Insertion of the Impella via the axillary artery for high-risk percutaneous coronary intervention.

Hemodynamic support with the Impella device is an important tool during high risk percutaneous coronary intervention. This device is usually inserted via the femoral artery. However, some patients have severe peripheral artery disease precluding the use of the femoral artery for this purpose. The axillary artery is a viable alternative in these cases. We reviewed the two access techniques for inserting the Impella via the axillary artery and also described 6 cases of successful implantation.

Effects of percutaneous revascularization of chronic total occlusions on clinical outcomes: a meta-analysis comparing successful versus failed percutaneous intervention for chronic total occlusion.

BACKGROUND: Chronic total occlusions (CTOs) represent the most complex and challenging coronary lesions for percutaneous coronary intervention (PCI). PCI for a CTO is a high-risk procedure and the long-term benefits of a successful percutaneous CTO recanalization over the medical management (as a result of failed PCI) are not clear, as the studies have shown conflicting results in the past. The goal of this analysis was to clarify this issue by performing a meta-analysis of the available literature. METHODS: Using major electronic databases, we searched for studies (randomized or observational) comparing death, major adverse cardiovascular events (MACE), myocardial infarction (MI), and target vessel revascularization (TVR) between patients who underwent PCI recanalization of CTOs versus those treated with medical management as a result of failed PCI attempts. RESULTS: We identified 23 observational studies comparing the desired clinical parameters between patients with successful CTO recanalization and those managed conservatively as a result of attempted but failed PCI. The total number of patients observed in all of the studies was 12,970 and the mean time of follow up was 3.7 ± 2.1 years. Our results indicated that successful recanalization of a CTO results in improved all-cause mortality (relative risk [RR] of 0.54, 95% confidence interval [CI] (0.45-0.65), P-value < 0.001), lower rates of MACE (RR of 0.70, 95% CI 0.60-0.83, P-value < 0.001) and reduced needs for subsequent bypass surgery (RR of 0.25, 95% CI (0.21-0.30), P-value < 0.001). The difference in long-term mortality remained statistically significant even after the adjustment for procedure related complications and in-hospital deaths. CONCLUSION: As compared to conservative management (as a result of failed intervention), successful PCI recanalization of a CTO appears to be associated with improved long-term clinical outcomes; however, randomized controlled trials (RCTs) are needed to further confirm these results.

The effects of poloxamer-188 on left ventricular function in chronic heart failure after myocardial infarction.

BACKGROUND: Poloxamer-188 (P-188) is a biological membrane sealant that prevents the unregulated entry of Ca into cardiomyocytes and has been shown to have the ability to act as a membrane-repair agent in isolated cardiac myocytes. The purpose of this study was to determine if treatment with P-188 would improve left ventricular (LV) function in a rat chronic heart failure (CHF) model. METHODS: We ligated the left coronary artery of adult male Sprague-Dawley rats to induce a myocardial infarction (MI). The rats were allowed to recover for 8 weeks until stable CHF was present and treated with a range of P-188 doses [1.5 mg/kg (N = 6), 4.6 mg/kg (N = 11), 15.3 mg/kg (N = 11), and 460 mg/kg (N = 6)] delivered via 30 minutes of intravenous infusion. The rats were randomized to study groups: control, 2 hours, 24 hours, 48 hours, 1 week, and 2 weeks posttreatment (N = 8 in each group). RESULTS: Two weeks after high dose (460 mg/kg) administration, P-188 improved (P < 0.05) left ventricular ejection fraction from 34% to 51%, which persisted over 38 hours and decreased (P < 0.05) LV end systolic diameter from 0.9 ± 0.07 to 0.6 ± 0.08 cm, in the rats with CHF. There was no statistical change in hemodynamics. Additionally, P-188 reduced (P < 0.05) circulating troponin levels 2 weeks after treatment. CONCLUSIONS: Treatment with P-188 improves the LV function and partially reverses maladaptive LV remodeling in rats with moderate CHF after MI. These data introduce the idea of using a biological membrane sealant as a new approach to treating CHF after MI.

Antibody to granulocyte macrophage colony-stimulating factor reduces the number of activated tissue macrophages and improves left ventricular function after myocardial infarction in a rat coronary artery ligation model.

Granulocyte macrophage colony-stimulating factor (GM-CSF) promotes infarct expansion and inappropriate collagen synthesis in a myocardial infarction (MI). This study was designed to determine if treatment with anti-GM-CSF will inhibit macrophage migration, preserve function, and limit left ventricular (LV) remodeling in the rat coronary artery ligation model. Treatment with a monoclonal antibody to GM-CSF (5 mg/kg) was initiated 24 hours before coronary artery ligation and continued every 3 days for 3 weeks. Left coronary arteries of rats were ligated, animals were recovered, and cardiac function was evaluated 3 weeks postligation. Tissue samples were processed for histochemistry. Anti-GM-CSF treatment increased LV ejection fraction (37 ± 3% vs 47 ± 5%) and decreased LV end systolic diameter (0.75 ± 0.12 vs 0.59 ± 0.05 cm) with no changes in LV systolic pressure (109 ± 4 vs 104 ± 5 mm Hg), LV end diastolic pressure (22 ± 4 vs 21 ± 2 mm Hg), LV end diastolic diameter (0.96 ± 0.04 vs 0.92 ± 0.05 cm), or the time constant of LV relaxation tau (25.4 ± +2.4 vs 22.7 ± 1.4 milliseconds) (P < 0.05). Significantly lower numbers of tissue macrophages and significant reductions in infarct size were found in the myocardium of antibody-treated animals (81 ± 21.24 vs 195 ± 31.7 positive cells per 0.105 mm, compared with controls. These findings suggest that inhibition of macrophage migration may be beneficial in the treatment of heart failure after MI.

Implantation of a three-dimensional fibroblast matrix improves left ventricular function and blood flow after acute myocardial infarction.

This study was designed to determine if a viable biodegradable three-dimensional fibroblast construct (3DFC) patch implanted on the left ventricle after myocardial infarction (MI) improves left ventricular (LV) function and blood flow. We ligated the left coronary artery of adult male Sprague-Dawley rats and implanted the 3DFC at the time of the infarct. Three weeks after MI, the 3DFC improved LV systolic function by increasing (p < 0.05) ejection fraction (37 +/- 3% to 62 +/- 5%), increasing regional systolic displacement of the infarcted wall (0.04 +/- 0.02 to 0.11 +/- 0.03 cm), and shifting the passive LV diastolic pressure volume relationship toward the pressure axis. The 3FDC improved LV remodeling by decreasing (p < 0.05) LV end-systolic and end-diastolic diameters with no change in LV systolic pressure. The 3DFC did not change LV end-diastolic pressure (LV EDP; 25 +/- 2 vs. 23 +/- 2 mmHg) but the addition of captopril (2mg/L drinking water) lowered (p < 0.05) LV EDP to 12.9 +/- 2.5 mmHg and shifted the pressure-volume relationship toward the pressure axis and decreased (p < 0.05) the LV operating end-diastolic volume from 0.49 +/- 0.02 to 0.34 +/- 0.03 ml. The 3DFC increased myocardial blood flow to the infarcted anterior wall after MI over threefold (p < 0.05). This biodegradable 3DFC patch improves LV function and myocardial blood flow 3 weeks after MI. This is a potentially new approach to cell-based therapy for heart failure after MI.

Aldosterone antagonism improves endothelial-dependent vasorelaxation in heart failure via upregulation of endothelial nitric oxide synthase production.

BACKGROUND: Altering the renin-angiotensin aldosterone system improve mortality in heart failure (HF) in part through an improvement in nitric oxide (NO)-mediated endothelial function. This study examined if spironolactone affects endothelial nitric oxide synthase (eNOS) and NO-mediated vasorelaxation in HF. METHODS AND RESULTS: Rats with HF after coronary artery ligation were treated with spironolactone for 4 weeks. Rats with HF had a decrease (P < .05) in left ventricular (LV) systolic pressure (130 +/- 7 versus 118 +/- 6 mm Hg) and LV pressure with respect to time (9,122 +/- 876 versus 4,500 +/- 1971 mm Hg/second) with an increase in LV end-diastolic pressure (4 +/- 2 versus 23 +/- 8 mm Hg). Spironolactone did not affect hemodynamics but it improved (P < .05) endothelial-dependent vasorelaxation at more than 10(-8) M acetylcholine that was abolished with N(G)-monomethyl-L-arginine. The eNOS levels were decreased (P < .05) in the LV and the aorta; spironolactone restored LV and aortic eNOs levels to normal. CONCLUSION: Spironolactone prevents the decrease in eNOS in the LV and aorta and improves NO-dependent vasorelaxation, suggesting that one potential mechanism of spironolactone is an improvement in vasoreactivity mediated though an increase in NO.

Thyroid hormone analog, DITPA, improves endothelial nitric oxide and beta-adrenergic mediated vasorelaxation after myocardial infarction.

This study was designed to determine if the thyroid hormone analog 3,5 diiodothyropropionic acid (DITPA), now in clinical trials for heart failure, alters endothelial function after myocardial infarction (MI). Three weeks after MI, adult Sprague-Dawley rats were randomly assigned to DITPA (375 microg/100 g subcutaneous) or no treatment of 3 weeks. In MI rats, left ventricular (LV) end-diastolic pressure and LV dP/dt decreased (P < 0.05). DITPA did not change MAP (87 +/- 10 versus 90 +/- 7 mm Hg) or LV end-diastolic pressure (23 +/- 3 versus 19 +/- 9 mm Hg) but did lower (P < 0.05) LV dP/dt (4,633 +/- 797 versus 3,650 +/- 1,236 mm Hg/s). In aortic segments from MI rats, DITPA enhanced the acetylcholine dependent vasorelaxation (59 +/- 11% at 10(-4) M, P < 0.05) and isoproterenol induced vasorelaxation (57 +/- 13% at 10(-4) M, P < 0.05). The increases in vasorelaxation were blocked with l-NAME and restored with L-arginine. Treatment with DITPA increased (P < 0.05) eNOS protein content in aortic tissue from sham rats (3.8 +/- 2.8 to 44.5 +/- 7.1 integrated intensity units (II)/microg) and in MI rats (5.3 +/- 3.4 to 28.3 +/- 8.9 II/microg). In endothelial cells, 24 hours' treatment with DITPA (10 microM) increased (P < 0.01) eNOS protein expression from 22.1 +/- 4.8 to 52.7 +/- 16.8 II/microg protein and DITPA (20 microM) increased eNOS to 49.1+/- 15.2 II/microg protein. The thyroid analog DITPA enhances endothelial nitric oxide and beta-adrenergic-mediated vasorelaxation by increasing nitric oxide in the vasculature.