ABSTRACT
The clinician's primary objective in treating a patient with decompensated heart failure is rapid and effective stabilization. This goal often is achieved through the use of inotropic support. Classic inotropic agents (beta-adrenergic agonists and phosphodiesterase III inhibitors) can provide short-term hemodynamic benefits, but their long-term use has been correlated with poor survival rates. Calcium sensitizers comprise a new drug class that offers hemodynamic and symptomatic improvements without increasing cAMP and intracellular calcium concentrations. These agents enhance contractility without a concurrent increase in the risk of cardiac events and thus represent a significant improvement over classic positive inotropic agents. Levosimendan is the most potent calcium sensitizer to date, exhibiting a unique dual mechanism of action that combines a positive inotropic action mediated via calcium sensitization and a vasodilator property via ATP-dependent potassium channels. Available clinical data suggest that calcium sensitizer agents represent a promising class of inotropic agents in a field that has seen few advances in recent decades.
Subject(s)
Cardiotonic Agents/therapeutic use , Heart Failure/drug therapy , Arrhythmias, Cardiac/chemically induced , Cardiotonic Agents/classification , Cardiotonic Agents/pharmacology , Humans , Hydrazones/pharmacology , Pyridazines/pharmacology , SimendanABSTRACT
Mycophenolate mofetil (MMF) has a better clinical profile than azathioprine in heart transplantation (HT). Forty-five recipients (aged 53 +/- 9 yr) were retrospectively evaluated (first year of follow-up) post-MMF introduction since its advent in 1997 (mean daily dose: 1.97 +/- 0.2 g). MMF was used (mean post-HT time: 40 +/- 27 months) for: (i) renal insufficiency attenuation (group 1 = 20); (ii) steroid reduction because of osteoporosis (group 2 = 12); (iii) treatment of persistent cellular rejection (group 3 = 7) and vascular graft disease (VGD) (group 4 = 6). Mean changes (groups 1-2) were: creatinine 172 +/- 59, 158 +/- 51, 153 +/- 57 mumol/L (at baseline, 6 and 12 months, respectively; p < 0.001). Cyclosporine daily dose: 219 +/- 37, 166 +/- 46, 176 +/- 98 mg, respectively (p < 0.001). Cyclosporine blood concentration: 151 +/- 40, 103 +/- 41, 83 +/- 34 ng/mL, respectively (p < 0.004). Prednisone daily dose: 8.3 +/- 2, 5.2 +/- 1, 4.1 +/- 1 mg, respectively (p < 0.001). Cellular rejection (group 3) was successfully treated (86%) but the outcome of VGD did not improve after the switch (group 4). Our limited experience (with caution) confirms the reported benefits of MMF particularly attenuating renal insufficiency.
Subject(s)
Heart Transplantation , Immunosuppressive Agents/administration & dosage , Mycophenolic Acid/analogs & derivatives , Postoperative Complications/drug therapy , Adolescent , Adult , Aged , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Mycophenolic Acid/administration & dosage , Retrospective Studies , Treatment OutcomeABSTRACT
Interstitial pneumonitis is a temporary side effect of sirolimus therapy and has been described mainly in renal transplant recipients. It is considered to be dose dependent and has been documented in patients receiving at least 5 mg daily, or in patients with blood concentration plateaus > 15 ng/ml. In general, clinical and radiologic features improve after discontinuation and, to the best of our knowledge, no reports of fatalities have been published. Our report documents the death in a heart transplant recipient (52-year-old man) that resulted from a loading-dose administration (15 mg), and we report the association of persistently increased blood concentrations (>20 ng/ml) during most of the scheduled administration period.
Subject(s)
Heart Transplantation , Immunosuppressive Agents/adverse effects , Lung Diseases, Interstitial/chemically induced , Sirolimus/adverse effects , Dose-Response Relationship, Drug , Fatal Outcome , Humans , Immunosuppressive Agents/administration & dosage , Male , Middle Aged , Sirolimus/administration & dosageABSTRACT
Classic inotropic agents such as beta-adrenergic agonists and phosphodiesterase III inhibitors have beneficial but transitory hemodynamic effects in patients with acute and chronic heart failure. In this context, the available data suggest that long term inotropic therapy has a negative impact on morbidity and mortality in patients with heart failure. For this reason, these agents are mainly used for the treatment of refractory episodes of decompensation and they are also used as a "bridge" (transplant, revascularization, recovery) or as a palliative measure. We present a revision of the general aspects of inotropes including main published clinical trials and some findings of its combined use with beta blockers. Furthermore, we describe a promising and differential therapeutic approach represented by calcium sensitizer agents (levosimendan).
Subject(s)
Cardiotonic Agents/therapeutic use , Heart Failure/drug therapy , Clinical Trials as Topic , Dobutamine/therapeutic use , Humans , Milrinone/therapeutic use , Treatment OutcomeABSTRACT
Los agentes inotrópicos clásicos, tales como los agonistas betaadrenérgicos y los inhibidores de la fosfodiesterasa III, tienen efectos hemodinámicos beneficiosos pero transitorios en pacientes con insuficiencia cardíaca aguda y crónica. En este contexto, la evidencia disponible indica que el tratamiento inotrópico a largo plazo tiene un impacto negativo en la morbimortalidad de pacientes con insuficiencia cardíaca. Por esta razón, la propuesta de uso de estos agentes incluye el tratamiento de episodios de descompensación rebelde al tratamiento, la utilización como puente (trasplante, revascularización, recuperación) o como medida paliativa. Presentamos una revisión de los aspectos generales de los inotrópicos que incluye los principales estudios clínicos realizados y algunas características de su uso combinado con bloqueadores beta. Además, describimos un abordaje terapéutico prometedor y diferencial representado por los agentes sensibilizadores del calcio (levosimendán) (AU)
