"The failing heart is not just an enlarged version of a normal heart." I know Dr. Louis Katz said it, but I never found out where. At any rate, he posthumously alerted me to recognize that patients with heart failure do not demonstrate the lower range of normal physiology, but rather their own special ranges. I recognize this in the exquisite load sensitivity of the failing heart or in noting how much atrioventricular synchrony contributes to the failing heart. I try to teach this all the time-I'll know it's time to retire when I overhear the medical students joking about me having them graph the relationship between cardiac output and vascular resistance. Nevertheless, it's a concept I use every day.-Marc A. Silver Similar to all disease states, the primary approach to and ultimate treatment of heart failure is prevention. For the entire human population, this means bringing systemic blood pressure into the currently recommended range, controlling the risk factors for atherosclerosis, aggressively managing ischemic syndromes, reversing valvular and congenital lesions before cardiac damage occurs, and so forth. Hopefully, over time, we'll be able to counter and reverse many of the predisposing genetic factors as well.-Carl V. Leier Ask patients to describe exactly how they take their medications. Heart failure patients are frequent victims of polypharmacy, and despite the best intentions of the health care providers and patients, inadvertent medication errors are common. For example, one of my patients mixed up his digoxin and isosorbide dinitrate; as a result, he was taking digoxin three times a day (and wondering why he was nauseated)! Ask routinely about the use of over-the-counter medications, especially cold preparations, "diet pills," and nonsteroidal anti-inflammatory drugs (NSAIDs). These widely available agents are frequently used by heart failure patients, who fail to recognize the potential for drug-drug and drug-disease interactions.-Michael W. RichThere are several things I routinely do for each patient who comes to see me. On the first visit, I examine current medications and simplify the regimen. I eliminate calcium channel blockers, NSAIDs, and albuterol (unless there is a pressing need to continue these). We routinely check digoxin levels and adjust the medication to keep the plasma level between 0.7 and 1.0 ng/mL. This is based on data from our laboratory showing that most of the benefit of this drug is at low dose (J Am Coll Cardiol. 1997;29:1206) and a post hoc analysis of the DIG study, which showed a relationship of plasma level and mortality with more toxicity at higher doses (Am Heart J. 1997;134:3). I optimize angiotensin-converting enzyme (ACE) inhibitor doses (in an attempt to use the doses shown to be efficacious in the clinical trials) and use a longer-acting, preferably once-a-day ACE inhibitor to simplify the patient's regimen. I often give this dose prior to bedtime so that any hypotension will be at night while the patient is sleeping. I also give nitrates to my heart failure pat...
Among the antihypertensive classes, CCBs were most effective in reducing the long-term incidence of stroke, whereas β-blockers were associated with significantly increased risk.
We wish to reintroduce an infrequently employed technique to re-establish intestinal continuity after extended resection of the left colon, transverse colon, and distal ascending colon. It involves bringing the proximal ascending colonic stump through the distal ileal mesenteric defect to reach the distal rectal stump in a tensionless fashion.
In advanced heart failure (HF), chronic inotropic therapy with intravenous milrinone, a phosphodiesterase III inhibitor, is used as a bridge to advanced management that includes transplantation, ventricular assist device implantation, or palliation. This is especially true when repeated attempts to wean off inotropic support result in symptomatic hypotension, worsened symptoms, and/or progressive organ dysfunction. Unfortunately, patients in this clinical predicament are considered hemodynamically labile and may escape the benefits of guideline-directed HF therapy. In this scenario, chronic milrinone infusion may be beneficial as a bridge to introduction of evidence based HF therapy. However, this strategy is not well studied, and in general, chronic inotropic infusion is discouraged due to potential cardiotoxicity that accelerates disease progression and proarrhythmic effects that increase sudden death. Alternatively, chronic inotropic support with milrinone infusion is a unique opportunity in advanced HF. This review discusses evidence that long-term intravenous milrinone support may allow introduction of beta blocker (BB) therapy. When used together, milrinone does not attenuate the clinical benefits of BB therapy while BB mitigates cardiotoxic effects of milrinone. In addition, BB therapy decreases the risk of adverse arrhythmias associated with milrinone. We propose that advanced HF patients who are intolerant to BB therapy may benefit from a trial of intravenous milrinone as a bridge to BB initiation. The discussed clinical scenarios demonstrate that concomitant treatment with milrinone infusion and BB therapy does not adversely impact standard HF therapy and may improve left ventricular function and morbidity associated with advanced HF.
Background BOLERO-2 phase III trial established the efficacy of everolimus (EVE) plus exemestane (EXE) for the treatment of postmenopausal patients with hormone receptor (HR)-positive, HER2-negative, advanced breast cancer (aBC). However, in this study only a minority (<10%) of patients were recruited from African and Asia Pacific countries. Considering the potential effects of ethnic and cultural differences on treatment effectiveness, it remains compelling to confirm the safety and efficacy profile of EVE+EXE in these populations. Methods EVEREXES is an open-label phase IIIb, single arm, multi-center trial, which from March 2013 to October 2014 enrolled 232 post-menopausal, HR-positive and HER2-negative, aBC patients previously treated with aromatase inhibitors, across 13 countries in Asia Pacific, Middle East, North and South Africa, with a significant majority of patients being of Asian ethnicity (196, 84.5%). Its primary objective was to investigate the safety and tolerability profile of EVE+EXE. Secondary objectives were the evaluation of efficacy (assessed by PFS, ORR, and CBR based on RECIST 1.1 criteria) and change in ECOG performance status. Results At data cut off of 31st of January 2015, at a median follow up of 11.7 months, median PFS for the ITT population was 9.5 months [9.2-11.6 months], based on local assessment, with the observation of 1 (0.4%) CR and 35 (15.4%) PR. Regarding safety and tolerability, a majority (81.1%) of grade (G) 1/2 adverse events (AEs) was reported. In particular, the following pattern was observed in terms of % of patients who developed G1/G2/G3 mTOR-inhibition induced AEs: stomatitis (36.1, 13.7, 10.6), rash (21.6/6.2/0), fatigue (10.6, 4.4, 2.2), hyperglycemia (6.2, 11.5, 7.0), weight decrease (7.5, 7, 0.9), pneumonitis (5.7, 7, 0.9). No Grade 4 AEs related to EVE+EXE treatment were observed, with exception of one case of non infectious pneumonitis (0.4%). Median dose intensity of everolimus was 9.2 mg/day. Conclusions Efficacy and safety results from EVEREXES trial further confirm the role of EVE+EXE for the treatment of HR+/Her2- advanced BC patients in Eastern countries. Results were consistent with data previously reported in BOLERO-2 trial. Citation Format: Im Y-H, Uslu R, Lee KS, Nagarkar R, Sohn J, Sevinc A, Altundag K, Chang Y-C, Abdel-Razeq H, Im S-A, Jeong J, Park HY, Arpornwirat W, Bastick P, Le TH, Ocak Arikan O, Xue HL, Canatar A, Valenti R, Kim S-B. Clinical effectiveness of everolimus and exemestane in advanced breast cancer patients from Asia and Africa: First efficacy and updated safety results from the phase IIIb EVEREXES study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-13-09.
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