TCT-34 Reduction of Infarct Size in Anterior ST-Segment Elevation Myocardial Infarction (STEMI) With LAD Occlusion and LV Unloading Using a Micro-axial Pump for 30 Minutes Before PCI: Per-Protocol Analysis of the STEMI Door to Unload (DTU) Pilot Study

Background: The STEMI-DTU pilot trial identified that LV unloading before PCI is safe and feasible in anterior STEMI without shock. We now report findings from patients who met all protocol inclusion and exclusion criteria. Methods: In a multicenter, randomized safety and feasibility trial, 50 patients with anterior STEMI were unloaded using the Impella CP followed by immediate (U-IR) or delayed PCI after 30 minutes of unloading (U-DR). Cardiac magnetic resonance (CMR) imaging assessed infarct size 3-5 days after PCI. Patients without CMR at 3-5 days (n = 10; 5/arm), without PCI of a culprit LAD lesion (n = 2; 1/arm) and without STEMI (n = 5; 4 U-IR, 1 U-DR) were not per protocol and thus excluded. Results: 33 patients met all inclusion and exclusion criteria (U-IR n = 15, U-DR n = 18) with respective door-to-balloon times of 75 ± 26 and 89 ± 23 minutes (P = 0.10) and mean unload-to-balloon times of 10 ± 5 and 34 ± 3 (P \u3c 0.01). In the total cohort 2-5 day IS was significantly associated with microvascular obstruction (MVO), 30-day IS normalized to total LV mass, 90 day LVEF, and 90 day LV end systolic volume with or without delayed reperfusion (Table) (R \u3e 0.5, P \u3c 0.005 for all). Despite longer symptom to balloon times in the U-DR arm (174 ± 59 vs 228 ± 78, P \u3c 0.01) IS/AAR was lower in the U-DR arm (62 ± 16 vs 48 ± 16, P = 0.04) and remained lower irrespective of STE magnitude. MVO was lower in the U-DR arm among patients with the highest STE (Figure). Conclusion: A per-protocol analysis of the STEMI-DTU Pilot trial identified reduced infarct size with unloading and delayed reperfusion. These findings are under investigation in the STEMI-DTU Pivotal trial. Categories: CORONARY: Acute Myocardial Infarctio

Distinct Effects of Unfractionated Heparin versus Bivalirudin on Circulating Angiogenic Peptides

Background: Human studies of therapeutic angiogenesis, stem-cell, and progenitor-cell therapy have failed to demonstrate consistent clinical benefit. Recent studies have shown that heparin increases circulating levels of anti-angiogenic peptides. Given the widely prevalent use of heparin in percutaneous and surgical procedures including those performed as part of studies examining the benefit of therapeutic angiogenesis and cell-based therapy, we compared the effects of unfractionated heparin (UFH) on angiogenic peptides with those of bivalirudin, a relatively newer anticoagulant whose effects on angiogenic peptides have not been studied. Methodology/Principal Findings: We measured soluble fms-like tyrosine kinase-1 (sFLT1), placental growth factor (PlGF), vascular endothelial growth factor (VEGF), and soluble Endoglin (sEng) serum levels by enzyme linked immunosorbent assays (ELISA) in 16 patients undergoing elective percutaneous coronary intervention. Compared to baseline values, sFLT1 and PlGF levels increased by 26296313 % and 253654%, respectively, within 30 minutes of UFH therapy (p,0.01 for both; n = 8). VEGF levels decreased by 93.265 % in patients treated with UFH (p,0.01 versus baseline). No change in sEng levels were observed after UFH therapy. No changes in sFLT1, PlGF, VEGF, or sEng levels were observed in any patients receiving bivalirudin (n = 8). To further explore the direct effect of anticoagulation on circulating angiogenic peptides, adult, male wild-type mice received venous injections of clinically dosed UFH or bivalirudin. Compared to saline controls, sFLT1 an

Alterations of renal phenotype and gene expression profiles due to protein overload in NOD-related mouse strains

BACKGROUND: Despite multiple causes, Chronic Kidney Disease is commonly associated with proteinuria. A previous study on Non Obese Diabetic mice (NOD), which spontaneously develop type 1 diabetes, described histological and gene expression changes incurred by diabetes in the kidney. Because proteinuria is coincident to diabetes, the effects of proteinuria are difficult to distinguish from those of other factors such as hyperglycemia. Proteinuria can nevertheless be induced in mice by peritoneal injection of Bovine Serum Albumin (BSA). To gain more information on the specific effects of proteinuria, this study addresses renal changes in diabetes resistant NOD-related mouse strains (NON and NOD.B10) that were made to develop proteinuria by BSA overload. METHODS: Proteinuria was induced by protein overload on NON and NOD.B10 mouse strains and histology and microarray technology were used to follow the kidney response. The effects of proteinuria were assessed and subsequently compared to changes that were observed in a prior study on NOD diabetic nephropathy. RESULTS: Overload treatment significantly modified the renal phenotype and out of 5760 clones screened, 21 and 7 kidney transcripts were respectively altered in the NON and NOD.B10. Upregulated transcripts encoded signal transduction genes, as well as markers for inflammation (Calmodulin kinase beta). Down-regulated transcripts included FKBP52 which was also down-regulated in diabetic NOD kidney. Comparison of transcripts altered by proteinuria to those altered by diabetes identified mannosidase 2 alpha 1 as being more specifically induced by proteinuria. CONCLUSION: By simulating a component of diabetes, and looking at the global response on mice resistant to the disease, by virtue of a small genetic difference, we were able to identify key factors in disease progression. This suggests the power of this approach in unraveling multifactorial disease processes

Revisión de la literatura integradora acerca de intervenciones de la enfermería volcadas hacia el incremento del autocuidado entre pacientes con insuficiencia cardiaca

Objective: to analyze and summarize knowledge concerning critical components of interventions that have been proposed and implemented by nurses with the aim of optimizing self-care by heart failure patients.Methods: PubMed and CINAHL were the electronic databases used to search full peer-reviewed papers, presenting descriptions of nursing interventions directed to patients or to patients and their families and designed to optimize self-care. Forty-two studies were included in the final sample (n=4,799 patients).Results: this review pointed to a variety and complexity of nursing interventions. As self-care encompasses several behaviors, interventions targeted an average of 3.6 behaviors. Educational/counselling activities were combined or not with cognitive behavioral strategies, but only about half of the studies used a theoretical background to guide interventions. Clinical assessment and management were frequently associated with self-care interventions, which varied in number of sessions (1 to 30); length of follow-up (2 weeks to 12 months) and endpoints.Conclusions: these findings may be useful to inform nurses about further research in self-care interventions in order to propose the comparison of different modalities of intervention, the use of theoretical background and the establishment of endpoints to evaluate their effectiveness.Objetivo:analisar e sintetizar o conchecimento relacionado aos componentes críticos das intervençoes que têm, sido propostas e implementadas por enfermeiros(as) com objetivo de optimizar o auto-cuidado de pacientes portadores de insuficiência cardíaca.Método:PubMed e CINAHL foram as bases de dados electrônicas utilizadas para investigar artigos revisados por pares (peer review), apresentando as descrições das intervenções dirigidas ao paciente ou ao paciente e sua familia, visando melhorar o auto-cuidado. Foram incluídos 42 estudos na amostra final (n=4799 pacientes).Resultados:esta revisão apontou variedade e complexidade das intervenções de enfermagem. Como o auto-cuidado envolve diferentes comportamentos, as intervenções visaram em média 3,6 comportamentos. As Atividades de educação e aconselhamento foram combinadas ou não com estratégias cognitivo-comportamentais, mas somente a metade dos estudos utilizaram suporte teórico para guiar as intervenções. A avaliação e o manejo clínico foram frequentemente associados às intervenções de auto-cuidado, as quais variam em número de sessões (1 a 30), duração do seguimento (2 semanas a 12 meses) e desfechos.Conclusão:estes resultados podem ser úteis para guiar os enfermeiros no que se refere à futuros estudos sobre intervenções de auto-cuidado, de maneira a propor a comparação de diferentes modalidades de intervenção, uso de suporte teórico e estabelecimento de desfechos para melhor avaliar sua eficácia.Objetivo:analizar y sintetizar el conocimiento relacionado a componentes críticos de intervenciones que han sido propuestas e implementadas por enfermeros(as) con el objetivo de optimizar el autocuidado entre pacientes con insuficiencia cardiaca.Método:PUBMED y CINAHL han sido las bases de datos electrónicas usadas para investigar artículos revisados por pares (peer review), presentando descripciones de intervenciones destinadas a perfeccionar el autocuidado dirigido al paciente o al paciente y a su familia. Se incluyeron 42 estudios en la muestra final (n=4799 pacientes).Resultados:esta revisión apuntó a una variedad y complejidad de intervenciones de enfermería. Como el autocuidado abarca varios comportamientos, las intervenciones tuvieron como blanco, en media, 3,6 comportamientos. Actividades de educación/consejería fueron combinadas o no con estrategias cognitivo-comportamentales, pero tan solo cerca de la mitad de los estudios tenían aporte teórico para guiar intervenciones. La gestión y la evaluación clínica fueron frecuentemente asociadas a intervenciones de autocuidado, las cuales oscilaron en número de sesiones (1 a 30), duración del seguimiento (2 semanas a 12 meses) y objetivos.Conclusiones:estos resultados pueden ser útiles para informar a las enfermeras acerca de nuevas investigaciones en intervenciones de autocuidado, de modo a proponer la comparación de distintas modalidades de intervención, el uso de un aporte teórico y el establecimiento de objetivos para evaluar su eficacia

The importance of organizational characteristics for improving outcomes in patients with chronic disease: a systematic review of congestive heart failure

Luci K. Leykum, Jacqueline Pugh, Valerie Lawrence, and Polly H. Noel are with the South Texas Veterans Health Care System and Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio TX, 78229, USA -- Michael Parchman is with the South Texas Veterans Health Care System and Department of Family and Community Medicine, University of Texas Health Science Center at San Antonio, San Antonio TX, 78229, USA -- Reuben R. McDaniel Jr. is with the McComb's School of Business, University of Texas at Austin, Austin TX, USABackground: Despite applications of models of care and organizational or system-level interventions to improve patient outcomes for chronic disease, consistent improvements have not been achieved. This may reflect a mismatch between the interventions and the nature of the settings in which they are attempted. The application of complex adaptive systems (CAS) framework to understand clinical systems and inform efforts to improve them may lead to more successful interventions. We performed a systematic review of interventions to improve outcomes of patients with congestive heart failure (CHF) to examine whether interventions consistent with CAS are more likely to be effective. We then examine differences between interventions that are most effective for improving outcomes for patients with CHF versus previously published data for type 2 diabetes to explore the potential impact of the nature of the disease on the types of interventions that are more likely to be effective. Methods: We conducted a systematic review of the literature between 1998 and 2008 of organizational interventions to improve care of patients with CHF. Two independent reviewers independently assessed studies that met inclusion criteria to determine whether each reported intervention reflected one or more CAS characteristics. The effectiveness of interventions was rated as either 0 (no effect), 0.5 (mixed effect), or 1.0 (effective) based on the type, number, and significance of reported outcomes. Fisher's exact test was used to examine the association between CAS characteristics and intervention effectiveness. Specific CAS characteristics associated with intervention effectiveness for CHF were contrasted with previously published data for type 2 diabetes. Results and discussion: Forty-four studies describing 46 interventions met eligibility criteria. All interventions utilized at least one CAS characteristic, and 85% were either 'mixed effect' or 'effective' in terms of outcomes. The number of CAS characteristics present in each intervention was associated with effectiveness (p < 0.001), supporting the idea that interventions consistent with CAS are more likely to be effective. The individual CAS characteristics associated with CHF intervention effectiveness were learning, self-organization, and co-evolution, a finding different from our previously published analysis of interventions for diabetes. We suggest this difference may be related to the degree of uncertainty involved in caring for patients with diabetes versus CHF. Conclusion: These results suggest that for interventions to be effective, they must be consistent with the CAS nature of clinical systems. The difference in specific CAS characteristics associated with intervention effectiveness for CHF and diabetes suggests that interventions must also take into account attributes of the disease.McCombs School of [email protected]

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402