Guillermo Cintron

Adrenomedullin, endothelin, neuropeptide Y, atrial, brain, and C-natriuretic prohormone peptides compared as early heart failure indicators

OBJECTIVES The present investigation was designed to determine the best endogenous plasma marker of early congestive heart failure (CHF). METHODS Forty volunteers with mild CHF (New York Heart Association Class I, n = 12), moderate (Class II, n = 8), or severe (Class III and Class IV, each = n of 5) and 10 age-matched healthy individuals had the simultaneous evaluation of their respective plasma samples by the following radioimmunoassays: atrial natriuretic peptide, ANP; three N-terminal ANP prohormone assays, i.e., proANPs 1-30, 31-67, and 79-98 with the numbers referring to their amino acid (a.a.) sequences in their 126 a.a. prohormone; brain (BNP) and C-natriuretic peptides; N-terminal BNP prohormone; adrenomedullin; neuropeptide Y and endothelin. RESULTS ProANPs 31-67, 1-30 and 79-98 had 100% (P = 0.01), 83% (P = 0.09) and 50% (P = 0.74) sensitivity in differentiating Class I CHF subjects from healthy subjects. The ANP, BNP, NT-proBNP, CNP, adrenomedullin, neuropeptide Y, and endothelin assays could not differentiate mild CHF subjects from healthy individuals. Logistic regression analysis revealed that only proANP 31-67 significantly (P = 0.0001) discriminated between early CHF (5226 +/- 377 pg/ml) and healthy individuals (1595 +/- 157 pg/ml). The positive and negative predicative values of proANP 31-67 were excellent (100% for each). The peptides measured in these assays were found to be independent markers of CHF with respect to left ventricular ejection fraction. CONCLUSIONS ProANPs 31-67 is the most sensitive marker in discriminating NYHA Class I CHF subjects from healthy individuals. The ANP, BNP, NT-proBNP, CNP, adrenomedullin, neuropeptide Y and endothelin radioimmunoassays cannot discern mild CHF. These peptides are independent of left ventricular ejection fraction.

Retransplantation in 7,290 primary transplant patients: a 10-year multi-institutional study

BACKGROUND Cardiac retransplantation is a controversial procedure due to the disparity between donor heart demand and supply. METHODS Of 7,290 patients undergoing primary cardiac transplantation between January 1990 and December 1999 at 42 institutions contributing to the Cardiac Transplant Research Database (CTRD), 106 patients later underwent a second and 1 patient a third cardiac transplant procedure. RESULTS The actuarial freedom from retransplantation was 99.2% and 96.8% at 1 and 10 years, respectively. Reasons for retransplantation included early graft failure (n = 34), acute cardiac rejection (n = 15), coronary allograft vasculopathy (CAV, n = 39), non-specific graft failure (n = 7), and miscellaneous (n = 10). The only risk factor associated with retransplantation was younger age, reflecting the policy of preferential retransplantation of younger patients. Survival after retransplantation was inferior to that after primary transplantation (56% and 38% at 1 and 5 years, respectively). Risk factors associated with death after retransplantation included retransplantation for acute rejection (p = 0.0005), retransplantation for early graft failure (p = 0.03), and use of a female donor (p = 0.005). Survival after retransplantation for acute rejection was poorest (32% and 8% at 1 and 5 years, respectively) followed by retransplantation for early graft failure (50% and 39% at 1 and 5 years, respectively). Survival after retransplantation for CAV has steadily improved with successive eras. CONCLUSIONS The results of retransplantation for acute rejection and early graft failure are poor enough to suggest that this option is not advisable. However, retransplantation for CAV is currently associated with satisfactory survival and should continue to be offered to selected patients.

Vessel Dilator Enhances Sodium and Water Excretion and Has Beneficial Hemodynamic Effects in Persons With Congestive Heart Failure

BACKGROUND Vessel dilator, a 37-amino acid peptide hormone synthesized in the heart, enhances urine flow 4- to 12-fold and sodium excretion 3- to 6-fold in healthy humans. The present investigation was designed to determine whether vessel dilator might have similar beneficial effects in persons with congestive heart failure (CHF). METHODS AND RESULTS Vessel dilator (100 ng/kg body weight per minute) given intravenously for 60 minutes to NYHA class III CHF subjects increased urine flow 2- to 13-fold, which was still increased (P<0.001) 3 hours after its infusion was stopped. Vessel dilator enhanced sodium excretion 3- to 4-fold in CHF subjects (P<0.01), which was still significantly (P<0.01) elevated 3 hours after infusion. Vessel dilator decreased systemic vascular resistance 24%, pulmonary vascular resistance 25%, pulmonary capillary wedge pressure 33%, and central venous pressure 27% while increasing cardiac output 34%, cardiac index 35%, and stroke volume index 24% without significantly affecting heart rate or pulmonary artery pressure in the CHF subjects. The control CHF patients did not have any changes in the above parameters. CONCLUSIONS These results indicate that vessel dilator has significant beneficial diuretic, natriuretic, and hemodynamic properties in humans with congestive heart failure.

Comparison of vessel dilator and long-acting natriuretic peptide in the treatment of congestive heart failure

BACKGROUND Long-acting natriuretic peptide (LANP; proANF 1-30) and vessel dilator (proANF 31-67) enhance sodium and water excretion in healthy human beings. The current investigation was designed to compare the beneficial effects of LANP and vessel dilator in persons with congestive heart failure (CHF). METHODS AND RESULTS LANP and vessel dilator (100 ng/kg body weight/min, respectively) were given intravenously for 60 minutes to subjects with New York Heart Association class III CHF (n = 17) while their urine volume and sodium and potassium excretion were monitored. Vessel dilator increased urine flow more than 5-fold, which was still increased (P <.001) 3 hours after stopping its infusion. Vessel dilator enhanced sodium excretion 3-fold in subjects with CHF (P <.01), which was still significantly (P <.01) elevated 3 hours after infusion. The effects of LANP were diminished, with urine flow only increasing 2-fold (P <.05). The fractional excretion of sodium increased maximally 6-fold secondary to vessel dilator and 3-fold with LANP. The CHF control patients had no changes in the above parameters. Part of the diminished response to LANP was found to be caused by its rapid decrease in the circulation of individuals with CHF. CONCLUSIONS These results indicate that vessel dilator has significant beneficial diuretic and natriuretic properties, which are not diminished, whereas the effects of LANP are diminished in human beings with CHF compared with healthy individuals.

Normalization of circulating atrial natriuretic peptides in cardiac transplant recipients

To assess whether heart transplantation (Htx) alters the marked elevation of circulating atrial natriuretic peptides usually found in patients with congestive heart failure (CHF), 14 subjects (nine with compensated and five with decompensated CHF), each with an ejection fraction < or = 28%, were evaluated. Immediately before and hourly for the first 12 hours after Htx, then daily for 21 days and every 1 to 4 weeks for 6 months, the circulating concentrations of the N-terminus (pro atrial natriuretic factor [ANF] 1-98), midportion of the N-terminus (pro ANF 31-67), and C-terminus (that is, ANF) of the 126 amino acid prohormone were measured. Increased (p < 0.001) levels of these peptides were found in superior vena cava, right atrial, and peripheral venous samples 1 hour after Htx in all subjects except one. The atrial natriuretic peptide levels correlated only with right atrial pressure (p < 0.01) in the first 24 hours. Circulating concentrations of these peptides returned to those of healthy adults between 5 and 12 days after Htx in 11 out of 14 Htx recipients. Thus successful Htx can restore the elevated circulating concentrations of atrial natriuretic peptides to those of healthy adults.

Comparison of the beta blocker bucindolol in younger versus older patients with heart failure.

E evidence and clinical trials have shown the beneficial effects of -adrenergic blockers (BBs) in patients with heart failure (HF). A large database supports the contention that BB therapy improves survival, reduces the rate of hospitalization, delays the progression of HF, and improves cardiac function. However, there is little information regarding how elderly patients with HF tolerate and respond to BBs. To test the hypothesis that BB therapy can be safely administered to, and improves cardiac function in elderly patients with HF, we analyzed, according to age, patients who were randomized to receive the BB bucindolol or placebo in the Beta-Blocker Evaluation of Survival Trial (BEST).

Lymphoproliferative disorder early after cardiac transplantation

Abstract In cardiac transplantation, extremely potent immunosuppressive agents are used, which leave the host vulnerable to a variety of infections and malignancies. Among the malignancies, lymphoproliferative disorders are the most common. 1 Most cases of posttransplant lymphoproliferative disorders have been described in patients who have undergone several months of immunosuppression. 2,3 This report describes our experience with patients who developed lymphoproliferative disorder within 3 months of heart transplantation.

Corrigendum to: “Adrenomedullin, endothelin, neuropeptide Y, atrial, brain, and C-natriuretic prohormone peptides compared as early heart failure indicators” [Cardiovascular Research 36 (1997) 246–255]

Fig. 1 of the article by Daggubati et al. in Cardiovascular Research 1997;36:246-255 was inadvertently the plotted values for high performance gel permeation chromatography (HP-GPC) of healthy individuals rather than the plotted values of patients with congestive heart failure as shown overleaf. Fig. 1 High-performance gel permeation chromatography evidence that (A) atrial natriuretic peptide prohormone (proANP) 1–30, (B) atrial natriuretic peptide prohormone (proANP) 31–67, (C) atrial natriuretic peptide (ANP), and (D) …