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BACKGROUND: Mixed reality head-mounted displays (MR-HMD) are a novel and emerging tool in healthcare. There is a paucity of data on the safety and efficacy of the use of MR-HMD in the cardiac catheterization laboratory (CCL). We sought to analyze and compare fluoroscopy time, procedure time, and complication rates with right heart catheterizations (RHCs) and coronary angiographies (CAs) performed with MR-HMD versus standard LCD medical displays. METHODS: This is a non-randomized trial that included patients who underwent RHC and CA with MR-HMD between August 2019 and January 2020. Their outcomes were compared to a control group during the same time period. The primary endpoints were procedure time, fluoroscopy time, and dose area product (DAP). The secondary endpoints were contrast volume and intra and postprocedural complications rate. RESULTS: 50 patients were enrolled in the trial, 33 had a RHC done, and 29 had a diagnostic CA performed. They were compared to 232 patients in the control group. The use of MR-HMD was associated with a significantly lower procedure time (20 min (IQR 14-30) vs. 25 min (IQR 18-36), p = 0.038). There were no significant differences in median fluoroscopy time (1.5 min (IQR 0.7-4.9) in the study group vs. 1.3 min (IQR 0.8-3.1), p = 0.84) or median DAP (165.4 mGy·cm2 (IQR 13-15,583) in the study group vs. 913 mGy·cm2 (IQR 24-6291), p = 0.17). There was no significant increase in intra- or post-procedure complications. CONCLUSION: MR-HMD use is safe and feasible and may decrease procedure time in the CCL.

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Safe and accurate pre-procedural assessment of cardiovascular anatomy, physiology, and pathophysiology prior to TAVR procedures can mean the difference between success and catastrophic failure. It is imperative that clinical care team members share a basic understanding of the preprocedural imaging technologies available for optimizing the care of TAVR patients. Herein, we review current imaging technology for assessing the anatomy, physiology, and pathophysiology of the aortic valvular complex, ventricular function, and peripheral vasculature, including echocardiography, cardiac catheterization, cardiac computed tomography, and cardiac magnetic resonance prior to a TAVR procedure. The authorship includes cardiac-trained anesthesiologists, anesthesiologists with expertise in pre-procedural cardiac assessment and optimization, and interventional cardiologists with expertise in cardiovascular imaging prior to TAVRs. Improving the understanding of all team members will undoubtedly translate into safer, more coordinated patient care.

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BACKGROUND: The optimal timing of aortic valve replacement (AVR) among patients with asymptomatic severe aortic stenosis (AS) remains uncertain and controversial. METHODS: We conducted a cohort study of consecutive patients with severe AS (mean gradient, 40 mm Hg; aortic valve area <1 cm², or peak velocity ≥4 m/s) who were asymptomatic at the time of echocardiography (2005-2015). Outcomes included mortality, AVR, or AS symptoms. Kaplan-Meier curves and the log-rank test were used to compare the outcomes of patients treated with AVR compared with conservative management. Cox proportional-hazards regression analysis was performed to identify predictors of long-term mortality. RESULTS: Of 1181 echocardiograms and medical records reviewed, a total of 324 patients met inclusion criteria. The mean age of the study cohort was 78 ± 10 years and 97% were male. The median follow-up time was 8 years (interquartile range [IQR], 7-10 years), during which 147 patients (51%) underwent AVR and 94 patients (29%) died. The median survival for patients treated with AVR was 10 years (IQR, 9-10 years) and for patients managed conservatively was 4.8 years (IQR, 3.7-5.7 years; P<.001). A total of 47 patients (14% of the cohort and 48% of deaths) expired before AS symptoms were documented in their medical records. Independent predictors of mortality were age (hazard ratio [HR] per increase in decile, 1.14; 95% CI, 1.05-1.24; P<.01) and performance of AVR during follow-up (HR, 0.15; 95% CI, 0.9-0.28; P<.01). CONCLUSION: A significant proportion of elderly patients with initially asymptomatic severe AS died before symptoms were identified. Our study highlights the difficulty of relying on symptoms alone for timely referral to AVR surgery.

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INTRODUCTION: Syncope/collapse is a common reason for emergency department visits, and approximately 30-40% of these individuals are hospitalized. We examined changes in hospitalization rates, in-hospital mortality, and cost of syncope/collapse-related hospital care in the United States from 2004 to 2013. METHODS: We used the US Nationwide Inpatient Sample (NIS) from 2004 to 2013 to identify syncope/collapse-related hospitalizations using ICD-9, code 780.2, as the principal discharge diagnosis. Data are presented as mean ± SEM. RESULTS: From 2004 to 2013, there was a 42% reduction in hospitalizations with a principal discharge diagnosis of syncope/collapse from 54,259 (national estimate 253,591) in 2004 to 31,427 (national estimate 156,820) in 2013 (P < 0.0001). The mean length of hospital stays decreased (2.88 ± 0.04 days in 2004 vs. 2.54 ± 0.02 in 2013; P < 0.0001), while in-hospital mortality did not change (0.28% in 2004 vs. 0.18% in 2013; P  =  0.12). However, mean charges (inflation adjusted) for syncope/collapse-related hospitalization increased by 43.6% from $17,514 in 2004 to $25,160 in 2013 (P < 0.0001). The rates of implantation of permanent pacemakers and implantable cardioverter defibrillator remained low during these hospitalizations, and decreased over time (P for both < 0.0001). CONCLUSIONS: Hospitalization rates for syncope/collapse have decreased significantly in the US from 2004 to 2013. Despite a modest reduction in length of stay, the cost of syncope/collapse-related hospital care has increased.

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xtracorporeal membrane oxygenation (ECMO) is used in cardiopulmonary resuscitation (CPR) of refractory cardiac arrest. We used a 2×2 study design to compare ECMO versus CPR and epinephrine versus placebo in a porcine model of ischemic refractory ventricular fibrillation (VF). Pigs underwent 5 minutes of untreated VF, 10 minutes of CPR, and were randomized to receive epinephrine versus placebo for another 35 minutes. Animals were further randomized to LAD reperfusion at minute 45 with ongoing CPR versus veno-arterial ECMO cannulation at minute 45 of CPR and subsequent LAD reperfusion. Four-hour survival was improved with ECMO while epinephrine showed no effect.

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Cardiomyopathy is common in long-term survivors of pediatric hematopoietic stem cell transplant (HSCT). Events occurring before and after HSCT when combined with specific insults during HSCT likely contribute to long-term risk. Strategies for detecting subclinical cardiomyopathy prior to patients developing overt heart failure are under investigation. Changes in HSCT preparative regimens and cardioprotective medications administered during chemotherapy may alter the risk for cardiomyopathy. Interventions in long-term survivors such as lifestyle modification and cardioactive medications are of increasing importance. Herein we review the causes of cardiac injury, discuss strategies for detection of cardiomyopathy, and evaluate therapeutic options for long-term HSCT survivors.

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INTRODUCTION: Sodium nitroprusside (SNP) enhanced CPR (SNPeCPR) demonstrates increased vital organ blood flow and survival in multiple porcine models. We developed a new, coronary occlusion/ischemia model of prolonged resuscitation, mimicking the majority of out-of-hospital cardiac arrests presenting with shockable rhythms. HYPOTHESIS: SNPeCPR will increase short term (4-h) survival compared to standard 2015 Advanced Cardiac Life Support (ACLS) guidelines in an ischemic refractory ventricular fibrillation (VF), prolonged CPR model. METHODS: Sixteen anesthetized pigs had the ostial left anterior descending artery occluded leading to ischemic VF arrest. VF was untreated for 5min. Basic life support was performed for 10min. At minute 10 (EMS arrival), animals received either SNPeCPR (n=8) or standard ACLS (n=8). Defibrillation (200J) occurred every 3min. CPR continued for a total of 45min, then the balloon was deflated simulating revascularization. CPR continued until return of spontaneous circulation (ROSC) or a total of 60min, if unsuccessful. SNPeCPR animals received 2mg of SNP at minute 10 followed by 1mg every 5min until ROSC. Standard ACLS animals received 0.5mg epinephrine every 5min until ROSC. Primary endpoints were ROSC and 4-h survival. RESULTS: All SNPeCPR animals (8/8) achieved sustained ROSC versus 2/8 standard ACLS animals within one hour of resuscitation (p=0.04). The 4-h survival was significantly improved with SNPeCPR compared to standard ACLS, 7/8 versus 1/8 respectively, p=0.0019. CONCLUSION: SNPeCPR significantly improved ROSC and 4-h survival compared with standard ACLS CPR in a porcine model of prolonged ischemic, refractory VF cardiac arrest.

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BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) affects primarily young women and impairs quality of life. We found that in a research setting, exercise training along with lifestyle intervention is effective as a nondrug therapy for POTS. OBJECTIVE: To evaluate the efficacy of our exercise training/lifestyle intervention in POTS patients in a community environment. METHODS: We established a POTS registry and enrolled 251 patients (86% women, aged 26 ± 11 [SD] years) through their physicians. A 3-month program involving mild- to moderate-intensity endurance training (progressing from semirecumbent to upright, 3-5 times/wk, 30-45 min/session) plus strength training was implemented along with increasing salt/water intake. The program was delivered to the physicians, who oversaw training in their patients. A 10-minute stand test was performed at the physician's office and patient quality of life was assessed using the 36-Item Short Form Health Survey. RESULTS: One hundred and three patients completed the program. Of those that completed, 71% no longer qualified for POTS and were thus in remission. The increase in heart rate from supine to 10-minute stand was markedly lower (23 ± 14 vs. 46 ± 17 beats/min before intervention; P < .001), while patient quality of life was improved dramatically after intervention (P < .001). Of those who were followed for 6-12 months (n = 31), the effect was persistent. CONCLUSIONS: A training/lifestyle intervention program can be implemented in a community setting with physician supervision and is effective in the treatment of POTS. It remains to be determined whether exercise can be an effective long-term treatment strategy for this condition, though patients are encouraged to maintain an active lifestyle indefinitely.

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Li-Fraumeni syndrome (LFS) is a highly penetrant, autosomal dominant, human familial cancer predisposition. Although a key role for the tumor suppressor p53 has been implicated in LFS, the genetic and cellular mechanisms underpinning this disease remain unknown. Therefore, modeling LFS in a vertebrate system that is accessible to both large-scale genetic screens and in vivo cell biological studies will facilitate the in vivo dissection of disease mechanisms, help identify candidate genes, and spur the discovery of therapeutic compounds. Here, we describe a forward genetic screen in zebrafish embryos that was used to identify LFS candidate genes, which yielded a p53 mutant (p53(I166T)) that as an adult develops tumors, predominantly sarcomas, with 100% penetrance. As in humans with LFS, tumors arise in heterozygotes and display loss of heterozygosity (LOH). This report of LOH indicates that Knudson's two-hit hypothesis, a hallmark of human autosomal dominant cancer syndromes, can be modeled in zebrafish. Furthermore, as with some LFS mutations, the zebrafish p53(I166T) allele is a loss-of-function allele with dominant-negative activity in vivo. Additionally, we demonstrate that the p53 regulatory pathway, including Mdm2 regulation, is evolutionarily conserved in zebrafish, providing a bona fide biological context in which to systematically uncover novel modifier genes and therapeutic agents for human LFS.

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In order to facilitate high throughput genotyping of zebrafish, we have developed a novel technique that uses High Resolution Melting Analysis (HRMA) to distinguish wild-type, heterozygous mutants and homogyzous mutants. This one hour technique removes the need for restriction enzymes and agarose gels. The generated melting curve profiles are sensitive enough to detect non-specific PCR products. We have been able to reliably genotype three classes of mutations in zebrafish, including point mutants, apc(hu745) (apc(mcr)), and p53(zy7) (p53(I166T)), a small deletion mutant (bap28(y75)) and a retroviral insertion mutant (wdr43(hi821a)). This technique can genotype individual zebrafish embryos and adults (by tail-clip) and is applicable to other model organisms.

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