Keeping pre-transplant patients alive while waiting for a suitable donor is still a major challenge. New pharmacological agents which can provide improved hemodynamics are urgently needed in patients with severe heart failure who are on the waiting list for cardiac transplantation. Intravenous enoximone therapy (an initial 0.5 mg/kg bolus, then 1.25-5.0 mcg/kg/min infusion) was administered to 35 transplant candidates with progressive heart failure despite optimal drug regimen including digoxin, diuretics, and ACE-inhibitors. In 18 out of 35 patients complete hemodynamic, echocardiographic, neurohumoral, and Holter-ECG studies were performed before and 24 hours after intravenous enoximone infusion. Patients were then continued on chronic oral therapy of 100 mg twice a day. Enoximone infusion increased the cardiac index (CI) (1.78 +/- 0.45 l/min/m2 vs 3.04 +/- 0.83 l/min/m2; p< 0.001) and stroke volume index (SVI)(22.33 +/- 9.45 ml/m2 vs 32.28 +/- 7.29 ml/m2; p< 0.05) and decreased wedge pressure (PCP)(24.1 +/- 11.98 mmHg vs 17.78 +/- 8.76 mmHg; p< 0.05) while mean arterial pressure (MAP) was unchanged. Left ventricular ejection time (LVET)(225.1 +/- 26.9 ms vs 242.2 +/- 25.8 ms; p< 0.05) was increased whereas other echocardiographic parameters were unchanged (Left ventricular end-diastolic dimension LVEDD, left ventricular end-systolic dimension LVESD, fractional shortening FS, early diastolic relaxation parameter Te). Plasma neurohumoral parameters did not change (Aldosterone, epinephrine, renin, atrial natriuretic factor) except for a significant drop in norepinephrine (936.7 +/- 443.2 pg/ml vs 522.4 +/- 287.6 pg/ml; p< 0.05). Holter-ECG parameters (ventricular premature beats VPB, couplets, ventricular tachycardia VT) were not influenced by enoximone infusion.
Adult ; Electrocardiography, Ambulatory ; Enoximone/*therapeutic use ; Female ; Heart Failure, Congestive/physiopathology/therapy ; *Heart Transplantation ; Hemodynamics/drug effects ; Human ; Male ; Middle Age ; Preoperative Care

BACKGROUNDThe purposes of this study were to confirm the changes in myocardial collagen level after left ventricular assist device (LVAD) support in dilated cardiomyopathy (DCM), find the relation between these changes and prognosis, and test a practical method to assess the level of myocardial collagen.

METHODSLeft ventricular samples were collected from DCM patients with different prognosis (transplanted group n = 8, weaning group n = 10) at the time when the LVADs were implanted and again during cardiac transplantation (n = 8). The level of neutral salt soluble collagen (NSC) and acid soluble collagen (ASC) was measured by Sircol collagen assay, and that of total collagen and insoluble collagen (ISC) by quantification of hydroxyproline (Hyp). Serum samples were collected from a portion of these patients (transplanted group, n = 6; weaning group n = 7) at the time the LVADs were implanted, 1 month after implantation and on explantation. Circulating concentration of carboxy-terminal propeptide of type I procollagen (P I CP), amino-terminal propeptide of type I procollagen (P I NP), amino-terminal propeptide of type III procollagen (P III NP) and type I collagen telopeptide (I CTP) were measured by the equilibrium type radioimmunoassay.

RESULTSBefore LVAD implantation the level of NSC and ISC in the weaning group was higher but ASC in the transplanted group was lower than in the controls (P < 0.05). After LVAD support, the level of total collagen was higher, but ASC was also lower in the transplanted group than in the controls (P < 0.05). In comparison of the pre- and post-LVAD subgroups of the transplanted and weaning groups, all collagen fraction levels before LVAD implantation were lower in the transplanted group than in the weaning group (P < 0.05); but this difference disappeared after LVAD support. Comparison of the pre- and post-LVAD subgroups of the transplanted group showed increased level of NSC and total collagen after LVAD support. The changes of serum peptide concentration showed that P III NP increased constantly in the transplanted group, but P I CP and P I NP increased in the weaning group after LVAD implantation.

CONCLUSIONSThe changes in myocardial collagen level as a sign of myocardial interstitial remodeling in DCM are not involved with total collagen but involved with collagen fractions, and they are related to prognosis. The changes of myocardial collagen content and serum procollagen peptide after LVAD support can be regarded as an expression of the reverse of maladaptive myocardial interstitial remodeling.

Adult ; Cardiomyopathy, Dilated ; physiopathology ; therapy ; Collagen ; analysis ; Female ; Heart Transplantation ; Heart-Assist Devices ; Humans ; Hydroxyproline ; analysis ; Male ; Middle Aged ; Myocardium ; chemistry ; Procollagen ; blood ; Prognosis