Slow hole diffusion limits the efficiency of p-type dye-sensitized solar cells based on the P1 dye.

NiO electrodes are widely applied in p-type dye-sensitized solar cells (DSSCs) and photoelectrochemical cells, but due to excessive charge recombination, the efficiencies of these devices are still too low for commercial applications. To understand which factors induce charge recombination, we studied electrodes with a varying number of NiO layers in benchmark P1 p-DSSCs. We obtained the most efficient DSSCs with four layers of NiO (0.134%), and further insights into this optimum were obtained via dye loading studies and in operando photoelectrochemical immittance spectroscopy. These results revealed that more NiO layers led to an increasing light harvesting efficiency (η LH), but a decreasing hole collection efficiency (η CC), giving rise to the maximum efficiency at four NiO layers. The decreasing η CC with more NiO layers is caused by longer hole collection times, which ultimately limits the overall efficiency. Notably, the recombination rates were independent of the number of NiO layers, and similar to those observed in the more efficient n-type DSSC analogues, but hole collection was an order of magnitude slower. Therefore, with more NiO layers, the beneficial increase in η LH can no longer counteract the decrease in η CC due to slow hole collection, resulting in the overall efficiency of the solar cells to maximize at four NiO layers.

Singular effect of linkage on long-term genetic gain in Fisher's infinitesimal model.

During the founding of the field of quantitative genetics, Fisher formulated in 1918 his "infinitesimal model" that provided a novel mathematical framework to describe the Mendelian transmission of quantitative traits. If the infinitely many genes in that model are assumed to segregate independently during reproduction, corresponding to having no linkage, directional selection asymptotically leads to a constant genetic gain at each generation. In reality, genes are subject to strong linkage because they lie on chromosomes and thus segregate in a correlated way. Various approximations have been used in the past to study that more realistic case of the infinitesimal model with the expectation that the asymptotic gain per generation is modestly decreased. To treat this system even in the strong linkage limit, we take the genes to lie on continuous chromosomes. Surprisingly, the consequences of genetic linkage are in fact rather singular, changing the nature of the long-term gain per generation: the asymptotic gain vanishes rather than being simply decreased. Nevertheless, the per-generation gain tends to zero sufficiently slowly for the total gain, accumulated over generations, to be unbounded.

A mechanohydraulic model supports a role for plasmodesmata in cotton fiber elongation.

Plant cell growth depends on turgor pressure, the cell hydrodynamic pressure, which drives expansion of the extracellular matrix (the cell wall). Turgor pressure regulation depends on several physical, chemical, and biological factors, including vacuolar invertases, which modulate osmotic pressure of the cell, aquaporins, which determine the permeability of the plasma membrane to water, cell wall remodeling factors, which determine cell wall extensibility (inverse of effective viscosity), and plasmodesmata, which are membrane-lined channels that allow free movement of water and solutes between cytoplasms of neighboring cells, like gap junctions in animals. Plasmodesmata permeability varies during plant development and experimental studies have correlated changes in the permeability of plasmodesmal channels to turgor pressure variations. Here, we study the role of plasmodesmal permeability in cotton fiber growth, a type of cell that increases in length by at least three orders of magnitude in a few weeks. We incorporated plasmodesma-dependent movement of water and solutes into a classical model of plant cell expansion. We performed a sensitivity analysis to changes in values of model parameters and found that plasmodesmal permeability is among the most important factors for building up turgor pressure and expanding cotton fibers. Moreover, we found that nonmonotonic behaviors of turgor pressure that have been reported previously in cotton fibers cannot be recovered without accounting for dynamic changes of the parameters used in the model. Altogether, our results suggest an important role for plasmodesmal permeability in the regulation of turgor pressure.

Temporal changes in CT-derived fractional flow reserve in patients after heart transplantation.

BACKGROUND: Adding functional information by CT-derived fractional flow reserve (FFRct) to coronary CT angiography (CCTA) and assessing its temporal change may provide insight into the natural history and physiopathology of cardiac allograft vasculopathy (CAV) in heart transplantation (HTx) patients. We assessed FFRct changes as well as CAV progression over a 2-year period in HTx patients undergoing serial CT imaging. METHODS: HTx patients from Erasmus MC and Mount Sinai Hospital, who had consecutive CCTAs 2 years apart were evaluated. FFRct analysis was performed for both scans. FFRct values at the most distal point in the left anterior descending (LAD), left circumflex (LCX), and right coronary artery (RCA) were measured after precisely matching the anatomical locations in both analyses. Also, the number of anatomical coronary stenoses of > 30% was scored. RESULTS: In total, 106 patients (median age 57 [interquartile range 47-67] years, 67% male) at 9 [6-13] years after HTx at the time of the baseline CCTA were included. Median distal FFRct values significantly decreased from baseline to follow-up for the LAD from 0.85 [0.79-0.90] to 0.84 [0.76-0.90] (p = 0.001), LCX from 0.92 [0.88-0.96] to 0.91 [0.85-0.95] (p = 0.009), and RCA from 0.92 [0.86-0.95] to 0.90 [0.86-0.94] (p = 0.004). The number of focal anatomical stenoses of > 30% increased from a median of 1 [0-2] at baseline to 2 [0-3] at follow-up (p = 0.009). CONCLUSIONS: The distal coronary FFRct values in post-HTX patients in each of the three major coronary arteries decreased, and the number of focal coronary stenoses increased over a 2-year period. Temporal FFRct change rate may become an additional parameter in the follow-up of HTx patients, but more research is needed to elucidate its role. CLINICAL RELEVANCE STATEMENT: CT-derived fractional flow reserve (FFRct) is important post-heart transplant because of additional information on coronary CT angiography for cardiac allograft vasculopathy (CAV) detection. The decrease and degree of reduction in distal FFRct value may indicate progression in anatomic CAV burden. KEY POINTS: CT-derived fractional flow reserve (FFRct) is important for monitoring cardiac allograft vasculopathy (CAV) in heart transplant patients. Over time, transplant patients showed a decrease in distal FFRct and an increase in coronary stenoses. Temporal changes in FFRct could be crucial for transplant follow-up, aiding in CAV detection.

New ion radii for oxides and oxysalts, fluorides, chlorides and nitrides.

Ion radii are derived here from the characteristic (grand mean) bond lengths for (i) 135 ions bonded to oxygen in 459 configurations (on the basis of coordination number) using 177 143 bond lengths extracted from 30 805 ordered coordination polyhedra from 9210 crystal structures; and (ii) 76 ions bonded to nitrogen in 137 configurations using 4048 bond lengths extracted from 875 ordered coordination polyhedra from 434 crystal structures. There are two broad categories of use for ion radii: (1) those methods which use the relative sizes of cation and anion radii to predict local atomic arrangements; (2) those methods which compare the radii of different cations (or the radii of different anions) to predict local atomic arrangements. There is much uncertainty with regard to the relative sizes of cations and anions, giving rise to the common failure of type (1) methods, e.g. Pauling's first rule which purports to relate the coordination adopted by cations to the radius ratio of the constituent cation and anion. Conversely, type (2) methods, which involve comparing the sizes of different cations with each other (or different anions with each other), can give very accurate predictions of site occupancies, physical properties etc. Methods belonging to type (2) can equally well use the characteristic bond lengths themselves (from which the radii are derived) in place of radii to develop correlations and predict crystal properties. Extensive quantum-mechanical calculations of electron density in crystals in the literature indicate that the radii of both cations and anions are quite variable with local arrangement, suggesting significant problems with any use of ion radii. However, the dichotomy between the experimentally derived ion radii and the quantum-mechanical calculations of electron density in crystals is removed by the recognition that ion radii are proxy variables for characteristic bond lengths in type (2) relations.

Increase of serum pancreatic enzymes during hospitalization for acute heart failure.

AIMS: Acute heart failure (AHF) is associated with end-organ dysfunction. The effect of AHF on the pancreas has not been studied. We aim to evaluate serum markers of pancreatic damage during hospitalization for AHF. METHODS AND RESULTS: In data from the Pragmatic Urinary Sodium-based treatment algoritHm in Acute Heart Failure (PUSH-AHF) study, amylase and lipase values were extracted from available serum samples at baseline, and at 24 and 72 h after hospitalization. The differences between pancreatic enzymes between timepoints were evaluated using the Friedman test. Associations with N-terminal pro-B-type natriuretic peptide (NT-proBNP) were tested using linear regression analysis. The study population consisted of 274 patients. Mean age was 73 ± 11 years, and 117 (43%) were women. Mean left ventricular ejection fraction (LVEF) was 38 ± 14%; 53 (19%) patients had HF with a preserved LVEF (≥50%). At baseline, median amylase and lipase were within normal range (47 [33-63] U/L and 30 [21-44] U/L, respectively). Both enzymes significantly increased in the first 72 h (P-value for trend <0.001); mean change was 9 ± 22 U/L for amylase, and 10 ± 22 U/L for lipase. Moreover, NT-proBNP at baseline showed a positive correlation with mean change in pancreatic enzymes in 72 h (P = 0.02 for amylase and P = 0.006 for lipase). CONCLUSION: Patients admitted for AHF exhibited a significant increase in serum values of pancreatic enzymes in the first 72 h, suggesting that an episode of AHF affects the pancreatic tissue. This rise in pancreatic enzymes was associated with HF severity, as reflected by NT-proBNP.

Network Latency in Teleoperation of Connected and Autonomous Vehicles: A Review of Trends, Challenges, and Mitigation Strategies.

With remarkable advancements in the development of connected and autonomous vehicles (CAVs), the integration of teleoperation has become crucial for improving safety and operational efficiency. However, teleoperation faces substantial challenges, with network latency being a critical factor influencing its performance. This survey paper explores the impact of network latency along with state-of-the-art mitigation/compensation approaches. It examines cascading effects on teleoperation communication links (i.e., uplink and downlink) and how delays in data transmission affect the real-time perception and decision-making of operators. By elucidating the challenges and available mitigation strategies, the paper offers valuable insights for researchers, engineers, and practitioners working towards the seamless integration of teleoperation in the evolving landscape of CAVs.

Serial cardiac biomarkers, pulmonary artery pressures and traditional parameters of fluid status in relation to prognosis in patients with chronic heart failure: Design and rationale of the BioMEMS study.

AIMS: Heart failure (HF), a global pandemic affecting millions of individuals, calls for adequate predictive guidance for improved therapy. Congestion, a key factor in HF-related hospitalizations, further underscores the need for timely interventions. Proactive monitoring of intracardiac pressures, guided by pulmonary artery (PA) pressure, offers opportunities for efficient early-stage intervention, since haemodynamic congestion precedes clinical symptoms. METHODS: The BioMEMS study, a substudy of the MONITOR-HF trial, proposes a multifaceted approach integrating blood biobank data with traditional and novel HF parameters. Two additional blood samples from 340 active participants in the MONITOR-HF trial were collected at baseline, 3-, 6-, and 12-month visits and stored for the BioMEMS biobank. The main aims are to identify the relationship between temporal biomarker patterns and PA pressures derived from the CardioMEMS-HF system, and to identify the biomarker profile(s) associated with the risk of HF events and cardiovascular death. CONCLUSION: Since the prognostic value of single baseline measurements of biomarkers like N-terminal pro-B-type natriuretic peptide is limited, with the BioMEMS study we advocate a dynamic, serial approach to better capture HF progression. We will substantiate this by relating repeated biomarker measurements to PA pressures. This design rationale presents a comprehensive review on cardiac biomarkers in HF, and aims to contribute valuable insights into personalized HF therapy and patient risk assessment, advancing our ability to address the evolving nature of HF effectively.

Contemporary guideline-directed medical therapy in de novo, chronic, and worsening heart failure patients: First data from the TITRATE-HF study.

AIMS: Despite clear guideline recommendations for initiating four drug classes in all patients with heart failure (HF) with reduced ejection fraction (HFrEF) and the availability of rapid titration schemes, information on real-world implementation lags behind. Closely following the 2021 ESC HF guidelines and 2023 focused update, the TITRATE-HF study started to prospectively investigate the use, sequencing, and titration of guideline-directed medical therapy (GDMT) in HF patients, including the identification of implementation barriers. METHODS AND RESULTS: TITRATE-HF is an ongoing long-term HF registry conducted in the Netherlands. Overall, 4288 patients from 48 hospitals were included. Among these patients, 1732 presented with de novo, 2240 with chronic, and 316 with worsening HF. The median age was 71 years (interquartile range [IQR] 63-78), 29% were female, and median ejection fraction was 35% (IQR 25-40). In total, 44% of chronic and worsening HFrEF patients were prescribed quadruple therapy. However, only 1% of HFrEF patients achieved target dose for all drug classes. In addition, quadruple therapy was more often prescribed to patients treated in a dedicated HF outpatient clinic as compared to a general cardiology outpatient clinic. In each GDMT drug class, 19% to 36% of non-use in HFrEF patients was related to side-effects, intolerances, or contraindications. In the de novo HF cohort, 49% of patients already used one or more GDMT drug classes for other indications than HF. CONCLUSION: This first analysis of the TITRATE-HF study reports relatively high use of GDMT in a contemporary HF cohort, while still showing room for improvement regarding quadruple therapy. Importantly, the use and dose of GDMT were suboptimal, with the reasons often remaining unclear. This underscores the urgency for further optimization of GDMT and implementation strategies within HF management.

Pulmonary artery pressure monitoring in chronic heart failure: effects across clinically relevant subgroups in the MONITOR-HF trial.

BACKGROUND AND AIMS: In patients with chronic heart failure (HF), the MONITOR-HF trial demonstrated the efficacy of pulmonary artery (PA)-guided HF therapy over standard of care in improving quality of life and reducing HF hospitalizations and mean PA pressure. This study aimed to evaluate the consistency of these benefits in relation to clinically relevant subgroups. METHODS: The effect of PA-guided HF therapy was evaluated in the MONITOR-HF trial among predefined subgroups based on age, sex, atrial fibrillation, diabetes mellitus, left ventricular ejection fraction, HF aetiology, cardiac resynchronization therapy, and implantable cardioverter defibrillator. Outcome measures were based upon significance in the main trial and included quality of life-, clinical-, and PA pressure endpoints, and were assessed for each subgroup. Differential effects in relation to the subgroups were assessed with interaction terms. Both unadjusted and multiple testing adjusted interaction terms were presented. RESULTS: The effects of PA monitoring on quality of life, clinical events, and PA pressure were consistent in the predefined subgroups, without any clinically relevant heterogeneity within or across all endpoint categories (all adjusted interaction P-values were non-significant). In the unadjusted analysis of the primary endpoint quality-of-life change, weak trends towards a less pronounced effect in older patients (Pinteraction = .03; adjusted Pinteraction = .33) and diabetics (Pinteraction = .01; adjusted Pinteraction = .06) were observed. However, these interaction effects did not persist after adjusting for multiple testing. CONCLUSIONS: This subgroup analysis confirmed the consistent benefits of PA-guided HF therapy observed in the MONITOR-HF trial across clinically relevant subgroups, highlighting its efficacy in improving quality of life, clinical, and PA pressure endpoints in chronic HF patients.

Influence of the Outflow Graft Angular Position on the Outcomes in Patients With a Left Ventricular Assist Device.

This study aimed to explore the potential impact of the angular position of the outflow graft on thromboembolic events and aortic valve regurgitation in people with a left ventricular assist device (LVAD). We analyzed contrast computed tomography (CT) data of patients with LVAD implantation between 2016 and 2021. Three-dimensional reconstructions of the outflow graft and aortic arch were performed to calculate the horizontal (azimuth) angle and vertical (polar) angle, as well as the relative distance between the outflow graft, aortic valve, and brachiocephalic artery. Among 59 patients (median age 57, 68% male), a vertical angle ≥107° correlated significantly with increased cerebrovascular accidents (hazard ratio [HR]: 5.8, 95% confidence interval [CI]: 1.3-26.3, p = 0.022) and gastrointestinal bleeding (HR: 3.4, 95% CI: 1.0-11.2, p = 0.049) during a median 25 month follow-up. No significant differences were found between the vertical angle and aortic valve regurgitation or survival. The horizontal angle and relative distance did not show differences regarding clinical adverse events. This study emphasizes the importance of the LVAD outflow graft angular position to prevent life-threatening thromboembolic events. This study suggests the need for prospective research to further validate these findings.

Cardiovascular screening outcomes in the Dutch survivorship care program for Hodgkin lymphoma survivors.

PURPOSE: Hodgkin lymphoma (HL) survivors are at increased risk of cardiovascular disease (CVD) due to former lymphoma treatment. In 2013, cardiovascular screening for 5-year HL survivors according to national guidelines was implemented in Dutch survivorship clinics. We aim to assess the following: (1) adherence to screening guidelines and (2) the yield of (risk factors for) CVD in the screening program. METHODS: The study population consisted of 5-year HL survivors who received survivorship care at three University Medical Centers from 2013 to 2016 through 2021. Patient characteristics, cardiovascular screening procedures, and outcomes were collected from the medical records. RESULTS: In 186 survivors eligible for cardiovascular screening (mean age 47.8 years, 60.8% female), the following diagnostics were performed: complete blood tests (81.0%, median frequency: yearly instead of advised 5-yearly evaluation), electrocardiogram (93.0%), echocardiography (94.6%). Fifty-five percent of survivors had at least one modifiable cardiovascular risk factor (i.e., current smoking, overweight, new/insufficiently controlled hypertension, dyslipidemia, or diabetes). Screening detected ≥ 1 CVD in 31.1% of survivors. Among survivors with available echocardiography report (n = 106), screening detected new aortic and/or mitral valve dysfunction(s) in 51.0% (with grades 3-4 in 4.9%) and impaired left ventricular ejection fraction in 10.3%. CONCLUSIONS: Adherence to the screening guidelines in the Dutch HL survivorship care program was reasonable to good and a substantial number of actionable (risk factors for) CVD were diagnosed. IMPLICATIONS FOR CANCER SURVIVORS: Our findings inform HL survivors at high risk of late cardiotoxicity about cardiovascular screening findings and demonstrate appropriate therapeutic actions after diagnosis of (risk factors for) CVD.

Biologically meaningful regulatory logic enhances the convergence rate in Boolean networks and bushiness of their state transition graph.

Boolean models of gene regulatory networks (GRNs) have gained widespread traction as they can easily recapitulate cellular phenotypes via their attractor states. Their overall dynamics are embodied in a state transition graph (STG). Indeed, two Boolean networks (BNs) with the same network structure and attractors can have drastically different STGs depending on the type of Boolean functions (BFs) employed. Our objective here is to systematically delineate the effects of different classes of BFs on the structural features of the STG of reconstructed Boolean GRNs while keeping network structure and biological attractors fixed, and explore the characteristics of BFs that drive those features. Using $10$ reconstructed Boolean GRNs, we generate ensembles that differ in BFs and compute from their STGs the dynamics' rate of contraction or 'bushiness' and rate of 'convergence', quantified with measures inspired from cellular automata (CA) that are based on the garden-of-Eden (GoE) states. We find that biologically meaningful BFs lead to higher STG 'bushiness' and 'convergence' than random ones. Obtaining such 'global' measures gets computationally expensive with larger network sizes, stressing the need for feasible proxies. So we adapt Wuensche's $Z$-parameter in CA to BFs in BNs and provide four natural variants, which, along with the average sensitivity of BFs computed at the network level, comprise our descriptors of local dynamics and we find some of them to be good proxies for bushiness. Finally, we provide an excellent proxy for the 'convergence' based on computing transient lengths originating at random states rather than GoE states.

Preponderance of generalized chain functions in reconstructed Boolean models of biological networks.

Boolean networks (BNs) have been extensively used to model gene regulatory networks (GRNs). The dynamics of BNs depend on the network architecture and regulatory logic rules (Boolean functions (BFs)) associated with nodes. Nested canalyzing functions (NCFs) have been shown to be enriched among the BFs in the large-scale studies of reconstructed Boolean models. The central question we address here is whether that enrichment is due to certain sub-types of NCFs. We build on one sub-type of NCFs, the chain functions (or chain-0 functions) proposed by Gat-Viks and Shamir. First, we propose two other sub-types of NCFs, namely, the class of chain-1 functions and generalized chain functions, the union of the chain-0 and chain-1 types. Next, we find that the fraction of NCFs that are chain-0 (also holds for chain-1) functions decreases exponentially with the number of inputs. We provide analytical treatment for this and other observations on BFs. Then, by analyzing three different datasets of reconstructed Boolean models we find that generalized chain functions are significantly enriched within the NCFs. Lastly we illustrate that upon imposing the constraints of generalized chain functions on three different GRNs we are able to obtain biologically viable Boolean models.

Preclinical Models of Cardiac Disease: A Comprehensive Overview for Clinical Scientists.

For recent decades, cardiac diseases have been the leading cause of death and morbidity worldwide. Despite significant achievements in their management, profound understanding of disease progression is limited. The lack of biologically relevant and robust preclinical disease models that truly grasp the molecular underpinnings of cardiac disease and its pathophysiology attributes to this stagnation, as well as the insufficiency of platforms that effectively explore novel therapeutic avenues. The area of fundamental and translational cardiac research has therefore gained wide interest of scientists in the clinical field, while the landscape has rapidly evolved towards an elaborate array of research modalities, characterized by diverse and distinctive traits. As a consequence, current literature lacks an intelligible and complete overview aimed at clinical scientists that focuses on selecting the optimal platform for translational research questions. In this review, we present an elaborate overview of current in vitro, ex vivo, in vivo and in silico platforms that model cardiac health and disease, delineating their main benefits and drawbacks, innovative prospects, and foremost fields of application in the scope of clinical research incentives.

Best practices for the execution, analysis, and data storage of plant single-cell/nucleus transcriptomics.

Single-cell and single-nucleus RNA-sequencing technologies capture the expression of plant genes at an unprecedented resolution. Therefore, these technologies are gaining traction in plant molecular and developmental biology for elucidating the transcriptional changes across cell types in a specific tissue or organ, upon treatments, in response to biotic and abiotic stresses, or between genotypes. Despite the rapidly accelerating use of these technologies, collective and standardized experimental and analytical procedures to support the acquisition of high-quality data sets are still missing. In this commentary, we discuss common challenges associated with the use of single-cell transcriptomics in plants and propose general guidelines to improve reproducibility, quality, comparability, and interpretation and to make the data readily available to the community in this fast-developing field of research.

Guideline implementation, drug sequencing, and quality of care in heart failure: design and rationale of TITRATE-HF.

AIMS: Current heart failure (HF) guidelines recommend to prescribe four drug classes in patients with HF with reduced ejection fraction (HFrEF). A clear challenge exists to adequately implement guideline-directed medical therapy (GDMT) regarding the sequencing of drugs and timely reaching target dose. It is largely unknown how the paradigm shift from a serial and sequential approach for drug therapy to early parallel application of the four drug classes will be executed in daily clinical practice, as well as the reason clinicians may not adhere to new guidelines. We present the design and rationale for the real-world TITRATE-HF study, which aims to assess sequencing strategies for GDMT initiation, dose titration patterns (order and speed), intolerance for GDMT, barriers for implementation, and long-term outcomes in patients with de novo, chronic, and worsening HF. METHODS AND RESULTS: A total of 4000 patients with HFrEF, HF with mildly reduced ejection fraction, and HF with improved ejection fraction will be enrolled in >40 Dutch centres with a follow-up of at least 3 years. Data collection will include demographics, physical examination and vital parameters, electrocardiogram, laboratory measurements, echocardiogram, medication, and quality of life. Detailed information on titration steps will be collected for the four GDMT drug classes. Information will include date, primary reason for change, and potential intolerances. The primary clinical endpoints are HF-related hospitalizations, HF-related urgent visits with a need for intravenous diuretics, all-cause mortality, and cardiovascular mortality. CONCLUSIONS: TITRATE-HF is a real-world multicentre longitudinal registry that will provide unique information on contemporary GDMT implementation, sequencing strategies (order and speed), and prognosis in de novo, worsening, and chronic HF patients.

Biomechanical response of ultrathin slices of hypertrophic cardiomyopathy tissue to myosin modulator mavacamten.

Hypertrophic cardiomyopathy (HCM) is the most common inherited myocardial disorder of the heart, but effective treatment options remain limited. Mavacamten, a direct myosin modulator, has been presented as novel pharmacological therapy for HCM. The aim of this study was to analyze the biomechanical response of HCM tissue to Mavacamten using living myocardial slices (LMS). LMS (n = 58) from patients with HCM (n = 10) were cultured under electromechanical stimulation, and Verapamil and Mavacamten were administered on consecutive days to evaluate their effects on cardiac biomechanics. Mavacamten and Verapamil reduced contractile force and dF/dt and increased time-to-relaxation in a similar manner. Yet, the time-to-peak of the cardiac contraction was prolonged after administration of Mavacamten (221.0 ms (208.8 - 236.3) vs. 237.7 (221.0 - 254.7), p = 0.004). In addition, Mavacamten prolonged the functional refractory period (FRP) (330 ms (304 - 351) vs. 355 ms (313 - 370), p = 0.023) and better preserved twitch force with increasing stimulation frequencies, compared to Verapamil. As such, Mavacamten reduced (hyper-)contractility and prolonged contraction duration of HCM LMS, suggesting a reduction in cardiac wall stress. Also, Mavacamten might protect against the development of ventricular tachyarrhythmias due to prolongation of the FRP, and improve toleration of tachycardia due to better preservation of twitch force at tachycardiac stimulation frequencies.