Percutaneous coronary intervention of chronic total occlusion (CTO PCI) is a challenging procedure with high complication rates and, as not yet fully understood long-term clinical benefits. Ischemic symptom relief in patients with high ischemic burden is to date the only established clinical indication to undergo CTO PCI, supported by randomized controlled trials. In this context, current guidelines suggest attempting CTO PCI only in non-invasively assessed viable CTO correspondent myocardial territories, with large ischemic areas. Hence, besides a comprehensive coronary angiography lesion evaluation, the information derived from non-invasive cardiac imaging techniques is crucial to selecting candidates who may benefit from the revascularization of the occluded vessel. Currently, there are no clear recommendations for a non-invasive myocardial evaluation or choice of imaging modality pre-CTO PCI. Therefore, selecting among available options is left to the physician’s discretion. As CTO PCI is strongly recommended to be carried out explicitly in experienced centers, full access to non-invasive imaging for risk-benefit assessment as well as a systematic institutional evaluation process has to be encouraged. In this framework, we opted to review the current myocardial imaging tools and their use for indicating a CTO PCI. Furthermore, based on our experience, we propose a cost-effective systematic approach for myocardial assessment to help guide clinical decision-making for patients presenting with chronic total occlusions.

Background: Despite tremendous therapeutic advancements, a significant proportion of coronary artery disease patients suffer from refractory angina pectoris, that is, quality-of-life-compromising angina that is non-manageable with established pharmacological and interventional treatment options. Adenoviral vascular endothelial growth factor-D^ΔNΔC (AdVEGF-D)-encoding gene therapy (GT) holds promise for the treatment of refractory angina. Methods: ReGenHeart is an investigator-initiated, multicentre, randomised, placebo-controlled and double-blinded phase 2 clinical trial that aims to study the safety and efficacy of intramyocardially administered angiogenic AdVEGF-D GT for refractory angina. Patients will be randomised in a 2:1 ratio and blocks of six to receive either AdVEGF-D or placebo. Primary endpoints are improvements in functional capacity assessed with the 6 min walking test and angina symptoms with Canadian Cardiovascular Society class after 6 month follow-up. Secondary endpoints are improvements in myocardial perfusion assessed with either positron emission tomography or single-photon emission CT after 6 month follow-up and functional capacity and angina symptoms after 12 months. In addition, changes in the quality of life, the use of angina medication and the incidence of major adverse cardiac and cerebrovascular events will be evaluated. Conclusions: The phase 2 ReGenHeart trial will provide knowledge of the safety and efficacy of AdVEGF-D GT to ameliorate symptoms in refractory angina patients, extending and further testing positive results from the preceding phase 1/2a trial.

Cardiac magnetic resonance (CMR) studies reported CMR abnormalities in patients with mild–moderate SARS-CoV-2 infection, suggesting ongoing myocardial inflammation. Patients (n = 278, 43 ± 13 years, 70.5% female) with post-acute sequelae of SARS-CoV-2 cardiovascular syndrome (PASC-CVS) were included prospectively into the Vienna POSTCOV Registry between March 2021 and March 2023 (clinicaltrials.gov NCT05398952). Clinical, laboratory, and CMR findings were recorded. Patients with abnormal CMR results were classified into isolated chronic pericardial (with/without pleural) effusion, isolated cardiac function impairment, or both (myopericarditis) groups. Medical treatment included a nonsteroidal anti-inflammatory agent (NSAID) for pericardial effusion and a condition-adapted maximal dose of heart failure (HF) treatment. Three months after medical therapy, clinical assessment and CMR were repeated in 82 patients. Laboratory analyses revealed normal hematological, inflammatory, coagulation, and cardiac biomarkers. CMR abnormalities were found in 155 patients (55.8%). Condition-adapted HF treatment led to a significant increase in the left ventricular ejection fraction (LVEF) in patients with initially reduced LVEF (from 49 ± 5% to 56 ± 4%, p = 0.009, n = 25). Low–moderate doses of NSAIDs for 3 months significantly reduced pericardial effusion (from 4/3;5.75/mm to 2/0;3/mm, median/interquartile ranges/p < 0.001, n = 51). Clinical symptoms improved markedly with a decrease in CMR abnormalities, which might be attributed to the maintenance of NSAID and HF medical treatment for PASC-CVS.

Endothelial dysfunction mediated by elevated levels of autoantibodies against vasoactive peptides occurring after COVID-19 infection is proposed as a possible pathomechanism for orthostatic intolerance in long COVID patients. This case-control study comprised 100 long COVID patients from our prospective POSTCOV registry and three control groups, each consisting of 20 individuals (Asymptomatic post-COVID group; Healthy group = pan-negative for antispike protein of SARS-CoV-2; Vaccinated healthy group = no history of COVID-19 and vaccinated). Autoantibodies towards muscarinic acetylcholine receptor M3, endothelin type A receptor (ETAR), beta-2 adrenergic receptor (Beta-2 AR), angiotensin II receptor 1 and angiotensin 1-7 (Ang1-7) concentrations were measured by enzyme-linked immunosorbent assay in long COVID patients and controls. Orthostatic intolerance was defined as inappropriate sinus tachycardia, postural tachycardia, orthostatic hypotonia and other dysautonomia symptoms, such as dizziness or blurred vision (n = 38 long COVID patients). Autoantibody concentrations were compared with routine laboratory parameters and quality of life questionnaires (EQ-5D). The concentration of ETAR autoantibodies were significantly higher in long COVID, Asymptomatic and Vaccinated groups compared to the antispike protein pan-negative Healthy group. A trend towards higher plasma levels of Beta-2 AR and Ang1-7 was measured in long COVID patients, not related to presence of orthostatic intolerance. ETAR autoantibody concentration showed significant positive correlation with the EQ-5D item “Problems in performing usual activities”.

Patients with long COVID syndrome present with various symptoms affecting multiple organs. Vaccination before or after SARS-CoV-2 infection appears to reduce the incidence of long COVID or at least limit symptom deterioration. However, the impact of vaccination on the severity and extent of multi-organ long COVID symptoms and the relationship between the circulating anti-spike protein antibody levels and the severity and extent of multi-organ symptoms are unclear. This prospective cohort study included 198 patients with previous PCR-verified SARS-CoV-2 infection who met the criteria for long COVID syndrome. Patients were divided into vaccinated (n = 138, 69.7%) or unvaccinated (n = 60, 30.3%) groups. Anti-spike protein antibody levels were determined at initial clinical presentation and compared between the groups. Long COVID symptoms were quantified on the basis of the number of affected organs: Class I (mild) with symptoms in three organs, Class II (moderate) with symptoms in four to five organs, and Class III (severe) with symptoms in six or more organ systems. Associations between time to infection and vaccination with anti-spike protein antibody levels were assessed. The anti-spike protein antibody levels were 1925 ± 938 vs. 481 ± 768 BAU/mL (p < 0.001) in the vaccinated vs. unvaccinated patients. The circulating anti-spike antibody cutoff of 665.5 BAU/mL allowed us to differentiate the vaccinated from the unvaccinated patients. Vaccinated patients had fewer class II and class III multi-organ symptoms (Class II 39.9% vs. 45.0%; Class III 10.1% vs. 23.3%, p-value 0.014). Anti-spike antibody level correlated negatively with multi-organ symptom classes (p = 0.016; 95% CI −1.229 to −0.126). Anti-spike antibody levels in unvaccinated patients declined markedly with time, in contrast to the persistence of high anti-spike antibody levels in the vaccinated patients. Multi-organ symptoms were lower in vaccinated long-COVID patients, especially in those with higher anti-spike antibody levels (≥665.5 BAU/mL). Classifying the symptoms on the basis of the number of affected organs enables a more objective symptom quantification.

Background: Transcatheter aortic valve replacement (TAVR) has evolved as first-line therapy for severe aortic valve stenosis (AS), with pre-procedural computed tomography (CT) providing critical anatomical information. While primarily used for anatomical planning, TAVR-CT also offers an opportunity to assess low bone mineral density (BMD), a known indicator of frailty. Despite this, the prognostic role of BMD in TAVR patients remains unknown. This study aimed to evaluate BMD on routine TAVR-CT and its impact on long-term survival. Methods: In this retrospective study, 770 consecutive TAVR patients (mean age 80.7 ± 6.7 years, 54.0% males) between November 2015 and March 2022 were included. BMD was measured from a single axial image at the thoracic vertebral level on unenhanced CT scans. Cox regression models assessed the impact of BMD on mortality, and Restricted Cubic Spline models identified potential mortality thresholds. Results: The mean BMD value, as measured on non-contrast CT, was 147.5 ± 5.4 Hounsfield units, demonstrating a noteworthy association with mortality (adjusted hazard ratio per 100 HU decrease: 1.27 [95%CI: 1.01–1.59], p = 0.041). Restricted cubic spline analysis indicated that BMD below 200 HU was linked to a substantial increase in mortality risk. Upon crude Cox regression analysis, every 100 HU decrease was associated with a 32% increase in risk for death (HR 1.32 [95%CI: 1.068–1.65)], p = 0.010). Conclusions: In conclusion, low BMD on TAVR-CT is independently associated with reduced survival, suggesting its potential as a tool for comprehensive frailty assessment and improved risk prediction in TAVR patients.