The use of PSDs in HF patients is associated with a reduced risk of death from, or hospitalization for, progressive HF or all-cause or cardiovascular death, compared with patients taking only a non-PSD.

Methadone is used for the treatment of opioid addiction and for treatment of chronic pain. The safety of methadone has been called into question by data indicating a large increase in the number of methadone-associated overdose deaths in recent years that has occurred in parallel with a dramatic rise in the use of methadone for chronic pain. The American Pain Society and the College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society, commissioned an interdisciplinary expert panel to develop a clinical practice guideline on safer prescribing of methadone for treatment of opioid addiction and chronic pain. As part of the guideline development process, the American Pain Society commissioned a systematic review of various aspects related Clinical practice guidelines are ''guides'' only and may not apply to all patients and all clinical situations. As part of a shared decision-making approach, it may be appropriate for the clinician to inform a patient that a particular recommendation may not be applicable, after considering all circumstances pertinent to that individual. This article is based on research conducted at the Oregon Evidence-based Practice Center (now the Pacific Northwest Evidence-based Practice Center) with funding from the American Pain Society (APS to safety of methadone. After a review of the available evidence, the expert panel concluded that measures can be taken to promote safer use of methadone. Specific recommendations include the need to educate and counsel patients on methadone safety, use of electrocardiography to identify persons at greater risk for methadone-associated arrhythmia, use of alternative opioids in patients at high risk of complications related to corrected electrocardiographic QTc interval prolongation, careful dose initiation and titration of methadone, and diligent monitoring and follow-up. Although these guidelines are based on a systematic review, the panel identified numerous research gaps, most recommendations were based on low-quality evidence, and no recommendations were based on high-quality evidence.Perspective: This guideline, based on a systematic review of the evidence on methadone safety, provides recommendations developed by a multidisciplinary expert panel. Safe use of methadone requires clinical skills and knowledge in use of methadone to mitigate potential risks, including serious risks related to risk of overdose and cardiac arrhythmias. M ethadone is a synthetic opioid used for the treatment of opioid addiction and for treatment of chronic pain. 15,61 The safety of methadone has been called into question by data indicating a large increase in the number of methadone-associated overdose deaths.38 This increase appears largely related to the dramatic rise in the use of methadone for chronic pain, though a small proportion of deaths occur in patients treated for opioid addiction. 21,37,68,76,91,103 Methadone poisoning deaths in the United States increased steadily from about 800 in 1999 to a high of about 5,500 in 2007; th...

Background: Levomethadyl acetate, methadone hydrochloride, and buprenorphine hydrochloride are equally effective treatments for opioid dependence. Each blocks the human ether-ago go related gene (hERG)associated channel in vitro and represents a risk for QT prolongation.To compare the effects of 3 known hERGassociated channel blockers on the corrected QT (QTc), we conducted a randomized, controlled trial of opioidaddicted subjects. Methods: We analyzed 12-lead electrocardiograms collected at baseline and every 4 weeks from 165 opioidaddicted participants in a 17-week randomized doubleblind clinical trial of equally effective doses of levomethadyl, methadone, and buprenorphine at a major referral center. Analyses were limited to the 154 patients with a normal baseline QTc = (QT/ ͱ R-R) who had at least 1 subsequent in-treatment electrocardiogram. Patients were randomized to receive treatment with levomethadyl, methadone, or buprenorphine (hereinafter, levomethadyl, methadone, and buprenorphine groups, respectively). The prespecified end points were a QTc greater than 470 milliseconds in men (or Ͼ490 milliseconds in women), or an increase from baseline in QTc greater than 60 milliseconds. Results: Baseline QTc was similar in the 3 groups. The levomethadyl and methadone groups were significantly more likely to manifest a QTc greater than 470 or 490 milliseconds (28% for the levomethadyl group vs 23% for the methadone group vs 0% for the buprenorphine group; PϽ.001) or an increase from baseline in QTc greater than 60 milliseconds (21% of the levomethadyl group [odds ratio, 15.8; 95% confidence interval, 3.7-67.1] and 12% of the methadone group [odds ratio, 8.4; 95% confidence interval, 1.9-36.4]) compared with the buprenorphine group (2% of subjects; PϽ.001). In subjects whose dosage of levomethadyl or methadone remained fixed over at least 8 weeks, the QTc continued to increase progressively over time (P=.08 for the levomethadyl group, P=.01 for the methadone group). Conclusion: Buprenorphine is associated with less QTc prolongation than levomethadyl or methadone and may be a safe alternative.

In postinfarction patients with severe left ventricular dysfunction, increased QT variability, a marker of repolarization lability, is associated with an increased risk for VT/VF.

Tachycardic pigs given furosemide had significant acceleration of both contractile and metabolic features of CHF, including left ventricular systolic dysfunction, elevated serum aldosterone levels, and altered calcium handling in a controlled experimental model of heart failure.