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BackgroundThe influence of atrial fibrillation (AF) and blood pressure (BP) on brain lesions and cognitive function is unclear. We aimed to investigate the association of BP with different types of brain lesions and cognitive decline in patients with AF.MethodsOverall, 1,213 AF patients underwent standardized brain magnetic resonance imaging at baseline and after 2 years, as well as yearly neurocognitive testing. BP was measured at baseline and categorized according to guidelines. New lesions were defined as new or enlarged brain lesions after 2 years. We defined cognitive decline using three different neurocognitive tests. Logistic and Cox regression analyses were performed to examine the associations of BP with new brain lesions and cognitive decline.ResultsThe mean age was 71 ± 8.4 years, 74% were male and mean BP was 135 ± 18/79 ± 12 mmHg. New ischemic lesions and white matter lesions were found in 5.4% and 18.4%, respectively. After multivariable adjustment, BP was not associated with the presence of new brain lesions after 2 years. There was no association between BP and cognitive decline over a median follow-up of 6 years when using the Montreal Cognitive Assessment or Digit Symbol Substitution Test. However, BP categories were inversely associated with cognitive decline using the Semantic Fluency Test, with the strongest association in patients with hypertension grade 1 [Hazard Ratio (95% Confidence Interval) 0.57(0.42 to 0.77)], compared to patients with optimal BP (p for linear trend: 0.025).ConclusionsIn a large cohort of AF patients, there was no association between BP and incidence of brain lesions after 2 years. Also, there was no consistent association between BP and cognitive decline over a follow-up of 6 years. Clinical Trial Registrationhttps://clinicaltrials.gov/study/NCT02105844, Identifier (NCT02105844).

Chronic total occlusions (CTOs) represent the most complex subset of coronary artery disease and therefore careful planning of CTO percutaneous coronary recanalization (PCI) strategy is of paramount importance aiming to achieve procedural success, and improve patient's safety and post CTO PCI outcomes. Intravascular imaging has an essential role in facilitating CTO PCΙ. First, intravascular ultrasound (IVUS), due to its higher penetration depth compared to optical coherence tomography (OCT), and the additional capacity of real-time imaging without need for contrast injection is considered the preferred imaging modality for CTO PCI. Secondly, IVUS can be used to resolve proximal cap ambiguity, facilitate wire re-entry when dissection and re-entry strategies are applied and most importantly to guide stent deployment and optimization post implantation. The role of OCT during CTO PCI is currently limited to stent sizing and optimization, however, due to its high spatial resolution, OCT is ideal for detecting stent edge dissections and strut malapposition. In this review, we describe the use of intravascular imaging for lesion crossing, plaque characterization and wire tracking, extra- or intra-plaque, and stent sizing and optimization during CTO PCI and summarize the findings of the major studies in this field.

BackgroundLongitudinal association studies of atrial fibrillation (AF) and cognitive functions have shown an unclear role of AF-type and often differ in methodological aspects. We therefore aim to investigate longitudinal changes in cognitive functions in association with AF-type (non-paroxysmal vs. paroxysmal) and comorbidities in the Swiss-AF cohort.MethodsSeven cognitive measures were administered up to five times between 2014 and 2022. Age-education standardized scores were calculated and association between longitudinal change in scores and baseline AF-type investigated using linear mixed-effects models. Associations between AF-type and time to cognitive drop, an observed score of at least one standard deviation below individual's age-education standardized cognitive scores at baseline, were studied using Cox proportional hazard models of each cognitive test, censoring patients at their last measurement. Models were adjusted for baseline covariates.Results2,415 AF patients (mean age 73.2 years; 1,080 paroxysmal, 1,335 non-paroxysmal AF) participated in this Swiss multicenter prospective cohort study. Mean cognitive scores increased longitudinally (median follow-up 3.97 years). Non-paroxysmal AF patients showed smaller longitudinal increases in Digit Symbol Substitution Test (DSST), Cognitive Construct Score (CoCo)and Trail Making Test part B (TMT-B) scores vs. paroxysmal AF patients. Diabetes, history of stroke/TIA and depression were associated with worse performance on all cognitive tests. No differences in time to cognitive drop were observed between AF-types in any cognitive test.ConclusionThis study indicated preserved cognitive functioning in AF patients, best explained by practice effects. Smaller practice effects were found in non-paroxysmal AF patients in the DSST, TMT-B and the CoCo and could indicate a marker of subtle cognitive decline. As diabetes, history of stroke/TIA and depression—but not AF-type—were associated with cognitive drop, more attention should be given to risk factors and underlying mechanisms of AF.

Inherited Arrhythmia Syndromes (IAS) including long QT and Brugada Syndrome, are characterized by life-threatening arrhythmias in the absence of apparent structural heart disease and are caused by pathogenic variants in genes encoding cardiac ion channels or associated proteins. Studies of large pedigrees of families affected by IAS have demonstrated incomplete penetrance and variable expressivity. Biological sex is one of several factors that have been recognized to modulate disease severity in IAS. There is a growing body of evidence linking sex hormones to the susceptibility to arrhythmias, yet, many sex-specific disease aspects remain underrecognized as female sex and women with IAS are underinvestigated and findings from male-predominant cohorts are often generalized to both sexes with minimal to no consideration of relevant sex-associated differences in prevalence, disease manifestations and outcome. In this review, we highlight current knowledge of sex-related biological differences in normal cardiac electrophysiology and sex-associated factors that influence IAS phenotypes.

Since the first groundbreaking procedure in 2002, transcatheter aortic valve implantation (TAVI) has revolutionized the management of aortic stenosis (AS). Through striking developments in pertinent equipment and techniques, TAVI has now become the leading therapeutic strategy for aortic valve replacement in patients with severe symptomatic AS. The procedure streamlining from routine use of conscious sedation to a single arterial access approach, the newly adapted implantation techniques, and the introduction of novel technologies such as intravascular lithotripsy and the refinement of valve-bioprosthesis devices along with the accumulating experience have resulted in a dramatic reduction of complications and have improved associated outcomes that are now considered comparable or even superior to surgical aortic valve replacement (SAVR). These advances have opened the road to the use of TAVI in younger and lower-risk patients and up-to-date data from landmark studies have now established the outstanding efficacy and safety of TAVI in patients with low-surgical risk impelling the most recent ESC guidelines to propose TAVI, as the main therapeutic strategy for patients with AS aged 75 years or older. In this article, we aim to summarize the most recent advances and the current clinical aspects involving the use of TAVI, and we also attempt to highlight impending concerns that need to be further addressed.

BackgroundRoutine coronary artery disease (CAD) secondary prevention strategies target standard modifiable cardiovascular risk factors (SMuRFs), which include: diabetes mellitus, dyslipidemia, hypertension, and smoking. However, a significant proportion of patients with acute coronary syndrome (ACS) present without any SMuRFs. The angiographic severity of disease in this population has not yet been investigated.MethodsAfter propensity score matching of patients without SMuRFs and patients with ≥1 SMuRFs (ratio 1:3), we used zero-inflated negative binomial regression modeling to investigate the relationship of SMuRF-less status with the angiographic severity of CAD, as measured by the SYNTAX score. Survival analysis was performed to investigate differences in all-cause mortality at 30 days and at the end of follow-up period.ResultsWe analyzed 534 patients presenting with ACS who underwent coronary angiography. Of them, 56 (10.5%) presented without any SMuRF. After propensity score matching, the median SYNTAX score was 13.8 (IQR 0–22.1) in 56 SMuRF-less patients and 14 (IQR 5–25) in 166 patients with ≥1 SMuRFs. SMuRF-less status was associated with increased odds of zero SYNTAX score [zero-part model: odds ratio = 2.11, 95% confidence interval (CI): 1.03–4.33], but not with decreased SYNTAX score among patients with non-zero SYNTAX score (count-part model: incidence rate ratio = 0.99, 95% CI: 0.79–1.24); the overall distribution of the SYNTAX score was similar between the two groups (p = 0.26). The 30-day risk for all-cause mortality was higher for SMuRF-less patients compared to patients with ≥1 SMuRFs [hazard ratio (HR) = 3.58, 95% CI: 1.30–9.88]; however, the all-cause mortality risk was not different between the two groups over a median 1.7-year follow-up (HR = 1.72, 95% CI: 0.83–3.57).ConclusionAmong patients with ACS, the absence of SMuRFs is associated with increased odds for non-obstructive CAD and with increased short-term mortality rates.

BackgroundThe relationship between inflammation and corrected QT (QTc) interval prolongation is currently not well defined in patients with COVID-19.ObjectiveThis study aimed to assess the effect of marked interval changes in the inflammatory marker C-reactive protein (CRP) on QTc interval in patients hospitalized with COVID-19.MethodsIn this retrospective cohort study of hospitalized adult patients admitted with COVID-19 infection, we identified 85 patients who had markedly elevated CRP levels and serial measurements of an ECG and CRP during the same admission. We compared mean QTc interval duration, and other clinical and ECG characteristics between times when CRP values were high and low. We performed mixed-effects linear regression analysis to identify associations between CRP levels and QTc interval in univariable and adjusted models.ResultsMean age was 58 ± 16 years, of which 39% were women, 41% were Black, and 25% were White. On average, the QTc interval calculated via the Bazett formula was 15 ms higher when the CRP values were “high” vs. “low” [447 ms (IQR 427–472 ms) and 432 ms (IQR 412–452 ms), respectively]. A 100 mg/L increase in CRP was associated with a 1.5 ms increase in QTc interval [β coefficient 0.15, 95% CI (0.06–0.24). In a fully adjusted model for sociodemographic, ECG, and clinical factors, the association remained significant (β coefficient 0.14, 95% CI 0.05–0.23).ConclusionAn interval QTc interval prolongation is observed with a marked elevation in CRP levels in patients with COVID-19.

Our study aims to develop a data-driven framework utilizing heterogenous electronic medical and clinical records and advanced Machine Learning (ML) approaches for: (i) the identification of critical risk factors affecting the complexity of Coronary Artery Disease (CAD), as assessed via the SYNTAX score; and (ii) the development of ML prediction models for accurate estimation of the expected SYNTAX score. We propose a two-part modeling technique separating the process into two distinct phases: (a) a binary classification task for predicting, whether a patient is more likely to present with a non-zero SYNTAX score; and (b) a regression task to predict the expected SYNTAX score accountable to individual patients with a non-zero SYNTAX score. The framework is based on data collected from the GESS trial (NCT03150680) comprising electronic medical and clinical records for 303 adult patients with suspected CAD, having undergone invasive coronary angiography in AHEPA University Hospital of Thessaloniki, Greece. The deployment of the proposed approach demonstrated that atherogenic index of plasma levels, diabetes mellitus and hypertension can be considered as important risk factors for discriminating patients into zero- and non-zero SYNTAX score groups, whereas diastolic and systolic arterial blood pressure, peripheral vascular disease and body mass index can be considered as significant risk factors for providing an accurate estimation of the expected SYNTAX score, given that a patient belongs to the non-zero SYNTAX score group. The experimental findings utilizing the identified set of important risk factors indicate a sufficient prediction performance for the Support Vector Machine model (classification task) with an F-measure score of ~0.71 and the Support Vector Regression model (regression task) with a median absolute error value of ~6.5. The proposed data-driven framework described herein present evidence of the prediction capacity and the potential clinical usefulness of the developed risk-stratification models. However, further experimentation in a larger clinical setting is needed to ensure the practical utility of the presented models in a way to contribute to a more personalized management and counseling of CAD patients.

Both aortic aneurysm and dissection are life threatening pathologies. In the lack of a conservative medical treatment, the only therapy consists of modifying cardiovascular risk factors and either surgical or endovascular treatment. Like many other cardiovascular diseases, in particular atherosclerosis, aortic aneurysm and dissection have a strong inflammatory phenotype. Inflammasomes are part of the innate immune system. Upon stimulation they form multi protein complexes resulting mainly in activation of interleukin-1β and other cytokines. Considering the gathering evidence, that inflammasomes are decisively involved in the emergence and progression of aortic diseases, inflammasome targeted therapy provides a promising new treatment approach. A systematic review following the PRISMA guidelines on the current preclinical data regarding the potential role of inflammasome targeted drug therapy as novel treatment option for aortic aneurysms and dissections was performed. Included were all rodent models of aortic disease (aortic aneurysm and dissection) evaluating a drug therapy with direct or indirect inhibition of inflammasomes and a suitable control group with the use of the same aortic model without the inflammasome targeted therapy. Primary and secondary outcomes were incidence of aortic disease, aortic rupture, aortic related death, and the maximum aortic diameter. The literature search of MEDLINE (via PubMed), the Web of Science, EMBASE and the Cochrane Central Registry of Registered Trials (CENTRAL) resulted in 8,137 hits. Of these, four studies met the inclusion criteria and were therefore eligible for data analysis. In all of them, targeting of the NOD-, LRR- and pyrin domain-containing protein 3 (NLRP3) inflammasome effectively reduced the incidence of aortic disease and aortic rupture, and additionally reduced destruction of the aortic wall. Treatment strategies aiming at other inflammasomes could not be identified. In conclusion, inflammasome targeted therapies, more precisely targeting the NLRP3 inflammasome, have shown promising results in rodent models and deserve further investigation in preclinical research to potentially translate them into clinical research for the treatment of human patients with aortic disease. Regarding other inflammasomes, more preclinical research is needed to investigate their role in the pathophysiology of aortic disease.Protocol Registration: PROSPERO 2021 CRD42021279893, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021279893

Background: Angiographic detection of thrombus in STEMI is associated with adverse outcomes. However, routine thrombus aspiration failed to demonstrate the anticipated benefit. Hence, management of high coronary thrombus burden remains challenging. We sought to assess for the first time extracted thrombotic material characteristics utilizing micro-computed tomography (micro-CT).Methods: One hundred thirteen STEMI patients undergoing thrombus aspiration were enrolled. Micro-CT was undertaken to quantify retrieved thrombus volume, surface, and density. Correlation of these indices with angiographic and electrocardiographic outcomes was performed.Results: Mean aspirated thrombus volume, surface, and density (±standard deviation) were 15.71 ± 20.10 mm3, 302.89 ± 692.54 mm2, and 3139.04 ± 901.88 Hounsfield units, respectively. Aspirated volume and surface were significantly higher (p < 0.001) in patients with higher angiographic thrombus burden. After multivariable analysis, independent predictors for thrombus volume were reference vessel diameter (RVD) (p = 0.011), right coronary artery (RCA) (p = 0.039), and smoking (p = 0.027), whereas RVD (p = 0.018) and RCA (p = 0.019) were predictive for thrombus surface. Thrombus volume and surface were independently associated with distal embolization (p = 0.007 and p = 0.028, respectively), no-reflow phenomenon (p = 0.002 and p = 0.006, respectively), and angiographically evident residual thrombus (p = 0.007 and p = 0.002, respectively). Higher thrombus density was correlated with worse pre-procedural TIMI flow (p < 0.001). Patients with higher aspirated volume and surface developed less ST resolution (p = 0.042 and p = 0.023, respectively).Conclusions: Angiographic outcomes linked with worse prognosis were more frequent among patients with larger extracted thrombus. Despite retrieving larger thrombus load in these patients, current thrombectomy devices fail to deal with thrombotic material adequately. Further studies of novel thrombus aspiration technologies are warranted to improve patient outcomes.Clinical Trial Registration: QUEST-STEMI trial ClinicalTrials.gov number: NCT03429608 Date of registration: February 12, 2018. The study was prospectively registered.

IntroductionThe aim of this study was to analyze age-associated myocardial injury and clinical outcome after non-ST-elevation myocardial infarction (NSTEMI).MethodsThis prospective, multicenter study consists of 440 patients with NSTEMI enrolled at 7 centers. All patients were treated with primary percutaneous coronary intervention and underwent cardiac magnetic resonance (CMR) imaging 1–10 days after study inclusion. CMR parameters of myocardial injury and clinical outcome were evaluated by creating 2 subgroups:

BackgroundDeep sternal wound infection (DSWI) remains a serious complication after coronary artery bypass grafting (CABG). We herein aimed to stratify diabetic patients who underwent CABG using bilateral internal mammary artery (BIMA) for levels of glycated hemoglobin A1C (HbA1c) and compare postoperative outcomes.MethodsBetween January 2010 and August 2020, 4,186 consecutive patients underwent isolated CABG at our center. In 3,229 patients, preoperative HbA1c levels were available. Primary endpoints were wound healing disorder (WHD), DSWI, and 30-day mortality. Patients were stratified according to preoperative HbA1c levels. Patients were further divided into subgroups according to utilization of BIMA.ResultsAfter adjustment, no differences in mortality and stroke rates were seen between group 1 (HbA1c

Critical care cardiology (CCC) in the modern era is shaped by a multitude of innovative treatment options and an increasingly complex, ageing patient population. Generating high-quality evidence for novel interventions and devices in an intensive care setting is exceptionally challenging. As a result, formulating the best possible therapeutic approach continues to rely predominantly on expert opinion and local standard operating procedures. Fostering the full potential of CCC and the maturation of the next generation of decision-makers in this field calls for an updated training concept, that encompasses the extensive knowledge and skills required to care for critically ill cardiac patients while remaining adaptable to the trainee’s individual career planning and existing educational programs. In the present manuscript, we suggest a standardized training phase in preparation of the first ICU rotation, propose a modular CCC core curriculum, and outline how training components could be conceptualized within three sub-specialization tracks for aspiring cardiac intensivists.

Ex vivo machine perfusion (EVMP) is an emerging technique for preserving explanted solid organs with primary application in allogeneic organ transplantation. EVMP has been established as an alternative to the standard of care static-cold preservation, allowing for prolonged preservation and real-time monitoring of organ quality while reducing/preventing ischemia–reperfusion injury. Moreover, it has paved the way to involve expanded criteria donors, e.g., after circulatory death, thus expanding the donor organ pool. Ongoing improvements in EVMP protocols, especially expanding the duration of preservation, paved the way for its broader application, in particular for reconditioning and modification of diseased organs and tumor and infection therapies and regenerative approaches. Moreover, implementing EVMP for in vivo-like preclinical studies improving disease modeling raises significant interest, while providing an ideal interface for bioengineering and genetic manipulation. These approaches can be applied not only in an allogeneic and xenogeneic transplant setting but also in an autologous setting, where patients can be on temporary organ support while the diseased organs are treated ex vivo, followed by reimplantation of the cured organ. This review provides a comprehensive overview of the differences and similarities in abdominal (kidney and liver) and thoracic (lung and heart) EVMP, focusing on the organ-specific components and preservation techniques, specifically on the composition of perfusion solutions and their supplements and perfusion temperatures and flow conditions. Novel treatment opportunities beyond organ transplantation and limitations of abdominal and thoracic EVMP are delineated to identify complementary interdisciplinary approaches for the application and development of this technique.

BackgroundValve-in-valve (ViV) transfemoral transcatheter aortic valve implantation (TAVI) for failing aortic surgical bioprostheses or transcatheter heart valves (THV) has demonstrated a reasonable clinical and hemodynamic efficacy. Traditionally, self-expanding (SE) supra-annular THV are considered to result in superior hemodynamics compared with balloon-expandable intra-annular THV after ViV. However, so far no data are found on latest-generation intra-annular SE THV for aortic ViV procedures which might be superior with regard to coronary access or subsequent valve reintervention.AimWe herein aim to evaluate a latest-generation SE intra-annular THV for aortic ViV procedures.Materials and methodsBetween May 2022 and November 2022, five consecutive patients (4/5 female with mean age of 76.2 years and mean Society of Thoracic Surgeons predicted risk of mortality score of 2.9%) received ViV TAVI using the Navitor system (Abbott, Chicago, IL, USA) for treatment of failing surgical bioprostheses or THV. Data were retrospectively analyzed according to updated Valve Academic Research Consortium 3 (VARC-3) definitions.ResultsAt 30 days, absence of mortality and VARC-3 adjudicated clinical endpoints were documented. Echocardiography at 30 days revealed complete absence of paravalvular leakage and single-digit mean transvalvular gradients (mean of 6.0 mmHg) in all patients.ConclusionThe investigated intra-annular SE THV results in excellent 30-day outcomes for aortic ViV procedures for failing surgical bioprostheses or THV. Despite the intra-annular design, hemodynamic results were excellent, even in small bioprostheses. Ease of use of this valve platform is reflected by only two cycles of resheathing in five ViV procedures with hemodynamic stability during all steps of valve deployment.

BackgroundStrain analyses derived from cardiovascular magnetic resonance-feature tracking (CMR-FT) provide incremental prognostic benefit in patients sufferring from acute myocardial infarction (AMI). This study aims to evaluate and revalidate previously reported prognostic implications of comprehensive strain analyses in a large independent cohort of patients with ST-elevation myocardial infarction (STEMI).MethodsOverall, 566 STEMI patients enrolled in the CONDITIONING-LIPSIA trial including pre- and/or postconditioning treatment in addition to conventional percutaneous coronary intervention underwent CMR imaging in median 3 days after primary percutaneous coronary intervention. CMR-based left atrial (LA) reservoir (Es), conduit (Ee), and boosterpump (Ea) strain analyses, as well as left ventricular (LV) global longitudinal strain (GLS), circumferential strain (GCS), and radial strain (GRS) analyses were carried out. Previously identified cutoff values were revalidated for risk stratification. Major adverse cardiac events (MACE) comprising death, reinfarction, and new congestive heart failure were assessed within 12 months after the occurrence of the index event.ResultsBoth atrial and ventricular strain values were significantly reduced in patients with MACE (p

IntroductionComplicated carotid artery plaques (cCAPs) are associated with an increased risk of rupture and subsequent stroke. The geometry of the carotid bifurcation determines the distribution of local hemodynamics and could thus contribute to the development and composition of these plaques. Therefore, we studied the role of carotid bifurcation geometry in the presence of cCAPs.MethodsWe investigated the association of individual vessel geometry with carotid artery plaque types in the Carotid Plaque Imaging in Acute Stroke (CAPIAS) study. After excluding arteries without plaque or with insufficient MRI quality, 354 carotid arteries from 182 patients were analyzed. Individual parameters of carotid geometry [i.e., internal carotid artery (ICA)/common carotid artery (CCA) ratio, bifurcation angle, and tortuosity) were derived from time-of-flight MR images. The lesion types of carotid artery plaques were determined according to the American Heart Association classification of lesions by multi-contrast 3T-MRI. The association between carotid geometry and a cCAP was studied using logistic regression after adjusting for age, sex, wall area, and cardiovascular risk factors.ResultsLow ICA/CCA ratios (OR per SD increase 0.60 [95%CI: 0.42–0.85]; p = 0.004) and low bifurcation angles (OR 0.61 [95%CI: 0.42–0.90]; p = 0.012) were significantly associated with the presence of cCAPs after adjusting for age, sex, cardiovascular risk factors, and wall area. Tortuosity had no significant association with cCAPs. Only ICA/CCA ratio remained significant in a model containing all three geometric parameters (OR per SD increase 0.65 [95%CI: 0.45–0.94]; p = 0.023).ConclusionsA steep tapering of the ICA relative to the CCA and, to a lesser extent, a low angle of the carotid bifurcation were associated with the presence of cCAPs. Our findings highlight the contribution of bifurcation geometry to plaque vulnerability. Thus, assessment of carotid geometry could be helpful in identifying patients at risk of cCAPs.

IntroductionDiazoxide is a powerful cardioprotective agent that activates mitochondrial ATP-dependent K-channels and stimulates mitochondrial respiration. Diazoxide reduced infarct size in isolated rodent heart preparations and upon pretreatment in juvenile pigs with coronary occlusion/reperfusion. We aimed to study the use of diazoxide in a more realistic adult pig model of reperfused acute myocardial infarction when diazoxide was administered just before reperfusion.Methods and resultsIn a first approach, we pretreated anaesthetised adult Göttingen minipigs with 7 mg kg−1 diazoxide (n = 5) or placebo (n = 5) intravenously over 10 min and subjected them to 60 min coronary occlusion and 180 min reperfusion; blood pressure was maintained by use of an aortic snare. The primary endpoint was infarct size (triphenyl tetrazolium chloride staining) as a fraction of area at risk; no-reflow area (thioflavin-S staining) was the secondary endpoint. In a second approach, diazoxide (n = 5) was given from 50 to 60 min coronary occlusion, and blood pressure was not maintained. There was a significant reduction in infarct size (22% ± 11% of area at risk with diazoxide pretreatment vs. 47% ± 11% with placebo) and area of no-reflow (14% ± 14% of infarct size with diazoxide pretreatment vs. 46% ± 20% with placebo). With diazoxide from 50 to 60 min coronary occlusion, however, there was marked hypotension, and infarct size (44% ± 7%) and area of no-reflow were not reduced (35% ± 25%).ConclusionsCardioprotection by diazoxide pretreatment was confirmed in adult pigs with reperfused acute myocardial infarction but is not feasible when diazoxide is administered in a more realistic scenario before reperfusion and causes hypotension.

BackgroundCoronary artery spasm (CAS), encompassing epicardial and microvascular spasm, is increasingly recognized as cause of angina in patients with non-obstructive coronary artery disease (ANOCA). However, various spasm provocation testing protocols and diagnostic criteria are used, making diagnosis and characterization of these patients difficult and interpretation of study results cumbersome. This review provides a structured overview of the prevalence, characterization and prognosis of CAS worldwide in men and women.MethodsA systematic review identifying studies describing ANOCA patients with CAS was performed. Multiple outcomes (prevalence, clinical features, and prognosis) were assessed. Data, except for prognosis were pooled and analysed using random effects meta-analysis models.ResultsTwenty-five publications (N = 14.554) were included (58.2 years; 44.2% women). Percentages of epicardial constriction to define epicardial spasm ranged from >50% to >90%. Epicardial spasm was prevalent in 43% (range 16–73%), with a higher prevalence in Asian vs. Western World population (52% vs. 33%, p = 0.014). Microvascular spasm was prevalent in 25% (range 7–39%). Men were more likely to have epicardial spasm (61%), women were more likely to have microvascular spasm (64%). Recurrent angina is frequently reported during follow-up ranging from 10 to 53%.ConclusionCAS is highly prevalent in ANOCA patients, where men more often have epicardial spasm, women more often have microvascular spasm. A higher prevalence of epicardial spasm is demonstrated in the Asian population compared to the Western World. The prevalence of CAS is high, emphasizing the use of unambiguous study protocols and diagnostic criteria and highlights the importance of routine evaluation of CAS in men and women with ANOCA.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=272100.

Cardiac anatomy and function vary considerably across the human population with important implications for clinical diagnosis and treatment planning. Consequently, many computer-based approaches have been developed to capture this variability for a wide range of applications, including explainable cardiac disease detection and prediction, dimensionality reduction, cardiac shape analysis, and the generation of virtual heart populations. In this work, we propose a variational mesh autoencoder (mesh VAE) as a novel geometric deep learning approach to model such population-wide variations in cardiac shapes. It embeds multi-scale graph convolutions and mesh pooling layers in a hierarchical VAE framework to enable direct processing of surface mesh representations of the cardiac anatomy in an efficient manner. The proposed mesh VAE achieves low reconstruction errors on a dataset of 3D cardiac meshes from over 1,000 patients with acute myocardial infarction, with mean surface distances between input and reconstructed meshes below the underlying image resolution. We also find that it outperforms a voxelgrid-based deep learning benchmark in terms of both mean surface distance and Hausdorff distance while requiring considerably less memory. Furthermore, we explore the quality and interpretability of the mesh VAE's latent space and showcase its ability to improve the prediction of major adverse cardiac events over a clinical benchmark. Finally, we investigate the method's ability to generate realistic virtual populations of cardiac anatomies and find good alignment between the synthesized and gold standard mesh populations in terms of multiple clinical metrics.

BackgroundImproved understanding of the mechanisms that sustain persistent and long-standing persistent atrial fibrillation (LSpAF) is essential for providing better ablation solutions. The findings of traditional catheter-based electrophysiological studies can be impacted by the sedation required for these procedures. This is not required in non-invasive body-surface mapping (ECGI). ECGI allows for multiple mappings in the same patient at different times. This would expose potential electrophysiological changes over time, such as the location and stability of extra-pulmonary vein drivers and activation patterns in sustained AF.Materials and methodsIn this electrophysiological study, 10 open-heart surgery candidates with LSpAF, without previous ablation procedures (6 male, median age 73 years), were mapped on two occasions with a median interval of 11 days (IQR: 8–19) between mappings. Bi-atrial epicardial activation sequences were acquired using ECGI (CardioInsight™, Minneapolis, MN, United States).ResultsBi-atrial electrophysiological abnormalities were documented in all 20 mappings. Interestingly, the anatomic location of focal and rotor activities changed between the mappings in all patients [100% showed changes, 95%CI (69.2–100%), p < 0.001]. Neither AF driver type nor their number varied significantly between the mappings in any patient (median total number of focal activities 8 (IQR: 1–16) versus 6 (IQR: 2–12), p = 0.68; median total number of rotor activities 48 (IQR: 44–67) versus 55 (IQR: 44–61), p = 0.30). However, individual zones showed a high number of quantitative changes (increase/decrease) of driver activity. Most changes of focal activity were found in the left atrial appendage, the region of the left lower pulmonary vein and the right atrial appendage. Most changes in rotor activity were found also at the left lower pulmonary vein region, the upper half of the right atrium and the right atrial appendage.ConclusionThis clinical study documented that driver location and activation patterns in patients with LSpAF changes constantly. Furthermore, bi-atrial pathophysiology was demonstrated, which underscores the importance of treating both atria in LSpAF and the significant role that arrhythmogenic drivers outside the pulmonary veins seem to have in maintaining this complex arrhythmia.

BackgroundThe risk of myocarditis after mRNA vaccination against COVID-19 has emerged recently. Current evidence suggests that young male patients are predominantly affected. In the majority of the cases, only mild symptoms were observed. However, little is known about cardiac magnetic resonance (CMR) imaging patterns in mRNA-related myocarditis and their differences when compared to classical viral myocarditis in the acute phase of inflammation.Methods and resultsIn total, 10 mRNA vaccination-associated patients with myocarditis were retrospectively enrolled in this study and compared to 10 patients suffering from viral myocarditis, who were matched for age, sex, comorbidities, and laboratory markers. All patients (n = 20) were hospitalized and underwent a standardized clinical examination, as well as an echocardiography and a CMR. Both, clinical and imaging findings and, in particular, functional and volumetric CMR assessments, as well as detailed tissue characterization using late gadolinium enhancement and T1 + T2-weighted sequences, were compared between both groups. The median age of the overall cohort was 26 years (group 1: 25.5; group 2: 27.5; p = 0.57). All patients described chest pain as the leading reason for their initial presentation. CMR volumetric and functional parameters did not differ significantly between both groups. In all cases, the lateral left ventricular wall showed late gadolinium enhancement without significant differences in terms of the localization or in-depth tissue characterization (late gadolinium enhancement [LGE] enlargement: group 1: 5.4%; group 2: 6.5%; p = 0.14; T2 global/maximum value: group 1: 38.9/52 ms; group 2: 37.8/54.5 ms; p = 0.79 and p = 0.80).ConclusionThis study yielded the first evidence that COVID-19 mRNA vaccine-associated myocarditis does not show specific CMR patterns during the very acute stage in the most affected patient group of young male patients. The observed imaging markers were closely related to regular viral myocarditis in our cohort. Additionally, we could not find any markers implying adverse outcomes in this relatively little number of patients; however, this has to be confirmed by future studies that will include larger sample sizes.

BackgroundCardiogenic shock (CS) alters whole body metabolism and circulating biomarkers serve as prognostic markers in CS patients. Percutaneous ventricular assist devices (pVADs) unload the left ventricle by actively ejecting blood into the aorta. The goal of the present study was to identify alterations in circulating metabolites and transcripts in a large animal model that might serve as potential prognostic biomarkers in acute CS and additional left ventricular unloading by Impella ® pVAD support.MethodsCS was induced in a preclinical large animal model by injecting microspheres into the left coronary artery system in six pigs. After the induction of CS, mechanical pVAD support was implemented for 30 min total. Serum samples were collected under basal conditions, after the onset of CS, and following additional pVAD unloading. Circulating metabolites were determined by metabolomic analysis, circulating RNA entities by RNA sequencing.ResultsCS and additional pVAD support alter the abundance of circulating metabolites involved in Aminoacyl-tRNA biosynthesis and amino acid metabolism. RNA sequencing revealed decreased abundance of the hypoxia sensitive miRNA-200b following the induction of CS, which was reversed following pVAD support.ConclusionThe hypoxamir miRNA-200b is a potential circulating marker that is repressed in CS and is restored following pVAD support. The early transcriptional response with increased miRNA-200b expression following only 30 min of pVAD support suggests that mechanical unloading alters whole body metabolism. Future studies are required to delineate the impact of serum miRNA-200b levels as a prognostic marker in patients with acute CS and pVAD unloading.

BackgroundPatients after out-of-hospital cardiac arrest (OHCA) are at increased risk for mortality and poor neurological outcome. We assessed the additive impact of interleukin 6 (IL-6) at admission to neuron-specific enolase (NSE) at day 3 for prognosis of 30-day mortality and long-term neurological outcome in OHCA patients.MethodsA total of 217 patients from the HAnnover COoling REgistry with return of spontaneous circulation (ROSC) after OHCA and IL-6 measurement immediately after admission during 2017–2020 were included to investigate the prognostic value and importance of IL-6 in addition to NSE obtained on day 3. Poor neurological outcome was defined by cerebral performance category (CPC) ≥ 3 after 6 months.ResultsPatients with poor outcome showed higher IL-6 values (30-day mortality: 2,224 ± 524 ng/l vs 186 ± 15 ng/l, p < 0.001; CPC ≥ 3 at 6 months: 1,440 ± 331 ng/l vs 180 ± 24 ng/l, p < 0.001). IL-6 was an independent predictor of mortality (HR = 1.013/ng/l; 95% CI 1.007–1.019; p < 0.001) and poor neurological outcome (HR = 1.004/ng/l; 95% CI 1.001–1.007; p = 0.036). In ROC-analysis, AUC for IL-6 was 0.98 (95% CI 0.96–0.99) for mortality, but only 0.76 (95% CI 0.68–0.84) for poor neurological outcome. The determined cut-off value for IL-6 was 431 ng/l for mortality (NPV 89.2%). In patients with IL-6 > 431 ng/l, the combination with NSE < 46 μg/l optimally identified those individuals with potential for good neurological outcome (CPC ≤ 2).ConclusionElevated IL-6 levels at admission after ROSC were closely associated with 30-day mortality. The combination of IL-6 and NSE provided clinically important additive information for predict poor neurological outcome at 6 months.

BackgroundMortality after out-of-hospital cardiac arrest (OHCA) with return of spontaneous circulation (ROSC) remains high despite numerous efforts to improve outcome. For patients with suspected coronary cause of arrest, coronary angiography is crucial. However, there are other causes and potentially life-threatening injuries related to cardiopulmonary resuscitation (CPR), which can be detected by routine computed tomography (CT).Materials and MethodsAt Hannover Medical School, rapid coronary angiography and CT are performed in successfully resuscitated OHCA patients as a standard of care prior to admission to intensive care. We analyzed all patients who received CT following OHCA with ROSC over a three-year period.ResultsThere were 225 consecutive patients with return of spontaneous circulation following out-of-hospital cardiac arrest. Mean age was 64 ± 13 years, 75% were male. Of them, 174 (77%) had witnessed arrest, 145 (64%) received bystander CPR, and 123 (55%) had a primary shockable rhythm. Mean time to ROSC was 24 ± 20 min. There were no significant differences in CT pathologies in patients with or without ST-segment elevations in the initial ECG. Critical CT findings qualifying as a potential cause for cardiac arrest were intracranial bleeding (N = 6), aortic dissection (N = 5), pulmonary embolism (N = 17), pericardial tamponade (N = 3), and tension pneumothorax (N = 11). Other pathologies were regarded as consequences of CPR and relevant for further treatment: aspiration (N = 62), rib fractures (N = 161), sternal fractures (N = 50), spinal fractures (N = 11), hepatic bleeding (N = 12), and intra-abdominal air (N = 3).ConclusionEarly CT fallowing OHCA uncovers a high number of causes and consequences of OHCA and CPR. Those are relevant for post-arrest care and are frequently life-threatening, suggesting that CT can contribute to improving prognosis following OHCA.

BackgroundIncreased cortisol exposure is a risk factor for coronary artery disease (CAD). It is not clear to what degree this risk is independent from the standard modifiable risk factors (SMuRFs) dyslipidemia, hypertension, and diabetes.AimTo use path analysis to test the direct and indirect association, mediated by SMuRFs, between long-term cortisol levels measured in hair cortisol concentration (HCC) and CAD.MethodsHair was sampled from patients admitted with acute myocardial infarction (n = 203) and a population-based sample without a diagnosis or symptoms of CAD (n = 3,134). The HCC was analyzed using radioimmunoassay and all the participants reported whether they were diagnosed with or treated for diabetes, hypertension, and hyperlipidemia. Path analysis was used to test to what degree the association between logarithmized (ln) HCC and CAD was direct or indirect, mediated by SMuRFs.ResultsParticipants with CAD had elevated HCC compared to those without elevated HCC [median interquartile range (IQR): 75.2 (167.1) vs. 23.6 (35.0) pg/mg, p < 0.0001]. Higher HCC was associated with diabetes, hypertension, and hyperlipidemia, which, in turn, were associated with CAD. In path models, 80% of the association between ln(HCC) and CAD were mediated by SMuRFs, while the direct path between ln(HCC) and CAD was not statistically significant.ConclusionThe SMuRFs diabetes, hyperlipidemia, and hypertension mediate the association between ln(HCC) and CAD. Some association between ln(HCC) and CAD did not operate via the SMuRFs considered and might have a pathway through atherosclerosis or inflammation.

Objectives: Transcatheter aortic valve implantation (TAVI) is routinely performed in patients with severe aortic stenosis (AS). For patients with pure non-calcified aortic regurgitation (AR) who are not suitable for open heart surgery no clear recommendations exist and use of TAVI has been largely off-label. We herein report a series of patients treated with the self-expandable AcurateNeo and Neo2 (Boston Scientific Co., Marlborough, MS, USA) transcatheter heart valve (THV) for pure AR.Methods: Between 05/2017 and 03/2021, 9 patients (88.8% female, 74.4 ± 7.1 years, logEuroSCORE II 5.5 ± 3.6%, STS PROM 6.2 ± 3.0%) received transfemoral (TF) TAVI for pure non-calcified AR following an adjusted valve sizing algorithm. Data were retrospectively analyzed according to updated Valve Academic Research Consortium (VARC-2) definitions.Results: Device success was 100%. Early safety was 77.7% (7/10), due to two (22.2%) cases of acute kidney injury. Thirty-day mortality was 0%, in seven (77.7%) patients no or trace paravalvular leakage (PVL) was seen and mild PVL in two (22.2%) patients at 30-day follow-up. No permanent pacemaker (PPM) was required during 30-day follow-up.Conclusion: In this series of selected patients using the Acurate neo THV for pure non-calcified AR, safety and efficacy were demonstrated. Thirty-day mortality as well as PPM implantation and PVL rates showed excellent results in this high-risk patient cohort. These results will have to be confirmed in larger patient cohorts.

Background: Acute myocardial damage is common in severe COVID-19. Post-mortem studies have implicated microvascular thrombosis, with cardiovascular magnetic resonance (CMR) demonstrating a high prevalence of myocardial infarction and myocarditis-like scar. The microcirculatory sequelae are incompletely characterized. Perfusion CMR can quantify the stress myocardial blood flow (MBF) and identify its association with infarction and myocarditis.Objectives: To determine the impact of the severe hospitalized COVID-19 on global and regional myocardial perfusion in recovered patients.Methods: A case-control study of previously hospitalized, troponin-positive COVID-19 patients was undertaken. The results were compared with a propensity-matched, pre-COVID chest pain cohort (referred for clinical CMR; angiography subsequently demonstrating unobstructed coronary arteries) and 27 healthy volunteers (HV). The analysis used visual assessment for the regional perfusion defects and AI-based segmentation to derive the global and regional stress and rest MBF.Results: Ninety recovered post-COVID patients {median age 64 [interquartile range (IQR) 54–71] years, 83% male, 44% requiring the intensive care unit (ICU)} underwent adenosine-stress perfusion CMR at a median of 61 (IQR 29–146) days post-discharge. The mean left ventricular ejection fraction (LVEF) was 67 ± 10%; 10 (11%) with impaired LVEF. Fifty patients (56%) had late gadolinium enhancement (LGE); 15 (17%) had infarct-pattern, 31 (34%) had non-ischemic, and 4 (4.4%) had mixed pattern LGE. Thirty-two patients (36%) had adenosine-induced regional perfusion defects, 26 out of 32 with at least one segment without prior infarction. The global stress MBF in post-COVID patients was similar to the age-, sex- and co-morbidities of the matched controls (2.53 ± 0.77 vs. 2.52 ± 0.79 ml/g/min, p = 0.10), though lower than HV (3.00 ± 0.76 ml/g/min, p< 0.01).Conclusions: After severe hospitalized COVID-19 infection, patients who attended clinical ischemia testing had little evidence of significant microvascular disease at 2 months post-discharge. The high prevalence of regional inducible ischemia and/or infarction (nearly 40%) may suggest that occult coronary disease is an important putative mechanism for troponin elevation in this cohort. This should be considered hypothesis-generating for future studies which combine ischemia and anatomical assessment.

Coronary artery bypass graft (CABG) surgery effectively relieves symptoms and improves outcomes. However, patients undergoing CABG surgery typically have advanced coronary atherosclerotic disease and remain at high risk for symptom recurrence and adverse events. Functional non-invasive testing for ischaemia is commonly used as a gatekeeper for invasive coronary and graft angiography, and for guiding subsequent revascularisation decisions. However, performing and interpreting non-invasive ischaemia testing in patients post CABG is challenging, irrespective of the imaging modality used. Multiple factors including advanced multi-vessel native vessel disease, variability in coronary hemodynamics post-surgery, differences in graft lengths and vasomotor properties, and complex myocardial scar morphology are only some of the pathophysiological mechanisms that complicate ischaemia evaluation in this patient population. Systematic assessment of the impact of these challenges in relation to each imaging modality may help optimize diagnostic test selection by incorporating clinical information and individual patient characteristics. At the same time, recent technological advances in cardiac imaging including improvements in image quality, wider availability of quantitative techniques for measuring myocardial blood flow and the introduction of artificial intelligence-based approaches for image analysis offer the opportunity to re-evaluate the value of ischaemia testing, providing new insights into the pathophysiological processes that determine outcomes in this patient population.

Aims: Unclear neurological outcome often precludes severely compromised patients after out-of-hospital cardiac arrest (OHCA) from mechanical circulatory support (MCS), while it may be considered as rescue therapy for patients with refractory cardiogenic shock (rCS) in the absence of OHCA. This analysis sought to investigate the role of left ventricular (LV) unloading in patients with rCS related to acute myocardial infarction (AMI) after OHCA.Methods: Of 273 consecutive patients receiving microaxial pumps in the Hannover Cardiac Unloading Registry between January 2013 and August 2018, 47 presented with AMI–rCS following successful resuscitation. Subsequently, the patients were compared by propensity score matching to patients with OHCA AMI–rCS without MCS. The patient data for OHCA without LV unloading was available from 280 patients of the Hannover Cooling Registry for the same time period. Furthermore, the patients with OHCA without rCS were compared to the patients with OHCA AMI–rCS and LV unloading.Results: In total, 15 OHCA AMI–rCS patients without MCS were matched to patients with AMI–rCS and Impella. Patients without LV support had a higher proportion of a cardiac cause of death (n = 7 vs. n = 3; p = 0.024). LV unloading with Impella counteract rCS status and was associated with a preferable 30-day survival (66.7 vs. 20%, p = 0.01) and a favorable neurological outcome after 30 days (Cerebral Performance Category ≤2, 47 vs. 27%). Impella support is associated with a higher 30-day survival (odds ratio, 2.67; 95% confidence interval, 1.02–13.66).Conclusion: In patients after OHCA with AMI–rCS, Impella support incorporated in a strict standardized treatment algorithm results in a preferable 30-day survival and counteracts severe rCS status.

Background: Acute myocardial infarction-related cardiogenic shock (AMI-CS) still has high likelihood of in-hospital mortality. The only trial evidence currently available for the intra-aortic balloon pump showed no benefit of its routine use in AMI-CS. While a potential benefit of complete revascularisation has been suggested in urgent revascularisation, the CULPRIT-SHOCK trial demonstrated no benefit of multivessel compared to culprit-lesion only revascularisation in AMI-CS. However, mechanical circulatory support was only used in a minority of patients.Objectives: We hypothesised that more complete revascularisation facilitated by Impella support is related to lower mortality in AMI-CS patients.Methods: We analysed data from 202 consecutive Impella-treated AMI-CS patients at four European high-volume shock centres (age 66 ± 11 years, 83% male). Forty-seven percentage (n = 94) had cardiac arrest before Impella implantation. Revascularisation was categorised as incomplete if residual SYNTAX-score (rS) was >8.Results: Overall 30-day mortality was 47%. Mortality was higher when Impella was implanted post-PCI (Impella-post-PCI: 57%, Impella-pre-PCI: 38%, p = 0.0053) and if revascularisation was incomplete (rS ≤ 8: 37%, rS > 8: 56%, p = 0.0099). Patients with both pre-PCI Impella implantation and complete revascularisation had significantly lower mortality (33%) than those with incomplete revascularisation and implantation post PCI (72%, p < 0.001).Conclusions: Our retrospective analysis suggests that complete revascularisation supported by an Impella microaxial pump implanted prior to PCI is associated with lower mortality than incomplete revascularisation in patients with AMI-CS.

Objective: We evaluated the short and long-term effect of peri-interventional dabigatran therapy on vasomotion, endothelialization, and neointimal formation in a porcine coronary artery stenting model.Background: Stenting of coronary arteries induces local inflammation, impairs vasomotion and delays endothelialization.Methods: Twenty-eight animals underwent percutaneous coronary intervention (PCI) with drug eluting stents. Sixteen pigs started dabigatran therapy 4 days prior to PCI and continued for 4 days post-stenting, while 12 animals served as controls. Post-stenting dual antiplatelet therapy (75 mg clopidogrel and 100 mg aspirin) was continued in both groups until termination. Immediately post-stenting and at day 3 optical coherence tomography (OCT) was performed in all animals, followed by euthanasia of 8 dabigatran and 4 control animals. The remaining pigs (8 of each group) were followed up for 1 month, with control angiography and OCT. Tissue burden (degree of peri-strut structure—thrombus and/or fibrin) was evaluated. After euthanasia coronary arteries were harvested for in-vitro myometry and histology.Results: Thrombin generation was lower (p < 0.001) and tissue burden (0.83 ± 0.98 vs. 3.0 ± 2.45; p = 0.031) was significantly decreased in dabigatran treated animals. After 3 days post-PCI endothelium-dependent vasodilation was significantly improved (77 ± 40% vs. 41 ± 31%, p = 0.02) in dabigatran animals. Neither quantitative angiography nor histomorphometry showed differences between the groups. Endothelialization was faster in the dabigatran group as compared with controls (p = 0.045).Conclusion: Short-term peri-interventional triple therapy with dabigatran, aspirin, and clopidogrel led to an enhanced endothelium dependent vasodilation and faster endothelialization. However, neointimal formation 1-month after stent implantation was comparable between groups.

Objectives: Surgical exposure of groin vessels to establish cardiopulmonary bypass (CPB) for minimally-invasive valve surgery (MIS) is standard of care but may result in postoperative wound healing disorders or seroma formation. Therefore, adaption of transcatheter techniques for fully percutaneous insertion of CPB cannulae may improve clinical results. We herein analyze a single center experience with a novel plug-based vascular closure device for MIS.Methods: Between 03/2020 and 02/2021 MIS using the MANTA™ (Teleflex Medical Inc., Wayne, PA, USA) vascular closure device was performed in 28 consecutive patients (58.8 ± 10.6 years, 60.3% male, logEuroSCORE II 1.1 ± 0.8%) receiving mitral and/or tricuspid valve repair/replacement. Concomitant procedures were left atrial appendage occlusion and cryoablation for atrial fibrillation in 21.4% (6/28) and 10.7% (3/28) of patients, respectively. Data were retrospectively analyzed in accordance with standardized M-VARC definitions. MANTA™ device success and early safety was defined as absence of any access site or access related vascular injury and major and life-threatening bleeding complications.Results: MANTA™ device success with immediate hemostasis and early safety were 96.4% (27/28). In one case, device failure necessitated surgical cut down without further complications. Mean aortic cross clamp time and cardiopulmonary bypass were 96.5 ± 24.2 min and 150.2 ± 33.6 min. Stroke, renal failure or myocardial infarction were not observed. Intensive care unit and total hospital stay were 1.7 ± 0.8 days and 10.1 ± 5.7 days. Overall 30-day mortality was 0%. Post-procedure echocardiography presented one case of residual moderate tricuspid regurgitation and competent valves in all other cases.Conclusions: The MANTA™ device is safe and effective in MIS. Its ease of use and effectiveness to achieve immediate hemostasis have further simplified MIS.

Background: Heart failure (HF) is a multifactorial syndrome with pathophysiological complexities still not fully understood. Higher mean platelet volume (MPV), a potential marker of platelet activation, and high concentrations of parathyroid hormone (PTH) have been implicated in the pathogenesis of HF.Aim: This study aims to investigate sex-specifically the association between PTH concentrations and platelet indices in phenotypes of HF.Methods and Results: PTH and platelet indices (MPV and platelet count) were available in 1,896 participants from the MyoVasc study in Mainz, Germany. Multivariable linear regression models, adjusted for age, sex, season, vitamin D status, cardiovascular risk factors, comorbidities, estimated glomerular filtration rate, and medication, were used to assess the associations between platelet indices and PTH. The results showed distinct sex-specific associations between PTH and platelet indices. A positive association between PTH and MPV was found in females with symptomatic HF with reduced ejection fraction (HFrEF) only [β = 0.60 (0.19; 1.00)]. Platelet count was inversely associated with PTH in male HFrEF individuals [β = −7.6 (−15; −0.30)] and in both males and females with HF with preserved ejection fraction (HFpEF).Conclusion: This study reports differential, sex-specific relationships between PTH and platelet indices in HF individuals independent of vitamin D status and clinical profile. Particularly in phenotypes of symptomatic HF, distinct associations were observed, suggesting a sex-specific mechanism involved in the interaction between PTH and platelets.

Aims: Cigarette smoking is one of the most complex and least understood cardiovascular risk factors. Importantly, differences in the tobacco-related pathophysiology of endothelial dysfunction, an early event in atherogenesis, between circulatory beds remain elusive. Therefore, this study evaluated how smoking impacts endothelial function of conduit and resistance arteries in a large population-based cohort.Methods and results: 15,010 participants (aged 35–74 years) of the Gutenberg Health Study were examined at baseline from 2007 to 2012. Smoking status, pack-years of smoking, and years since quitting smoking were assessed by a computer-assisted interview. Endothelial function of conduit and resistance arteries was determined by flow-mediated dilation (FMD) of the brachial artery, reactive hyperemia index (RHI) using peripheral arterial tonometry, as well as by reflection index (RI) derived from digital photoplethysmography, respectively. Among all subjects, 45.8% had never smoked, 34.7% were former smokers, and 19.4% were current smokers. Mean cumulative smoking exposure was 22.1 ± 18.1 pack-years in current smokers and mean years since quitting was 18.9 ± 12.7 in former smokers. In multivariable linear regression models adjusted for typical confounders, smoking status, pack-years of smoking, and years since quitting smoking were independently associated with RHI and RI, while no association was found for FMD. Overall, no clear dose-dependent associations were observed between variables, whereby higher exposure tended to be associated with pronounced resistance artery endothelial dysfunction.Conclusions: Cigarette smoking is associated with altered endothelial function of resistance, but not conduit arteries. The present results suggest that smoking-induced endothelial dysfunction in different circulatory beds may exhibit a differential picture.

Background: Measurement of myocardial T1 is increasingly incorporated into standard cardiovascular magnetic resonance (CMR) protocols, however accuracy may be reduced in patients with metallic cardiovascular implants. Measurement is feasible in segments free from visual artifact, but there may still be off-resonance induced error.Aim: To quantify off-resonance induced T1 error in patients with metallic cardiovascular implants, and validate a method for error correction for a conventional MOLLI pulse sequence.Methods: Twenty-four patients with cardiac implantable electronic devices (CIEDs: 46% permanent pacemakers, PPMs; 33% implantable loop recorders, ILRs; and 21% implantable cardioverter-defibrillators, ICDs); and 31 patients with aortic valve replacement (AVR) (45% metallic) were studied. Paired mid-myocardial short-axis MOLLI and single breath-hold off-resonance field maps were acquired at 1.5 T. T1 values were measured by AHA segment, and segments with visual artifact were excluded. T1 correction was applied using a published relationship between off-resonance and T1. The accuracy of the correction was assessed in 10 healthy volunteers by measuring T1 before and after external placement of an ICD generator next to the chest to generate off-resonance.Results: T1 values in healthy volunteers with an ICD were underestimated compared to without (967 ± 52 vs. 997 ± 26 ms respectively, p = 0.0001), but were similar after correction (p = 0.57, residual difference 2 ± 27 ms). Artifact was visible in 4 ± 12, 42 ± 31, and 53 ± 27% of AHA segments in patients with ILRs, PPMs, and ICDs, respectively. In segments without artifact, T1 was underestimated by 63 ms (interquartile range: 7–143) per patient. The greatest error for patients with ILRs, PPMs and ICDs were 79, 146, and 191 ms, respectively. The presence of an AVR did not generate T1 error.Conclusion: Even when there is no visual artifact, there is error in T1 in patients with CIEDs, but not AVRs. Off-resonance field map acquisition can detect error in measured T1, and a correction can be applied to quantify T1 MOLLI accurately.

Introduction: Evidence of sex-related differences in patients with pacemakers regarding comorbidities is insufficiently investigated. The aim of this study was to determine the relationship of cardiovascular comorbidities and sex category with properties of pacemaker implantation, pacemaker follow-up, and long-term survival.Methods: This retrospective, single-center cohort study consisted of 6,362 pacemaker-patients (39.7% female) enrolled between May 2000 and April 2015. Functional pacemaker parameters were registered at regular pacemaker controls. Survival status and cause of death were analyzed in relation to comorbidities, implanted pacing devices, and echocardiography. Survival analyses were plotted for a 10-year follow-up.Results: Patients with hypertension or hyperlipidemia had higher rates of implantations due to sick sinus syndrome (28.6 vs. 25.5% without hypertension, P < 0.001; 30.7 vs. 25.7% without hyperlipidemia, P < 0.001), while endocarditis was associated with higher rates of implantations due to AV block (46.7 vs. 33.4%, P < 0.001). Patients with valvular heart disease had higher rates of pacemaker implantation due to bradycardic atrial fibrillation (24.9 vs. 21.0% without valvular heart disease, P < 0.001). Ventricular pacing threshold increased in both sexes during the follow-up and was higher in women in the final follow-up (0.94 vs. 0.91 V in men, P = 0.002). During the 10-years follow-up, 6.1% of women and 8.6% of men underwent lead replacement (P = 0.054). Device and lead replacement rates were increased if the comorbidities coronary artery disease, heart failure, hypertension, hyperlipidemia, valvular heart disease, previous stroke/TIA, atrial arrhythmias, chronic kidney disease, or endocarditis were present. Diabetes and previous CABG increase the rates of device replacement, but not the rate of lead replacement. Severe tricuspid regurgitation after implantation of pacemaker was present in more men than women (14.4 vs. 6.1%, P < 0.001). In a multivariate COX regression, the following variables were associated with independent decrease of 10-year survival: hypertension (HR 1.34, 95% CI 1.09–1.64), chronic kidney disease (HR 1.83, 95% CI 1.53–2.19), tricuspid regurgitation after pacemaker implantation (HR 1.48, 95% CI 1.26–1.74). Survival was independently increased in female sex (HR 0.83, 95% CI 0.70–0.99) and hyperlipidemia (HR 0.81, 95% CI 0.67–0.97).Conclusions: Cardiovascular comorbidities influenced significantly pacemaker implantations and long-term outcome.Trial Registration:ClinicalTrials.gov Unique identifier: NCT03388281.