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A study to explain the efficacy of ezetimibe, which reduces LDL cholesterol on the progression of atherosclerosis, is conducted. Results indicate that a combination of simvastatin and ezetimibe does not show any significant changes in hypercholesterolemia but simvastatin alone did work better.

Background: Reduction in low-density lipoprotein cholesterol (LDL-C) improves clinical outcomes in patients with chronic coronary artery disease and acute coronary syndromes (ACSs). The combination of ezetimibe/simvastatin produces greater reductions in LDL-C compared to simvastatin monotherapy. The IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) is a multicenter, randomized, double-blind, active-control trial designed to test the hypothesis that the addition of ezetimibe to statin therapy, using ezetimibe/simvastatin, will translate into increased clinical benefit on cardiovascular outcomes relative to simvastatin monotherapy in patients with ACS. Study Design: The study will recruit up to 18,000 moderate- to high-risk patients stabilized after ACS. Patients are randomized in a 1:1 ratio to once-daily doses of either ezetimibe/simvastatin 10/40 mg or simvastatin monotherapy 40 mg. Follow-up visits are at 1 and 4 months, and every 4 months thereafter. If consecutive measures of LDL-C are >79 mg/dL at follow-up visits, the simvastatin dose will be increased to 80 mg in a double-blind manner. The primary end point is the first occurrence of cardiovascular death, nonfatal myocardial infarction, rehospitalization for unstable angina, coronary revascularization (occurring at least 30 days after randomization), or stroke. Patients will be followed for a minimum of 2.5 years and until at least 5,250 patients experience a primary end point. Summary: IMPROVE-IT will determine whether the addition of ezetimibe to statin therapy, using ezetimibe/simvastatin, improves cardiovascular outcomes compared with simvastatin monotherapy in patients after ACS. In addition, the difference in achieved LDL-C levels between the groups will provide data on whether the target for LDL-C lowering should be reduced further. [Copyright &y& Elsevier]

Background: Levels of cholesterol are regulated by its synthesis, absorption, and elimination. Plasma levels of phytosterols (e.g., sitosterol, campesterol) and ratios of these sterols to total cholesterol (TC) are reported to correlate with efficiency of intestinal cholesterol absorption, whereas levels of certain cholesterol precursor sterols (e.g., desmosterol, lathosterol) and their ratios to TC correlate with cholesterol biosynthesis. However, there is a paucity of published data concerning the effects of combined treatment using HMG-CoA reductase inhibitors (statins) and a cholesterol absorption inhibitor (ezetimibe) on these parameters.Objectives: To characterize the effects of ezetimibe co-administered with statins, compared with each treatment alone, on cholesterol precursor sterols and plasma phytosterol levels.Methods: A post-hoc analysis was performed to determine the effects of treatment with ezetimibe 10 mg, simvastatin (10-80 mg), and atorvastatin (10-80 mg), alone or in combination, on these non-cholesterol sterols using plasma samples from two randomized controlled trials involving patients with primary hypercholesterolemia (low-density lipo protein [LDL-C] = 145-250 mg/dL; triglycerides < or = 350 mg/dL; N = 975) but without a recent (< or = 6-month) history of coronary heart disease (CHD) or either uncontrolled or newly diagnosed diabetes mellitus.Results: Ezetimibe monotherapy significantly reduced plasma sitosterol and campesterol concentrations from baseline compared with placebo (both p < 0.001), whereas statins significantly lowered desmo sterol and lathosterol levels (p < 0.001 vs. placebo). Co-administration of ezetimibe and statins significantly decreased plasma levels of all of these sterols (p < 0.001).Conclusions: The observed effects of co-administration of ezetimibe and statins on non-cholesterol sterols are consistent with net inhibition of sterol absorption (driven by ezetimibe) in conjunction with net inhibition of cholesterol synthesis (driven by statins). The potential influence of treatment-induced changes in phytosterols on cardiovascular risk warrants further investigation in long-term, prospective, randomized controlled trials. This post-hoc study was by nature exploratory, and, because data from such analyses are not customarily adjusted for multiple comparisons, some associations may have emerged as statistically significant by chance. Future prospective randomized controlled studies may help to confirm our findings and address other research issues, such as the generalizability of our findings to patients with CHD or diabetes mellitus and possible dose:response relationships between escalating statin (or ezetimibe-statin) doses and circulating non-cholesterol levels. [ABSTRACT FROM AUTHOR]

Background: Lipid lowering through statin therapy significantly reduces the risk of cardiovascular events. The ENHANCE study is an international 2-year, randomized, double-blind, controlled trial designed to test the hypothesis that treatment of hypercholesterolemia by use of 2 complementary agents, ezetimibe (a specific cholesterol absorption inhibitor) and simvastatin (a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor), will result in larger beneficial effects on carotid artery intima-media thickness (CA IMT) than simvastatin monotherapy. Methods: The study will recruit 725 men and women with heterozygous familial hypercholesterolemia. After a placebo washout period, participants are randomized to receive daily administration of either simvastatin 80 mg and ezetimibe 10 mg or simvastatin 80 mg and placebo. The ENHANCE trial uses novel state-of-the-art single-frame digital image acquisition and rigorous quality assurance and control. Results: The primary end point is mean change from baseline to 2 years in CA IMT, using composite measures from the right and left far wall common carotid artery, carotid bulb, and internal carotid artery. Secondary end points include (1) the proportion of participants who exhibit reductions in CA IMT, (2) the change in maximum far wall IMT, (3) the proportion of participants who develop new carotid artery plaques, and (4) the changes in carotid plus common femoral artery IMT. Conclusions: This study addresses the question of whether a regimen that uses drugs with different mechanisms of action will be of further benefit in terms of atherosclerosis reduction compared to statin monotherapy. [ABSTRACT FROM AUTHOR]

During a 6-year cumulative experience, 163 patients with drug-refractory ventricular tachycardia/fibrillation (VT/VF) underwent automatic implantable defibrillator (AID) and/or automatic implantable cardioverter defibrillator (AICD) implantation at our institutions. Baseline preimplantation programmed electrical stimulation was performed in 160 patients revealing induction of sustained arrhythmias in 115 patients (71%), nonsustained arrhythmia in 20 patients (13%), and noninducible arrhythmia in 25 patients (16%). Operative mortality was 4.9%. At 22 ± 15 (mean ± standard deviation) months follow-up 77 patients (50%) had experienced at least one appropriate AID/AICD discharge. The actuarial incidence of sudden cardiac death (VT/VF death within 1 hour of symptoms or during sleep) in the AICD population was 1.8% and 4.1% at 1 and 2 years, respectively. Excluding patients with operative death and those responding to concomitant subendocardial resection (no longer inducible arrhythmias), the incidence of clinical arrhythmic event (AICD discharge and/or VT/VF death) in patients with sustained, nonsustained, and noninducible arrhythmias were not significantly different. We conclude that the AICD appears to reduce the expected incidence of sudden cardiac death in patients with drug-refractory VT/VF and that selection for AICD therapy should not be based on results of baseline programmed electrical stimulation alone. [ABSTRACT FROM AUTHOR]

Holiday heart syndrome is defined as the occurrence of cardiac arrhythmia in alcohol users without overt heart disease after the ingestion of alcohol. Additionally, alcohol has been implicated as a potential etiology of sudden cardiac death in susceptible individuals. We report on a 53-year-old black woman with mild nonischemic dilated congestive cardiomyopathy and alcohol-provoked ventricular tachyarrhythmias who received an automatic implantable cardioverter defibrillator (AICD). She subsequently had recurrent cardiac arrest during bouts of alcohol intoxication and with out-of-hospital AICD rescue. Electrophysiological study using alcohol infusion confirmed alcohol as the etiology of arrhythmogenicity. We propose that holiday heart be expanded to include people with overt heart disease. These individuals have a high risk of sudden cardiac death after alcohol ingestion, irrespective of underlying cardiac substrate; the AICD is an effective back-up modality of therapy. [ABSTRACT FROM AUTHOR]

Investigates the effects of amiodarone, a benzofuran derivative, on defibrillation. Impact of ventricular fibrillation (VF) duration on defibrillation threshold (DFT); Serum and tissue amiodarone and desethylamiodarone levels after one to three weeks of oral amiodarone therapy; Comparison between DFT control and amiodarone dogs DFT; Increase in DFT in amiodarone-treated dogs.

The article informs that current antitachycardia systems such as the automatic implantable cardioverter/defibrillator (AlCD) detect tachyarrhythmias primarily by sensing rate and thereby perform inadequately in differentiating hemodynamically stable from unstable arrhythmias. Hemodynamic parameters have been previously proposed for incorporation into a rate responsive pacing system. Such parameters may also be important in improving the function of current antitachycardia devices. The antitachycardia systems presently in use detect arrhythmias primarily by sensing rate and, thus, are inadequate to differentiate a hemodynamically stable from an unstable rhythm.

Presents a letter to the editor about sudden cardiac death, published in the journal "Pace."

The AICD uses an automatic gain control amplifier for detecting the small electrograms during ventricular fibrillation. The latest generation of the AICD appears to have a more sensitive lock on gain amplifier, as 6 of 76 patients implanted with the new AICD had double counting of the QRS-T wave complex resulting in asymptomatic discharges. Solutions to the problem of limiting these asymptomatic discharges are difficult and include slowing of the heart rate with beta blockers, changing the lead system, or replacement of the device. One of the six patients was treated with beta blockers. Three patients had their device changed, two patients requested the inactivation of their device until a rate programmable unit was available. The potential for T wave sensing in a lock on gain amplifier represents the unique dilemma between detecting small electrograms of ventricular fibrillation, and detecting diastolic events which occur shortly after the QRS complex. [ABSTRACT FROM AUTHOR]

The hemodynamic responses to rapid atrial and ventricular pacing were examined in 10 closed-chest anesthetized dogs in an attempt to distinguish hemodynamically stable from unstable tachycardias. Pressure monitoring catheters were placed in the femoral artery, right atrium, and right ventricle to measure mean arterial pressure, mean right atrial pressure, and mean right ventricular pressure at baseline heart rate and after rapid high right atria! and right ventricular apex pacing. Pressures recorded during rapid pacing (average of the pressures at 30 and 60 seconds of pacing) at pacing rates of 180, 250, and 280/minute were compared to those recorded initially at baseline heart rates. Rapid right ventricular apex pacing resulted in significant increases in mean right atrial pressure (from 6 ± 1 mmHg (mean ± standard error) to 12 ± 1 mmHg, a 100% increase, P < 0.001) and mean right ventricular pressure (from 11 ± 1 mmHg to 16 ± 1 mmHg, a 45% increase, p < 0.02) with marked hemodynamic compromise (mean arterial pressure decreased from 85 ± 6 mmHg to 50 ± 6 mmHg, a 41% decrease, P < 0.01). These parameters remained stable (no statistically significant difference from baseline) during high right atrial pacing. In half of the dogs high right atrial pacing at rates ≥ 250 resulted in atrioventricular Wenckebach. Thus, it is concluded that mean right atrial pressure and mean right ventricular pressure may be useful in distinguishing hemodynamically significant tachycardias, and in the future design of antitachycardia devices. [ABSTRACT FROM AUTHOR]

Presents an overview of the ambulatory management of patients of the automatic implantable cardioverter–defibrillator before and following their discharge from the hospital. Information included on the discharge summary of the patients; List of specific tests recommended prior the to the discharge of the patients; Recommendations for out&#x2013ofȓhospital follow–up.

Twiddler's syndrome, characterized by dislodgment of pacemaker leads due to twisting of pulse generators within the subcutaneous pocket with subsequent retraction of leads and loss of pacing function, has been well described in patients with permanent pacemakers implanted for bradyarrhythmias. The case presented here is the first report of a patient with an internal automatic cardioverter-defibrillator with lead dislodgment due to pulse generator rotation. This case exemplifies a new subset of patients prone to the Twiddler's syndrome. [ABSTRACT FROM AUTHOR]