Evaluation of SARS-CoV-2 antibody levels on hospital admission as a correlate of protection against mortality.

BACKGROUND: Millions of people have now been vaccinated against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, it is still unclear which antibody levels provide protection against mortality. It is further unknown whether measuring antibody concentrations on hospital admission allows for identifying patients with a high risk of mortality. OBJECTIVES: To evaluate whether anti-SARS-CoV2-spike antibodies on hospital admission predict in-hospital mortality in patients with coronavirus disease 2019. METHODS: We conducted a prospective, multicentre cohort study on 1152 hospitalized patients who tested positive for SARS-CoV-2 with a polymerase chain reaction-based assay. Patients were classified by vaccination status. Anti-SARS-CoV-2 spike antibodies were determined on hospital admission. The investigated end point was in-hospital mortality for any cause. RESULTS: Spike antibodies on hospital admission were significantly lower in non-survivors in both non-vaccinated (73 U/ml, 95%CI 0-164 vs. 175 U/ml, 95%CI 124-235, p = 0.002) and vaccinated patients (1056 U/ml, 95%CI 701-1411 vs. 1668 U/ml, 95%CI 1580-1757, p < 0.001). Further, spike antibodies were significantly lower in fully vaccinated and boostered patients who died compared to those who survived (mean 883 U/ml, 95%CI 406-1359 vs. 1292 U/ml, 95%CI 1152-1431, p = 0.017 and 1485 U/ml, 95%CI 836-2133 vs. 2050 U/ml, 95%CI 1952-2149, p = 0.036). Patients infected with the currently prevailing Omicron variant were three times more likely to die if spike antibodies were <1200 U/ml (OR 3.458, 95%CI 1.562-7.656, p = 0.001). After adjusting for potential confounders, this value increased to an aOR of 4.079 (95%CI 1.809-9.198, p < 0.001). CONCLUSION: Anti-SARS-CoV2 spike-antibody levels on hospital admission are inversely associated with in-hospital mortality. Hospitalized patients with lower antibody levels have a higher risk of mortality.

Long-term performance of an atrial lead capable of accelerometer based detection of cardiac contractility in patients receiving cardiac resynchronisation therapy.

OBJECTIVES: To evaluate the long-term performance of the SonRtip atrial lead. BACKGROUND: To optimize atrioventricular and interventricular timing and thereby potentially improving cardiac resynchronization therapy (CRT) responder rates, a lead integrated technology and a cardioverter/defibrillator-based algorithm measuring peak endocardial acceleration have been introduced. Long-term performance of the atrial lead (SonRtip PS55D, Sorin/MicroPort CRM, Italy) embedded with such a sensor has not been reported so far. METHODS: Between 2012 and 2018, 143 patients underwent implantation of the SonRtip atrial lead in four Austrian medical centers. Conventional bipolar atrial leads implanted during the same period in 526 patients receiving CRT were used as control cohort. RESULTS: Among 669 patients included in the study, 10 (1.5%) showed increased atrial pacing thresholds and/or decreased atrial sensing amplitudes and/or sudden increase in atrial lead impedance (above 3000 Ω) after an uneventful early postoperative period. Seven (70%) of the malfunctioning leads were SonRtip leads (p <0.001). Lead replacement was needed in 4.2% of SonRtip leads (six out of 143) and in 0.38% of all other conventional atrial leads (two out of 526) (p <0.001). Because of unaltered atrial sensing properties, a wait and see strategy was chosen in two patients-one of them with a SonRtip lead. The implanted atrial lead in the latter person experienced a sudden increase in pacing threshold (4V/0.35ms). CONCLUSIONS: While short-term safety and stable technical performance of the SonRtip atrial lead could be confirmed, our study found an unexpectedly high malfunction rate over a longer follow-up period.

Sex differences in independent factors associated with coronary artery disease.

BACKGROUND: Women undergoing coronary angiography (CA) due to chest pain are more likely to present with less extensive coronary artery disease (CAD) than men, which might be attributed to different effects of cardiovascular risk factors on coronary atherogenesis between sexes. The aim of the present study was to evaluate sex differences in independent factors associated with obstructive and non-obstructive CAD in a large consecutive cohort of patients undergoing elective CA. METHODS: Data from 7819 patients (2653 women and 5184 men), including cardiovascular risk factors, clinical presentation, CAD severity and treatment decisions were analysed. RESULTS: Women were older than men (65 ± 11 vs. 63 ± 11 years, p < 0.001); low-density lipoprotein cholesterol (LDL; 125 ± 38 vs. 122 ± 37 mg/dL, p < 0.001) and high-density lipoprotein cholesterol (HDL) cholesterol levels (62 ± 18 vs. 51 ± 15 mg/dL, p < 0.001) were higher in women; and smokers were more frequently men (14.4 vs. 20.1%, p < 0.001). Men more frequently had an obstructive CAD (41.1 vs. 65.6%, p < 0.001). Multivariable analyses revealed age, HDL cholesterol, hypercholesterolaemia, diabetes mellitus, arterial hypertension and a positive family history being associated with obstructive CAD in both sexes, whereas smoking was independently associated with obstructive CAD only in women. The association of hypercholesterolaemia with obstructive CAD was stronger in men. For non-obstructive CAD, no sex-specific associated factors could be identified. CONCLUSION: The impact of smoking and hypercholesterolaemia on coronary atherosclerosis is different between women and men. This might be taken into account when planning individual interventions to reduce cardiovascular risk.

Prognostic value of peripheral arterial tonometry in patients with coronary artery disease and a high cardiovascular risk profile.

AIM: Data regarding the prognostic value of peripheral endothelial function testing in patients with cardiovascular disease are conflicting. Peripheral arterial tonometry(PAT) is increasingly used to measure the peripheral endothelial function. The prognostic value of this method has not been investigated thus far in patients with cardiovascular disease and/or a high cardiovascular risk profile. METHODS: In 96 patients with significant coronary artery disease(CAD) or＜70% stenosis and ≥ three cardiovascular risk factors, reactive hyperemia was induced following upper arm occlusion and the PAT-ratio between baseline and hyperemia was calculated. The patients were followed for cardiovascular events(revascularization, acute coronary syndrome, ischemic stroke, cardiovascular death, repeat coronary angiography due to chest pain) for 44±14 months. The first event was included in the combined end point. RESULTS: The study cohort was divided according to the median PAT-ratio(1.91). The combined end point occurred in 14 patients with a PAT-ratio below the median(1.91) and in 12 patients with a PAT-ratio of ≥1.91 (p=0.65). In a subgroup of 76 patients, the PAT-ratio was reassessed after six months. No differences in the event rate were found between the patients who exhibited deterioration(n=50) and those who exhibited an improvement in the PAT-ratio of ＞0.1(n=26; 22 vs. 32%, p=0.32). The combined end point occurred earlier in the patients with a PAT-ratio within the 1st tertile than in those with a PAT-ratio within the 2nd/3rd tertile(11.3±11.0 vs. 27.5±18.6 months, p=0.03). CONCLUSIONS: In patients with established CAD or a high cardiovascular risk profile, the PAT-ratio cannot be used to predict the risk of future cardiovascular events. However, a lower PAT-ratio may be associated with the earlier occurrence of cardiovascular events.

Comparison of brachial artery wall thickness versus endothelial function to predict late cardiovascular events in patients undergoing elective coronary angiography.

An increased brachial artery intima media thickness (BA-IMT) has been shown to be of prognostic value. Conflicting prognostic data have been reported for brachial artery flow-mediated vasodilation (BA-FMD), and the longest evaluated follow-up period to date is 5.5 years. We sought to investigate the very late prognostic value of BA-IMT and BA-FMD in 396 consecutive patients (age 54 ± 9 years) admitted for invasive evaluation of chest pain. BA-IMT and BA-FMD were measured using high-resolution ultrasonography. The patients were divided according to the median BA-IMT (0.37 mm) and median BA-FMD (7.6%). After a mean follow-up of 141 ± 12 months, cardiovascular events were documented. More cardiovascular events were found in patients with an increased BA-IMT (50 vs 78 events, p = 0.003). When the groups were compared according to the median BA-FMD, no differences in the number of events were documented (70 vs 75 events, p = 0.60). On multivariate Cox regression analysis, including age, number of risk factors, BA diameter, presence of coronary artery disease, BA-FMD, and BA-IMT, only the presence of coronary artery disease and BA-IMT remained significantly associated with outcome. In conclusion, BA-IMT, but not BA-FMD, predicted cardiovascular events and cardiovascular death with ≤12 years of follow-up in patients undergoing an invasive evaluation of chest pain. Our results represent, by far, the longest follow-up of BA-IMT and peripheral endothelial function testing compared with previously reported data.

Comparison of peripheral endothelial function in shift versus nonshift workers.

Shift working is related to increased cardiovascular morbidity. Peripheral endothelial dysfunction, an inherent feature of early atherosclerosis, has been suggested as a surrogate marker of cardiovascular risk. Whether shift working is associated with peripheral endothelial dysfunction has not been investigated to date. A total of 48 male shift workers (SWs) and 47 male nonshift workers (NSWs) (mean age 43 ± 5 years) were recruited from a glass manufactory. The SWs and NSWs were matched according to age, body mass index, smoking habits, family history of premature coronary artery disease, prevalence of hypercholesterolemia and hypertension, and work place. Their sport habits were also documented. Peripheral endothelial function was assessed using the EndoPAT technique to determine the peripheral arterial tone (PAT) index. According to the study design, no difference was found in the risk factor profiles between the SWs and NSWs. Despite a greater percentage of regular physical activity among the SWs (16.7 vs 4.3%, p = 0.05), shift working was associated with a reduced PAT index compared to working only on the day shift (PAT index 1.73 ± 0.4 vs 1.94 ± 0.5, p = 0.03). In the NSW group, the participants with regular physical training (n = 16) had a greater PAT index than those without regular physical activity (n = 12; PAT index 2.28 ± 0.45 vs 1.86 ± 0.51, p = 0.03). No such difference was found in the SWs. In conclusion, SWs had a reduced PAT index compared with NSWs, suggesting endothelial dysfunction. Therefore, the known increased cardiovascular risk in those shift working might be related to endothelial dysfunction.

[STEMI guidelines 2008--Do they influence today's myocardial infarction treatment strategies in rural areas?]. / STEMI-Guidelines 2008--Konsequenzen für die heutige Infarktversorgung im ländlichen Raum?

2008 new guidelines for the management of patients with ST-elevation myocardial infarction were published by the European Society of Cardiology. For daily clinical practice, changes in recommendations concerning the preferred revascularization therapy according to different time delays are of great interest. This review focuses on possible implications of these new guidelines on the choice of reperfusion strategies in rural areas.

Neopterin, CD4+CD28- lymphocytes and the extent and severity of coronary artery disease.

OBJECTIVES: Macrophages and pro-inflammatory CD3+CD4+CD28- T lymphocytes are involved in atherosclerotic plaque destabilization. Whether neopterin, a macrophage-specific activation-marker, and circulating CD3+CD4+CD28- cells are also related to the severity and extent of coronary artery disease (CAD) in stable patients is still unclear. METHODS: Coronary angiograms of 30 patients with stable angina pectoris were graded using the Gensini severity and an extent score. Patients were grouped according to the median of each score. Lymphocyte subsets were determined by FACS analysis and neopterin by radioimmunoassay. Peripheral endothelial function of the brachial artery (FMD) shown to correlate with cardiovascular risk factors was evaluated using high-resolution ultrasound. RESULTS: More extensive CAD was associated with increased neopterin levels (8.3 +/- 3.3 vs. 5.5 +/- 1.2 nmol/L, p < 0.001) and increased CD3+CD4+CD28- cells (3.1 +/- 1.6 vs. 2.0 +/- 1.2%, p < 0.05). A high Gensini severity score was associated with increased neopterin levels (7.8 +/- 2.7 vs. 6.3 +/- 1.7 nmol/L, p < 0.05), but not with CD3+CD4+CD28- cells. Neopterin correlated with both the extent (r = 0.59, p < 0.001) and the Gensini score (r = 0.57, p < 0.003). FMD was not correlated with both scores. CONCLUSIONS: Neopterin and CD3+CD4+CD28- lymphocytes are associated with CAD extent in stable patients, thereby emphasizing the inherent role of inflammation in atherogenesis itself beyond plaque destabilization. Neopterin's correlation with CAD severity might be additionally useful in identifying patients eligible for revascularization procedures.

Gender-related outcome following percutaneous coronary intervention for ST-elevation myocardial infarction: data from the Austrian acute PCI registry.

AIMS: Whether or not primary percutaneous coronary intervention (P-PCI) is equally effective and safe in women and men in a real world setting is still a matter of debate. The aim of this study was to evaluate the effect of gender on in-hospital outcome after P-PCI for ST-elevation myocardial infarction (STEMI) in a prospective national registry. METHODS AND RESULTS: This registry includes in-hospital outcome data from 19 PCI-performing hospitals. During 12 months, 1087 patients with STEMI were registered (mean age 62 +/- 13 years; 27% women). Women were older than men (67 +/- 13 vs. 60 +/- 13 years; p < 0.001) and more often had diabetes mellitus (21% vs. 13%; p < 0.001) or cardiogenic shock (15% vs. 9%; p=0.004). PCI was performed in 1004 patients (92.4%) and more frequently in men than in women (93.9 vs. 88.3%, p=0.002), whereas conservative treatment was more often decided in women (9.3% vs 4.3%; p=0.002). No differences were found between women and men in primary success rate (TIMI 2+3 flow, 92.9% vs. 93%; p=0.96). On univariate analysis, in-hospital mortality was higher in women than in men (13.7% vs. 7.2%; p=0.001). On multivariable analysis age, shock, diabetes and TIMI flow before PCI remained associated with mortality. CONCLUSIONS: Women have higher in-hospital mortality following PCI for STEMI. On multivariate analysis age, shock, diabetes and TIMI flow, but not gender, were associated with mortality in this national register. Older age and more comorbidity are likely to explain the higher mortality in female patients undergoing P-PCI.

Role of 16-multidetector computed tomography in the assessment of coronary artery stenoses: A prospective study of consecutive patients.

BACKGROUND: Recent studies have demonstrated a high sensitivity (S) of 16-multidetector computed tomography (16-MDCT) for the detection of significant coronary artery stenoses. Whether these results are applicable to clinical practice is unclear. Therefore, the aim of the present study was to compare 16-MDCT angiography with conventional coronary angiography (CCA) for the detection of significant coronary artery stenoses in a consecutive series of patients. METHOD: A total of 93 consecutive patients (mean [+/- SD] age 59+/-9 years), in whom CCA was performed for stable angina pectoris, underwent 16-MDCT angiography (16x0.75 mm, table feed 6.5 mm/s, rotation time 0.42 s; Sensation 16, Siemens Medical Solutions, Germany) the day before performing CCA. Patients with diabetes mellitus, serum creatinine level higher than 132.6 mumol/L and/or acute coronary syndromes were excluded. Two observers blinded to CCA results evaluated MDCT angiograms according to standard criteria. Segment-based (13 segments per patient) and patient-based (at least one stenosis greater than 50% lumen diameter reduction) analyses were performed. RESULTS: A total of 1209 segments were analyzed. Of these segments, 173 (14%) were excluded due to poor image quality or massive calcification. In 86 segments, CCA revealed significant coronary artery stenosis (greater than 50% diameter reduction). However, 16-MDCT detected only 47 of these, resulting in a S of 55% and a specificity (SP) of 97% (positive predictive value 64%; negative predictive value 96%). On a patient-based analysis, the S increased to 89%, whereas the SP still remained high (87%). CONCLUSION: In this relatively large consecutive cohort, S for the detection of significant coronary artery stenoses was moderate on a segment-based analysis but increased on a patient-based analysis using 16-MDCT. In contrast, SP was high in both analyses, supporting the use of 16-MDCT for the exclusion of significant coronary artery stenoses. Further improvement of spatial and temporal resolution in MDCT technology may lead to a lower exclusion rate and higher S.

Effect of atorvastatin on circulating proinflammatory T-lymphocyte subsets and soluble CD40 ligand in patients with stable coronary artery disease--a randomized, placebo-controlled study.

BACKGROUND: Coronary atherosclerosis includes an activation of circulating T lymphocytes. Statins exert anti-inflammatory effects beyond lipid lowering. Whether these properties influence systemic T lymphocytes is unclear. METHODS: To investigate the effect of atorvastatin on circulating T-lymphocyte subsets producing proinflammatory and anti-inflammatory cytokines (interferon gamma [IFN-gamma(+)], interleukin 2 [IL-2(+)], IL-4(+), and IL-10(+)) and on the T-cell-activating soluble CD40 ligand (sCD40L), 30 hypercholesterolemic patients with angiographically documented stable coronary artery disease (CAD) were randomized to placebo or atorvastatin (20 mg/d) for 3 months. Eight healthy volunteers served as controls. Levels of peripheral cytokine-producing CD4+ and CD8+ T cells and their CD28- subsets were determined by FACS. Serum soluble CD40L was measured with ELISA. RESULTS: IL-2(+) T lymphocytes and sCD40L levels were higher in patients with CAD compared with controls, whereas IFN-gamma(+) and anti-inflammatory IL-4(+) and IL-10(+) T lymphocytes were similar. Levels of IL-2(+), IFN-gamma(+), IL-4(+), and IL-10(+) T-cell subsets as well as CD28- T lymphocytes were neither changed by atorvastatin nor by placebo, whereas sCD40L was lowered only in atorvastatin-treated patients (P < .01). CONCLUSION: Circulating IL-2(+) T lymphocytes are increased in patients with stable CAD reflecting an activation of the global immune system, but are not influenced by atorvastatin therapy. The elevated levels of platelet-derived T-lymphocyte-stimulating sCD40L are decreased by atorvastatin probably reflecting an atheroprotective effect. Hence, sCD40L may be an additional biomarker to be considered when evaluating the treatment effects of statins in patients with stable CAD.

Association of improvement of brachial artery flow-mediated vasodilation with cardiovascular events.

The aim of this pilot study was to test the prognostic value of serial measurements of peripheral endothelial function, assessed by brachial artery flow-mediated dilation (FMD), in patients with angiographically proven coronary artery disease. In 68 patients, FMD was measured on the day after coronary angiography and again after a mean of 14 +/- 12 months. Patients were divided into two groups: absolute improvement in FMD > or = 3% (FMD-improver = FMD-i) and < 3% (FMD-non-improver = FMD-ni). After a mean follow-up of 44 +/- 12 months, cardiovascular events were recorded. Baseline characteristics were similar between groups, except the number of risk factors which was smaller in FMD-i (1.6 +/- 0.7 vs 2.1 +/- 0.9, p < 0.02). Cardiovascular events were more frequent in FMD-ni (9 vs 1 event; p < 0.05). In Kaplan-Meier analysis, a trend towards a better outcome in patients with improved FMD was found using the log-rank test (p = 0.08). The single baseline FMD showed no relationship with late cardiovascular events. Thus, 'delta-FMD' may be more closely related to prognosis than a single FMD measurement.

Relationship of sonographic wall components of the brachial artery to hypertension and coronary atherosclerosis.

The aim of this study was to determine whether sonographically assessed intimal (echodense, ED) or medial (echolucent, EL) thickening of the brachial artery is associated with coronary artery disease (CAD) and/or arterial hypertension (HT). In 201 patients the ED and EL wall components, as well as the total wall thickness of the brachial artery, were measured with high-resolution ultrasound (13 MHz). According to the presence or absence of CAD and HT, the patients were divided into four groups: no HT and no CAD (n = 26, group 1), CAD (> or = 30% diameter stenosis in > or = 1 major branch) only (n = 63, group 2), HT only (n = 34, group 3), and HT and CAD (n = 78, group 4). EL (p < 0.001) and combined wall thickness (p < 0.001), but not the ED wall component, were significantly different between the groups, with the highest values occurring in group 4. On logistic regression analyses adjusting for age, coronary risk factors and body mass index, EL, but not ED, thickness correlated independently with the presence of CAD (p = 0.04) and HT (p < 0.001). High-resolution ultrasound examination of the brachial artery wall structure may contribute to the noninvasive assessment of early atherosclerosis.

Prognostic value of brachial artery endothelial function and wall thickness.

OBJECTIVES: We sought to examine the prognostic value of brachial artery (BA) flow-mediated vasodilation (FMD) and intima-media thickness (IMT) in patients admitted for invasive evaluation of chest pain. BACKGROUND: Both FMD and IMT of the BA have been associated with coronary risk factors and the presence of coronary artery disease (CAD). Recent studies on the prognostic value of FMD have been conflicting. METHODS: In 398 consecutive patients (age 54 +/- 9 years) undergoing coronary angiography, FMD and IMT of the BA were measured using high-resolution ultrasound (13 MHz). Patients were divided into two groups according to the FMD median (7.6%). After a mean follow-up of 39 +/- 12 months, cardiovascular events were documented. RESULTS: No difference was found in the number of cardiovascular events between groups. On multivariate Cox regression analysis, including age, number of risk factors, BA diameter, presence of CAD, FMD, and IMT, only the presence of CAD and IMT remained significantly associated with cardiovascular events. CONCLUSIONS: Intima-media thickness predicted late (up to 4 years) cardiovascular events in a large population admitted for evaluation of chest pain. In contrast, the long-term prognostic value of a single baseline measure of BA-FMD seems to be limited.

[The role of inflammation in the pathophysiology of acute coronary syndromes]. / Die Rolle der Inflammation in der Pathophysiologie akuter Koronarsyndrome.

All stages of atherosclerotic plaques are characterized by an inflammatory component, in which T lymphocytes and macrophages orchestrate lesion progression and destabilization by releasing cytokines (e.g., interferon-gamma, tumor necrosis factor-alpha, tissue factor). At the extreme end of this process plaque rupture occurs, which may manifest clinically as an acute coronary syndrome. Hence, measuring this atherosclerosis-inherent inflammation may help predicting cardiovascular events. Accordingly, different soluble inflammatory markers were studied for their predictive value in acute coronary syndromes. Special attention was paid to high-sensitivity C-reactive protein (hs-CRP) and soluble CD40 ligand (sCD40L). The latter seems not only to be a marker of inflammation and platelet activation, but is suggested to directly destabilize atherosclerotic plaques by stimulating pro-inflammatory T lymphocytes. Therefore, reduction of soluble inflammatory markers is an attractive target for future therapeutic strategies. Statins and glycoprotein IIb/IIIa antagonists, well-established treatments in acute coronary syndromes, were demonstrated to decrease hs-CRP and sCD40L. Whether this reduction translates into a better prognosis has to be investigated in further studies.