Dimitrios Koudoumas

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.

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 hearts electrical properties, accompanied by a decrease in frequency of ventricular arrhythmias.

No effect of stem cell mobilization with GM-CSF on infarct size and left ventricular function in experimental acute myocardial infarction.

Abstract.Objectives:To evaluate the effect of bone marrowpluripotent stem cell mobilization with granulocyte-monocyte colony stimulating factor (GMCSF) on infarct size and left ventricular function, in the setting of acute myocardial infarction, with a protocol easily applicable in clinical practice.Methods:Ten pigs underwent left thoracotomy and left anterior descending coronary artery occlusion for 1 h, followed by reperfusion. After 50 min of arterial occlusion, the animals were randomly divided between treatment with placebo (Group 1) and subcutaneous GM-CSF (Group 2). The thoracotomy was closed and the animals recovered. In Group 2, GM-CSF, 20 µg/kg, was administered daily, 5 days/week, for 3 weeks. Echocardiograms were obtained at 5 and 28 days after acute myocardial infarction. At 30 days, infarct size, expressed as a percentage of the whole left ventricular mass, was measured.Results:The white blood cell count increased from 13000 ± 3338/µl to 28700 ± 4916/µl (p = 0.001) in the GM-CSF-treated group. Infarct size was 7.8 ± 6.1% in Group 1 vs 7.5 ± 7.7% in Group 2 (ns). Similarly, no significant difference was observed between the 2 study groups in any of the echocardiographic measurements made at 28 days.Conclusions:Subcutaneous GMCSF administered during the early post acute myocardial infarction period neither decreased infarct size nor improved left ventricular function. Other protocols for mobilization of stem cells and their concentration in the injured area should be developed to combine efficacy and clinical applicability.

Increase in coronary blood flow by intra-aortic balloon counterpulsation in a porcine model of myocardial reperfusion

BACKGROUND Studies of the IABP have reported variable effects on coronary blood flow (CBF). The purpose of the present study was to measure the changes in coronary blood flow induced by intra-aortic balloon pump (IABP) counterpulsation in normal and reperfused porcine myocardium. METHODS A 30-ml IABP was placed in the descending aorta of 6 open-chest pigs. Each pig underwent occlusion of the mid-left anterior descending (LAD) coronary artery for 1 h, followed by reperfusion for 2 h. The effects of IABP support on systolic aortic pressure (SAP) and aortic end-diastolic pressure were recorded. The mean CBF, distal to the LAD occlusion site was measured at baseline and during reperfusion, with and without IABP counterpulsation. RESULTS The IABP decreased SAP and aortic end-diastolic pressure in normal and reperfused myocardium, and maintained a peak aortic diastolic augmentation at the level of SAP. In normal myocardium, the IABP decreased mean CBF by 8.4+/-2.2% (p<0.001). At 2, 15, 30, 60, 90 and 120 min of reperfusion, the IABP increased mean CBF by 11.5+/-6.8%, 8.0+/-7.0%, 11.2+/-6.9%, 12.4+/-12.9%, 23.5+/-9.9% and 8.9+/-6.9%, of the corresponding value without the assistance of the IABP (all p<0.05). CONCLUSIONS In the normal heart, IABP counterpulsation decreased CBF, probably because of a decrease in myocardial oxygen demand from a decreased afterload. During reperfusion the IABP increased CBF, suggesting that it might effectively mitigate the no-reflow phenomenon.

Long-Term Intra-Aortic Balloon Pump Support as Bridge to Left Ventricular Assist Device Implantation.

The intra‐aortic balloon pump (IABP) can be used to bridge critically ill end‐stage heart failure patients to left ventricular assist device (LVAD) implantation. However, the IABPs potential association with hemorrhagic complications raises concerns regarding its utilization in these patients.