TEMPORAL TRENDS IN PERCUTANEOUS CORONARY INTERVENTION AND ASSOCIATED IMPACT ON CLINICAL AND PATIENT-REPORTED OUTCOMES

Cardiovascular disease remains the leading cause of mortality and morbidity in the 21st century accounting for about one-fifth of deaths overall each year in the United States. Percutaneous coronary intervention (PCI), used initially in the 1970s, is now the most commonly performed non-surgical procedure for atherosclerotic coronary disease. PCI, in the last three decades, witnessed rapid advancements, both technologically (from balloons to stents and atherectomy devices) as well as in adjunct therapy (antithrombotics, fibrinolytics and antiplatelet agents). The purpose of this dissertation, designed as three research papers, was to capture this evolution and the associated impact on clinical and patient-reported outcomes, in the prospective, multicenter NHLBI-sponsored 1985-86 PTCA (era of balloon angioplasty) and 1997-2004 Dynamic (era of stents, brachytherapy and drug-eluting stents) registries. Temporal trends in clinical practice revealed the heterogeneity in patients (and lesions) undergoing PCI and yet, consistent dramatic improvements were seen in procedural success with reduced need for repeat procedures; little impact was observed in one-year mortality rates. In the Dynamic Registry, significant reductions in one year prevalence and risk of patient-reported angina were observed concurrent to use of new evidence-based secondary pharmacological therapy. In contemporary practice, women and patients with prior/repeat PCI continued to be at high-risk for post-procedural symptoms. Supplemental therapy, following initial PCI, was more often pharmacological with concomitant reduction in bypass surgery and repeat PCI. On average, patient-reported quality of life improved over time and was influenced by both symptom status and the need and type of supplemental therapy. Indeed, these findings reflect the dynamic nature of PCI with an increasingly heterogeneous treatment population and yet favorable procedural outcomes (procedural success, reduced repeat procedures, greater relief of symptoms). More importantly, they highlight the continued lack of impact on mortality and identify symptom-prone subsets in contemporary practice. This time-sensitive documentation is especially fitting given the 300% increase in the number of PCIs since its initial use. From a public health point of view, any treatment modality applied in this magnitude warrants constant surveillance, more so with the emerging safety concerns, and this underscores the importance of well-designed registries

Is sclerostin antibody an effective agent for alveolar bone regeneration in animal models? A scoping review

Objectives The use of Sclerostin Antibody(Scl-Ab) as a bone anabolic agent has shown significant benefit in bone disorders in preclinical animal models and human clinical trials. Currently available evidence on the use of Scl-Ab in alveolar bone regeneration is limited to animal studies and hence this scoping review encompasses the animal studies conducted to ascertain the effectiveness of Scl-Ab on alveolar bone regeneration. Materials and methods The search strategy was aimed to locate published animal studies in which the treatment arm includes Sclerostin antibody administration for alveolar bone preservation or regeneration. The search terms used were (((Animal model) OR Rodent) AND Alveolar bone defect) AND Anti sclerostin antibody) OR Sclerostin antibody) AND Alveolar bone regeneration) OR Bone regeneration) AND Bone fill. Results Of the 559 results from Medline/PubMed, Scopus, Web of Science, Google scholar and additional articles from the references, six were included in the review. Scl-Ab was found to be effective in improving the bone quality and quantity. It was also observed that Scl-Ab was useful in reduced bone density associated with diseases and conditiona affecting osteoblast activity. Conclusion The review concluded that Scl-Ab promotes alveolar bone augmentation and improves bone quality without surgical interventions

Temporal trends in the management of severe hyperglycemia among patients hospitalized with acute myocardial infarction [abstract]

Poster sesssionBackground: Elevated blood glucose (BG) is associated with an adverse prognosis in acute myocardial infarction (AMI) patients. While guidelines recommend insulin therapy to lower markedly elevated BG in AMI patients, it is unknown whether these recommendations have impacted BG management over time. Methods: We studied 39,775 AMI patients hospitalized from 2000 to 2008 in 55 US medical centers contributing to Health Facts, a national database with extensive data on in-hospital BG and insulin use. Using all available BG measures during the hospital stay, we restricted our analysis to patients with a mean BG ≥200mg/dl and examined temporal trends in insulin use with hierarchical logistic regression models. Results: Overall, 4330 patients (11% of the entire cohort) had mean hospitalization BG ≥ 200 mg/dL and this proportion decreased from 2000 to 2008 (12% to 8%, p for trend<0.001); 75% of these patients had diabetes. In total, 61% of AMI patients with mean BG ≥ 200 received any insulin and only 16% received intravenous (IV) insulin during hospitalization. Hierarchical multivariable models showed an increased likelihood of insulin use over time (Figure). However, about one in three patients continued to receive no treatment for markedly elevated BG. Conclusions: Despite some improvement over time, insulin treatment rates among hospitalized AMI patients with severe, sustained hyperglycemia remain low. These findings likely reflect continuing uncertainty regarding optimal BG management during AMI

Trends in the Prevalence of Acute Kidney Injury in Patients with Acute Myocardial Infarction

Comparative Medicine - OneHealth and Comparative Medicine Poster SessionIntroduction: Acute kidney injury (AKI) is common in patients (pts) with acute myocardial infarction (AMI), and associated with permanent renal impairment and death. While guidelines increasingly emphasize the importance of AKI prevention, whether the rates of AKI changed over time is unknown. Methods: We studied 35,425 pts hospitalized with AMI in 66 U.S. centers from 2000-08 using Health Facts, a national database with detailed information on in-hospital renal function. AKI was defined as absolute creatinine increase of ≥ 0.3 mg/dL or relative increase of ≥50%. Temporal trends in AKI during the 9-year study period were evaluated using hierarchical logistic regression, adjusting for secular changes in baseline creatinine and other known AKI predictors. Results: From 2000-08, mean age increased (66.9 vs 68.8 yrs), as did baseline creatinine (1.4 vs 1.5 mg/dL), rate of cardiogenic shock (5.1 vs 6.3%), diabetes (30.4 vs 35.8%), coronary angiography (57 vs 68%), and PCI (30.2 vs 45.2%, P<0.001 for all comparisons). Despite increase in AKI risk factors, the rates of AKI declined steadily (Figure). The trend of decreasing AKI rates persisted after multivariable adjustment (P=0.01). Conclusions: While AKI still affects nearly 1 in 4 AMI pts, the rates of AKI declined significantly from 2000-08, despite the aging population and rising prevalence of AKI risk factors. These findings may reflect the impact of increased clinician awareness, better risk stratification, and AKI prevention efforts during this time period

Identification of novel single nucleotide polymorphisms associated with acute respiratory distress syndrome by exome-seq.

Acute respiratory distress syndrome (ARDS) is a lung condition characterized by impaired gas exchange with systemic release of inflammatory mediators, causing pulmonary inflammation, vascular leak and hypoxemia. Existing biomarkers have limited effectiveness as diagnostic and therapeutic targets. To identify disease-associating variants in ARDS patients, whole-exome sequencing was performed on 96 ARDS patients, detecting 1,382,399 SNPs. By comparing these exome data to those of the 1000 Genomes Project, we identified a number of single nucleotide polymorphisms (SNP) which are potentially associated with ARDS. 50,190SNPs were found in all case subgroups and controls, of which89 SNPs were associated with susceptibility. We validated three SNPs (rs78142040, rs9605146 and rs3848719) in additional ARDS patients to substantiate their associations with susceptibility, severity and outcome of ARDS. rs78142040 (C>T) occurs within a histone mark (intron 6) of the Arylsulfatase D gene. rs9605146 (G>A) causes a deleterious coding change (proline to leucine) in the XK, Kell blood group complex subunit-related family, member 3 gene. rs3848719 (G>A) is a synonymous SNP in the Zinc-Finger/Leucine-Zipper Co-Transducer NIF1 gene. rs78142040, rs9605146, and rs3848719 are associated significantly with susceptibility to ARDS. rs3848719 is associated with APACHE II score quartile. rs78142040 is associated with 60-day mortality in the overall ARDS patient population. Exome-seq is a powerful tool to identify potential new biomarkers for ARDS. We selectively validated three SNPs which have not been previously associated with ARDS and represent potential new genetic biomarkers for ARDS. Additional validation in larger patient populations and further exploration of underlying molecular mechanisms are warranted

Serum potassium levels and mortality in acute myocardial infarction

Clinical practice guidelines recommend maintaining serum potassium levels between 4.0 and 5.0 mEq/L in patients with acute myocardial infarction (AMI). These guidelines are based on small studies that associated low potassium levels with ventricular arrhythmias in the pre-β-blocker and prereperfusion era. Current studies examining the relationship between potassium levels and mortality in AMI patients are lacking.status: publishe