Hemodynamic Reactivity to Mental Stress and Cognitive Function in Coronary Artery Disease.

OBJECTIVE: People with coronary artery disease (CAD) are at higher risk of cognitive impairment than those without CAD. Psychological stress is a risk factor for both conditions, and assessing the hemodynamic reactivity to mental stress could explain the link between stress and cognitive function. METHODS: A total of 779 individuals with stable CAD from two prospective cohort studies were included. All individuals underwent acute mental stress testing, as well as conventional stress testing. Cognitive function was assessed both at baseline and at a 2-year follow-up. The rate-pressure product (RPP) was calculated as the mean systolic blood pressure times the mean heart rate at rest. RPP reactivity was defined as the maximum RPP during standardized mental stress test minus the RPP at rest. RESULTS: After multivariable adjustment, every standard deviation decrease in RPP reactivity with mental stress was associated with slower completion of Trail-A and Trail-B in both cohorts (13% and 11% in cohort 1, and 15% and 16% in cohort 2, respectively; p for all <.01). After a 2-year follow-up period, every standard deviation decrease in RPP reactivity with mental stress was associated with a 8% and 9% slower completion of Trail-A and Trail-B, respectively ( p for all <.01). There was no significant association between RPP reactivity with conventional stress testing and any of the cognitive tests. CONCLUSION: In the CAD population, a blunted hemodynamic response to mental stress is associated with slower visuomotor processing and worse executive function at baseline and with greater decline in these abilities over time.

Sex Differences in Vascular Response to Mental Stress and Adverse Cardiovascular Events Among Patients With Ischemic Heart Disease.

BACKGROUND: Microvascular measures of vascular dysfunction during acute mental stress may be important determinants of major adverse cardiovascular events (MACE), especially among younger and middle-aged women survivors of an acute myocardial infarction. METHODS: In the MIMS2 study (Myocardial Infarction and Mental Stress 2), individuals who had been hospitalized for a myocardial infarction in the past 8 months were prospectively followed for 5 years. MACE was defined as a composite index of cardiovascular death and first/recurring events for nonfatal myocardial infarction and hospitalizations for heart failure. Reactive hyperemia index and flow-mediated dilation were used to measure microvascular and endothelial function, respectively, before and 30 minutes after a public-speaking mental stress task. Survival models for recurrent events were used to examine the association between vascular response to stress (difference between poststress and resting values) and MACE. Reactive hyperemia index and flow-mediated dilation were standardized in analyses. RESULTS: Of 263 patients (the mean age was 51 years; range, 25-61), 48% were women, and 65% were Black. During a median follow-up of 4.3 years, 64 patients had 141 adverse cardiovascular events (first and repeated). Worse microvascular response to stress (for each SD decrease in the reactive hyperemia index) was associated with 50% greater risk of MACE (hazard ratio, 1.50 [95% CI, 1.05-2.13]; P=0.03) among women only (sex interaction: P=0.03). Worse transient endothelial dysfunction in response to stress (for each SD decrease in flow-mediated dilation) was associated with a 35% greater risk of MACE (hazard ratio, 1.35 [95% CI, 1.07-1.71]; P=0.01), and the association was similar in women and men. CONCLUSIONS: Peripheral microvascular dysfunction with mental stress was associated with adverse events among women but not men. In contrast, endothelial dysfunction was similarly related to MACE among both men and women. These results suggest a female-specific mechanism linking psychological stress to adverse outcomes.

Racial Differences in Mental Stress-Induced Transient Endothelial Dysfunction and Its Association With Cardiovascular Outcomes.

OBJECTIVE: This study aimed to investigate differences in transient endothelial dysfunction (TED) with mental stress in Black and non-Black individuals with coronary heart disease (CHD), and their potential impact on cardiovascular outcomes. METHODS: We examined 812 patients with stable CHD between June 2011 and March 2016 and followed through February 2020 at a university-affiliated hospital network. Flow-mediated vasodilation (FMD) was assessed before and 30 minutes after mental stress. TED was defined as a lower poststress FMD than prestress FMD. We compared prestress FMD, post-stress FMD, and TED between Black and non-Black participants. In both groups, we examined the association of TED with an adjudicated composite end point of cardiovascular death or nonfatal myocardial infarction (first and recurring events) after adjusting for demographic, clinical, and socioeconomic factors. RESULTS: Prestress FMD was lower in Black than non-Black participants (3.7 [2.8] versus 4.9 [3.8], p < .001) and significantly declined with mental stress in both groups. TED occurred more often in Black (76%) than non-Black patients (67%; multivariable-adjusted odds ratio = 1.6, 95% confidence interval = 1.5-1.7). Over a median (interquartile range) follow-up period of 75 (65-82) months, 142 (18%) patients experienced either cardiovascular death or nonfatal myocardial infarction. Black participants had a 41.9% higher risk of the study outcome than non-Black participants (95% confidence interval = 1.01-1.95). TED with mental stress explained 69% of this excess risk. CONCLUSIONS: Among CHD patients, Black individuals are more likely than non-Black individuals to develop endothelial dysfunction with mental stress, which in turn explains a substantial portion of their excess risk of adverse events.

Impaired Peripheral Microvascular Function and Risk of Major Adverse Cardiovascular Events in Patients With Coronary Artery Disease.

[Figure: see text].

Associations Between Inflammation, Cardiovascular Regenerative Capacity, and Cardiovascular Events: A Cohort Study.

Objective: Circulating progenitor cells possess immune modulatory properties and might mitigate inflammation that is characteristic of patients with coronary artery disease. We hypothesized that patients with fewer circulating progenitor cells (CPCs) will have higher inflammatory markers and worse outcomes. Approach and Results: Patients with stable coronary artery disease were enrolled in a prospective study enumerating CPCs as CD (cluster of differentiation)-34-expressing mononuclear cells (CD34+) and inflammation as levels of IL (interleukin)-6 and high-sensitivity CRP (C-reactive protein) levels. Patients were followed for 5 years for the end points of death and myocardial infarction with repeat inflammatory biomarkers measured after a median of 2 years. In the entire cohort of 392 patients, IL-6 and high-sensitivity CRP levels remained unchanged (0.3+/-2.4 pg/mL and 0.1+/-1.0 mg/L; P=0.45) after 2 years. CPC counts (log-transformed) were inversely correlated with the change in IL-6 levels (r, -0.17; P<0.001). Using linear regression, IL-6 and high-sensitivity CRP levels declined by -0.59 (95% CI, -0.90 to -0.20) pg/mL and -0.13 (-0.28 to 0.01) mg/L per 1 log higher CPC counts after adjustment for the demographic and clinical variables, as well as medications. Using Cox models adjusted for these risk factors, a rise in 1 pg/mL of IL-6 was associated with a 11% (95% CI, 9-13) greater risk of death/myocardial infarction. We found that the change in IL6 level partly (by 40%) mediated the higher risk of adverse events among those with low CPC counts. Conclusions: Reduced cardiovascular regenerative capacity is independently associated with progressive inflammation in patients with coronary artery disease that in turn is associated with poor outcomes.

The association between baseline circulating progenitor cells and vascular function: The role of aging and risk factors.

BACKGROUND: To investigate the cross-sectional and longitudinal relationships between vascular function and circulating progenitor cell (CPC) counts with respect to aging and exposure to risk factors. METHODS: In 797 adult participants, CPCs were enumerated by flow cytometry as CD45med mononuclear cells expressing CD34 epitope and its subsets co-expressing CD133, and chemokine C-X-C motif receptor 4 (CXCR4+). Arterial stiffness was evaluated by tonometry-derived pulse wave velocity (PWV) and microvascular function was assessed as digital reactive hyperemia index (RHI). RESULTS: In cross-sectional analyses, for every doubling in CD34+ cell counts, PWV was 15% higher and RHI was 9% lower, after adjusting for baseline characteristics and risk factors (p for all < 0.01). There were significant CPC-by-age-by-risk factor interactions (p <0.05) for both vascular measures. Among younger subjects (< 48 years), CPC counts were higher in those with risk factors and vascular function was better in those with higher compared to those with lower CPC counts (p for all < 0.0l). In contrast, in older participants, CPCs were not higher in those with risk factors, and vascular function was worse compared to the younger age group. A lower CPC count at baseline was an independent predictor of worsening vascular function during 2-year follow-up. CONCLUSION: A higher CPC count in the presence of risk factors is associated with better vascular function among younger individuals. There is no increase in CPC count with risk factors in older individuals who have worse vascular function. Moreover, a higher CPC count is associated with less vascular dysfunction with aging.

Local intramuscular transplantation of autologous bone marrow mononuclear cells for critical lower limb ischaemia.

BACKGROUND: Peripheral arterial disease is a major health problem, and in about 1% to 2% of patients, the disease progresses to critical limb ischaemia (CLI), also known as critical limb-threatening ischaemia. In a substantial number of individuals with CLI, no effective treatment options other than amputation are available, with around a quarter of these patients requiring a major amputation during the following year. This is the second update of a review first published in 2011. OBJECTIVES: To evaluate the benefits and harms of local intramuscular transplantation of autologous adult bone marrow mononuclear cells (BMMNCs) as a treatment for CLI. SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 8 November 2021. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) of CLI in which participants were randomly allocated to intramuscular administration of autologous adult BMMNCs or control (either no intervention, conventional conservative therapy, or placebo). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes of interest were all-cause mortality, pain, and amputation. Our secondary outcomes were angiographic analysis, ankle-brachial index (ABI), pain-free walking distance, side effects and complications. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included four RCTs involving a total of 176 participants with a clinical diagnosis of CLI. Participants were randomised to receive either intramuscular cell implantation of BMMNCs or control. The control arms varied between studies, and included conventional therapy, diluted autologous peripheral blood, and saline. There was no clear evidence of an effect on mortality related to the administration of BMMNCs compared to control (risk ratio (RR) 1.00, 95% confidence interval (CI) 0.15 to 6.63; 3 studies, 123 participants; very low-certainty evidence). All trials assessed changes in pain severity, but the trials used different forms of pain assessment tools, so we were unable to pool data. Three studies individually reported that no differences in pain reduction were observed between the BMMNC and control groups. One study reported that reduction in rest pain was greater in the BMMNC group compared to the control group (very low-certainty evidence). All four trials reported the rate of amputation at the end of the study period. We are uncertain if amputations were reduced in the BMMNC group compared to the control group, as a possible small effect (RR 0.52, 95% CI 0.27 to 0.99; 4 studies, 176 participants; very low-certainty evidence) was lost after undertaking sensitivity analysis (RR 0.52, 95% CI 0.19 to 1.39; 2 studies, 89 participants). None of the included studies reported any angiographic analysis. Ankle-brachial index was reported differently by each study, so we were not able to pool the data. Three studies reported no changes between groups, and one study reported greater improvement in ABI (as haemodynamic improvement) in the BMMNC group compared to the control group (very low-certainty evidence). One study reported pain-free walking distance, finding no clear difference between BMMNC and control groups (low-certainty evidence). We pooled the data for side effects reported during the follow-up, and this did not show any clear difference between BMMNC and control groups (RR 2.13, 95% CI 0.50 to 8.97; 4 studies, 176 participants; very low-certainty evidence). We downgraded the certainty of the evidence due to the concerns about risk of bias, imprecision, and inconsistency. AUTHORS' CONCLUSIONS: We identified a small number of studies that met our inclusion criteria, and these differed in the controls they used and how they measured important outcomes. Limited data from these trials provide very low- to low-certainty evidence, and we are unable to draw conclusions to support the use of local intramuscular transplantation of BMMNC for improving clinical outcomes in people with CLI. Evidence from larger RCTs is needed in order to provide adequate statistical power to assess the role of this procedure.

Higher Activation of the Rostromedial Prefrontal Cortex During Mental Stress Predicts Major Cardiovascular Disease Events in Individuals With Coronary Artery Disease.

BACKGROUND: Psychological stress is a risk factor for major adverse cardiovascular events (MACE) in individuals with coronary artery disease. Certain brain regions that control both emotional states and cardiac physiology may be involved in this relationship. The rostromedial prefrontal cortex (rmPFC) is an important brain region that processes stress and regulates immune and autonomic functions. Changes in rmPFC activity with emotional stress (reactivity) may be informative of future risk for MACE. METHODS: Participants with stable coronary artery disease underwent acute mental stress testing using a series of standardized speech/arithmetic stressors and simultaneous brain imaging with high-resolution positron emission tomography brain imaging. We defined high rmPFC activation as a difference between stress and control scans greater than the median value for the entire cohort. Interleukin-6 levels 90 minutes after stress, and high-frequency heart rate variability during stress were also assessed. We defined MACE as a composite of cardiovascular death, myocardial infarction, unstable angina with revascularization, and heart failure hospitalization. RESULTS: We studied 148 subjects (69% male) with mean±SD age of 62±8 years. After adjustment for baseline demographics, risk factors, and baseline levels of interleukin-6 and high-frequency heart rate variability, higher rmPFC stress reactivity was independently associated with higher interleukin-6 and lower high-frequency heart rate variability with stress. During a median follow-up of 3 years, 34 subjects (21.3%) experienced a MACE. Each increase of 1 SD in rmPFC activation with mental stress was associated with a 21% increase risk of MACE (hazard ratio, 1.21 [95% CI, 1.08-1.37]). Stress-induced interleukin-6 and high-frequency heart rate variability explained 15.5% and 32.5% of the relationship between rmPFC reactivity and MACE, respectively. Addition of rmPFC reactivity to conventional risk factors improved risk reclassification for MACE prediction, and C-statistic improved from 0.71 to 0.76 (P=0.03). CONCLUSIONS: Greater rmPFC stress reactivity is associated with incident MACE. Immune and autonomic responses to mental stress may play a contributory role.

Everyday Discrimination and Mental Stress-Induced Myocardial Ischemia.

OBJECTIVE: Mental stress-induced myocardial ischemia (MSIMI), a transient myocardial ischemic response to mental stress, is associated with poorer outcomes among patients with coronary heart disease and is more likely to occur among women. However, predictors of MSIMI are not well explored. The current study investigated the association between experiences of everyday discrimination and MSIMI among patients with recent myocardial ischemia and contrasted the results with conventional stress-induced myocardial ischemia (CSIMI). We examined sex differences in associations. METHODS: We studied 295 post-MI patients (145 women, 150 men). Provocation of myocardial ischemia with mental stress (speech task) and conventional stress (exercise or pharmacologic) was assessed by myocardial perfusion imaging. Frequency of exposure to everyday discrimination was assessed via questionnaire using the Everyday Discrimination Scale (EDS). RESULTS: The mean age was 51 years in both women and men, and the EDS score ranged from 10 to 38 (mean [standard deviation] = 17 [6] years). After multivariable analysis, each standard deviation increase in the EDS score (more frequent exposure) was associated with an increased odds of MSIMI (odds ratio [OR] = 1.57 [1.10-2.23]). The EDS score was not associated with CSIMI (OR = 0.86 [0.64-1.17]). Women demonstrated a twofold increase (OR = 1.96 [1.13-3.38], p = .02) in the adjusted odds of MSIMI, with each standard deviation increase in the EDS score compared with a 1.4-fold increase (OR = 1.40 [0.80-2.44], p = .24) among men; however, interaction was not statistically significant. CONCLUSIONS: Among post-MI patients, everyday discrimination was positively associated with occurrence of MSIMI, but not with CSIMI; associations were more pronounced among women.

Association of mid-life serum lipid levels with late-life brain volumes: The atherosclerosis risk in communities neurocognitive study (ARICNCS).

BACKGROUND: Limited information exists regarding the association between midlife lipid levels and late-life total and regional brain volumes. METHODS: We studied 1872 participants in the longitudinal community-based Atherosclerosis Risk in Communities Neurocognitive Study. Serum lipid levels were measured in 1987-1989 (mean age, 53 ± 5 years). Participants underwent 3T brain MRI scans in 2011-2013. Brain volumes were measured using FreeSurfer image analysis software. Linear regression models were used to assess the associations between serum lipids and brain volumes modeled in standard deviation (SD) units, adjusting for potential confounders. RESULTS: In adjusted analyses, one SD higher low-density lipoprotein cholesterol (LDL) levels were associated with larger total brain volumes (ß 0.033, 95% CI 0.006-0.060) as well as larger volumes of the temporal (ß 0.038, 95% CI 0.003-0.074) and parietal lobes (ß 0.044, 95% CI 0.009-0.07) and Alzheimer disease-related region (ß 0.048, 95% CI 0.048-0.085). Higher triglyceride levels were associated with smaller total brain volumes (ß -0.033, 95% CI -0.060, -0.007). The associations between LDL levels and brain volumes were modified by age (P for interaction <0.001), with higher LDL levels associated with larger total and regional brain volumes only among adults >53 years at baseline, and were attenuated after application of weights to account for informative attrition, although associations with the parietal and Alzheimer's disease-related region remained significant. High-density lipoprotein cholesterol was not associated with brain volumes. CONCLUSION: Higher LDL levels in late midlife were associated with larger brain volumes later in life, while higher triglyceride levels were associated with smaller brain volumes. These associations were driven by adults >53 years at baseline.

Neural Correlates of Stress and Abdominal Obesity in Patients With Coronary Artery Disease.

OBJECTIVE: This study aimed to investigate the relationship between waist circumference as a measure of abdominal obesity and brain responses to stress among patients with coronary artery disease (CAD). METHODS: Patients with CAD (N = 151) underwent acute mental stress tasks in conjunction with high-resolution positron emission tomography and radiolabeled water imaging of the brain. Brain responses to mental stress were correlated with waist circumference. RESULTS: Waist circumference was positively correlated with increased activation in the right and left frontal lobes (ß values ranging from 2.81 to 3.75 in the paracentral, medial, and superior gyri), left temporal lobe, left hippocampal, left amygdala, left uncus, and left anterior and posterior cingulate gyri (ß values ranging from 2.93 to 3.55). Waist circumference was also negatively associated with the left and right parietal lobes, right superior temporal gyrus, and right insula and precuneus (ß values ranging from 2.82 to 5.20). CONCLUSION: Increased brain activation in the brain regions involved in the stress response and autonomic regulation of the cardiovascular system during psychological stress may underlie stress-induced overeating and abdominal obesity in patients with CAD.

Sex differences in the inflammatory response to stress and risk of adverse cardiovascular outcomes among patients with coronary heart disease.

Stress may contribute to progression of coronary heart disease (CHD) through inflammation, especially among women. Thus, we sought to examine whether increased inflammatory response to stress among patients with CHD is associated with a greater risk of cardiovascular events and whether this risk is higher in women. We examined inflammatory biomarkers known to increase with mental stress (speech task), including interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), and matrix metallopeptidase-9 (MMP-9) among 562 patients with stable CHD. Inflammatory response, the difference between post-stress and resting values, was examined as a predictor of major adverse cardiovascular events (MACE) using subdistribution hazards models for competing risks adjusting for demographics, cardiovascular risk factors, and medications. MACE was defined as a composite endpoint of cardiovascular death, myocardial infarction, unstable angina with revascularization, and heart failure. All biomarkers were standardized. The mean age was 63 years (range 34-79) and 24% were women. During a median follow-up of 3 years, 71 patients experienced MACE. Overall, there was no significant association between inflammatory response to stress and risk of MACE, but there were sex-based interactions for IL-6 (p = 0.001) and MCP-1 (p = 0.01). The risk of MACE increased 56% (HR: 1.56; 95% CI: 1.21, 2.01; p = 0.001) and 30% (HR: 1.30; 95% 1.09, 1.55; p = 0.004) for each standard deviation increase in IL-6 and MCP-1 response to mental stress for women, respectively, while there was no association among men. Increased inflammation in response to stress is associated with future adverse cardiovascular outcomes among women with CHD.

Utilization and in-hospital complications of cardiac resynchronization therapy: trends in the United States from 2003 to 2013.

Aims: Cardiac resynchronization therapy (CRT) device implantation has been shown to reduce morbidity and mortality in selected patients with heart failure. We sought to investigate the utilization and in-hospital complications of cardiac resynchronization therapy defibrillator (CRT-D) and pacemaker (CRT-P) implantations in the United States from 2003 to 2013. Methods and results: Patients receiving CRT-D or CRT-P were identified in the National Inpatient Sample database (NIS), using the International Classification of Diseases-Ninth Revision-Clinical Modification procedure codes. Annual implantation rates, patient demographics, co-morbidities, in-hospital complications, and length of stay were analysed. From 2003 to 2013, an estimated total of 439 010 (95% CI: 406 723-471 296) inpatient CRT implantations were performed in the U.S. The median age of patients was 72 and 71% were male. Overall, 6.1% had at least one complication. During the study period, comorbidity index and overall complication rate increased (P = 0.002 and P = 0.01, respectively). Mortality and length of stay showed no significant trend. Predictors of complications included: age 65 and older, female sex (OR: 1.19; 95% CI: 1.12-1.27), Deyo-Charlson Comorbidity Index, and elective admission (OR: 0.61; 95% CI: 0.57-0.66). Conclusion: From 2003 to 2013, the severity of comorbid conditions increased and a rising trend was observed in the rate of periprocedural complications among patients undergoing CRT in the United States. In-hospital mortality and length of stay showed no uniform trend.

S-Nitrosylation of Calcium-Handling Proteins in Cardiac Adrenergic Signaling and Hypertrophy.

RATIONALE: The regulation of calcium (Ca(2+)) homeostasis by ß-adrenergic receptor (ßAR) activation provides the essential underpinnings of sympathetic regulation of myocardial function, as well as a basis for understanding molecular events that result in hypertrophic signaling and heart failure. Sympathetic stimulation of the ßAR not only induces protein phosphorylation but also activates nitric oxide-dependent signaling, which modulates cardiac contractility. Nonetheless, the role of nitric oxide in ßAR-dependent regulation of Ca(2+) handling has not yet been explicated fully. OBJECTIVE: To elucidate the role of protein S-nitrosylation, a major transducer of nitric oxide bioactivity, on ßAR-dependent alterations in cardiomyocyte Ca(2+) handling and hypertrophy. METHODS AND RESULTS: Using transgenic mice to titrate the levels of protein S-nitrosylation, we uncovered major roles for protein S-nitrosylation, in general, and for phospholamban and cardiac troponin C S-nitrosylation, in particular, in ßAR-dependent regulation of Ca(2+) homeostasis. Notably, S-nitrosylation of phospholamban consequent upon ßAR stimulation is necessary for the inhibitory pentamerization of phospholamban, which activates sarcoplasmic reticulum Ca(2+)-ATPase and increases cytosolic Ca(2+) transients. Coincident S-nitrosylation of cardiac troponin C decreases myocardial sensitivity to Ca(2+). During chronic adrenergic stimulation, global reductions in cellular S-nitrosylation mitigate hypertrophic signaling resulting from Ca(2+) overload. CONCLUSIONS: S-Nitrosylation operates in concert with phosphorylation to regulate many cardiac Ca(2+)-handling proteins, including phospholamban and cardiac troponin C, thereby playing an essential and previously unrecognized role in cardiac Ca(2+) homeostasis. Manipulation of the S-nitrosylation level may prove therapeutic in heart failure.

In-Hospital Outcomes and Complications of Coronary Artery Bypass Grafting in the United States Between 2008 and 2012.

OBJECTIVE: To investigate the frequency and predictors of in-hospital complications among patients undergoing coronary artery bypass grafting (CABG) in the United States. DESIGN: Retrospective national database analysis SETTINGS: United States hospitals. PARTICIPANTS: A weighted sample of 1,910,236 patients undergoing CABG surgery identified from the National (Nationwide) Inpatient Sample from 2008 to 2012. INTERVENTIONS: CABG surgery MEASUREMENTS AND MAIN RESULTS: The number of CABG surgeries decreased from 436,275 in 2008 to 339,749 in 2012. The Deyo comorbidity index showed a steady increase from 2008 to 2012. The rate of in-hospital mortality decreased from 2.7% in 2008 to 2.2% in 2012 (p<0.001). The most common in-hospital complication was postoperative hemorrhage (30.4%), followed by cardiac (11.34%) and respiratory complications (2.3%). During the 5-year period, the rates of in-hospital cardiac, respiratory and infectious complications decreased (p<0.001), while the rate of postoperative hemorrhage showed a 35.8% relative increase in 2012 compared to 2008. CONCLUSION: The annual number of CABG surgeries is declining in the United States. While the burden of comorbidities is increasing, the rates of mortality and most in-hospital complications are improving. The increasing rate of postoperative bleeding necessitates the need to develop strategies to improve the risk of bleeding in this patient population.

Chordae Tendineae Rupture in the United States: Trends of Outcomes, Costs and Surgical Interventions.

OBJECTIVES: To describe national trends in the incidence and outcomes of patients with chordae tendineae rupture (CTR). METHODS: Patients who were diagnosed with CTR between 2000 and 2012 were identified in National (Nationwide) Inpatient Sample (NIS) registry. CTR was defined using validated International Classification of Diseases, 9th Edition, Clinical Modification diagnosis (ICD9-CM) codes. Results: A total of 37,287 (14,833 mitral valve repair, 7780 mitral valve replacement) CTR cases were identified. Overall, in-hospital mortality in CTR decreased by 3% from 2000 to 2012 (P < 0.001). From 2000 to 2012, the rate of mitral valve repair increased from 27.2% to 46.4%, (P < 0.001) with a concurrent decrease in the rate of mitral valve replacement (from 27.8 to 17.7%, P < 0.001). After multivariate adjustment, patient age (OR = 1.04, 95% CI 1.03-1.06, P < 0.001), congestive heart failure (CHF) (OR = 2.08, 95% CI 1.19-3.64, P = 0.01), myocardial infarction (MI) (OR = 3.58, 95% CI 2.10-6.11, P < 0.001), Deyo/Charlson comorbidity index (OR = 1.23, 95% CI 1.07-1.41, P < 0.003) and use of the intra aortic balloon pump (IABP) (OR = 4.81 95% CI 2.71-8.55, P < 0.001) were found to be independently associated with greater odds of mortality in these patients. Additionally, mitral valve replacement was significantly associated with higher costs of hospitalization (coefficient 15693, 95% CI 12638-18749, P < 0.001)Conclusion: Mitral valve repair is associated with reduced inpatient mortality and costs compared with mitral valve replacement. A substantial increase in the percentage of cases undergoing mitral valve repair with a concurrent decrease in cases undergoing mitral valve replacement were observed. Increasing age and comorbidity index, history of CHF and MI, and use of IABP were identified as factors that could increase the risk of mortality in patients with CTR.

Association of PTPN22 Gene Polymorphisms with Susceptibility to Juvenile Idiopathic Arthritis in Iranian Population.

Juvenile idiopathic arthritis (JIA), the most common cause of chronic arthritis in children, is a complex immune-mediated disease with considerable long-term morbidity and mortality. According to previous studies, PTPN22 gene has been associated with JIA in several populations. In the present study, we attempted to determine the association of PTPN22 single nucleotide polymorphisms (SNPs) with susceptibility to JIA in Iranian population. Using the Real-time PCR allelic discrimination method, samples consisting of 55 unrelated patients and 93 healthy controls were genotyped. Using Fisher exact test or Chi-square test, genotypic and allelic frequencies were estimated. The results of our study indicated a significantly decreased association of rs1310182 (OR = 0.59, 95% CI = 0.36 -0.97, p = 0.037) with JIA. This association may indicate a protective role for rs1310182 SNP against JIA. More research would be needed to elucidate the mechanistic role of this association.

Maternal mobile phone exposure alters intrinsic electrophysiological properties of CA1 pyramidal neurons in rat offspring.

Some studies have shown that exposure to electromagnetic field (EMF) may result in structural damage to neurons. In this study, we have elucidated the alteration in the hippocampal function of offspring Wistar rats (n = 8 rats in each group) that were chronically exposed to mobile phones during their gestational period by applying behavioral, histological, and electrophysiological tests. Rats in the EMF group were exposed to 900 MHz pulsed-EMF irradiation for 6 h/day. Whole cell recordings in hippocampal pyramidal cells in the mobile phone groups did show a decrease in neuronal excitability. Mobile phone exposure was mostly associated with a decrease in the number of action potentials fired in spontaneous activity and in response to current injection in both male and female groups. There was an increase in the amplitude of the afterhyperpolarization (AHP) in mobile phone rats compared with the control. The results of the passive avoidance and Morris water maze assessment of learning and memory performance showed that phone exposure significantly altered learning acquisition and memory retention in male and female rats compared with the control rats. Light microscopy study of brain sections of the control and mobile phone-exposed rats showed normal morphology.Our results suggest that exposure to mobile phones adversely affects the cognitive performance of both female and male offspring rats using behavioral and electrophysiological techniques.

Long-Term Outcome of Patients With Idiopathic Ventricular Fibrillation: A Meta-Analysis.

BACKGROUND: The long-term outcome of the patients with idiopathic ventricular fibrillation (IVF) is not well known. METHODS AND RESULTS: Relevant studies published through May 21, 2014 were searched and identified in the MEDLINE, PsycINFO, Cochrane Library, CINAHL, and EMBASE databases and a hand search of article references was also performed. Random-effect models were used for pooling proportions of mortality and recurrent events. Twenty-three studies were included with a total of 639 patients (449 males) with a mean age ranging from 33 to 51 years. Eighty percent of patients had received ICD implantation. Over an average of 5.3 years follow-up, 167 patients (31%) experienced a recurrence of ventricular arrhythmic events (proportion, 0.29 [95% CI 0.21-0.38]). Moreover, 17 patients (3.1%) died among all studies (proportion, 0.01 [95% CI 0.00-0.04]). No association was found between the induction of sustained ventricular tachycardia or ventricular fibrillation at baseline electrophysiological study and risk of recurrent ventricular arrhythmias (risk difference: 0.12 [95% CI, 0.08-0.32]). CONCLUSIONS: In patients with IVF, this meta-analysis revealed an estimated recurrent event rate of 31% and a pooled mortality rate of 3.1% during an average of 5 years follow-up. The results of baseline electrophysiological studies are not predictive of future ventricular arrhythmias.

A translational approach to probe the proarrhythmic potential of cardiac alternans: a reversible overture to arrhythmogenesis?

Electrocardiographic alternans, a phenomenon of beat-to-beat alternation in cardiac electrical waveforms, has been implicated in the pathogenesis of ventricular arrhythmias and sudden cardiac death (SCD). In the clinical setting, a positive microvolt T-wave alternans test has been associated with a heightened risk of arrhythmic mortality and SCD during medium- and long-term follow-up. However, rather than merely being associated with an increased risk for SCD, several lines of preclinical and clinical evidence suggest that cardiac alternans may play a causative role in generating the acute electrophysiological substrate necessary for the onset of ventricular arrhythmias. Deficiencies in Ca(2+) transport processes have been implicated in the genesis of alternans at the subcellular and cellular level and are hypothesized to contribute to the conditions necessary for dispersion of refractoriness, wave break, reentry, and onset of arrhythmia. As such, detecting acute surges in alternans may provide a mechanism for predicting the impending onset of arrhythmia and opens the door to delivering upstream antiarrhythmic therapies. In this review, we discuss the preclinical and clinical evidence to support a causative association between alternans and acute arrhythmogenesis and outline the potential clinical implications of such an association.