The effect of kidney function on guideline-directed medical therapy implementation and prognosis in heart failure with reduced ejection fraction.

BACKGROUND: Kidney dysfunction (KD) is a main limiting factor of applying guideline-directed medical therapy (GDMT) and reaching the recommended target doses (TD) in heart failure (HF) with reduced ejection fraction (HFrEF). HYPOTHESIS: We aimed to assess the success of optimization, long-term applicability, and adherence of neurohormonal antagonist triple therapy (TT:RASi [ACEi/ARB/ARNI] + ßB + MRA) according to the KD after a HF hospitalization and to investigate its impact on prognosis. METHODS: The data of 247 real-world, consecutive patients were analyzed who were hospitalized in 2019-2021 for HFrEF and then were followed-up for 1 year. The application and the ratio of reached TD of TT at hospital discharge and at 1 year were assessed comparing KD categories (eGFR: ≥90, 60-89, 45-59, 30-44, <30 mL/min/1.73 m2 ). Moreover, 1-year all-cause mortality and rehospitalization rates in KD subgroups were investigated. RESULTS: Majority of the patients received TT at hospital discharge (77%) and at 1 year (73%). More severe KD led to a lower application ratio (p < .05) of TT (92%, 88%, 80%, 73%, 31%) at discharge and at 1 year (81%, 76%, 76%, 68%, 40%). Patients with more severe KD were less likely (p < .05) to receive TD of MRA (81%, 68%, 78%, 61%, 52%) at discharge and a RASi (53%, 49%, 45%, 21%, 27%) at 1 year. One-year all-cause mortality (14%, 15%, 16%, 33%, 48%, p < .001), the ratio of all-cause rehospitalizations (30%, 35%, 40%, 43%, 52%, p = .028), and rehospitalizations for HF (8%, 13%, 18%, 20%, 38%, p = .001) were significantly higher in more severe KD categories. CONCLUSIONS: KD unfavorably affects the application of TT in HFrEF, however poorer mortality and rehospitalization rates among them highlight the role of the conscious implementation and up-titration of GDMT.

The Impact of Specialised Heart Failure Outpatient Care on the Long-Term Application of Guideline-Directed Medical Therapy and on Prognosis in Heart Failure with Reduced Ejection Fraction.

(1) Background: Besides the use of guideline-directed medical therapy (GDMT), multidisciplinary heart failure (HF) outpatient care (HFOC) is of strategic importance in HFrEF. (2) Methods: Data from 257 hospitalised HFrEF patients between 2019 and 2021 were retrospectively analysed. Application and target doses of GDMT were compared between HFOC and non-HFOC patients at discharge and at 1 year. 1-year all-cause mortality (ACM) and rehospitalisation (ACH) rates were compared using the Cox proportional hazard model. The effect of HFOC on GDMT and on prognosis after propensity score matching (PSM) of 168 patients and the independent predictors of 1-year ACM and ACH were also evaluated. (3) Results: At 1 year, the application of RASi, MRA and triple therapy (TT: RASi + ßB + MRA) was higher (p < 0.05) in the HFOC group, as was the proportion of target doses of ARNI, ßB, MRA and TT. After PSM, the composite of 1-year ACM or ACH was more favourable with HFOC (propensity-adjusted HR = 0.625, 95% CI = 0.401-0.974, p = 0.038). Independent predictors of 1-year ACM were age, systolic blood pressure, application of TT and HFOC, while 1-year ACH was influenced by the application of TT. (4) Conclusions: HFOC may positively impact GDMT use and prognosis in HFrEF even within the first year of its initiation.

Investigation of Vegetable Oils and Their Derivatives for the Synthesis of Extreme Pressure Additives.

The harmful effects of wear can be reduced through proper lubrication of the frictional parts. When exposed to excessive loads, the lubricant film is displaced from the surfaces, and even the adhesive lubricant layer may rupture. Additives known as Extreme Pressure (EP) are frequently incorporated into lubricants to minimise wear and avert seizures under high temperature and pressure. Mechanistically, these additives generate a film on the surface through chemisorption. These additives are extensively applied in various lubricants, with the largest quantities being employed in metalworking fluids and lubricating greases. Sulfurized vegetable oils and their derivates can be used as EP additives for lubricants. To conduct the investigations, sulfurized additives were synthesized using different vegetable-based oils and fatty acid esters, and alpha-olefins. In this study, the Four-ball test results were compared to gain a more accurate comprehension of how various raw-material-based additives influence wear and friction. The goal was to select raw materials that could be used with favorable results for the production of EP additives. The objective was to achieve a minimum Four-ball weld load parameter of 2000 N. The experiments revealed that the functional impacts of the synthesized samples are dependent on the type of raw materials employed. Based on the experimental data and the stated criteria, the examined raw materials were found to be suitable for the synthesis of EP additives.

[The effect of kidney function on the optimization of medical therapy and on mortality in heart failure with reduced ejection fraction]. / A vesefunkció hatása a gyógyszeres terápia optimalizálására és a mortalitásra csökkent ejekciós frakciójú szívelégtelenségben.

INTRODUCTION: Renal dysfunction is a main limiting factor of applying and up-titrating guideline-directed medical therapy (GDMT) among patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVE: Our retrospective monocentric observational study aimed to analyse the application ratio of combined neurohormonal antagonist therapy (RASi: ACEI/ARB/ARNI + ßB + MRA) and 12-month all-cause mortality differences in terms of renal dysfunction among HFrEF patients hospitalized for heart failure. METHOD: We retrospectively analysed the cohort of consecutive HFrEF patients, hospitalized at the Heart Failure Unit of our tertiary cardiological centre in 2019-2021. The application ratio of discharge triple therapy (TT) in five groups established on admission eGFR parameters, representing severity of renal dysfunction (eGFR≥90, eGFR = 60-89, eGFR = 45-59, eGFR = 30-44, eGFR<30 ml/min/1.73 m2) was investigated with chi-square test, while 12-month mortality differences were analysed with Kaplan-Meier method and log-rank test. RESULTS: 257 patients were included. Median eGFR was 57 (39-75) ml/min/1.73 m2, 54% of patients had eGFR<60 ml/min/1.73 m2. The proportion of patients in eGFR≥90, 60-89, 45-59, 30-44, <30 ml/min/1.73 m2 subgroups was 12%, 34%, 18%, 21%, 15%, respectively. 2% of patients were on dialysis. Even though the application rate of TT was notably high (77%) in the total cohort, more severe renal dysfunction led to a significantly lower implementation rate of TT (94%, 86%, 91%, 70%, 34%; p<0.0001): the application rate of RASi (100%, 98%, 96%, 89%, 50%, p<0.0001), ßB (94%, 88%, 96%, 79%, 68%; p = 0.003) and MRA therapy (97%, 99%, 98%, 94%, 82%; p = 0.001) differed significantly. 12-month all-cause mortality was 23% in the whole cohort. Mortality rates were higher in more severe renal dysfunction (3%, 15%, 22%, 31%, 46%; p<0.0001). CONCLUSION: Even though the proportion of patients on TT in the whole cohort was remarkably high, renal dysfunction led to a significantly lower application ratio of TT, associating with worse survival. Our results highlight that despite renal dysfunction the application of HFrEF cornerstone pharmacotherapy is essential. Orv Hetil. 2023; 164(35): 1387-1396.

Modular Synthesis of (Borylmethyl)silanes through Orthogonal Functionalization of a Carbon Atom.

(Borylmethyl)trimethylsilanes are important building blocks in organic synthesis displaying a unique reactivity. Yet, the synthesis of more advanced derivatives is limited by the advanced silicon intermediates required for their preparation. Herein, a one-pot synthesis of (borylmethyl)silanes is developed, sourced on available alkyl-, aryl-, alkoxy-, aryloxy-, and silyl-hydrosilane materials. The privileged reactivity of N-hydroxyphthalimidyl diazoacetate (NHPI-DA) in Si-H insertion and α-silyl redox-active esters in different decarboxylative borylation reactions are scrutinized.

The Optimization of Guideline-Directed Medical Therapy during Hospitalization among Patients with Heart Failure with Reduced Ejection Fraction in Daily Clinical Practice.

INTRODUCTION: Hospitalization due to heart failure (HF) progression is associated with poor prognosis. This highlights the role of the implementation of guideline-directed medical therapy (GDMT) in improving the morbidity and mortality of patients with heart failure with reduced ejection fraction (HFrEF). There are limited data about the intrahospital applicability of GDMT in real-world circumstances. We aimed to assess retrospectively the use of cornerstone GDMT including RASi (ACEI/ARB/ARNI), ßB, MRA, and SGLT2i treatment in a consecutive real-world HFrEF patient population admitted with signs and symptoms of HF to the HF Unit of a Hungarian tertiary cardiac center between 2019 and 2021. The independent predictors of therapy optimization and the applicability of new HFrEF medication (ARNI, SGLT2i, vericiguat) were also investigated. METHODS: Statistical comparison of admission and discharge medication was accomplished with Fisher's exact test. The independent predictors of the introduction of triple therapy (RASi + ßB + MRA) were analyzed using univariate and multivariate logistic regression. The proportion of patients eligible for vericiguat based on the inclusion and exclusion criteria of the VICTORIA trial was also investigated, as well as the number of patients suitable for ARNI and SGLT2i, taking into account the contraindications of application contained in the ESC 2021 HF Guidelines. RESULTS: 238 patients were included. During hospitalization, the use of RASi (69% vs. 89%) (ACEI/ARBs [58% vs. 70%], ARNI [10% vs. 19%]), ßBs (69% vs. 85%), and MRAs (61% vs. 95%) increased significantly (p < 0.05) compared to at admission, and the use of SGLT2i (3% vs. 11%) also rose (p = 0.0005). The application ratio of triple (RASi + ßB + MRA; 43% vs. 77%) and quadruple (RASi + ßB + MRA + SGLT2i; 2% vs. 11%) therapy increased as well (p < 0.0001). The independent predictors of discharge application of triple therapy revealed through multivariate logistic regression analysis were age, duration of hospitalization, eGFR, NTproBNP, and presence of diabetes mellitus. Sixty-eight percent of the cohort would have been suitable for vericiguat, 83% for ARNI, and 84% for SGLT2i. CONCLUSION: High rates of application of disease-modifying drugs are achievable among hospitalized HFrEF patients in severe clinical condition; thus, awareness of the need for their initiation must be raised.

How to best handle vaccine decliners: scientific facts and psychological approach.

There is currently no curative drug therapy for COVID-19. The spread of the virus seems relentless despite the unprecedented epidemiological measures. Prevention remains the only feasible option to stop the pandemic; without population-level vaccination, we are unlikely to regain the quality of social life and the unrestricted economy/commerce we enjoyed before. Anti-vaxxers and conspiracy theorists are seemingly oblivious to the detrimental effect of COVID-19 both at an individual and societal level. These groups have (and probably will) continue to attempt to undermine efforts to eradicate the virus despite the fact that the major reduction in morbidity/and mortality of infectious diseases of the past century was achieved through the development of vaccines and improved hygiene. Conspiracy theories are directly associated with reduced vaccine uptake and unfortunately neither anti-vaxxers nor vaccine hesitants cannot be persuaded (debunked) with logical arguments; hence, prescribers must not only be aware of the truth underlying the dense web of misinformation but must fully understand the psychological aspects as well to be able to efficiently counsel about the potential benefits and harms. Such knowledge is pivotal to help the lay public to make informed decisions about SARS CoV-2 in general and vaccination in particular; as the COVID-19 situation can probably be best controlled with mass inoculation and novel immune therapies. The lessons learnt regarding the importance of efficient communication and the adherence to the proven epidemiological measures hopefully would be leaving us better prepared for the future if challenged by novel communicable diseases of pandemic potential.

Rationale and feasibility of the atrioventricular single-lead ICD systems with a floating atrial dipole (DX) in clinical practice.

Cardiac implantable electronic devices establish proper therapy for the prevention of sudden cardiac death, significantly reducing the morbidity and mortality of patients with arrhythmias and heart failure. It is well-known that the number of electrodes increases the risk of complications. To preserve the benefit of atrial sensing without the need to implant an additional lead, a single-lead ICD system with a floating atrial dipole (DX ICD lead) has been developed. Besides all of the potential benefits, the necessity of a reliable and stable atrial sensing via the floating dipole could be the main concern against the use of this lead type. In the current generation of DX devices, the specially filtered atrial signal seems to be high enough and stable over time, which is crucial in the early detection of atrial arrhythmias, discrimination between different forms of tachycardias in order to prevent inappropriate ICD therapy, and achieving an optimal atrioventricular and interventricular synchrony in patients with a two-lead CRT-DX system. The present review summarizes the benefits and potential drawbacks of the DX ICD systems based on the available literature, furthermore, proposes an evidence-based algorithm of ICD type selection.

Aerobic Oxidations in Asymmetric Synthesis: Catalytic Strategies and Recent Developments.

Despite the remarkable advances in the area of asymmetric catalytic oxidations over the past decades, the development of sustainable and environmentally benign enantioselective oxidation techniques, especially with the efficiency level similar to natural enzymes, still represents a challenge. The growing demand for enantiopure compounds and high interest to industry-relevant green technological advances continue to encourage the research pursuits in this field. Among various oxidants, molecular oxygen is ubiquitous, being available at low cost, environmentally benign and easy-to-handle material. This review highlights recent achievements in catalytic enantioselective oxidations utilizing molecular oxygen as the sole oxidant, with focus on the mechanisms of dioxygen activation and chirogenesis in these transformations.

Mortality benefit of crystalloids administered in 1-6 hours in septic adults in the ED: systematic review with narrative synthesis.

BACKGROUND: Based on the 2018 update of the Surviving Sepsis Campaign, the Committee for Quality Improvement of the NHSs of England recommended the instigation of the elements of the 'Sepsis-6 bundle' within 1 hour to adult patients screened positive for sepsis. This bundle includes a bolus infusion of 30 mL/kg crystalloids in the ED. Besides the UK, both in the USA and Australia, compliance with similar 1-hour targets became an important quality indicator. However, the supporting evidence may neither be contemporaneous nor necessarily valid for emergency medicine settings. METHOD: A systematic review was designed and registered at PROSPERO to assess available emergency medicine/prehospital evidence published between 2012 and 2020, investigating the clinical benefits associated with a bolus infusion of a minimum 30 mL/kg crystalloids within 1 hour to adult patients screened positive for sepsis. Due to the small number of papers that addressed this volume of fluids in 1 hour, we expanded the search to include studies looking at 1-6 hours. RESULTS: Seven full-text articles were identified, which investigated various aspects of the fluid resuscitation in adult sepsis. However, none answered completely to the original research question aimed to determine either the effect of time-to-crystalloids or the optimal fluid volume of resuscitation. Our findings demonstrated that in the USA/UK/Australia/Canada, adult ED septic patients receive 23-43 mL/kg of crystalloids during the first 6 hours of resuscitation without significant differences either in mortality or in adverse effects. CONCLUSION: This systematic review did not find high-quality evidence supporting the administration of 30 mL/kg crystalloid bolus to adult septic patients within 1 hour of presentation in the ED. Future research must investigate both the benefits and the potential harms of the recommended intervention.

Multiparameter diagnostic sensor measurements during clinically stable periods and worsening heart failure in ambulatory patients.

AIMS: This study aims to characterize the range of implantable device-based sensor values including heart sounds, markers of ventilation, thoracic impedance, activity, and heart rate for patients with heart failure (HF) when patients were deemed to be in clinically stable periods against the time course of acute decompensation and recovery from HF events. METHODS AND RESULTS: The MultiSENSE trial followed 900 patients implanted with a COGNIS CRT-D for up to 1 year. Chronic, ambulatory diagnostic sensor data were collected and evaluated during clinically stable periods (CSP: unchanged NYHA classification, no adverse events, and weight change ≤2.27 kg), and in the timeframe leading up to and following HF events (HF admissions or unscheduled visits with intravenous HF treatment). Physiologic sensor data from 1667 CSPs occurring in 676 patients were compared with those data leading up to and following 192 HF events in 106 patients. Overall, the mean age was 66.6 years, and the population were predominantly male (73%). Patients were primarily in NYHA II (67%), with a mean LVEF of 29.6% and median NT-proBNP of 754.5 pg/mL. Sensor values during CSP were poorer in patients who had HF events during the study period than those without HF events, including first heart sound (S1: 2.18 ± 0.84 mG vs. 2.62 ± 0.95 mG, P = 0.002), third heart sound (S3: 1.13 ± 0.36 mG vs. 0.91 ± 0.30 mG, P < 0.001), thoracic impedance (45.66 ± 8.78 Ohm vs. 50.33 ± 8.43 Ohm, P < 0.001), respiratory rate (19.09 ± 3.10 br/min vs. 17.66 ± 2.39 br/min, P = 0.002), night time heart rate (73.39 ± 8.36 b.p.m. vs. 69.56 ± 8.09 b.p.m., P = 0.001), patient activity (1.69 ± 1.84 h vs. 2.56 ± 2.20 h, P = 0.006), and HeartLogic index (11.07 ± 12.14 vs. 5.31 ± 5.13, P = 0.001). Sensor parameters measured worsening status leading up to HF events with recovery of values following treatment. CONCLUSIONS: Device-based physiologic sensors not only revealed progressive worsening leading up to HF events but also differentiated patients at increased risk of HF events when presumed to be clinically stable.

The impact of serum concentration-guided digoxin therapy on mortality of heart failure patients: A long-term follow-up, propensity-matched cohort study.

BACKGROUND: Recently published studies suggested that digoxin may increase mortality in heart failure with reduced ejection fraction (HFrEF). However, in the vast majority of former trials serum digoxin concentration (SDC) was not measured and therapy was not SDC-guided. AIM: To assess the impact of SDC-guided digoxin therapy on mortality in HFrEF patients. METHODS: Data of 580 HFrEF patients were retrospectively analyzed. In patients on digoxin, SDC was measured every 3 months and digoxin dosage was SDC-guided (target SDC: 0.5-0.9 ng/mL). All-cause mortality of digoxin users and nonusers was compared after propensity score matching (PSM). RESULTS: After 7.1 ± 4.7 years follow-up period (FUP) all-cause mortality of digoxin users (n = 180) was significantly higher than nonusers (n = 297) (propensity-adjusted HR = 1.430; 95% CI = 1.134-1.804; P = .003). Patients having SDC of 0.9 to 1.1 ng/mL (n = 60) or > 1.1 ng/mL (n = 44) at any time during the FUP had an increased risk of all-cause mortality (HR = 1.750; 95% CI = 1.257-2.436, P = .001 and HR = 1.687; 95% CI = 1.153-2.466, P = .007), while patients having a maximal SDC < 0.9 ng/mL (n = 76) had similar mortality risk (HR = 1.139; 95% CI = 0.827-1.570, P = .426), compared to digoxin nonusers. CONCLUSIONS: According to our propensity-matched analysis, SDC-guided digoxin therapy was associated with increased all-cause mortality in optimally treated HFrEF patients, especially with SDC ≥0.9 ng/mL. These results reinforce the expert opinion that digoxin in HFrEF can only be used among carefully selected patients with close SDC monitoring.

Smouldering ashes: burning questions after the outbreak of electronic cigarette or vaping-associated lung injury (EVALI).

In the summer of 2019, the Center for Disease Control and Prevention (CDC) declared an emergency of electronic cigarettes and/or vaping (vaping)-associated lung injury (EVALI) in the USA. The outbreak abated by January 2020, which the CDC attributed to heightened public awareness, 'user actions to reduce risk' and potentially the removal of vitamin E acetate (VEA) from vaping products (VEA is an oily chemical cutting agent, strongly associated with the disease). Even though the EVALI outbreak appears to be over, numerous epidemiological and medical questions are left still open. First, why were there practically no cases outside the USA, which represents nearly a quarter of the global vaping market? Comparative studies to map the differences in device/fluids/user habits between countries might be needed urgently. Second, what is the pathomechanism that sickens vapers irrespective of VEA exposure? VEA was only confirmed in about half of the cases and the presumed toxicity is yet to be determined. Aetiology/epidemiology focused research is needed to investigate/interpret the broader context to explain the outbreak. Third, could any socioeconomic/environmental factors have influenced the course of the outbreak? Finally, what should we expect in the years to come? Was EVALI a serious but reversible emergency medicine condition or is vaping as detrimental to long-term health as smoking? Besides the complex legislative, regulatory, ethical aspects of EVALI, biomedical research is also difficult: in-vitro experiments have limited inferential value to real real-life vaping due to its complexity; user habits are self-reported and under-researched; there is an active black market pouring unknown quality counterfeit products and, in the USA, federal restrictions limit cannabis research. Vaping is a toxicological, multidimensional conundrum; therefore, stringent quality control, transparent legal/ethical boundaries, meticulous international research and user education are paramount to prevent potential future outbreaks and determine the parameters safe vaping (if these exist).

Generation of Mixed Anhydrides via Oxidative Fragmentation of Tertiary Cyclopropanols with Phenyliodine(III) Dicarboxylates.

Oxidative fragmentation of tertiary cyclopropanols with phenyliodine(III) dicarboxylates in aprotic solvents (dichloromethane, chloroform, toluene) produces mixed anhydrides. The fragmentation reaction is especially facile with phenyliodine(III) reagents bearing electron-withdrawing carboxylate ligands (trifluoroacetyl, 2,4,6-trichlorobenzoyl, 3-nitrobenzoyl), and affords 95-98% yields of the corresponding mixed anhydride products. The latter can be straightforwardly applied for the acylation of various nitrogen, oxygen and sulfur-centered nucleophiles (primary and secondary amines, hydroxylamines, primary alcohols, phenols, thiols). Intramolecular acylation yielding macrocyclic lactones can also be performed. The developed transformation has bolstered the synthetic utility of cyclopropanols as pluripotent intermediates in diversity-oriented synthesis of bioactive natural products and their synthetic congeners. For example, it was successfully applied for the last-stage modification of a cyclic peptide to produce a precursor of a known histone deacetylase inhibitor.

Needle aspiration for treating iatrogenic pneumothorax after cardiac electronic device implantation: a pilot study.

PURPOSE: Pneumothorax (PTX) following cardiac implantable electronic device procedures is traditionally treated with chest tube drainage (CTD). We hypothesized that, in a subset of patients, the less invasive needle aspiration (NA) may also be effective. We compared the strategy of primary NA with that of primary CTD in a single-center observational study. METHODS: Of the 970 procedures with subclavian venous access between January 2016 and June 2018, 23 patients had PTX requiring intervention. Beginning with March 2017, the traditional primary CTD (9 cases) has been replaced by the "NA first" strategy (14 patients). Outcome measures were procedural success rate and duration of hospitalization evaluated both as time to event (log-rank test) and as a discrete variable (Wilcoxon-Mann-Whitney test). RESULTS: Needle aspiration was successful in 8/14 (57.1%) of the cases (95% CI 28.9-82.3%), whereas PTX resolved in all patients after CTD was 9/9 (100%, 95% CI 66.4-100.0%, p = 0.0481). Regarding length of hospital stay, intention to treat time to event analysis showed no difference between the two approaches (p = 0.73). Also, the median difference was not statistically significant (- 2.0 days, p = 0.17). In contrast, per protocol evaluation revealed reduced risk of prolonged hospitalization for NA patients (p = 0.0025) with a median difference of - 4.0 days (p = 0.0012). Failure of NA did not result in a meaningful delay in discharge timing as median difference was 1.5 days (p = 0.28). CONCLUSIONS: Our data suggest that in a number of patients iatrogenic PTX may be successfully treated with NA resulting in shorter hospitalization without the risk of meaningful discharge delay in unsuccessful cases.

Divergent Access to Histone Deacetylase Inhibitory Cyclopeptides via a Late-Stage Cyclopropane Ring Cleavage Strategy. Short Synthesis of Chlamydocin.

A unified step-economical strategy for accessing histone deacetylase inhibitory peptides is proposed, based on the late-stage installation of multiple zinc-binding functionalities via the cleavage of the strained cyclopropane ring in the common pluripotent cyclopropanol precursor. The efficacy of the proposed diversity-oriented approach has been validated by short stereoselective synthesis of natural product chlamydocin, containing a challenging-to-install fragment of (2S,9S)-2-amino-8-oxo-9,10-epoxydecanoic acid (Aoe) and a range of its analogues, derivatives of 2-amino-8-oxodecanoic and 2-aminosuberic acids.

Association of Remote Monitoring With Survival in Heart Failure Patients Undergoing Cardiac Resynchronization Therapy: Retrospective Observational Study.

BACKGROUND: Remote monitoring is an established, guideline-recommended technology with unequivocal clinical benefits; however, its ability to improve survival is contradictory. OBJECTIVE: The aim of our study was to investigate the effects of remote monitoring on mortality in an optimally treated heart failure patient population undergoing cardiac resynchronization defibrillator therapy (CRT-D) implantation in a large-volume tertiary referral center. METHODS: The population of this single-center, retrospective, observational study included 231 consecutive patients receiving CRT-D devices in the Medical Centre of the Hungarian Defence Forces (Budapest, Hungary) from January 2011 to June 2016. Clinical outcomes were compared between patients on remote monitoring and conventional follow-up. RESULTS: The mean follow-up time was 28.4 (SD 18.1) months. Patients on remote monitoring were more likely to have atrial fibrillation, received heart failure management at our dedicated heart failure outpatient clinic more often, and have a slightly lower functional capacity. Crude all-cause mortality of remote-monitored patients was significantly lower compared with patients followed conventionally (hazard ratio [HR] 0.368, 95% CI 0.186-0.727, P=.004). The survival benefit remained statistically significant after adjustment for important baseline parameters (adjusted HR 0.361, 95% CI 0.181-0.722, P=.004). CONCLUSIONS: In this single-center, retrospective study of optimally treated heart failure patients undergoing CRT-D implantation, the use of remote monitoring systems was associated with a significantly better survival rate.

Newborn screening for homocystinurias: Recent recommendations versus current practice.

PURPOSE: To assess how the current practice of newborn screening (NBS) for homocystinurias compares with published recommendations. METHODS: Twenty-two of 32 NBS programmes from 18 countries screened for at least one form of homocystinuria. Centres provided pseudonymised NBS data from patients with cystathionine beta-synthase deficiency (CBSD, n = 19), methionine adenosyltransferase I/III deficiency (MATI/IIID, n = 28), combined remethylation disorder (cRMD, n = 56) and isolated remethylation disorder (iRMD), including methylenetetrahydrofolate reductase deficiency (MTHFRD) (n = 8). Markers and decision limits were converted to multiples of the median (MoM) to allow comparison between centres. RESULTS: NBS programmes, algorithms and decision limits varied considerably. Only nine centres used the recommended second-tier marker total homocysteine (tHcy). The median decision limits of all centres were ≥ 2.35 for high and ≤ 0.44 MoM for low methionine, ≥ 1.95 for high and ≤ 0.47 MoM for low methionine/phenylalanine, ≥ 2.54 for high propionylcarnitine and ≥ 2.78 MoM for propionylcarnitine/acetylcarnitine. These decision limits alone had a 100%, 100%, 86% and 84% sensitivity for the detection of CBSD, MATI/IIID, iRMD and cRMD, respectively, but failed to detect six individuals with cRMD. To enhance sensitivity and decrease second-tier testing costs, we further adapted these decision limits using the data of 15 000 healthy newborns. CONCLUSIONS: Due to the favorable outcome of early treated patients, NBS for homocystinurias is recommended. To improve NBS, decision limits should be revised considering the population median. Relevant markers should be combined; use of the postanalytical tools offered by the CLIR project (Collaborative Laboratory Integrated Reports, which considers, for example, birth weight and gestational age) is recommended. tHcy and methylmalonic acid should be implemented as second-tier markers.

Physical activity detection in patients with intracardiac leadless pacemaker.

INTRODUCTION: The Micra Transcatheter Pacing System provides a rate adaptive pacing using an individually programmable three-axis accelerometer. We evaluated the short- and mid-term performance of the Micra activity sensor by testing all three available activity vectors during the exercise tests. METHODS AND RESULTS: Implantation and follow-up data were prospectively collected from the patients undergoing Micra implantation at our institution. Patients underwent a 5-minute exercise test for each vector at predischarge (initial testing) and at scheduled in-office visits (repeat testing). On the basis of measurements of activity counts during the test, vectors were categorized to be adequate (excellent or acceptable) or poor. A total of 278 tests with 818 vector measurements were analyzed in 51 patients during follow-up (median duration was 18 months). Initial testing revealed the adequate quality of the nominal Vector 1 in 74.5% of the patients. Upon repeated testing at subsequent in-office visits, Vectors 1 and 3 were comparable (adequate quality in 64.7% vs 68.6% of the patients; P = 0.65) but better compared with Vector 2 (51.0%; P = 0.10 vs Vector 1, P = 0.01 vs Vector 3). In a subgroup of 45 patients programmed to VVIR mode, Vector 1 was selected in 46.7% of the patients after the initial test (Vector 2, 8.9%; Vector 3, 44.4%). Vector change was performed in 10 patients (22.2%) following repeated tests within 3 months of postimplantation. CONCLUSION: The three-axis accelerometer-based rate adaptive pacing feature proved to be feasible after manual selection of an adequate activity vector. Vector testing in Micra patients with chronotropic incompetence appears to be beneficial compared with the use of nominal Vector 1.