Long-term follow-up of medically treated patients with spontaneous coronary artery dissection: a prospective, Swiss single-centre cohort study.

AIMS OF THE STUDY: Spontaneous coronary artery dissection (SCAD) is an increasingly diagnosed cause of acute myocardial infarction. However, there is still a limited number of larger cohorts with long-term follow-up. We report on the largest Swiss single-centre cohort to date, with follow-up of up to 22 years. METHODS: We prospectively collected SCAD cases from June 1998 until December 2020. A strategy of systematic follow-up angiography was applied. Information on long-term follow-up was collected up to the end of 2020. Major cardiovascular events (MACE) were defined as all-cause death, non-fatal MI, and non-fatal cardiac arrest. RESULTS: We identified 105 SCAD patients (mean age 53 ± 11 years, 98 female, 5 peripartum). Presentation was myocardial infarction in all patients. In 102 patients, there was one contiguous dissection. Three patients had two (n = 2) or three (n = 1) non-contiguous dissections. In the majority of patients (n = 97), the primary treatment approach was conservative (dual antiplatelet therapy for 12 months in 90% of patients, statins in 91%). Seven patients were treated with percutaneous coronary intervention (PCI) and one patient underwent bypass surgery. Elective follow-up angiograms were performed in 73 asymptomatic patients after a median follow-up of 6.0 months (interquartile range [IQR] 5.5-6.5). These showed healing of the dissection (n = 65) or a good result after PCI (n = 5) in 70 patients. Three patients had a persistent dissection but conservative treatment was continued. After a median follow-up of 7.5 years (IQR 3.6-12.5) (longest follow-up: 22.5 years) there were 15 MACE. Five MACE occurred within 30 days of the index event: death following catastrophic peripartum left main SCAD (n = 1), out-of-hospital cardiac arrest with successful resuscitation 16 days after SCAD (n = 1), ST-segment elevation myocardial infarction due to occlusion of the dissected artery 10 hours after the index angiogram with subsequent PCI (n = 1), SCAD of a second vessel 8 days after the index SCAD (n = 1), and non-ST-segment elevation myocardial infarction with persistent, multisite SCAD 10 days after the index event (n = 1). There were 10 late MACE, including myocardial infarction and recurrent SCAD (different vessel/lesion) a median of 7.6 years (IQR 3.9-9.6) after the index event in eight patients and death with unclear cause in two patients. CONCLUSION: This SCAD series highlights its highly variable clinical course during the acute phase and in the long term. Although most SCAD patients can be treated conservatively with subsequent healing of the dissection and good clinical outcome, there are also patients with dramatic acute presentation or MACE several years after the initial presentation.

Impact of a volume challenge on haemodynamics and prognosis in patients with severe aortic stenosis.

AIMS: A volume challenge can unmask pulmonary hypertension (PH) and its mechanism. We evaluated the impact of a volume challenge on mean pulmonary artery pressure (mPAP) and mean pulmonary artery wedge pressure (mPAWP) and its prognostic implications in patients with severe aortic stenosis (AS) undergoing aortic valve replacement (AVR). METHODS AND RESULTS: In 285 patients with severe AS (indexed aortic valve area 0.41 ± 0.13 cm2 /m2 ), mPAP and mPAWP were measured before and after administration of 150 ± 58 mL of low-osmolal or iso-osmolal contrast. Following contrast, mPAP and mPAWP rose from 25 ± 10 and 16 ± 8 mmHg by 5 ± 4 and 4 ± 4 mmHg to 30 ± 11 and 20 ± 8 mmHg. There were 112 (39%) patients with pre-contrast PH and 70 (40% of those without pre-contrast PH) patients with post-contrast PH only. Post-contrast PH patients were intermediate between pre-contrast PH and no PH in terms of AS severity, cardiac dysfunction, and haemodynamics. After a median follow-up of 43 months post-AVR, pre-contrast PH patients had numerically the highest mortality driven by those with pre-contrast combined pre-capillary and post-capillary PH (n = 35), while post-contrast changes in mPAP and mPAWP were not related to mortality. Patients with any post-contrast mPAWP > 18 mmHg had significantly higher mortality than those with post-contrast mPAWP ≤ 18 mmHg, CONCLUSIONS: In severe AS, a contrast challenge leads to post-contrast PH in ~40% of patients without pre-contrast PH. However, post-contrast haemodynamic changes do not adversely affect outcomes in patients undergoing AVR. Post-contrast PH represents an intermediate stage of 'cardiac damage', which may be attenuated or reversible after AVR.

Modulation of Working Memory Using Transcranial Electrical Stimulation: A Direct Comparison Between TACS and TDCS.

Transcranial electrical stimulation (TES) has been considered a promising tool for improving working memory (WM) performance. Recent studies have demonstrated modulation of networks underpinning WM processing through application of transcranial alternating current (TACS) as well as direct current (TDCS) stimulation. Differences between study designs have limited direct comparison of the efficacy of these approaches, however. Here we directly compared the effects of theta TACS (6 Hz) and anodal TDCS on WM, applying TACS to the frontal-parietal loop and TDCS to the dorsolateral prefrontal cortex (DLPFC). WM was evaluated using a visual 2-back WM task. A within-subject, crossover design was applied (N = 30) in three separate sessions. TACS, TDCS, and sham stimulation were administered in a counterbalanced order, and the WM task was performed before, during, and after stimulation. Neither reaction times for hits (RT-hit) nor accuracy differed according to stimulation type with this study design. A marked practice effect was noted, however, with improvement in RT-hit irrespective of stimulation type, which peaked at the end of the second session. Pre-stimulation RT-hits in session three returned to the level observed pre-stimulation in session two, irrespective of stimulation type. The participants who received sham stimulation in session one and had therefore improved their performance due to practice alone, had thus reached a plateau by session two, enabling us to pool RT-hits from sessions two and three for these participants. The pooling allowed implementation of a within-subject crossover study design, with a direct comparison of the effects of TACS and TDCS in a subgroup of participants (N = 10), each of whom received both stimulation types, in a counterbalanced order, with pre-stimulation performance the same for both sessions. TACS resulted in a greater improvement in RT-hits than TDCS (F(2,18) = 4.31 p = 0.03). Our findings suggest that future work optimizing the application of TACS has the potential to facilitate WM performance.

Spontaneous Coronary Artery Dissection: Angiographic Follow-Up and Long-Term Clinical Outcome in a Predominantly Medically Treated Population.

OBJECTIVE: We sought to assess the angiographic and long-term clinical outcomes in a predominantly medically treated population with spontaneous coronary artery dissection (SCAD). BACKGROUND: There are little data on the angiographic and long-term outcome in patients with SCAD. METHODS: We studied 64 patients with SCAD (mean age 53 years, 94% females, three peripartum) with acute coronary syndrome who were treated using coronary bypass grafting (n = 1), percutaneous coronary intervention (n = 7), or medical therapy (n = 56). A repeat angiogram was performed in 40/64 (63%) patients. The median clinical follow-up was 4.5 years. RESULTS: Five (8%) patients had a major cardiac event. One patient with peripartum left main SCAD and cardiogenic shock died during PCI. One patient with conservatively treated SCAD of the posterior descending artery suffered out-of-hospital cardiac arrest 16 days after the initial angiogram but survived. Three patients experienced a second SCAD in another vessel 3.7, 4.7, and 7.9 years after the index event while the initial dissection had healed. Thirty medically treated patients underwent a scheduled repeat angiogram showing healing of the dissection in all but one patient. After a median follow-up of 4.5 (1.8-8.4) years, all 63 patients surviving the index event were alive and free of symptoms suggestive of myocardial ischemia. CONCLUSIONS: In general, the long-term outcome of patients with SCAD is excellent, and medical therapy can be safely applied in the majority of patients. However, SCAD can be a life-threatening and sometimes catastrophic event, and some patients experience early or late complications including SCAD of another vessel. © 2015 Wiley Periodicals, Inc.

A virus-like particle-based vaccine selectively targeting soluble TNF-alpha protects from arthritis without inducing reactivation of latent tuberculosis.

Neutralization of the proinflammatory cytokine TNF-alpha by mAbs or soluble receptors represents an effective treatment for chronic inflammatory disorders such as rheumatoid arthritis, psoriasis, or Crohn's disease. In this study, we describe a novel active immunization approach against TNF-alpha, which results in the induction of high titers of therapeutically active autoantibodies. Immunization of mice with virus-like particles of the bacteriophage Qbeta covalently linked to either the entire soluble TNF-alpha protein (Qbeta-C-TNF(1-156)) or a 20-aa peptide derived from its N terminus (Qbeta-C-TNF(4-23)) yielded specific Abs, which protected from clinical signs of inflammation in a murine model of rheumatoid arthritis. Whereas mice immunized with Qbeta-C-TNF(1-156) showed increased susceptibility to Listeria monocytogenes infection and enhanced reactivation of latent Mycobacterium tuberculosis, mice immunized with Qbeta-C-TNF(4-23) were not immunocompromised with respect to infection with these pathogens. This difference was attributed to recognition of both transmembrane and soluble TNF-alpha by Abs elicited by Qbeta-C-TNF(1-156), and a selective recognition of only soluble TNF-alpha by Abs raised by Qbeta-C-TNF(4-23). Thus, by specifically targeting soluble TNF-alpha, Qbeta-C-TNF(4-23) immunization has the potential to become an effective and safe therapy against inflammatory disorders, which might overcome the risk of opportunistic infections associated with the currently available TNF-alpha antagonists.

Impact of a lead glass screen on scatter radiation to eyes and hands in interventional cardiologists.

The objective of this study was to assess the impact of a transparent lead glass screen (TLGS) on scatter radiation to the eyes and the hands in interventional cardiologists and to compare the results to the recommended annual threshold values of 150 and 500 mSv, respectively. Local radiation doses to the left eye and the ring finger of the left hand of three operators (A, B, C) were assessed by thermoluminiscence dosimeters during 813 coronary angiographies (CAs), including 190 ad hoc percutaneous coronary interventions (PCIs) either with a TLGS placed between patient and operator [615 CAs including 138 ad hoc PCIs; dose-area product (DAP) = 84.9 +/- 71.3 Gy x cm(2)], or without (198 CAs including 52 PCIs; DAP = 85.7 +/- 61.5 Gy x cm(2)). To determine the efficacy of the TLGS, average DAP-normalized local doses were calculated. Using a TLGS, operator A, B, and C performed 259 (in 9 months), 211 (in 8 months), and 145 CAs (in 8 months) with TLGS and acquired cumulative eye lens doses of 5.5, 1.5, and 1.0 mSv corresponding to extrapolated annual doses of 7.3, 2.3, and 1.5 mSv. The cumulative finger doses were 9.6, 10.3, and 6.4 mSv, resulting in extrapolated annual doses of 12.8, 15.5, and 9.6 mSv. Compared to 139 (in 5 months), 36 (in 2 months), and 23 CAs (in 2 months) without TLGS, the use of a TLGS reduced the DAP-normalized eye dose by a factor of 19 (with TLGS 0.153 vs. without TLGS 2.924 microSv/Gy x cm(2)), whereas only a weak effect on the dose to the hands was observed (with TLGS 0.504 vs. without TLGS 0.578 microSv/Gy x cm(2)). The consequent use of a TLGS efficiently reduces scatter radiation to the operator's eyes in daily practice, but has only minimal effects on the dose to the hands.

A therapeutic vaccine for nicotine dependence: preclinical efficacy, and Phase I safety and immunogenicity.

Nicotine is the principal addictive component in tobacco, and following uptake acts in the central nervous system. The smoking-cessation efforts of most smokers fail because a single slip often delivers sufficient nicotine to the brain to reinstate the drug-seeking behaviour. Blocking nicotine from entering the brain by induction of specific antibodies may be an effective means to prevent such relapses. The hapten nicotine was coupled to virus-like particles (VLP) formed by the coat protein of the bacteriophage Qb. In preclinical experiments, this Nicotine-Qb VLP (NicQb) vaccine induced strong antibody responses. After intravenous nicotine challenge, vaccinated mice exhibited strongly reduced nicotine levels in the brain compared with control mice. In a phase I study, 32 healthy non-smokers were immunized with NicQb. The vaccine was safe and well-tolerated. All volunteers who received NicQb showed nicotine-specific IgM antibodies at day 7 and nicotine-specific IgG antibodies at day 14. Antibody levels could be boosted by a second injection or the addition of Alum as an adjuvant and the antibodies had a high affinity for nicotine. These data suggest that antibodies induced by NicQb may prevent relapses by sequestering nicotine in the blood of immunized smokers.