Reverse electrophysiologic remodeling after cardiac mechanical unloading for end-stage nonischemic cardiomyopathy.

BACKGROUND: Left ventricular assist devices (LVAD)-induced unloading appear to cause reverse cardiac remodeling. However, its effect on arrhythmogenicity is a controversial issue, and prospective data are lacking. We sought to investigate the impact of LVAD-induced unloading on the electrical properties of the failing heart. METHODS: We prospectively studied the effects of LVAD therapy on QRS, QT, and QTc durations and ventricular arrhythmias from electrocardiograms and 24-hour ambulatory electrocardiograms recorded before and during 6 months of mechanical support in 12 LVAD patients and 7 other patients with advanced nonischemic cardiomyopathy untreated with LVAD. RESULTS: After 1 week of LVAD support, QTc duration had decreased from 479 ± 79 ms to 411 ± 57 ms (p = 0.037), and QRS duration from 150 ± 46 ms to 134 ± 32 ms (p = 0.029). At 6 months, QTc was found to be 372 ± 56 ms (p = 0.046 versus baseline, 15% shortening) and QRS 118 ± 25 ms (p = 0.028 versus baseline, 11% shortening). A strong correlation was found between QTc shortening and increase in left ventricular ejection fraction and decrease in left ventricular filling pressures. After 2 months of LVAD support, premature ventricular contractions had decreased from 3,507 ± 4,252 to 483 ± 417 in 24 hours (p = 0.043), ventricular couplets from 82 ± 99 to 29 ± 25 in 24 hours (p = 0.05), and ventricular runs from 9 ± 8 to 10 ± 9 (not significant). No patient died suddenly or suffered a symptomatic arrhythmic event during follow-up. No significant electrocardiographic, functional, or hemodynamic change was observed in the 7 patients untreated with LVAD. CONCLUSIONS: The LVAD support caused progressive shortening of QTc and QRS intervals, consistent with reverse remodeling of the failing heart's electrical properties, accompanied by a decrease in frequency of ventricular arrhythmias.

Myocardial sympathetic innervation and long-term left ventricular mechanical unloading.

OBJECTIVES: The purpose of this study was to analyze the effects of left ventricular assist devices (LVADs) on myocardial sympathetic innervation of the failing heart. BACKGROUND: Ventricular unloading by LVADs seems to cause reverse remodeling of the failing heart, but little is known about the sympathetic nerve activity during long-term mechanical unloading. METHODS: We studied the effects of LVADs on myocardial sympathetic innervation, by iodine 123-meta-iodobenzylguanidine (123I-mIBG) scintigraphy performed before and 3 months after LVAD implantation in 12 end-stage heart failure patients. We calculated the: 1) heart-to-mediastinum (H/M) uptake ratio on early and delayed images, indicating myocardial accumulation of 123I-mIBG; and 2) rate of 123I-mIBG washout after initial accumulation. Similar 123I-mIBG imaging and functional and hemodynamic measurements were made 3 months apart in 6 other heart failure patients not treated with an LVAD. RESULTS: After 3 months of LVAD support, the mean left ventricular ejection fraction had increased from 19+/-6% to 29 +/- 9% (p=0.006), peak oxygen consumption increased from 9+/-4 ml/kg/min to 13+/-3 ml/kg/min (p=0.058), serum sodium increased from 135+/-4 mEq/l to 140+/-2 mEq/l (p=0.014), whereas the left ventricular end-diastolic diameter decreased from 72+/-7 mm to 56+/-3 mm (p=0.002), pulmonary capillary wedge pressure decreased from 30+/-6 mm Hg to 5+/-3 mm Hg (p=0.012), serum creatinine decreased from 1.5+/-0.6 mg/dl to 1.0+/-0.4 mg/dl (p=0.011), and B-type natriuretic peptide decreased from 2,279+/-1,900 pg/ml to 102+/-5 pg/ml (p=0.003). After 3 months of LVAD, the H/M ratio increased on delayed images from 1.25+/-0.18 to 1.43+/-0.13 (p=0.01) and on early images from 1.35+/-0.19 to 1.44+/-0.11 (p=0.028), and the washout rate decreased from 51.0+/-23.2% to 30.6+/-8.7%, (p=0.015). There was a significant correlation between the late H/M mIBG ratio and B-type natriuretic peptide (R=0.77, p=0.01) and systolic pulmonary pressure (R=0.7, p=0.05). No significant scintigraphic, functional or hemodynamic change was observed between the 2 evaluations in the 6 patients not treated with an LVAD. CONCLUSIONS: Ventricular unloading caused clinical, functional, and hemodynamic improvements accompanied by improvements in sympathetic innervation in the failing heart.

Multicenter randomized trial of facilitated percutaneous coronary intervention with low-dose tenecteplase in patients with acute myocardial infarction: the Athens PCI trial.

OBJECTIVES: To examine the safety and efficacy of low-dose tenecteplase, administered before facilitated percutaneous coronary intervention (PCI) to restore Thrombolysis In Myocardial Infarction (TIMI) grade 2 or 3 blood flow in the infarct related artery (IRA) in patients with ST elevation myocardial infarction (STEMI) scheduled to undergo PCI with a shortest anticipated delay of 30 min. BACKGROUND: PCI preceded by administration of glycoprotein IIb/IIIa inhibitors, full-dose thrombolytics, or both, is associated with no benefit or a higher incidence of adverse events than PCI alone. METHODS: Patients with STEMI < 6 hr in duration were randomly assigned to PCI preceded by tenecteplase, 10 mg (facilitated PCI group, n = 143) versus standard PCI (control group, n = 141). All patients received aspirin and unfractionated heparin (70 IU/kg bolus) at time of randomization. Both groups received IIb/IIIa inhibitors in the catheterization laboratory and for at least 20 hr after PCI. RESULTS: The median door-to-balloon time was 122 min (91-175) in the facilitated PCI versus 120 min (89-175) in the control group. IRA patency on arrival in the catheterization laboratory was 59.5% in the facilitated PCI (24% TIMI-2, 35% TIMI-3), versus 37% in the control (8% TIMI-2, 29% TIMI-3) group (P = 0.0001). During hospitalization, 9 patients (6%) died in the facilitated PCI versus 5 patients (3.5%) in the control group (P = 0.572). A single patient in the facilitated PCI group suffered a non-fatal ischemic stroke. CONCLUSIONS: Facilitated PCI with low-dose tenecteplase in patients presenting with STEMI was associated with a high IRA patency rate before PCI.

Hemodynamic effects of levosimendan in acute myocardial infarction complicated by cardiogenic shock and high systemic vascular resistance.

BACKGROUND: Levosimendan (LEVO), a new inodilator, improves hemodynamic function in patients with decompensated heart failure and preserved arterial blood pressure. Data on its use in patients with cardiogenic shock (CS) are scarce. The present study was undertaken to evaluate the hemodynamic effects of supplemental therapy with levosimendan (LEVO) in acute myocardial infarction (MI) and refractory cardiogenic shock (CS). METHODS: In 25 patients presenting in CS after acute MI, LEVO was administered for 24 h in doses ranging between 0.05 and 0.20 microg/kg/min, as tolerated, preceded by 6-microg/kg over 10 min, in addition to catecholamines. Hemodynamic measurements were made before and 24 h after initiation of the LEVO infusion. RESULTS: Hemodynamic improvement was limited to 13 patients with systemic vascular resistances (SVR) > or =18 W. LEVO increased the cardiac index from 1.5+/-0.3 l/min/m2 to 2.1+/-0.4 l/min/m2 (P = 0.002) and cardiac power from 0.462+/-0.164 W to 0.645+/-0.179 W (P = 0.022), and decreased SVR from 23+/-5 to 21+/-6.7 Wood units (P = 0.001) and pulmonary capillary wedge pressure from 24+/-9 mmHg to 16+/-11 mmHg (P = 0.059). No hemodynamic improvement was observed during LEVO administration in 12 patients with SVR < 18 W. CONCLUSION: The hemodynamic benefit conferred by LEVO added to catecholamines in patients with CS after acute MI was limited to patients with high SVR.