Microbial Enrichment Techniques on Syngas and CO2 Targeting Production of Higher Acids and Alcohols.

(1) Background: Microbial conversion of gaseous molecules, such as CO2, CO and H2, to valuable compounds, has come to the forefront since the beginning of the 21st century due to increasing environmental concerns and the necessity to develop alternative technologies that contribute to a fast transition to a more sustainable era. Research efforts so far have focused on C1-C2 molecules, i.e., ethanol and methane, while interest in molecules with higher carbon atoms has also started to emerge. Research efforts have already started to pay off, and industrial installments on ethanol production from steel-mill off-gases as well as methane production from the CO2 generated in biogas plants are a reality. (2) Methodology: The present study addresses C4-C6 acids and butanol as target molecules and responds to how the inherent metabolic potential of mixed microbial consortia could be revealed and exploited based on the application of different enrichment methods (3) Results and Conclusions: In most of the enrichment series, the yield of C4-C6 acids was enhanced with supplementation of acetic acid and ethanol together with the gas substrates, resulting in a maximum of 43 and 68% (e-mol basis) for butyric and caproic acid, respectively. Butanol formation was also enhanced, to a lesser degree though and up to 9% (e-mol basis). Furthermore, the microbial community exhibited significant shifts depending on the enrichment conditions applied, implying that a more profound microbial analysis on the species level taxonomy combined with the development of minimal co-cultures could set the basis for discovering new microbial co-cultures and/or co-culturing schemes.

Prediction of methane yield and pretreatment efficiency of lignocellulosic biomass based on composition.

Lignocellulosic biomass is considered a key resource for the future expansion of biogas production through anaerobic digestion (AD), and research on the development of pretreatment technologies for improving biomass conversion is an intensive and fast-growing field. Consequently, there is a need for creating tools able to predict the efficiency of a certain pretreatment on different biomass types, fast and accurately, and to assist in selecting a pretreatment technology for a specific biomass. In this study, seven different types of raw lignocellulosic biomass of industrial relevance were systematically analyzed regarding their composition (carbohydrates, lignin, lipids, ash, extractives, etc.) and subjected to a common pretreatment. The aim of the study was to identify the most important characteristics that make a biomass good receptor of the specific pretreatment prior to AD. A simple ammonia pretreatment was chosen as a case study and partial least squares regression (PLS-R) was used for modeling initially the ultimate methane yield of raw and pretreated biomass. In the sequel, PLS-R was used for modeling the efficiency of the pretreatment on increasing the ultimate methane yield and hydrolysis rate as a function of the biomass composition. The fit of the models was satisfactory, ranging from R2 = 0.89 to R2 = 0.97. The results showed that the most decisive characteristics for predicting the efficiency of the pretreatment were the lipid (r = -0.88), ash (r = +0.79), protein (r = -0.61), and hemicellulose/lignin (r = -0.53) content of raw biomass. Finally, the approach followed in this study facilitated an improved understanding of the mechanism of the pretreatment and presented a methodology to be followed for developing tools for the prediction of pretreatment efficiency in the field of lignocellulosic biomass valorization.

Real-world treatment patterns, patient-reported outcomes, and effectiveness of flexibledosing etanercept in patients with plaque psoriasis in Greece.

Etanercept is approved for continuous or intermittent use and flexible dosing in plaque psoriasis (PsO). The objectives of this study were to investigate real-world treatment patterns with etanercept in Greek adults with moderate-to-severe PsO. This non-interventional multicenter study included a retrospective-to-prospective (RP) cohort, previously treated with etanercept for ≥24 months and followed for an additional 6 months, and a biologic-naïve, prospective-only (PO) cohort, followed for 6 months after treatment initiation. Parameters assessed included Psoriasis Area and Severity Index (PASI), percentage of body surface area (BSA) affected, Dermatology Life Quality Index (DLQI), and adverse events (AEs). This study enrolled 123 patients (RP, n = 56; PO, n = 67), who mostly adhered to continuous treatment (RP, 68%; PO, 95%). The two cohorts had similar mean baseline-to-endpoint decreases in PASI (-9.5 vs -10.1) and BSA (-11.9 vs -12.3). The PO-CTP population had a mean DLQI baseline-to-endpoint score decrease of -5.8, which was statistically significant and clinically meaningful. Treatment-emergent AE rates were 58.9% (RP) versus 26.9% (PO). These real-world data suggest a similar effectiveness of continuous and intermittent etanercept treatment in Greek patients with PsO.

Variables and Mechanisms Affecting Electro-Membrane Extraction of Bio-Succinic Acid from Fermentation Broth.

The production of succinic acid from fermentation is a promising approach for obtaining building-block chemicals from renewable sources. However, the limited bio-succinic yield from fermentation and the complexity of purification has been making the bio-succinic acid production not competitive with petroleum-based succinic acid. Membrane electrolysis has been identified to be a promising technology in both production and separation stages of fermentation processes. This work focuses on identifying the key operational parameters affecting the performance of the electrolytic cell for separating succinic acid from fermentation broth through an anionic exchange membrane. Indeed, while efforts are mainly focused on studying the performance of an integrated fermenter-electrolytic cell system, a lack of understanding remains in how to tune the electrolytic cell and which main parameters are involved. The results show that a single electrolytic cell of operating volume 250 mL was able to extract up to 3 g L-1 h-1 of succinic acid. The production of OH- ions by water electrolysis can act as a buffer for the fermenter and it could be tuned as a function of the extraction rate. Furthermore, as the complexity of the solution in terms of the quantity and composition of the ions increased, the energy required for the separation process decreased.

Arrhythmic risk stratification in ischemic, non-ischemic and hypertrophic cardiomyopathy: A two-step multifactorial, electrophysiology study inclusive approach.

Annual arrhythmic sudden cardiac death ranges from 0.6% to 4% in ischemic cardiomyopathy (ICM), 1% to 2% in non-ischemic cardiomyopathy (NICM), and 1% in hypertrophic cardiomyopathy (HCM). Towards a more effective arrhythmic risk stratification (ARS) we hereby present a two-step ARS with the usage of seven non-invasive risk factors: Late potentials presence (≥ 2/3 positive criteria), premature ventricular contractions (≥ 30/h), non-sustained ventricular tachycardia (≥ 1episode/24 h), abnormal heart rate turbulence (onset ≥ 0% and slope ≤ 2.5 ms) and reduced deceleration capacity (≤ 4.5 ms), abnormal T wave alternans (≥ 65µV), decreased heart rate variability (SDNN < 70ms), and prolonged QTc interval (> 440 ms in males and > 450 ms in females) which reflect the arrhythmogenic mechanisms for the selection of the intermediate arrhythmic risk patients in the first step. In the second step, these intermediate-risk patients undergo a programmed ventricular stimulation (PVS) for the detection of inducible, truly high-risk ICM and NICM patients, who will benefit from an implantable cardioverter defibrillator. For HCM patients, we also suggest the incorporation of the PVS either for the low HCM Risk-score patients or for the patients with one traditional risk factor in order to improve the inadequate sensitivity of the former and the low specificity of the latter.

Structural and functional characterization of a novel biosurfactant from Bacillus sp. IITD106.

Plant saponins are attractive biosurfactants and have been used to enhance phytoremediation. There are only limited reports on saponins produced by bacteria. Here, we report structural and functional characterization of a novel saponin produced by Bacillus sp. IITD106. Biosurfactant production was determined by emulsion index, drop collapse, oil displacement and hemolytic assays. The biosurfactant was stable over a range of temperature (30 °C to 70 °C), salinity (0-150 g liter-1) and pH (4-10). The surface tension of the medium reduced from 58.89 mN/m to 27.29 mN/m using the isolated biosurfactant. Chromatographic analysis revealed the biosurfactant to be a glycolipid. LCMS, FT-IR and NMR analysis identified the biosurfactant to be a saponin containing two sugar groups and a 5 ringed triterpene sapogenin unit. Genome sequencing of the strain revealed the presence of genes responsible for biosynthesis of saponin. Statistical optimization of culture medium resulted in 9.3-fold increase in biosurfactant production. Kinetics study of biosurfactant production performed in a stirred tank batch bioreactor resulted in 6.04 g liter-1 and 6.9 g liter-1 biomass and biosurfactant concentration, respectively. The biosurfactant was found to solubilize polycyclic aromatic hydrocarbons. The potential of cell free biosurfactant containing broth to enhance oil recovery was tested in a sand pack column and recovery of 63% of residual oil was observed. To our knowledge this is the first report of saponin production by any of the strains of Bacillus.

Multipoint left ventricular pacing effects on hemodynamic parameters and functional status: HUMVEE single-arm clinical trial (NCT03189368).

OBJECTIVES: The aim of this study was to assess the capacity of optimized multipoint pacing (MPP) over optimized cardiac resynchronization therapy (CRT), in terms of clinical, functional, and echocardiographic parameters among patients with dyssynchronous heart failure (HF). METHODS: Eighty patients (Caucasian, 77.5% male, 68.4 ± 10.1 years, and 53.8% ischemic cardiomyopathy) sequentially received optimized CRT and optimized MPP over 6- and 12-month periods in a single-arm clinical trial. Clinical, laboratory, and echocardiographic assessment was conducted at baseline and after the completion of each step. RESULTS: Significant additive effects of optimized MPP over optimized CRT were noted with regard to 6-min walking distance (baseline/optCRT/optMPP: 293 ± 120 m vs 367 ± 94 m vs 405 ± 129 m and p < 0.001), NYHA class (2.36 vs 2.19 vs 1.45 and p < 0.001), VTIlvot (14.25 ± 3.2 cm vs 16.2 ± 4 cm vs 17.5 ± 3.4 cm and p < 0.001), stroke volume (48 ± 13.5 ml vs 55 ± 15 ml vs 59 ± 15 ml and p < 0.001), left ventricular ejection fraction (LVEF) (29% ± 7.1% vs 33% ± 7.3% vs 37% ± 7.7% and p < 0.001), maximal left atrial volume (77.2 ± 34.2 ml vs 74.2 ± 39.5 ml vs 67.7 ± 32 ml and p = 0.02), pulmonary artery systolic pressure (35.9 mmHg vs 33.5 mmHg vs 31 mmHg and p < 0.001), and right ventricular strain (-8.3% ± 6.9% vs -8.8% ± 6.6% vs -11.8% ± 6.1% and p = 0.022). With regard to VAC, stroke work (SW), and CP as percentages of maximal, there was a significant difference detected as compared to baseline for both CRT and MPP. Additive effects persisted only if suitable MPP dipoles were present. Exploratory analysis revealed that ischemic cardiomyopathy continued to exhibit significant differences that favor MPP, whereas nonischemic cardiomyopathy had similar findings with regard to total left atrial strain and quality of life. CONCLUSIONS: Optimized MPP showed significant improvements in hemodynamic parameters and ventricular function in patients with HF over optimized CRT. The beneficial effect was more prominent in men and in those with rather reduced LVEF, consistent with findings that suggest a beneficial trend in VAC and CP with more homogeneous depolarization offered by optimized MPP.

Asphaltene biotransformation for heavy oil upgradation.

Globally, the reserves of heavy crude oil are seven times more abundant than that of light crude, and yet, they are underutilized because of their high viscosity and density, which is largely due to the presence of large amounts of asphaltenes. Biotransformation of heavy oil asphaltenes into smaller metabolites can be used for reducing their viscosity. Several microorganisms capable of asphaltene biodegradation have been reported but only few have been characterized for its biotransformation. In the present study, a 9-membered microbial consortium was isolated from an oil contaminated soil. About 72% and 75% asphaltene biotransformation was achieved by growing cells at shake flask level and in a 1.5 l bioreactor, respectively. A representative structure of asphaltene was constructed based on LC-MS, 1H-NMR, 13C-NMR, FT-IR, ICPMS and elemental analysis (CHNS) of n-heptane purified asphaltene from Maya crude oil. Biotransformation of asphaltene, as analyzed by performing 1H-NMR, FT-IR and elemental analysis, resulted in 80% decrease in S and N when compared to the control along with incorporation of oxygen in the structure of asphaltene. About 91% decrease in the viscosity of the Maya crude oil was observed after two weeks when oil: aqueous phase ratio was 1:9. The results suggest that the isolated microbial consortium can be used for biological upgradation of heavy crude oil. To our knowledge, this is the first report where a microbial consortium resulted in such high asphaltene biotransformation.

Permanent pacemaker implantation in unexplained syncope patients with borderline sinus bradycardia and electrophysiology study-proven sinus node disease.

BACKGROUND: Significant sinus bradycardia (SB) in the context of sinus node dysfunction (SND) has been associated with neurological symptoms. The objective was to evaluate the effect of permanent pacing on the incidence of syncope in patients with rather mild degrees of SB, unexplained syncope, and "positive" invasive electrophysiologic testing. METHODS: This was an observational study based on a prospective registry of 122 consecutive mild SB patients (61.90 ± 18.28 years, 61.5% male, 57.88 ± 7.73 bpm) presenting with recurrent unexplained pre and syncope attacks admitted to our hospital for invasive electrophysiology study (EPS). Τhe implantation of a permanent antibradycardia pacemaker (ABP) was offered to all patients according to the results of the EPS. Eighty patients received the ABP, while 42 denied. RESULTS: The mean of reported syncope episodes was 2.23 ± 1.29 (or presyncope 2.36 ± 1.20) in the last 12 months before they were referred for a combined EP guided diagnostic and therapeutic approach. Over a mean follow-up of approximately 4 years (50.39 ± 32.40 months), the primary outcome event (syncope) occurred in 18 of 122 patients (14.8%), 6 of 80 (7.5%) in the ABP group as compared to 12 of 42 (28.6%) in the no pacemaker group (P = .002). CONCLUSIONS: Among patients with mild degree of SB and a history of unexplained syncope, a set of positivity criteria for the presence of EPS defined SND after differentiating reflex syncope, identifies a subset of patients who will benefit from permanent pacing.

Right drug, wrong dosage: insights from the PAVE-AF antithrombotic study in older patients with atrial fibrillation.

Optimal antithrombotic treatment of older patients is usually impeded by several prevailing misconceptions. The aim of our study was to assess the type, dosage and predictors of antithrombotic therapy in older patients with non-valvular atrial fibrillation (NVAF). PAVE-AF was a prospective, cross-sectional study, including NVAF patients ≥ 80 years from 30 participating centers. Demographic data, comorbidities and treatment patterns were documented in a single visit. Patients treated with non-vitamin K oral anticoagulants (NOACs) were further classified into three dosing categories (recommended, underdosing and overdosing). Among 1018 patients (85.4±4.0 years), 88.4% received anticoagulants (AC), 8% antiplatelets (AP) and 3.6% no treatment. The primary reason for AP administration was physician concern of bleeding followed by patient denial. Patients ≥90 years had two times greater probability to receive AP therapy compared to patients < 90 years. Among patients treated with AC, one third received vitamin K antagonists, while two thirds received NOACs [34.6% apixaban, 9.5% dabigatran and 22.6% rivaroxaban]. Independent predictors of AC prescription over AP or no treatment were low HAS-BLED score, hypertension, labile INR, permanent AF, absence of uncontrolled hypertension, prior stroke/systemic embolism, age and male gender. In total, 37% of NOAC recipients received inappropriate dosage, while the number of patients receiving recommended dosing differed significantly among NOAC subgroups (p < 0.001). In our study, a minority of older NVAF patients received AP or no therapy for stroke prevention. Among patients treated with anticoagulants, two thirds were on NOAC treatment, though with a considerable proportion of inappropriate dosing.

Biofouling Mitigation Approaches during Water Recovery from Fermented Broth via Forward Osmosis.

Forward Osmosis (FO) is a promising technology that can offer sustainable solutions in the biorefinery wastewater and desalination fields, via low energy water recovery. However, microbial biomass and organic matter accumulation on membrane surfaces can hinder the water recovery and potentially lead to total membrane blockage. Biofouling development is a rather complex process and can be affected by several factors such as nutrient availability, chemical composition of the solutions, and hydrodynamic conditions. Therefore, operational parameters like cross-flow velocity and pH of the filtration solution have been proposed as effective biofouling mitigation strategies. Nevertheless, most of the studies have been conducted with the use of rather simple solutions. As a result, biofouling mitigation practices based on such studies might not be as effective when applying complex industrial mixtures. In the present study, the effect of cross-flow velocity, pH, and cell concentration of the feed solution was investigated, with the use of complex solutions during FO separation. Specifically, fermentation effluent and crude glycerol were used as a feed and draw solution, respectively, with the purpose of recirculating water by using FO alone. The effect of the abovementioned parameters on (i) ATP accumulation, (ii) organic foulant deposition, (iii) total water recovery, (iv) reverse glycerol flux, and (v) process butanol rejection has been studied. The main findings of the present study suggest that significant reduction of biofouling can be achieved as a combined effect of high-cross flow velocity and low feed solution pH. Furthermore, cell removal from the feed solution prior filtration may further assist the reduction of membrane blockage. These results may shed light on the challenging, but promising field of FO process dealing with complex industrial solutions.

Cryopreservation and fast recovery of enriched syngas-converting microbial communities.

Over the last decades, the use of mixed microbial communities has attracted increasing scientific attention due to their potential biotechnological applications in several emerging technological platforms such as the carboxylate, bioplastic, syngas and bio-electrochemical synthesis platforms. However, this increasing interest has not been accompanied by a parallel development of suitable cryopreservation techniques for microbial communities. While cryopreservation methods for the long-term storage of axenic cultures are well established, their effectiveness in preserving the microbial diversity and functionality of microbial communities has rarely been studied. In this study, the effect of the addition of different cryopreservation agents on the long-term storage of microbial communities at -80 °C was studied using a stable enrichment culture converting syngas into acetate and ethanol. The cryopreservation agents considered in the study were glycerol, dimethylsulfoxide, polyvinylpyrrolidone, Tween 80 and yeast extract, as well as with no addition of cryopreservation agent. Their effectiveness was evaluated based on the microbial activity recovery and the maintenance of the microbial diversity and community structure upon revival of the microbial community. The results showed that the commonly used glycerol and no addition of cryopreservation agent were the least recommendable methods for the long-term frozen storage of microbial communities, while Tween 80 and polyvinylpyrrolidone were overall the most effective. Among the cryoprotectants studied, polyvinylpyrrolidone and especially Tween 80 were the only ones assuring reproducible results in terms of microbial activity recovery and microbial community structure preservation.

Comparison of left ventricular and biventricular pacing: Rationale and clinical implications.

Cardiac resynchronization therapy constitutes a cornerstone in advanced heart failure treatment, when there is evidence of dyssynchrony, especially by electrocardiography. However, it is plagued both by persistently high (~30%) rates of nonresponse and by deterioration of right ventricular function, owing to iatrogenic dyssynchrony in the context of persistent apical pacing to ensure delivery of biventricular pacing. Left ventricular pacing has long been considered an alternative to standard biventricular pacing and can be achieved as easily as inserting a single pacing electrode in the coronary sinus. Although monoventricular left ventricular pacing has been proven to yield comparable results with the standard biventricular modality, it is the advent of preferential left ventricular pacing, combining both the powerful resynchronization potential of multipolar coronary sinus and right-sided electrodes acting in concert and the ability to preserve intrinsic, physiological right ventricular activation. In this review, we aim to present the underlying principles and modes for delivering left ventricular pacing, as well as to highlight advantages of preferential over monoventricular configuration. Finally, current clinical evidence, following implementation of automated algorithms, regarding performance of left ventricular as compared with biventricular pacing will be discussed. It is expected that the field of preferential left ventricular pacing will grow significantly over the following years, and its combination with other advanced pacing modalities may promote clinical status and prognosis of patients with advanced dyssynchronous heart failure.

On the Effect of Aqueous Ammonia Soaking Pre-Treatment on Continuous Anaerobic Digestion of Digested Swine Manure Fibers.

(1) Background: The continuously increasing demand for renewable energy sources renders anaerobic digestion as one of the most promising technologies for renewable energy production. Due to the animal production intensification, manure is being used as the primary feedstock for most biogas plants. Their economical profitable operation, however, relies on increasing the methane yield from the solid fraction of manure, which is not so easily degradable. The solid fraction after anaerobic digestion, the so-called digested fibers, consists mainly of hardly biodegradable material and comes at a lower mass per unit volume of manure compared to the solid fraction before anaerobic digestion. Therefore, investigation on how to increase the biodegradability of digested fibers is very relevant. So far, Aqueous Ammonia Soaking (AAS), has been successfully applied on digested fibers separated from the effluent of a manure-fed, full-scale anaerobic digester to enhance their methane productivity in batch experiments. (2) Methods: In the present study, continuous experiments at a mesophilic (38 °C) CSTR-type anaerobic digester fed with swine manure first and a mixture of manure with AAS-treated digested fibers in the sequel, were performed. Anaerobic Digestion Model 1 (ADM1) previously fitted on manure fed digester was used in order to assess the effect of the addition of AAS-pre-treated digested manure fibers on the kinetics of anaerobic digestion process. (3) Results and Conclusions: The methane yield of AAS-treated digested fibers under continuous operation was 49-68% higher than that calculated in batch experiments in the past. It was found that AAS treatment had a profound effect mainly on the disintegration/hydrolysis rate of particulate carbohydrates. Comparison of the data obtained in the present study with the data obtained with AAS-pre-treated raw manure fibers in the past revealed that hydrolysis kinetics after AAS pre-treatment were similar for both types of biomasses.

Enrichment of syngas-converting mixed microbial consortia for ethanol production and thermodynamics-based design of enrichment strategies.

BACKGROUND: The production of ethanol through the biochemical conversion of syngas, a mixture of H2, CO and CO2, has been typically studied using pure cultures. However, mixed microbial consortia may offer a series of benefits such as higher resilience and adaptive capacity, and non-sterile operation, all of which contribute to reducing the utility consumption when compared to pure culture-based processes. This work focuses on the study of strategies for the enrichment of mixed microbial consortia with high ethanologenic potential, investigating the effect of the operational conditions (pH and yeast extract addition) on both the ethanol yield and evolution of the microbial community along the enrichment process. The pH was selected as the main driver of the enrichment as it was expected to be a crucial parameter for the selection of carboxydotrophic bacteria with high ethanologenic potential. Additionally, a thermodynamic analysis of the network of biochemical reactions carried out by syngas-converting microbial consortia was performed and the potential of using thermodynamics as a basis for the selection of operational parameters favoring a specific microbial activity was evaluated. RESULTS: All enriched consortia were dominated by the genus Clostridium with variable microbial diversity and species composition as a function of the enrichment conditions. The ethanologenic potential of the enriched consortia was observed to increase as the initial pH was lowered, achieving an ethanol yield of 59.2 ± 0.2% of the theoretical maximum in the enrichment at pH 5. On the other hand, yeast extract addition did not affect the ethanol yield, but triggered the production of medium-chain fatty acids and alcohols. The thermodynamic analysis of the occurring biochemical reactions allowed a qualitative prediction of the activity of microbial consortia, thus enabling a more rational design of the enrichment strategies targeting specific activities. Using this approach, an improvement of 22.5% over the maximum ethanol yield previously obtained was achieved, reaching an ethanol yield of 72.4 ± 2.1% of the theoretical maximum by increasing the initial acetate concentration in the fermentation broth. CONCLUSIONS: This study demonstrated high product selectivity towards ethanol using mixed microbial consortia. The thermodynamic analysis carried out proved to be a valuable tool for interpreting the metabolic network of microbial consortia-driven processes and designing microbial-enrichment strategies targeting specific biotransformations.

Combined polyhydroxyalkanoates (PHA) and 1,3-propanediol production from crude glycerol: Selective conversion of volatile fatty acids into PHA by mixed microbial consortia.

Crude glycerol is an important by-product of the biodiesel industry, which can be converted into volatile fatty acids (VFA) and/or 1,3-propanediol (1,3-PDO) by fermentation. In this study, a selective conversion of VFA to polyhydroxyalkanoates (PHA) was attained while leaving 1,3-PDO in the supernatant by means of mixed microbial consortia selection strategies. The process showed highly reproducible results in terms of PHA yield, 0.99 ±â€¯0.07 Cmol PHA/Cmol S (0.84 g COD PHA/g COD S), PHA content (76 ±â€¯3.1 g PHA/100 g TSS) and 1,3-PDO recovery (99 ±â€¯2.1%). The combined process had an ultimate yield from crude glycerol of 0.19 g COD PHA and 0.42 g COD 1,3-PDO per g of input COD. The novel enrichment strategy applied for selectively transforming fermentation by-products into a high value product (PHA) demonstrates the significance of the enrichment process for targeting specific bio-transformations and could potentially prove valuable for other biotechnological applications as well.

Programmed ventricular stimulation predicts arrhythmic events and survival in hypertrophic cardiomyopathy.

BACKGROUND: Sudden cardiac death (SCD) risk stratification in hypertrophic cardiomyopathy (HCM) in the context of primary prevention remains suboptimal. The purpose of this study was to examine the additional contribution of programmed ventricular stimulation (PVS) on established risk assessment. METHODS: Two-hundred-and-three consecutive patients with diagnosed HCM and ≥1 noninvasive risk factors were prospectively enrolled over 19years. Patients were risk stratified, submitted to PVS and received an implantable cardioverter-defibrillator (ICD) according to then-current American Heart Association (AHA) guidelines and inducibility. Participants were prospectively followed-up for primary endpoint occurrence (appropriate ICD therapy or SCD). Contemporary (2015) AHA and European Society of Cardiology (ESC) guidelines were retrospectively assessed. RESULTS: During a median follow-up period of 60months the primary endpoint occurred in 20 patients, 19 of whom were inducible and received an ICD. Overall, 79 patients (38.9%) were inducible and 92 patients (45.3%) received an ICD (PVS sensitivity=95%, specificity=67.2%, positive predictive value=24%, negative predictive value=99.2%). AHA and ESC guidelines application misclassified 3 and 9 primary endpoint-meeting patients, respectively. Inducibility was the most important determinant of event-free survival in multivariate Cox regression (hazard ratio=33.3). A combined approach of ESC score≥6% or AHA indication for ICD with PVS inducibility yielded absolute sensitivity and negative predictive value, the former at a more cost-effective and specific way. CONCLUSIONS: Inducibility at PVS predicts SCD or appropriate device therapy in HCM. Non-inducibility is associated with prolonged event-free survival, while the procedure was proven safe. Reintegration of PVS into established risk stratification models in HCM may improve patient assessment.

Heart failure study of multipoint pacing effects on ventriculoarterial coupling: Rationale and design of the HUMVEE trial.

Cardiac resynchronization therapy (CRT) is an established therapy for symptomatic heart failure (HF). Unfortunately, many recipients remain nonresponders. Studies have revealed the potential role of multipoint pacing (MPP) in improving response and outcomes. The aim of this study is to compare the effects of MPP against those of standard biventricular pacing (BVP) on (i) ventriculoarterial coupling (VAC) and energy efficiency of the failing heart, (ii) diastolic function, (iii) quality of life, and (iv) NT-proBNP levels and glomerular filtration rate (GFR) during a follow-up of 13 months. HUMVEE is a single-center, prospective, observational, crossover cohort study. Seventy-six patients with BVP indication will be implanted with a system able to deliver both pacing modes. BVP will be activated at implantation and optimized 1 month after. At 6 months postoptimization MPP will be activated and optimized. Optimization will be performed based on stroke volume maximization, as assessed by ultrasound. Laboratory measurements (GFR and NT-proBNP) and echocardiographic studies (VAC calculation, strain rate, diastolic function) will be performed at implantation, 6 months post-BVP optimization and at the end of 13 months of follow-up (6 months post-MPP optimization). Potential reduction in arrhythmogenesis by MPP will also be assessed. MPP is a pacing modality with the potential to improve HF patients' outcomes. The HUMVEE trial will attempt to associate any potential added beneficial effects of MPP over standard BVP with alterations in VAC and energy efficiency of the heart, thus uncovering a novel mechanistic link between MPP and improved outcomes in HF.