Citations

Background The temporal incidence of high‐grade atrioventricular block (HAVB) after transcatheter aortic valve replacement (TAVR) is uncertain. As a result, periprocedural monitoring and pacing strategies remain controversial. This study aimed to describe the temporal incidence of initial episode of HAVB stratified by pre‐ and post‐TAVR conduction and identify predictors of delayed events. Methods and Results Consecutive patients undergoing TAVR at a single center between February 2012 and June 2019 were retrospectively assessed for HAVB within 30 days. Patients with prior aortic valve replacement, permanent pacemaker (PPM), or conversion to surgical replacement were excluded. Multivariable logistic regression was performed to assess predictors of delayed HAVB (initial event >24 hours post‐TAVR). A total of 953 patients were included in this study. HAVB occurred in 153 (16.1%). After exclusion of those with prophylactic PPM placed post‐TAVR, the incidence of delayed HAVB was 33/882 (3.7%). Variables independently associated with delayed HAVB included baseline first‐degree atrioventricular block or right bundle‐branch block, self‐expanding valve, and new left bundle‐branch block. Forty patients had intraprocedural transient HAVB, including 16 who developed HAVB recurrence and 6 who had PPM implantation without recurrence. PPM was placed for HAVB in 130 (13.6%) (self‐expanding valve, 23.7% versus balloon‐expandable valve, 11.9%; P <0.001). Eight (0.8%) patients died by 30 days, including 1 unexplained without PPM present. Conclusions Delayed HAVB occurs with higher frequency in patients with baseline first‐degree atrioventricular block or right bundle‐branch block, new left bundle‐branch block, and self‐expanding valve. These findings provide insight into optimal monitoring and pacing strategies based on periprocedural ECG findings.

Matrix stiffness is a central regulator of fibroblast function. However, the transcriptional mechanisms linking matrix stiffness to changes in fibroblast phenotype are incompletely understood. Here, we evaluated the effect of matrix stiffness on genome-wide chromatin accessibility in freshly isolated lung fibroblasts using ATAC-seq. We found higher matrix stiffness profoundly increased global chromatin accessibility relative to lower matrix stiffness, and these alterations were in close genomic proximity to known profibrotic gene programs. Motif analysis of these regulated genomic loci identified ZNF416 as a putative mediator of fibroblast stiffness responses. Genome occupancy analysis using ChIP-seq confirmed that ZNF416 occupies a broad range of genes implicated in fibroblast activation and tissue fibrosis, with relatively little overlap in genomic occupancy with other mechanoresponsive and profibrotic transcriptional regulators. Using loss- and gain-of-function studies, we demonstrated that ZNF416 plays a critical role in fibroblast proliferation, extracellular matrix synthesis, and contractile function. Together, these observations identify ZNF416 as novel mechano-activated transcriptional regulator of fibroblast biology.

Introduction: Patients with D-TGA palliated with atrial switch operations have the morphologic right ventricle in the systemic position. There is increased risk of atrial arrhythmias and systemic right ventricle (SRV) failure. We sought to analyze the long term outcomes of these patients. Methods: All patients with D-TGA and SRV followed in the Adult Congenital Heart Disease Clinic of a large tertiary care institution were reviewed. A comprehensive retrospective analysis of the medical record was performed, including consult notes, ECGs, echocardiograms and electrophysiology reports. Results: A total of 154 patients (63% male) aged 29±11 years were followed for a mean of 10±9 years (range 0-51). During follow-up, 3 patients underwent cardiac transplantation and 15 died; 5 had sudden death, 2 had cardiogenic shock, 5 had non-cardiac death (i.e., infective endocarditis, sepsis) and 3 had unknown causes of death. Heart failure symptoms were present in 53(34%) patients. Severe SRV systolic dysfunction occurred in 37(24%) patients, with a mean EF of 23±5.5%; moderate SRV dysfunction occurred in 67(44%) patients, mean EF 35±4%. Sinus node dysfunction was present in 75(49%) patients, complete AV block in 9(5%) patients, and a pacemaker placed in 60(39%) patients, with cardiac resynchronization therapy in 5. Atrial arrhythmias occurred in 94(61%) patients and ablations were performed in 47(31%) patients. An ICD was implanted in 37 patients; 5 patients had appropriate shocks, but 7 had inappropriate shocks due to atrial arrhythmias. Age (HR 1.07, p=001), heart failure symptoms (HR 4.9, p= 0.007), severe SRV enlargement (HR 3.7, p=0.03), severe systolic dysfunction (HR 5.4, p=0.003), severe systemic AV valve regurgitation (HR 5.2, p=0.002) and a QRS duration> 122ms (HR 3.7, p=0.02) were significant predictors of mortality. The 15 year probability of sudden death was 3.2%(95% CI 0-6.9%). Conclusions: Atrial arrhythmias are common after atrial switch operations secondary to atriotomy scars. Further studies will need to determine whether restoration of sinus rhythm or cardiac synchrony may prevent further deterioration of the systemic right ventricle. Severe SRV dysfunction and prolonged QRS duration >122ms were significantly correlated with mortality.

ABSTRACT Matrix resorption is essential to the clearance of the extracellular matrix (ECM) after normal wound healing. A disruption in these processes constitutes a main component of fibrotic diseases, characterized by excess deposition and diminished clearance of fibrillar ECM proteins, such as collagen type I. The mechanisms and stimuli regulating ECM resorption in the lung remain poorly understood. Recently, agonism of dopamine receptor D1 (DRD1), which is predominantly expressed on fibroblasts in the lung, has been shown to accelerate tissue repair and clearance of ECM following bleomycin injury in mice. Therefore, we investigated whether DRD1 receptor signaling promotes the degradation of collagen type I by lung fibroblasts. For cultured fibroblasts, we found that DRD1 agonism enhances extracellular cleavage, internalization and lysosomal degradation of collagen I mediated by cathepsin K, which results in reduced stiffness of cell-derived matrices, as measured by atomic force microscopy. In vivo agonism of DRD1 similarly enhanced fibrillar collagen degradation by fibroblasts, as assessed by tissue labeling with a collagen-hybridizing peptide. Together, these results implicate DRD1 agonism in fibroblast-mediated collagen clearance, suggesting an important role for this mechanism in fibrosis resolution. This article has an associated First Person interview with the first author of the paper.

AbstractObjectiveThis study sought to determine if single‐chamber operation and/or loss of rate response (RR) during elective replacement indicator (ERI) in patients with dual‐chamber pacemakers lead to increased symptom burden, healthcare utilization, and atrial fibrillation (AF).BackgroundDual‐chamber pacemakers often change from dual‐ to single‐chamber pacing mode and/or lose RR functionality at ERI to preserve battery. Single‐chamber pacing increases the incidence of heart failure, AF, and pacemaker syndrome suggesting these changes may be deleterious.MethodsA retrospective analysis of 700 patients was completed. Three comparisons were analyzed: Comparison 1: mode change and RR loss versus no change; Comparison 2: RR loss only versus no change; Comparison 3: mode change only versus no change (in patients with no RR programmed at baseline).ResultsIn Comparison 1, 121 (46%) patients with setting changes experienced symptoms (most often dyspnea and fatigue/exercise intolerance) versus 3 (4%) without setting changes (p < .0001). Similar results were noted in Comparisons 2 and 3 (p = .0016 and p = .0001, respectively). In Comparison 1, patients with setting change sought provider contact more than patients without setting changes (p = .0001). A significant difference was not noted in Comparison 2 or 3. Overall 14 (2%) patients were hospitalized, all of whom had setting changes.ConclusionsSetting changes at ERI including a change from dual‐ to single‐chamber pacing and/or loss of RR results in a significantly increased symptom burden and increased healthcare utilization.

Rationale, aims, and objectives: Post-hospitalization follow-up within 30 days following discharge has been shown to positively impact time to readmission, healthcare costs, and patient self-reported adherence and satisfaction. We aimed to improve resident satisfaction with the process of establishing post-hospitalization, primary care provider (PCP) follow-up. Methods: In this quality improvement study we surveyed all internal medicine residents at our institution regarding their satisfaction with the process of establishing PCP follow-up at the time of hospital discharge. A streamlined process was developed and two subsequent interventions were enacted; a dedicated teaching session and distribution of pocket cards outlining the process. Residents were then surveyed following each intervention to assess for impact on overall satisfaction and burden of work. Results: Initially, 77.3% of residents were not satisfied with the process of establishing post-hospitalization PCP follow-up. Following the first intervention there was a trend towards increasing satisfaction rates by 16.7% (p= 0.20), and after the second intervention there was a statistically significant increase in satisfaction rates from baseline by 44% (p= 0.007). There was also a reduction in the feeling of workload burden associated with establishing PCP follow-up from 32% to 25%, and over 67% of participants either agreed or strongly agreed that the workload was not too burdensome. Conclusion: This quality improvement initiative established that resident physicians at our institution previously found the process of establishing PCP follow-up at the time of patient discharge both confusing and burdensome. Through the implementation of our interventions we were able to achieve our aims of improving resident satisfaction.

Pharmacologic stimulation of a G protein–coupled receptor preferentially expressed on fibroblasts reverses experimental lung and liver fibrosis.

Abstract Introduction Multiple myeloma (MM) has characteristics that influence the prognosis and are useful to make decisions regarding treatment. Diagnosis and treatment patterns of hematological malignancies have not been described in Colombia and having access to this regional information could guide public health policies and help design clinical trials. The Colombian Association of Hematology and Oncology (ACHO) designed a registry for Hemato-Oncological diseases to fill this information gap. This is the first report of RENEHOC focusing on MM. Methods We conducted an ambispective multi-centric cohort study of clinical records available from patients with MM that were diagnosed in the most populated regions of Colombia. We collected demographic, diagnostic, clinical and treatment data at different time points from diagnosis to the most current follow up. The computerized de-identified data was consolidated and analyzed using basic statistical measures of central tendency and dispersion. The most current follow up included data available from last clinic visit, loss of follow up, death or withdrawal of consent. This study was approved by local and centralized institutional review board. Results We analyzed data from 206 MM patients (pts). Average age at diagnosis was 62.9 (SD 10.2) years and 51.4% of pts were male. Most common symptoms at diagnosis were bone pain (74.2%), anemia related (58.2%) and pathological fractures (45.1%). Mean time from symptoms to diagnosis was 7.3 (Range 1-44) months. Baseline mean hemoglobin, creatinine and calcium serum levels were 10.5 g/dL, 1.58 mg/dL and 9.2 mg/dL respectively. At diagnosis, 22% of patients presented with renal failure and 30% required dialysis. Immunoglobulin (Ig) subtype distribution was: IgG 50.6%, IgA 20.6%, only light chain secretion (61% Kappa) and IgM 1.1%. In 11.6% all Igs were low. Most pts were diagnosed at advanced stages (64.5% Durie-Salmon III, and 37% and 47% International Staging System II and III respectively). Molecular prognostic characterization was performed only in 39 patients (18.4%). Four patients were considered too fragile for active treatment. The most common initial treatment was triple combinations that included Bortezomib (84% of patients). Among those, CyBorD was the most frequently used first line therapy (58.3%), followed by VTD (14.6%). Mean number of cycles was 4.8 (SD 2.5). Overall Response Rate (ORR) 74.7% was observed. Only 40% of patients treated with intense induction therapy received autologous transplant. Response to treatment including transplant are shown in table 1. Second and further lines of treatment were highly variable. 18 patients were treated with a second autologous transplantation consolidating 2nd line therapy. 12 patients received Carfilzomib combinations, all of them in 2nd line. 5 patients were treated with Daratumumab, all >2nd line. Mean follow-up time was 33.53 (SD 3.6) months. After a median follow up of 27 months we observed in our cohort an overall survival of 82% and 68% of patients progression-free. . Conclusions This first report focusing on MM highlights important differences on patient's characteristics and treatment in Colombian patients. This includes and treatment initiation due to insurance barriers; high risk clinical characteristics and complications upon diagnosis and low rate of transplantation in patients otherwise eligible for this procedure. Rates of response to induction seem slightly lower than reported (CB Reeder 2009). However, overall survival and progression-free survival met the expectations for this type of patients. The development of country specific databases may influence the design of policies, allocation and use of resources and improve patient outcomes. Only cooperative efforts like the one spearheaded by RENEHOC can achieve those goals. Disclosures No relevant conflicts of interest to declare.

AbstractIntroductionTo evaluate the outcomes of video‐assisted thoracoscopic surgery (VATS) during transvenous lead extractions (TLEs).Methods and resultsNinety‐one high‐risk patients who underwent TLE in the operating room from January 1, 2015, to March 31, 2017, were included in the study. Of these, 9 patients underwent VATS during TLE. Their clinical characteristics, indications for lead extraction, and complications associated with TLE in the 9 patients who had VATS were compared with those for the 82 patients who did not have VATS. The mean (SD) age of the study patients was 61 (17) years (64.8% were male). The lead dwell time, number of leads extracted, and clinical comorbidities were similar between the 2 groups. Superior vena cava (SVC) tear occurred in 2 of the 9 patients in VATS group and in 1 of the 82 in the non‐VATS group (22.2% vs. 1.2%, P = 0.03). Of the 2 patients in the VATS group who had SVC tears, in 1 the tear was visualized immediately and there was no hemodynamic compromise. In the other patient, the SVC tear was within the pericardium; the blood pressure recovered quickly after sternotomy and repair. Both patients had complete lead extraction and survived hospitalization. The patient in the non‐VATS group who had an SVC tear had a successful repair but died of postoperative complications.ConclusionsUtilization of VATS to facilitate TLE is beneficial for early recognition of SVC tear and timely surgical repair in select high‐risk patients.