Pacing left ventricular

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. 

Conduction system abnormalities are common in chronic heart failure, occurring in 15-30% of the population with low left ventricular ejection fraction (LVEF) [1-3]. The prevalence in ischemic heart disease is roughly similar to that seen in other forms of dilated cardiomyopathy. Conduction system disease can occur both at the time of an acute myocardial infarction as well as slowly progressing in chronic ischemic heart disease. Intraventricular conduction delays are associated with a poor prognosis in heart failure, with up to a 70% increase in the risk of death, and are also more prevalent in patients with advanced symptoms [2,4]. In ischemic heart disease, all components of the conduction system are at risk of ischemic injury, from the sinoatrial node to the His-Pukinje system. These conduction system abnormalities have the potential to impair cardiac function by a number of mechanisms. Since conduction abnormalities impair cardiac function, it is logical that pacing therapies to correct or improve these conduction abnormalities may improve cardiac function. 

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Fig. 11. Changes In gated NMR spectra during the cardiac cycle. Top panel isovolumic left ventricular pressure In a ferret heart paced at 0.99 Hz in 8 mM [Ca +]. NMR spectra were acquired at the two times indicated on the pressure record (a) 10 ms prior to stimulation (b) 75 ms after stimulation. Middle panel shows gated F NMR spectra (each from 800 acquisitions) recorded at (a) and (b), as indicated. The bound (B) and free (F) peaks of 5F-BAPTA exhibit distinct chemical shifts at approximately 8 and 2 ppm, respectively, downfield from a standard of 1 mM 6-Ftryptophan at 0 ppm. It appears that the free [Ca +] varied during the cardiac cycle. Bottom panel shows gated P spectra (400 scans) acquired at times a and b in the same heart. The major peaks correspond to phosphocreatine (0 ppm), ATP (the three peaks upfield from phosphocreatine), and inorganic phosphate (the small peak at 4-5 ppm) (Reproduced from Marban et al. Circ. Res. 1988 63 673-678 [311] with permission of Lippincott, Williams Wilkins).

Patients with normal sinus rhythm and a wide QRS interval, eg, greater than 120 ms, have impaired synchronization of ventricular contraction. Poor synchronization of left ventricular contraction results in diminished cardiac output. Resynchronization, with left ventricular or biventricular pacing, has been shown to reduce mortality in patients with chronic heart failure who were already receiving optimal medical therapy. 

Left ventricular pressure measurements are monitored continuously by use of a 5F end-hole pig-tail catheter in the left ventricular apex and a 6F femoral sheath in order to be able to assess the gradient, If the outflow gradient is absent or small under the basal conditions, the magnitude of provocable obstruction is most appropriately assessed with maneuvers (Valsalva, ventricular pacing, extrasystoles, physiological exercise, amyl nitrate), The inability to elicit any provocable gradient is a contraindication to the procedure,... 

Isolated right ventricular tissues were used to measure the contribution of P-AR signaling to contractility. Cardiac inotropy was monitored in isolated, paced right ventricular muscle strips. Preparations from pr AR-KO mice failed to show any responsiveness to isoproterenol administration, while wild-type preparations showed robust inotropic responses (28). This lack of contractile response is not caused by generalized hyporesponsiveness of the contractile apparatus because prAR-KO ventricles responded normally to activators of adenylyl cyclase such as forskolin. Surprisingly, disruption of both pr and P2-ARs has only modest effects on resting left ventricular contractility in vivo. When contractility was assessed with a micromanometer-tipped catheter, -i-dP/dt was reduced by 20% and -dP/dt was reduced by 12% in p /prAR-KO mice compared to wild-type mice (30). 

Figure 5. A, Schematic of a Largerdortf perfused rat heart model. Retrograde perfusion is established through the aorta. Perfusate oxygenated with 95% O, and 5% CO, is circulated by a peristaltic pump and the flow can be adjusted. Left ventricular pressure is monitored Ihrough a balloon which is inserted into the empty left ventricle. Heart rhythm is controlled by pacing.

Cardiac resynchronization therapy (CRT) for systolic congestive heart failure (CHF) represents a new paradigm in cardiology the use of an electrical therapy (cardiac pacing) to treat a mechanical problem. Multiple randomized clinical trials have proven that resynchronization therapy improves symptoms and functional status, increases quality of life, reduces hospitalizations, and prolongs survival in appropriately selected patients. As a result, this therapy has been quickly established as a standard treatment for patients with severe left ventricular dysfunction, moderate-to-severely symptomatic CHF despite optimal medical therapy, and prolonged QRS duration (1,2). 

PAVE and OPSITE stand out among the published randomized trials of CRT in enrolling patients irrespective of pre-implant ejection fraction. In fact, nearly half of the patients in PAVE had a left ventricular ejection fraction above 45%. Post hoc analysis of PAVE suggests that the majority of the benefit in the trial was confined to the subgroup with a pre-implant ejection fraction of less than 45% (39). However, the opposite pattern was observed in OPSITE. In that trial, the comparative benefit to biventricular pacing was greatest in those patients with normal baseline left ventricular function (40). It is possible that these discordant results reflect the play of chance. A larger trial is necessary to resolve the issue. 

Data also exist to suggest that patients with transmural myocardial infarctions of the lateral wall are unlikely to improve with lateral left ventricular pacing (56). Echocardiographic substudies of MIRACLE (23) and MUSTIC (22) have shown greater reverse remodeling in patients with nonischemic as opposed to ischemic cardiomyopathies. It is, however, important to recognize that substudy analysis shows no difference in clinical outcomes between patients with ischemic versus nonischemic heart disease (10,21,30). 

Auricchio A, Stellbrink C, Butter C, et al. Clinical efficacy of cardiac resynchronization therapy using left ventricular pacing in heart failure patients stratified by severity of ventricular conduction delay. J Am Coll Cardiol 2003 42 2109-16. 

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Prinzen FW, Peschar M. Relation between the pacing induced sequence of activation and left ventricular pump function in animals. Pacing Clin Electrophysiol 2002 25(pt l) 484-98. 

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Tondo C, Mantica M, Russo G,etal. Pulmonary vein vestibule ablation for the control of atrial fibrillation in patients with impaired left ventricular function. Pacing Clin Electrophysiol 2006 29 962-70. 

Fig. 6.11 D uration of efficacy pig study. After a single intracoronary injection of 1v.p. AdSFGF-4, pacing-induced left ventricular functional deficit was reversed at 2 weeks after gene injection, and maintained for up to 12 weeks. Numbers in columns indicate mean number of experiments error bars denote 1 SD.

Coronary venous lead connectors were initially developed to accommodate patients with heart failure who were previously implanted for other reasons and were considered eligible for an upgrade to biventricular pacing. For these patients, the ventricular output of the PM generator was divided via a Y connector from one bipolar output to two separate outputs - one for the previously implanted RV lead and the other for the new left ventricular (LV) lead. 

Pastore G, Noventa F, Piovesana PG et al (2008) Left ventricular dyssynchrony resulting from right ventricular apical pacing. Relevance of baseline assessment. Pacing Clin Electrophysiol 31 1456-1462... 

TLR, transvenous lead removal A, atrial RV, right ventricular LV, left ventricular PL, pacing leads ICD, implantable cardioverter defibrillator L, leads... 

De Martino G, Orazi S, Bisignani G et al (2005) Safety and feasibility of coronary sinus left ventricular pacing leads extraction a preliminary report. J Interv Card Electrophysiol 13(l) 35-38... 

Cesario DA, Shenoda M, Brar R, Shivkumar K (2006) Left ventricular lead stabilization utilizing a coronary stent. Pacing Clin Electrophysiol 29(4) 427 28... 

Zucchelli G, Soldati E, Segreti L et al (2008) Cardiac resynchronization after left ventricular lead extraction usefulness of angioplasty in coronary sinus stenosis. Pacing Clin Electrophysiol 31 908-911... 

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