Coronary artery disease risk reclassification using an acoustic-based score in view of the new European Society of Cardiology 2019 guidelines on Chronic Coronary Syndromes.

In August 2019, ESC published new guidelines on Chronic Coronary Syndromes including a new risk assessment paradigm for estimation of pre-test-probability. The CAD-score is an acoustic-based score for ruling-out of coronary artery disease (CAD). In the current letter to the editor we re-evaluate the re-classification potential the CAD-score in the view of the new guidelines.

Coronary artery disease risk reclassification by a new acoustic-based score.

To determine the potential of a non-invasive acoustic device (CADScor®System) to reclassify patients with intermediate pre-test probability (PTP) and clinically suspected stable coronary artery disease (CAD) into a low probability group thereby ruling out significant CAD. Audio recordings and clinical data from three studies were collected in a single database. In all studies, patients with a coronary CT angiography indicating CAD were referred to coronary angiography. Audio recordings of heart sounds were processed to construct a CAD-score. PTP was calculated using the updated Diamond-Forrester score and patients were classified according to the current ESC guidelines for stable CAD: low < 15%, intermediate 15-85% and high > 85% PTP. Intermediate PTP patients were re-classified to low probability if the CAD-score was ≤ 20. Of 2245 patients, 212 (9.4%) had significant CAD confirmed by coronary angiography ( ≥ 50% diameter stenosis). The average CAD-score was higher in patients with significant CAD (38.4 ± 13.9) compared to the remaining patients (25.1 ± 13.8; p < 0.001). The reclassification increased the proportion of low PTP patients from 13.6% to 41.8%, reducing the proportion of intermediate PTP patients from 83.4% to 55.2%. Before reclassification 7 (3.1%) low PTP patients had CAD, whereas post-reclassification this number increased to 28 (4.0%) (p = 0.52). The net reclassification index was 0.209. Utilization of a low-cost acoustic device in patients with intermediate PTP could potentially reduce the number of patients referred for further testing, without a significant increase in the false negative rate, and thus improve the cost-effectiveness for patients with suspected stable CAD.

Supplementation of linoleic acid (C18:2n-6) or α-linolenic acid (C18:3n-3) changes microbial agonist-induced oxylipid biosynthesis.

Oxylipids are derived from polyunsaturated fatty acids (PUFA) in cellular membranes and the relative abundance or balance may contribute to disease pathogenesis. Previous studies documented unique oxylipid profiles from cows with either coliform or Streptococcus uberis mastitis, suggesting that lipid mediator biosynthesis may be dependent on the type of microbial-derived agonist. Changing the fatty acid content of peripheral blood leukocytes also may be critical to the relative expression of oxylipid profiles and the outcome of bacterial infection. No information is available in dairy cows describing how changing cellular PUFA content will modify oxylipids in the context of a microbial agonist challenge. Therefore, the hypothesis for the current study was that PUFA supplementation would change bovine leukocyte fatty acid content and respective oxylipid profiles from ex vivo microbial agonist-challenged leukocytes. Fatty acid content of leukocytes and plasma was quantified in (1) samples from cows not supplemented with PUFA, (2) cows supplemented with linoleic acid (LnA), and (3) cows supplemented with α-linolenic acid (ALA). Plasma oxylipids were assessed after S. uberis or lipopolysaccharide exposure and was compared with unstimulated oxylipid profiles. Fatty acid supplementation with ALA significantly increased ALA content of blood leukocytes and plasma relative to LnA. Fatty acid supplementation affected several S. uberis-induced oxylipids, but only S. uberis-induced 15-oxoETE was greater with ALA supplementation compared with LnA. Notably, only LPS-induced 5,6 LXA4 was altered with fatty acid supplementation, but no significant effect of LnA vs. ALA treatment was identified. Future studies are needed to understand how leukocyte activation and membrane PUFA availability collectively contribute to differential oxylipid profiles.

Genetic parameters of three methods of temperament evaluation of Brahman calves.

The objective of this study was to estimate the heritability of 3 measures of temperament in Brahman and Brahman-influenced calves (n = 1,209). Individual animal pen scores (PS) were determined by a trained observer who evaluated groups of 5 or 4 calves at a time for willingness to be approached by a human. Exit velocity (EV) was the rate (m/s) at which each calf exited a squeeze chute. Temperament score (TS) was calculated individually as (PS + EV)/2. Temperament was evaluated at 5 different times of record (28 d preweaning, weaning, 28 d postweaning, 56 d postweaning, and yearling). Contemporary groups (n = 34) comprised calves of the same sex born in the same season of the same year. There were an average of 36 calves per contemporary group and group size ranged from 3 to 78 calves. Average weaning age (186 d) ranged from 105 to 304 d. Calves were born from 2002 through 2012. Random effects included additive genetic and the permanent environmental variance. The fixed effects analyzed were age of dam, sex of calf, contemporary group, fraction of Brahman (2 levels: 1 and 0.5), age of calf at record, and weaning age. At weaning, the mean PS was 2.68 ± 0.1, the mean EV was 2.41 ± 0.1, and the mean TS was 2.48 ± 0.1. The PS was affected by fraction of Brahman (P = 0.034) and tended to be affected by age of dam (P = 0.06). The EV was affected by contemporary group (P < 0.001) and tended to be affected by weaning age (P = 0.074). Contemporary group affected TS (P < 0.001). All 3 methods of temperament evaluation were affected by time of record (P < 0.001). The regression coefficients for PS, EV, and TS were 0.0023 ± 0.0014, 0.0022 ± 0.0012, and 0.0015 ± 0.0012 m·s(-1)·d(-1) of age, respectively. Estimates of maternal genetic effects were always 0 and omitted from final models. Estimates of heritability were 0.27 ± 0.1, 0.49 ± 0.1, and 0.43 ± 0.1 for EV, PS, and TS, respectively. Estimates of permanent environmental variances as proportions of phenotypic variance were 0.33 ± 0.1, 0.23 ± 0.1, and 0.33 ± 0.1 for EV, PS, and TS, respectively. There appears to be sufficient additive genetic variance for selective improvement of temperament characteristics in Brahman cattle.

Segmentation of heart sound recordings by a duration-dependent hidden Markov model.

Digital stethoscopes offer new opportunities for computerized analysis of heart sounds. Segmentation of heart sound recordings into periods related to the first and second heart sound (S1 and S2) is fundamental in the analysis process. However, segmentation of heart sounds recorded with handheld stethoscopes in clinical environments is often complicated by background noise. A duration-dependent hidden Markov model (DHMM) is proposed for robust segmentation of heart sounds. The DHMM identifies the most likely sequence of physiological heart sounds, based on duration of the events, the amplitude of the signal envelope and a predefined model structure. The DHMM model was developed and tested with heart sounds recorded bedside with a commercially available handheld stethoscope from a population of patients referred for coronary arterioangiography. The DHMM identified 890 S1 and S2 sounds out of 901 which corresponds to 98.8% (CI: 97.8-99.3%) sensitivity in 73 test patients and 13 misplaced sounds out of 903 identified sounds which corresponds to 98.6% (CI: 97.6-99.1%) positive predictivity. These results indicate that the DHMM is an appropriate model of the heart cycle and suitable for segmentation of clinically recorded heart sounds.

Gene expression profiling of bovine endometrium during the oestrous cycle: detection of molecular pathways involved in functional changes.

The endometrium plays a central role among the reproductive tissues in the context of early embryo-maternal communication and pregnancy. It undergoes typical changes during the sexual/oestrous cycle, which are regulated by the ovarian hormones progesterone and oestrogen. To identify the underlying molecular mechanisms we have performed the first holistic screen of transcriptome changes in bovine intercaruncular endometrium at two stages of the cycle--end of day 0 (late oestrus, low progesterone) and day 12 (dioestrus, high progesterone). A combination of subtracted cDNA libraries and cDNA array hybridisation revealed 133 genes showing at least a 2-fold change of their mRNA abundance, 65 with higher levels at oestrus and 68 at dioestrus. Interestingly, genes were identified which showed differential expression between different uterine sections as well. The most prominent example was the UTMP (uterine milk protein) mRNA, which was markedly upregulated in the cranial part of the ipsilateral uterine horn at oestrus. A Gene Ontology classification of the genes with known function characterised the oestrus time by elevated expression of genes, for example related to cell adhesion, cell motility and extracellular matrix and the dioestrus time by higher expression of mRNAs encoding for a variety of enzymes and transport proteins, in particular ion channels. Searching in pathway databases and literature data-mining revealed physiological processes and signalling cascades, e.g. the transforming growth factor-beta signalling pathway and retinoic acid signalling, which are potentially involved in the regulation of changes of the endometrium during the oestrous cycle.

Bilateral internal thoracic artery operations in the elderly.

BACKGROUND: Elderly surgical patients have higher operative morbidity and mortality than younger cohorts, particularly when the procedure is lengthy and complex. While use of bilateral internal thoracic arteries (BITA) is often associated with increased surgical risk, we nevertheless hypothesized that the use of BITA in elderly coronary artery bypass patients would not significantly increase their operative risk beyond that encountered using single internal thoracic arterial (SITA) or saphenous vein grafts (SVG). We maintained that arterial grafts remain essentially unaffected by arteriosclerosis, and that extension of a high-quality life is a desirable outcome regardless of age at operation. EXPERIMENTAL DESIGN: We studied myocardial revascularization in 673 patients over 65 years of age at the time of operation. All operations were conducted or supervised by a single surgeon during a ten-year period from January 1986 to January 1996. Preoperative and operative dates were recorded prospectively. SETTING: All patients underwent coronary artery bypass grafting. INTERVENTIONS: The study compared outcomes in patients having all veins, SITA or BITA operations. For the first analysis, 673 patients were divided into three groups: 163 patients (Group 1) had saphenous vein used for all bypasses; 338 patients had a SITA with supplemental vein grafts (Group 2); and 172 patients (Group 3) had BITAs with additional vein grafts as needed. In the second analysis, Group 3 was subdivided and grouped by the coronary arteries which received the ITA grafts, and the analysis was repeated. One hundred and sixteen patients (Group 3A) underwent traditional placement of ITA bypasses (left ITA to the LAD, right ITA to the RCA); in Group 3B, 56 patients received revascularization of branches of the left coronary artery (left ITA to the circumflex system, right ITA to the LAD). MEASURES: We communicated directly with 90.5% of the patients, their families, or their physicians. The survival status of the remainder was determined through the National Social Security Death Index Network. This allowed us to obtain follow-up longevity data for 100% of the study sample at a mean observation period of 5.03+/-3.1 years with variation between 10.8 years to 2.4 years. RESULTS: A multivariate analysis showed that placement of both ITA grafts to left-sided arteries in older patients independently improved long-term survival (p=0.031). CONCLUSIONS: The BITA procedure does not have greater operative morbidity or mortality in the elderly despite the length or complexity of the surgery. To realize improved long-term survival rates, however, both ITAs must be grafted to the left coronary artery branches.

Lasers in the treatment of ischaemic heart disease.

Mounting evidence showing that transmyocardial laser revascularization (TMR) is a safe and effective treatment for angina pectoris arrives just as an increasing number of patients who have undergone angioplasty and coronary artery bypass grafting experience failure with time. TMR, nevertheless, remains controversial. It appears to relieve the symptoms without treating the underlying atherosclerotic disease, and its method of action is unproven. Like angioplasty and coronary bypass, TMR in fact offers palliation rather than a cure for atherosclerotic heart disease. The most sensible current formulations of the therapeutic mechanism of TMR posit a reconfiguration of the microcirculation, with blood shunted from epicardial to endocardial areas. These unresolved issues notwithstanding, TMR benefits patients with end-stage coronary disease and represents a pioneering effort to remodel the microcirculation of patients with arteriosclerotic occlusive disease.

Holmium:YAG laser transmyocardial revascularization relieves angina and improves functional status.

BACKGROUND: Transmyocardial revascularization (TMR) surgery uses laser channeling of diseased myocardium to treat ischemia and angina. Rigorous prospective randomized studies have been previously unavailable. METHODS: Forty-three patients were randomized to a medication group and 43 to a group scheduled for TMR surgery and medication. All had advanced cardiac ischemia with CCSA class 3 or 4 angina, took at least 2 cardiac medications at maximum doses, and were ineligible for angioplasty or bypass. RESULTS: Forty-two of 43 TMR group patients received surgery and were discharged after hospitalizations averaging 3.2 days. Two suffered perioperative MIs, with one death. Four others died within 12 months of surgery, 3 from cardiac events and 1 from pneumonia. Five medical group patients died from cardiac events within 12 months. Three, 6, and 12 month exams showed angina class improvement in TMR patients compared to preoperative values (3.86 +/- 0.05 vs 1.71 +/- 0.2, P < 0.0001), and to controls at 12 months (3.77 +/- 0.07 vs 1.71 +/- 0.2, P < 0.0001). Exercise tolerance improved in TMR patients over preoperative values, and was better than medication group scores after 12 months (490 +/- 17 sec. vs 294 +/- 12 sec., p = 0.0002). CONCLUSIONS: Holmium:YAG laser channeling of the myocardium improves function and reduces angina in advanced cardiac patients who lack alternative therapeutic options.

Surgical myocardial revascularization.

In conclusion, surgical myocardial revascularization has utilized diverse methods to increase blood flow to the starving myocardium. These methods initially used the microcirculation as the portal to reach myocytes until angiography showed that the obstructions were macrovascular. This resulted in a 30-year era of direct attack on the coronary blockages by coronary bypass. Surgical conduits unfortunately have longevity considerably less than that of native arteries and are limited in number. Alternative conduits, both biologic and prosthetic, have not yet proved to have the same clinical results as the ITA. More patients are living long enough to have the extensiveness of their disease exhaust conventional therapies. Newer therapy, restricted thus far to untreatables, revisits the microcirculation by making laser channels. These many innovative procedures have benefited hundreds of thousands of patients. They emerged from the probity and innovation of many individual surgeons.

Improved survival with multiple left-sided bilateral internal thoracic artery grafts.

BACKGROUND: Although conceptually sound, the use of multiple internal thoracic artery (ITA) bypass grafts to improve long-term clinical results remains controversial. This operation typically involves grafting the left ITA to the anterior descending artery and the right ITA to the right coronary artery. Past clinical studies of bilateral ITA operations have not examined comparative results associated with which coronary arteries received the ITA bypass grafts. Because grafting a superior conduit to an artery of lesser physiologic importance might reduce the clinical benefits, we compared the outcomes of patients receiving different configurations of bilateral ITA operations. METHODS: The study group was 498 consecutive bilateral ITA operations, constituting the 10-year experience of a single surgeon. Follow-up averaged 7.1 years (mode 7.3 years), and was 94.2% complete. These patients were divided into two groups, 311 patients (group I) who underwent the traditional operation (left ITA to the left anterior descending artery, right ITA to the right coronary artery), and 187 patients (group II) who received revascularization of branches of the left coronary artery (left ITA to the circumflex system and right ITA to the left anterior descending artery). RESULTS: The study groups were similar in age, severity of disease, number of bypassed arteries, ejection fraction, diabetes, hypertension, and duration of operation. There were more male patients in group II (91.4% versus 82.3%). A multivariate analysis showed that the location of ITA bypass grafts influenced survival independent of gender (p = 0.0288). Operative morbidity and mortality were similar between groups. Ninety-three patients had repeat angiography with equivalent patency rates of the ITA conduits (91.7% versus 89.6%; p = 0.67). The Kaplan-Meier actuarial survival estimate demonstrated a significant improvement in survival of patients in group II who received both ITA bypass grafts to left-sided arteries (p = 0.021), with the survival curves diverging at 6 years. More patients in group II were in New York Heart Association class I or II, but the difference was not statistically significant (94.6% versus 91.6%). Only 2 patients required reoperation. CONCLUSIONS: It appears that maximum long-term benefit from bilateral ITA operations is achieved by grafting the ITA conduits to coronary arteries that supply more left ventricular muscle.

Suitability and durability of multiple internal thoracic artery coronary artery bypasses.

OBJECTIVE: The authors evaluate operative and extended outcomes of coronary artery bypass surgery using the bilateral internal thoracic arteries (ITAs) as bypass grafts. The authors conclude that the procedure is viable and of long-term benefit to most patients. SUMMARY BACKGROUND DATA: Multiple ITA grafting was met with early enthusiasm by the surgical profession, but skepticism and controversy arose with reports of increased operative morbidity, insufficient graft blood flow, a high incidence of failure of the right ITA, and uncertainty about durability and long-term benefits. METHODS: To assess the actual incidence and impact of these complications and long-term results, the authors prospectively studied 500 consecutive patients with multiple ITA bypasses, constituting the closely observed and carefully documented experience of one surgeon over an 11-year period. RESULTS: Operative mortality in the series of 500 patients was 1.8%, perioperative myocardial infarction (new Q wave) rate was 0.6%, and deep sternal wound infection occurred in 1%. Six patients (1.2%) had strokes, and nine patients (1.8%) were returned to the operating room to control bleeding. One hundred ninety-eight patients who had abnormal stress test results before surgery were retested within 3 months of surgery. Ninety-four percent of these were normal, 3% were nondiagnostic, and 3% were abnormal. After a mean follow-up of 7.1 years (mode, 7.2 years), 87.5% of patients in the sample were alive, and 93.2% of this group have experienced continuing good clinical results (New York Heart Association class I or II). Eighty-nine patients who underwent an angiogram had 90.8% patency rates of ITA bypasses and 84.5% patency of vein grafts. Only two patients required repeat operations. CONCLUSIONS: The operative results did not support the contention that the coronary artery bypass using ITA procedure produces higher than acceptable mortality and morbidity rates. Multiple ITA bypasses can be performed without excessive morbidity, with low reoperation rates and long-term outcomes that should encourage skeptics to reconsider the procedure's clinical value.