Respiratory sinus arrhythmia (RSA), vagal tone and biobehavioral integration: Beyond parasympathetic function.

Linchpin to the entire area of psychophysiological research and discussion of the vagus is the respiratory and cardiovascular phenomenon known as respiratory sinus arrhythmia (RSA; often synonymous with high-frequency heart-rate variability when it is specifically linked to respiratory frequency), i.e. rhythmic fluctuations in heart rate synchronized to inspiration and expiration. This article aims 1) to clarify concepts, terms and measures commonly employed during the last half century in the scientific literature, which relate vagal function to psychological processes and general aspects of health; and 2) to expand upon an earlier theoretical model, emphasizing the importance of RSA well beyond the current focus upon parasympathetic mechanisms. A close examination of RSA and its relations to the vagus may 1) dispel certain commonly held beliefs about associations between psychological functioning, RSA and the parasympathetic nervous system (for which the vagus nerve plays a major role), and 2) offer fresh perspectives about the likely functions and adaptive significance of RSA, as well as RSA's relationship to vagal control. RSA is neither an invariably reliable index of cardiac vagal tone nor of central vagal outflow to the heart. The model here presented posits that RSA represents an evolutionarily entrenched, cardiovascular and respiratory phenomenon that significantly contributes to meeting continuously changing metabolic, energy and behavioral demands.

Fundamental challenges and likely refutations of the five basic premises of the polyvagal theory.

The polyvagal collection of hypotheses is based upon five essential premises, as stated by its author (Porges, 2011). Polyvagal conjectures rest on a primary assumption that brainstem ventral and dorsal vagal regions in mammals each have their own unique mediating effects upon control of heart rate. The polyvagal hypotheses link these putative dorsal- vs. ventral-vagal differences to socioemotional behavior (e.g. defensive immobilization, and social affiliative behaviors, respectively), as well as to trends in the evolution of the vagus nerve (e.g. Porges, 2011 & 2021a). Additionally, it is essential to note that only one measurable phenomenon-as index of vagal processes-serves as the linchpin for virtually every premise. That phenomenon is respiratory sinus arrhythmia (RSA), heart-rate changes coordinated to phase of respiration (i.e. inspiration vs. expiration), often employed as an index of vagally, or parasympathetically, mediated control of heart rate. The polyvagal hypotheses assume that RSA is a mammalian phenomenon, since Porges (2011) states "RSA has not been observed in reptiles." I will here briefly document how each of these basic premises have been shown to be either untenable or highly implausible based on the available scientific literature. I will also argue that the polyvagal reliance upon RSA as equivalent to general vagal tone or even cardiac vagal tone is conceptually a category mistake (Ryle, 1949), confusing an approximate index (i.e. RSA) of a phenomenon (some general vagal process) with the phenomenon, itself.

Outcomes in patients with electrocardiographic left ventricular dyssynchrony following transcatheter aortic valve replacement.

BACKGROUND: Left bundle branch block (LBBB) and atrioventricular (AV) conduction abnormalities requiring permanent pacemaker (PPM) implantation occur frequently following transcatheter aortic valve replacement (TAVR). The resultant left ventricular (LV) dyssynchrony may be associated with adverse clinical events. OBJECTIVES: The purpose of this study was to assess the adverse outcomes associated with LV dyssynchrony due to high-burden right ventricular (RV) pacing or permanent LBBB following TAVR in patients with preserved left ventricular ejection fraction (LVEF). METHODS: Consecutive TAVR patients at the University of Michigan from January 2012 to June 2017 were included. Pre-existing cardiac implantable electronic device, previous LBBB, LVEF <50%, or follow-up period <1 year were excluded. The primary outcome was all-cause mortality. Secondary outcomes included cardiomyopathy (defined as LVEF ≤45%), a composite endpoint of cardiomyopathy or all-cause mortality, and the change in LVEF at 1-year follow-up. RESULTS: A total of 362 patients were analyzed (mean age 77 years). LV dyssynchrony group (n = 91 [25.1%]) included 56 permanent LBBB patients, 12 permanent LBBB patients with PPM, and 23 non-LBBB patients with PPM and high-burden RV pacing. Remaining patients served as control (n = 271 [74.9%]). After adjusted analysis, LV dyssynchrony had significantly higher all-cause mortality (adjusted hazard ratio [HR] 2.16; 95% confidence interval [CI] 1.07-4.37) and cardiomyopathy (adjusted HR 14.80; 95% CI 6.31-14.69). The LV dyssynchrony group had mean LVEF decline of 10.5% ± 10.2% compared to a small increase (0.5% ± 7.7%) in control. CONCLUSION: Among TAVR patients with preserved LVEF and normal AV conduction, development of postprocedural LV dyssynchrony secondary to high-burden RV pacing or permanent LBBB was associated with significantly higher risk of death and cardiomyopathy at 1-year follow-up.

Transcatheter Aortic Valve Replacement with a Self-Expanding Prosthesis.

The self-expanding transcatheter heart valve (Medtronic Cardiovascular Corevalve and Evolut) is a supra-annular, trileafet porcine pericardial valves on a diamond lattice nickel-titanium alloy frame. The TAVR device has undergone significant improvements in design and procedural techniques to further increase safety, efficacy, and durability since they it was first released. Unique design characteristics, as well as patient and procedural factors, favor self-expanding over balloon-expandable prostheses in certain situations. The self-expanding transcatheter heart valve has proven to be an excellent option for severe aortic stenosis patients with any level of surgical risk and preliminary data suggest a comparable durability to surgical tissue valves.

Using data-driven approaches to improve delivery of animal health care interventions for public health.

Rabies kills ∼60,000 people per year. Annual vaccination of at least 70% of dogs has been shown to eliminate rabies in both human and canine populations. However, delivery of large-scale mass dog vaccination campaigns remains a challenge in many rabies-endemic countries. In sub-Saharan Africa, where the vast majority of dogs are owned, mass vaccination campaigns have typically depended on a combination of static point (SP) and door-to-door (D2D) approaches since SP-only campaigns often fail to achieve 70% vaccination coverage. However, D2D approaches are expensive, labor-intensive, and logistically challenging, raising the need to develop approaches that increase attendance at SPs. Here, we report a real-time, data-driven approach to improve efficiency of an urban dog vaccination campaign. Historically, we vaccinated ∼35,000 dogs in Blantyre city, Malawi, every year over a 20-d period each year using combined fixed SP (FSP) and D2D approaches. To enhance cost effectiveness, we used our historical vaccination dataset to define the barriers to FSP attendance. Guided by these insights, we redesigned our vaccination campaign by increasing the number of FSPs and eliminating the expensive and labor-intensive D2D component. Combined with roaming SPs, whose locations were defined through the real-time analysis of vaccination coverage data, this approach resulted in the vaccination of near-identical numbers of dogs in only 11 d. This approach has the potential to act as a template for successful and sustainable future urban SP-only dog vaccination campaigns.

Acute Myocardial Infarction and Papillary Muscle Rupture in the COVID-19 Era.

Mechanical complications of acute myocardial infarction are infrequent in the modern era of primary percutaneous coronary intervention, but they are associated with high mortality rates. Papillary muscle rupture with acute severe mitral regurgitation is one such life-threatening complication that requires early detection and urgent surgical intervention. (Level of Difficulty: Beginner.).

Factors associated with mobile phone ownership and potential use for rabies vaccination campaigns in southern Malawi.

BACKGROUND: Rabies is a fatal but preventable viral disease, which causes an estimated 59 000 human deaths globally every year. The vast majority of human rabies cases are attributable to bites from infected domestic dogs and consequently control of rabies in the dog population through mass vaccination campaigns is considered the most effective method of eliminating the disease. Achieving the WHO target of 70% vaccination coverage has proven challenging in low-resource settings such as Sub Saharan Africa, and lack of public awareness about rabies vaccination campaigns is a major barrier to their success. In this study we surveyed communities in three districts in Southern Malawi to assess the extent of and socio-economic factors associated with mobile phone ownership and explore the attitudes of communities towards the use of short message service (SMS) to inform them of upcoming rabies vaccination clinics. METHODS: This study was carried out between 1 October-3 December 2018 during the post-vaccination assessment of the annual dog rabies campaign in Blantyre, Zomba and Chiradzulu districts, Malawi. 1882 questionnaires were administered to households in 90 vaccination zones. The surveys gathered data on mobile phone ownership and use, and barriers to mobile phone access. A multivariable regression model was used to understand factors related to mobile phone ownership. RESULTS: Most survey respondents owned or had use of a mobile phone, however there was evidence of an inequality of access, with higher education level, living in Blantyre district and being male positively associated with mobile phone ownership. The principal barrier to mobile phone ownership was the cost of the phone itself. Basic feature phones were most common and few owned smartphones. SMS was commonly used and the main reason for not using SMS was illiteracy. Attitudes to receiving SMS reminders about future rabies vaccination campaigns were positive. CONCLUSIONS: The study showed a majority of those surveyed have the use of a mobile phone and most mobile phone owners indicated they would like to receive SMS messages about future rabies vaccination campaigns. This study provides insight into the feasibility of distributing information about rabies vaccination campaigns using mobile phones in Malawi.

The initial U.S. experience with the Tempo active fixation temporary pacing lead in structural heart interventions.

OBJECTIVES: This multicenter retrospective study of the initial U.S. experience evaluated the safety and efficacy of temporary cardiac pacing with the Tempo® Temporary Pacing Lead. BACKGROUND: Despite increasing use of temporary cardiac pacing with the rapid growth of structural heart procedures, temporary pacing leads have not significantly improved. The Tempo lead is a new temporary pacing lead with a soft tip intended to minimize the risk of perforation and a novel active fixation mechanism designed to enhance lead stability. METHODS: Data from 269 consecutive structural heart procedures were collected. Outcomes included device safety (absence of clinically significant cardiac perforation, new pericardial effusion, or sustained ventricular arrhythmia) and efficacy (clinically acceptable pacing thresholds with successful pace capture throughout the index procedure). Postprocedure practices and sustained lead performance were also analyzed. RESULTS: The Tempo lead was successfully positioned in the right ventricle and achieved pacing in 264 of 269 patients (98.1%). Two patients (0.8%) experienced loss of pace capture. Procedural mean pace capture threshold (PCT) was 0.7 ± 0.8 mA. There were no clinically significant perforations, pericardial effusions, or sustained device-related arrhythmias. The Tempo lead was left in place postprocedure in 189 patients (71.6%) for mean duration of 43.3 ± 0.7 hr (range 2.5-221.3 hr) with final PCT of 0.84 ± 1.04 mA (n = 80). Of these patients, 84.1% mobilized out of bed with no lead dislodgment. CONCLUSION: The Tempo lead is safe and effective for temporary cardiac pacing for structural heart procedures, provides stable peri and postprocedural pacing and allows mobilization of patients who require temporary pacing leads.

Outcomes of Veterans Undergoing TAVR Within Veterans Affairs Medical Centers: Insights From the Veterans Affairs Clinical Assessment, Reporting, and Tracking Program.

OBJECTIVES: This study sought to describe clinical and procedural characteristics of veterans undergoing transcatheter aortic valve replacement (TAVR) within U.S. Department of Veterans Affairs (VA) centers and to examine their association with short- and long-term mortality, length of stay (LOS), and rehospitalization within 30 days. BACKGROUND: Veterans with severe aortic stenosis frequently undergo TAVR at VA medical centers. METHODS: Consecutive veterans undergoing TAVR between 2012 and 2017 were included. Patient and procedural characteristics were obtained from the VA Clinical Assessment, Reporting, and Tracking system. The primary outcomes were 30-day and 1-year survival, LOS >6 days, and rehospitalization within 30 days. Logistic regression and Cox proportional hazards analyses were performed to evaluate the associations between pre-procedural characteristics and LOS and rehospitalization. RESULTS: Nine hundred fifty-nine veterans underwent TAVR at 8 VA centers during the study period, 860 (90%) by transfemoral access, 50 (5%) transapical, 36 (3.8%) transaxillary, and 3 (0.3%) transaortic. Men predominated (939 of 959 [98%]), with an average age of 78.1 years. There were 28 deaths within 30 days (2.9%) and 134 at 1 year (14.0%). Median LOS was 5 days, and 141 veterans were rehospitalized within 30 days (14.7%). Nonfemoral access (odds ratio: 1.74; 95% confidence interval [CI]: 1.10 to 2.74), heart failure (odds ratio: 2.51; 95% CI: 1.83 to 3.44), and atrial fibrillation (odds ratio: 1.40; 95% CI: 1.01 to 1.95) were associated with increased LOS. Atrial fibrillation was associated with 30-day rehospitalization (hazard ratio: 1.79; 95% CI: 1.22 to 2.63). CONCLUSIONS: Veterans undergoing TAVR at VA centers are predominantly elderly men with significant comorbidities. Clinical outcomes of mortality and rehospitalization at 30 days and 1-year mortality compare favorably with benchmark outcome data outside the VA.

Improving anti-platelet therapy adherence in the Veterans Health Administration: A randomized multi-site hybrid effectiveness-implementation study protocol.

BACKGROUND: P2Y12 inhibitors are critical following percutaneous coronary intervention (PCI) with stent placement; they reduce the risk of stent thrombosis and myocardial infarction. Despite the importance of the therapy, non-adherence is common among Veterans. METHODS AND RESULTS: Our main objective is to conduct a multi-site randomized stepped wedge trial to test the effectiveness of a multi-faceted intervention to improve adherence to P2Y12 inhibitors and PCI outcomes as well as formatively evaluate and refine the intervention implementation process. The primary outcomes of the study are the proportion of patients whose P2Y12 inhibitor prescription was filled at the time of hospital discharge following PCI with stent placement as well as the proportion of patients who were adherent based on the pharmacy refill data in the year after PCI hospital discharge. We will also assess the secondary outcomes such as bleeding, myocardial infarction, stroke, and mortality among these patients, and the cost-effectiveness of the intervention. The study was conducted at Veterans Health Administration (VA) PCI sites. At each site, we enrolled patients over a 6-month period and followed them for 12 months after PCI. Additionally, we collected qualitative data to identify contextual factors and to assess barriers and facilitators to the implementation and maintenance of the intervention. CONCLUSIONS: The study will add to the current state of knowledge on improving medication adherence in patients receiving PCI with stent implantation. Moreover, the study includes an extensive examination of the implementation process and will contribute to the field of implementation science. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01609842 https://clinicaltrials.gov/ct2/show/NCT01609842?term=clopidogrel+adherence&cntry1=NA%3AUS&rank=1.

Mindfulness and sustainability: correlation or causation?

Mindfulness-based approaches have been suggested as a potential remedy for an increasingly unsustainable consumption level in early industrialized countries. This article reviews twelve current empiric papers (2005ø2013) on five different potential pathways in which mindfulness is thought to unfold its effects on sustainable behaviors. Unfortunately, robust empiric evidence on the instrumentality of mindfulness-based interventions to promote sustainable lifestyles is still rare. Most of the available data originates from cross-sectional studies evidencing a small, positive relationship between some facets of dispositional mindfulness and diverse consumption behaviors. Null-effects of one prospective study blunt claims on the effectiveness of mindfulness practice to directly change consumption patterns though. Nevertheless, indirect effects including promotion of subjective well-being and decline of materialistic values are encouraging enough to justify future research on the topic. Specific recommendations for such future research are given.

On the porosity of subject and object in 'mindfulness' scientific study: challenges to 'scientific' construction, operationalization and measurement of mindfulness.

Mindfulness, derived from Buddhist psychology and philosophy, has gained broad popularity in the last decades, due importantly to scientific interest and findings. Yet Buddhist mindfulness developed in Asian pre-scientific culture and religion, and is predicated upon long-term cultivation of introspective awareness of lived experience, not highly accessible to empirical study. Further complicating the 'science' of mindfulness, mindfulness's very definition is multifaceted, resistant to dismantling and requires substantial amounts of personal practice to gain expertise. Most scientists investigating mindfulness have not achieved a high level of this expertise. Here I address how mindfulness is currently being invented as a scientific fact or object of inquiry. The intrinsic porosity of subjective and objective factors influencing the investigation of mindfulness is highlighted: the evolving body of 'scientific' experts, instruments used to measure mindfulness, the alliances of funders and other supporters of mindfulness research, and the public representation of the related findings.

VEGF and IGF Delivered from Alginate Hydrogels Promote Stable Perfusion Recovery in Ischemic Hind Limbs of Aged Mice and Young Rabbits.

Biomaterial-based delivery of angiogenic growth factors restores perfusion more effectively than bolus delivery methods in rodent models of peripheral vascular disease, but the same success has not yet been demonstrated in clinically relevant studies of aged or large animals. These studies explore, in clinically relevant models, a therapeutic angiogenesis strategy for the treatment of peripheral vascular disease that overcomes the challenges encountered in previous clinical trials. Alginate hydrogels providing sustained release of vascular endothelial growth factor (VEGF) and insulin-like growth factor-1 (IGF) were injected into ischemic hind limbs in middle-aged and old mice, and also in young rabbits, as a test of the scalability of this local growth factor treatment. Spontaneous perfusion recovery diminished with increasing age, and only the combination of VEGF and IGF delivery from gels significantly rescued perfusion in middle-aged (13 months) and old (20 months) mice. In rabbits, the delivery of VEGF alone or in combination with IGF from alginate hydrogels, at a dose 2 orders of magnitude lower than the typical doses used in past rabbit studies, enhanced perfusion recovery when given immediately after surgery, or as a treatment for chronic ischemia. Capillary density measurements and angiographic analysis demonstrated the benefit of gel delivery. These data together suggest that alginate hydrogels providing local delivery of low doses of VEGF and IGF constitute a safe and effective treatment for hind-limb ischemia in clinically relevant animal models, thereby supporting the potential clinical translation of this concept.

Coronary artery perforations after contemporary percutaneous coronary interventions: Evaluation of incidence, risk factors, outcomes, and predictors of mortality.

OBJECTIVES: We sought to evaluate the incidence, risk factors, in-hospital, and long-term outcomes and predictors of mortality of coronary artery perforations (CAP) in the contemporary percutaneous coronary intervention (PCI) era. BACKGROUND: CAP is a rare but serious complication of PCI associated with increased risk of morbidity and mortality. METHODS: We included 181,590 procedures performed across 47 hospitals in Michigan from January 1, 2010 to December 31, 2015. Endpoints evaluated included the incidence of CAP and its association with in-hospital outcomes. Logistic regression analysis was utilized to determine independent risk factors for CAP and to examine whether the effect of CAP on mortality varied by gender. RESULTS: CAP occurred in 625 (0.34%) patients. Independent predictors for CAP included older age, peripheral arterial disease, presence of left ventricular dysfunction or cardiomyopathy, lower body mass index, pre-PCI insertion of a mechanical ventricular support device, treatment of complex lesions (Type C), and treatment of chronic total occlusions, the latter of which was the strongest predictor of perforation (adjusted odds ratio (OR) 7.01, P < 0.001). After adjusting for baseline risk, the incidence of adverse outcomes remained substantially greater in patients with a perforation, with an adjusted OR estimate of 5.00 for mortality (95% CI 3.42-7.31), 3.25 for acute kidney injury (95% CI 2.30-4.58), and 5.26 for transfusion (95% CI 4.03-6.87) (all P < 0.001). Perforation was associated with a higher mortality in women than men (interaction P value = 0.01). CONCLUSIONS: CAP is a rare complication but is associated with high morbidity and mortality especially in women. Further investigation is warranted to determine why women fare worse after CAP. © 2017 Wiley Periodicals, Inc.

Temporal trends in peripheral arterial interventions: Observations from the blue cross blue shield of michigan cardiovascular consortium (BMC2 PVI).

OBJECTIVES: The aim is to examine trends in procedural indication, arterial beds treated, and device usage in peripheral arterial interventions (PVIs). BACKGROUND: There is little data on indication, vascular beds treated and devices utilized for peripheral arterial interventions. METHODS: We used data from 43 hospitals participating in the BMC2 VIC registry. PVIs were separated by year and divided by arterial segment. Lower extremity PVIs were subclassified as having been performed for claudication or critical limb ischemia (CLI). Yearly device usage was also included. A repeated measure ANOVA was used to determine trends. RESULTS: 44,650 PVIs were performed from 2006 to 2013. Renal interventions decreased from 18% of interventions in 2006 to 5.6% in 2013 (P < 0.001) and femoral-popliteal increased from 54.9% in 2006 to 64.5% in 2013 (P < 0.001). No significant trend was seen for aorta-iliac or below-the-knee interventions. 58.6% of PVIs were performed for claudication in 2006 and this decreased to 44.6% in 2013 (P = 0.025). Indications for CLI were 24.1% in 2006 and 47.5% in 2013 (P < 0.001). There were significant increases in the use of balloon angioplasty (P = 0.029) and cutting/scoring balloons (P < 0.001) while cryoballoon usage decreased (P < 0.001). No significant changes were found with stenting, atherectomy, and laser. CONCLUSIONS: There is a significant increase in patients presenting with CLI. Renal artery intervention rates are decreasing while femoral-popliteal interventions are increasing. Additionally, balloon angioplasty and cutting/scoring balloon usage is increasing. © 2017 Wiley Periodicals, Inc.

Students' satisfaction with general practitioners' feedback to their reflective writing: a randomized controlled trial.

BACKGROUND: Reflective Writing (RW) is increasingly being implemented in medical education. Feedback to students' reflective writing (RW) is essential, but resources for individualized feedback often lack. We aimed to determine whether general practitioners (GPs) teaching students clinical skills could also provide feedback to RW and whether an instruction letter specific to RW feedback increases students' satisfaction. METHODS: GPs were randomized to the two study arms using block randomization. GPs in both groups received an instruction letter on giving students feedback on clinical skills. Additionally, intervention group GPs received specific instructions on providing feedback to students' RW. Students completed satisfaction questionnaires on feedback received on clinical skills and RW. T-tests were employed for all statistical analysis to compare groups. RESULTS: Eighty-three out of 134 physicians participated: 38 were randomized to the control, 45 to the intervention group. Students were very satisfied with the feedback on RW and clinical skills regardless of tutors' group allocation. A specific instruction letter had no additional effect on students' satisfaction. CONCLUSION: Based on student satisfaction, GPs who give students feedback on clinical skills are also well suited to provide feedback on RW. This approach can facilitate the introduction of mandatory RW into the regular medical curriculum.

Mindfulness-Based Intervention Does Not Influence Cardiac Autonomic Control or the Pattern of Physical Activity in Fibromyalgia During Daily Life: An Ambulatory, Multimeasure Randomized Controlled Trial.

OBJECTIVES: Fibromyalgia (FM) is a syndrome characterized by severe pain, fatigue and sleep disturbance. There is evidence of central hyper-responsiveness to sensory stimulation and impaired cardiovascular autonomic control. Laboratory investigations suggest that mindfulness-based stress reduction (MBSR) may improve autonomic functioning in FM. However, these findings may not reflect what occurs during naturalistic conditions, and MBSR studies during real-life functioning are lacking. We conducted a randomized controlled, 3-armed study with 168 female FM patients. This report describes cardiac, respiratory, and physical activity findings. METHODS: Eight-week MBSR was compared with wait-list and active control intervention. Ambulatory accelerometry and cardiorespiratory function were monitored over 24-h periods at 3 time points: preintervention, postintervention, and at the 8-week follow-up. Also, baseline levels were compared with an age-matched group of 33 healthy women. FINDINGS: Activity heart rate, respiratory sinus arrhythmia, and ventilation were measured. Comparison with controls confirmed differences in cardiac autonomic tone and activity pattern among patients. Most measures also showed effects of time of day and point of measurement. Regarding the intervention study, there were no effects of treatment. In addition, there were no relations between patient-reported clinical improvement and objective physiological or accelerometry parameters. Intervention-related benefits in wellbeing were not associated with changes in daytime cardiorespiratory measures or pattern of physical activity. CONCLUSIONS: MBSR did not produce cardiac autonomic benefits or changes in daily activity in FM. Furthermore, the lack of an association between patient-experienced clinical improvement and objective physiological measures suggests that subjective changes in the wellbeing of FM patients over time are not related to alterations in the cardiorespiratory autonomic function or activity levels.

The optimal definition of contrast-induced acute kidney injury for prediction of inpatient mortality in patients undergoing percutaneous coronary interventions.

BACKGROUND: It is unknown which definition of contrast-induced acute kidney injury (CI-AKI) in the setting of percutaneous coronary interventions is best associated with inpatient mortality and whether this association is stable across patients with various preprocedural serum creatinine (SCr) values. METHODS: We applied logistic regression models to multiple CI-AKI definitions used by the Kidney Disease Improving Global Outcomes guidelines and previously published studies to examine the impact of preprocedural SCr on a candidate definition's correlation with the adverse outcome of inpatient mortality. We used likelihood ratio tests to examine candidate definitions and identify those where association with inpatient mortality remained constant regardless of preprocedural SCr. These definitions were assessed for specificity, sensitivity, and positive and negative predictive values to identify an optimal definition. RESULTS: Our study cohort included 119,554 patients who underwent percutaneous coronary intervention in Michigan between 2010 and 2014. Most commonly used definitions were not associated with inpatient mortality in a constant fashion across various preprocedural SCr values. Of the 266 candidate definitions examined, 16 definition's association with inpatient mortality was not significantly altered by preprocedural SCr. Contrast-induced acute kidney injury defined as an absolute increase of SCr ≥0.3 mg/dL and a relative SCr increase ≥50% was selected as the optimal candidate using Perkins and Shisterman decision theoretic optimality criteria and was highly predictive of and specific for inpatient mortality. CONCLUSIONS: We identified the optimal definition for CI-AKI to be an absolute increase in SCr ≥0.3 mg/dL and a relative SCr increase ≥50%. Further work is needed to validate this definition in independent studies and to establish its utility for clinical trials and quality improvement efforts.

Mortality Predictors in Patients Referred for but Not Undergoing Transcatheter Aortic Valve Replacement.

Although transcatheter aortic valve replacement (TAVR) has expanded the proportion of patients with aortic stenosis (AS) who are candidates for valve replacement, some patients remain untreated, and their outcomes are not clear. We evaluated 172 consecutive patients with severe symptomatic AS referred for TAVR who declined (n = 55) or were not candidates for (n = 117) intervention. We examined clinical and echocardiographic variables associated with mortality. There were 77 deaths, and mean follow-up was 17.9 ± 10.9 months for survivors. Mortality rate at 1 and 2 years was 39.2% and 52.6%, respectively. There was a significant difference in mortality rate between patients who declined the procedure and those who were not candidates (p = 0.001), with 1-year mortality rates of 20.6% and 48.4%, respectively. On multivariate analysis, 4 variables were independently associated with all-cause mortality: New York Heart Association Class IV heart failure (hazard ratio [HR] 2.6, 95% confidence interval [CI] 1.6 to 4.2, p <0.001), glomerular filtration rate <48 ml/min (HR 2.1, 95% CI 1.3 to 3.4, p = 0.002), albumin <3.9 g/dl (HR 1.9, 95% CI 1.2 to 3.1, p = 0.007), and ejection fraction <50% (HR 1.9, 95% CI 1.4 to 3.0, p = 0.01). In this new era with expanded treatment options, patients with severe symptomatic AS who remain untreated after referral for TAVR experience a mortality rate of 39% at 1 year. The presence of advanced heart failure, renal dysfunction, low albumin, and/or left ventricular dysfunction identifies patients at higher risk of mortality.

Metabolic decoupling in daily life in patients with panic disorder and agoraphobia.

Various studies have assessed autonomic and respiratory underpinnings of panic attacks, yet the psychophysiological functioning of panic disorder (PD) patients has rarely been examined under naturalistic conditions at times when acute attacks were not reported. We hypothesized that emotional activation in daily life causes physiologically demonstrable deviations from efficient metabolic regulation in PD patients. Metabolic coupling was estimated as within-individual correlations between heart rate (HR) and indices of metabolic activity, i.e., physical activity (measured by 3-axial accelerometry, Acc), and minute ventilation (Vm, measured by calibrated inductive plethysmography, as proxy for oxygen consumption). A total of 565 daytime hours were recorded in 19 PD patients and 20 healthy controls (HC). Pairwise cross-correlations of minute-by-minute averages of these metabolic indices were calculated for each participant and then correlated with several indices of self-reported anxiety. Ambulatory HR was elevated in PD (p = .05, d = 0.67). Patients showed reduced HR-Acc (p < .006, d = 0.97) and HR-Vm coupling (p < .009, d = 0.91). Combining Vm and Acc to predict HR showed the strongest group separation (p < .002, d = 1.07). Discriminant analyses, based on the combination of Vm and Acc to predict HR, classified 77% of all participants correctly. In PD, HR-Acc coupling was inversely related to trait anxiety sensitivity, as well as tonic and phasic daytime anxiety. The novel method that was used demonstrates that anxiety in PD may reduce efficient long-term metabolic coupling. Metabolic decoupling may serve as physiological characteristic of PD and might aid diagnostics for PD and other anxiety disorders. This measure deserves further study in research on health consequences of anxiety and psychosocial stress.