Indexing peak rapid filling velocity to both relaxation and filling volume to estimate left ventricular filling pressures.

AIMS: The peak transmitral velocity/peak mitral annular velocity (E/e') ratio has been used as a left ventricular (LV) filling pressure (LVFP) correlate. However, the E/e' and its changes with haemodynamic alterations have not always correlated with changes in LVFP's. We hypothesized that indexing E/e' to a measure of LV filling volume may enhance the correlation with LVFP and LVFP changes. METHODS AND RESULTS: We summarized previously obtained haemodynamic and Doppler echo data in 137 dogs with coronary microsphere embolization induced-chronic LV dysfunction prior to and following haemodynamic induced alterations in LVFP's. E/e' values were obtained as E*tau where tau is the inverse logarithmic LV pressure decay. E*tau was indexed to LV filling volume by dividing by the diastolic time velocity integral (DVI) and correlated with LV mean diastolic pressure (LVmDP). Similarly, the relationship of E/e' and E/e'/DVI to LV pre A wave pressure was evaluated in 84 patients by invasive haemodynamics and Doppler echo. Combining data from all interventions, LVmDP correlated with E*tau (r = 0.408) but more strongly with E*tau/DVI (r = 0.667, z = 3.03, P = 0.0008). The change in LVmDP correlated with the change in E*tau/DVI (r = 0.742) more strongly than E*Tau (r = 0.187, Z = 4.01, P < 0.0001). In the patient cohort, E/e' was modestly correlated with LV pre A wave pressure (r = 0.301) but more strongly correlated with E/e'/DVI (r = 0.636, z = 2.36, P = 0.0161). CONCLUSION: Indexing E to both LV relaxation and filling volume results in a more robust relation with LVFP's and with LVFP changes.

Achieving timely percutaneous reperfusion for rural ST-elevation myocardial infarction patients by direct transport to an urban PCI-hospital.

BACKGROUNDS: ST-elevation myocardial infarction (STEMI) guidelines recommend reperfusion by primary percutaneous coronary intervention (PCI) ≤ 90 min from time of first medical contact (FMC). This strategy is challenging in rural areas lacking a nearby PCI-capable hospital. Recommended reperfusion times can be achieved for STEMI patients presenting in rural areas without a nearby PCI-capable hospital by ground transportation to a central PCI-capable hospital by use of protocol-driven emergency medical service (EMS) STEMI field triage protocol. METHODS: Sixty STEMI patients directly transported by EMS from three rural counties (Nassau, Camden and Charlton Counties) within a 50-mile radius of University of Florida Health-Jacksonville (UFHJ) from 01/01/2009 to 12/31/2013 were identified from its PCI registry. The STEMI field triage protocol incorporated three elements: (1) a cooperative agreement between each of the rural emergency medical service (EMS) agency and UFHJ; (2) performance of a pre-hospital ECG to facilitate STEMI identification and laboratory activation; and (3) direct transfer by ground transportation to the UFHJ cardiac catheterization laboratory. FMC-to-device (FMC2D), door-to-device (D2D), and transit times, the day of week, time of day, and EMS shift times were recorded, and odds ratio (OR) of achieving FMC2D times was calculated. RESULTS: FMC2D times were shorter for in-state STEMIs (81 ± 17 vs. 87 ± 19 min), but D2D times were similar (37 ± 18 vs. 39 ± 21 min). FMC2D ≤ 90 min were achieved in 82.7% in-state STEMIs compared to 52.2% for out-of-state STEMIs (OR = 4.4, 95% CI: 1.24-15.57; P = 0.018). FMC2D times were homogenous after adjusting for weekday vs. weekend, EMS shift times. Nine patients did not meet FMC2D ≤ 90 min. Six were within 10 min of target; all patient achieved FMC2D ≤ 120 min. CONCLUSIONS: Guideline-compliant FMC2D ≤ 90 min is achievable for rural STEMI patients within a 50 mile radius of a PCI-capable hospital by use of protocol-driven EMS ground transportation. As all patients achieved a FMC2D time ≤ 120 min, bypass of non-PCI capable hospitals may be reasonable in this situation.

Routine diversion of patients with STEMI to high-volume PCI centres: modelling the financial impact on referral hospitals.

OBJECTIVE: To quantify possible revenue losses from proposed ST-elevation myocardial infarction (STEMI) patient diversion policies for small hospitals that lack high-volume percutaneous coronary intervention (PCI) capability status (ie, 'STEMI referral hospitals'). BACKGROUND: Negative financial impacts on STEMI referral hospitals have been discussed as an important barrier to implementing regional STEMI bypass/transfer protocols. However, there is little empirical data available that directly quantifies this potential financial impact. METHODS: Using detailed financial charges from Florida hospital discharge data, we examined the potential negative financial impact on 112 STEMI referral hospitals from losing all inpatient STEMI revenue. The main outcome was projected revenue loss (PRL), defined as total annual patient with STEMI charges as a proportion of total annual charges for all patients. We hypothesised that for most community hospitals (>90%), STEMI revenue represented only a small fraction of total revenue (<1%). We further examined the financial impact of the 'worst case' scenario of loss of all acute coronary syndrome (ACS) (ie, chest pain) patients. RESULTS: PRLs were $0.33 for every $100 of patient revenue statewide for STEMI and $1.73 for ACS. At the individual hospital level, the 90th centile PRL was $0.74 for STEMI and $2.77 for ACS. PRLs for STEMI were not greater in rural areas compared with major metropolitan areas. Hospital revenue centres that would be most impacted by loss of patients with STEMI were cardiology procedures and intensive care units. CONCLUSIONS: Loss of patient with STEMI revenues would result in only a small financial impact on STEMI referral hospitals in Florida under proposed STEMI diversion/rapid transfer protocols. However, spillover loss of patients with ACS would increase revenue loss for many hospitals.

Association of cardiac events with coronary artery disease detected by 64-slice or greater coronary CT angiography: a systematic review and meta-analysis.

BACKGROUND: The value of ≥64-slice coronary CT angiography (CCTA) to determine odds of cardiac death or non-fatal myocardial infarction (MI) needs further clarification. METHODS: We performed a systematic review and meta-analysis using publications reporting events/severity of coronary artery disease (CAD) in patients with suspected CAD undergoing CCTA. Patients were divided into: no CAD, non-obstructive CAD (maximal stenosis <50%), and obstructive CAD (≥50% stenosis). Odds ratios with 95% confidence intervals were calculated using a fixed or random effects model. Heterogeneity was assessed using the I(2) index. RESULTS: We included thirty-two studies comprising 41,960 patients with 363 all-cause deaths (15.0%), 114 cardiac deaths (4.7%), 342 MI (14.2%), 69 unstable angina (2.8%), and 1527 late revascularizations (63.2%) over 1.96 (SD 0.77) years of follow-up. Cardiac death or MI occurred in 0.04% without, 1.29% with non-obstructive, and 6.53% with obstructive CAD. OR for cardiac death or MI was: 14.92 (95% CI, 6.78 to 32.85) for obstructive CAD, 6.41 (95% CI, 2.44 to 16.84) for non-obstructive CAD versus no CAD, and 3.19 (95% CI, 2.29 to 4.45) for non-obstructive versus obstructive CAD and 6.56 (95% CI, 3.07 to 14.02) for no versus any CAD. Similar trends were noted for all-cause mortality and composite major adverse cardiovascular events. CONCLUSIONS: Increasing CAD severity detected by CCTA is associated with cardiac death or MI, all-cause mortality, and composite major adverse cardiovascular events. Absence of CAD is associated with very low odds of major adverse events, but non-obstructive disease significantly increases odds of cardiac adverse events in this follow-up period.

An algorithm for identification of ST-elevation myocardial infarction patients by emergency medicine services.

OBJECTIVE: ST-elevation myocardial infarction (STEMI) identification by emergency medicine services (EMS) leading to pre-hospital catheterization laboratory (CL) activation shortens ischemic time and improves outcomes. We examined the incremental value of addition of a screening clinical tool (CT), containing clinical information and a Zoll electrocardiogram (ECG)-resident STEMI identification program (ZI) to ZI alone. METHODS: All EMS-performed and ZI-analyzed ECGs transmitted to a percutaneous coronary intervention hospital from October 2009 to January 2011 were reviewed for diagnostic accuracy. ZI performance was also compared to ECG interpretations by 2 experienced readers The CT was then retrospectively applied to determine the incremental benefit above the ZI alone. RESULTS: ST-elevation myocardial infarction was confirmed in 23 (7.5%) of 305 patients. ZI was positive in 37 (12.1%): sensitivity: 95.6% and specificity: 94.6%, positive predictive value (PPV), 59.5%, negative predictive value (NPV), 99.6%, and accuracy of 93.8%. Moderate agreement was observed among the readers and ZI. CT criteria for CL activation were met in 24 (7.8%): 20 (83.3%) were confirmed STEMIs: sensitivity: 86.9%, specificity: 98.5%, a PPV: 83.3%, and NPV: 98.6%, accuracy of 97.7%. CT + ZI increased PPV (P<0.05) and specificity (P<0.003) by reducing false positive STEMI identifications from 15 (4.9%) to 4 (1.3%). CONCLUSIONS: In an urban cohort of all EMS transmitted ECGs, ZI has high sensitivity and specificity for STEMI identification. Whereas the PPV was low, reflecting both low STEMI prevalence and presence of STEMI-mimics, the NPV was very high. These findings suggest that a simplified CT combined with computer STEMI interpretation can identify patients for pre-hospital CL activation. Confirmation of these results could improve the design of STEMI care systems.

Candidates for transcatheter aortic valve replacement: fitting the PARTNERS criteria.

OBJECTIVES: To determine an estimate patient volume with severe AS meeting PARTNER-B criteria, with the objective of providing insights into the annual volume needed to sustain a TAVR program. BACKGROUND: While the prevalence of AS is well documented, potential TAVR candidates remains less established. A better understanding of this population is critical for the development of TAVR programs. Though no clear volume has been determined, societies suggest a minimum of 20-24 annual cases to establish a TAVR program. METHODS: A total of 21,652 patients were screened from a single center echocardiography registry over a 3-year period. From them, 833 patients with AS were identified representing our study population. Severity was stratified by echocardiographic criteria. Those identified to have moderate-to-severe and severe AS were further investigated to determine clinical status and surgical candidacy. Nonsurgical candidates were cross referenced with the PARTNER-B exclusion criteria to determine eligibility for TAVR. RESULTS: Symptomatic AS was present in 133 patients (16%). Fifty (38%) were considered nonsurgical candidates. Nonsurgical patients had higher STS score (11.1 ± 10.8 vs. 4.0 ± 3.3, P < 0.001). After applying PARTNERS-B exclusion criteria, only 18 patients (14%) were considered TAVR candidates. These findings indicate that to meet the recommended annual volume of 20-24 TAVR cases, a minimum of 150-170 symptomatic severe AS patients are required. CONCLUSION: In real world clinical practice, the prevalence of AS meeting PARTNERS-B criteria for TAVR can be low. These findings suggest that either high volume valvular centers or regional referral centers will need to be considered as part of the strategy to incorporate this new technology into clinical practice.

De Facto regionalization of care for ST-elevation myocardial infarction in Florida, 2001-2009.

ACC/AHA guidelines recommend STEMI patients receive percutaneous coronary intervention (PCI) at high volume hospitals performing ≥400 procedures/year. The objective of this study was to evaluate changes in the organization and implementation of care for STEMI patients in Florida. We assessed trends and predictors of STEMI patients first hospitalized at high PCI volume hospitals in Florida from 2001-2009. This is the first study to examine statewide trends in hospital admission for all STEMI patients. We classified Florida hospitals by PCI volume (high, medium, low, non-PCI) for each quarter from January, 2001 through June, 2009. Using hospital discharge data, we determined the percent of STEMI patients who went to each type of hospital and analyzed multiple predictors. From 2001-2009 the proportion of STEMI patients first hospitalized at high PCI volume hospitals rose from 62.4 to 89.7%, while admissions to non-PCI hospitals declined from 31% to 4.9%. Persistent barriers to high PCI volume hospital admission were age ≥85 years (OR 0.56, 95% CI 0.50-0.62), female gender (OR 0.85, 95% CI 0.79-0.91), and residence in a major metropolitan county. Through the efforts of local coalitions throughout Florida, by 2009 almost 90% of Florida STEMI patients were first admitted to high PCI volume hospitals. Greater hospital competition may explain lower admission rates to high PCI volume hospitals in major metropolitan counties. The age and gender disadvantage we observed requires further research to determine potential causes.

Effects of exogenous ubiquitin in a polytrauma model with blunt chest trauma.

OBJECTIVE: To determine whether treatment with the CXC chemokine receptor 4 agonist ubiquitin results in beneficial effects in a polytrauma model consisting of bilateral femur fractures plus blunt chest trauma (Injury Severity Score 18-25). DESIGN: Treatment study. SETTING: Research laboratory. SUBJECTS: Seventeen Yorkshire pigs. INTERVENTIONS: Intravenous injection of 1.5 mg/kg ubiquitin or albumin (control) at 60 mins after polytrauma. MEASUREMENTS AND MAIN RESULTS: Anesthetized, mechanically ventilated pigs underwent polytrauma, followed by a simulated 60-min shock phase. At the end of the shock phase, ubiquitin or albumin were administered and animals were resuscitated to a mean arterial blood pressure of 70 mm Hg until t=420 mins. After intravenous ubiquitin, ubiquitin plasma concentrations increased 16-fold to 2870±1015 ng/mL at t=90 mins and decreased with t1/2=60 mins. Endogenous plasma ubiquitin increased two-fold in the albumin group with peak levels of 359±210 ng/mL. Plasma levels of the cognate CXC chemokine receptor 4 ligand stromal cell-derived factor-1α were unchanged in both groups. Ubiquitin treatment reduced arterial lactate levels and prevented a continuous decrease in arterial oxygenation, which occurred in the albumin group during resuscitation. Wet weight to dry weight ratios of the lung contralateral from the injury, heart, spleen and jejunum were lower with ubiquitin. With ubiquitin treatment, tissue levels of Interleukin-8, Interleukin-10, Tumor Necrosis Factor α, and stromal cell-derived factor-1α were reduced in the injured lung and of Interleukin-8 in the contralateral lung, respectively. CONCLUSIONS: Administration of exogenous ubiquitin modulates the local inflammatory response, improves resuscitation, reduces fluid shifts into tissues, and preserves arterial oxygenation after blunt polytrauma with lung injury. This study further supports the notion that ubiquitin is a promising protein therapeutic and implies CXC chemokine receptor 4 as a drug target after polytrauma.

Systemic release of cytokines and heat shock proteins in porcine models of polytrauma and hemorrhage*.

OBJECTIVE: To define systemic release kinetics of a panel of cytokines and heat shock proteins in porcine polytrauma/hemorrhage models and to evaluate whether they could be useful as early trauma biomarkers. DESIGN: Prospective observational study. SETTING: Research laboratory. SUBJECTS: Twenty-one Yorkshire pigs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Pigs underwent polytrauma (femur fractures/lung contusion, P), hemorrhage (mean arterial pressure 25-30 mm Hg, H), polytrauma plus hemorrhage (P/H), or sham procedure (S). Plasma was obtained at baseline, in 5- to 15-min intervals during a 60-min shock period without intervention, and in 60- to 120-min intervals during fluid resuscitation for up to 300 min. Plasma was assayed for interleukin-1ß, interleukin-4, interleukin-5, interleukin-6, interleukin-8, interleukin-10, interleukin-12/interleukin-23p40, interleukin-13, interleukin-17, interleukin-18, interferonγ, transforming growth factor-ß, tumor necrosis factor-α, heat shock protein 40, heat shock protein 70, and heat shock protein 90 by enzyme-linked immunosorbent assay. All animals after S, P, and H survived (n = 5/group). Three of six animals after P/H died. Interleukin-10 increased during shock after P and this increase was attenuated after H. Tumor necrosis factor-α increased during the shock period after P, H, and also after S. P/H abolished the systemic interleukin-10 and tumor necrosis factor-α release and resulted in 20% to 30% increased levels of interleukin-6 during shock. As fluid resuscitation was initiated, tumor necrosis factor-α and interleukin-10 levels decreased after P, H, and P/H; heat shock protein 70 increased after P; and interleukin-6 levels remained elevated after P/H and also increased after P and S. CONCLUSIONS: Differential regulation of the systemic cytokine release after polytrauma and/or hemorrhage, in combination with the effects of resuscitation, can explain the variability and inconsistent association of systemic cytokine/heat shock protein levels with clinical variables in trauma patients. Insults of major severity (P/H) partially suppress the systemic inflammatory response. The plasma concentrations of the measured cytokines/heat shock proteins do not reflect injury severity or physiological changes in porcine trauma models and are unlikely to be able to serve as useful trauma biomarkers in patients.

Prevalence of major infections and adverse outcomes among hospitalized. ST-elevation myocardial infarction patients in Florida, 2006.

BACKGROUND: ST-elevation myocardial infarction (STEMI) patients have risk factors and co-morbidities and require procedures predisposing to healthcare acquired infections (HAIs). As few data exist on the extent and consequences of infections among these patients, the prevalence, predictors, and potential complications of major infections among hospitalized STEMI patients at all Florida acute care hospitals during 2006 were analyzed. METHODS: Sociodemographic characteristics, risk factors, co-morbidities, procedures, complications, and mortality were analyzed from hospital discharge data for 11, 879 STEMI patients age ≥ 18 years. We used multivariable logistic regression modeling to examine and adjust for multiple potential predictors of any infection, bloodstream infection (BSI), pneumonia, surgical site infection (SSI), and urinary tract infection (UTI). RESULTS: There were 2,562 infections among 16.6% of STEMI patients; 6.2% of patients had ≥2 infections. The most prevalent HAIs were UTIs (6.0%), pneumonia (4.6%), SSIs (4.1%), and BSIs (2.6%). Women were at 29% greater risk, Blacks had 23% greater risk, and HAI risk increased 11% with each 5 year increase in age. PCI was the only protective major procedure (OR 0.81, 95% CI, 0.69-0.95, p < .05). HAI lengthened hospital stays. STEMI patients with a BSI were almost 5 times more likely (31.3% vs. 6.5%, p < .0001), and those with pneumonia were 3 times more likely (19.6% vs. 6.5%, p < .0001) to die before discharge. CONCLUSIONS: The protective effect of PCI on risk of infection is likely mediated by its many benefits, including reduced length of hospitalizations.

Transfer travel times for primary percutaneous coronary intervention from low-volume and non-percutaneous coronary intervention-capable hospitals to high-volume centers in Florida.

STUDY OBJECTIVE: Current guidelines recommend that ST-elevation myocardial infarction (STEMI) patients receive percutaneous coronary intervention less than or equal to 90 minutes from first medical contact, preferably at high-volume percutaneous coronary intervention centers (≥400 percutaneous coronary interventions annually). Because many patients present to low-volume or non-percutaneous coronary intervention-capable STEMI referral hospitals, timely percutaneous coronary intervention treatment requires effective transfer systems, which include interfacility transport times of less than 30 minutes. We investigate the geographic feasibility of achieving timely interfacility transport from STEMI referral hospitals to percutaneous coronary intervention hospitals in Florida. METHODS: Using 2006 Florida hospital discharge data, we calculated driving times between STEMI referral hospitals and the nearest medium-/high-volume percutaneous coronary intervention centers. We plotted transfer travel time cumulative proportion survival curves for hospitals and patients to assess the feasibility of transfer within 30 minutes to higher-volume facilities. Differences by geographic location (rural versus urban) and patient race/ethnicity were examined. RESULTS: In 2006, 77% of STEMI referral hospitals had transfer travel times within 30 minutes; 90th percentile for interhospital driving time was 56 minutes. For patients at STEMI referral hospitals, 85.6% were at facilities within a 30-minute drive of a high-/medium-volume percutaneous coronary intervention center; 90th percentile was 31 minutes. We found marked rural/urban disparities, with longer average driving times for patients in rural and small metropolitan counties. Significant racial/ethnic disparities in transfer travel times were not observed, although 90th percentile driving times were highest for blacks. CONCLUSION: Driving times do not pose a major geographic barrier to transfer of STEMI patients in Florida. A majority of STEMI patients could be transferred from STEMI referral hospitals to high-volume percutaneous coronary intervention centers within 30 minutes.

Percutaneous coronary intervention, comorbidities, and mortality among emergency department-admitted ST-elevation myocardial infarction patients in Florida.

BACKGROUND: Risk of mortality following an ST-elevation myocardial infarction (STEMI) can be significantly reduced by prompt percutaneous coronary intervention (PCI). National guidelines specify primary PCI as the preferred recommended treatment for STEMI. In this study, we examined same-day PCI as an independent predictor of in-hospital mortality, after adjustment for comorbidities, other patient factors, and hospital PCI-volume using unselected surveillance data from Florida. METHODS: We analyzed hospital discharge data for adults, 18+ years old, with a primary diagnosis of STEMI who were admitted to PCI-capable hospitals through the emergency department during 2001-2005 (n = 43,849). Hierarchical (multilevel) logistic regression models were used for analysis. RESULTS: Overall, 4,143 STEMI patients (9.4%) did not survive to hospital discharge. In late 2005, the in-hospital mortality rates were 1.9% for those who received same-day PCI versus 13.0% for those who did not. After adjustment for multiple patient factors, same-day PCI was a significant predictor of in-hospital survival with a strong protective effect (adjusted OR = 0.35, 95% CI 0.31-0.38 P < 0.0001). Restriction of the analysis to those patients who survived the first day of admission did not appreciably change this result (adjust OR = 0.37, 95% CI 0.33-0.42, P < 0.0001). Hospital PCI-volume did not significantly impact mortality risk. CONCLUSIONS: Same-day PCI markedly reduced the risk of in-hospital mortality among STEMI patients after multivariate adjustment. Serious comorbidities and complications, older age, and female gender continued to predict elevated risk of mortality after control for treatment status. Our results provide additional evidence in support of national clinical recommendations and aggressive treatment of STEMI.

Disparities in use of same-day percutaneous coronary intervention for patients with ST-elevation myocardial infarction in Florida, 2001-2005.

Primary percutaneous coronary intervention (PCI) is the recommended treatment for ST-elevation myocardial infarction (STEMI), according to American College of Cardiology and American Heart Association guidelines published in 1999 and 2004. In this study, hospital and patient predictors of same-day primary PCI use for STEMI were examined across the period from 2001 to 2005. Inpatient discharge data for adults aged > or =18 years with primary diagnoses of STEMI who were admitted to Florida hospitals through emergency departments (ED) from 2001 to 2005 (n = 58,308) were analyzed. Hierarchical (multilevel) logistic regression models were used to assess hospital PCI volume and individual characteristics as predictors of same-day PCI use for patients at PCI-capable hospitals. The percentage of ED-admitted patients with a STEMI who received same-day PCI in Florida increased from 20% in early 2001 to 43% in late 2005. At PCI-capable hospitals, 50% of these patients received same-day PCI in late 2005. Patients admitted on weekends, women, patients aged > or = 75 years, patients with chronic obstructive pulmonary disease, and patients with end-stage renal disease were all significantly less likely to receive same-day PCI. Black patients were less likely to receive same-day PCI in early 2001 (adjusted odds ratio [OR] 0.7, 95% confidence interval 0.5 to 0.9, p <0.0001), but this racial disparity was not evident by late 2005 (adjusted OR 1.0). Men were more likely than women to receive same-day PCI, with a significant association remaining in late 2005 (adjusted OR 1.2, 95% confidence interval 1.1 to 1.4, p <0.0001). Throughout the study period, the strongest predictor of same-day PCI was admission to a high- or medium-volume PCI-capable hospital; the adjusted OR in late 2005 was 4.6 (95% confidence interval 2.8 to 7.6, p <0.0001). In conclusion, weekend admission, female gender, older age, and serious co-morbidities were all significant barriers to receiving same-day PCI. Among patients admitted to PCI-capable hospitals, total PCI volume (high or medium vs low) was associated with significantly greater odds of receiving primary PCI, independent of patient sociodemographics, risk factors, or co-morbidities. Statewide, despite an increase in the use of PCI over time, most ED-admitted patients with a STEMI in Florida did not receive primary PCI in late 2005.

Age-related changes in the aortic valve affect leaflet stress distributions: implications for aortic valve degeneration.

BACKGROUND AND AIM OF THE STUDY: The degeneration of aortic valve leaflets occurs primarily due to high mechanical stresses in zones of leaflet flexion. Aging, which has been identified as a risk factor for degenerative aortic stenosis, is associated with reductions in stretch and in compliance, and an increase in tissue thickness of the leaflet and root. The study aim was to investigate the effects of age-related tissue changes on valve opening dynamics and leaflet stress patterns, and its implications for valve degeneration. METHODS: A three-dimensional finite element model of the aortic valve and root was developed in Ansys. A transient, non-linear analysis was carried out of the valve opening phase. Three age groups were identified based on leaflet and root tissue properties: group I age <35 years; group II aged 33-55 years; and group III aged >55 years. The valve opening dynamics was studied and von Mises stresses in various regions of the leaflet were computed. RESULTS: Maximum leaflet stresses occurred along the leaflet-root attachment, analogous to the spatial distribution of calcific deposits in the aortic valve. With increasing age, the rate of valve opening decreased, and the magnitude of leaflet tip displacement in both radial and axial directions reduced progressively. At the leaflet-root attachment, groups II and III showed 19% and 32.7% increases in average stress over group I, respectively. At the free edge, the stresses in group III increased 2.7% over group I; however, the average stress at the free edge in group II decreased 3.5% over group I. In the leaflet belly, groups II and III showed 27.6% and 60.9% increases in stresses over group I, respectively. CONCLUSION: Changes in leaflet and root tissue properties lead to altered leaflet dynamics and increased stresses. This not only emphasizes the role of aging on the development and progression of degenerative aortic valve disease, but also has implications in the design of bioprosthetic heart valves.

Microneedle-based automated therapy for diabetes mellitus.

This article discusses the use of microneedles in automated diabetes therapy systems. Advanced bioengineered systems have the potential to close the loop between diagnostic and therapeutic elements of diabetes treatment, thus constituting a "smart" system. Prevalent insulin therapies, and most glucose sensing techniques, involve the transfer of physical entities through the skin. Micromachined needles (microneedles) can achieve this in a noninvasive or minimally invasive manner while contributing various other technological merits. The dynamics of autonomous diabetes therapy systems include highly complex interdependencies between the various physical and biological entities involved, thus warranting multidisciplinary research initiatives. The iterative development of a noninvasive, bioengineered interface such as microneedles necessitates a better understanding of the human skin, its molecular architecture as a polymer film, and its role as a functional biological unit. This review addresses application-specific requirements of a microneedle-based interface system specifically for autonomous diabetes therapy. Key design issues and related parametric interdependencies specific to this application are discussed.

Effects of aging on the diagnostic assessment of valvular heart disease.

The diagnostic assessment of the severity of valvular heart disease in the older population is impacted by the anatomic and physiologic changes that accompany normal aging and by the interposition of diseases prevalent in the elderly. In this paper, the impact of those changes on the assessment of valvular heart disease will be reviewed. Special attention will be paid to the effects of age and disease on the measurement of the pressure drop and orifice area.