 0.001) for the combined endpoint of mortality and/or HF hospitalisation after a mean follow-up of 3.3 years. CONCLUSIONS: This study shows that protocolised up-titration in a nurse-led HF clinic leads to high doses of GDMT and improvement of LVEF in patients with new-onset HFrEF.

BIO FOr CARE: biomarkers of hypertrophic cardiomyopathy development and progression in carriers of Dutch founder truncating MYBPC3 variants-design and status.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is the most prevalent monogenic heart disease, commonly caused by truncating variants in the MYBPC3 gene. HCM is an important cause of sudden cardiac death; however, overall prognosis is good and penetrance in genotype-positive individuals is incomplete. The underlying mechanisms are poorly understood and risk stratification remains limited. AIM: To create a nationwide cohort of carriers of truncating MYBPC3 variants for identification of predictive biomarkers for HCM development and progression. METHODS: In the multicentre, observational BIO FOr CARe (Identification of BIOmarkers of hypertrophic cardiomyopathy development and progression in Dutch MYBPC3 FOunder variant CARriers) cohort, carriers of the c.2373dupG, c.2827C > T, c.2864_2865delCT and c.3776delA MYBPC3 variants are included and prospectively undergo longitudinal blood collection. Clinical data are collected from first presentation onwards. The primary outcome constitutes a composite endpoint of HCM progression (maximum wall thickness ≥ 20 mm, septal reduction therapy, heart failure occurrence, sustained ventricular arrhythmia and sudden cardiac death). RESULTS: So far, 250 subjects (median age 54.9 years (interquartile range 43.3, 66.6), 54.8% male) have been included. HCM was diagnosed in 169 subjects and dilated cardiomyopathy in 4. The primary outcome was met in 115 subjects. Blood samples were collected from 131 subjects. CONCLUSION: BIO FOr CARe is a genetically homogeneous, phenotypically heterogeneous cohort incorporating a clinical data registry and longitudinal blood collection. This provides a unique opportunity to study biomarkers for HCM development and prognosis. The established infrastructure can be extended to study other genetic variants. Other centres are invited to join our consortium.