Lower ejection fractions

In a single-center non-randomized study in patients undergoing primary cardiac operations, 3334 were given aprotinin and 3417 were not [203 ]. The former were older, and had more unstable symptoms, lower ejection fractions, more preoperative hemodynamic support, more urgent operations, and more combined coronary or valvular operations. Postoperative bleeding and blood product transfusion were considerably reduced by aprotinin, as was median duration of mechanical ventilation. Aprotinin was not related to postoperative myocardial infarction, renal insufficiency, neurological dysfunction, or operative death. 

Neurohumoral (extrinsic) compensation involves two major mechanisms (previously presented in Figure 6-7)—the sympathetic nervous system and the renin-angiotensin-aldosterone hormonal response—plus several others. Some of the pathologic as well as beneficial features of these compensatory responses are illustrated in Figure 13-2. The baroreceptor reflex appears to be reset, with a lower sensitivity to arterial pressure, in patients with heart failure. As a result, baroreceptor sensory input to the vasomotor center is reduced even at normal pressures sympathetic outflow is increased, and parasympathetic outflow is decreased. Increased sympathetic outflow causes tachycardia, increased cardiac contractility, and increased vascular tone. Vascular tone is further increased by angiotensin II and endothelin, a potent vasoconstrictor released by vascular endothelial cells. The result is a vicious cycle that is characteristic of heart failure (Figure 13-3). Vasoconstriction increases afterload, which further reduces ejection fraction and cardiac output. Neurohumoral antagonists and vasodilators... 

There is evidence that coronary blood flow is improved in patients pretreated with statins after acute infarct PCI (73,74). Celik et al, (74) found that Thrombolysis In Myocardial Infarction (TIMI) frame counts were lower, implying better coronary blood flow, in patients who underwent successful acute infarct PCI and were taking atorvastatin for >6 months compared to patients not taking statins. Iwakura et al. found a lower incidence of coronary no-reflow in patients on chronic statin therapy compared to those not taking statin after successful Ml (9,1 % vs. 34% P = 0.003). Multivariate analysis indicated that statin pretreatment was a protective factor against no-reflow. In this study, the statin-treated patients also had better wall motion, smaller left ventricular dimensions and ejection fraction (73). These studies suggest that statin therapy may help to preserve coronary microvascular function in the setting of acute infarct PCI. 

Coenzyme QIO is a powerful antioxidant naturally occurring in the mitochondria of myocardium, and it is an electron carrier in the mitochondrial synthesis of ATP. Patients with heart failure have lower myocardial levels of coenzyme QIO, but supplementation has been demonstrated to have variable benefits in randomized controlled trials. One meta-analysis on the use in congestive heart failure showed improvements in stroke volume, ejection fraction, cardiac output, cardiac index, and end diastolic volume index. " Another antioxidant associated with beneficial effects in cardiac patients is lycopene, a natural constituent of tomatoes. Lycopene is the major carotenoid found in human serum, and epidemiological studies have indicated an effect of dietary supplementation in reducing heart disease. Few dietary interventions have been reported one study showed a mild but significant hypocholesterolemic effect, and another showed a significant reduction in LDL oxidation. " Animal studies show an antiatherogenic effect of DHEA, and a review of the clinical trials and studies on DHEA in males with coronary heart disease reported a favorable or neutral effect. Plasma levels of DHEA are decreased in patients with chronic heart failure in proportion to its severity. ... 

In the Randomized Aldactone Evaluation Study (RALES) in 1663 patients with New York Heart Association (NYHA) class III (70%) or IV (30%) symptoms and an ejection fraction less than 35%, the addition of spironolactone 25 mg/day to conventional treatment (an ACE inhibitor, a loop diuretic, in most cases digoxin, and in 11% a beta-blocker) for an average of 24 months lowered the risk of all-cause mortality by 30% (from 46% to 35%), death from progressive heart failure, and sudden death (28). There were similar reductions in hospital admissions for worsening heart failure and for all cardiac causes. The magnitude of the overall effect was similar and additional to the proven benefit from ACE inhibition in severe heart failure. 

Hawthorn extracts purportedly dilate coronary blood vessels, decrease blood pressure, increase myocardial contractility, and lower serum cholesterol (9). Benefits have been demonstrated in patients with heart failure (10). In patients with stage II New York Heart Association (NYHA) heart failure, doses of 160-900 mg/day of the aqueous-alcoholic extract for up to 56 days showed an increase in exercise tolerance, decrease in rate/pressure product, and increased ejection fraction (11). Degenring and colleagues, in a randomized, double-blind, placebo-controlled trial, studied a standardized extract of fresh Crataegus berries (Crataegisan ) for the treatment of patients with... 

The importance of other factors additional to amount ofnecrosis has also been studied. In patients with first acute MI treated with PCI, LAD-related MI show for a similar amount of myocardial necrosis as determined by enzymatic infarct size, lower left-ventricular ejection fraction (LVEF) when compared to non-LAD-related MI. LVEF-measured 6-month post-MI showed a decrease, for every 1000 cumulative lactate dehydrogenase release, of 4.8% for LAD and 2.4% for non-LAD-related infarcts (p < 0.0001), and these results remain in the multivariate analysis (Elsman et al., 2006). 

This combination is useful, as the two effects of the drugs synergize, allowing lower doses of each drug to be used. The cardiodepressant actions of the beta-blocker decrease the rate and force of contraction. Concurrently administered, the nitrates decrease cardiac afterload, which increases the ejection fraction of the heart and reduces end diastolic volume, in addition to decreasing myocardial oxygen consumption. Additionally, the compensatory sympathetic reflexes produced by the nitrates are inhibited by the presence of the beta receptor blockers. 

In heart failure, contractility is decreased, filling is increased, and ejection fraction is decreased. Thus, desirable changes include lowering afterload (to increase ejection fraction), lowering preload (to decrease filling), lowering of fluid volume, and increasing cardiac contractility. 

Diuretics lower fluid volume, which decreases both preload and afterload. This decreases myocardial stretch and increases ejection fraction. 

Comparative studies Unlike traditional inotropic agents, levosimendan is thought to have a lower potential to cause dysrhythmias, because it does not increase intracellular calcium concentrations and myocardial oxygen consumption. Levosimendan and dobuta-mine have been compared in 50 patients with acute decompensated heart failure (NYHA class III-IV, ejection fraction <35%), mean age 68 years [20 ]. Heart rate and the number of ventricular extra beats increased significantly during infusion of levosimendan and dobutamine, but the increase in ventricular coupled beats was significant only with dobutamine. There were more episodes of non-sustained ventricular tachycardia and paroxysmal atrial fibrillation with levosimendan, but the difference was not significant. 

CAST-11 compared moricizine with placebo. The protocol for the CAST-11 was modified in an attempt to enroll patients more likely to experience serious arrhythmias and to observe for early risk of antiarrhythmic drugs. The qualifying ejection fraction was lowered to < 0.40, a higher dose of moricizine could be used, and the definition of disqualifying ventricular tachycardia was changed to allow patients with more serious arrhythmias to be entered into the trial. CAST II was subsequently terminated prematurely because patients treated with moricizine had an increased cardiac mortality rate during the first... 

Sunitinib (kinase inhibitor) QT prolongation and torsades, cardiac toxicity including left ventricular ejection fraction declines to below the lower limit of normal and cardiac failure including death, hypertension, hemorrhagic events... 

DINNAR Relating to Figure 18. You plotted ejection fraction as a function of developed stress for various preload values, Ved, and there was a crossing of the optimal curve with those at lower values of Ved. What is it in your model that gives a better ejection fraction with less stress ... 

Cardiovascular Heart failure (New York Heart Association classes II-IV) has been observed in patients receiving trastuzumab, alone or in combination with paclitaxel or docetaxel, particularly after chemotherapy containing an anthracycline (doxorubicin or epirubicin) [303, 304, 305, 306. It can be moderate or severe and can be fatal. The results of many randomized trials have shown that the degree of cardiotoxicity is generally acceptable the incidence of cardiac damage caused by trastuzumab was 0.4-4.1% [307 ]. Older age, lower left ventricular ejection fraction, and antihypertensive medications are associated with an increased risk of cardiac dysfunction in patients receiving trastuzumab [308 "]. The cardiac dysfunction associated with trastuzumab is usually reversible on withdrawal and standard medical therapy [309 ]. In one case, trastuzumab-associated cardiomyopathy presented with complete left bundle-branch block mimicking acute coronary syndrome [310" ]. 

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