Cardiomyopathy ischemic

Mast cells are present in the normal human heart and even more abundant in diseased hearts [ 16-18,25,47]. Within heart tissue, mast cells he between myocytes and are in close contact with blood vessels. They are also found in the coronary adventitia and in the shoulder regions of coronary atheroma [20, 21], The density of cardiac mast cells is higher in patients with dilated and ischemic cardiomyopathy than in accident victims without cardiovascular diseases [25], Importantly, in some of these conditions there is in situ evidence of mast cell activation [16,34],... 

Patella V, Marino I, Arbustini E. Lamparter-Schummert B, Verga L, Adt M. Marone G Stem cell factor in mast cells and increased mast cell density in idiopathic and ischemic cardiomyopathy. Circulation 1998 97 971. 

Di Carh MF, Asgarzadie F, Schelbert HR, Brunken RC, Laks H, Phelps ME et al. Quantitative relation between myocardial viabihty and improvement in heart failure symptoms after revascularization in patients with ischemic cardiomyopathy. Circulation 1995 92 3436-3444... 

Santana CA, Shaw LJ, Garcia EV, Soler-Peter M, Candell-Riera J, Grossman GB et al. Incremental prognostic value of left ventricular function by myocardial ECG-gated FDG PET imaging in patients with ischemic cardiomyopathy. J Nucl Cardiol 2004 11 542-550... 

Abstract Two thirds of the nearly half a million deaths per year in the United States due to sudden cardiac death (SCD) is attributed to coronary artery disease (CAD) and most commonly results from untreated ventricular tachyarrhythmias. Patients with ischemic cardiomyopathy and left ventricular dysfunction are at highest risk for SCD, but this still defines only a small subset of patients who will suffer SCD. Multiple lines of evidence now support the superiority of implantable cardioverter defibrillator (ICD) therapy over antiarrhythmic therapy for both primary and secondary prevention of SCD in advanced ischemic heart disease. Optimization of ICD therapy in advanced ischemic cardiomyopathy includes preventing right ventricular pacing as well as the use of highly effective anti-tachycardia pacing to reduce the number of shocks. While expensive, ICD therapy has been shown to compare favorably to the accepted standard of hemodialysis in cost effectiveness analyses. 

Not all patients with MI and depressed LV function develop SCD or ventricular arrhythmias—it is estimated that 20-30% of patients with ischemic cardiomyopathy will develop SCD or ventricular arrhythmias [5, 8-10]. SCD rates vary with severity of heart failure (Fig. 3.2). The proportion of SCDs decreases with increasing severity of heart failure by NYHA functional class [11]. SCD accounts for the majority of deaths in those with NYHA II or III heart failure, while progressive heart failure... 

Identification of Risk of Sudden Cardiac Death in Ischemic Cardiomyopathy... 

A significant mortality benefit of ICD therapy was shown in the largest of the three studies, the AVID study. In this study, over 1,000 patients with ischemic cardiomyopathy and an EF < 40% who were resuscitated from VF or from symptomatic, sustained VT were randomized to antiarrhythmic medications (>90% amiodarone) or ICD implantation. The trial was stopped early because the ICD showed a significant survival benefit with an 11.3% absolute and 31.5% RR reduction for all-cause mortality over 3 years. Persistent benefit with the ICD was seen even after adjustment for age, beta blocker use, and baseline EF. 

Since survival rates for out-of-hospital cardiac arrest are quite low, ranging from 2 to 25% in the United States [32], secondary prevention strategies only address a small minority of ischemic cardiomyopathy patients at risk for SCD. A more substantial reduction in SCD will result from primary prevention of SCD with ICD implantation. Evidence for this strategy comes from several recent trials. The findings of primary prevention trials for SCD in ischemic cardiomyopathy are summarized in Table 3.1. 

The Multicenter Automatic Defibrillator Implantation Trial (MADIT) randomized 196 patients with ischemic cardiomyopathy, EF < 35%, a documented episode of nonsustained VT (NSVT), and inducible VT on electrophysiology study (EPS) to ICD versus conventional medical therapy [9]. After a mean follow-up of 27 months, the RR reduction for allcause mortality in the ICD arm was 59% [p = 0.009]. 

Table 3.1 Summary of ICD primary prevention trials in ischemic cardiomyopathy ...

As a result of the weight of evidence for ICD therapy in prevention of SCD in patients with ischemic cardiomyopathy, the American College of Cardiology, American Heart Association, and the North American Society for Pacing and Electrophysiology (now Heart Rhythm Society) revised guidelines for ICD implantation in October 2002... 

Kadish A, Dyer A, Daubert JP, et al., for the Defibrillators in Non-Ischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Investigators. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy. N Engl J Med. 2004 350 2151-2158. 

Table 7.3 Cell therapy trials in patients with ischemic cardiomyopathy...

Clinical trials of skeletal myoblasts have focused on the treatment of patients with ischemic cardiomyopathy and systolic dysfunction. Overall, these trials have resulted in improved segmental contractility and global LVEF. The preferred delivery route has been surgical intramyocardial injection, and one feasibility trial of transendocardial injection has been reported in the literature so far. 

Fig. 8.1 Examples of 12 lead high frequency QRS electrocardiograms from a patient with ischemic cardiomyopathy (A) and an age and gender matched healthy control (B)...

The concept of cell-based cardiac repair has gained a large amount of focus over the past decade and is discussed in previous chapters. This modality will only become more widely used in the future. There have been several studies utilizing skeletal muscle in ischemic cardiomyopathy [37-39]. No conclusions can be made but there are some indications of improvement in function but arrhythmias have been a concern. 

Dewald O, Sharma S, Adrogue J, et al. Downregulation of peroxisome proliferator-activated receptor-alpha gene expression in a mouse model of ischemic cardiomyopathy is dependent on reactive oxygen species and prevents lipotoxicity. Circulation. Jul 19 2005 112(3) 407 15. 

In patients suffering from heart failure due to ischemic cardiomyopathy Severs [1994a, b] described two main alterations (1) changes in the normal spatial distribution of gap junctions at the border zone of healed infarcts, and (2) a reduction in the quantity of Cx43 in regions distant from infarct scars. 

Uses Acute CHF, ischemic cardiomyopathy Action Inotrope w/ vasodilator Dose IV bolus 0.75 mg/kg over 2-3 min maint 5-10 mcg/kg/min, 10 mg/kg/d max i if CrCl <10 mL/min Caution [C, ] Contra Bisulfite allergy Disp Inj SE Monitor fluid, electrolyte, renal changes Interactions Diuretics cause significant hypovolemia T effects OF cardiac glycosides EMS Avoid diuretic use, can cause profound hypovolemia incompatible w/ dextrose solns monitor ECG for hypokalemia (flattened T waves) OD May cause profound hypotension use IV fluids w/ caution d/t fluid buildup in lungs, pressors may be used... 

Schillinger, W., Meyer, M., Kuwajima, G., et al., 1996, Unaltered ryanodine receptor protein levels in ischemic cardiomyopathy. Mol Cell Biochem, 160-161, pp 297—302. 

Askari, A., Unzek, S., Goldman, C. K., Ellis, S. G., Thomas, J. D., Di Corleto, P. E., Topol, E. J. and Penn, M. S. (2004). Cellular, but not direct, adenoviral delivery of vascular endothelial growth factor results in improved left ventricular function and neovascularization in dilated ischemic cardiomyopathy. J. Am. Coll. Cardiol. 19, 1908-1914. 

Dib N, McCarthy P Campbell A, et al, Feasibility and safety of autologous myoblast transplantation in patients with ischemic cardiomyopathy. Cell Transplant 2005 14 1 1-19,... 

Perin EC, Dohmann Hp Borojevic R, et al, Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy. Circulation 2004 I 10 11213-11218. 

Autologous bone marrow stem cells for chronic stable angina and ischemic cardiomyopathy without the option of revascularization... 

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