Heart failure definition

D. Inhibition of Na-KATPase leads to an elevation of intracellular Na. This results in an increase in intracellular Ca" " and an enhanced myocardial contractibility. There is no definitive evidence that digitalis improves survival of patients in heart failure, but it clearly improves the symptoms of this condition. 

Cardiotoxicity, which can lead to congestive heart failure and death, is a toxic effect of the anticancer drug, doxorubicin. A cumulative dose-effect analysis demonstrated that doxorubicin cardiotoxicity is related to the lifetime dose of the drug (Figure 18.12) and provided the basis for the definition of safe lifetime dose levels (7). The lifetime dose of doxorubicin is now limited to less than 400-450 mg/m, which is associated with a <5% risk of developing congestive heart failure. 

An example of a project definition in the biophar-maceutical industry would be the development of a new chemical entity for the indication of treating mild to severe congestive heart failure (CHE)/ with both an oral and an intravenous formulation being developed/ and with a projected development time of 3 years to NDA submission and a budget of 75/000/000. A sub-project would be to complete a clinical POC for the severe CHE indication for the intravenous formulation in 1 year with a budget of 9/000/000. 

Milrinone is an inhibitor of phosphodiesterase type III. Although the long-term oral use of such inhibitors is associated with an increase in mortality (SEDA-17, 217), milrinone has been used intravenously in patients with heart failure, both for short-term and longer-term therapy (SEDA-21, 196) (SEDA-22, 203) (SEDA-23, 109). It has been suggested to be particularly useful in tiding patients over while they are waiting for definitive treatment. 

The beneficial effects were related to these plasma concentrations, as were the time to the first bout of atrial fibrillation, the frequency of bouts of atrial fibrillation, and the time between episodes. However, when atrial fibrillation occurred there was no difference in the ventricular rate in the different groups. Adverse effects necessitated drug withdrawal in four patients one had heart failure and two had gastrointestinal symptoms. These effects were not dose-related, although there were too few occurrences for a definitive conclusion. The authors suggested that this stepwise approach, with increasing doses of propafenone and increasing doses of quinidine could be beneficial in the treatment of paroxysmal atrial fibrillation. 

There are no definitive trials to guide therapy in patients with diastolic heart failure, and one is therefore unable to initiate treatment in anticipation of attenuating disease progression or reducing mortality. It is, however, possible to make some general comments regarding mechanistic considerations in selecting treatment. 

Definition of abbreviations BMS, bone marrow suppression CCS, cell-cycle specific CHF, congestive heart failure GI, gastrointestinal. 

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