A multicenter prospective randomized controlled trial of cardiac resynchronization therapy guided by invasive dP/dt

Background: No periprocedural metric has demonstrated improved cardiac resynchronization therapy (CRT) outcomes in a multicenter setting. Objective: We sought to determine if left ventricular (LV) lead placement targeted to the coronary sinus (CS) branch generating the best acute hemodynamic response (AHR) results in improved outcomes at 6 months. Methods: In this multicenter randomized controlled trial, patients were randomized to guided CRT or conventional CRT. Patients in the guided arm had LV dP/dtmax measured during biventricular (BIV) pacing. Target CS branches were identified and the final LV lead position was the branch with the best AHR and acceptable threshold values. The primary endpoint was the proportion of patients with a reduction in LV end-systolic volume (LVESV) of ≥15% at 6 months. Results: A total of 281 patients were recruited across 12 centers. Mean age was 70.8 ± 10.9 years and 54% had ischemic etiology. Seventy-three percent of patients in the guided arm demonstrated a reduction in LVESV of ≥15% at 6 months vs 60% in the conventional arm (P = .02). Patients with AHR ≥ 10% were more likely to demonstrate a reduction of ESV ≥ 15% (84% of patients with an AHR ≥10% vs 28% with an AHR <10%; P < 0.001). Procedure duration and fluoroscopy times were longer in the pressure wire-guided arm (104 ± 39 minutes vs 142 ± 39 minutes; P < .001 and 20 ±16 minutes vs 28 ± 15 minutes; P = .002). Conclusions: AHR determined by invasively measuring LV dP/dtmax during BIV pacing predicts reverse remodeling 6 months after CRT. Patients in whom LV dP/dtmax was used to guide LV lead placement demonstrated better rates of reverse remodeling

Standard care vs. TRIVEntricular pacing in Heart Failure (STRIVE HF): a prospective multicentre randomized controlled trial of triventricular pacing vs. conventional biventricular pacing in patients with heart failure and intermediate QRS left bundle branch block

AIMS: To determine whether triventricular (TriV) pacing is feasible and improves CRT response compared to conventional biventricular (BiV) pacing in patients with left bundle branch block (LBBB) and intermediate QRS prolongation (120-150 ms). METHODS AND RESULTS: Between October 2015 and November 2019, 99 patients were recruited from 11 UK centres. Ninety-five patients were randomized 1:1 to receive TriV or BiV pacing systems. The primary endpoint was feasibility of TriV pacing. Secondary endpoints assessed symptomatic and remodelling response to CRT. Baseline characteristics were balanced between groups. In the TriV group, 43/46 (93.5%) patients underwent successful implantation vs. 47/49 (95.9%) in the BiV group. Feasibility of maintaining CRT at 6 months was similar in the TriV vs. BiV group (90.0% vs. 97.7%, P = 0.191). All-cause mortality was similar between TriV vs. BiV groups (4.3% vs. 8.2%, P = 0.678). There were no significant differences in echocardiographic LV volumes or clinical composite scores from baseline to 6-month follow-up between groups. CONCLUSION: Implantation of two LV leads to deliver and maintain TriV pacing at 6 months is feasible without significant complications in the majority of patients. There was no evidence that TriV pacing improves CRT response or provides additional clinical benefit to patients with LBBB and intermediate QRS prolongation and cannot be recommended in this patient group. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT02529410

The antiparallel loops in gal DNA

Interactions between proteins bound to distant sites along a DNA molecule require bending and twisting deformations in the intervening DNA. In certain systems, the sterically allowed protein–DNA and protein–protein interactions are hypothesized to produce loops with distinct geometries that may also be thermodynamically and biologically distinct. For example, theoretical models of Gal repressor/HU-mediated DNA-looping suggest that the antiparallel DNA loops, A1 and A2, are thermodynamically quite different. They are also biologically different, since in experiments using DNA molecules engineered to form only one of the two loops, the A2 loop failed to repress in vitro transcription. Surprisingly, single molecule measurements show that both loop trajectories form and that they appear to be quite similar energetically and kinetically

Frailty assessment: An emerging concept in aged People Living with HIV (PLHIV)

Introduction: As the life expectancy of People Living with HIV (PLHIV) has improved with effective antiretroviral treatment (ART), they now face the challenges of accelerated ageing. Frailty is an emerging concept in the management of PLHIV and up to 28% of PLHIV are identified as frail. Frailty is a determinant of adverse clinical outcomes and is a complex clinical endpoint that has not been studied in India. This exploratory study was done to evaluate frailty and its determinants among PLHIV in India. Materials and Methods: This was a cross-sectional study in 76 PLHIV aged 50 years or more. All the study subjects underwent a comprehensive clinical assessment. The Fried's criteria and Veterans Aging Cohort Study (VACS) Index were used to evaluate for frailty. Socio-demographic, clinical, immunological, and virological variables were assessed for their association with frailty. The study was registered under Clinical Trials Registry-India (ICMR-NIMS): REF/2019/05/025616. Results: The mean age of the subjects was 56.05 ± 5.8 years (range 50-76), and males constituted 81.57% (62/76) of the subjects and majority (60.53%) were underweight. On frailty assessment, 57.89% of the PLHIV were identified as prefrail/frail. Frailty had a significant association with low CD4 count (P = 0.0001) and number of comorbidities (P = 0.017) especially when comorbidities ≥2 (P = 0.04) and polypharmacy (P = 0.033). VACS index, polypharmacy, and low CD4 count ≤200 cells/mm3 were strong predictors of frailty. On multivariate regression analysis, CD4 count ≤200 emerged as the strongest independent predictor of frailty. Conclusion: The study highlighted the high prevalence of frailty and under nutrition among aged PLHIV. The study emphasizes the need for a shift away from traditional clinical endpoints to other outcome measures for a holistic approach to PLHIV

Impact of COVID-19 Infection on the Clinical Outcomes of Pulmonary Embolism Hospitalizations : A Nationwide Analysis

There is an increased risk of venous thromboembolism among patients with COVID-19 infection, with the risk being higher among those needing the intensive level of care. Existing data is, however, limited regarding the outcomes of patients admitted with concurrent COVID-19 infection and pulmonary embolism (PE). All acute PE admissions were identified from the National Inpatient Sample database during 2020 using ICD-10 codes. Patients were subsequently classified into those with and without COVID-19 infection. The primary outcome of interest was in-hospital mortality. Using multivariate logistic regression, the predictors of mortality were assessed for patients with concurrent acute PE and COVID-19. The database query generated 278,840 adult patients with a primary diagnosis of PE. Of these, 4580 patients had concurrent PE and COVID-19 infection. The concurrent PE and COVID-19 infection group had a higher proportion of Black-American and Hispanic patients, and those living in the zip codes associated with the lowest annualized income compared to the PE alone group. Furthermore, patients in the concurrent PE and COVID-19 infection group had an increased risk of in-hospital mortality (adjusted odds ratio [aOR]:1.62; 95% CI: 1.17-2.24; P = 0.004), septic shock (aOR: 1.66; 95% CI 1.10-2.52; P = 0.016), respiratory failure (aOR: 1.78; 95% CI 1.53-2.06; P = 0.001), and a longer hospital stay [5.5 days vs 4.59 days; P = 0.001). Concurrent COVID-19 and PE admissions is associated with an increased in-hospital mortality, risk of septic shock and respiratory failure, and a longer length of hospital stay

Incidence and Prognostic Implications of Cardiac-Implantable Device-Associated Tricuspid Regurgitation: A Meta-Analysis and Meta-Regression Analysis

New-onset or worsening tricuspid regurgitation (TR) is a well-established complication encountered after cardiac implantable electronic devices (CIEDs). However, there are limited and conflicting data on the true incidence and prognostic implications of this complication. This study aimed to bridge this current gap in the literature. Electronic databases MEDLINE, Embase, and Web of Science were systematically searched from inception to March 2023, for studies reporting the incidence and/or prognosis of CIED-associated new or worsening TR. Potentially eligible studies were screened and selected according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A random effect model meta-analysis and meta-regression analysis were performed, and I-squared statistic was used to assess heterogeneity. A total of 52 eligible studies, with 130,759 patients were included in the final quantitative analysis with a mean follow-up period of 25.5 months. The mean age across included studies was 69.35 years, and women constituted 46.6% of the study population. The mean left ventricular ejection fraction was 50.15%. The incidence of CIED-associated TR was 24% (95% confidence interval [CI] 20% to 28%, p \u3c 0.001) with an odds ratio of 2.44 (95% CI 1.58 to 3.77, p \u3c 0.001). CIED-associated TR was independently associated with an increased risk of all-cause mortality (adjusted hazard ratio [aHR] 1.52, 95% CI 1.36 to 1.69, p \u3c 0.001), heart failure (HF) hospitalizations (aHR 1.82, 95% CI 1.19 to 2.78, p = 0.006), and the composite of mortality and HF hospitalizations (aHR 1.96, 95% CI 1.33 to 2.87, p = 0.001) in the follow-up period. In conclusion, CIED-associated TR occurred in nearly one-fourth of patients after device implantation and was associated with an increased risk of all-cause mortality and HF hospitalizations

Invasive Mechanical Ventilation and Death Was More Likely in Patients with Lower LDL Cholesterol Levels during COVID-19 Hospitalization: A Retrospective Propensity-Matched Cohort Study

Hyperlipidemia has been associated with worse outcomes in patients with Coronavirus disease 2019 (COVID-19). However, lower LDL-C (low-density lipoprotein cholesterol) levels have been associated with increased COVID-19 severity and mortality. We conducted a retrospective observational study of patients with COVID-19 admitted to New York City Health and Hospitals from 1 March 2020 to 31 October 2020, comparing pre-COVID-19 LDL-C levels or LDL-C levels obtained during COVID-19 hospitalization, with the need for invasive mechanical ventilation and death. Propensity score matching was performed using logistic regression models, and standardized mean differences were calculated. A total of 3020 patients (median age 61 years; 36% women) were included. In the matched cohort, on multivariate logistic regression analysis, LDL was inversely associated with in-hospital death (OR: 0.99, 95% CI: 0.986–0.999, p = 0.036). As a categorical variable, LDL > 70 mg/dL was associated with 47% lower likelihood of invasive mechanical ventilation (OR: 0.53, 95% CI: 0.29–0.95, p = 0.034). No significant association between pre-COVID-19 LDL and death or invasive mechanical ventilation was found (OR: 1.00, 95% CI 0.99–1.01, p = 0.833). Low LDL-C level measured during COVID-19 was associated with a higher likelihood of invasive mechanical ventilation and in-hospital death. A similar association was not found between pre-COVID-19 LDL-C and these outcomes. LDL-C levels obtained during COVID-19 are likely not reflective of the baseline lipid profile

A multicenter prospective randomized controlled trial of cardiac resynchronization therapy guided by invasive dP/dt

BACKGROUND: No periprocedural metric has demonstrated improved cardiac resynchronization therapy (CRT) outcomes in a multicenter setting. OBJECTIVE: We sought to determine if left ventricular (LV) lead placement targeted to the coronary sinus (CS) branch generating the best acute hemodynamic response (AHR) results in improved outcomes at 6 months. METHODS: In this multicenter randomized controlled trial, patients were randomized to guided CRT or conventional CRT. Patients in the guided arm had LV dP/dt(max) measured during biventricular (BIV) pacing. Target CS branches were identified and the final LV lead position was the branch with the best AHR and acceptable threshold values. The primary endpoint was the proportion of patients with a reduction in LV end-systolic volume (LVESV) of ≥15% at 6 months. RESULTS: A total of 281 patients were recruited across 12 centers. Mean age was 70.8 ± 10.9 years and 54% had ischemic etiology. Seventy-three percent of patients in the guided arm demonstrated a reduction in LVESV of ≥15% at 6 months vs 60% in the conventional arm (P = .02). Patients with AHR ≥ 10% were more likely to demonstrate a reduction of ESV ≥ 15% (84% of patients with an AHR ≥10% vs 28% with an AHR <10%; P < 0.001). Procedure duration and fluoroscopy times were longer in the pressure wire–guided arm (104 ± 39 minutes vs 142 ± 39 minutes; P < .001 and 20 ±16 minutes vs 28 ± 15 minutes; P = .002). CONCLUSIONS: AHR determined by invasively measuring LV dP/dt(max) during BIV pacing predicts reverse remodeling 6 months after CRT. Patients in whom LV dP/dt(max) was used to guide LV lead placement demonstrated better rates of reverse remodeling

Modeling the Lac repressor-operator assembly: The influence of DNA looping on Lac repressor conformation

Repression of transcription of the Escherichia coli Lac operon by the Lac repressor (LacR) is accompanied by the simultaneous binding of LacR to two operators and the formation of a DNA loop. A recently developed theory of sequence-dependent DNA elasticity enables one to relate the fine structure of the LacR–DNA complex to a wide range of heretofore-unconnected experimental observations. Here, that theory is used to calculate the configuration and free energy of the DNA loop as a function of its length and base-pair sequence, its linking number, and the end conditions imposed by the LacR tetramer. The tetramer can assume two types of conformations. Whereas a rigid V-shaped structure is observed in the crystal, EM images show extended forms in which two dimer subunits are flexibly joined. Upon comparing our computed loop configurations with published experimental observations of permanganate sensitivities, DNase I cutting patterns, and loop stabilities, we conclude that linear DNA segments of short-to-medium chain length (50–180 bp) give rise to loops with the extended form of LacR and that loops formed within negatively supercoiled plasmids induce the V-shaped structure

Standard care vs. TRIVEntricular pacing in Heart Failure (STRIVE HF):a prospective multicentre randomized controlled trial of triventricular pacing vs. conventional biventricular pacing in patients with heart failure and intermediate QRS left bundle branch block

AIMS: To determine whether triventricular (TriV) pacing is feasible and improves CRT response compared to conventional biventricular (BiV) pacing in patients with left bundle branch block (LBBB) and intermediate QRS prolongation (120–150 ms). METHODS AND RESULTS: Between October 2015 and November 2019, 99 patients were recruited from 11 UK centres. Ninety-five patients were randomized 1:1 to receive TriV or BiV pacing systems. The primary endpoint was feasibility of TriV pacing. Secondary endpoints assessed symptomatic and remodelling response to CRT. Baseline characteristics were balanced between groups. In the TriV group, 43/46 (93.5%) patients underwent successful implantation vs. 47/49 (95.9%) in the BiV group. Feasibility of maintaining CRT at 6 months was similar in the TriV vs. BiV group (90.0% vs. 97.7%, P = 0.191). All-cause mortality was similar between TriV vs. BiV groups (4.3% vs. 8.2%, P = 0.678). There were no significant differences in echocardiographic LV volumes or clinical composite scores from baseline to 6-month follow-up between groups. CONCLUSION: Implantation of two LV leads to deliver and maintain TriV pacing at 6 months is feasible without significant complications in the majority of patients. There was no evidence that TriV pacing improves CRT response or provides additional clinical benefit to patients with LBBB and intermediate QRS prolongation and cannot be recommended in this patient group. CLINICAL TRIAL REGISTRATION NUMBER: Clinicaltrials.gov: NCT02529410