Effects of a patient-centered digital health intervention in patients referred to cardiac rehabilitation: the Smart HEART clinical trial.

BACKGROUND: Cardiac rehabilitation (CR) improves outcomes in heart disease yet remains vastly underutilized. Remote CR enhanced with a digital health intervention (DHI) may offer higher access and improved patient-centered outcomes over non-technology approaches. We sought to pragmatically determine whether offering a DHI improves CR access, cardiac risk profile, and patient-reported outcome measures. METHODS: Adults referred to CR at a tertiary VA medical center between October 2017 and December 2021 were offered enrollment into a DHI alongside other CR modalities using shared decision-making. The DHI consisted of remote CR with a structured, 3-month home exercise program enhanced with multi-component coaching, a commercial smartphone app, and wearable activity tracker. We measured completion rates among DHI participants and evaluated changes in 6-min walk distance, cardiovascular risk factors, and patient-reported outcomes from pre- to post-intervention. RESULTS: Among 1,643 patients referred to CR, 258 (16%) consented to the DHI where the mean age was 60 ± 9 years, 93% were male, and 48% were black. A majority (90%) of the DHI group completed the program. Over 3-months, significant improvements were seen in 6MWT (mean difference [MD] -29 m; 95% CI, 10 to 49; P < 0.01) and low-density lipoprotein cholesterol (MD -11 mg/dL; 95% CI, -17 to -5; P < 0.01), and the absolute proportion of patients who reported smoking decreased (10% vs 15%; MD, -5%; 95% CI, -8% to -2%; P < 0.01) among DHI participants with available data. No adverse events were reported. CONCLUSIONS: The addition of a DHI-enhanced remote CR program was delivered in 16% of referred veterans and associated with improved CR access, markers of cardiovascular risk, and healthy behaviors in this real-world study. These findings support the continued implementation of DHIs for remote CR in real-world clinical settings. TRIAL REGISTRATION: This trial was registered on ClinicalTrials.gov: NCT02791685 (07/06/2016).

Novel Biomarker of Oxidative Stress Is Associated With Risk of Death in Patients With Coronary Artery Disease.

BACKGROUND: Free radical scavengers have failed to improve patient outcomes, promoting the concept that clinically important oxidative stress may be mediated by alternative mechanisms. We sought to examine the association of emerging aminothiol markers of nonfree radical mediated oxidative stress with clinical outcomes. METHODS AND RESULTS: Plasma levels of reduced (cysteine and glutathione) and oxidized (cystine and glutathione disulphide) aminothiols were quantified by high performance liquid chromatography in 1411 patients undergoing coronary angiography (mean age 63 years, male 66%). All patients were followed for a mean of 4.7 ± 2.1 years for the primary outcome of all-cause death (n=247). Levels of cystine (oxidized) and glutathione (reduced) were associated with risk of death (P<0.001 both) before and after adjustment for covariates. High cystine and low glutathione levels (>+1 SD and <-1 SD, respectively) were associated with higher mortality (adjusted hazard ratio [HR], 1.63; 95% confidence interval [CI], 1.19-2.21; HR, 2.19; 95% CI, 1.50-3.19; respectively) compared with those outside these thresholds. Furthermore, the ratio of cystine/glutathione was also significantly associated with mortality (adjusted HR, 1.92; 95% CI, 1.39-2.64) and was independent of and additive to high-sensitivity C-reactive protein level. Similar associations were found for other outcomes of cardiovascular death and combined death and myocardial infarction. CONCLUSIONS: A high burden of oxidative stress, quantified by the plasma aminothiols, cystine, glutathione, and their ratio, is associated with mortality in patients with coronary artery disease, a finding that is independent of and additive to the inflammatory burden. Importantly, these data support the emerging role of nonfree radical biology in driving clinically important oxidative stress.

Circulating CD34+ progenitor cells and risk of mortality in a population with coronary artery disease.

RATIONALE: Low circulating progenitor cell numbers and activity may reflect impaired intrinsic regenerative/reparative potential, but it remains uncertain whether this translates into a worse prognosis. OBJECTIVES: To investigate whether low numbers of progenitor cells associate with a greater risk of mortality in a population at high cardiovascular risk. METHODS AND RESULTS: Patients undergoing coronary angiography were recruited into 2 cohorts (1, n=502 and 2, n=403) over separate time periods. Progenitor cells were enumerated by flow cytometry as CD45(med+) blood mononuclear cells expressing CD34, with additional quantification of subsets coexpressing CD133, vascular endothelial growth factor receptor 2, and chemokine (C-X-C motif) receptor 4. Coefficient of variation for CD34 cells was 2.9% and 4.8%, 21.6% and 6.5% for the respective subsets. Each cohort was followed for a mean of 2.7 and 1.2 years, respectively, for the primary end point of all-cause death. There was an inverse association between CD34(+) and CD34(+)/CD133(+) cell counts and risk of death in cohort 1 (ß=-0.92, P=0.043 and ß=-1.64, P=0.019, respectively) that was confirmed in cohort 2 (ß=-1.25, P=0.020 and ß=-1.81, P=0.015, respectively). Covariate-adjusted hazard ratios in the pooled cohort (n=905) were 3.54 (1.67-7.50) and 2.46 (1.18-5.13), respectively. CD34(+)/CD133(+) cell counts improved risk prediction metrics beyond standard risk factors. CONCLUSIONS: Reduced circulating progenitor cell counts, identified primarily as CD34(+) mononuclear cells or its subset expressing CD133, are associated with risk of death in individuals with coronary artery disease, suggesting that impaired endogenous regenerative capacity is associated with increased mortality. These findings have implications for biological understanding, risk prediction, and cell selection for cell-based therapies.

Myocardial ischemia and angiotensin-converting enzyme inhibition: comparison of ischemia during mental and physical stress.

OBJECTIVE: Mental stress provokes myocardial ischemia in many patients with stable coronary artery disease (CAD). Mental stress-induced myocardial ischemia (MSIMI) portends a worse prognosis, independent of standard cardiac risk factors or outcome of traditional physical stress testing. Angiotensin II plays a significant role in the physiological response to stress, but its role in MSIMI remains unknown. Our aim was to evaluate whether the use of angiotensin-converting enzyme inhibitors (ACEIs) is associated with a differential effect on the incidence of MSIMI compared with ischemia during physical stress. METHODS: Retrospective analysis of 218 patients with stable CAD, including 110 on ACEI, was performed. 99m-Tc-sestamibi myocardial perfusion imaging was used to define ischemia during mental stress, induced by a standardized public speaking task, and during physical stress, induced by either exercise or adenosine. RESULTS: Overall, 40 patients (18%) developed MSIMI and 80 patients (37%) developed ischemia during physical stress. MSIMI occurred less frequently in patients receiving ACEIs (13%) compared with those not on ACEIs (24%; p = .030, adjusted odds ratio = 0.42, 95% confidence interval = 0.19-0.91). In contrast, the frequency of myocardial ischemia during physical stress testing was similar in both groups (39% versus 35% in those on and not on ACEIs, respectively); adjusted odds ratio = 0.91, 95% confidence interval = 0.48-1.73). CONCLUSION: In this retrospective study, patients using ACEI therapy displayed less than half the risk of developing ischemia during mental stress but not physical stress. This possible beneficial effect of ACEIs on MSIMI may be contributing to their salutary effects in CAD.

Coronary angiographic scoring systems: an evaluation of their equivalence and validity.

BACKGROUND: Multiple scoring systems have been devised to quantify angiographic coronary artery disease (CAD) burden, but it is unclear how these scores relate to each other and which scores are most accurate. The aim of this study was to compare coronary angiographic scoring systems (1) with each other and (2) with intravascular ultrasound (IVUS)-derived plaque burden in a population undergoing angiographic evaluation for CAD. METHODS: Coronary angiographic data from 3600 patients were scored using 10 commonly used angiographic scoring systems and interscore correlations were calculated. In a subset of 50 patients, plaque burden and plaque area in the left anterior descending coronary artery were quantified using IVUS and correlated with angiographic scores. RESULTS: All angiographic scores correlated with each other (range for Spearman coefficient [ρ] 0.79-0.98, P < .0001); the 2 most widely used scores, Gensini and CASS-70, had a ρ = 0.90 (P < .0001). All scores correlated significantly with average plaque burden and plaque area by IVUS (range ρ 0.56-0.78, P < .0001 and 0.43-0.62, P < .01, respectively). The CASS-50 score had the strongest correlation (ρ 0.78 and 0.62, P < .0001) and the Duke Jeopardy score the weakest correlation (ρ 0.56 and 0.43, P < .01) with plaque burden and area, respectively. CONCLUSIONS: Angiographic scoring systems are strongly correlated with each other and with atherosclerotic plaque burden. Scoring systems therefore appear to be a valid estimate of CAD plaque burden.

Mitochondrial reactive oxygen species and calcium uptake regulate activation of phagocytic NADPH oxidase.

Production of superoxide (O(2)(·-)) by NADPH oxidases contributes to the development of hypertension and atherosclerosis. Factors responsible for activation of NADPH oxidases are not well understood; interestingly, cardiovascular disease is associated with both altered NADPH oxidase activity and age-associated mitochondrial dysfunction. We hypothesized that mitochondrial dysfunction may contribute to activation of NADPH oxidase. The effect of mitochondrial inhibitors on phagocytic NADPH oxidase in human lymphoblasts and whole blood was measured at the basal state and upon PKC-dependent stimulation with PMA using extracellular 1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl-trimethylammonium or mitochondria-targeted 1-hydroxy-4-[2-triphenylphosphonio)-acetamido]-2,2,6,6-tetramethylpiperidine spin probes and electron spin resonance (ESR). Intracellular cytosolic calcium [Ca(2+)](i) was measured spectrofluorometrically using fura-2 AM. Incubation of lymphoblasts with the mitochondrial inhibitors rotenone, antimycin A, CCCP, or ruthenium red (an inhibitor of mitochondrial Ca(2+) uniporter) did not significantly change basal activity of NADPH oxidase. In contrast, preincubation with the mitochondrial inhibitors prior to PMA stimulation of lymphoblasts resulted in two- to three-fold increase of NADPH oxidase activity compared with stimulation with PMA alone. Most notably, the intracellular Ca(2+)-chelating agent BAPTA-AM abolished the effect of mitochondrial inhibitors on NADPH oxidase activity. Cytosolic Ca(2+) measurements with fura-2 AM showed that the mitochondrial inhibitors increased [Ca(2+)](i), while BAPTA-AM abolished the increase in [Ca(2+)](i). Furthermore, depletion of cellular Ca(2+) with thapsigargin attenuated CCCP- and antimycin A-mediated activation of NADPH oxidase in the presence of PMA by 42% and 31%, correspondingly. Our data suggest that mitochondria regulate PKC-dependent activation of phagocytic NADPH oxidase. In summary, increased mitochondrial O(2)(·-) and impaired buffering of cytosolic Ca(2+) by dysfunctional mitochondria result in enhanced NADPH oxidase activity, which may contribute to the development of cardiovascular diseases.

Angiotensin receptor type 1 single nucleotide polymorphism 1166A/C is associated with malignant arrhythmias and altered circulating miR-155 levels in patients with chronic heart failure.

BACKGROUND: Sudden cardiac death (SCD) from ventricular tachyarrhythmias accounts for approximately 450,000 annual deaths in the United States; many of these cases involve patients with chronic heart failure (HF). Prediction of which HF patients are most susceptible to SCD is difficult, and it is uncertain whether gene polymorphisms associated with HF outcomes are also linked to arrhythmic risk. METHODS: We evaluated 485 patients with chronic HF to see whether the angiotensin receptor type 1 (AT1R) 1166A/C or angiotensin-converting enzyme insertion/deletion (ACE I/D) polymorphisms were associated with a higher rate of ventricular arrhythmias requiring implantable cardioverter defibrillator (ICD) therapies over a 5-year period. We assessed the correlation between polymorphisms and antitachycardia pacing (ATP) and/or ICD shocks. RESULTS: Patients with AT1R-1166CC genotype had an increased rate of all events: ATP plus ICD shocks (P = .02). There was no association between ACE I/D genotype and ICD therapies. Furthermore, circulating levels of microRNA-155 (miR-155), a microRNA known to posttranscriptionally regulate AT1R expression, were significantly decreased in the CC compared with the AC and AA genotypes and were associated with ICD events. CONCLUSION: Our study suggests that the AT1R-1166CC genotype is associated with increased ICD therapies in patients with chronic HF, and the level of circulating miR-155 may be a potential marker for arrhythmic risk. Although these findings are novel, they will need replication and validation in larger cohorts of chronic HF patients.

A common variant in the CDKN2B gene on chromosome 9p21 protects against coronary artery disease in Americans of African ancestry.

A 58 kb region on chromosome 9p21.3 has consistently shown strong association with coronary artery disease (CAD) in multiple genome-wide association studies in populations of European and East Asian ancestry. In this study, we sought to further characterize the role of genetic variants in 9p21.3 in African American individuals. Apparently healthy African American siblings (n = 548) of patients with documented CAD < 60 years of age were genotyped and followed for incident CAD for up to 17 years. Tests of association for 86 single-nucleotide polymorphisms (SNPs) across the 9p21.3 region in a generalized estimating equation logistic framework under an additive model adjusting for traditional risk factors, family, follow-up time and population stratification were performed. A single SNP within the CDKN2B gene met stringent criteria for statistical significance, including permutation-based evaluations. This variant, rs3217989, was common (minor allele (G) frequency 0.242), conveyed protection against CAD (odds ratio (OR) = 0.19, 95% confidence interval (CI): 0.07 to 0.50, P = 0.0008) and was replicated in a combined analysis of two additional case/control studies of prevalent CAD/MI in African Americans (n = 990, P = 0.024, OR = 0.779, 95% CI: 0.626-0.968). This is the first report of a CAD association signal in a population of African ancestry with a common variant within the CDKN2B gene, independent from previous findings in European and East Asian ancestry populations. The findings demonstrate a significant protective effect against incident CAD in African American siblings of persons with premature CAD, with replication in a combination of two additional African American cohorts.

The chromosome 9p21 risk locus is associated with angiographic severity and progression of coronary artery disease.

AIMS: we tested the hypothesis that the 9p21 risk locus promotes atherosclerosis by examining the association between rs10757278 and coronary artery disease (CAD) severity and progression determined by semi-quantitative angiographic scores. METHODS AND RESULTS: the rs10757278 single nucleotide polymorphism (SNP) was genotyped as the marker for the 9p21 locus in 2334 Caucasian patients undergoing cardiac catheterization (mean age 63, male 67%). Angiographic CAD was assessed using two semi-quantitative scoring systems with one estimating severity (Gensini) and the other extent (Sullivan). A subset of 308 patients who underwent two or more coronary angiograms at least 6 months apart were examined for net change in Gensini and Sullivan scores over time to determine the rate of CAD progression by genotype and were further classified as 'progressors' or 'non-progressors' based on absolute change per year in angiographic severity score. We replicated the association between the rs10757278 SNP and myocardial infarction and binary (presence/absence) angiographic classifications of CAD. Furthermore, we observed a significant additive association with this SNP, and both severity and extent of CAD using angiographic scores, after adjustment for age, gender, body mass index, traditional cardiovascular risk factors, myocardial infarction, and statin use (Gensini P = 0.016, Sullivan P = 0.005). In addition, there was a significant linear association with CAD progression before and after adjustment for covariates (Gensini P = 0.023, Sullivan P = 0.003) with homozygotes for the risk variant having three-fold greater odds of CAD progression compared with the referent group. CONCLUSION: the 9p21 risk locus is associated with angiographically defined severity, extent, and progression of CAD, suggesting a role for this locus in influencing atherosclerosis and its progression.

Sex-specific association of depression and a haplotype in leukotriene A4 hydrolase gene.

OBJECTIVE: To assess whether genetic variants involved in inflammation play a role in the sex difference in depression. Depression is, in part, genetically determined and inflammation has been implicated. Women are twice as likely to develop depression as men. METHODS: We examined the association, separately in men and women, between seven single nucleotide polymorphisms (SNPs) in the arachidonate 5-lipoxygenase-activating protein (ALOX5AP) gene and 12 SNPs in the leukotriene A4 hydrolase (LTA4H) gene and depression in 1368 white subjects (30.4% female) referred for cardiovascular evaluation. Depression was defined as a score of >or=10 in the Patient Health Questionnaire 9. Single marker analysis was assessed by the chi(2) test. Haplotype-specific associations were performed, using likelihood ratio tests. Empirical significance levels were determined by permutation tests. RESULTS: Depressed individuals, comprising 14.5% of the total, were more likely to be female, current smokers, have a history of diabetes and myocardial infarction. None of the SNPs in the ALOX5AP gene, either singly or in combination, was associated with depression. The 12 SNPs in the LTA4H gene were not individually associated with depression. However, a six-SNP haplotype in LTA4H gene, named HapE, showed a significant protective effect on depression in women, but not in men, after correcting for cardiovascular effects. The interaction between HapE and sex on depression was statistically significant. CONCLUSION: This study provides the first evidence for a sex-specific association of a novel haplotype in the LTA4H gene on depression. Although replication is needed, our study suggests that genetic variations may underlie sex differences in depression.

Human heart failure is associated with abnormal C-terminal splicing variants in the cardiac sodium channel.

Heart failure (HF) is associated with reduced cardiac Na+ channel (SCN5A) current. We hypothesized that abnormal transcriptional regulation of this ion channel during HF could help explain the reduced current. Using human hearts explanted at the transplantation, we have identified 3 human C-terminal SCN5A mRNA splicing variants predicted to result in truncated, nonfunctional channels. As compared with normal hearts, the explanted ventricles showed an upregulation of 2 of the variants and a downregulation of the full-length mRNA transcript such that the E28A transcript represented only 48.5% (P<0.01) of the total SCN5A mRNA. This correlated with a 62.8% (P<0.01) reduction in Na+ channel protein. Lymphoblasts and skeletal muscle expressing SCN5A also showed identical C-terminal splicing variants. Variants showed reduced membrane protein and no functional current. Transfection of truncation variants into a cell line stably transfected with the full-length Na+ channel resulted in dose-dependent reductions in channel mRNA and current. Introduction of a premature truncation in the C-terminal region in a single allele of the mouse SCN5A resulted in embryonic lethality. Embryonic stem cell-derived cardiomyocytes expressing the construct showed reductions in Na+ channel-dependent electrophysiological parameters, suggesting that the presence of truncated Na+ channel mRNA at levels seen in HF is likely to be physiologically significant. In summary, chronic HF was associated with an increase in 2 truncated SCN5A variants and a decrease in the native mRNA. These splice variations may help explain a loss of Na+ channel protein and may contribute to the increased arrhythmic risk in clinical HF.

Narrative review: cardiopulmonary resuscitation and emergency cardiovascular care: review of the current guidelines.

Sudden cardiac death is a major clinical problem, causing 300,000 to 400,000 deaths annually and 63% of all cardiac deaths. Despite the overall decrease in cardiovascular mortality, the proportion of cardiovascular death from sudden cardiac death has remained constant. Survival rates among patients who have out-of-hospital cardiac arrest vary from 5% to 18%, depending on the presenting rhythm. The latest guidelines for cardiopulmonary resuscitation (CPR) and emergency cardiovascular care published by the American Heart Association include substantial changes to the algorithms for basic life support and advanced cardiovascular life support. For unwitnessed cardiac arrest, immediate defibrillation of the patient is no longer recommended. Rather, 2 minutes of CPR before defibrillation is now recommended. People in cardiac arrest should no longer receive stacked shocks. The compression-ventilation ratio has been changed from 15:2 to 30:2. This article is a contemporary review of the management of CPR and emergency cardiovascular care. It examines current practice and data supporting use of CPR, along with changes in the management of sudden cardiac death.

Long-term survival after successful inhospital cardiac arrest resuscitation.

BACKGROUND: Little is known about long-term outcomes of patients who survive inhospital cardiac arrest. METHODS: We examined long-term survival after inhospital cardiac arrest and whether procedural changes that improved survival to discharge impacted long-term survival. Consecutive inhospital arrests in the Atlanta Veterans Affairs Medical Center (Atlanta, GA) from 1995 to 2004 (n = 732) were retrospectively analyzed. Data regarding the arrest was obtained, including age, left ventricular ejection fraction, medications, and comorbidities, presenting rhythm, location of arrest, code duration, and outcomes. Long-term mortality data was obtained based on chart and Social Security Death Index reviews. Further data was gathered on internal cardioverter-defibrillator presence and use in survivors. RESULTS: Overall, 49 subjects (6.6%) survived to discharge. Univariate analysis found that ventricular tachycardia/ventricular fibrillation and the use of beta-blockers, angiotensin-converting enzyme inhibitors, and antiarrhythmics at the time of arrest were associated with increased survival, whereas advancing age and comorbidities were associated with a higher risk of mortality. Multivariate analysis determined that age, rhythm, and comorbidities independently affected survival. Implementation of a resuscitation program previously documented to improve survival to discharge did not translate to durable long-term survival. Three-year survival rate after discharge was only 41%. Alternatively, subjects with internal cardioverter-defibrillator showed a 36% improvement in 3-year survival rate to 77% (P = .001). CONCLUSIONS: Subjects with inhospital cardiac arrest have poor long-term prognoses. A strategy that improved inhospital survival did not alter long-term mortality rate. Thus, survival to discharge may not be a sufficient end point for future resuscitation trials.

Production of extracellular superoxide by human lymphoblast cell lines: comparison of electron spin resonance techniques and cytochrome C reduction assay.

Superoxide production by NADPH oxidases plays an important role in the development and progression of cardiovascular disease (CVD). However, measurement of superoxide (O(2)(-)), a marker of oxidative stress, remains a challenging task in clinical and translational studies. In this study we analyzed O(2)(-) production in cultured human lymphoblast cell lines by three different methods: (a) superoxide dismutase (SOD)-inhibitable cytochrome C reduction, (b) spin trapping of superoxide with 5-(ethoxycarbonyl)-5-methyl-1-pyrroline N-oxide (EMPO) and 5-diethoxyphosphoryl-5-methyl-1-pyrroline N-oxide (DEPMPO), and (c) using electron spin resonance (ESR) with the cell-permeable spin probe 1-hydroxy-3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine (CMH). Lymphocytes were isolated and immortalized by an Epstein-Barr Virus (EBV)-transformation procedure. Superoxide was measured in cultured lymphoblast cell lines at baseline and upon stimulation with phorbol 12-myristate 13-acetate (PMA). Cytochrome C and the spin traps EMPO and DEPMPO detected two to five times less superoxide compared to CMH. Thus, CMH provided the most quantitative measurement of superoxide generation in human lymphoblast cell lines. Superoxide detection with CMH was linear dependent on cell concentration and was inhibited by SOD but not by catalase. Both cell-permeable polyethylene glycol (PEG)-SOD and extracellular Cu,Zn-SOD inhibited O(2)(-) detection by 90% in PMA-stimulated cells, suggesting a predominantly extracellular O(2)(-) generation in human lymphoblasts. Our study describes a new technique for O(2)(-) measurement in cultured human lymphoblasts using ESR and CMH. A highly sensitive in vitro measurement of O(2)(-) in human cell lines would allow investigators to study genotype/phenotype interactions in translational studies.

Pathway-Specific Aggregate Biomarker Risk Score Is Associated With Burden of Coronary Artery Disease and Predicts Near-Term Risk of Myocardial Infarction and Death.

BACKGROUND: Inflammation, coagulation, and cell stress contribute to atherosclerosis and its adverse events. A biomarker risk score (BRS) based on the circulating levels of biomarkers C-reactive protein, fibrin degradation products, and heat shock protein-70 representing these 3 pathways was a strong predictor of future outcomes. We investigated whether soluble urokinase plasminogen activator receptor (suPAR), a marker of immune activation, is predictive of outcomes independent of the aforementioned markers and whether its addition to a 3-BRS improves risk reclassification. METHODS AND RESULTS: C-reactive protein, fibrin degradation product, heat shock protein-70, and suPAR were measured in 3278 patients undergoing coronary angiography. The BRS was calculated by counting the number of biomarkers above a cutoff determined using the Youden's index. Survival analyses were performed using models adjusted for traditional risk factors. A high suPAR level ≥3.5 ng/mL was associated with all-cause death and myocardial infarction (hazard ratio, 1.83; 95% confidence interval, 1.43-2.35) after adjustment for risk factors, C-reactive protein, fibrin degradation product, and heat shock protein-70. Addition of suPAR to the 3-BRS significantly improved the C statistic, integrated discrimination improvement, and net reclassification index for the primary outcome. A BRS of 1, 2, 3, or 4 was associated with a 1.81-, 2.59-, 6.17-, and 8.80-fold increase, respectively, in the risk of death and myocardial infarction. The 4-BRS was also associated with severity of coronary artery disease and composite end points. CONCLUSIONS: SuPAR is independently predictive of adverse outcomes, and its addition to a 3-BRS comprising C-reactive protein, fibrin degradation product, and heat shock protein-70 improved risk reclassification. The clinical utility of using a 4-BRS for risk prediction and management of patients with coronary artery disease warrants further study.

A program encouraging early defibrillation results in improved in-hospital resuscitation efficacy.

OBJECTIVES: The purpose of this study was to determine whether survival to discharge after in-hospital cardiopulmonary arrest could be improved by a program encouraging early defibrillation that included switching from monophasic to biphasic devices. BACKGROUND: In-hospital resuscitation continues to have a low success rate. Biphasic waveform devices have demonstrated characteristics that might improve survival, and outside the hospital, automated external defibrillators (AEDs) have shown promise in improving survival of patients suffering cardiopulmonary arrest. METHODS: A program including education and replacement of all manual monophasic defibrillators with a combination of manual biphasic defibrillators used in AED mode and AEDs in all outpatient clinics and chronic care units was implemented. RESULTS: With program implementation, the percentage survival of all patients with resuscitation events improved 2.6-fold, from 4.9% to 12.8%. Factors independently predicting survival included event location outside an intensive care unit, younger age, an initial rhythm of pulseless ventricular tachycardia (VT) or ventricular fibrillation (VF), pre-arrest beta-blocker, and program initiation. The outcome was independent of gender, race, work shift, number of previous resuscitation attempts, body mass index, comorbidity index, presence of diabetes, presence of hypertension, or use of angiotensin-converting enzyme inhibitors. The improvement in mortality was attributable solely to an effect on patients presenting with VT/VF. Patients with these initial rhythms were 14-fold (odds ratio = 0.07 of death, confidence interval = 0.02 to 0.3) more likely to survive to discharge after program initiation. Automated external defibrillators performed similarly to biphasic manual defibrillators in AED mode. CONCLUSIONS: A program including education and use of biphasic manual defibrillators in AED mode and selective use of AEDs improved survival to discharge in hospitalized patients suffering from cardiopulmonary arrest.

Endothelial nitric oxide synthase intron 4 polymorphism is a marker for coronary artery disease in African-American and Caucasian men.

OBJECTIVES: We investigated the association of the intron 4 polymorphism of the endothelial nitric oxide synthase (eNOS) gene with coronary artery disease (CAD). BACKGROUND: Genetic alterations in the gene encoding for eNOS could contribute to the development and progression of CAD. METHODS: We genotyped for the eNOS intron 4 polymorphism in 194 subjects undergoing coronary angiography. Genotyping was performed with polymerase chain reaction-restriction fragment length polymorphism for the variable number of tandem repeats in intron 4. Coronary artery disease (CAD) was assessed by quantitative coronary angiography, and endothelial function was measured by brachial ultrasonography. We performed logistic regression analysis for the effect of eNOS intron 4 polymorphism and other coronary risk factors on multi-vessel CAD and endothelial function. RESULTS: The 4a-allele frequency in African Americans was 0.31, while the 4a-allele frequency in Caucasians was 0.15 (P<.001). The prevalence of the 4a-allele was highest among subjects with multi-vessel disease both for African Americans and for Caucasians. A race-adjusted comparison of the prevalence of the 4a-allele among subjects with multi-vessel disease vs those without was statistically significant (P=.03). No correlation was found between the eNOS intron 4 polymorphism and endothelial function. CONCLUSIONS: The eNOS intron 4 polymorphism may be a marker of multi-vessel CAD in African Americans and Caucasians.