Annie Laurie Shroyer

Long-Term Follow-Up Assessment of a Phase 1 Trial of Angiogenic Gene Therapy Using Direct Intramyocardial Administration of an Adenoviral Vector Expressing the VEGF121 cDNA for the Treatment of Diffuse Coronary Artery Disease

On the basis of studies in experimental animals demonstrating that AdVEGF121, an E1(-)E3(-) serotype 5 adenovirus coding the 121 isoform of vascular endothelial growth factor (VEGF), could mediate the generation of new blood vessels and reverse coronary ischemia, a clinical study of direct myocardial administration of AdVEGF121 was initiated in patients with late-stage, diffuse coronary artery disease. This study provides long-term (median, 11.8 years) follow-up on these patients. From 1997 to 1999, AdVEGF121 was administered by direct myocardial injection to an area of reversible ischemia in 31 patients with severe coronary disease, either as an adjunct to conventional coronary artery bypass grafting (group A) or as minimally invasive sole (MIS) therapy, using a minithoracotomy (group B). There was no control group; the study participants served as the control subjects. The 5- and 10-year survival was 10 of 15 (67%) and 6 of 15 (40%) for the group A patients, and 11 of 16 (69%) and 5 of 16 (31%) for group B sole therapy patients, respectively. In comparison, maximal medical therapy in comparable groups in the literature have a 3- to 5-year survival rate of 52 to 59%. For the survivors, the angina score for group A was 3.4±0.5 at time 0 and 1.9±1.0 at last follow-up, and for group B it was 3.4±0.6 and 2.0±1.1, respectively. The incidences of malignancy and retinopathy were no greater than that expected for the age-matched general population. We conclude that adenovirus-mediated VEGF direct myocardial administration to patients with severe coronary artery disease is safe, and future larger trials are warranted to assess efficacy.

Concordance between administrative data and clinical review for mortality in the randomized on/off bypass follow-up study (ROOBY-FS)

The optimal methodology to identify cardiac versus non‐cardiac cause of death following cardiac surgery has not been determined.

ROOBY trial data demonstrates revascularization had no impact on POAF

As a summary of the potential benefits of off-pump versus on-pump procedures, we read with interest the review article by Houlind entitled, ‘On-pump versus off-pump coronary artery bypass surgery: what is the status after ROOBY, DOORS, CORONARY and GOPCABE?’ as published in your Future Cardiology journal (9[4], 569–579 [2013]; PubMed PMID: 23834696). We appreciated the very thoughtful and detailed review of these large-scale, randomized trials. We would, however, like to correct the statement on page 573, “...the incidence of postoperative atrial fibrillation (POAF) has not been reported in the CORONARY, ROOBY, GOPCABE or DOORS studies”. The ROOBY trial’s POAF findings were published in January 2012 documenting that “POAF developed in 268 of 1056 patients (25.4%) in the ONCAB group and in 283 of 1047 patients (27%) in the OPCAB cohort (p = 0.40). Thus, there was no difference in POAF rates based on ONCAB versus OPCAB strategy of revascularization” [1]. Unlike previous publications on this topic, the ROOBY trial’s prospectively collected POAF data demonstrated that the strategy of revascularization had no impact on POAF. Towards the goal of providing complete and accurate information to facilitate this dialogue, it is hoped our letter will augment Dr Houlind’s excellent review publication.

Epidemiological trends among preterm infants with apnea. A twelve-year database review

OBJECTIVES This study sought to characterize trends in the diagnosis of apnea, associated comorbidities and complications, and 30-day readmission rates in preterm singleton infants. SUBJECTS AND METHODS The study design was a retrospective, longitudinal, observational study. 2003-2014 New York State Statewide Planning and Research Cooperative System and New York City Vital Statistics databases were merged identifying preterm live singleton births. Hospitalizations of preterm newborns with and without apnea were compared; multivariable logistic regression and log-linear Poisson regression models applied. RESULTS Of 1,384,013 singleton births, 7.5% were identified as preterm. While relative risk of preterm birth rates declined (RR = 0.987, 95% CI = 0.982-0.991), the diagnosis of apnea increased significantly (RR = 1.069, 95% CI = 1.049-1.089). Multivariable analysis identified two apnea predictors, gastric reflux (OR = 3.19, 95% CI = 2.80-3.63) and early gestational age (OR = 0.83 for 1 week GA increase, 95% CI = 0.82-0.84). Preterm newborns with apnea were more likely to be readmitted within the first 30 days and total charges were 5.4 times higher. CONCLUSIONS While the preterm birth rate has declined the rate of diagnosis of apnea with associated comorbidities and complications has increased. Given the additional findings of higher 30-day readmission rates and charges, more multidisciplinary research appears warranted to identify ways to optimize the quality of high risk newborn care.

PATIENT-REPORTED SYMPTOMS AND REVASCULARIZATION STATUS AFTER CORONARY ARTERY BYPASS GRAFT SURGERY IN DIABETICS AND NON-DIABETICS

In patients with multivessel coronary artery disease, bypass surgery improves long-term angina symptoms compared to percutaneous coronary intervention, presumably by providing a more complete revascularization (CR). However, data correlating patient-reported symptoms and CR post-bypass are lacking

Extraesophageal Reflux in Patients Undergoing General Endotracheal Tube Anesthesia

Objectives: Explore hypopharyngeal exposure to abnormally high or low pH during surgery performed under general endotracheal tube anesthesia and to compare results to published normative 24-hour data. Methods: Twenty volunteers for this prospective cohort study were recruited from June through September 2013. A wireless Dx-pH monitoring system was used during surgery. A drop from baseline to pH <5.5 was defined as a hypopharyngeal event, with thresholds pH 4.0, 4.5, and 5.0 also examined. Results were compared with supine events published by Chheda et al in 2009. Results: The number and duration of hypopharyngeal events <15 minutes with pH below 4.0, 4.5, 5.0 and percentage of surgery time in hypopharyngeal events (from a pH = 5.5 to return to baseline) were similar to comparative data. However, including all duration events (> ≤ 15 minutes), the number and duration of events at all thresholds and the percentage of surgery time in hypopharyngeal events were consistently higher than comparative data. Most analyses with the potential predictive/confounding variables (ie, body mass index, Reflux Symptom Index, Voice Handicap Index-10) yielded nonsignificant results. Conclusions: Extended pharyngeal exposure to moderately reduced pH levels (greater than sleeping or resting in a supine position) were documented. Approximately 20% of surgical patients may experience extensive exposure to pH <5.5 (over 1 hour, >30% of surgery time) and an additional 20% may experience moderate exposure to pH <5.5 (5-20 minutes and/or 4% to 10% of surgery time). Additional studies are needed to predict which patients might be at elevated risk for this exposure as well as the impact of this exposure on clinical outcomes.

The Challenges with Interpreting Cost-Effectiveness Data

from the DOORS Study Group reported the cost- effectiveness of off pump and on pump bypass surgery. We applaud the authors for addressing this ques-tion, as the issue of value (money spent per outcome gained) is a critical question right now in the United States. Having just published a similar paper in the Annals of Thoracic Surgery,