ranolazine study: speckle tracking derived myocardial strain

Conditions: Severe Coronary Artery Disease; Ischaemic Myocardial Dysfunction

Summary: the purpose of this study is to collect data to determine if the medication, ranolazine, effects heart muscle function in patients who have areas of non-revascularizable heart muscle.

many cardiac patients with severe coronary artery disease have areas of ischemic lv myocardium that cannot be revascularized (non-r). the investigators propose to identify such patients via retrospective case review of cmri data, as well as identify the exact regions which specify non-r coronary anatomy. this selected study group will have a specific echocardiographic imaging protocol performed, which includes the known ischemic regions. all segments will be collected and analyzed as a pre-therapeutic baseline using specialized ste software to derive strain values. following eight (8) weeks of ranolazine therapy, each subject will be re-interrogated with the same echocardiographic imaging protocol and have identical measurements of regional strain performed. ranolazine will be added to the patients' usual medical therapy. each patient will serve as their own control, from baseline to post therapeutic state. it is the hypothesis of the investigators, that additional therapeutic dosing of ranolazine will improve regional and perhaps global myocardial function. improvement in lv mechanical function (regional and global) will be quantitated and objectively elucidated by ste derived myocardial strain as described further in this document.

Eligibility criteria:
inclusion criteria: * age \> 18 stable gdmt for 60 days prior to enrollment normal sinus rhythm coronary artery revascularization \> 60 days prior to enrollment non-revascularizable area of myocardial ischemia as determined by stress mri able to perform the bicycle stress echocardiograms able to provide written, informed consent women of childbearing potential with negative pregnancy test at the index visit, and consent to use effective contraception throughout the study period and up to at least 14 days following the last dose of study drug exclusion criteria: * more than 1+mr, aortic stenosis, aortic insufficiency, mitral stenosis serious co-morbidities with predicted life expectancy \<1 year patients not in normal sinus rhythm (nsr) patients who have undergone coronary artery revascularization (pci, cabg) within 60 days pregnant or unknown pregnancy status liver cirrhosis patients unwilling/unable to provide written, informed consent concomitant use of qtc prolonging drugs, potassium channel variants resulting in a long qt interval, patients with a family history of (or congenital) long qt syndrome, and patients with known acquired qt interval prolongation concomitant use of strong cyp3a inhibitors including ketoconazole, itraconazole, clarithromycin, nefazodone, nelfinavir, ritonavir, indinavir, and saquinavir concomitant use of cyp3a4 inducers such as rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and st. john's wort breast feeding atrial fibrillation or frequent atrial or ventricular ectopy moderate cyp3a inhibitors (e.g., diltiazem, verapamil, erythromycin) p-gp inhibitors (e.g., cyclosporine) which increase ranolazine exposure renal failure. patients with creatinine clearance less than 30ml/min . safety considerations for patients with the following drugs/conditions cyp3a substrates: limit simvastatin to 20 mg when used with ranolazine. doses of other sensitive cyp3a substrates (e.g., lovastatin) and cyp3a substrates with narrow therapeutic range (e.g., cyclosporine, tacrolimus, sirolimus) may need to be reduced with ranolazine oct2 substrates: limit the dose of metformin to 1700 mg daily when used with ranolazine 1000 mg twice daily. doses of other oct2 substrates may require adjusted doses drugs transported by p-gp (e.g., digoxin), or drugs metabolized by cyp2d6 (e.g., tricyclic antidepressants) may need reduced doses when used with ranolazine renal failure: patients with creatinine clearance less than 30ml/min are excluded from participation in this study. monitor renal function after initiation and periodically in patients with moderate to severe renal impairment (crcl \< 60 ml/min). if acute renal failure develops, discontinue ranolazine.