Intensification Of Medical Therapy Research Articles

P4666Higher BNP levels after transcatheter aortic valve implantation are associated with increased mortality and hospitalizations

Abstract Background Among patients with aortic stenosis (AS), the adverse association between increased B-type natriuretic peptide (BNP) levels and worse clinical outcomes, including mortality and hospitalization after valve replacement, has been demonstrated. However, little attention has been paid to the clinical consequences of BNP levels after valve replacement, which may have implications for medical therapy prescribed after the procedure. Purpose Evaluate the association between BNP levels after transcatheter aortic valve implantation (TAVI) and subsequent mortality and hospitalizations. Methods Among intermediate, high, and extreme risk patients with severe symptomatic AS who received TAVI for native valve AS in the PARTNER II and S3 clinical trials or registries, we included 3260 patients who had BNP measured at baseline. Patients from sites which measured NTproBNP were excluded. To account for factors that influence BNP levels, we developed a regression equation–including age, sex, BMI, creatinine, study site, and the upper limit of normal of the BNP assay used for a given measurement–to determine expected BNP. BNP ratio was determined pre-TAVR and at discharge, 30 days, and 1 year and calculated as the actual BNP/expected BNP. Using a landmark approach, the relationships between (1) BNP ratio at 30 days or (2) delta BNP ratio between discharge and 30 days and subsequent outcomes between 30 days and 1 year were assessed. The primary outcome was a composite of cardiovascular (CV) mortality or hospitalization. Adjustment was made for 20 baseline and post-procedural factors known to influence outcomes. Results Higher BNP ratio at 30 days was associated with higher CV mortality or hospitalization between 30 days and 1 year (adjusted hazard ratio [aHR] 1.07 per increase of 1 in the BNP ratio, 95% CI 1.04–1.10, p<0.001), whereas baseline BNP ratio was not (p=0.38). A similar relationship was shown for the components of this composite: CV mortality (aHR 1.08, 95% CI 1.04–1.12, p<0.001) and hospitalizations (aHR 1.04, 95% CI 1.01–1.08, p=0.01). Adjusted for discharge BNP ratio and other factors, a greater decrease in BNP ratio between discharge and 30 days was also associated with lower CV mortality or hospitalization between 30 days and 1 year (aHR 0.95 per decrease of 1 in the BNP ratio, 95% CI 0.92–0.99, p=0.006). Similar relationships were observed for all-cause mortality and when examining the relationship between 1 year BNP ratio and outcomes between 1 and 2 years. Conclusion Higher BNP ratio after TAVI is associated with higher subsequent all-cause and CV mortality and hospitalizations, whereas baseline BNP ratio was not. Greater decrease in BNP ratio between discharge and 30 days is associated with better outcomes. Further investigation is warranted to understand these findings and determine whether intensification of medical therapy to decrease BNP after TAVR may improve patient outcomes. Acknowledgement/Funding The PARTNER 2 Trial was funded by Edwards Lifesciences

Surveillance and Management of Troponin Elevation after Vascular Surgery

Postopertive troponin elevation may occur without typical or atypical cardiac symptoms and is associated with an increased 30-day morbidity and mortality. The objective of the study was to implement a quality improvement initiative of postoperative troponin surveillance algorithm aimed at intensifying medical management after vascular surgery. We conducted a single-center study of postoperative troponin surveillance after vascular surgery (n=201) at a tertiary care, academic medical center from January to December 2016. Troponin surveillance was performed on postoperative days 1-3 after carotid endarterectomy, endovascular aortic repair, infrainguinal bypass, open abdominal aortic aneurysm repair, peripheral vascular intervention, and suprainguinal bypass, regardless of cardiac symptoms. Patients with troponin I elevation (>0.034ng/mL) were managed with a treatment algorithm which included single or dual antiplatelet (AP) agent, high-intensity statin therapy, smoking cessation consultation, and outpatient cardiology consultation and stress testing. Patients with troponin elevation ≥1.0ng/mL received inpatient cardiology consultation. We assessed adherence to the protocol for intensification of best medical therapy defined as high-dose statin therapy, increase in AP therapy, and smoking cessation consultation according to the established algorithm. Troponin elevation was recorded in 17% (34/201) of patients and was associated with cardiac symptoms in 8 patients (24%), while 26 (76%) patients had an asymptomatic abnormal troponin on postoperative surveillance. One patient was excluded due to death immediately after SUPRA, resulting in 200 patients. Troponin elevation ≥1.0ng/mL occurred in 11 asymptomatic patients (5.5%). Any intensification of medical therapy was instituted in 76% of patients with elevated troponin and included high-intensity statin therapy (58%), increase in AP therapy (18%), and smoking cessation consultation (66%). Once an elevated troponin level was recognized, 52% of our patients received cardiology consultation with an increased likelihood (100%) in patients with troponin ≥1ng/mL (P<0.001). Adherence to outpatient stress testing was 66%. Intensification of medical therapy was not significantly different between patients with abnormal troponin values, >0.034-1.0 (n=23) versus ≥1.0ng/mL (n=10); statin therapy (P=1.0), AP (P=0.34), and smoking cessation (P=1.0). One-year mortality was higher in patients with postoperative troponin elevation than those with normal postoperative troponin levels (12% vs. 2.4%; P=0.03). Routine postoperative troponin surveillance results in intensification of statin therapy in patients with asymptomatic troponin elevation. Further study is needed to determine if this approach reduces long-term cardiovascular morbidity and mortality.

Under-recognised ethical dilemmas of diabetes care in resource-poor settings.

Ineffective diabetes management results in suboptimal glycaemic control and adverse health outcomes. In resource-poor settings, a combination of high burden of medication nonadherence in patients and therapeutic inertia amongst clinicians is largely attributed to the failure to achieve glycaemic targets in diabetic populations. The potential health risks from intensification of medical therapy for aggressive lowering of glucose levels in Type 2 diabetes patients represents an ethical dilemma between averting risk from overtreatment and preventing future harm from raised blood glucose levels. However, the ethical dilemmas experienced by clinicians in most of the developing world when contemplating prescription of additional oral hypoglycaemic agents or initiating insulin have received little attention from the medical community. Such ethical dilemmas unique to resource-poor settings often emerge from poor availability of drugs, diagnostics and physician consultation time for diabetic patients. Furthermore, existing evidence-based guidelines for diabetes management assume a standard of care which is lacking in such settings. This often compels the developing world clinicians when confronted with such diabetes-related ethical dilemmas to rely solely on their clinical judgement which could be ethically unjust and medically prone to error. Newer research needs to generate evidence to develop best practice guidelines for optimal therapeutic outcomes, while acknowledging the reality of limited healthcare services available in resource-poor settings.

Post-operative recurrence of Crohn's disease after definitive stoma: an underestimated risk.

Crohn's disease (CD) is a progressive inflammatory disease affecting the entire gastrointestinal tract. The need for a definitive stoma (DS) is considered as the ultimate phase of damage. It is often believed that the risk of further disease progression is small when a DS has been performed. The goals of the study were to establish the rate of CD recurrence above the DS and to identify predictive factors of CD recurrence at the time of DS. We retrospectively reviewed all medical records of consecutive CD patients having undergone DS between 1973 and 2010. We collected clinical data at diagnosis, CD phenotype, treatment, and surgery after DS and mortality. Stoma was considered as definitive when restoration of continuity was not possible due to proctectomy, rectitis, anoperineal lesions (APL), or fecal incontinence. Clinical recurrence (CR) was defined as the need for re-introduction or intensification of medical therapy, and surgical recurrence (SR) was defined as a need for a new intestinal resection. Eighty-three patients (20 males, 63 females) with a median age of 34years at CD diagnosis were included. The median time between diagnosis and DS was 9years. The median follow-up after DS was 10years. Thirty-five patients (42%) presented a CR after a median time of 28months (2-211) and 32 patients (38%) presented a SR after a median time of 29months (4-212). In a multivariate analysis, APL (HR=5.1 (1.2-21.1), p=0.03) and colostomy at time of DS (HR=3.8 (1.9-7.3), p=0.0001) were associated factors with the CR. After DS for CD, the risk of clinical recurrence was high and synonymous with surgical recurrence, especially for patients with APL and colostomy.

Symptom Severity and Clinical Variables of Polycythemia Vera Patients with Splenomegaly, Phlebotomy Requirements and/or Hydroxyurea Use: a Retrospective Evaluation of 1334 Patients

BackgroundPolycythemia vera (PV) is a clonal myeloproliferative disorder characterized by erythrocytosis, splenomegaly and a frequently burdensome symptom profile. Despite current guidelines of aspirin, phlebotomy, and selective cytoreduction, many patients have inadequately controlled PV-related symptoms and/or disease features. We performed a comparison of PV symptom burden/disease feature phenotypes to understand unmet needs in current medical management.MethodsData was collected prospectively amongst an international cohort of PV patients including symptom burden, demographics, and disease features. Subgroups were identified who had previously failed hydroxyurea (PV-HU), required ongoing phlebotomy (PV-P), had palpable splenomegaly (PV-S), or had all 3 features (PV-HUPS). Control groups were derived from the remaining PV patients lacking the specified subgroup trait; patients in whom the trait status was unknown were excluded from each respective control group. All participants completed the MPN specific symptom burden questionnaire (MPN-SAF TSS (MPN-10 – Table 1)) and had no prior history of splenectomy. Surveyed symptoms on the MPN-10 included the patient’s perceptions of common MPN-related symptoms and overall quality of life (QOL) on a 0 (absent) to 10 (worst imaginable) scale. PV risk scores were calculated using the 2013 criteria (Leukemia 2013). Comparison of symptoms between groups employed t-tests.ResultsPatient Demographics and Disease Features Between Phenotypic GroupsA total of 1334 PV patients completed the MPN-10, and were assigned to categories of PV-HU (499 [37%]), PV-P (646 [48%]), PV-S (369, [28%]), and PV-HUPS (148 [12%]). The demographics between these groups were similar (comparable age (median range 60-63), PV risk scores (mean risk range: Low 16.4-23.7%; Intermediate 31.4%-36.6%; High 42.8%-47%). Mean hemoglobin was similar among PV subgroups (range 14.4-14.9); PV-HUPS had a higher mean WBC count (20.3 g/dL vs. 8.8-11.8 g/dL) and platelet count (703.5 x 10(9)/L vs. 327.5-462.8 x 10(9)/L), and disease duration (11.5 years vs. 6.4-8.8 years). Prior thrombosis was most common in PV-S patients (28.5% vs. 21.8-25.2%) and prior hemorrhage was most common in PV-HUPS patients (23.8% vs. 13.7-15.8%).Symptom BurdenThe MPN-10 scores of each problematic PV phenotype (HU, P, S, HUPS) were compared to the remainder of the PV cohort lacking the trait (PV-control; Table 1). Both individual symptom scores and TSS were highest for PV-HUPS patients (mean TSS 32.5 vs. 27.7-29.2). All problematic PV subgroups demonstrated significant differences for individual symptoms and TSS compared to PV-control. Comparing “problematic” subgroup responses, PV-HU patients described more inactivity whereas PV-S patients described more early satiety and pruritus. No statistical differences were noted in PV-HU, PV-P and PV-HUPS patient responses to MPN-10 items of “fever” and “weight loss”.DiscussionPV patients who have either failed HU, are undergoing phlebotomy and/or have splenomegaly exhibit moderate to severe symptomatology and demonstrate unmet medical need for management. As evidenced in this study, considerable overlap in symptomatology exists in PV-HU, PV-P, PV-S and PV-HUPS. Current randomized trials of JAK inhibitors have demonstrated benefits in a PV-HUPS phenotype. This data suggests that PV patients with any evidence of inadequate control (PV-HU, P, or S) have similarly unmet needs and may be candidates for clinical trials, intensification of medical therapy or perhaps JAK inhibitor therapy. [Display omitted] DisclosuresKiladjian:Shire Pharmaceuticals: Honoraria, Membership on an entity’s Board of Directors or advisory committees. Zweegman:Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Millennium: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Besses:Shire Pharmaceuticals: honoraria for educational lectures Other. Birgegard:Shire Pharmaceuticals: Consultancy, Honoraria, Research Funding. Etienne:Novartis, BMS, Pfizer, Ariad: Honoraria. Roy:Merck: Peg-Interferon provided for academic clinical trial in CML Other. te Boekhorst:Novartis: Consultancy. Griesshammer:Novartis: Honoraria; Shire: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; Roche: Honoraria. Mesa:Incyte Corporation, CTI, NPS Pharma, Inc., Gilead Science Inc., Celgene: Research Funding.

Therapie chronisch-entzündlicher Darmerkrankungen

Inflammatory Bowel Disease (i. e. Crohn's Disease and Ulcerative Colitis) show a rising incidence throughout Switzerland. An early and individualized therapy usually enables the effective treatment of both diseases and prevents structural gastrointestinal damage or surgical interventions. The goal of medical therapy is not only the relief of symptoms but rather the control of the disease's activity leading to mucosal healing and "deep" remission. Patients with unfavorable predictive parameters should receive a prompt intensification of medical therapy (as "early step-up" or even "top-down") with established immunosuppressive agents. Several updated practice guidelines respond to the most important medical questions, however, distinct clinical experience as well as a special dedication to these challenging patients are still a prerequisite for the effective and sustained therapy of inflammatory bowel disease.

P534 Endoscopic balloon dilatation and/or intensification of medical therapy can achieve and maintain remission in patients with symptomatic intestinal strictures of Crohn's disease

P534 Endoscopic balloon dilatation and/or intensification of medical therapy can achieve and maintain remission in patients with symptomatic intestinal strictures of Crohn's disease

Computed Tomographic Cardiovascular Imaging

Over the last decade, there has been increased recognition that atherosclerosis imaging adds greatly to the ability to identify patients at high risk for cardiac events. Technologies such as electron beam computed tomography and carotid intimal media thickness have contributed significantly to our understanding of the prevalence of preclinical atherosclerosis and its consequences. Current data suggest that elevated calcium scores are predictive of future cardiac events, independently and incrementally to traditional cardiac risk factors. The approximate predictive power is 10-fold for scores > 100, based upon current studies now reported. Guidelines and policy toward these modalities have shifted, with increased recognition of the importance among experts in cardiology, lipidology, and preventive medicine. Because most adverse events related to atherosclerosis occur in individuals at an intermediate risk, data suggest that it will be most cost-effective to concentrate screening efforts on this group of patients. This article reviews the current understanding of the value of coronary artery calcium screening in asymptomatic and symptomatic patients. Accurate measurement of subclinical coronary atherosclerosis should significantly improve the accuracy of global cardiovascular risk prediction, and allow for tracking of atherosclerosis burden, as well as better prediction of future cardiovascular events. Finally, by identifying high-risk patients, CAC may help select those patients who would benefit most from additional testing (e.g., non-invasive stress imaging) and intensification of medical therapy; CAC should have a significant impact on early detection and management of CAD.