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Objectives The study aimed to investigate the alterations of myocardial deformation responding to long-standing pressure overload and the effects of focal myocardial fibrosis using feature-tracking cardiac magnetic resonance (FT-CMR) in patients with resistant hypertension (RH). Methods Consecutive RH patients were prospectively recruited and underwent CMR at a single institution. FT-CMR analyses based on cine images were applied to measure left ventricular (LV) peak systolic global longitudinal (GLS), radial (GRS), and circumferential strain (GCS). Functional and morphological CMR variables, and late gadolinium enhancement (LGE) imaging were also obtained. Results A total of 50 RH patients (63 ± 12 years, 32 men) and 18 normotensive controls (57 ± 8 years, 12 men) were studied. RH patients had a higher average systolic blood pressure than controls (166 ± 21 mmHg vs. 116 ± 8 mmHg, p 2 vs. 61 ± 9 g/m2, p p = 0.001) and GRS (41 ± 12% vs. 48 ± 8%, p = 0.037), and GCS was reduced by trend (− 17 ± 4% vs. − 19 ± 4%, p = 0.078). Twenty-one (42%) RH patients demonstrated a LV focal myocardial fibrosis (LGE +). LGE + RH patients had higher LV mass index (85 ± 14 g/m2 vs. 73 ± 15 g/m2, p = 0.007) and attenuated GRS (37 ± 12% vs. 44 ± 12%, p = 0.048) compared to LGE − RH patients, whereas GLS (p = 0.146) and GCS (p = 0.961) were similar. Conclusion Attenuation of LV GLS and GRS, and GCS decline by tendency, might be adaptative changes responding to chronic pressure overload. There is a high incidence of focal myocardial fibrosis in RH patients, which is associated with reduced LV GRS. Clinical relevance statement Feature-tracking CMR-derived myocardial strain offers insights into the influence of long-standing pressure overload and of a myocardial fibrotic process on cardiac deformation in patients with resistant hypertension. Key Points • Variations of left ventricular strain are attributable to the degree of myocardial impairment in resistant hypertensive patients. • Focal myocardial fibrosis of the left ventricle is associated with attenuated global radial strain. • Feature-tracking CMR provides additional information on the attenuation of myocardial deformation responding to long-standing high blood pressure.

Algorithms for automated analysis of intravascular ultrasound (IVUS) images can be disturbed by guidewires, which are often encountered when treating bifurcations in percutaneous coronary interventions. Detecting guidewires in advance can therefore help avoiding potential errors. This task is not trivial, since guidewires appear rather small compared to other relevant objects in IVUS images. We employed CNNs with additional multi-task learning as well as different guidewire-specific regularizations to enable and improve guidewire detection. In this context, we developed a network block which generates heatmaps that highlight guidewires without the need of localization annotations. The guidewire detection results reach values of 0.931 in terms of the F1-score and 0.996 in terms of area under curve (AUC). Comparing thresholded guidewire heatmaps with ground truth segmentation masks leads to a Dice score of 23.1 % and an average Hausdorff distance of 1.45 mm. Guidewire detection has proven to be a task that CNNs can handle quite well. Employing multi-task learning and guidewire-specific regularizations further improve detection results and enable generation of heatmaps that indicate the position of guidewires without actual labels.

Background The recently updated European Society of Cardiology (ESC) dyslipidaemia guidelines recommend a lower low-density lipoprotein cholesterol (LDL-C) goal of Aims We aim to quantify the need for PCSK9i and the related costs to achieve the revised LDL-C goal in ASCVD patients compared to former ESC recommendations, in particular the risk-based 2017 ESC consensus update. Methods and results We included patients with ASCVD from an observational cohort study ongoing since 2015. A Monte Carlo simulation incorporating a treatment algorithm adding sequentially a statin, ezetimibe, and a PCSK9i was applied with consideration of partial and total statin intolerance. The need for PCSK9i was calculated for three different ESC recommendations (2019 guidelines, 2016 guidelines, 2017 consensus update). Preventable events and treatment costs due to PCSK9i were calculated for a range of annual event rates from 2% to 8% and annual treatment costs of ca. 6050 €. We included 1780 patients (mean age 69.5 years). Median LDL-C at baseline was 85.0 mg/dL, with 61% of patients taking lipid-lowering medication. The need for PCSK9i was simulated to be 42.0% (ESC 2019), 31.9% (ESC 2016), and 5.0% (ESC 2017). The LDL-C goals were achieved in 97.9%, 99.1%, and 60.9% of patients, respectively. Annual treatment cost for PCSK9i per 1 000 000 ASCVD patients would be 2.54 billion € (ESC 2019) compared to 0.30 billion € (ESC 2017). Costs per prevented event due to PCSK9i initiation differed widely, e.g. 887 000 € for an event rate of 3% and a treatment goal of Conclusion The revised LDL-C treatment goals increase the projected need for PCSK9i with a substantial increase in associated treatment cost. An allocation strategy based on residual LDL-C and clinical or angiographic risk factors leads to a more tailored target population for PCSK9i with a reasonable benefit/cost ratio.

PURPOSE: Implanting stents to re-open stenotic lesions during percutaneous coronary interventions is considered a standard treatment for acute or chronic coronary syndrome. Intravascular ultrasound (IVUS) can be used to guide and assess the technical success of these interventions. Automatically segmenting stent struts in IVUS sequences improves workflow efficiency but is non-trivial due to a challenging image appearance entailing manifold ambiguities with other structures. Manual, ungated IVUS pullbacks constitute a challenge in this context. We propose a fully data-driven strategy to first longitudinally detect and subsequently segment stent struts in IVUS frames. APPROACH: A cascaded deep learning approach is presented. It first trains an encoder model to classify frames as “stent,” “no stent,” or “no use.” A segmentation model then delineates stent struts on a pixel level only in frames with a stent label. The first stage of the cascade acts as a gateway to reduce the risk for false positives in the second stage, the segmentation, which is trained on a smaller and difficult-to-annotate dataset. Training of the classification and segmentation model was based on 49,888 and 1826 frames of 74 sequences from 35 patients, respectively. RESULTS: The longitudinal classification yielded Dice scores of 92.96%, 82.35%, and 94.03% for the classes stent, no stent, and no use, respectively. The segmentation achieved a Dice score of 65.1% on the stent ground truth (intra-observer performance: 75.5%) and 43.5% on all frames (including frames without stent, with guidewires, calcium, or without clinical use). The latter improved to 49.5% when gating the frames by the classification decision and further increased to 57.4% with a heuristic on the plausible stent strut area. CONCLUSIONS: A data-driven strategy for segmenting stents in ungated, manual pullbacks was presented—the most common and practical scenario in the time-critical clinical workflow. We demonstrated a mitigated risk for ambiguities and false positive predictions.

The purpose of this prospective study was to analyze the relationship between ventricular morphology and parameters of cardiac function in two different athletic groups and controls, using feature tracking cardiac magnetic resonance (FT-CMR). Twenty-three professional soccer players (22 ± 4 years), 19 competitive triathletes (28 ± 6 years) and 16 controls (26 ± 3 years) were included in the study. CMR was performed using a 1.5 T scanner. Cardiac chamber volumes, mass and biventricular global myocardial strain were obtained and compared. In comparison to the control subjects, athletes were characterized by a higher cardiac volume (p p p p p 2, p p p p r = 0.47, p r = − 0.28, p

Robotic-assisted percutaneous coronary interventions (rPCI) have proven feasible and safe while reducing radiation exposure for the operator. Recently, rPCI systems have been refined to facilitate the treatment of complex lesions. The aim of the current study was to evaluate challenges and opportunities of establishing an rPCI program at a tertiary referral center. rPCI was performed using the CorPath GRX Vascular Robotic System (Corindus Inc., a Siemens Healthineers Company, Waltham, USA). Baseline, procedural, and in-hospital follow-up data were prospectively assessed. rPCI success was defined as completion of the PCI without or with partial manual assistance. The safety endpoint was the composite of missing angiographic success or procedure-related adverse events during hospital stay. Overall, 86 coronary lesions were treated in 71 patients (28.2% female) from January to April 2021. Median age was 71.0 years (IQR 60.3; 79.8). Indications for rPCI were stable angina pectoris (71.8%), unstable angina (12.7%) and non-ST elevation myocardial infarction (15.5%). Most lesions were complex (type B2/C: 88.4%) and included 7 cases of rPCI for chronic total occlusions. Angiographic and rPCI success were achieved in 100.0% and 94.2%, respectively. Partial manual assistance was used in 25.6%. Conversion to manual PCI was required in 5.8%. The safety endpoint occurred in 7.0% of patients. rPCI when applied as clinical routine for complex coronary lesions is effective with good immediate angiographic and clinical results. Future investigations should focus on the identification of patients that particularly benefit from robotic-assisted vs. manual PCI despite higher resource utilization.

Background The 2019 ESC dyslipidaemia guidelines recommend a more intense LDL-cholesterol (LDL-C) reduction for patients with coronary artery disease (CAD). As a result the need for PCSK9 inhibitors (PCSK9i) is projected to increase significantly, with a concomitant substantial impact on treatment cost. Adding the novel lipid lowering agent bempedoic acid (BA) to established oral lipid lowering therapy could provide an affordable alternative to PCSK9i to attain the LDL-C treatment target, particularly in patients with statin intolerance. Aims To quantify the target populations for BA and PCSK9i as well as the related treatment costs to achieve the LDL-C target of the 2019 ESC dyslipidaemia guidelines assuming addition of BA to lipid lowering medication. Methods We included 1922 patients (mean age 69.3 years) with angiographically documented CAD from an observational cohort study ongoing since 2015. A Monte Carlo simulation incorporating an algorithm for intensification of lipid lowering medication was applied in order to achieve the LDL-C treatment goal of Results Figure 1 displays the baseline LDL-C distribution (median LDL-C 86.0 mg/dL) and lipid lowering medications. The need for PCSK9i in scenario 1 would be 41.4% for a moderate and 46.1% for a high rate of statin intolerance. Addition of BA in scenario 2 would reduce the need for PCSK9i to 25.3% and 29.4%. Figure 2 displays the LDL-C distributions and lipid lowering medications for scenarios 1 and 2 assuming a moderate rate of statin intolerance. Use of BA would lower the annual overall treatment cost incurred through use of PCSK9i ± BA per 1,000,000 CAD patients by 13.3% and 10.5%. The cost per prevented event in the entire cohort would be lower (−5.0 and −6.3%), however at the price of less prevented cardiovascular events (−8.7% and −4.5%). Amongst patients with full statin intolerance, the cost per prevented event would be reduced (−6.8% for both rates of statin intolerance) whilst more cardiovascular events would be prevented (+7.5% and +6.9%). Conclusion Use of BA in patients with CAD would reduce the need for PCSK9i as well as the overall treatment cost for add-on lipid lowering therapy. The subpopulation of patients with full statin intolerance might profit particularly. Funding Acknowledgement Type of funding sources: None. Figure 1. Baseline LDL-C distribution and LLMFigure 2. LDL-C and LLM after LLM intensification

Background High-sensitivity Troponin T and I (hsTnT/I) concentration is independently associated with coronary artery disease (CAD) severity and cardiovascular outcome. Here we explored whether hsTnT/I blood levels add predictive information irrespective of CAD severity and further confounders in unselected stable patients with angiographically characterized CAD. Methods Between 2015 and 2020, 3,012 patients undergoing coronary angiography were included in the observational Hamburg INTERCATH study. In 2,209 consecutive patients Troponin levels were quantified for hsTnT (Roche Diagnostics Elecsys) and hsTnI (Abbott Diagnostics ARCHITECT STAT). Patients presenting with acute coronary syndromes and heart transplant recipients were excluded, leaving 1,841 patients for analyses. CAD severity was graded according to the Gensini score. Major adverse cardiac events (MACE) as a composite of cardiovascular death, stroke, myocardial infarction, and coronary revascularization were defined as endpoint. Kaplan-Meier analyses stratified by hsTnT/I quartiles were performed. Multivariable Cox models were computed for the association of hsTnT/I with MACE adjusting for age, gender, arterial hypertension, hyperlipoproteinemia, smoking, diabetes mellitus, body-mass index, eGFR and Gensini Score. Results Mean age was 68.5±10.9 years (27.9% female). 81.1% were diagnosed with CAD by coronary angiography. Gensini score was 21.0±30.2. Median follow-up time was 4.42 years. hsTnT quartiles differentiated MACE across all categories (Figure 1A). For hsTnI, cardiovascular risk was differentiated between the lowest and highest quartiles as well as the 1st and 2nd quartile particularly beyond 24 months of follow-up (Figure 1B). However, MACE after 3 years was not associated with hsTnT after adjustment for classical cardiovascular risk factors and CAD severity (Figure 1C), whereas the hazard of MACE was increased in the 3rd and 4th hsTnI quartiles compared to the 1st quartile (HR 1.3, IQR 1.1–1.6 for both categories; Figure 1D). Conclusion Increasing hsTn concentration was related to intermediate term cardiovascular outcome in unselected stable patients. Only hsTnI concentration remained as independent predictor after testing for most possible confounders, including CAD severity. This data underpins the role of hsTnI in outcome prediction. Funding Acknowledgement Type of funding sources: None.

Knowing the shape of vascular calcifications is crucial for appropriate planning and conductance of percutaneous coronary interventions. The clinical workflow can therefore benefit from automatic segmentation of calcified plaques in intravascular ultrasound (IVUS) images. To solve segmentation problems with convolutional neural networks (CNNs), large datasets are usually required. However, datasets are often rather small in the medical domain. Hence, developing and investigating methods for increasing CNN performance on small datasets can help on the way towards clinically relevant results. We compared two state-of-the-art CNN architectures for segmentation, U-Net and DeepLabV3, and investigated how incorporating auxiliary image data with vessel wall and lumen annotations improves the calcium segmentation performance by using these either for pretraining or multi-task training. DeepLabV3 outperforms U-Net with up to 6.3 % by means of the Dice coefficient and 36.5 % by means of the average Hausdorff distance. Using auxiliary data improves the segmentation performance in both cases, whereas the multi-task approach outperforms the pre-training approach. The improvements of the multi-task approach in contrast to not using auxiliary data at all is 5.7 % for the Dice coefficient and 42.9 % for the average Hausdorff distance. Automatic segmentation of calcified plaques in IVUS images is a demanding task due to their relatively small size compared to the image dimensions and due to visual ambiguities with other image structures. We showed that this problem can generally be tackled by CNNs. Furthermore, we were able to improve the performance by a multi-task learning approach with auxiliary segmentation data.

BackgroundStroke after a cardiovascular procedure (CVP) is a devastating complication adversely affecting outcome. Mechanical thrombectomy (MT) has not been investigated systematically in this population.ObjectiveTo carry out a retrospective study in patients undergoing MT for early stroke after CVP, aiming to further characterize this cohort of patients, and to evaluate the efficacy, safety, procedural characteristics, and outcome of MT.MethodsA single-center stroke registry of patients who received MT was analyzed. Baseline and procedural parameters, mortality, functional outcome, recanalization rates, and complications were evaluated. Propensity score matching was carried out, identifying a control cohort with non-periprocedural large vessel occlusion (LVO).ResultsOverall 913 patients were included (mean age 73.0 (±13.0) years, 52.5% female, median National Institutes of Health Stroke Scale score 15 (10–19)). Eleven patients with a LVO after a recent (ConclusionsUse of MT for LVO stroke in patients after a recent CVP is a safe and efficient treatment in comparison with patients with a non-periprocedural LVO undergoing MT.

Automatic delineation of relevant structures in intravascular imaging can support percutaneous coronary interventions (PCIs), especially when dealing with rather demanding cases. We found three major error types which occur regularly when segmenting lumen and wall of morphologically complex vessels with convolutional neural networks (CNNs). In order to reduce these three error types, we developed three IVUS-specific methods which are able to improve generalizability of state-of-the-art CNNs for IVUS segmentation tasks. These methods are based on three concepts: speckle statistics, artery shape priors via independent component analysis (ICA) and the concentricity condition of lumen and vessel wall. We found that all three methods outperform the baseline. Since all three concepts can be readily transferred to intravascular optical coherence tomography (IVOCT), we expect these findings can support the segmentation of corresponding images as well.

Ischemic heart disease remains one of the leading causes of death worldwide. Percutaneous coronary interventions (PCIs) for implanting coronary stents are preferred for patients with acute myocardial infarction but may also be performed in patients with chronic coronary syndromes to improve symptoms and outcome. During the PCI, the assessment of stent apposition, evaluation of in-stent restenosis or guidance for complex stenting of bifurcation lesions may be improved by intravascular imaging such as intravascular ultrasound (IVUS). However, advanced interpretation of the image often requires expertise and training. To approach this issue, we introduce an automatic delineation of stent struts within the IVUS pullback. We propose a cascaded segmentation based on data-driven learning with a neural encoder-decoder architecture. The learning process uses 80 IVUS sequences from 28 patients which were acquired and partially annotated by the Department of Cardiology, University Heart and Vascular Center Hamburg, Germany. The annotations include 1108, 555 and 355 frames with delineated lumen, stent and calcium as well as 13696 and 10689 frame-wise stent and no-stent indications. The network was pre-trained on lumen segmentation and refined to first identify stent frames using an encoder network and subsequently segment the struts with a decoder. Quantitative evaluation using 3-fold cross-validation revealed 88.3% precision, 92.4% recall and 0.824 Dice for the encoder and 67.0%, 60.3% and 0.611 for the decoder. We conclude that the encoder successfully leverages the larger number of high-level annotations to reject non-stent frames avoiding unnecessary false positives for the decoder trained on much less, but fine-granular annotations.

Coronary intravascular lithotripsy (IVL) has recently been evaluated for the treatment of severely calcified native coronary lesions. Evidence for its use in in-stent restenosis is sparse and is still an off-label indication. Therefore, we aimed to evaluate the feasibility, safety, and acute and mid-term angiographic outcomes after IVL for the treatment of calcium-mediated coronary in-stent restenosis.A retrospective, single-center analysis was performed for 6 cases with undilatable instent restenosis due to calcium-mediated stent underexpansion and/ or calcified neointima from January to November 2019. Lesions were treated with IVL (Shockwave Medical) and subsequent drug-eluting stent or drug-coated balloon. Angiographic success was defined as residual lumen stenosis20% and Thrombolysis in Myocardial Infarction 3 flow. Follow-up angiography was performed at a median of 141.5 days.Six patients presented with symptomatic in-stent restenoses (65.8% to 87.9%) at 11 to 175 months after implantation. Intravascular and angiographic imaging detected calcium-mediated stent underexpansion (n = 2), calcified neointima (n = 2), or a combination of both (n = 2) as cause of restenosis. In-stent IVL, subsequent high-pressure balloon dilation, and drug-eluting stent or drug-coated balloon implantation were performed successfully in all cases. Acute angiographic success and angina relief were achieved in 5 of 6 cases and sustained during follow-up. No major acute cardiovascular events occurred.The application of IVL for the treatment of calcium-mediated coronary in-stent restenosis was feasible and safe, and yielded promising short- and mid-term results in the majority of cases.

Introduction The recently updated ESC guidelines on the management of dyslipidaemias recommend a more intense LDL-cholesterol (LDL-C) reduction. For patients with atherosclerotic cardiovascular disease (ASCVD) the LDL-C goal has been revised to ≤55 mg/dl with a concomitant class IA upgrade for cost intensive PCSK9 inhibitors. Purpose We aim to quantify the need for PCSK9 inhibitors to achieve the revised LDL-C target compared to former ESC recommendations in ASCVD patients Methods We included all patients with ASCVD (angiographically documented coronary artery disease, history of peripheral artery disease or stroke) from an observational cohort study ongoing since 2015. A simulation treatment algorithm adding sequentially a high intensity statin, ezetimibe and a PCSK9 inhibitor in case of a missed treatment target was applied with consideration of both partial and total statin intolerance. The need for PCSK9 inhibitors was calculated for 3 recommendations: 1. LDL-C treatment target ≤55 mg/dl (ESC 2019 Guidelines), 2. LDL-C treatment target ≤70 mg/dl (ESC 2016 Guidelines) and 3. risk-based use of PCSK9 inhibitors restricted to patients with a residual LDL-C >140 mg/dl or >100 mg/dl with clinical/angiographic risk factors (ESC consensus update 2017). Results We included 1936 patients (mean age 69 years, 74% male). Median LDL-C at inclusion was 86 mg/dl, with 60% of patients taking lipid lowering medication (55% statin only, 4% statin + ezetimibe, 1% ezetimibe only). Table 1 shows the distribution of medications required to meet recommendations 1–3. After simulated stepwise intensification of lipid lowering therapy 99% of patients achieved the revised LDL-C target of ≤55 mg/dl, with a need of 23.5% for a PCSK9 inhibitor. For the former LDL-C target of ≤70 mg/dl the need for PCSK9 inhibitors was 10.5%. Restricting the use of PCSK9 inhibitors to the highest risk patients according to the ESC 2017 consensus statement reduced the need for PCSK9 inhibition to only 1.4% with slightly fewer patients achieving their LDL-C target (78% for ≤55 mg/dl and 91% for ≤70 mg/dl respectively). Conclusion The revised LDL-C treatment goals substantially increase the projected need for PCSK9 inhibitors with an unclear health economic impact. Identification of ASCVD patients with a reasonable benefit/cost-ratio of PCSK9 inhibition remains to be investigated urgently. Funding Acknowledgement Type of funding source: None

Cardiac allograft vasculopathy (CAV) remains a major long-term complication in heart transplant (HT) recipients related to increased mortality. We aimed to identify non-immune recipient- and donor-related risk factors for the development of CAV in HT patients.40,647 recipients, prospectively enrolled from April 1995 to January 2019 in the Organ Procurement and Transplantation Network (OPTN), were analyzed after exclusion of pediatric patients, those with missing information on CAV, and re-transplantation. Multivariable-adjusted Cox regression analyses were performed to identify recipient- and donor-related risk factors for CAV. 5-year population attributable risk for classical cardiovascular risk factors was calculated to estimate the recipients' CAV risk. Analyses were based on OPTN data (June 30, 2019).Of 40,647 post-transplant patients, 14,698 (36.2%) developed CAV with a higher incidence in males (37.3%) than in females (32.6%) (p0.001). The mean follow-up time was 68.2 months. In recipients, male sex, African American and Asian ethnicity, ischemic cardiomyopathy, body mass index and smoking were associated with CAV occurrence. In donors, older age, male sex, smoking, diabetes and arterial hypertension were related to CAV. Results remained fairly stable after analysis of different time periods. 5-year attributable CAV risk for classical cardiovascular risk factors was 9.1%.In this large registry with known limitations concerning data completeness, CAV incidence was higher in males than in females. Next to male sex and donor age, the classical cardiovascular risk factors were related to incident CAV. Classical cardiovascular risk factors played only a minor role for the 5-year attributable CAV risk.

Aims The first reports of declining hospital admissions for major cardiovascular emergencies during the COVID-19 pandemic attracted public attention. However, systematic evidence on this subject is sparse. We aimed to investigate the rate of emergent hospital admissions, subsequent invasive treatments and comorbidities during the COVID-19 pandemic in Germany. Methods and results This was a retrospective analysis of health insurance claims data from the second largest insurance fund in Germany, BARMER. Patients hospitalized for acute myocardial infarction, acute limb ischemia, aortic rupture, stroke or transient ischemic attack (TIA) between January 1, 2019, and May 31, 2020, were included. Admission rates per 100,000 insured, invasive treatments and comorbidities were compared from January–May 2019 (pre-COVID) to January–May 2020 (COVID). A total of 115,720 hospitalizations were included in the current analysis (51.3% females, mean age 72.9 years). Monthly admission rates declined from 78.6/100,000 insured (pre-COVID) to 70.6/100,000 (COVID). The lowest admission rate was observed in April 2020 (61.6/100,000). Administration rates for ST-segment elevation myocardial infarction (7.3–6.6), non-ST-segment elevation myocardial infarction (16.8–14.6), acute limb ischemia (5.1–4.6), stroke (35.0–32.5) and TIA (13.7–11.9) decreased from pre-COVID to COVID. Baseline comorbidities and the percentage of these patients treated with interventional or open-surgical procedures remained similar over time across all entities. In-hospital mortality in hospitalizations for stroke increased from pre-COVID to COVID (8.5–9.8%). Conclusions Admission rates for cardiovascular and cerebrovascular emergencies declined during the pandemic in Germany, while patients’ comorbidities and treatment allocations remained unchanged. Further investigation is warranted to identify underlying reasons and potential implications on patients’ outcomes. Graphic abstract

Background and aims Cardiac troponin blood levels are frequently elevated in patients with impaired renal function. Their predictive value for the severity of stable coronary artery disease (CAD) remains unclear in these cases. Therefore, we aimed to evaluate the blood levels of high-sensitivity troponin T and I (hsTnT/I) and their association with the severity of stable CAD in patients with chronic kidney disease. Methods Overall, 2209 patients with suspected stable CAD undergoing invasive coronary angiography were included in an ongoing prospective cohort study. We identified 595 patients with impaired renal function defined as an estimated glomerular filtration rate (eGFR) Results Mean age was 72.9 ± 9.8 years (33.6% female). Median eGFR was 47.5 ml/min/1.73 m2 (interquartile range [IQR] 34.9, 54.1). For the association of Roche-hsTnT, Abbott-hsTnI, and Singulex-hsTnI with the CAD classification, odds ratios per standard deviation (OR) were 1.27 (95% confidence interval [CI] 1.07–1.51), 1.21 (CI 1.02–1.44), and 1.24 (CI 1.04–1.47), respectively. The associations for the investigated assays with SYNTAX and Gensini scores, respectively, were OR 1.40, CI 1.11–1.78 and OR 1.24, CI 1.01–1.51 (Roche-hsTnT), OR 1.42, CI 1.12–1.78 and OR 1.25, CI 1.02–1.52 (Abbott-hsTnI), OR 1.38, CI 1.09–1.74 and OR 1.25, CI 1.02–1.53 (Singulex-hsTnI). Conclusions In patients with impaired renal function, blood levels of hsTnT/I were significantly associated with the severity of stable CAD. These findings may help clinicians guide further diagnostic assessment.

Rationale: Phosphodiesterase 2 is a dual substrate esterase, which has the unique property to be stimulated by cGMP, but primarily hydrolyzes cAMP. Myocardial phosphodiesterase 2 is upregulated in human heart failure, but its role in the heart is unknown. Objective: To explore the role of phosphodiesterase 2 in cardiac function, propensity to arrhythmia, and myocardial infarction. Methods and Results: Pharmacological inhibition of phosphodiesterase 2 (BAY 60–7550, BAY) led to a significant positive chronotropic effect on top of maximal β-adrenoceptor activation in healthy mice. Under pathological conditions induced by chronic catecholamine infusions, BAY reversed both the attenuated β-adrenoceptor–mediated inotropy and chronotropy. Conversely, ECG telemetry in heart-specific phosphodiesterase 2-transgenic (TG) mice showed a marked reduction in resting and in maximal heart rate, whereas cardiac output was completely preserved because of greater cardiac contraction. This well-tolerated phenotype persisted in elderly TG with no indications of cardiac pathology or premature death. During arrhythmia provocation induced by catecholamine injections, TG animals were resistant to triggered ventricular arrhythmias. Accordingly, Ca 2+ -spark analysis in isolated TG cardiomyocytes revealed remarkably reduced Ca 2+ leakage and lower basal phosphorylation levels of Ca 2+ -cycling proteins including ryanodine receptor type 2. Moreover, TG demonstrated improved cardiac function after myocardial infarction. Conclusions: Endogenous phosphodiesterase 2 contributes to heart rate regulation. Greater phosphodiesterase 2 abundance protects against arrhythmias and improves contraction force after severe ischemic insult. Activating myocardial phosphodiesterase 2 may, thus, represent a novel intracellular antiadrenergic therapeutic strategy protecting the heart from arrhythmia and contractile dysfunction.

Introduction Modifiable lifestyle risk factors (modRF) of coronary artery disease (CAD) such as smoking, lack of physical activity (PA) and poor diet are associated with high inflammatory burden. An optimisation of modRF might significantly affect the target population for pharmacological anti-inflammatory treatment (AIT) as determined by a hsCRP ≥2 mg/l. Aim To analyse the influence of modRF on hsCRP in a contemporary CAD cohort and model the effect of modRF optimisation on hsCRP in a target population with high inflammatory burden. Methods We included all patients with angiographically documented CAD from an observational cohort study ongoing since 2015 and excluded patients with recent myocardial infarction, malignancy, infectious disease, and immunosuppressive medication. ModRF were assessed by questionnaire at enrolment. Lack of PA was defined as PA Results Of the 1003 patients (mean age 69 years, 72% male) included, 48% (N=479) had a hsCRP ≥2 mg/l. HsCRP increased with the incremental number of modRF (median hsCRP-values for 0–3 modRF: 1.1, 1.6, 2.1, 2.7 mg/l, p12, and smoking (Table 1). Recalculation of hsCRP levels identified 21% (N=102/479) of patients with hsCRP ≥2 mg/l who could achieve a hsCRP Table 1. Linear regression results Univariate Multivariate exp(β) (95% CI) p-value exp(β) (95% CI) p-value PA ≥1.5 h/week 0.63 (0.54, 0.72) 12 0.74 (0.65, 0.86) Conclusion Modifiable lifestyle risk factors are independently associated with hsCRP levels in CAD patients. A relevant portion of patients with high inflammatory burden might achieve a hsCRP

To investigate the effects of renal denervation (RDN) on left ventricular (LV) mass, myocardial strain and diastolic function in patients with treatment-resistant arterial hypertension by cardiac magnet resonance imaging on a 12-month follow-up. Sixteen patients (38% female) were examined before and 12 months after RDN. LV morphology and strain were analyzed. Diastolic function was determined by early (EPFR) and atrial peak filling rates (APFR) derived from differential volume–time-curve analysis. Clinical visits included 24-h ambulant blood pressure monitoring (ABPM). Twelve months after RDN LV mass decreased from 80 ± 21 g/m2 to 74 ± 20 g/m2 (P

Background: The relevance of blood lipid concentrations to long-term incidence of cardiovascular disease and the relevance of lipid-lowering therapy for cardiovascular disease outcomes is unclear. We investigated the cardiovascular disease risk associated with the full spectrum of bloodstream non-HDL cholesterol concentrations. We also created an easy-to-use tool to estimate the long-term probabilities for a cardiovascular disease event associated with non-HDL cholesterol and modelled its risk reduction by lipid-lowering treatment. Methods: In this risk-evaluation and risk-modelling study, we used Multinational Cardiovascular Risk Consortium data from 19 countries across Europe, Australia, and North America. Individuals without prevalent cardiovascular disease at baseline and with robust available data on cardiovascular disease outcomes were included. The primary composite endpoint of atherosclerotic cardiovascular disease was defined as the occurrence of the coronary heart disease event or ischaemic stroke. Sex-specific multivariable analyses were computed using non-HDL cholesterol categories according to the European guideline thresholds, adjusted for age, sex, cohort, and classical modifiable cardiovascular risk factors. In a derivation and validation design, we created a tool to estimate the probabilities of a cardiovascular disease event by the age of 75 years, dependent on age, sex, and risk factors, and the associated modelled risk reduction, assuming a 50% reduction of non-HDL cholesterol. Findings: Of the 524 444 individuals in the 44 cohorts in the Consortium database, we identified 398 846 individuals belonging to 38 cohorts (184 055 [48·7%] women; median age 51·0 years [IQR 40·7–59·7]). 199 415 individuals were included in the derivation cohort (91 786 [48·4%] women) and 199 431 (92 269 [49·1%] women) in the validation cohort. During a maximum follow-up of 43·6 years (median 13·5 years, IQR 7·0–20·1), 54 542 cardiovascular endpoints occurred. Incidence curve analyses showed progressively higher 30-year cardiovascular disease event-rates for increasing non-HDL cholesterol categories (from 7·7% for non-HDL cholesterol

Background and aims Guidelines recommend a healthy diet as a cornerstone of cardiovascular disease (CVD) prevention. Although the Mediterranean diet (MD) is the best studied dietary pattern for CV outcomes, data on association between MD and severity of CAD are limited. Therefore, we analysed dietary data in association with the SYNTAX score in coronary artery disease (CAD) patients from the INTERCATH study. Methods The INTERCATH study is an observational study in patients undergoing coronary angiography at the University Heart Center Hamburg. Coronary morphology is assessed by the SYNTAX score. A lifestyle questionnaire collects dietary data with food frequency questions at baseline. Based on seven dietary characteristics, we calculated an established Mediterranean diet score (MDS) with a range of 0–28 points at which 28 points reflect maximal adherence to MD. To investigate the association of MD with severity of CAD, we performed logistic regression analysis after adjustment for confounding factors. Results Of 1121 patients, 27% were women. The median age was 70.7 years (interquartile range (IQR) 61.1,77.0). CV risk factors were distributed as expected for a CAD cohort (31.3% diabetes, 81.1% arterial hypertension, 34.0% smoking, median BMI 26.6 kg/m2 (IQR 24.1, 30.3), median LDL-C 87 mg/dL (IQR 65.0,116,6). Of all variables included, the strongest correlation with MDS was found for log (hs-CRP) (r = −0.21, p Conclusions In this contemporary data set, we found an independent association of adherence to MD with a less complex CAD. Hs-CRP correlated significantly with adherence to MD and may be a marker of the vasoprotective effects of MD. These results strengthen the evidence for the protective effect of an MD pattern in CVD prevention.

Aims: As promising compounds to lower Lipoprotein(a) (Lp(a)) are emerging, the need for a precise characterization and comparability of the Lp(a)-associated cardiovascular risk is increasing. Therefore, we aimed to evaluate the distribution of Lp(a) concentrations across the European population, to characterize the association with cardiovascular outcomes and to provide high comparability of the Lp(a)-associated cardiovascular risk by use of centrally determined Lp(a) concentrations. Methods and results: Based on the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE)-project, we analysed data of 56 804 participants from 7 prospective population-based cohorts across Europe with a maximum follow-up of 24 years. All Lp(a) measurements were performed in the central BiomarCaRE laboratory (Biokit Quantia Lp(a)-Test; Abbott Diagnostics). The three endpoints considered were incident major coronary events (MCE), incident cardiovascular disease (CVD) events, and total mortality. We found lower Lp(a) levels in Northern European cohorts (median 4.9 mg/dL) compared to central (median 7.9 mg/dL) and Southern European cohorts (10.9 mg/dL) (Jonckheere-Terpstra test P&thinsp

The determination of cardiac troponin is essential for diagnosing myocardial infarction. A troponin I assay has recently been developed that provides the highest analytical sensitivity to date.The analysis included 1560 patients with chest pain, of whom 1098 were diagnosed with non-coronary chest pain, 189 with unstable angina pectoris and 273 with non-ST-segment elevation myocardial infarction. The troponin I concentration was determined on admission (0 hours) and 3 hours later. The diagnostic algorithm incorporated troponin I elevation above the gender-specific 99th percentile as well as predefined relative or absolute 3-hour changes in the troponin I concentration (delta).The diagnostic criterion of troponin I above the 99th percentile resulted in a negative predictive value of 98.0% and 98.2% in men and women, respectively. For rule-in of non-ST-segment elevation myocardial infarction, the use of absolute deltas yielded higher positive predictive values and sensitivities compared to relative deltas. With detection rates of about 85% and 82% in men and women, respectively, non-ST-segment elevation myocardial infarction was diagnosed with a positive predictive value close to 84% in men and 80% in women.The investigational troponin I assay provides an excellent non-ST-segment elevation myocardial infarction rule out. With gender-specific differences, the application of absolute changes in troponin concentration was superior to relative changes to rule in patients with non-ST-segment elevation myocardial infarction.

Although the efficacy of lipid-lowering medication (LLM) in patients with coronary artery disease (CAD) is well established, the majority of patients fail to achieve their LDL-C goals. The evidence for measurement of LDL-C to achieve these goals is limited. The goal of the present study, therefore, was to analyze ambulatory LLM management in relation to performance of LDL-C measurements and achieved LDL-C levels after the initial diagnosis of CAD.The study followed up a subcohort of 200 patients with newly diagnosed CAD of the INTERCATH trial, an observational study including patients undergoing coronary angiography. In addition to baseline information, data were collected on LLM, performance of lipid measurements, and laboratory results at a minimum of 6 months' postdischarge.The mean age of the sample was 67.9 years, and 36.0% were women. In 34.5% of all patients, no measurement of LDL-C levels was performed during follow-up. We found no differences in baseline characteristics between patients with and without LDL-C measurements during follow-up. In patients with measurement of LDL-C levels, the frequency of intensification of statin medication according to LDL-C reduction was higher compared with those patients without LDL-C measurement (23.6% vs 4.3%; P0.001); all other categories of intensity adjustment were comparable. In patients with 3 LDL-C measurements, achieved LDL-C levels were significantly lower (mean, 81 mg/dL), and a higher proportion reached an LDL-C level70 mg/dL (44.7%) compared with patients with 1 (95 mg/dL [P = 0.013]; 21.8%) or 2 (91 mg/dL [P = 0.037]; 28.9%) LDL-C measurements despite comparable LDL-C levels at baseline. Ezetimibe was used in 3.5% of the entire study cohort.We found no differences in patient characteristics between patients with and without LDL-C measurements after being newly diagnosed with CAD. Performance and frequency of LDL-C measurements were clearly associated with better, higher frequency of intensification of statin medication, lower achieved LDL-C levels, and a higher proportion of patients achieving the LDL-C goal of70 mg/dL. These results suggest an important role of LDL-C measurements for secondary prevention after the initial diagnosis of CAD.

The 99th percentile of cardiac troponin levels, determined in a reference population, is accepted as threshold for diagnosis of acute myocardial infarction (AMI). However, there is no common consensus of how to define the reference population. The aim of the present study was to determine 99th percentile reference values, determined by a high-sensitivity assay (hsTnI), according to different health status and cardiovascular risk factor prevalence in a large population-based sample.Troponin I was determined using the Abbott ARCHITECT STAT highly sensitive troponin I immunoassay in 4138 participants of the Gutenberg Health Study.hsTnI was detectable in 81.6% of all individuals. The 99th percentile of the overall population was 27 ng/L. Age and gender had a prominent influence on these values. Exclusion of individuals with elevated natriuretic peptide levels or cardiac abnormalities resulted in lower 99th percentile values, whereas exclusion of individuals with an impaired estimated glomerular filtration rate (eGFR) or with prevalent coronary artery disease/myocardial infarction (CAD/MI) did not result in a meaningful change.Troponin I, measured by a high-sensitivity assay, can be reliably detected in the vast majority of the general population. hsTnI values were dependent on age, gender as well as structural and functional cardiac abnormalities.

Purpose: The favorite biomarker in diagnosing acute myocardial infarction (AMI) is cardiac troponin. Allowing troponin detection in >50% of the presumably healthy population high-sensitivity cardiac troponin assays have been established to improve accuracy of AMI diagnosis. Recently, detecting troponin in >95% of the general population, super-sensitivity cardiac troponin assays have been developed. The clinical utility of these troponin assays for the diagnosis of AMI is unclear. Aim of the study was to directly compare diagnostic performance of a super-sensitivity cardiac troponin assay with a high-sensitivity cardiac troponin assay in patients with suspected AMI. Methods: 1389 patients with new-onset chest pain were included in the study. 934 patients were diagnosed with non-coronary chest-pain, 184 with unstable angina pectoris, 271 with AMI. Cardiac troponin I (cTnI) concentration was measured on admission (0h) and 3 hours later (3h) by a high-sensitivity (h-s) assay (ARCHITECT STAT highly sensitive Troponin I immunoassay, Abbott Diagnostics, Abbott Park, IL, USA) and a super-sensitivity (s-s) assay (Erenna® cTnI immunoassay, Singulex, Inc., Alameda, CA, USA). As diagnostic cutoff concentration (P99) assay- and gender specific 99th percentiles, derived from the same reference population, were used. The diagnostic algorithm incorporated cTnI elevation (>P99) at either time point and predefined relative 3-h changes in cTnI concentration (ΔcTnI). Accordingly, for rule-in AMI, patients were divided in two subgroups: those with cTnI (0h) >P99 + ΔcTnI and that with cTnI (0h) ≤P99 and cTnI (3h) >P99 + ΔcTnI. Results: Rule-out AMI was achieved by a cTnI (3h) ≤P99 with negative predictive values of 98.6% (s-s assay) and 99.5% (h-s assay; P=0.008) and with specificities of 95.1% (s-s assay) and 88.3% (h-s assay; P P99, rule-in AMI via ΔcTnI ≥100% resulted in sensitivities of 53.8% (s-s assay) and 50.2% (h-s assay; P=0.25) and a positive predictive value (PPV) of 95% for both assays. In patients with cTnI (0h) ≤P99, cTnI (3h) >P99 and assay-specific ΔcTnI (≥100% s-s assay, ≥250% h-s assay) yielded sensitivities of 85.9% (s-s assay) and 90.9% (h-s assay; P=0.24) and PPVs of 83.9% (s-s assay) and 83.3% (h-s assay). Conclusions: Using assay-specific relative changes of cTnI concentration to rule-in AMI in patients with new-onset chest pain, the diagnostic performance of both assays were found to be equivalent. The direct comparison of super- and high-sensitivity troponin assay shows only minor differences in ruling-out AMI.