Permeability glycoprotein (P-gp) mediates the export of drugs from cells located in the small intestine, blood-brain barrier, hepatocytes, and kidney proximal tubule, serving a protective function for the body against foreign substances. Intestinal absorption, biliary excretion, and urinary excretion of P-gp substrates can therefore be altered by either the inhibition or induction of P-gp. A wide spectrum of drugs, such as anticancer agents and steroids, are known P-gp substrates and/or inhibitors, and many cardiovascular drugs have recently been observed to have clinically relevant interactions as well. We review the interactions among commonly prescribed cardiovascular drugs that are P-gp substrates and observe interactions involving P-gp that may be relevant to clinical practice. Cardiovascular drugs with narrow therapeutic indexes (e.g., antiarrhythmic agents, anticoagulant agents) have demonstrated large increases in concentrations when coadministered with potent P-gp inhibitors, thus increasing the risk for drug toxicity. Therefore, dose adjustment or use of alternative agents should be considered when strong P-gp-mediated drug-drug interactions are present. Finally, interactions between novel drugs and known P-gp inhibitors are now being systematically evaluated during drug development, and recommended guidelines for the administration of P-gp substrate drugs will be expanded.

Background: In patients with heart failure (HF), malnutrition and dietary sodium excess are common and may worsen outcomes. No prior studies have provided low-sodium, nutritionally-complete meals following HF hospitalization. Methods and Results: The Geriatric OUt-of-hospital Randomized MEal Trial in Heart Failure (GOURMET-HF) study randomized patients discharged from HF hospitalization to four weeks of home-delivered sodium-restricted Dietary Approaches to Stop Hypertension meals (DASH/SRD; 1,500 mg sodium/day) vs. usual care. The primary outcome was the between-group change in the Kansas City Cardiomyopathy Questionnaire (KCCQ) Summary Score from discharge to four weeks post-discharge. Additional outcomes included changes in the KCCQ Clinical Summary Score and cardiac biomarkers. All patients were followed 12 weeks for death/all-cause readmission and potential diet-related adverse events (symptomatic hypotension, hyperkalemia, acute kidney injury). 66 patients were randomized 1:1 at discharge to DASH/SRD vs. usual care (age 71±8 years, 30% female, ejection fraction 39±18%). The KCCQ Summary Score increased similarly between groups (DASH/SRD 46±23 to 59±20 vs. usual care 43±19 to 53±24, p=0.38) but the KCCQ Clinical Summary Score increase tended to be greater in DASH/SRD participants (47±22 to 65±19 vs. 45±20 to 55±26, p=0.053). Potentially diet-related adverse events were uncommon; 30-day HF readmissions (11% vs. 27%, p=0.06) and days rehospitalized within that timeframe (17 vs. 55, p=0.055) trended lower in DASH/SRD participants. Conclusions: Home-delivered DASH/SRD following HF hospitalization appeared safe in selected patients, and had directionally favorable effects on HF clinical status and 30-day readmissions. Larger studies are warranted to clarify the effects of post-discharge nutritional support in patients with HF. Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT02148679

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Prior studies report 9–27% of persons receiving a hematopoietic cell transplant develop arrhythmias, but the effect on outcomes is largely unknown. We reviewed data from 1177 consecutive patients {greater than or equal to}40 years old receiving a hematopoietic cell transplant at one center during 1999–2009. Transplant indication was predominately leukemia, lymphoma and multiple myeloma. Overall, 104 patients were found to have clinically significant arrhythmia: 43 prior to and 61 following transplant. Post-transplant arrhythmias were most frequently atrial fibrillation(N=30), atrial flutter(N=7) and supraventricular tachycardia(N=11). Subjects with an arrhythmia post-transplant were more likely to have longer median hospital stays (32 days vs 23, P=<.001,) a greater probability of an ICU admission (52% vs 7%; P<.001), more inhospital deaths (28% vs 3%, P<0.001), and more deaths within one year of transplant (41% vs 15%; P<0.001) than patients without arrhythmia at any time. In a multivariate model including age at transplant, diagnosis, history of pre-transplant arrhythmia, and transplant-related variables, post-transplant arrhythmia was associated with a greater risk of death within a year of transplant (OR 3.5, 95% CI: 2.1, 5.9; P < 0.001). Our data suggest arrhythmias after transplants are associated with significant morbidity and mortality. A prospective study of arrhythmia in the transplant setting is warranted.

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