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Jerome A Yesavage,1,2 Lisa M Kinoshita,1,2 Art Noda,2 Laura C Lazzeroni,2 Jennifer Kaci Fairchild,1,2 Joy Taylor,1,2 Doina Kulick,3 Leah Friedman,1,2 Jauhtai Cheng,1,2 Jamie M Zeitzer,1,2 Ruth O’Hara1,21Department of Veterans Affairs Health Care System, Palo Alto, CA, USA; 2Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA, USA; 3Department of Medicine, University of Nevada School of Medicine, Reno, NV, USABackground: Well-known risk factors for cognitive impairment are also associated with obesity. Research has highlighted genetic risk factors for obesity, yet the relationship of those risk factors with cognitive impairment is unknown. The objective of this study was to determine the associations between cognition, hypertension, diabetes, sleep-disordered breathing, and obesity. Genetic risk factors of obesity were also examined.Methods: The sample consisted of 369 nondemented individuals aged 50 years or older from four community cohorts. Primary outcome measures included auditory verbal memory, as measured by the Rey Auditory Verbal Learning Test, and executive functioning, as measured by the Color–Word Interference Test of the Delis–Kaplan Executive Function System battery. Apnea–hypopnea index indicators were determined during standard overnight polysomnography. Statistical analyses included Pearson correlations and linear regressions.Results: Poor executive function and auditory verbal memory were linked to cardiovascular risk factors, but not directly to obesity. Genetic factors appeared to have a small but measureable association to obesity.Conclusion: A direct linkage between obesity and poor executive function and auditory verbal memory is difficult to discern, possibly because nonobese individuals may show cognitive impairment due to insulin resistance and the “metabolic syndrome”.Keywords: sleep-disordered breathing, hypertension, diabetes, sleep apnea, BMI, obesity

Ketones are well-known biomarkers of fat oxidation produced in the liver as a result of lipolysis. These biomarkers include acetoacetic acid and β-hydroxybutyric acid in the blood/urine and acetone in our breath and skin. Monitoring ketone production in the body is essential for people who use caloric intake deficit to reduce body weight or use ketogenic diets for wellness or therapeutic treatments. Current methods to monitor ketones include urine dipsticks, capillary blood monitors, and breath analyzers. However, these existing methods have certain disadvantages that preclude them from being used more widely. In this work, we introduce a novel acetone sensor device that can detect acetone levels in breath and overcome the drawbacks of existing sensing approaches. The critical element of the device is a robust sensor with the capability to measure acetone using a complementary metal oxide semiconductor (CMOS) chip and convenient data analysis from a red, green, and blue deconvolution imaging approach. The acetone sensor device demonstrated sensitivity of detection in the micromolar-concentration range, selectivity for detection of acetone in breath, and a lifetime stability of at least one month. The sensor device utility was probed with real tests on breath samples using an established blood ketone reference method.

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by the death of upper and lower motor neurons. While causative genes have been identified, 90% of ALS cases are not inherited and are hypothesized to result from the accumulation of genetic and environmental risk factors. While no specific causative environmental toxin has been identified, previous work has indicated that the presence of the organochlorine pesticide cis- chlordane in the blood is highly correlated with ALS incidence. Never before tested on the motor system, here, we show that cis- chlordane is especially toxic to motor neurons in vitro- and in vivo-independent of its known antagonism of the GABA A receptor. We find that human stem-cell-derived motor neurons are more sensitive to cis -chlordane than other cell types and their action potential dynamics are altered. Utilizing zebrafish larvae, we show that cis- chlordane induces motor neuron and neuromuscular junction degeneration and subsequent motor deficits in a touch-evoked escape response. Together, our work points to cis -chlordane as a potential sporadic ALS exacerbating environmental pollutant.

ALS-linked mutations induce aberrant conformations within the SOD1 protein that are thought to underlie the pathogenic mechanism of SOD1-mediated ALS. Although clinical trials are underway for gene silencing of SOD1 , these approaches reduce both wild-type and mutated forms of SOD1. Here, we sought to develop anti-SOD1 nanobodies with selectivity for mutant and misfolded forms of human SOD1 over wild-type SOD1. Characterization of two anti-SOD1 nanobodies revealed that these biologics stabilize mutant SOD1 in vitro. Further, SOD1 expression levels were enhanced and the physiological subcellular localization of mutant SOD1 was restored upon co-expression of anti-SOD1 nanobodies in immortalized cells. In human motor neurons harboring the SOD1 A4V mutation, anti-SOD1 nanobody expression promoted neurite outgrowth, demonstrating a protective effect of anti-SOD1 nanobodies in otherwise unhealthy cells. In vitro assays revealed that an anti-SOD1 nanobody exhibited selectivity for human mutant SOD1 over endogenous murine SOD1, thus supporting the preclinical utility of anti-SOD1 nanobodies for testing in animal models of ALS. In sum, the anti-SOD1 nanobodies developed and presented herein represent viable biologics for further preclinical testing in human and mouse models of ALS.

Energy Expenditure (EE) (kcal/day), a key element to guide obesity treatment, is measured from CO 2 production, VCO 2 (mL/min), and/or O 2 consumption, VO 2 (mL/min). Current technologies are limited due to the requirement of wearable facial accessories. A novel system, the Smart Pad, which measures EE via VCO 2 from a room's ambient CO 2 concentration transients was evaluated. Resting EE (REE) and exercise VCO 2 measurements were recorded using Smart Pad and a reference instrument to study measurement duration's influence on accuracy. The Smart Pad displayed 90% accuracy (±1 SD) for 14-19 min of REE measurement and for 4.8-7.0 min of exercise, using known room's air exchange rate. Additionally, the Smart Pad was validated measuring subjects with a wide range of body mass indexes (BMI = 18.8 to 31.4 kg/m 2 ), successfully validating the system accuracy across REE's measures of ~1200 to ~3000 kcal/day. Furthermore, high correlation between subjects' VCO 2 and λ for CO 2 accumulation was observed ( p < 0.00001, R = 0.785) in a 14.0 m 3 sized room. This finding led to development of a new model for REE measurement from ambient CO 2 without λ calibration using a reference instrument. The model correlated in nearly 100% agreement with reference instrument measures ( y = 1.06 x , R = 0.937) using an independent dataset (N = 56).

Background & Aims: Resting Energy Expenditure (REE) quantitatively describes the calories used to support body function (e.g. breathing, blood circulation, etc.) at resting condition. Assessment of the REE is essential for successful weight management and the understanding of metabolic health. REE is typically determined via indirect calorimetry. Current biomedical indirect calorimetry technologies, utilizing assessment of oxygen consumption (VO 2 ) and carbon dioxide production (VCO 2 ) rates (which are typically in the form factor of a metabolic cart) are bulky and require on-site calibration and/or trained professionals to operate. We introduce a novel wearable medical device with FDA clearance to determine REE accurately, portable, and user-friendly format, which can be used both by health professionals in a clinical environment and by the patient at home. Previously, we have reported the validation of Breezing Med (also named as Breezing Pro™) through Douglas Bag Method, a gold standard for gas exchange measurement, and excellent agreement has been found between the two methods for the determination of REE, VO 2 , and VCO 2 rates (Mora et al., 2020). Now we present the validation of Breezing Med against Medical Graphics (MGC) CPX Ultima™, a FDA 510 k cleared metabolic cart, which principle is based on breath-by-breath analysis. In addition, we present Breezing Med as a tool for daily measurement of metabolic rate by the lay person at home., Methods: A) The validation study was executed via parallel measurement of 20 healthy participants under resting conditions using both the Breezing Med and the MGC Ultima CPX™ (10 min test). B) Breezing Med measurements were carried out by six subjects at home during stay-at-home order due to COVID-19 for 30 days., Results: A) The resulting measurements from both devices was compared with correlation slope's and R-squared coefficients close to 1. B) Results were recorded and analyzed for variability. The pilot study demonstrated the advantage of Breezing Med device to be easy-to-use at home by lay people, which make the valuable device for telemedicine applications related to weight management from home., Conclusions: This result shows that the MGC Ultima CPX™ and Breezing Med are substantially equivalent for REE measurement; and an advantage of this device for metabolic assessment under the current COVID-19 pandemic situation, for people with impaired physical mobility, and for those who lives in rural areas or face impediments that limit physical access to care., Competing Interests: Declaration of competing interest All authors, excepting Erica Forzani and Xiaojun Xian, currently with Breezing Co., declare no conflict of interest., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Weight disorders are strikingly prevalent globally and can contribute to a wide array of potentially fatal diseases spanning from type II diabetes to coronary heart disease. These disorders have a common cause: poor calorie balance. Since energy expenditure (EE) (kcal d -1 ) constitutes one half of the calorie balance equation (the other half being food intake), its measurement could be of great value to those suffering from weight disorders. A technique for contact free assessment of EE is presented, which only relies on CO 2 concentration monitoring within a sealed office space, and assessment of carbon dioxide production rate (VCO 2 ). Twenty healthy subjects were tested in a cross-sectional study to evaluate the performance of the aforementioned technique in measuring both resting EE (REE) and exercise EE using the proposed system (the 'SmartPad') and a U.S. Food and Drug Administration (FDA) cleared gold standard reference instrument for EE measurement. For VCO 2 and EE measurements, the method showed a correlation slope of 1.00 and 1.03 with regression coefficients of 0.99 and 0.99, respectively, and Bland-Altman plots with a mean bias = -0.232% with respect to the reference instrument. Furthermore, two subjects were also tested as part of a proof-of-concept longitudinal study where EE patterns were simultaneously tracked with body weight, sleep, stress, and step counts using a smartwatch over the course of a month, to determine correlation between the aforementioned parameters and EE. Analysis revealed moderately high correlation coefficients (Pearson's r ) for stress ( r average = 0.609) and body weight ( r average = 0.597) for the two subjects. The new SmartPad method was demonstrated to be a promising technique for EE measurement under free-living conditions., (© 2021 IOP Publishing Ltd.)

This work investigates the use of an intelligent and unobstructive sensing technique for maintaining vehicle cabin's indoor air quality while simultaneously assessing the driver metabolic rate. CO 2 accumulation patterns are of great interest because CO 2 can have negative cognitive effects at higher concentrations and also since CO 2 accumulation rate can potentially be used to determine a person's metabolic rate. The management of the vehicle's ventilation system was controlled by periodically alternating the air recirculation mode within the cabin, which was actuated based on the CO 2 levels inside the vehicle's cabin. The CO 2 accumulation periods were used to assess the driver's metabolic rate, using a model that considered the vehicle's air exchange rate. In the process of the method optimization, it was found that the vehicle's air exchange rate (λ [h -1 ]) depends on the vehicle speeds, following the relationship: λ = 0.060 × (speed) - 0.88 when driving faster than 17 MPH. An accuracy level of 95% was found between the new method to assess the driver's metabolic rate (1620 ± 140 kcal/day) and the reference method of indirect calorimetry (1550 ± 150 kcal/day) for a total of N = 16 metabolic assessments at various vehicle speeds. The new sensing method represents a novel approach for unobstructive assessment of driver metabolic rate while maintaining indoor air quality within the vehicle cabin.

Background/objectives: Obesity is an important risk factor for the development of diseases such as diabetes mellitus, hypertension, and dyslipidemia; however, a small number of individuals with long-standing obesity do not present with these cardiometabolic diseases. Such individuals are referred to as metabolically healthy obese (MHO) and potentially represent a subgroup of the general population with a protective genetic predisposition to obesity-related diseases. We hypothesized that individuals who were metabolically healthy, but significantly obese (BMI ≥ 35 kg/m 2 ) would represent a highly homogenous subgroup, with which to investigate potential genetic associations to obesity. We further hypothesized that such a cohort may lend itself well to investigate potential genotypes that are protective with respect to the development of cardiometabolic disease., Subjects/methods: In the present study, we implemented this novel selection strategy by screening 892 individuals diagnosed as Class 2 or Class 3 obese and identified 38 who presented no manifestations of cardiometabolic disease. We then assessed these subjects for single-nucleotide polymorphisms (SNPs) that associated with this phenotype., Results: Our analysis identified 89 SNPs that reach statistical significance (p < 1 × 10 -5 ), some of which are associated with genes of biological pathways that influences dietary behavior; others are associated with genes previously linked to obesity and cardiometabolic disease as well as neuroimmune disease. This study, to the best of our knowledge, represents the first genetic screening of a cardiometabolically healthy, but significantly obese population.

The present work introduces the use of environmental sensors to assess indoor air quality (IAQ) in combination with human biometrics. The sensor array included temperature, relative humidity, carbon dioxide, and noise monitors. The array was used in a classroom as well as in a vehicle cabin to assess the carbon dioxide production rate of individuals in a closed ventilation environment. Analysis of carbon dioxide production allowed for the quantification of the average metabolic rate of the group of individuals in the classroom, and for one individual in the vehicle cabin. These results yielded a mere 5% difference from the values assessed using commercial metabolic rate instruments, and averaged values from epidemiological studies. The results presented in this work verify the feasibility of determining an individual's metabolic rate using passive environmental sensors; these same sensors are able to provide a metric of IAQ that helps characterize the safety of the environment in which the individual is present.

txt4health is an innovative, 14-week, interactive, population-based mobile health program for individuals at risk of type 2 diabetes, developed under the Beacon Community Program in the Greater New Orleans, La., area. A comprehensive social marketing campaign sought to enroll hard-to-reach, at-risk populations using a combination of mass media and face-to-face engagement in faith-based and retail environments. Little is known about the effectiveness of social marketing for mobile technology application in the general population. A systematic evaluation of the campaign identified successes and barriers to implementing a population-based mobile health program. Face-to-face engagement helped increase program enrollment after the initial launch; otherwise, enrollment leveled off over time. Results show positive trends in reaching target populations and in the use of mobile phones to record personal health information and set goals for reducing the risk of type 2 diabetes. The lessons from the txt4health campaign can help inform the development and programmatic strategies to provide a person-level intervention using a population-level approach for individuals at risk for diabetes as well as aid in chronic disease management.

Background: We hypothesized that higher concentrations of LDL particles (LDL-P) and leptin, and lower concentrations of HDL particles (HDL-P), and total and high molecular weight (HMW) adiponectin, would predict incident coronary heart disease (CHD) among severely obese postmenopausal women., Methods: In a case-cohort study nested in the Women's Health Initiative Observational Study, we sampled 677 of the 1852 white or black women with body mass index (BMI) ≥40 kg/m 2 and no prevalent cardiovascular disease (CVD), including all 124 cases of incident CHD over mean 5.0 year follow-up. Biomarkers were assayed on stored blood samples., Results: In multivariable-adjusted weighted Cox models, higher baseline levels of total and small LDL-P, and lower levels of total and medium HDL-P, and smaller mean HDL-P size were significantly associated with incident CHD. In contrast, large HDL-P levels were inversely associated with CHD only for women without diabetes, and higher total and HMW adiponectin levels and lower leptin levels were associated with CHD only for women with diabetes. Higher total LDL-P and lower HDL-P were associated with CHD risk independently of confounders including CV risk factors and other lipoprotein measures, with adjusted HR (95%CIs) of 1.55(1.28, 1.88) and (0.70 (0.57, 0.85), respectively, and similar results for medium HDL-P., Conclusions: Higher CHD risk among severely obese postmenopausal women is strongly associated with modifiable concentrations of LDL-P and HDL-P, independent of diabetes, smoking, hypertension, physical activity, BMI and waist circumference., General Significance: Severely obese postmenopausal women should be considered high risk candidates for lipid lowering therapy.

Background: Diet is the first line of treatment for elevated cholesterol. High-intensity dietary counseling (≥360 minutes/year of contact with providers) improves blood lipids, but is expensive and unsustainable in the current healthcare settings. Low-intensity counseling trials (≤30 minutes/year) have demonstrated modest diet changes, but no improvement in lipids. This pilot study evaluated the feasibility and the effects on lipids and diet of a low-intensity dietary counseling intervention provided by the primary care physician (PCP), in patients at risk for cardiovascular diseases., Methods: Six month study with a three month randomized-controlled phase (group A received the intervention, group B served as controls) followed by three months of intervention in both groups.Sixty-one adults age 21 to 75 years, with LDL-cholesterol≥3.37 mmol/L, possessing Internet access and active email accounts were enrolled. Diet was evaluated using the Rate-Your-Plate questionnaire. Dietary counseling was provided by the PCP during routine office visits, three months apart, using printed educational materials and a minimally interactive counseling website. Weekly emails were sent reminding participants to use the dietary counseling resources. The outcomes were changes in LDL-cholesterol, other lipid subclasses, and diet quality., Results: At month 3, group A (counseling started at month 1) decreased their LDL-cholesterol by -0.23 mmol/L, (-0.04 to -0.42 mmol/L, P=0.007) and total cholesterol by -0.26 mmol/L, (-0.05 to -0.47 mmol/L, P=0.001). At month 6, total and LDL-cholesterol in group A remained better than in group B (counseling started at month 3). Diet score in group A improved by 50.3 points (38.4 to 62.2, P<0.001) at month 3; and increased further by 11.8 (3.5 to 20.0, P=0.007) at month 6. Group B made the largest improvement in diet at month 6, 55 points (40.0 to 70.1, P<0.001), after having a small but significant improvement at month 3, 22.3 points (12.9 to 31.7, P<0.001). No significant changes occurred in HDL-cholesterol in either group., Conclusions: A low-intensity dietary counseling provided by the PCP in patients at risk for cardiovascular diseases produced clinically meaningful improvements in both diet and lipids of magnitude similar to changes reported with high intensity interventions., Trial Registration: ClinicalTrials.gov: NCT01695837.

Specialized nutrition support should be offered to patients who are malnourished or at risk of becoming malnourished when it would benefit patient outcomes or quality of life. Improving the nutritional value of ingested food and tailoring intake to the patient's preferences, abilities, and schedule should be the first measures in addressing nutritional needs. When these interventions alone are insufficient to meet nutritional requirements, oral nutritional supplements should be considered. Nutritional status should be evaluated in patients before specialized nutrition sup- port is considered. Enteral nutrition is used when patients have a functional gastrointestinal tract but are unable to safely swallow. Although a variety of enteral formulas are available, evidence for choosing a specific formula is often lacking. Parenteral nutrition should be used only when enteral nutrition is not feasible. There are no known benefits of parenteral nutrition over the enteral route, and the risk of serious complications is much greater with parenteral nutrition. Even when the parenteral route is necessary, some enteral nutrition is beneficial when possible. Specialized nutrition support can provide an effective bridge until patients are able to return to normal food and, in rare cases, may be continued as long-term home enteral or parenteral nutrition. Specialized nutrition support is not obligatory and can be harmful in cases of futile care and at the end of life.

Between 1998 and 2004, the total number of bariatric procedures increased almost 10-fold, from 13,386 procedures in 1998 to 121,055 in 2004. Current estimates suggest the number of bariatric operations will exceed 220,000 in 2010. Bariatric surgery encompasses several surgical techniques classified as restrictive or malabsorptive, based on the main mechanism of weight loss. Clinical studies and meta-analyses show that bariatric surgery decreases morbidity and mortality when compared with nonsurgical treatments. A successful long-term outcome of bariatric surgery is dependent on the patient's commitment to a lifetime of dietary and lifestyle changes. The registered dietitian (RD) is an important member of the bariatric team and provides critical instructions to help patients adhere to the dietary changes consistent with surgery. Referencing current literature, this article outlines the indications, contraindications, and types of bariatric surgery. The role of the RD for preoperative and postoperative nutrition assessment and medical nutrition therapy is highlighted. Management of long-term nutrition issues is also reviewed. The current recommendations include a multivitamin/mineral supplement plus vitamin B-12, calcium, vitamin D-3, iron, and folic acid. Given the increasing prevalence of obesity and bariatric surgery procedures, caring for patients who have undergone surgery will be an expanding role for the RD. Close postoperative follow-up and careful monitoring will improve the odds for successful surgical outcomes, and RDs play a very important part in this process., (Copyright (c) 2010 American Dietetic Association. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary xenotransplantation is currently limited by hyperacute rejection mediated in part by xenoreactive natural antibody and complement. Transgenic swine organs that express the human complement regulatory protein CD59 have demonstrated improved survival in models of pig-to-primate xenotransplantation., Objective: The purpose of this study was to evaluate transgenic swine lungs that express the human complement regulatory protein CD59 in a model of pig-to-human xenotransplantation., Methods: Transgenic swine lungs (n = 5, experimental group) and outbred swine lungs (n = 6, control group) were perfused with fresh, whole human blood through a centrifugal pump on an ex vivo circuit. Functional data were collected throughout perfusion. Immunoglobulin and complement studies were performed on perfusate samples, and both histologic and immunofluorescent analyses were performed on tissue sections., Results: Mean lung survival for the experimental group was increased when compared with controls, 240 +/- 0 minutes versus 35.3 +/- 14.5 minutes, respectively, with a P value of less than.01. A decreased rise in pulmonary vascular resistance at 15 minutes was observed in the experimental group (343 +/- 87 mm Hg. L(-1). min(-1), in contrast to the control group (1579 +/- 722 mm Hg. L(-1). min(-1); P <.01). Pulmonary compliance at 15 minutes was improved for the experimental group versus control group (9.31 +/- 1.41 mL. cm(-2) H(2)O and 4.11 +/- 2.84 mL. cm(-2) H(2)O, respectively; P <.01). SC5b-9 generation in the plasma perfusate was delayed for the experimental group versus the control group. Immunofluorescent examination of tissue sections demonstrated equivalent deposition of immunoglobulin G, immunoglobulin M, C1q, and C3 in both groups, with reduced deposition of C9 in the experimental group., Conclusions: Transgenic swine pulmonary xenografts that express the human complement regulatory protein CD59 demonstrated improved function and survival in an ex vivo model of pig-to-human xenotransplantation.

Background: Extracorporeal photopheresis is an immunomodulatory technique in which a patient's leukocytes are exposed to ultraviolet-A light after pretreatment with 8-methoxypsoralen (methoxsalen). There have been few reports describing the use of extracorporeal photopheresis in lung transplant recipients., Methods: We reviewed our experience using extracorporeal photopheresis in 8 lung transplant recipients since 1992. All 8 patients had progressively decreasing graft function and 7 were in bronchiolitis obliterans syndrome grade 3 before the initiation of photopheresis. One patient had undergone a second transplant operation for obliterative bronchiolitis. Two patients had a pretransplantation diagnosis of chronic obstructive pulmonary disease, 1 alpha1-antitrypsin deficiency, 1 cystic fibrosis, 1 bronchiectasis, 1 idiopathic pulmonary fibrosis, and 2 primary pulmonary hypertension. Before refractory rejection developed, all patients had been treated with 3-drug immunosuppression and anti-T-cell therapy. The median time from transplantation to the start of extracorporeal photopheresis was 16.5 months and the median number of treatments was 6., Results: The condition of 5 of 8 patients subjectively improved after extracorporeal photopheresis therapy. In these 5 patients photopheresis was associated with stabilization of the forced expiratory volume in 1 second. In 2 patients there was histologic reversal of rejection after photopheresis. With a median follow-up of 36 months, 7 patients are alive and well. Three patients required retransplantation at a median of 21 months after completion of the treatments. Four patients have remained in stable condition after photopheresis. There were no complications related to extracorporeal photopheresis., Conclusion: We believe that this treatment is a safe option for patients with refractory lung allograft rejection when increased immunosuppression is contraindicated or ineffective.

Coronary arteriography maintains a major role in the management of patients with stable and unstable anginal syndromes, in the establishment of diagnosis and prognosis, and in guiding the choice of therapeutic alternatives. Included in this article are discussions of assessment of coronary artery disease, and coronary arteriography in patients with stable and unstable angina pectoris.

With the reduction in profile of balloon dilation catheters, until recently, it has been the internal dimensions and performance of the guiding catheter that has mandated the use of 7, 8 or 9 French (F) systems for the performance of percutaneous transluminal coronary angioplasty (PTCA). A new 5F catheter design (Sherwood Medical Co., St. Louis, MO) provided a large inner lumen (0.4") permitting use of 0.20-0.22" fixed-wire PTCA balloon catheters with good coronary visualization. Potential advantages include reduced coronary artery ostial trauma and catheter induced damping and enhanced patient comfort. We report our initial experience in 14 patients undergoing PTCA with a 5 and 6F guide/fixed-wire system. Mean age was 63 +/- 10 (43-78 years). PTCA indications: Cardiogenic shock (1), post-myocardial infarction angina pectoris (2), grade III angina (5) and unstable angina pectoris (6). Vessel attempted: Left anterior descending (3), circumflex (4), obtuse marginal (2), diagonal (1), right coronary artery (3), and internal thoracic artery (1). Twelve patients had femoral approach; two brachial approach. The USCI Probe (USCI Division, Billerica, MA) was used in 8 lesions and SCIMED ACE (SCIMED Life Systems, Maplegrove, MN) catheter in 7 lesions. Successful 5 or 6F guide/fixed-wire dilations reduced the stenosis (77 +/- 14 to 37 +/- 30%) and were successfully performed in 79% (11/14). One 5F patient required 8F guiding catheter and was dilated with 2.0 fixed-wire balloon. A second failed 5F PTCA could not be dilated with any larger conventional system. A third total occlusion could not be crossed with a guidewire or fixed wire balloon. No patient had a complication.(ABSTRACT TRUNCATED AT 250 WORDS)

Day to day reproducibility of the response to programmed ventricular stimulation has not been evaluated in survivors of acute myocardial infarction. Programmed ventricular stimulation was performed prospectively on 2 consecutive days in 56 patients on an average of 12 +/- 5 days (range 7 to 29) after an acute myocardial infarction. No patient had a history of documented or suspected sustained ventricular tachycardia or fibrillation occurring greater than 48 h after infarction. During initial programmed ventricular stimulation, 21 patients had induction of sustained ventricular tachycardia or fibrillation (Group I), and 35 patients had induction of either nonsustained ventricular tachycardia or no ventricular tachycardia (Group II). Repeat programmed ventricular stimulation in Group I patients induced sustained ventricular tachycardia or fibrillation in 16 of 21 patients (reproducibility 76%); the maximal induced response in the other 5 patients was nonsustained ventricular tachycardia in 2 patients and fewer than six repetitive ventricular responses in 3 patients. The day to day reproducibility was significantly higher for inducible sustained ventricular tachycardia of cycle length greater than or equal to 240 ms compared with rapid sustained ventricular tachycardia of cycle length less than 240 ms (100% versus 44%, p less than 0.009) or ventricular fibrillation (100% versus 43%, p less than 0.009). Repeat programmed ventricular stimulation in Group II patients did not induce sustained ventricular arrhythmias in 31 of 35 patients (reproducibility 89%). Thus, in survivors of acute myocardial infarction, inducible slow sustained ventricular tachycardia was a highly reproducible finding, whereas inducibility of rapid sustained ventricular tachycardia and ventricular fibrillation showed a significant day to day variability.(ABSTRACT TRUNCATED AT 250 WORDS)

In patients with dilated cardiomyopathy, hemodynamic decompensation has been postulated to increase vulnerability to reentrant ventricular arrhythmias. To test this hypothesis, we performed programmed ventricular stimulation with three extrastimuli on nine patients with dilated cardiomyopathy and asymptomatic complex ventricular arrhythmias during a period of acute hemodynamic decompensation; programmed ventricular stimulation was then repeated following hemodynamic improvement with nitroprusside. These patients did not have a history of documented or suspected sustained ventricular tachycardia or fibrillation. The mean left ventricular ejection fraction was 0.21 +/- 0.04 (range 0.15 to 0.26). In the baseline state, mean right atrial pressure was 8 +/- 4 mm Hg, pulmonary artery wedge pressure was 20 +/- 3 mm Hg, and cardiac index was 3.2 +/- 0.5 L/min/m2. Following acute hemodynamic decompensation, mean right atrial pressure increased to 16 +/- 5 mm Hg and pulmonary artery wedge pressure to 33 +/- 8 mm Hg; cardiac index decreased to 2.1 +/- 0.5 L/min/m2. In this decompensated state, programmed ventricular stimulation failed to induce sustained or nonsustained ventricular arrhythmias in any patient. Following nitroprusside administration (mean dose 1.5 +/- 1.1 micrograms/kg/min), there were significant decreases in mean right atrial pressure (11 +/- 3 mm Hg) and pulmonary artery wedge pressure (16 +/- 3 mm Hg), and a significant increase in cardiac index (3.1 +/- 1.1 L/min/m2) (p less than 0.05 for all values versus the decompensated state). In the improved hemodynamic state, programmed ventricular stimulation induced nonsustained ventricular tachycardia (six beats) in only one patient, and sustained arrhythmias in none.(ABSTRACT TRUNCATED AT 250 WORDS)

From the foregoing discussion, it becomes apparent that although noninvasive risk stratification is a reasonable approach to assessment of patients following an uncomplicated myocardial infarction, the performance of early cardiac catheterization and angiography on nearly all such patients is not unreasonable and may in fact be the most practical approach. The basis for this rationalization may be summarized as follows: 1. Many subgroups will need early catheterization anyway a. Myocardial infarction complicated by recurrent ischemia, heart failure, or complex ventricular arrhythmias b. Patients receiving thrombolytic treatment c. "Young" patients (less than 50 years old?) d. "Older" patients (over ages 65 to 70?) in otherwise good medical condition e. Patients unable to exercise f. Patients with abnormal or inconclusive noninvasive test results (approximately 70 percent of patients) 2. Cardiac catheterization and angiography as a single test provides the two most powerful prognostic variables following myocardial infarction, namely, the extent of coronary artery disease and residual left ventricular function. This knowledge is reassuring to both physician and patient and allows for planning of optimal long-term management. 3. Certain limitations exist in noninvasive risk assessment strategies. 4. This approach need not be significantly more costly, if all tests are used wisely. The major risk inherent in the definition of the extent of coronary artery disease in all survivors of acute myocardial infarction might be the performance of unnecessary revascularization procedures (percutaneous transluminal coronary angioplasty or coronary bypass surgery). The burden rests with the individual clinician to (1) collect all useful and necessary data; (2) assess reliability and accuracy of various tests available at one's own institution; (3) avoid performing unnecessary and repetitive tests; (4) interpret the data in the proper context; and (5) counsel patients appropriately, correctly, and judiciously about their prognosis and therapeutic options. In this manner, all patients who might benefit appropriately from revascularization can be discovered early and offered this therapeutic option. Other patients can also be managed more appropriately; for example, those who are truly at very low risk (normal left ventricular function and either normal coronary arteries or "mild" coronary artery disease). However, it is most important to avoid unnecessary revascularization procedures. Although this discussion has focused on noninvasive and invasive testing following myocardial infarction, it is necessary to emphasize that comprehensive management of coronary artery disease and its complications should not be neglected in these patients; for example, control or amelioration of risk factors for coronary artery disease is mandatory in all these patients, and in their families as well.

Transdermal systems for delivery of nitroglycerin have been shown to provide sustained blood levels of the drug for at least 24 hours. Investigations of hemodynamic effects of transdermal nitroglycerin in patients with heart failure have demonstrated a transient reduction in pressure lasting less than the expected 24 hours. These findings could be due to the development of circulatory tolerance to the vasodilatory effects of nitroglycerin or to insufficient drug dosing. In the present study, we compared the hemodynamic effects of the first and the second doses of high dose (120 mg) transdermal nitroglycerin given 24 hours apart in 11 responders (greater than or equal to 20% reduction in mean pulmonary artery wedge pressure lasting greater than or equal to 2 hours). Initiation of nitroglycerin therapy resulted in a significant reduction in mean right atrial pressure lasting for 14 hours and in a reduction in mean pulmonary artery and mean pulmonary artery wedge pressures lasting 24 hours. After administration of the second dose, mean right atrial pressure at 2 hours (9 +/- 5 versus 7 +/- 4 mm Hg), 4 hours (8 +/- 5 versus 6 +/- 4 mm Hg) and 8 hours (8 +/- 5 versus 6 +/- 3 mm Hg) was higher than after the first dose (p less than 0.05). Both mean pulmonary artery and mean pulmonary artery wedge pressures were significantly higher after the second nitroglycerin dose.(ABSTRACT TRUNCATED AT 250 WORDS)

To evaluate the potential value of nitrate therapy in patients with chronic mitral regurgitation, the hemodynamic and angiographic effects of intravenous nitroglycerin were studied in 10 such patients. Nitroglycerin infusion, titrated to reduce mean pulmonary artery wedge pressure at least 20%, resulted in a significant reduction in mean blood pressure (from 91 +/- 12 to 77 +/- 13 mm Hg, p less than 0.0001), mean right atrial pressure (12 +/- 6 to 7 +/- 4 mm Hg, p less than 0.001), left ventricular end-diastolic pressure (22 +/- 7 to 13 +/- 5 mm Hg, p less than 0.0001) and peak V wave of indirect left atrial pressure (34 +/- 9 to 20 +/- 10 mm Hg, p less than 0.001). Changes in systemic vascular resistance (1,986 +/- 468 vs 1,582 +/- 534 dynes s cm-5) and forward stroke volume (39 +/- 14 vs 45 +/- 8 ml) were not statistically significant. Angiographic data showed a decrease in both end-diastolic and end-systolic left ventricular volumes (248 +/- 51 to 216 +/- 54 ml, p = 0.06 and 127 +/- 69 to 99 +/- 48 ml, p less than 0.05, respectively) and an improvement in ejection fraction, from 0.52 +/- 0.15 to 0.55 +/- 0.15 (p less than 0.05). There was no significant change in the group values for mitral regurgitant volume and fraction (from 85 +/- 32 to 72 +/- 32 ml and 67 +/- 10 to 64 +/- 5%, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous transluminal coronary angioplasty (PTCA) of shepherd's crook right coronary arteries presents a difficult technical challenge. Presented here are two cases demonstrating the use of an internal mammary guiding catheter for PTCA of shepherd's crook right coronary arteries. The advantages of this guiding catheter, a short tip with an acute distal angle, are emphasized.

Oral isosorbide dinitrate has been widely used to lower elevated left ventricular filling pressure in patients with chronic heart failure. Although the recommended dose of this drug is 40 mg every 6 h, failure to respond to this dose has been observed in many patients with heart failure. In the present study the incidence of resistance to isosorbide dinitrate was evaluated and an attempt was made to identify baseline hemodynamic predictors for this phenomenon in 50 patients with severe chronic heart failure due to left ventricular systolic dysfunction (mean left ventricular ejection fraction 0.23 +/- 0.08). Twenty-seven (54%) of the 50 patients responded to 40 mg of isosorbide dinitrate (greater than 20% decrease in mean pulmonary artery wedge pressure sustained greater than or equal to 1 h) and 23 patients (46%) failed to respond. Nonresponders to 40 mg of isosorbide dinitrate had a significantly higher baseline right atrial pressure than did responders (14 +/- 5 versus 10 +/- 6 mm Hg, p less than 0.02). In addition, all 7 patients with a baseline right atrial pressure of less than 7 mm Hg and 12 of 14 patients with a baseline right atrial pressure less than 10 mm Hg responded to 40 mg. No significant differences were noted between responders and nonresponders in any other baseline hemodynamic or clinical variables, or in peak isosorbide dinitrate serum levels (32 +/- 19 ng/ml in nonresponders versus 44 +/- 36 ng/ml in responders). Of the 23 nonresponders to 40 mg, 22 received a higher dose (80 to 120 mg).(ABSTRACT TRUNCATED AT 250 WORDS)

The interaction between nifedipine and propranolol on cardiac hemodynamics and function was investigated in 9 patients with normal left ventricular (LV) function who were undergoing cardiac catheterization for complaints of chest pain. Only 2 patients had angiographic evidence of significant coronary artery disease but no patient had clinical evidence of ischemia during the study. All patients were pre-treated with propranolol, 30 to 320 mg/day (mean +/- standard deviation 210 +/- 122); the propranolol serum level ranged from 43 to 246 ng/ml (mean 203 +/- 62). The administration of nifedipine resulted in a decrease in blood pressure (from 94 +/- 11 to 85 +/- 13 mm Hg, p less than 0.05), increase in heart rate (from 59 +/- 6 to 65 +/- 7 beats/min, p less than 0.05), and an increase in both mean right atrial and mean pulmonary artery wedge pressures (from 8 +/- 3 to 9 +/- 3 mm Hg and from 13 +/- 3 to 14 +/- 4 mm Hg, respectively, both p less than 0.05). Cardiac index increased (from 2.3 +/- 0.3 to 2.7 +/- 0.2 liters/min/m2, p less than 0.01). Stroke volume index also increased significantly (from 39 +/- 5 to 43 +/- 6 ml/m2) and systemic vascular resistance decreased (from 1,715 +/- 369 to 1,255 +/- 271 dynes s cm-5, p less than 0.01). No significant change was noted in pulmonary vascular resistance (148 +/- 94 vs 140 +/- 62 dynes s cm-5), LV stroke work index (44 +/- 9 vs 42 +/- 10 g-m/m2), LV end-diastolic pressure (15 +/- 2 vs 16 +/- 2 mm Hg).(ABSTRACT TRUNCATED AT 250 WORDS)