SARS-CoV-2 vaccine protection and deaths among US veterans during 2021.

We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine effectiveness against infection (VE-I) and death (VE-D) by vaccine type in 780,225 veterans in the Veterans Health Administration, covering 2.7% of the US population. From February to October 2021, VE-I declined for all vaccine types, and the decline was greatest for the Janssen vaccine, resulting in a VE-I of 13.1%. Although breakthrough infection increased risk of death, vaccination remained protective against death in persons who became infected during the Delta variant surge. From July to October 2021, VE-D for age <65 years was 73.0% for Janssen, 81.5% for Moderna, and 84.3% for Pfizer-BioNTech; VE-D for age ≥65 years was 52.2% for Janssen, 75.5% for Moderna, and 70.1% for Pfizer-BioNTech. Findings support continued efforts to increase vaccination, booster campaigns, and multiple additional layers of protection against infection.

A finite element model of the cardiac ventricles with coupled circulation: Biventricular mesh generation with hexahedral elements, airbags and a functional mockup interface to the circulation.

INTRODUCTION: Finite element (FE) mechanics models of the heart are becoming more sophisticated. However, there is lack of consensus about optimal element type and coupling of FE models to the circulation. We describe biventricular (left (LV) and right (RV) ventricles) FE mechanics model creation using hexahedral elements, airbags and a functional mockup interface (FMI) to lumped-parameter models of the circulation. METHODS: Cardiac MRI (CMR) was performed in two healthy volunteers and a single patient with ischemic heart disease (IHD). CMR images were segmented and surfaced, meshing with hexahedral elements was performed with a "thin butterfly with septum" topology. LV and RV inflow and outflow airbags were coupled to lumped-parameter circulation models with an FMI interface. Pulmonary constriction (PAC) and vena cava occlusion (VCO) were simulated and end-systolic pressure-volume relations (ESPVR) were calculated. RESULTS: Mesh construction was prompt with representative contouring and mesh adjustment requiring 32 and 26 min Respectively. The numbers of elements ranged from 4104 to 5184 with a representative Jacobian of 1.0026 ± 0.4531. Agreement between CMR-based surfaces and mesh was excellent with root-mean-squared error of 0.589 ± 0.321 mm. The LV ESPVR slope was 3.37 ± 0.09 in volunteers but 2.74 in the IHD patient. The effect of PAC and VCO on LV ESPVR was consistent with ventricular interaction (p = 0.0286). CONCLUSION: Successful co-simulation using a biventricular FE mechanics model with hexahedral elements, airbags and an FMI interface to lumped-parameter model of the circulation was demonstrated. Future studies will include comparison of element type and study of cardiovascular pathologies and device therapies.

A kinematic model-based analysis framework for 3D Cine-DENSE-validation with an axially compressed gel phantom and application in sheep before and after antero-apical myocardial infarction.

PURPOSE: Myocardial strain is increasingly used to assess left ventricular (LV) function. Incorporation of LV deformation into finite element (FE) modeling environment with subsequent strain calculation will allow analysis to reach its full potential. We describe a new kinematic model-based analysis framework (KMAF) to calculate strain from 3D cine-DENSE (displacement encoding with stimulated echoes) MRI. METHODS: Cine-DENSE allows measurement of 3D myocardial displacement with high spatial accuracy. The KMAF framework uses cine cardiovascular magnetic resonance (CMR) to facilitate cine-DENSE segmentation, interpolates cine-DENSE displacement, and kinematically deforms an FE model to calculate strain. This framework was validated in an axially compressed gel phantom and applied in 10 healthy sheep and 5 sheep after myocardial infarction (MI). RESULTS: Excellent Bland-Altman agreement of peak circumferential (Ecc ) and longitudinal (Ell ) strain (mean difference = 0.021 ± 0.04 and -0.006 ± 0.03, respectively), was found between KMAF estimates and idealized FE simulation. Err had a mean difference of -0.014 but larger variation (±0.12). Cine-DENSE estimated end-systolic (ES) Ecc , Ell and Err exhibited significant spatial variation for healthy sheep. Displacement magnitude was reduced on average by 27%, 42%, and 56% after MI in the remote, adjacent and MI regions, respectively. CONCLUSIONS: The KMAF framework allows accurate calculation of 3D LV Ecc and Ell from cine-DENSE.

Finite-element based optimization of left ventricular passive stiffness in normal volunteers and patients after myocardial infarction: Utility of an inverse deformation gradient calculation of regional diastolic strain.

INTRODUCTION: Left ventricular (LV) diastolic dysfunction (DD) is common after myocardial infarction (MI). Whereas current clinical assessment of DD relies on indirect markers including LV filling, finite element (FE) -based computational modeling directly measures regional diastolic stiffness. We hypothesized that an inverse deformation gradient (DG) method calculation of diastolic strain (IDGDS) allows the FE model-based calculation of regional diastolic stiffness (material parameters; MP) in post-MI patients with DD. METHODS: Cardiac magnetic resonance (CMR) with tags (CSPAMM) and late gadolinium enhancement (LGE) was performed in 10 patients with post-MI DD and 10 healthy volunteers. The 3-dimensional (3D) LV DG from end-diastole (ED) to early diastolic filling (EDF; DGED→EDF) was calculated from CSPAMM. Diastolic strain was calculated from DGEDF→ED by inverting the DGED→EDF. FE models were created with MI and non-MI (remote; RM) regions determined by LGE. Guccione MPs C, and exponential fiber, bf, and transverse, bt , terms were optimized with IDGDS strain. RESULTS: 3D circumferential and longitudinal diastolic strain (Ecc;Ell) calculated using IDGDS in CSPAMM obtained in volunteers and MI patients were [Formula: see text]  = 0.27 ± 0.01, [Formula: see text]  = 0.24 ± 0.03 and [Formula: see text]  = 0.21 ± 0.02, and [Formula: see text]  = 0.15 ± 0.02, respectively. MPs in the volunteer group were CH = 0.013 [0.001, 0.235] kPa, [Formula: see text]  = 20.280 ± 4.994, and [Formula: see text]  = 7.460 ± 2.171 and CRM = 0.0105 [0.010, 0.011] kPa, [Formula: see text]  = 50.786 ± 13.511 (p = 0.0846), and [Formula: see text]  = 17.355 ± 2.743 (p = 0.0208) in the remote myocardium of post-MI patients. CONCLUSION: Diastolic strain, calculated from CSPAMM with IDGDS, enables calculation of FE model-based regional diastolic material parameters. Transverse stiffness of the remote myocardium, , may be a valuable new metric for determination of DD in patients after MI.

Sharing Lessons Learned to Prevent Adverse Events in Anesthesiology Nationwide.

OBJECTIVES: The Veterans Health Administration (VHA) lessons learned process for Anesthesia adverse events was developed to alert the field to the occurrences and prevention of actual adverse events. This article details this quality improvement project and perceived impact. METHODS: As part of ongoing quality improvement, root cause analysis related to anesthesiology care are routinely reported to the VHA National Center for Patient Safety. Since May 2012, the National Anesthesia Service subject matter experts, in collaboration with National Center for Patient Safety, review actual adverse events in anesthesiology and detailed lessons learned are developed. A survey of anesthesiology chiefs to determine perceived usefulness and accessibility of the project was conducted in April 2018. RESULTS: The distributed survey yielded a response rate of 69% (84/122). Most of those who have seen the lessons learned (85%, 71/84) found them valuable. Ninety percent of those aware of the lessons learned (64/71) shared them with staff and 75% (53/71) reported a changed or reinforced patient safety behavior in their facility. The lessons learned provided 72% (51/71) of chiefs with new knowledge about patient safety and 75% (53/71) gained new knowledge for preventing adverse events. CONCLUSIONS: This nationwide VHA anesthesiology lessons learned project illustrates the tenets of a learning organization. implementing team and systems-based safeguards to mitigate risk of harm from inevitable human error. Sharing lessons learned provides opportunities for clinician peer-to-peer learning, communication, and proactive approaches to prevent future similar errors.

Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study.

OBJECTIVES: SARS-CoV-2 enters cells using the ACE2 receptor. Medications that affect ACE2 expression or function such as angiotensin receptor blockers (ARBs) and ACE inhibitors (ACE-I) and metformin have the potential to counter the dysregulation of ACE2 by the virus and protect against viral injury. Here, we describe COVID-19 survival associated with ACE-I, ARB and metformin use. DESIGN: This is a hospital-based observational study of patients with COVID-19 infection using logistic regression with correction for pre-existing conditions and propensity score weighted Cox proportional hazards models to estimate associations between medication use and mortality. SETTING: Medical record data from the US Veterans Affairs (VA) were used to identify patients with a reverse transcription PCR diagnosis of COVID-19 infection, to classify patterns of ACE inhibitors (ACE-I), ARB, beta blockers, metformin, famotidine and remdesivir use, and, to capture mortality. PARTICIPANTS: 9532 hospitalised patients with COVID-19 infection followed for 60 days were analysed. OUTCOME MEASURE: Death from any cause within 60 days of COVID-19 diagnosis was examined. RESULTS: Discontinuation of ACE-I was associated with increased risk of death (OR: 1.4; 95% CI 1.2-1.7). Initiating (OR: 0.3; 95% CI 0.2-0.5) or continuous (OR: 0.6; 95% CI 0.5-0.7) ACE-I was associated with reduced risk of death. ARB and metformin associations were similar in direction and magnitude and also statistically significant. Results were unchanged when accounting for pre-existing morbidity and propensity score adjustment. CONCLUSIONS: Recent randomised clinical trials support the safety of continuing ACE-I and ARB treatment in patients with COVID-19 where indicated. Our study extends these findings to suggest a possible COVID-19 survival benefit for continuing or initiating ACE-I, ARB and metformin medications. Randomised trials are appropriate to confirm or refute the therapeutic potential for ACE-I, ARBs and metformin.

Combined Intravenous Sildenafil and L-Arginine Administration in a Porcine Animal Model: Hemodynamic Safety Profile and Effects on Coronary Blood Flow.

BACKGROUND: Endothelial dysfunction in the nitric oxide-cyclic guanosine monophosphate pathway is a potential contributor to perioperative myocardial ischemia. The nitric oxide precursor, L-arginine, and the cyclic guanosine monophosphate degradation blocker, sildenafil, have vasodilatory effects under high dosage. OBJECTIVE: This study examined the hemodynamic safety and effect profiles of the combined administration of L-arginine and sildenafil using an in-vivo pig model. METHODS: Hemodynamic safety including mean arterial pressure, central venous pressure, heart rate, coronary vascular resistance, and systemic vascular resistance, as well as effect profiles including cardiac output and left anterior descending blood flow were measured in ten female swine after administrations of L-arginine, sildenafil, as well as combined L-arginine and sildenafil. Measurements were compared using repeated-measures analysis of variance and linear mixed models. RESULTS: The combination of L-arginine and sildenafil produced a significant dose-dependent increase in left anterior descending flow and cardiac output. In contrast, mean arterial pressure, heart rate, central venous pressure, coronary vascular resistance, and systemic vascular resistance did not show any significant changes. No significant change in serum osmolality was observed after administrations of L-arginine. CONCLUSIONS: The combined intravenous administration of sildenafil and L-arginine in a porcine animal model was safe, well tolerated, and had at least additive effects on left anterior descending artery blood flow. Simultaneous application of both drugs might have dose-sparing effects leading to desired coronary effects at lower and safer sildenafil and L-arginine plasma concentrations. Hyperosmolality was only a minor factor in L-arginine hemodynamic effects.

Left ventricular geometry during unloading and the end-systolic pressure volume relationship: Measurement with a modified real-time MRI-based method in normal sheep.

The left ventricular (LV) end-systolic (ES) pressure volume relationship (ESPVR) is the cornerstone of systolic LV function analysis. We describe a 2D real-time (RT) MRI-based method (RTPVR) with separate software tools for 1) semi-automatic level set-based shape prior method (LSSPM) of the LV, 2) generation of synchronized pressure area loops and 3) calculation of the ESPVR. We used the RTPVR method to measure ventricular geometry, ES pressure area relationship (ESPAR) and ESPVR during vena cava occlusion (VCO) in normal sheep. 14 adult sheep were anesthetized and underwent measurement of LV systolic function. Ten of the 14 sheep underwent RTMRI and eight of the 14 underwent measurement with conductance catheter; 4 had both RTMRI and conductance measurements. 2D cross sectional RTMRI were performed at apex, mid-ventricle and base levels during separate VCOs. The Dice similarity coefficient was used to compare LSSPM and manual image segmentation and thus determine LSSPM accuracy. LV cross-sectional area, major and minor axis length, axis ratio, major axis orientation angle and ESPAR were measured at each LV level. ESPVR was calculated with a trapezoidal rule. The Dice similarity coefficient between LSSPM and manual segmentation by two readers was 87.31±2.51% and 88.13±3.43%. All cross sections became more elliptical during VCO. The major axis orientation shifted during VCO but remained in the septo-lateral direction. LV chamber obliteration at the apical level occurred during VCO in 7 of 10 sheep that underwent RTMRI. ESPAR was non-linear at all levels. Finally, ESPVR was non-linear because of apical collapse. ESPVR measured by conductance catheter (EES,Index = 2.23±0.66 mmHg/ml/m2) and RT (EES,Index = 2.31±0.31 mmHg/ml/m2) was not significantly different. LSSPM segmentation of 2D RT MRI images is accurate and allows calculation of LV geometry, ESPAR and ESPVR during VCO. In the future, RTPVR will facilitate determination of regional systolic material parameters underlying ESPVR.

Myocardial injection of a thermoresponsive hydrogel with reactive oxygen species scavenger properties improves border zone contractility.

The decrease in contractility in myocardium adjacent (border zone; BZ) to a myocardial infarction (MI) is correlated with an increase in reactive oxygen species (ROS). We hypothesized that injection of a thermoresponsive hydrogel, with ROS scavenging properties, into the MI would decrease ROS and improve BZ function. Fourteen sheep underwent antero-apical MI. Seven sheep had a comb-like copolymer synthesized from N-isopropyl acrylamide (NIPAAm) and 1500 MW methoxy poly(ethylene glycol) methacrylate, (NIPAAm-PEG1500), injected (20 × 0.5 mL) into the MI zone 40 min after MI (MI + NIPAAm-PEG1500) and seven sheep were MI controls. Cardiac MRI was performed 2 weeks before and 6 weeks after MI + NIPAAm-PEG1500. BZ wall thickness at end systole was significantly higher for MI + NIPAAm-PEG1500 (12.32 ± 0.51 mm/m2 MI + NIPAAm-PEG1500 vs. 9.88 ± 0.30 MI; p = .023). Demembranated muscle force development for BZ myocardium 6 weeks after MI was significantly higher for MI + NIPAAm-PEG1500 (67.67 ± 2.61 mN/m2 MI + NIPAAm-PEG1500 vs. 40.53 ± 1.04 MI; p < .0001) but not significantly different from remote myocardium or BZ or non-operated controls. Levels of ROS in BZ tissue were significantly lower in the MI + NIPAAm-PEG1500 treatment group (hydroxyl p = .0031; superoxide p = .0182). We conclude that infarct injection of the NIPAAm-PEG1500 hydrogel with ROS scavenging properties decreased ROS and improved contractile protein function in the border zone 6 weeks after MI.

Investigation of possible aqueous phase formation during vaporization of sevoflurane.

BACKGROUND AND AIMS: Ultane® (sevoflurane; AbbVie Inc., North Chicago, IL, USA) has a dissolved water content of approximately 0.035% weight/weight (w/w). A previous report described formation of an aqueous layer in 4 of 13 sevoflurane vaporizers used in operating rooms. We investigated the conditions under which an aqueous layer could develop during vaporization of sevoflurane-water mixtures. MATERIAL AND METHODS: A temperature-controlled glass reactor was used to simulate a vaporizer. In four experiments, the vaporization of different sevoflurane-water mixtures was monitored over approximately 3-4 days. Samples were removed at regular intervals for analysis of water content. For confirmation, one experiment was replicated in a Tec 7 vaporizer. RESULTS: Saturation of sevoflurane with water occurred at 0.11%-0.13% w/w at an ambient temperature; at greater water concentrations a separate aqueous phase was initially present. The sevoflurane-water azeotrope contained approximately 1.2% w/w water at 25°C. When the initial water content was <1.2% w/w (0.11%-1.03% w/w), vaporization resulted in a single phase of drier sevoflurane (final water concentration 0.02%-0.08% w/w). When the starting water concentration exceeded the azeotropic concentration (5.0% w/w), vaporization increased the water content, reaching 13% w/w at 71 h. Results under the low initial water condition were similar in the Tec 7 vaporizer. CONCLUSIONS: An increase in water concentration following vaporization of sevoflurane can only occur when the starting water content is higher than the azeotropic concentration and therefore cannot originate from the dissolved water present in the marketed product because the water concentration in Ultane® is 34 times lower than the azeotropic concentration.

Freedom From Opioids After Total Knee Arthroplasty.

BACKGROUND: In the United States, opioids are commonly prescribed to treat knee pain after total knee arthroplasty (TKA). While surgery leads to decreased pain in most patients, a sizable minority continue to experience severe pain and consume opioids chronically after TKA. We sought to determine the population-level effect of TKA on opioid consumption by detailing the pattern of opioid prescriptions before and after surgery. METHODS: We retrospectively identified US Veterans Health Administration TKA patients from 2010 to 2015. Outpatient opioid prescriptions were identified from 18 months before to 18 months after surgery, and mean daily opioid doses were calculated. Our primary end point was the achievement of opioid-freedom, defined as a period of at least 6 months without opioids. We compared the percentage of patients who were opioid-free preoperatively to the percentage who were opioid-free 18 months after surgery (no prescriptions after postoperative month 12). We identified factors associated with opioid-freedom. RESULTS: In a cohort of 33,927 patients, 41% were opioid-free in the month before surgery compared to 54% 18 months after surgery (P < .001). Preoperative freedom from opioids (odds ratio, 4.59; 95% confidence interval, 4.34 to 4.85; P < .001) was more strongly associated with postoperative freedom from opioids than patient medical and social factors. CONCLUSION: TKA was associated with an increase in postoperative freedom from opioids. Low preoperative dose of opioids was more strongly associated with postoperative opioid-freedom than patient characteristics, suggesting that opioid prescription patterns are a chief driver of opioid use after surgery. LEVEL OF EVIDENCE III: Retrospective cohort study.

E-cigarettes versus nicotine patches for perioperative smoking cessation: a pilot randomized trial.

INTRODUCTION: Cigarette smoking by surgical patients is associated with increased complications. E-cigarettes have emerged as a potential smoking cessation tool. We sought to determine the feasibility and acceptability of e-cigarettes, compared to nicotine patch, for perioperative smoking cessation in veterans. METHODS: Preoperative patients were randomized to either the nicotine patch group (n = 10) or the e-cigarette group (n = 20). Both groups were given a free 6-week supply in a tapering dose. All patients received brief counseling, a brochure on perioperative smoking cessation, and referral to the California Smokers' Helpline. The primary outcome was rate of smoking cessation on day of surgery confirmed by exhaled carbon monoxide. Secondary outcomes included smoking habits, pulmonary function, adverse events, and satisfaction with the products on day of surgery and at 8-weeks follow-up. RESULTS: Biochemically verified smoking cessation on day of surgery was similar in both groups. Change in forced expiratory volume in one second (FEV1) was 592 ml greater in the e-cigarette group (95% CI [153-1,031] ml, p = 0.01) and change in forced expiratory volume in one second to forced vital capacity ratio (FEV1/FVC ratio) was 40.1% greater in the e-cigarette group (95% CI [18.2%-78.4%], p = 0.04). Satisfaction with the product was similar in both groups. DISCUSSION: E-cigarettes are a feasible tool for perioperative smoking cessation in veterans with quit rates comparable to nicotine replacement patch. Spirometry appears to be improved 8-weeks after initiating e-cigarettes compared to nicotine patch, possibly due to worse baseline spirometry and more smoking reduction in the e-cigarette group. An adequately powered study is recommended to determine if these results can be duplicated.

Short term doxycycline treatment induces sustained improvement in myocardial infarction border zone contractility.

Decreased contractility in the non-ischemic border zone surrounding a MI is in part due to degradation of cardiomyocyte sarcomeric components by intracellular matrix metalloproteinase-2 (MMP-2). We recently reported that MMP-2 levels were increased in the border zone after a MI and that treatment with doxycycline for two weeks after MI was associated with normalization of MMP-2 levels and improvement in ex-vivo contractile protein developed force in the myocardial border zone. The purpose of the current study was to determine if there is a sustained effect of short term treatment with doxycycline (Dox) on border zone function in a large animal model of antero-apical myocardial infarction (MI). Antero-apical MI was created in 14 sheep. Seven sheep received doxycycline 0.8 mg/kg/hr IV for two weeks. Cardiac MRI was performed two weeks before, and then two and six weeks after MI. Two sheep died prior to MRI at six weeks from surgical/anesthesia-related causes. The remaining 12 sheep completed the protocol. Doxycycline induced a sustained reduction in intracellular MMP-2 by Western blot (3649±643 MI+Dox vs 9236±114 MI relative intensity; p = 0.0009), an improvement in ex-vivo contractility (65.3±2.0 MI+Dox vs 39.7±0.8 MI mN/mm2; p<0.0001) and an increase in ventricular wall thickness at end-systole 1.0 cm from the infarct edge (12.4±0.6 MI+Dox vs 10.0±0.5 MI mm; p = 0.0095). Administration of doxycycline for a limited two week period is associated with a sustained improvement in ex-vivo contractility and an increase in wall thickness at end-systole in the border zone six weeks after MI. These findings were associated with a reduction in intracellular MMP-2 activity.

Sevoflurane Contamination: Water Accumulation in Sevoflurane Vaporizers Can Allow Bacterial Growth in the Vaporizer.

Sevoflurane vaporizers (GE Tec 7) were difficult to fill with "slow flow" and a need to "burp." Evaluation of the bottle of sevoflurane (AbbVie Ultane) demonstrated a contaminant. Four of the facilities' 13 sevoflurane vaporizers had the contaminant. Unopened sevoflurane bottles did not have evidence of contamination. The contaminant was found to be water at pH 6.0 growing Staphylococcus epidermidis. Gas chromatography revealed the production of multiple metabolites of sevoflurane, including primarily urea and 1,3,5-triazine-2,4,6(1H,3H,5H)-trione (83% and 9.6% of volatiles) in addition to multiple other organic molecules. Sevoflurane contains water that can accumulate in vaporizers allowing bacterial growth.

Moderate Ischemic Mitral Regurgitation After Posterolateral Myocardial Infarction in Sheep Alters Left Ventricular Shear but Not Normal Strain in the Infarct and Infarct Borderzone.

BACKGROUND: Chronic ischemic mitral regurgitation (CIMR) is associated with poor outcome. Left ventricular (LV) strain after posterolateral myocardial infarction (MI) may drive LV remodeling. Although moderate CIMR has been previously shown to affect LV remodeling, the effect of CIMR on LV strain after posterolateral MI remains unknown. We tested the hypothesis that moderate CIMR alters LV strain after posterolateral MI. METHODS: Posterolateral MI was created in 10 sheep. Cardiac magnetic resonance imaging with tags was performed 2 weeks before and 2, 8, and 16 weeks after MI. The left and right ventricular volumes were measured, and regurgitant volume indexed to body surface area (regurgitant volume index) was calculated as the difference between left ventricle and right ventricle stroke volumes divided by body surface area. Three-dimensional strain was calculated. RESULTS: Circumferential strain (Ecc) and longitudinal strain (Ell) were reduced in the infarct proper, MI borderzone, and remote myocardium 16 weeks after MI. In addition, radial circumferential (Erc) and radial longitudinal (Erl) shear strains were reduced in remote myocardium but increased in the infarct and borderzone 16 weeks after MI. Of all strain components, however, only Erc was affected by regurgitant volume index (p = 0.0005). There was no statistically significant effect of regurgitant volume index on Ecc, Ell, Erl, or circumferential longitudinal shear strain (Ecl). CONCLUSIONS: Moderate CIMR alters radial circumferential shear strain after posterolateral MI in sheep. Further studies are needed to determine the effect of shear strain on myocyte hypertrophy and the effect of mitral repair on myocardial strain.

Association between Withholding Angiotensin Receptor Blockers in the Early Postoperative Period and 30-day Mortality: A Cohort Study of the Veterans Affairs Healthcare System.

BACKGROUND: Despite widespread use, there is limited information to guide perioperative management of angiotensin receptor blockers (ARBs). METHODS: In this retrospective cohort study, the authors evaluated the patterns of postoperative ARB use in veterans regularly prescribed ARBs admitted for noncardiac surgery at the Veterans Affairs Healthcare system between 1999 and 2011. Multivariable and propensity score-matched Cox proportional hazards models were used to determine the independent effect of failure to resume ARB by postoperative day 2 on the primary outcome of all-cause 30-day mortality. RESULTS: Out of 1,167,482 surgical admissions, 30,173 inpatient surgical admissions met inclusion criteria. Approximately 10,205 patients (33.8%) in the cohort did not resume ARB by day 2. Those that resumed ARB had a 30-day mortality rate of 1.3% (260 of 19,968), whereas 3.2% (323 of 10,205) died in the group that withheld ARB. The unadjusted hazard ratio (HR) for 30-day mortality was 2.45 (95% CI, 2.08 to 2.89; P < 0.001) for those that withheld ARB compared with those that resumed, whereas the multivariable adjusted HR was 1.74 (95% CI, 1.47 to 2.06; P < 0.001). When restricted to a propensity score-matched subset of 19,490, the HR was similar (1.47; 95% CI, 1.22 to 1.78; P < 0.001). Withholding ARB in younger patients increased mortality risk (HR = 2.52; 95% CI, 1.69 to 3.76; P < 0.001 for age <60 yr) compared with older patients (HR = 1.42; 95% CI, 1.09 to 1.85; P = 0.01 for age >75 yr). CONCLUSIONS: Postoperative delay in resuming ARB is common, particularly in patients who are frail after surgery. Withholding ARB is strongly associated with increased 30-day mortality, especially in younger patients, although residual confounding may be present.

Thirty-day mortality risk associated with the postoperative nonresumption of angiotensin-converting enzyme inhibitors: a retrospective study of the Veterans Affairs Healthcare System.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACE-Is) are a widely used class of cardiovascular medication. However, limited data exist on the risks of postoperative nonresumption of an ACE-I. OBJECTIVE: To evaluate the factors and 30-day mortality risks associated with the postoperative nonresumption of an ACE-I. DESIGN: A retrospective cohort study. SETTING: Veterans Affairs (VA) Healthcare System. PATIENTS: A total of 294,505 admissions in 240,978 patients with multiple preoperative prescription refills (>3) for an ACE-I who underwent inpatient surgery from calendar years 1999 to 2012. INTERVENTION: None. MEASUREMENTS: We classified surgical admissions based upon the timing of postoperative resumption of an ACE-I prescription from the day of surgery through postoperative days 0 to 14 and 15 to 30, and collected 30-day mortality data. We evaluated the relationship between 30-day mortality and the nonresumption of an ACE-I from postoperative day 0 to 14 using proportional hazard regression models, adjusting for patient- and hospital-level risk factors. Sensitivity analyses were conducted using more homogeneous subpopulations and propensity score models. RESULTS: Twenty-five percent of our cohort did not resume an ACE-I during the 14 days following surgery. Nonresumption of an ACE-I within postoperative day 0 to 14 was independently associated with increased 30-day mortality (hazard ratio: 3.44; 95% confidence interval: 3.30-3.60; P < 0.001) compared to the restart group. Sensitivity analyses maintained this relationship. CONCLUSIONS: Nonresumption of an ACE-I is common after major inpatient surgery in the large VA Health Care System. Restarting of an ACE-I within postoperative day 0 to 14 is, however, associated with decreased 30-day mortality. Careful attention to the issue of timely reinstitution of chronic medications such as an ACE-I is indicated.

Effectiveness of preoperative beta-blockade on intra-operative heart rate in vascular surgery cases conducted under regional or local anesthesia.

BACKGROUND: Preoperative ß-blockade has been posited to result in better outcomes for vascular surgery patients by attenuating acute hemodynamic changes associated with stress. However, the incremental effectiveness, if any, of ß-blocker usage in blunting heart rate responsiveness for vascular surgery patients who avoid general anesthesia remains unknown. METHODS: We reviewed an existing database and identified 213 consecutive vascular surgery cases from 2005-2011 conducted without general anesthesia (i.e., under monitored anesthesia care or regional anesthesia) at a tertiary care Veterans Administration medical center and categorized patients based on presence or absence of preoperative ß-blocker prescription. For this series of patients, with the primary outcome of maximum heart rate during the interval between operating room entry to surgical incision, we examined the association of maximal heart rate and preoperative ß-blocker usage by performing crude and multivariate linear regression, adjusting for relevant patient factors. RESULTS: Of 213 eligible cases, 137 were prescribed preoperative ß-blockers, and 76 were not. The two groups were comparable across baseline patient factors and intraoperative medication doses. The ß-blocker group experienced lower maximal heart rates during the period of evaluation compared to the non-ß-blocker group (85 ± 22 bpm vs. 98 ± 36 bpm, respectively; p = 0.002). Adjusted linear regression confirmed a statistically-significant association between lower maximal heart rate and the use of ß-blockers (Beta = -11.5; 95% CI [-3.7, -19.3] p = 0.004). CONCLUSIONS: The addition of preoperative ß-blockers, even when general anesthesia is avoided, may be beneficial in further attenuating stress-induced hemodynamic changes for vascular surgery patients.

Left ventricular pressure gating in ovine cardiac studies: a software-based method.

Cardiac imaging using magnetic resonance requires a gating signal in order to compensate for motion. Human patients are routinely scanned using an electrocardiogram (ECG) as a gating signal during imaging. However, we found that in sheep the ECG is not a reliable method for gating. We developed a software based method that allowed us to use the left ventricular pressure (LVP) as a reliable gating signal. By taking the time derivative of the LVP (dP/dt), we were able to start imaging at both end-diastole for systolic phase images, and end-systole for diastolic phase images. We also used MR tissue tagging to calculate 3D strain information during diastole. Using the LVP in combination with our digital circuit provided a reliable and time efficient method for ovine cardiac imaging. Unlike the ECG signal the left ventricular pressure was a clean signal and allowed for accurate, nondelay based triggering during systole and diastole.