Psychophysical responses to a speech stressor: Correlation of plasma beta-endorphin levels at rest and after psychological stress with thermally measured pain threshold in patients with coronary artery disease

Objectives. We tested the hypothesis that psychological stress alters plasma levels of opioid peptides and that these plasma levels are related to pain perception in patients with coronary artery disease.

Background. Public speaking psychological stress has previously been shown to be associated with silent ischemia.

Methods. After instrumentation and a 30-min rest period, venous blood samples for beta-endorphin were obtained before and immediately after psychological stress in 20 patients with coronary artery disease. Pain threshold was then assessed using a thermal probe technique at baselin and immediately after stress. Patients gave three brief speeches lasting a total of 15 min about real-life hassle situations.

Results. Psychological stress significantly increases plasma beta-endorphin levels (4.3 ± 0.9 pmol/liter [mean ± SE] at rest to 8.3 ± 2 pmol/liter after stress, p < 0.05). There was a significant positive correlation between pain threshold and beta-endorphin levels after stress (r = 0.577, p = 0.008). This significant positive correlation was still present while rest blood pressure and change in blood pressure during stress were controlled for by analysis of covariance techniques.

Conclusions. In patients with coronary artery disease and exercise-induced ischemia, public speaking produces psychological stress manifested by increased cardiovascular reactivity and causes an increase in plasma beta-endorphin levels that is significantly correlated with pain thresholds. These findings may explain the predominance of silent ischemia during psychological stress in patients with coronary artery disease.     

Semi-Quantitative Scoring of Late Gadolinium Enhancement of the Left Ventricle in Patients with Ischemic Cardiomyopathy: Improving Interobserver Reliability and Agreement Using Consensus Guidance from the Asian Society of Cardiovascular Imaging-Practical Tutorial (ASCI-PT) 2020

ObjectiveThis study aimed to evaluate the effect of implementing the consensus statement from the Asian Society of Cardiovascular Imaging-Practical Tutorial 2020 (ASCI-PT 2020) on the reliability of cardiac MR with late gadolinium enhancement (CMR-LGE) myocardial viability scoring between observers in the context of ischemic cardiomyopathy.Materials and MethodsA total of 17 cardiovascular imaging experts from five different countries evaluated CMR obtained in 26 patients (male:female, 23:3; median age [interquartile range], 55.5 years [50–61.8]) with ischemic cardiomyopathy. For LGE scoring, based on the 17 segments, the extent of LGE in each segment was graded using a five-point scoring system ranging from 0 to 4 before and after exposure according to the consensus statement. All scoring was performed via web-based review. Scores for slices, vascular territories, and total scores were obtained as the sum of the relevant segmental scores. Interobserver reliability for segment scores was assessed using Fleiss’ kappa, while the intraclass correlation coefficient (ICC) was used for slice score, vascular territory score, and total score. Inter-observer agreement was assessed using the limits of agreement from the mean (LoA).ResultsInterobserver reliability (Fleiss’ kappa) in each segment ranged 0.242–0.662 before the consensus and increased to 0.301–0.774 after the consensus. The interobserver reliability (ICC) for each slice, each vascular territory, and total score increased after the consensus (slice, 0.728–0.805 and 0.849–0.884; vascular territory, 0.756–0.902 and 0.852–0.941; total score, 0.847 and 0.913, before and after implementing the consensus statement, respectively. Interobserver agreement in scoring also improved with the implementation of the consensus for all slices, vascular territories, and total score. The LoA for the total score narrowed from ± 10.36 points to ± 7.12 points.ConclusionThe interobserver reliability and agreement for CMR-LGE scoring for ischemic cardiomyopathy improved when following guidance from the ASCI-PT 2020 consensus statement.     

Prognostic value of combined magnetic resonance myocardial perfusion imaging and late gadolinium enhancement

Late gadolinium enhancement (LGE) and myocardial perfusion study by cardiac magnetic resonance (CMR) have a diagnostic and prognostic value in patients with suspected coronary artery disease (CAD). The purpose of this study was to determine the prognostic value of combined myocardial perfusion CMR and LGE in patients with known or suspected CAD. We studied patients with known or suspected CAD. All patients underwent CMR for functional study, myocardial perfusion and LGE. Myocardial ischemia by CMR was defined as a perfusion defect in patients without LGE or a perfusion defect beyond the LGE area. Patients were followed up for cardiovascular outcomes including hard cardiac events (cardiac death or non-fatal myocardial infarction) and major adverse cardiac events (MACE) which included cardiac death, non-fatal myocardial infarction, hospitalization for unstable angina, and heart failure. There were a total of 587 men and 645 women. Average age was 64.6 ± 11.1 years. LGE was detected in 326 patients (26.5%). Myocardial ischemia by CMR was detected in 423 patients (34.3%). Average follow-up duration was 34.9 ± 15.6 months. Univariate analysis showed that age, diabetes, use of beta blocker, left ventricular ejection fraction, left ventricular mass, wall motion abnormality, LGE, and myocardial ischemia are predictors for hard cardiac events and MACE. Multivariable analysis revealed that myocardial ischemia was the strongest predictor for hard cardiac events and MACE. Other independent predictors were age, use of beta blocker, and left ventricular mass. Myocardial ischemia by CMR has an incremental prognostic value for cardiac events in patients with known or suspected CAD.     

The cardiac MRI substudy to ongoing telmisartan alone and in combination with ramipril global endpoint trial/telmisartan randomized assessment study in ACE-intolerant subjects with cardiovascular disease: analysis protocol and baseline characteristics

Background  The ONTARGET and TRANSCEND clinical trials were designed to investigate the cardioprotective effects of telmisartan 80 mg and ramipril 10 mg, alone and in combination, in patients at high risk of cardiovascular disease. Cardiac MRI enables investigation of mechanistic effects of these agents on cardiac structural and functional variables. Here, we report the design, analysis protocol, reproducibility and relevant quality control procedures, and baseline patient characteristics of the ONTARGET/TRANSCEND cardiac MRI substudy. MRI was undertaken in 330 subjects enrolled in ONTARGET, and 38 subjects in TRANSCEND, across eight centers in six countries. Analyses were performed by two independent analysts using guide-point modeling. Cases with discrepancies in LV mass (LVM) of >5% were independently reanalyzed. Cases with discrepancies in end-diastolic volume (EDV) of >5%, or end-systolic volume (ESV) of >12%, were then reconciled by consensus. Results  Baseline characteristics were broadly similar to the main ONTARGET/TRANSCEND trials, except for a higher frequency of coronary artery disease and Asian ethnicity in the substudy. Reproducibility of MRI analyses (mean ± SD) were 2.8 ± 3.7 ml in EDV, −0.3 ± 3.6 ml in ESV, 3.1 ± 3.3 ml in SV, 1.1 ± 1.8% in EF, and 0.4 ± 4.5 g in LVM. Subgroup analyses revealed increased ESV and LVM, and reduced EF, in subjects with a history of either coronary artery disease or myocardial infarction. Conclusions  The ONTARGET/TRANSCEND cardiac MRI substudy protocol provides for a reliable assessment of the effects of telmisartan and ramipril, alone and in combination, on cardiac structural and functional parameters over a 2-year follow-up period. For the ONTARGET Investigators.     

Simple,Efficient, and Cost-Effective Multiplex Genotyping with Matrix Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry of Hemoglobin Beta Gene Mutations

A number of common mutations in the hemoglobin β (HBB) gene cause β-thalassemia, a monogenic disease with high prevalence in certain ethnic groups. As there are 30 HBB variants that cover more than 99.5% of HBB mutant alleles in the Thai population, an efficient and cost-effective screening method is required. Three panels of multiplex primer extensions, followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry were developed. The first panel simultaneously detected 21 of the most common HBB mutations, while the second panel screened nine additional mutations, plus seven of the first panel for confirmation; the third panel was used to confirm three HBB mutations, yielding a 9-Da mass difference that could not be clearly distinguished by the previous two panels. The protocol was both standardized using 40 samples of known genotypes and subsequently validated in 162 blind samples with 27 different genotypes (including a normal control), comprising heterozygous, compound heterozygous, and homozygous β-thalassemia. Results were in complete agreement with those from the genotyping results, conducted using three different methods overall. The method developed here permitted the detection of mutations missed using a single genotyping procedure. The procedure should serve as the method of choice for HBB genotyping due to its accuracy, sensitivity, and cost-effectiveness, and can be applied to studies of other gene variants that are potential disease biomarkers.To date, 739 point mutations in the hemoglobin, β (HBB) gene causing β-thalassemia (MIM# 141900) have been reported in HbVar: A Database of Human Hemoglobin Variants and Thalassemias (http://globin.cse.psu.edu/globin/hbvar/menu.html, accessed March 2009), but each ethnic group has a limited number of common mutations and a considerable number of rarer mutations.¹ The c.79G>A (also known as CD26G>A or Hb E) is the most frequent HBB variant in Southeast Asia including Thailand.² “Thai” generally refers to speakers of Thai (Tai) languages. The ethnic groups of Thailand comprise Thais (constituting 85% of the population) and Hill Peoples living primarily in the north, as well as other groups including the Chinese and minorities in the south.³ In the Thai population, approximately 40 HBB mutations have been identified,⁴ of which 30 variants account for more than 99.5% of all mutant HBB alleles

Soluble ST2 in the prediction of heart failure and death in patients with atrial fibrillation

BackgroundBiomarkers may be a useful marker for predicting heart failure (HF) or death in patients with atrial fibrillation (AF).HypothesisSoluble ST2 (sST2) may be a good biomarker for the prediction of HF or death in patients with AF.MethodsThis is a prospective study of patients with nonvalvular AF. Clinical outcomes were HF or death. Clinical and laboratory data were compared between those with and without clinical outcomes. Univariate and multivariate analysis was performed to determine whether sST2 is an independent predictor for heart failure or death in patients with nonvalvular AF.ResultsA total of 185 patients (mean age: 68.9 ± 11.0 years) were included, 116 (62.7%) were male. The average sST2 and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels were 31.3 ± 19.7 ng/ml and 2399.5 ± 6853.0 pg/ml, respectively. Best receiver operating characteristic (ROC) cut off of sST2 for predicting HF or death was 30.14 ng/ml. Seventy‐three (39.5%) patients had an sST2 level ≥30.14 ng/ml, and 112 (60.5%) had an sST2 level <30.14 ng/dl. The average follow‐up was 33.1 ± 6.6 months. Twenty‐nine (15.7%) patients died, and 33 (17.8%) developed HF during follow‐up. Multivariate analysis revealed that high sST2 to be an independent risk factor for death or HF with a HR and 95% CI of 2.60 (1.41–4.78). The predictive value of sST2 is better than NT‐proBNP, and it remained significant in AF patients irrespective of history of HF, and NT‐proBNP levels.ConclusionssST2 is an independent predictor of death or HF in patients with AF irrespective of history of HF or NT‐proBNP levels.     

Catastrophic health expenditure on acute coronary events in Asia: a prospective study

Objective

To estimate out-of-pocket costs and the incidence of catastrophic health expenditure in people admitted to hospital with acute coronary syndromes in Asia.

Methods

Participants were enrolled between June 2011 and May 2012 into this observational study in China, India, Malaysia, Republic of Korea, Singapore, Thailand and Viet Nam. Sites were required to enrol a minimum of 10 consecutive participants who had been hospitalized for an acute coronary syndrome. Catastrophic health expenditure was defined as out-of-pocket costs of initial hospitalization > 30% of annual baseline household income, and it was assessed six weeks after discharge. We assessed associations between health expenditure and age, sex, diagnosis of the index coronary event and health insurance status of the participant, using logistic regression models.

Findings

Of 12 922 participants, 9370 (73%) had complete data on expenditure. The mean out-of-pocket cost was 3237 United States dollars. Catastrophic health expenditure was reported by 66% (1984/3007) of those without insurance versus 52% (3296/6366) of those with health insurance (P < 0.05). The occurrence of catastrophic expenditure ranged from 80% (1055/1327) in uninsured and 56% (3212/5692) of insured participants in China, to 0% (0/41) in Malaysia.

Conclusion

Large variation exists across Asia in catastrophic health expenditure resulting from hospitalization for acute coronary syndromes. While insurance offers some protection, substantial numbers of people with health insurance still incur financial catastrophe.     

Heart rate variability at rest and during mental stress in patients with coronary artery disease: Differences in patients with high and low depression scores

This study tested the hypothesis that coronary artery disease (CAD) patients with high depressed mood scores differ in sympatho-vagal balance during mental stress compared to patients with low depressed mood scores. Using electrocardiographic monitoring, heart variability data from spectral analysis and hemodynamic parameters were obtained prior to and during mental stress from 34 men and 7 women. A public speaking task was used as the mental stressor. Patients were grouped by a median split of their Minnesota Multiphasic Personality Inventory-Depression score. During mental stress, patients with higher depression scores had greater changes in peak heart rate (p > .05) and low frequency to high frequency power ratio (p > 0.05) than patients with lower scores suggesting a shift toward more sympathetic activity during mental stress. These findings may be related to the reported relation between depression and survival risk in patients with CAD. This study was supported by Grant 1-R01-HL-47477 from the National Heart, Lung and Blood Institute, General Clinical Research Center Grant RR00046 from the National Institutes of Health, and Cooperative Agreement CR817643 from the Environmental Protection Agency.     

Heart rate variability in patients with Brugada syndrome in Thailand.

AIMS: Since patients with Brugada syndrome usually have symptoms at nighttime, we hypothesize that changes in autonomic modulation have an important role in the occurrence of the ventricular fibrillation episodes. The objective of this study was to determine the changes in heart rate variability (HRV) in patients with Brugada syndrome compared to asymptomatic subjects with Brugada ECG and controls. METHODS AND RESULTS:We studied 17 patients with Brugada syndrome, 10 asymptomatic subjects with Brugada ECG and 45 controls. Patients with Brugada syndrome and asymptomatic subjects with Brugada ECG underwent echocardiography, exercise stress testing, 24-h Holter monitoring, signal-averaged ECG. Patients with Brugada syndrome also underwent coronary angiography and electrophysiologic study. Time domain and frequency domain HRV analysis were performed at daytime and nighttime. The results of this study showed that patients with Brugada syndrome had lower HRV or lower vagal tone at night compared to the controls. They also had lower heart rate during the day and higher during the night compared to asymptomatic subjects and the controls. CONCLUSION: Patients with Brugada syndrome had low heart rate variability at night which may predispose to the occurrence of VF episodes.