Retrospective study of propionic acidemia using natural language processing in Mayo Clinic electronic health record data.

BACKGROUND: Propionic acidemia (PA) is a rare autosomal recessive organic acidemia that classically presents within the first days of life with a metabolic crisis or via newborn screening and is confirmed with laboratory tests. Limited data exist on the natural history of patients with PA describing presentation, treatments, and clinical outcomes. OBJECTIVE: To retrospectively describe the natural history of patients with PA in a clinical setting from a real-world database using both structured and unstructured electronic health record (EHR) data using novel data extraction techniques in a unique care setting. DESIGN/METHODS: This retrospective study used EHR data to identify patients with PA seen at the Mayo Clinic. Unstructured clinical text (medical notes, pathology reports) were analyzed using augmented curation natural language processing models to enhance analysis of data extracted by structured data fields (International Classification of Diseases 9th or 10th revision [ICD-9/-10] codes, Current Procedural Terminology [CPT] codes, and medication orders). De-identified health records were also manually reviewed by clinical scientists to ensure data accuracy and completeness. The index date was defined as the patient's date of PA diagnosis at the Mayo Clinic. Results were reported as aggregate descriptive statistics relative to patients' index dates. Complications, therapeutic interventions, laboratory tests, procedures, and hospitalization encounters related to PA were described at and within 6 months of the patient's index date, and from medical history available before the index date. RESULTS: In total, 13 patients with PA were identified, with visits occurring from 1998 to 2022. Age at diagnosis ranged from birth to 3 years; age at initial evaluation at the Mayo Clinic ranged from 3 days to 28 years. The mean number of Mayo Clinic outpatient visits was 31 (median duration of care, 2 years). PA-related complications were documented in 85% of patients and included nutritional difficulties (46%), metabolic decompensation events (MDEs; 38%), neurologic abnormalities (38%), and cardiomyopathy (7%). One pair of affected siblings had mild symptoms and no complications or MDEs. All 5 patients with a history of MDEs presented with developmental delays. Among patients with MDEs, the mean frequency of outpatient clinical care visits was 10 per year, and 3 patients required inpatient hospitalization (mean duration, 16 days). The incidence of severe complications was higher among patients with MDEs than those without MDEs. Of the patients with MDEs, 2 experienced crises while receiving treatment at the Mayo Clinic, with 9 total MDEs occurring between the 2 patients. Symptoms at presentation included hyperammonemia (78%), fever and/or decreased nutritional intake (67%), hyperglycemia/hypoglycemia (56%), intercurrent upper respiratory infection and/or lethargy (44%), constipation (33%), altered mental status (33%), and cough (33%). CONCLUSIONS: This study highlights the range and frequency of clinical outcomes experienced by patients with PA and demonstrates the clinical burden of MDEs.

Inhibition of p38 MAP kinase in patients with ST-elevation myocardial infarction - findings from the LATITUDE-TIMI 60 trial.

BACKGROUND: p38 mitogen activated kinase (MAPK) mediates the response to pro-inflammatory cytokines following myocardial infarction (MI) and is inhibited by losmapimod. METHODS: LATITUDE-TIMI 60 (ClinicalTrials.gov NCT02145468) randomized patients with MI to losmapimod or placebo for 12 weeks (24 weeks total follow-up). In this pre-specified analysis, we examined outcomes based on MI type [ST-segment elevation MI (STEMI) (865, 25%) and non-STEMI (2624, 75%)]. RESULTS: In patients with STEMI, inflammation, measured by hs-CRP, was significantly attenuated with losmapimod at 48 hours (P <0.001) and week 12 (P = 0.01). Losmapimod lowered NT-proBNP in patients with STEMI at 48 hours (P = 0.04) and week 12 (P = 0.02). The effects of losmapimod on CV death (CVD), MI, or severe recurrent ischemia requiring urgent coronary artery revascularization at 24 weeks [MACE] differed in patients with STEMI (7.0% vs 10.8%; HR 0.65, 95%CI 0.41 - 1.03; P= 0.06) and NSTEMI (11.4% vs 8.5%; HR 1.30, 95%CI 1.02 - 1.66; P = 0.04; p[int] = 0.009). CVD or HHF among patients with STEMI were 5.6% (losmapimod) and 8.3% (placebo) (HR 0.66; 95%CI 0.40 - 1.11; P = 0.12) and in NSTEMI were 4.8% (losmapimod) and 4.4% (placebo) (HR 1.09; 95%CI 0.76 - 1.56) in patients with NSTEMI. CONCLUSIONS: Patients with STEMI treated with losmapimod had an attenuated inflammatory response. Our collective findings raise the hypothesis that mitigating the inflammatory response may result in different outcomes in patients with STEMI and NSTEMI. While the difference in outcomes is exploratory, these findings do support separate examination of patients with STEMI and NSTEMI and increased emphasis on heart failure in future investigation of modulators of inflammation in MI.

Effect of Losmapimod on Cardiovascular Outcomes in Patients Hospitalized With Acute Myocardial Infarction: A Randomized Clinical Trial.

IMPORTANCE: p38 Mitogen-activated protein kinase (MAPK)-stimulated inflammation is implicated in atherogenesis, plaque destabilization, and maladaptive processes in myocardial infarction (MI). Pilot data in a phase 2 trial in non-ST elevation MI indicated that the p38 MAPK inhibitor losmapimod attenuates inflammation and may improve outcomes. OBJECTIVE: To evaluate the efficacy and safety of losmapimod on cardiovascular outcomes in patients hospitalized with an acute myocardial infarction. DESIGN, SETTING, AND PATIENTS: LATITUDE-TIMI 60, a randomized, placebo-controlled, double-blind, parallel-group trial conducted at 322 sites in 34 countries from June 3, 2014, until December 8, 2015. Part A consisted of a leading cohort (n = 3503) to provide an initial assessment of safety and exploratory efficacy before considering progression to part B (approximately 22,000 patients). Patients were considered potentially eligible for enrollment if they had been hospitalized with an acute MI and had at least 1 additional predictor of cardiovascular risk. INTERVENTIONS: Patients were randomized to either twice-daily losmapimod (7.5 mg; n = 1738) or matching placebo (n = 1765) on a background of guideline-recommended therapy. Patients were treated for 12 weeks and followed up for an additional 12 weeks. MAIN OUTCOMES AND MEASURES: The primary end point was the composite of cardiovascular death, MI, or severe recurrent ischemia requiring urgent coronary revascularization with the principal analysis specified at week 12. RESULTS: In part A, among the 3503 patients randomized (median age, 66 years; 1036 [29.6%] were women), 99.1% had complete ascertainment for the primary outcome. The primary end point occurred by 12 weeks in 123 patients treated with placebo (7.0%) and 139 patients treated with losmapimod (8.1%; hazard ratio, 1.16; 95% CI, 0.91-1.47; P = .24). The on-treatment rates of serious adverse events were 16.0% with losmapimod and 14.2% with placebo. CONCLUSIONS AND RELEVANCE: Among patients with acute MI, use of losmapimod compared with placebo did not reduce the risk of major ischemic cardiovascular events. The results of this exploratory efficacy study did not justify proceeding to a larger efficacy trial in the existing patient population. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02145468.

Rationale and design of the LosmApimod To Inhibit p38 MAP kinase as a TherapeUtic target and moDify outcomes after an acute coronary syndromE trial.

BACKGROUND: p38 mitogen-activated protein kinase (MAPK) mediates cytokine production and amplification of the inflammatory cascade. Through inhibition of p38 MAPK, losmapimod appears to attenuate the inflammatory response in the vascular wall and thus may help stabilize plaques. STUDY DESIGN: The LATITUDE-TIMI 60 trial is a randomized, double-blind, placebo-controlled, parallel-group, multicenter study planned to be conducted in a 3-stage design. Overall, the trial is designed to include 25,500 patients hospitalized with non-ST-elevation or ST-elevation myocardial infarction (MI) randomized to oral losmapimod (7.5 mg twice daily) versus matching placebo. Part A consists of a leading cohort (n = 3,500) that will provide an initial assessment of safety and exploratory efficacy before progressing to part B. Part B (n = ~22,000) of the study is event driven and will provide the primary assessment of efficacy. An independent safety review will be conducted after 3,500 patients in part B1 to determine whether a more focused schedule of clinic visits and laboratory assessments can be implemented (part B2). All patients are to be treated with study drug until week 12 and followed up until week 24. The primary end point is the composite of cardiovascular death, MI, or severe recurrent ischemia requiring urgent coronary revascularization. The key secondary end point is the composite of cardiovascular death or MI. The trial is designed to provide ≥90% power for the primary end point. CONCLUSIONS: The LATITUDE-TIMI 60 trial will determine the efficacy and safety of short-term p38 MAPK inhibition with losmapimod in acute MI. The trial design adopts a stepwise approach to decision making and collection of data.

An effect of moderate hepatic impairment on the pharmacokinetics and safety of darapladib.

AIM/METHODS: This was a phase 1, open label, non-randomized study designed to assess the pharmacokinetics and safety/tolerability of 10 consecutive once daily 40 mg oral doses of darapladib in subjects with moderate hepatic impairment (n = 12) compared with matched healthy volunteers (n = 12). RESULTS: For total darapladib, a small increase in total and peak exposure was observed in the subjects with moderate hepatic impairment compared with the subjects with normal hepatic function. The area under the plasma concentration-time curve during a dosing interval of duration τ (AUC(0,τ), geometric mean 223 ng ml(-1) h [90% CI 158, 316 ng ml(-1 ) h], in moderate hepatic impaired subjects, vs. geometric mean 186 ng ml(-1 ) h [90% CI 159, 217 ng ml(-1 ) h], in healthy subjects) and maximum concentration (Cmax ) were 20% and 7% higher, respectively, in the subjects with moderate hepatic impairment than in the healthy control subjects and there was no change in time to maximum concentration (tmax ). Protein binding was performed to measure the amount of unbound drug vs. bound. Steady-state was achieved by day 10 for darapladib and its metabolites (M4, M3 and M10). Darapladib was generally well tolerated, with adverse events (AEs) reported by seven subjects in the hepatic impairment group and three subjects in the healthy matched group (five and one of which were drug-related AEs, respectively). The most common AEs were gastrointestinal. These AEs were mostly mild to moderate and there were no deaths, serious AEs or withdrawals due to AEs. CONCLUSIONS: The results of this phase 1 study show that darapladib (40 mg) is well tolerated and its pharmacokinetics remain relatively unchanged in patients with moderate hepatic impairment.

Presence of Erdheim-Chester disease and Langerhans cell histiocytosis in the same patient: a report of 2 cases.

The histiocytic disorders Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD), can both present with multisystem involvement, with the central nervous system and the bone, skin, neuroendocrine, cardiac, respiratory, and gastrointestinal systems potentially affected. The 2 entities occasionally can be difficult to distinguish. Both rarely affect the orbit and the central nervous system, and although there are rare reports of patients with coexistent LCH and ECD, there are no reported cases of the 2 diseases that involve both the orbital and neuroendocrine systems. We report 2 such cases, and review the literature of cases of LCH and ECD occurring in the same patient. The presentation of LCH and ECD in certain patients suggests a possible abnormality in the common CD34 progenitor cell. The coexistence of the 2 disease states should be suspected in patients with atypical presentations of either disorder.

Gender-based outcomes in percutaneous coronary intervention with drug-eluting stents (from the National Heart, Lung, and Blood Institute Dynamic Registry).

Gender-based outcomes have not been evaluated in unselected patients undergoing percutaneous coronary intervention (PCI) with drug-eluting stents (DESs). We investigated whether gender influences the relative safety and efficacy of DESs compared with bare metal stents (BMSs) in routine clinical practice. Using the National Heart, Lung, and Blood Institute Dynamic Registry, in-hospital and 1-year outcomes were stratified by gender in patients who received > or =1 DES (486 women, 974 men) or BMS (631 women, 1,132 men). There were significant baseline differences by gender, including older age and a higher prevalence of co-morbidities in women and more previous coronary artery disease in men. There were no gender-related differences in in-hospital myocardial infarction, coronary artery bypass grafting, and death in those treated with BMSs or DESs. Antiplatelet use and stent thrombosis (1.3% of women vs 1.2% of men, p = 0.85) were similar at 1 year with DESs. At 1 year, patients with DESs had a lower rate of repeat PCI (14.1% in women vs 9.5%, p = 0.02; 12.0% in men vs 8.8%, p = 0.02). Adjusted 1-year outcomes in patients with BMSs and DESs, including death and myocardial infarction, were independent of gender. Use of DESs was the only factor, other than age, that conferred a lower risk for the need for repeat PCI in women (relative risk 0.61, 95% confidence interval 0.41 to 0.89, p = 0.01) and men (relative risk 0.68, 95% confidence interval 0.51 to 0.91, p = 0.001). In conclusion, the widespread use of DESs is safe and has decreased clinically driven revascularization compared with BMSs equally in women and men.

Clinical progression of incidental, asymptomatic lesions discovered during culprit vessel coronary intervention.

BACKGROUND: With the reduction in restenosis rates by drug-eluting stents, there is new controversy concerning the optimal management of incidental, nontarget lesions identified during percutaneous coronary intervention (PCI). Such lesions have been treated conservatively because of risk of restenosis but now are being considered for PCI to prevent plaque instability. However, the impact of incidental stenoses on future cardiac events remains unknown. METHODS AND RESULTS: We performed a retrospective cohort study to determine the rate and features of clinical plaque progression using the National Heart, Lung, and Blood Institute Dynamic Registry of consecutive patients undergoing PCI at multiple centers in 1997 to 1998 and 1999. Of 3747 PCI patients, 216 (5.8%) required additional nontarget lesion PCI for clinical plaque progression at 1 year. Fifty-nine percent presented with new unstable angina, and 9.3% presented with nonfatal myocardial infarction. Patients with multivessel coronary artery disease during original PCI were more likely to require nontarget lesion PCI during follow-up (adjusted odds ratio, 1.72 [95% CI, 1.18 to 2.52] for 2 vessels; adjusted odds ratio, 3.37 [95% CI, 2.32 to 4.89] for 3 vessels). Angiographic review showed that the majority (86.9%) of lesions requiring subsequent PCI were < or =60% in severity during original PCI, with the mean lesion stenosis 41.8+/-20.8% at the time of the initial PCI and 83.9+/-13.9% during the recurrent event. CONCLUSIONS: Approximately 6% of PCI patients will have clinical plaque progression requiring nontarget lesion PCI by 1 year. Greater coronary artery disease burden confers a significantly higher risk for clinical plaque progression.

Effect of gender on prognosis following percutaneous coronary intervention for stable angina pectoris and acute coronary syndromes.

Women with non-ST-elevation acute coronary syndromes (NSTACSs) may have better outcomes than men, but the effect of NSTACSs in women undergoing percutaneous coronary intervention (PCI) has not been examined. We performed a prospective, multicenter, cohort study of consecutive patients who underwent PCI for NSTACS and stable angina during 3 National Heart, Lung, and Blood Institute Dynamic Registry recruitment waves (1997 to 2002) to examine the effect of female gender on adverse clinical events after PCI or stable angina for NSTACS. The primary end point was the combined rate of death, myocardial infarction, or rehospitalization for cardiac causes at 1 year. Compared with men with NSTACS (n = 2,124), women (n = 1,338) were older and more often had hypertension, diabetes mellitus, and history of heart failure (p <0.001 for all), whereas multivessel disease was less frequent (p <0.01). Procedural success and in-hospital adverse event rates were similar. Women with NSTACS had the highest 1-year rate of death/myocardial infarction/cardiac rehospitalization compared with women with stable angina pectoris (n = 462) or men (n = 995; women with NSTACS 37.6%, men with NSTACS 29.8%, women with stable angina 29.4%, men with stable angina 27.7%, p <0.001). The higher rate remained after adjustment for differences in baseline characteristics (adjusted hazard ratio 1.37, 95% confidence interval 1.20 to 1.56). Among women, NSTACS conferred a significantly higher risk for adverse events compared with stable angina (adjusted hazard ratio 1.41, p = 0.001), whereas the risk of adverse events was not different in men (adjusted hazard ratio 1.05, p = 0.5). In conclusion, women undergoing PCI for NSTACS have a higher risk of major adverse cardiac events than men or women undergoing PCI for stable angina.

Smooth muscle cells, but not myocytes, of host origin in transplanted human hearts.

BACKGROUND: There is increasing evidence to support a role for stem cells in the regeneration and repair of the human cardiovascular system. However, significant controversy still remains about the extent of chimerism present in blood vessels and myocytes of transplanted human hearts. METHODS AND RESULTS: We investigated the contribution of infiltrating host cells to human cardiac allografts by evaluating the origin of vascular smooth muscle cells and cardiac myocytes in hearts after orthotopic cardiac transplantation. Smooth muscle cells were identified in pathological human coronary artery specimens with antibodies against smooth muscle alpha-actin. DNA in situ hybridization for the human Y chromosome was then performed on the same samples to identify cells of male origin. Both myocytes and vascular smooth muscle cells were examined for the presence of the Y chromosome in sex-mismatched specimens. In positive control samples, 34.7% of nuclei contained a detectable Y chromosome; in sex-mismatched samples, 2.6% of the smooth muscle cells examined were of host origin. The Y chromosome in myocyte nuclei in male positive controls was detected; however, despite examination of >6000 myocyte nuclei in sex-mismatched specimens, we were unable to detect any nuclei with the clear presence of the Y chromosome. CONCLUSIONS: Vascular smooth muscle cells of infiltrating host cell origin can be found in human cardiac allografts. However, unlike prior reports, we found no evidence that chimerism is present in cardiac myocytes.

FilterWire distal embolic protection device for vein graft stenting: initial single-center experience.

BACKGROUND: Saphenous vein graft (SVG) intervention is associated with a significant incidence of major adverse cardiac events (MACE) related to distal vessel embolization. The FilterWire distal embolic protection device has recently been approved as an adjunct to SVG intervention. We report here our initial experience in a single center in 30 consecutive patients using this device in SVG stenting. HYPOTHESIS: This study examined the outcomes and complications associated with these devices, as well as whether proficiency with the devices increased with greater experience and whether there were measurable outcome differences between devices. METHODS: We retrospectively identified all patients in whom a FilterWire device was placed at our hospital between June 2001 and June 2004. RESULTS: The device was successfully deployed in 29 of 30 patients, and all patients were stented successfully. Overall MACE rate was 6.6%, consistent with reports in larger multicenter clinical trials. Transient decreases in flow were noted while the device was in place in six patients, but improved in five patients with device removal. CONCLUSIONS: This early experience in a single center using FilterWire embolic protection indicates that excellent clinical results can be obtained by the adoption of filter protection for SVG intervention, without evidence for a detrimental learning curve.

Utility of concentration-effect modeling and simulation in a thorough QT study of losmapimod.

A thorough QT study was conducted in healthy volunteers with losmapimod. Four treatment regimens were included: a therapeutic dose (7.5 mg BID for 5 days), a supratherapeutic dose (20 mg QD for 5 days), a positive control (400 mg moxifloxacin single dose on Day 5), and placebo for 5 days. Baseline and on treatment ECGs were measured on Day 1 (3 timepoints predose) and Day 5, respectively. The primary statistical analysis failed to demonstrate a lack of effect of losmapimod on the QT interval leading to a positive finding. However, simulations using the concentration-effect model established for QTcF vs. losmapimod concentration at concentrations 4× the maximum concentration of the therapeutic dose did not exceed the regulatory thresholds of concern of 5 milliseconds for the mean (4.57 milliseconds) and 10 milliseconds for the upper bound of the 90%CI (90%CI 2.88, 6.10). Modeling demonstrated that the discrepant results may have been due to a baseline shift after repeat dosing and baseline differences between the treatments. Considering the results of the concentration-effect modeling, previous losmapimod data, and the high false-positive rate associated with the ICH E14 statistical analysis, the statistical analysis was likely a false-positive.

Placental growth factor and B-type natriuretic peptide as independent predictors of risk from a multibiomarker panel in suspected acute coronary syndrome (Acute Risk and Related Outcomes Assessed With Cardiac Biomarkers [ARROW]) study.

Most patients presenting to the emergency department with possible cardiac symptoms have low cardiac troponin (cTn) concentrations. A combination of biomarkers that improves risk stratification in patients at very low risk for major adverse cardiovascular events (MACEs) would be beneficial. In this multicenter prospective cohort study, specimens from 598 subjects presenting to 5 emergency departments with suspected acute coronary syndromes were collected on arrival and serially for traditional and novel biomarkers. Subjects were evaluated for MACEs, defined as death, myocardial infarction, or revascularization at 30 and 365 days. Classification and regression tree analysis assessed biomarker and clinical factors associated with MACEs. The 1-year rate of MACE was 10.5% (47 of 449). Rates of death, myocardial infarction, and revascularization were 4.2%, 1.6%, and 4.7%, respectively. The combination of B-type natriuretic peptide (BNP), placental growth factor (PlGF), and estimated glomerular filtration rate (eGFR) was the most accurate predictor of MACEs compared to any other biomarker or clinical factors including cTnI. If BNP was ≤ 65 ng/L and PlGF was ≤ 19.5 ng/L, the negative predictive value for 1-year MACEs was 99.1%. Conversely, BNP >150 ng/L and eGFR ≤ 68 ml/min/1.73 m(2) predicted a very high (36.5%) MACE rate. Prognostic values of BNP and PlGF were incremental (none increased, 2 of 212, 0.9%; only PlGF increased, 30 of 170, 17.6%; only BNP increased, 33 of 153, 21.6%; BNP and PlGF increased, 18 of 86, 20.9%). Considering only initial emergency department samples, 97% and 96% of patients with normal PlGF, BNP, and cTnI levels were event-free at 30 and 365 days, respectively. In conclusion, the combination of BNP, PlGF, and eGFR is the most accurate in risk-stratifying patients with suspected acute coronary syndrome.

Comparison of drug-eluting and bare metal stents for saphenous vein graft lesions (from the National Heart, Lung, and Blood Institute Dynamic Registry).

The effectiveness and safety of drug-eluting stents (DES) compared with bare-metal stents (BMS) in saphenous vein graft (SVG) disease remains unclear. In particular, there is a paucity of data on long-term outcomes. In this study, 395 patients enrolled in the National Heart, Lung, and Blood Institute Dynamic Registry who underwent stenting of SVG lesions with BMS (n = 192) from 1999 to 2006 or DES (n = 203) from 2004 to 2006 were analyzed. Patients were followed prospectively for the occurrence of cardiovascular events and death at 3 years. Patients treated with DES were more likely to have diabetes mellitus and other co-morbidities and previous percutaneous coronary intervention. Treated lesions in DES patients were more complex than those in BMS patients. At 3 years of follow-up, the adjusted risk for target vessel revascularization (hazard ratio 1.03, 95% confidence interval 0.65 to 1.62, p = 0.91) and death or myocardial infarction (hazard ratio 0.72, 95% confidence interval 0.49 to 1.04, p = 0.08) was similar in patients treated with DES and those treated with BMS. The combined outcome of death, myocardial infarction, or target vessel revascularization excluding periprocedural myocardial infarction was also similar (adjusted hazard ratio 0.82, 95% confidence interval 0.62 to 1.09, p = 0.16). In conclusion, this multicenter nonrandomized study of unselected patients showed no benefit of DES in SVG lesions, including no reduction in target vessel revascularization, compared with BMS at 3 years. An adequately powered randomized controlled trial is needed to determine the optimal stent type for SVG percutaneous coronary intervention.

Patient satisfaction is comparable to early discharge versus overnight observation after elective percutaneous coronary intervention.

BACKGROUND: Previous investigation has suggested that early discharge after percutaneous coronary intervention (PCI) is feasible and safe, but these studies have utilized largely radial approaches or been conducted in non-U.S. cohorts. We sought to assess patient satisfaction, safety and cost of a strategy of selective early discharge in U.S. patients undergoing PCI via a femoral approach with contemporary adjunctive pharmacologic and hemostasis agents. METHODS AND RESULTS: Patients with stable coronary artery disease undergoing elective PCI were prospectively recruited and randomized to either routine care, with an overnight hospital stay, versus early discharge 2 hours following successful PCI with adjunctive bivalirudin therapy and a femoral arterial closure device at the end of the procedure. The primary endpoints were safety and patient satisfaction as measured by a validated patient satisfaction survey during the index hospital stay and at 30 days. A total of 39 patients were randomized, with 20 to routine care and 19 to early discharge. There was no difference in major safety endpoints including death, non-fatal MI, urgent target lesion revascularization and thrombolysis in myocardial infarction (TIMI) major bleeding, with none in either group. Mean patient satisfaction scores were similar and high in both groups (89.6 for early discharge patients and 90.7 for routine care patients, p = 0.68). There was lower cost in the early discharge group, with a mean cost of 8,604 USD versus 10,565 USD in the routine care group (mean difference 1,961 USD, 95% confidence interval, -96 USD to 4,017 USD). CONCLUSION: Patients undergoing elective PCI for stable coronary artery disease may have similar safety and satisfaction with early discharge when using a careful strategy that incorporates optimal stent and hemostasis results and contemporary adjunctive anticoagulation therapy, with lower cost. This strategy may serve as a basis for a larger-scale randomized trial.

Factors associated with poorer prognosis for patients undergoing primary percutaneous coronary intervention during off-hours: biology or systems failure?

OBJECTIVES: We sought to determine whether poorer outcomes in patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (MI) during off-hours are related to delays in treatment, circadian changes in biology, or differences in operator-related quality of care. BACKGROUND: Previous investigation has suggested that patients undergoing primary PCI during off-hours are more likely to have adverse cardiac events than routine-hours patients, but the reasons for this remain poorly defined. METHODS: Clinical, angiographic, and procedural characteristics were compared in consecutive patients (n = 685) undergoing primary PCI in the National Heart, Lung, and Blood Institute Dynamic Registry between 1997 and 2006 that were classified as occurring during routine-hours (07:00 to 18:59) or off-hours (19:00 to 06:59). The primary end points were in-hospital death, MI, and target vessel revascularization. RESULTS: Median time from symptom onset to PCI was similar (off-hours 3.4 h vs. routine-hours 3.3 h). Patients presenting in off-hours were more likely to present with cardiogenic shock and multivessel coronary artery disease but were equally likely to present with complete occlusion of the infarct-related artery. Procedural complications including dissection were more frequent in off-hours patients. In-hospital death, MI, and target vessel revascularization were significantly higher in off-hours patients (adjusted odds ratio [OR]: 2.66, p = 0.001), and differences in outcomes were worse even if the procedure was immediately successful (adjusted OR: 2.58, p = 0.005, adjusting for angiographic success). Patients undergoing PCI on weekends had better outcomes during the daytime than nighttime. CONCLUSIONS: Patients undergoing primary PCI for acute MI during off-hours are at significantly higher risk for in-hospital death, MI, and target vessel revascularization. These findings appear related to both diurnal differences in presentation and lesion characteristics, as well as differences in procedural complication and success rates that extend beyond differences in symptom-to-balloon time.

Volume-to-creatinine clearance ratio: a pharmacokinetically based risk factor for prediction of early creatinine increase after percutaneous coronary intervention.

OBJECTIVES: This study sought to validate a pharmacokinetically derived measure of the risk of an early increase in serum creatinine after percutaneous coronary intervention (PCI). BACKGROUND: The ratio of the volume of contrast media to the creatinine clearance (V/CrCl) has been shown to correlate with the area under the curve of contrast media concentration over time. METHODS: We calculated V/CrCl in 3,179 consecutive patients undergoing PCI. An increase in serum creatinine of >0.5 mg/dl by 24 to 48 h was considered abnormal. Receiver-operator characteristic methods were used to identify the optimal sensitivity and specificity for the observed range of V/CrCl. The predictive value of V/CrCl for the risk of an early increase in creatinine was assessed using multivariable logistic regression. RESULTS: The overall incidence of an abnormal, early increase in creatinine was 1.5%. The mean and median values of V/CrCl for patients with (mean 5.2 +/- 4.4, median 4.3, interquartile range 2.7 to 6.0) and without (mean 3.0 +/- 2.0, median 2.5, interquartile range 1.7 to 3.8) an early creatinine increase were each significantly (p < 0.001) different between groups. Furthermore, there was a significant association between V/CrCl and an early increase in creatinine (overall and trend, p < 0.001). The receiver-operator characteristic curve analysis indicated that a V/CrCl ratio of 3.7 was a fair discriminator for the early creatinine increase (C-statistic 0.69). After adjusting for other known predictors of post-PCI creatinine increase, V/CrCl > or =3.7 remained significantly associated with an early abnormal increase in serum creatinine (odds ratio 3.84; 95% confidence interval 2.0 to 7.3, p < 0.001). CONCLUSIONS: A V/CrCl ratio >3.7 was a significant and independent predictor of an early abnormal increase in serum creatinine after PCI in this unselected patient population.