Assessing cardiac resynchronization therapy response in heart failure patients: a comparative analysis of efficacy and outcomes between transvenous and epicardial leads.

Cardiac resynchronization therapy (CRT) is an effective treatment for selected heart failure (HF) patients. Although transvenous implantation is the standard method, it is not feasible in some patients, so the epicardial lead emerges as an alternative. We aim to compare CRT response, procedure-related complications, and the occurrence of clinical outcomes between patients with transvenous and epicardial leads. In a single-center retrospective study, we enrolled consecutive HF patients submitted to CRT implantation with a defibrillator between 2013 and 2022. Clinical response was defined as an improvement of at least one of the New York Heart Association classes with no occurrence of cardiovascular death or HF hospitalization in the first year of follow-up. Echocardiographic response was attained with an increase in left ventricular ejection fraction 10% or a reduction of left ventricular end-diastolic volume >15% at 6-12 months after CRT implantation. Major adverse cardiovascular events (MACE) (cardiovascular mortality and HF hospitalization) and all-cause mortality were evaluated. From a total of 149 patients, 38% (n=57) received an epicardial lead. Clinical (63% versus 60%, p=0.679) and echocardiographic (63% versus 60%, p=0.679) responses were similar between the transvenous and epicardial groups. Patients in the transvenous group had a shorter hospital stay (2 versus 7 days, p<0.001). Procedure-related complications were comparable between groups (24% versus 28%, p=0.572), but left ventricular lead-related complications were more frequent in the transvenous group (14% versus 2%). During a median follow-up of 4.7 years, the rate of MACE was 30% (n=44), with no differences in both groups (p=0.591), neither regarding HF hospitalization (p=0.917) nor cardiovascular mortality (p=0.060). Nevertheless, the epicardial group had a higher rate of all-cause mortality (35% versus 20%, p=0.005), the majority occurring during long-term follow-up (>12 months), with no deaths in the postoperative period. Considering the comparable rates of CRT response, procedure-related complications, and MACE between groups, we conclude that epicardial lead is a feasible alternative for CRT when transvenous lead implantation is not possible. The occurrence of a higher number of all-cause deaths in epicardial patients in the long-term follow-up was mainly due to infectious complications (unrelated to the lead) and the progression of oncological/chronic diseases.

Genetic testing as a supporting tool in prescribing psychiatric medication: Design and protocol of the IMPACT study.

OBJECTIVE: Pharmacotherapy is one of the primary treatments for psychiatric disorders. Given the variation in individual response, a more personalized approach is needed. This paper will discuss methods for user-friendly referrals, recruitment criteria, data storage and dissemination, biological sample and clinical questionnaire collection, and advertising. METHODS: The Individualized Medicine: Pharmacogenetics Assessment and Clinical Treatment (IMPACT) study is one of the first to use pharmacogenetic testing on a large scale in psychiatry as a tool to predict individual drug response and tolerability. As IMPACT's eligibility criteria includes all diagnoses and comorbidities, the participant population will reflect the diversity amongst mental health consumers. IMPACT's innovative study design will demonstrate the utility of this testing within the health care system. RESULTS: IMPACT has successfully implemented pharmacogenetic testing on a relatively large scale, and in both tertiary level and primary care settings. It represents a novel approach to psychiatric care and from its initial stages the design has evolved to accommodate the nature and needs of the health care community. CONCLUSION: It is anticipated that IMPACT will continue to demonstrate the feasibility of pharmacogenetic testing and facilitate its introduction and implementation in routine healthcare practice.

Crowd-funded micro-grants for genomics and "big data": an actionable idea connecting small (artisan) science, infrastructure science, and citizen philanthropy.

Biomedical science in the 21(st) century is embedded in, and draws from, a digital commons and "Big Data" created by high-throughput Omics technologies such as genomics. Classic Edisonian metaphors of science and scientists (i.e., "the lone genius" or other narrow definitions of expertise) are ill equipped to harness the vast promises of the 21(st) century digital commons. Moreover, in medicine and life sciences, experts often under-appreciate the important contributions made by citizen scholars and lead users of innovations to design innovative products and co-create new knowledge. We believe there are a large number of users waiting to be mobilized so as to engage with Big Data as citizen scientists-only if some funding were available. Yet many of these scholars may not meet the meta-criteria used to judge expertise, such as a track record in obtaining large research grants or a traditional academic curriculum vitae. This innovation research article describes a novel idea and action framework: micro-grants, each worth $1000, for genomics and Big Data. Though a relatively small amount at first glance, this far exceeds the annual income of the "bottom one billion"-the 1.4 billion people living below the extreme poverty level defined by the World Bank ($1.25/day). We describe two types of micro-grants. Type 1 micro-grants can be awarded through established funding agencies and philanthropies that create micro-granting programs to fund a broad and highly diverse array of small artisan labs and citizen scholars to connect genomics and Big Data with new models of discovery such as open user innovation. Type 2 micro-grants can be funded by existing or new science observatories and citizen think tanks through crowd-funding mechanisms described herein. Type 2 micro-grants would also facilitate global health diplomacy by co-creating crowd-funded micro-granting programs across nation-states in regions facing political and financial instability, while sharing similar disease burdens, therapeutics, and diagnostic needs. We report the creation of ten Type 2 micro-grants for citizen science and artisan labs to be administered by the nonprofit Data-Enabled Life Sciences Alliance International (DELSA Global, Seattle). Our hope is that these micro-grants will spur novel forms of disruptive innovation and genomics translation by artisan scientists and citizen scholars alike. We conclude with a neglected voice from the global health frontlines, the American University of Iraq in Sulaimani, and suggest that many similar global regions are now poised for micro-grant enabled collective innovation to harness the 21(st) century digital commons.

The brain-derived neurotrophic factor gene confers susceptibility to bipolar disorder: evidence from a family-based association study.

Bipolar disorder (BP) is a severe psychiatric disease, with a strong genetic component, that affects 1% of the population worldwide and is characterized by recurrent episodes of mania and depression. Brain-derived neurotrophic factor (BDNF) has been implicated in the pathogenesis of mood disorders, and the aim of the present study was to test for the presence of linkage disequilibrium between two polymorphisms in the BDNF gene and BP in 283 nuclear families. Family-based association test (FBAT) results for the dinucleotide repeat (GT)(N) polymorphism at position -1040 bp showed that allele A3 was preferentially transmitted to the affected individuals (Z=2.035 and P=.042). FBAT results for the val66met SNP showed a significant association for allele G (Z=3.415 and P=.00064). Transmission/disequilibrium test (TDT) haplotype analysis showed a significant result for the 3-G allele combination (P=.000394), suggesting that a DNA variant in the vicinity of the BDNF locus confers susceptibility to BP. Given that there is no direct evidence that either of the polymorphisms we examined alters function, it is unlikely that the actual risk-conferring allele is from these two sites. Rather, the causative site is likely nearby and in linkage disequilibrium with the 3-G haplotype that we have identified.