Design of a Phase 3 trial of intracoronary administration of human adenovirus 5 encoding human adenylyl cyclase type 6 (RT-100) gene transfer in patients with heart failure with reduced left ventricular ejection fraction: The FLOURISH Clinical Trial.

The prognosis of patients with HFrEF remains poor despite the use of current medical and device therapies. Preclinical studies of HFrEF using IC delivery of RT-100, a replication deficient, E1/E3-deleted human adenovirus 5 encoding human AC6 was associated with favorable effects on LV function and remodeling. A recent multicenter, double-blind, placebo-controlled, phase 2 study demonstrated the safety of IC delivery of RT-100 in HFrEF patients and potential efficacy at the higher doses.

Intracoronary Gene Transfer of Adenylyl Cyclase 6 in Patients With Heart Failure: A Randomized Clinical Trial.

Importance: Gene transfer has rarely been tested in randomized clinical trials.

Objective: To evaluate the safety and efficacy of intracoronary delivery of adenovirus 5 encoding adenylyl cyclase 6 (Ad5.hAC6) in heart failure.

Primary endpoint results of the OMEGA Study: One-year clinical outcomes after implantation of a novel platinum chromium bare metal stent.

Background/purpose: Bare metal stents (BMS) have similar rates of death and myocardial infarction (MI) compared to drug-eluting stents (DES). DES lower repeat revascularization rates compared to BMS, but may have higher rates of late stent thrombosis (ST) potentially due to impaired endothelialization requiring longer dual anti-platelet therapy (DAPT). OMEGA evaluated a novel BMS designed to have improved deliverability and radiopacity, in comparison to currently available platforms.

Two hour bivalirudin infusion after PCI for ST elevation myocardial infarction.

The standard of care for STEMI PCI for the past decade has been aspirin, clopidogrel, heparin, and a glycoprotein IIbIIIa receptor inhibitor (GPI). A bivalirudin strategy was shown to be superior to a GPI strategy in the HORIZONS AMI trial for net adverse clinical events (combined MACE and bleeding). An increased risk of acute stent thrombosis in the bivalirudin arm may have prevented broader adoption of bivalirudin for this indication.

Extravascular closure for patients with high-risk femoral anatomy.

Background: Vascular closure devices (VCDs) improve patient comfort and decrease time to ambulation. However, VCD studies have excluded patients with high-risk femoral artery anatomy; we examined the safety and efficacy of clip-based extravascular closure in this high-risk group.

Methods: We performed a prospective registry enrolling 98 consecutive patients undergoing diagnostic coronary angiography.

Effects of Ad5FGF-4 in patients with angina: an analysis of pooled data from the AGENT-3 and AGENT-4 trials.

Objectives: The goal of this study was to explore the effects of angiogenic gene therapy.

Background: Preclinical studies with intracoronary administration of Ad5FGF-4 (alferminogene tadenovec, Generx, Berlex Biosciences, Richmond, California) suggested it could induce angiogenesis and provide a new clinical approach to the treatment of chronic angina pectoris. Two preliminary clinical trials provided evidence that it could improve exercise treadmill test (ETT) time and myocardial perfusion.

Detection of coronary artery stenosis using 40-channel computed tomography with multi-segment reconstruction.

Coronary angiographic studies performed with 16-channel multidetector computer tomographic scanners have demonstrated accurate detection of coronary vessel stenosis but are limited by a significant number of non-evaluable segments. To date, only single-center experience with multidetector computer tomography has been reported. We performed a prospective, blinded study at 2 institutions to determine the feasibility and diagnostic accuracy of coronary angiography using 40-channel multidetector computer tomography with multi-segment reconstruction for the detection of obstructive coronary artery disease (CAD).

Relation of leukocytosis to C-reactive protein and interleukin-6 among patients undergoing percutaneous coronary intervention.

An elevated white blood cell (WBC) count and elevated C-reactive protein (CRP) have been associated with an increased risk of adverse cardiac events. The relation between these 2 parameters of heightened systemic inflammation was characterized in patients who underwent percutaneous coronary intervention (PCI). Femoral arterial blood samples from a prospective registry of 100 patients who underwent PCI were obtained immediately before the procedure.

Systemic inflammation after drug-eluting stent placement.

Background: Systemic inflammation after coronary intervention identifies patients at increased risk of subsequent cardiac events. Cardiac events are less frequent after use of drug eluting stents (DES) compared with bare metal stents (BMS). Thus, we sought to determine whether attenuation of the systemic inflammatory response was contributing to the improved outcomes.

Angiogenic gene therapy with adenovirus 5 fibroblast growth factor-4 (Ad5FGF-4): a new option for the treatment of coronary artery disease.

Angiogenic gene therapy for stable angina is aimed at promoting new blood vessel formation in the heart, thus providing enhanced cardiac perfusion, symptom relief, increased exercise capacity, improved quality of life, and reduced risk of coronary events. Ad5FGF-4 is a replication-deficient serotype 5 adenovirus encoding the gene for fibroblast growth factor-4 (FGF-4) driven by a cytomegalovirus promoter. In preclinical studies using a pig model of myocardial ischemia, a single intracoronary infusion of Ad5FGF-4 improved cardiac contractile function and regional blood flow in the ischemic region during stress.

A randomized, double-blind, placebo-controlled trial of Ad5FGF-4 gene therapy and its effect on myocardial perfusion in patients with stable angina.

Objectives: The primary objective of this study was to determine whether intracoronary administration of the adenoviral gene for fibroblast growth factor (Ad5FGF-4) can improve myocardial perfusion compared with placebo.

Background: Animal studies and observational clinical studies have shown improvement in perfusion of the ischemic myocardium using genes encoding angiogenic growth factors; however, randomized, double-blind data in humans are lacking.

Methods: We performed a randomized, double-blind, placebo-controlled trial of intracoronary injection of 10(10) adenoviral particles containing a gene encoding fibroblast growth factor (Ad5FGF-4) to determine the effect on myocardial perfusion.

Outcomes of percutaneous coronary intervention among elderly patients in cardiogenic shock: a multicenter, decade-long experience.

Objectives: The objective of this study was to determine the characteristics and hospital mortality rate for elderly patients in cardiogenic shock undergoing emergent percutaneous coronary intervention (PCI).

Background: Early revascularization for patients with acute myocardial infarction complicated by cardiogenic shock is recommended for patients < 75 years of age. This age-restricted recommendation is based upon evidence that elderly shock patients undergoing early revascularization have extremely high hospital mortality rates.

Predicting vascular complications in percutaneous coronary interventions.

Objectives: Using a large, current, regional registry of percutaneous coronary interventions (PCI), we identified risk factors for postprocedure vascular complications and developed a scoring system to estimate individual patient risk.

Background: A vascular complication (access-site injury requiring treatment or bleeding requiring transfusion) is a potentially avoidable outcome of PCI.

Methods: Data were collected on 18,137 consecutive patients undergoing PCI in northern New England from January 1997 to December 1999.

Gender-related changes in the practice and outcomes of percutaneous coronary interventions in Northern New England from 1994 to 1999.

Objectives: We sought to determine whether the changing practice of interventional cardiology has been associated with improved outcomes for women, and how these outcomes compare with those for men.

Background: Previous work from the early 1990s suggested women are at a higher risk than men for adverse outcomes after percutaneous coronary interventions (PCIs). From 1994 to 1999 data were collected on 33,666 consecutive hospital admissions for a PCI in Northern New England.

Angiogenic Gene Therapy (AGENT) trial in patients with stable angina pectoris.

Background: The angiogenic response to myocardial ischemia can be augmented in animal models by gene transfer with the use of a replication defective adenovirus (Ad) containing a human fibroblast growth factor (FGF) gene.

Methods And Results: The objectives of the Angiogenic GENe Therapy (AGENT) trial were to evaluate the safety and anti-ischemic effects of 5 ascending doses of Ad5-FGF4 in patients with angina and to select potentially safe and effective doses for subsequent study. Seventy-nine patients with chronic stable angina Canadian Cardiovascular Society class 2 or 3 underwent double-blind randomization (1:3) to placebo (n=19) or Ad5-FGF4 (n=60).