Latent Pulmonary Vascular Disease May Alter the Response to Therapeutic Atrial Shunt Device in Heart Failure.

BACKGROUND: In REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure), implantation of an atrial shunt device did not provide overall clinical benefit for patients with heart failure with preserved or mildly reduced ejection fraction. However, prespecified analyses identified differences in response in subgroups defined by pulmonary artery systolic pressure during submaximal exercise, right atrial volume, and sex. Shunt implantation reduces left atrial pressures but increases pulmonary blood flow, which may be poorly tolerated in patients with pulmonary vascular disease (PVD). On the basis of these results, we hypothesized that patients with latent PVD, defined as elevated pulmonary vascular resistance during exercise, might be harmed by shunt implantation, and conversely that patients without PVD might benefit. METHODS: REDUCE LAP-HF II enrolled 626 patients with heart failure, ejection fraction ≥40%, exercise pulmonary capillary wedge pressure ≥25 mm Hg, and resting pulmonary vascular resistance <3.5 Wood units who were randomized 1:1 to atrial shunt device or sham control. The primary outcome-a hierarchical composite of cardiovascular death, nonfatal ischemic stroke, recurrent HF events, and change in health status-was analyzed using the win ratio. Latent PVD was defined as pulmonary vascular resistance ≥1.74 Wood units (highest tertile) at peak exercise, measured before randomization. RESULTS: Compared with patients without PVD (n=382), those with latent PVD (n=188) were older, had more atrial fibrillation and right heart dysfunction, and were more likely to have elevated left atrial pressure at rest. Shunt treatment was associated with worse outcomes in patients with PVD (win ratio, 0.60 [95% CI, 0.42, 0.86]; P=0.005) and signal of clinical benefit in patients without PVD (win ratio, 1.31 [95% CI, 1.02, 1.68]; P=0.038). Patients with larger right atrial volumes and men had worse outcomes with the device and both groups were more likely to have pacemakers, heart failure with mildly reduced ejection fraction, and increased left atrial volume. For patients without latent PVD or pacemaker (n=313; 50% of randomized patients), shunt treatment resulted in more robust signal of clinical benefit (win ratio, 1.51 [95% CI, 1.14, 2.00]; P=0.004). CONCLUSIONS: In patients with heart failure with preserved or mildly reduced ejection fraction, the presence of latent PVD uncovered by invasive hemodynamic exercise testing identifies patients who may worsen with atrial shunt therapy, whereas those without latent PVD may benefit.

Long-term follow-up of the platinum chromium TAXUS Element (ION) stent: The PERSEUS Workhorse and Small Vessel trial five-year results.

BACKGROUND: The TAXUS Element (ION) platinum chromium paclitaxel-eluting stent (PtCr-PES) incorporates a thin (81 µm) strut design with a similar polymer and drug dose density as prior PES. The pivotal PERSEUS trial program consisted of two studies: PERSEUS Workhorse (WH) and PERSEUS Small Vessel (SV). The PERSEUS WH trial demonstrated the PtCr-PES to be non-inferior to the predicate TAXUS Express PES (TE-PES) for target lesion failure (TLF) at 1 year and in-segment angiographic percent diameter stenosis at 9 months. The PERSEUS SV trial demonstrated the PtCr-PES to be superior to a historical bare metal stent (BMS) for angiographic late lumen loss at 9 months. Long-term (5-year) clinical outcomes following PtCr-PES have not been previously reported. METHODS: PERSEUS WH was a prospective, Bayesian, 3:1 randomized (PtCr-PES vs. TE-PES) trial in patients with lesion length ≤28 mm and vessel diameter ≥2.75 to ≤4.0 mm. PERSEUS SV was a prospective, single-arm trial in patients with lesion length ≤20 mm and vessel diameter ≥2.25 to <2.75 mm comparing PtCr-PES to a matched historical BMS control. RESULTS: Among randomized subjects in the PERSEUS WH study, clinical event rates at 5 years were similar between treatment groups, including TLF (12.9% TE-PES vs. 12.1% PtCr-PES; P = 0.66). In the PERSEUS SV study, 5-year rates of MACE, and TLF were significantly lower for PtCr-PES (vs. BMS) following adjustment for baseline characteristics and were primarily due to lower target lesion revascularization rates (27.2% BMS vs. 14.9% PtCr-PES; P = 0.049). CONCLUSIONS: At 5 years, the PtCr-PES provides efficacy and safety that is comparable to the TE-PES and superior efficacy with similar safety when compared with BMS in smaller caliber vessels. Cumulative stent thrombosis rates remained low and similar through 5 years for both DES platforms.

Medical management of stable coronary artery disease.

All patients with stable coronary artery disease require medical therapy to prevent disease progression and recurrent cardiovascular events. Three classes of medication are essential to therapy: lipid-lowering, antihypertensive, and antiplatelet agents. Lipid-lowering therapy is necessary to decrease low-density lipoprotein cholesterol to a target level of less than 100 mg per dL, and physicians should consider a goal of less than 70 mg per dL for very high-risk patients. Statins have demonstrated clear benefits in morbidity and mortality in the secondary prevention of coronary artery disease; other medications that can be used in addition to statins to lower cholesterol include ezetimibe, fibrates, and nicotinic acid. Blood pressure therapy for patients with coronary artery disease should start with beta blockers and angiotensin-converting enzyme inhibitors. If these medications are not tolerated, calcium channel blockers or angiotensin receptor blockers are acceptable alternatives. Aspirin is the first-line antiplatelet agent except in patients who have recently had a myocardial infarction or undergone stent placement, in which case clopidogrel is recommended. Anginal symptoms of coronary artery disease can be treated with beta blockers, calcium channel blockers, nitrates, or any combination of these. Familiarity with these medications and with the evidence supporting their use is essential to reducing morbidity and mortality in patients with coronary artery disease.

Poor acute outcome in congestive heart failure is associated with increases in the plasma static oxidation-reduction potentials (sORP) in men but not in women.

OBJECTIVES: In congestive heart failure (CHF), men are younger, more likely to have reduced ejection fraction (HF-rEF), and to be diabetic compared to women. Despite this, sex differences in oxidative stress have yet to be explored in CHF. METHODS: Data from 67 males and 63 females hospitalized for CHF were collected. Static oxidation-reduction potential (sORP), a relative indicator of oxidative stress, and capacity ORP (icORP), a relative indicator of antioxidant capacity, were measured from plasma samples. We examined whether sex modified the relationship between ORP and hospital discharge disposition (poor outcome: death, hospice), along with other demographics, medications, and diagnostic parameters. RESULTS: Males with poor outcomes had higher sORP and icORP values than females (P < 0.05). For those with a good outcome, there were no differences between the sexes (P > 0.05). Males were younger and more likely to have HF-rEF and diabetes. Controlling for these variables did not account for the sex differences in ORP measures. Regardless of sex, higher creatinine was related to higher sORP and icORP, while lower magnesium and potassium were related to higher sORP and icORP, respectively. DISCUSSION: Increases in sORP during CHF are partially affected by sex and acute outcomes, but are also related to variables without sexual biases.

Pharmacologically dosed oral glutamine reduces myocardial injury in patients undergoing cardiac surgery: a randomized pilot feasibility trial.

BACKGROUND AND OBJECTIVE: Glutamine (GLN) has been shown to protect against in vitro and in vivo myocardial injury. In humans, perioperative ischemia/reperfusion (I/R) injury during cardiac surgery is associated with higher morbidity and mortality. The objective of this safety and feasibility pilot trial was to determine if pharmacologically dosed, preoperative oral GLN attenuates myocardial injury in cardiac surgery patients. METHODS: Patients undergoing elective cardiac surgery, requiring cardiopulmonary bypass, were enrolled in a randomized, double-blind pilot trial to receive 25 g twice of oral alanyl-glutamine (GLN; n = 7) or maltodextrin (CONT; n = 7) daily for 3 days preoperatively. Serum troponin (TROP I), creatine kinase (CK-MB), and myoglobin (MG) were measured at multiple perioperative time points. Clinical outcomes were also recorded and assessed. RESULTS: GLN therapy significantly decreased TROP I levels at 24, 48, and 72 hours postoperatively (all P < .05) vs CONT. GLN also reduced CK-MB at 24 and 48 hours (P < .05, P < .001) vs CONT. MG was reduced at 24 hours vs control (P = .0397). GLN also significantly reduced pooled clinical complications vs CONT (P = .03). CONCLUSION: This pilot study showed that pharmacologically dosed oral GLN therapy prior to cardiac surgery was safe, well tolerated, and feasible. GLN therapy reduced myocardial injury and clinical complications in this small randomized, blinded feasibility trial. These data indicate that a larger trial of preoperative GLN therapy in patients undergoing cardiac surgery is needed to confirm clinical benefit.

Clinical and angiographic outcomes after treatment of de novo coronary stenoses with a novel platinum chromium thin-strut stent: primary results of the PERSEUS (Prospective Evaluation in a Randomized Trial of the Safety and Efficacy of the Use of the TAXUS Element Paclitaxel-Eluting Coronary Stent System) trial.

OBJECTIVES: The aim of this study was to evaluate the safety and efficacy of the novel platinum chromium TAXUS Element paclitaxel-eluting stent (PES) compared with the TAXUS Express PES (Boston Scientific, Natick, Massachusetts) in treating coronary artery stenoses. BACKGROUND: The TAXUS Element is a novel thin-strut (81 microm), platinum chromium alloy PES designed to improve radial strength, radiopacity, and deliverability, while safely providing comparable restenosis benefit compared with a previous-generation PES. METHODS: The PERSEUS (Prospective Evaluation in a Randomized Trial of the Safety and Efficacy of the Use of the TAXUS Element Paclitaxel-Eluting Coronary Stent System) Workhorse (WH) trial is a prospective, randomized (3:1), controlled, multicenter study of the TAXUS Element (vs. TAXUS Express) PES for the treatment of de novo coronary atherosclerotic lesionsor=2.75 to