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The impact of tafamidis on myocardial strain in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) have been barely investigated. We aimed to determine tafamidis-induced changes using serial speckle tracking echocardiography and to identify imaging parameters for specific therapy monitoring.ATTR-CM patients underwent serial TTE with two-dimensional (2 D) speckle tracking imaging. Patients receiving tafamidis free acid 61 mg (Treatment with tafamidis free acid 61 mg in ATTR-CM patients delays the deterioration of LA and LV longitudinal function, resulting in significant clinical benefits compared with natural history. Serial TTE with 2 D speckle tracking imaging may be appropriate for disease-specific therapy monitoring.

Aims The presence of pulmonary hypertension (PH) severely aggravates the clinical course of heart failure with preserved ejection fraction (HFpEF). To date, neither established heart failure therapies nor pulmonary vasodilators proved beneficial. This study investigated the efficacy of chronic treatment with the oral soluble guanylate cyclase stimulator riociguat in patients with PH-HFpEF. Methods and Results The phase IIb, randomized, double-blind, placebo-controlled, parallel-group, multicentre DYNAMIC trial assessed riociguat in PH-HFpEF. Patients were recruited at five hospitals across Austria and Germany. Key eligibility criteria were mean pulmonary artery pressure ≥25 mmHg, pulmonary arterial wedge pressure >15 mmHg, and left ventricular ejection fraction ≥50%. Patients were randomized to oral treatment with riociguat or placebo (1:1). Patients started at 0.5 mg three times daily (TID) and were up-titrated to 1.5 mg TID. The primary efficacy endpoint was change from baseline to week 26 in cardiac output (CO) at rest, measured by right heart catheterization. Primary efficacy analyses were performed on the full analysis set. Fifty-eight patients received riociguat and 56 patients placebo. After 26 weeks, CO increased by 0.37 ± 1.263 L/min in the riociguat group and decreased by −0.11 ± 0.921 L/min in the placebo group (least-squares mean difference: 0.54 L/min, 95% confidence interval 0.112, 0.971; P = 0.0142). Five patients dropped out due to riociguat-related adverse events but no riociguat-related serious adverse event or death occurred. Conclusion The vasodilator riociguat improved haemodynamics in PH-HFpEF. Riociguat was safe in most patients but led to more dropouts as compared to placebo and did not change clinical symptoms within the study period.

Aims Tafamidis treatment positively affects left ventricular (LV) structure and function and improves outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). We aimed to investigate the relationship between treatment response and cardiac amyloid burden identified by serial quantitative 99mTc-DPD SPECT/CT. We furthermore aimed to identify nuclear imaging biomarkers that could be used to quantify and monitor response to tafamidis therapy. Methods and results Forty wild-type ATTR-CM patients who underwent 99mTc-DPD scintigraphy and SPECT/CT imaging at baseline and after treatment with tafamidis 61 mg once daily [median, 9.0 months (interquartile range 7.0–10.0)] were divided into two cohorts based on the median (−32.3%) of the longitudinal percent change in standardized uptake value (SUV) retention index. ATTR-CM patients with a reduction greater than or equal to the median (n = 20) had a significant decrease in SUV retention index (P < 0.001) at follow-up, which translated into significant benefits in serum N-terminal prohormone of brain natriuretic peptide levels (P = 0.006), left atrial volume index (P = 0.038), as well as LV [LV global longitudinal strain: P = 0.028, LV ejection fraction (EF): P = 0.027, LV cardiac index (CI): P = 0.034] and right ventricular (RV) [RVEF: P = 0.025, RVCI: P = 0.048] functions compared with patients with a decrease less than the median (n = 20). Conclusion Treatment with tafamidis in ATTR-CM patients results in a significant reduction in SUV retention index, associated with significant benefits for LV and RV function and cardiac biomarkers. Serial quantitative 99mTc-DPD SPECT/CT imaging with SUV may be a valid tool to quantify and monitor response to tafamidis treatment in affected patients. Translational perspective 99mTc-DPD SPECT/CT imaging with determination of SUV retention index as part of a routine annual examination can provide evidence of treatment response in ATTR-CM patients receiving disease-modifying therapy. Further long-term studies with 99mTc-DPD SPECT/CT imaging may help to evaluate the relationship between tafamidis-induced reduction in SUV retention index and outcome in patients with ATTR-CM and will demonstrate whether highly disease-specific 99mTc-DPD SPECT/CT imaging is more sensitive than routine diagnostic monitoring.

BackgroundDiagnosis of cardiac amyloidosis (CA) requires advanced imaging techniques. Typical surface ECG patterns have been described, but their diagnostic abilities are limited.ObjectiveThe aim was to perform a thorough electrophysiological characterisation of patients with CA and derive an easy-to-use tool for diagnosis.MethodsWe applied electrocardiographic imaging (ECGI) to acquire electroanatomical maps in patients with CA and controls. A machine learning approach was then used to decipher the complex data sets obtained and generate a surface ECG-based diagnostic tool.FindingsAreas of low voltage were localised in the basal inferior regions of both ventricles and the remaining right ventricular segments in CA. The earliest epicardial breakthrough of myocardial activation was visualised on the right ventricle. Potential maps revealed an accelerated and diffuse propagation pattern. We correlated the results from ECGI with 12-lead ECG recordings. Ventricular activation correlated best with R-peak timing in leads V1–V3. Epicardial voltage showed a strong positive correlation with R-peak amplitude in the inferior leads II, III and aVF. Respective surface ECG leads showed two characteristic patterns. Ten blinded cardiologists were asked to identify patients with CA by analysing 12-lead ECGs before and after training on the defined ECG patterns. Training led to significant improvements in the detection rate of CA, with an area under the curve of 0.69 before and 0.97 after training.InterpretationUsing a machine learning approach, an ECG-based tool was developed from detailed electroanatomical mapping of patients with CA. The ECG algorithm is simple and has proven helpful to suspect CA without the aid of advanced imaging modalities.

Objectives Post-operative atrial fibrillation (POAF) represents a common complication after cardiac surgery that is associated with unfavorable clinical outcome. Identifying patients at risk for POAF is crucial but challenging. Purpose This study aimed to investigate the prognostic potential of speckle tracking echocardiography (STE) on POAF and fatal adverse events from a long-term perspective. Methods A total of 124 patients undergoing elective cardiac surgery were prospectively enrolled and underwent pre-operative STE. Patients were followed prospectively for the occurrence of POAF within the entire hospitalization and reaching the secondary endpoints cardiovascular (CV) and all-cause mortality. Results Within the study population 43.5% (n=53) of enrolled individuals developed POAF. After a median follow-up of 3.9 years, 25 (20.2%) patients died. We observed that patients presenting with POAF had lower global peak atrial longitudinal strain (PALS) values compared to the non-POAF arm (POAF: 14.8% [95% CI: 10.9–17.8] vs. non-POAF: 19.4% [95% CI: 14.8–23.5], p Conclusion Global PALS is associated with the development of POAF following surgery in an unselected patient population undergoing CABG and/or valve surgery. Since patients with global PALS Funding Acknowledgement Type of funding sources: None.

Background: In patients with transthyretin amyloid cardiomyopathy, tafamidis was shown to slow the decline in 6-minute walking distance as compared with placebo. We aimed to define the impact of tafamidis and optimal background treatment on functional capacity as determined by cardiopulmonary exercise testing (CPET). Methods: Seventy-eight consecutive patients were enrolled in the study. They underwent CPET at baseline, and outcome defined as death or heart failure hospitalization was obtained for a time period of up to 30 months. Fifty-four patients completed a follow-up CPET at 9±3 months (range, 4–16 months). Improvement in peak VO 2 at follow-up was defined as ∆peak VO 2 ≥1.0 mL/(kg·min), stable peak VO 2 was defined as 0≤∆peak VO 2 2 was defined by ∆peak VO 2 Results: Baseline peak VO 2 >14 mL/(kg·min) as well as minute ventilation/carbon dioxide production slope≤34 were associated with a lower risk of death or heart failure hospitalization ( P =0.002, P =0.007, respectively). In 54 patients, who received tafamidis and underwent repeat CPET testing, an improvement in physical performance ( P =0.002) was observed at follow-up. When comparing pre and post-treatment parameters, 29 patients (54%) showed an increase in percent predicted peak VO 2 ( P 2 ( P P 2 had less advanced heart disease at baseline ( P =0.046). Conclusions: Our findings demonstrate that baseline peak VO 2 and baseline minute ventilation/carbon dioxide production slope predict outcomes and an improvement in physical performance as measured by CPET was observed in patients receiving tafamidis, who had less advanced disease at baseline, emphasizing the importance of early diagnosis.

Background The diagnosis of cardiac amyloidosis (CA) requires advanced imaging techniques. Typical surface ECG patterns have been described, but their diagnostic value is limited. Purpose The aim of this study was to perform a comprehensive electrophysiological characterization in CA patients and to develop a robust, easy-to-use diagnostic tool. Methods First, we applied electrocardiographic imaging (ECGI) to generate detailed electroanatomical maps in CA patients and controls. Then, a machine learning approach was used to generate a surface ECG-based diagnostic algorithm from the complex dataset. Results Areas of low voltage were localized in the basal inferior regions of both ventricles and the remaining right ventricular segments in CA. The earliest epicardial breakthrough of myocardial activation was visualized in the right ventricle. Potential maps showed an accelerated and diffuse propagation pattern. We correlated the results from ECGI with 12-lead ECG recordings. Ventricular activation correlated best with R-peak timing in leads V1 to V3. Epicardial voltage showed a strong positive correlation with R-peak amplitude in inferior leads II, III, aVF. Ten blinded cardiologists were then asked to identify CA patients by analyzing 12-lead ECGs before and after training for the defined ECG patterns. Training resulted in significant improvements in the detection rate of CA with an AUC of 0.69 before and 0.97 after training (Figure). Conclusion Using a machine learning approach, a robust ECG-based tool was developed to detect CA from detailed electroanatomical mapping of CA patients. The developed tool proved to be a simple and reliable diagnostic tool to suspect CA without the aid of advanced imaging modalities. Funding Acknowledgement Type of funding sources: None.

Background Heart failure with preserved ejection fraction (HFpEF) is the most common form of HF and its prevalence is approaching epidemic proportions. Current treatment strategies aim to improve clinical status and reduce mortality rates. Episodes of acute HF are one of the main reasons for hospitalization in people over 65 years; however, they have not been well studied in HFpEF patients yet. Objectives The aim of this study was to investigate the impact of recurrent HF hospitalizations on long-term outcomes and to find predictors for subsequent events. Methods Between December 2010 and December 2019, 422 patients with confirmed HFpEF were enrolled in this study and prospectively followed. Results During follow-up, 190 HFpEF patients (45%) experienced HF hospitalizations with a median frequency of 2 (IQR: 1–4). Those presenting with acute HF had higher body mass indices (p=0.018), worse performance in 6-minute walking tests (p Conclusions HFpEF patients experiencing recurrent HF hospitalizations have worse long-term outcome. Intensive efforts should be made to maintain HFpEF patients compensated over time. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Novartis

Aims Tafamidis improves outcomes in patients with transthyretin amyloid cardiomyopathy (ATTR-CM). However, it is not yet known whether tafamidis affects cardiac amyloid deposition and structural changes in the myocardium. We aimed to determine disease-modifying effects on myocardial amyloid progression and to identify imaging parameters that could be applied for specific therapy monitoring. Methods and results ATTR-CM patients underwent serial cardiac magnetic resonance (CMR) imaging using T1 mapping techniques to derive extracellular volume (ECV). Patients receiving tafamidis 61 mg (n = 35) or 20 mg (n = 15) once daily showed stable measurements at follow-up (FU) {61 mg: 9.0 [interquartile range (IQR) 7.0–11.0] months, 20 mg: 11.0 (IQR 8.0–18.0) months} in left ventricular (LV) ejection fraction (LVEF; 61 mg: 47.6% vs. 47.5%, P = 0.935; 20 mg: 52.4% vs. 52.1%, P = 0.930), LV mass index (LVMI; 61 mg: 110.2 vs. 106.2 g/m2, P = 0.304; 20 mg: 114.5 vs. 115.4 g/m2, P = 0.900), and ECV (61 mg: 47.5% vs. 47.7%, P = 0.861; 20 mg: 56.7% vs. 57.5%, P = 0.759), whereas treatment-naïve ATTR-CM patients (n = 19) had clear signs of disease progression at the end of the observation period [12.0 (IQR 10.0–21.0) months; LVEF: 53.3% vs. 45.7%, P = 0.031; LVMI: 98.9 vs. 106.9 g/m2, P = 0.027; ECV: 49.3% vs. 54.6%, P = 0.023]. Between-group comparison at FU revealed positive effects in tafamidis 61 mg-treated compared to treatment-naïve patients (LVEF: P = 0.035, LVMI: P = 0.036, ECV: P = 0.030), while those treated with 20 mg showed no difference in the above LV measurements when compared with treatment-naïve (P = 0.120, P = 0.287, P = 0.158). However, both treatment groups showed clinically beneficial effects compared to the natural course [61 mg, 6-min walk distance (6-MWD): P = 0.005, N-terminal prohormone of brain natriuretic peptide (NT-proBNP): P = 0.002; 20 mg, 6-MWD: P = 0.023, NT-proBNP: P = 0.003]. Conclusion Tafamidis delays myocardial amyloid progression in ATTR-CM patients, resulting in structural, functional, and clinical benefits compared to the natural course. Serial CMR including measurement of ECV may be appropriate for disease-specific therapy monitoring.

Drugs which interact with the renin angiotensin aldosterone system (RAAS) aim to reduce the negative effects of angiotensin (Ang) II. Treatment with these drugs anticipate a compensatory up-regulation of renin, however, it has been shown that there is a large variability in circulating plasma renin (PRA), even in patients with optimal medical therapy in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Our aim was to measure plasma renin activity (PRA-S), its response to RAAS inhibitor (RAASi) therapies and its effects on outcome in patients with HF with preserved ejection fraction (HFpEF). For this purpose, 150 HFpEF patients were included into a prospective single-center registry. Equilibrium (eq) angiotensin metabolites were measured from serum samples using mass spectroscopy. PRA-S (eqAng I + eqAng II) was calculated and compared in respect to the primary endpoint defined as all-cause death. PRA-S in patients with RAASi therapy was not significantly higher than in patients without RAASi (p = 0.262). Even after adjusting for confounding factors, PRA-S remained predictive for all-cause death in the multivariable model with a hazard ratio of 2.14 (95%CI 1.20–3.82, p = 0.010). We conclude that high PRA-S is associated with poor prognosis in patients with HFpEF, regardless of RAASi treatment, which could ultimately result in hyperactivated RAAS and consecutive negative effects on the cardiovascular and renal system, leading to poor outcome in patients with HFpEF.

Background Twiddler’s syndrome is a rare complication after implantation of cardiac pacemakers or cardioverter-defibrillators that usually occurs within the first year after the procedure. However, it has not yet been described following implantation of baroreflex activation therapy (BAT). Case summary A 61-year-old female patient was referred to the cardiology outpatient clinic due to uncontrolled arterial hypertension despite maximal doses of several established drugs. Therefore, right-sided BAT implantation was successfully performed in February 2017 with good clinical response. Because of sustained neck pain at the site of stimulator, surgical revision was performed in November 2019 including a switch of the lead to the contralateral position. Approximately 1 month later, Twiddler’s syndrome was identified on the basis of recurrent pain at the generator site necessitating pocket-revision, however, the lead was only untwisted but not replaced. A few weeks afterwards, unfortunately, lead revision was indispensable due to lead fracture. Discussion This case presents the uncommon phenomenon of Twiddler’s syndrome after BAT implantation. In addition, the commonly twisted lead should always be replaced as well during surgical pocket-revision in order to ensure proper long-term function.

Background: Diagnosis of cardiac amyloidosis (CA) requires advanced imaging techniques. Typical surface ECG patterns have been described, but their diagnostic abilities are limited. Objectives: The aim was to perform a thorough electrophysiological characterization in CA patients and derive an easy-to-use tool for diagnosis. Methods: We applied electrocardiographic imaging (ECGI) to acquire electroanatomical maps in CA patients and controls. A machine learning approach was then utilized to decipher the complex data sets obtained and generate a surface ECG-based diagnostic tool. Findings: Areas of low-voltage were localized in the basal inferior regions of both ventricles and the remaining right ventricular segments in CA. The earliest epicardial breakthrough of myocardial activation was visualized on the right ventricle. Potential maps revealed an accelerated and diffuse propagation pattern. We correlated the results from ECGI with 12-lead ECG recordings. Ventricular activation correlated best with R-peak timing in leads V1 to V3. Epicardial voltage showed a strong positive correlation with R-peak amplitude in the inferior leads II, III, aVF. Respective surface ECG leads showed two characteristic patterns. Ten blinded cardiologists were asked to identify CA patients by analyzing 12-lead ECGs before and after training on the defined ECG patterns. Training led to significant improvements in the detection rate of CA with an AUC of 0.69 before and 0.97 after training. Interpretation: Using a machine learning approach, an ECG-based tool was developed from detailed electroanatomical mapping of CA patients. The ECG algorithm is simple and has proven helpful to suspect CA without the aid of advanced imaging modalities.. Funding Information: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Declaration of Interests: None to declare. Ethics Approval Statement: The study was part of a registry approved by the local ethics committee (EK #796/2010) and conducted according to good clinical practice as outlined in the declaration of Helsinki. All patients gave written informed consent.

Background Established heart failure (HF) treatments have shown no effects in HF and preserved ejection fraction (HFpEF). Subgroup analyses of the HFpEF populations suggest that certain patients benefit from HF treatments. This underlines the importance of individualized therapy regimens in HFpEF. Sodium-glucose transporter 2 (SGLT-2) inhibitors are emerging as a promising treatment of HF. The mechanisms leading to improved outcomes include 1) treatment of diabetes, 2) osmodiuresis preventing volume overload, 3) enhancement of the cardio protective Angiotensin (Ang) 1–7 pathway, instead of Ang II. We aimed to characterize patients by factors which are modified by SGLT-2 inhibitors to identify individuals who may benefit from these drugs. Methods HFpEF patients were included in a single center registry. Baseline evaluation included assessment of HbA1c, fluid status measured by body composition monitor and plasma angiotensin concentration. A “SGLT-2 score” with a maximum of 3 points was calculated using the following parameters: 1) HbA1c >6.5%, 2) overhydration, defined as a fluid overload of >1,5L and 3) plasma renin activity (PRA) levels above the median as a parameter of over-all RAS activity. Primary outcome was defined as all-cause death or HF hospitalization. All parameters used in the “SGLT-2 score” were independently predictive for the chosen endpoint. Kaplan Meier analyses was used to show the association between the score and outcomes. Results 90 patients were included in this registry. Median HbA1c was 6.0%, median fluid status was 1.2L and the median Ang II levels in the “high PRA-group” were 5.35.1 pmol/L. After a mean follow up time of 44.0±38.7 months, 60 patients (66.6%) reached the endpoint. Kaplan Meier analysis showed an association between SGLT-2 score and outcome (p=0.003). Conclusion Patients with HbA1c >6.5%, overhydration and high RAS activity have poor outcomes. We propose the future use of this score to identify a subgroup of HFpEF patients who may benefit from SGLT-2 inhibitors. Kaplan Meier analysis Funding Acknowledgement Type of funding source: None

Background Data on cardiac remodeling in athletes are conflicting and rarely available in veteran athletes. Purpose Therefore, in this study we aimed to define echocardiographic features of healthy endurance athletes older than 50 years. Methods We included probands aged >50 years, who have performed endurance sports at 70% of their maximum heart rate for at least 1 hour 3 times per week over the previous 5 years. Results Between November 2018 and May 2019, 69 probands were recruited. Median age was 57 years (IQR 52–64) and 26% were female. Groups were formed according to the median training time of 6 hours per week: (A) 45 probands with ≥6 hours (IQR 6–10) and (B) 24 probands with Global right and left ventricular (LV) strain were similar, but LA reservoir strain was higher in group A than in B (27% (IQR 22–34) vs. 20% (IQR 15–29), p=0.016). Conclusion Endurance training in healthy athletes older than 50 years does not result in relevant chamber dilatation or LV hypertrophy and a weekly training duration of ≥6 hours seems beneficial to preserve diastolic function associated with an increased LA reservoir function. Funding Acknowledgement Type of funding source: None

Background Amyloid cardiomyopathy (CA) is a life-threatening disease that arises from the accumulation of insoluble fibrous deposits of misfolded proteins in the myocardium. Infiltration of the conduction system results in a high prevalence of atrial fibrillation (AF). Due to a notable thromboembolic risk, long-term anticoagulation is preferred once AF is detected in amyloidosis. However, anticoagulation may exacerbate the hemorrhagic tendency, previously described in amyloid light-chain (AL) amyloidosis. Therefore, the potential benefits of anticoagulation must be carefully weighed against hemorrhagic complications. Methods We recorded bleeding events in a prospective cohort of CA patients. Results Out of 140 patients (median age of 73 years (IQR 62–77) and 77.1% of male gender) 65 (46.4%) were diagnosed with AL amyloidosis and 69 (49.3%) had transthyretin amyloid deposits (ATTR). Median NYHA functional class was 3 (IQR 2–3) and NT-proBNP 2574 pg/mL (1070–7173). 42.1% of patients (n=59) were treated with OAC with 13 (22.0%) receiving vitamin-K-antagonists (VKA) and 46 (78.0%) novel oral anticoagulants (NOACS). During a median follow up time of 23 months (IQR 9–35) 22 bleeding events occurred. In total, we recorded 1 cerebral bleeding, 7 gastrointestinal bleedings, 8 urogenital bleedings, 4 hematomas and 2 nasal bleedings. Of those, fifteen (68.2%) were observed in orally anticoagulated patients (p=0.198). 4 (30.8%) bleeding events occurred in the VKA treated group and 11 (23.9%) under NOAC treatment (p=0.335). Bleeding events were more prevalent in patients with AL compared to TTR amyloidosis (14, 63.6% vs 8, 36.4%, p=0.011). No difference was observed in terms of CHA2DS2-VASc score: 4 (IQR 2–5) in the bleeding group versus 3 (IQR 1–4) in the control group (p=0.579). On the contrary, HASBLED score was higher in patients with bleeding events: 4 (IQR 4–5) versus 2 (IQR 1–3) (p Conclusion Although CA is associated with potentially life-threatening hemorrhage, our cohort did not reveal a higher prevalence of fatal bleeding in patients treated with oral anticoagulation. Patients who experienced bleeding events did not show worse outcomes. Figure 1. Kaplan Meier survival estimates Funding Acknowledgement Type of funding source: None

(1) Background: Cardiac amyloidosis (CA) is a rare and complex condition with poor prognosis. While novel therapies improve outcomes, many affected individuals remain undiagnosed due to a lack of awareness among clinicians. This study was undertaken to develop an expert-independent machine learning (ML) prediction model for CA relying on routinely determined laboratory parameters. (2) Methods: In a first step, we developed baseline linear models based on logistic regression. In a second step, we used an ML algorithm based on gradient tree boosting to improve our linear prediction model, and to perform non-linear prediction. Then, we compared the performance of all diagnostic algorithms. All prediction models were developed on a training cohort, consisting of patients with proven CA (positive cases, n = 121) and amyloidosis-unrelated heart failure (HF) patients (negative cases, n = 415). Performances of all prediction models were evaluated on a separate prognostic validation cohort with 37 CA-positive and 124 CA-negative patients. (3) Results: Our best model, based on gradient-boosted ensembles of decision trees, achieved an area under the receiver operating characteristic curve (ROC AUC) score of 0.86, with sensitivity and specificity of 89.2% and 78.2%, respectively. The best linear model had an ROC AUC score of 0.75, with sensitivity and specificity of 84.6 and 71.7, respectively. (4) Conclusions: Our work demonstrates that ML makes it possible to utilize basic laboratory parameters to generate a distinct CA-related HF profile compared with CA-unrelated HF patients. This proof-of-concept study opens a potential new avenue in the diagnostic workup of CA and may assist physicians in clinical reasoning.

Objectives and background Polymer coatings of drug-eluting stents (DES) may induce allergic reactions and inflammation, resulting in late-acquired stent malapposition (LASM) with the risk of stent thrombosis. This study evaluated, if biodegradable polymer (BP) reduces the incidence of LASM compared to permanent polymer (PP) after treatment with newer generation DES. Methods and results Fifty patients with 59 lesions were randomized (2:1) to elective treatment with second generation PP-DES (n = 32, 39 stents), either Everolimus-eluting or Zotarolimus-eluting stents, or with BP-DES (Biolimus-eluting stents [BES]; n = 18, 20 stents) and underwent optical coherence tomography directly after implantation and after 1 year. After implantation acute stent malappositions (ASM) were documented in 30 stents (51%) distributed to 22 stents treated with PP-DES (56%) and 8 with BP-DES (40%; n.s.). After 1 year, late stent malappositions (LSM) were detected in 14 stents (24 %); ASM persisted (APSM) in 9 stents after one year (7 PP-DES-18%, 2 BES-10%), whereas ASM resolved in 21 stents. In addition, LASM was documented in nine stents including five stents without and four stents with additional APSM. All LASM were located in PP-DES (n = 9; 23%), none in BP-DES (P = 0.022). Compared to the reference lumen area, in-stent lumen area of stents without LASM was smaller due to neointimal hyperplasia (P = 0.021), whereas in-stent lumen area at maximum LASM of stents with LASM was larger due to positive remodeling (P = 0.002). Conclusions In conclusion the use of BP-DES reduced the occurrence of LASM due to positive remodeling compared to second generation PP-DES.

Idiopathic ventricular fibrillation (IVF) is diagnosed in up to 14% of sudden cardiac death (SCD) survivors. Early repolarization syndrome (ERS) in patients with ventricular tachyarrhythmia is characterized by an elevated J-point in inferior and/or antero-lateral leads. Our objectives were to determine the prevalence of ERS in IVF patients, and to evaluate potential differences in clinical outcome. Out of 3,552 implantable cardioverter defibrillator (ICD) carriers, 758 SCD survivors were retrospectively identified from the databases of the Medical Universities of Vienna and Innsbruck within the last three decades. Early repolarization pattern (ERP) was classified either as "notching" or "slurring". Endpoints were defined as appropriate ICD therapies for ventricular tachyarrhythmia, either anti-tachycardia pacing or shock, and all-cause mortality. After exclusion of recognized reasons for SCD, 50 patients were assigned to the diagnosis of IVF (6.6%). An ERP was identified in 10 patients, most of them with notching (n = 8). After a mean follow-up of 11.2 ± 6.7 years (539.3 patient years), appropriate ICD therapies were found in 50% of ERS and 43% of IVF patients without ERP (p = 0.732). In ERS patients, all ICD therapies were found in patients with notching pattern. Similarly, incidence of inappropriate ICD therapies, and all-cause mortality was comparable (30% vs. 23%, p = 0.707; 10% vs. 5%, p = 0.496, respectively). In 758 SCD survivors, we found a low prevalence of IVF and ERS. Similar event rates were reported concerning all-cause mortality and ICD therapies for ventricular tachyarrhythmia after long-term follow-up in this cohort.

Previous studies suggested an association between heart failure (HF) and hepatic disorders. Liver function parameters have been shown to predict outcome in HF with reduced ejection fraction, but their impact in HF with preserved ejection fraction (HFpEF) has not yet been investigated. Between January 2011 and February 2017, 274 patients with confirmed HFpEF were enrolled (age 71.3 ± 8.4 years, 69.3% female) in a prospective registry. During a median follow-up of 21.5 ± 18.6 months, 97 patients (35.4%) reached the combined endpoint defined as hospitalization due to HF and/ or death from any cause. By multivariable cox regression, serum gamma-glutamyltransferase (GT) was independently associated with outcome (Hazard Ratio (HR) 1.002, p = 0.004) along with N-terminal pro brain natriuretic peptide (HR 2.213, p = 0.001) and hemoglobin (HR 0.840, p = 0.006). Kaplan-Meier analysis showed that patients with serum gamma-GT levels above a median of 36 U/L had significantly more events as compared to the remainder of the group (log-rank p = 0.012). By multivariable logistic regression, higher early mitral inflow velocity/ mitral peak velocity of late filling (Odds Ratio (OR) 2.173, p = 0.024), higher right atrial (RA) pressure (OR 1.139, p 36 U/L. Serum levels of gamma-GT are associated with both left and right-sided cardiac alterations and may serve as a simple tool for risk prediction in HFpEF, especially when further diagnostic modalities are not available.

There is growing evidence that low levels of the circulating soluble receptor of advanced glycation end products (sRAGE) are a valuable predictor of cardiovascular disease (CVD). The aim of this prospective study was to investigate the influence of long-term physical activity on serum sRAGE levels. 109 subjects were recruited, and 98 completed the study. Participants were asked to perform exercise within the calculated training pulse for 8 months. The performance gain was measured/quantified by bicycle stress tests at the beginning and end of the observation period. sRAGE was measured at baseline and after 2/6/8 months by ELISA. Backwards, multiple linear regression analysis was performed to investigate the association of co-variables age, sex, BMI, and performance at baseline, HbA1c, and lipoprotein a with baseline sRAGE levels. We identified BMI and lipoprotein a as significant predictors for baseline sRAGE levels. Compared to subjects with a performance gain ≤ 4.9% subjects with a gain > 5% showed a significant increase in sRAGE levels up to 22%. sRAGE serum levels correlate negatively with lipoprotein a levels and BMI and long-term physical activity leads to a significant increase in serum sRAGE levels (9–22%), whereby the sRAGE increase is most pronounced in subjects with initially low-performance levels, suggesting that in particular, these subject profit the most from increased physical activity. The sport-mediated increase of sRAGE might be a sign of decreased AGE-mediated inflammation and highlight the protective effect of sports on CVD and other disease which are at least partly mediated by an increased inflammation status.Clinical trials registration NCT02097199.

Purpose To investigate whether the pulmonary artery (PA)-to-ascending aorta (Ao) ratio is associated with outcome in unselected patients referred for cardiac magnetic resonance (MR) imaging. Materials and Methods This study prospectively enrolled 650 consecutive patients (47.2% women; mean age, 56.1 years ± 17.7 [standard deviation]). Diameters of PA and Ao were measured in axial black blood images. On the basis of previous results, a PA-to-Ao ratio of 1.0 or greater was chosen as the cutoff for further analysis. Univariable and multivariable Cox regression models were used to investigate the primary end point, which was defined as a composite of cardiovascular hospitalization and death. Results A PA-to-Ao ratio of 1.0 or greater was present in 131 (20.2%) patients. Patients with a PA-to-Ao ratio of 1.0 or greater were predominantly women (P = .010); more frequently presented with atrial fibrillation (P.001), diabetes (P.001), and impaired renal function (P.001); and had higher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels (P.001), larger left (P = .023) and right ventricles (RV; P = .002), and worse RV function (P.001). Patients were followed for 17.8 months ± 12.9, during which 110 patients (16.9%) reached the primary end point. By Kaplan-Meier analysis, event-free survival was significantly worse in patients with a PA-to-Ao ratio of 1.0 or greater (log-rank test, P.001). A PA-to-Ao ratio of 1.0 or greater was independently associated with outcome by multivariable Cox regression analysis, in addition to age, NT-proBNP serum levels, and RV size. Conclusion A PA-to-Ao ratio of 1.0 or greater identified patients at risk, most likely because of elevated PA pressures. On the basis of these results, the PA-to-Ao ratio should routinely be reported at cardiac MR imaging.

Most heart failure with preserved ejection fraction (HFpEF) patients, at some point, present to an emergency department with typical symptoms of volume overload. Clinically, most respond well to standard diuretic therapy, sometimes at the cost of renal function. The study sought to define the prognostic significance of fluid status versus renal function in patients with HFpEF.One hundred sixty-two consecutive patients with HFpEF were enrolled in our prospective registry. Twelve patients with clinically overt decompensation were excluded. Fluid status at baseline was determined by bioelectrical impedance spectroscopy. The primary outcome measure was a combined end point consisting of hospitalization for heart failure and/or death for cardiac reason.Mean age was 74.4±8.4years. Ninety-one (61%) patients were hypo- or normovolemic (relative fluid overload [Rel. FO] -0.7±5.7%) while 59 (39%) patients presented with fluid overload (Rel. FO 11.5±2.7%). During a median follow-up of 24.3months (interquartile range: 19.8-33.2), 34% of patients reached the combined end point. Multivariate Cox hazard analysis identified fluid overload (hazard ratio: 3.09; 95% confidence interval: 1.68-5.68; p0.001) as an independent predictor of adverse outcome. Patients with fluid overload and normal renal function showed a worse event-free survival compared to the subgroup with normohydration and impaired renal function (log-rank: p=0.042).HFpEF patients with measurable fluid overload face a dismal prognosis as compared to euvolemic patients. Our data, while preliminary, suggest that patients with fluid overload may face a better outcome under continued fluid removal irrespective of changes in eGFR.

Background and aim Automated image recognition based on machine learning methods was proven to be feasible in several medical imaging applications recently. Beside image classification methods to categorize input images for example into healthy or suspicious, image segmentation allows accurate localization of pathologies and thereby facilitates a wide area of applications. Because of the unique composition of every machine learning problem the applicability of image segmentation methods for detecting coronary pathologies in optical coherence tomography images remains unclear. Furthermore, the prediction accuracy of deep learning methods usually depends on vast amounts of training data which are often not available for particular medical questions. Therefore special strategies need to be applied to achieve satisfying results with smaller training datasets. We aimed to investigate the applicability of machine learning methods for plaque detection in coronary OCT images, especially considering the challenge of a small training dataset. Methods Originating from a dataset of 104 OCT frames containing calcified plaques, we performed image preprocessing using a custom build OCT image processing software to crop the luminal part as well as the areas outside the circular OCT signal to reduce entropy. Furthermore, plaques were identified and marked by an experienced OCT analyst, drawing plaque-enclosing polygonal masks using the same software. We also performed common image augmentation strategies, primarily applying rotation and zoom operations. Subsequently, we split the samples randomly into training, validation and test datasets (80:10:10%). To train the segmentation model, we fed the training and validation samples into an U-Net Convolutional Neuronal Network implementation with domain-specific adaptions using the RMSprop optimizer based on the publicly available PyTorch library. Results After 50 training epochs, we could achieve a prediction accuracy of 74.4% with the current configuration measured by the Sørensen–Dice coefficient comparing the similarity of the predicted plaque masks with the ground truth samples (figure 1 illustrates an exemplary comparison between predicted and ground truth plaque masks). Exemplary projection of a predicted mask Conclusion We were able to show that image segmentation based on machine learning strategies is a feasible way for automated plaque detection in coronary OCT imaging even based on small training datasets. Larger training datasets are necessary to raise prediction accuracy.

Aims Lipoprotein(a) [Lp(a)] is associated with coronary artery disease in population studies, however studies on its predictive value in patients with established cardiovascular disease, in particular after acute coronary syndromes (ACS), are conflicting. The aim of this study was to investigate whether Lp(a) is associated with survival after ACS. Methods and results We analyzed 4469 consecutive patients that underwent coronary angiography for ACS. Lp(a) measurement at time of ACS was available in 1245 patients and median follow-up for cardiovascular and total mortality was 5.0 (IQR 3.2–8.0) years. 655 (52.6%) presented with ST-segment elevation myocardial infarction (STEMI), 424 (34.1%) with Non-ST-segment elevation myocardial infarction (NSTEMI) and 166 (13.3%) underwent coronary angiography for unstable angina. Cardiovascular mortality was 9.1% and total mortality was 15.7%. Patients were stratified into four groups to their Lp(a) levels. (≤15 mg/dL, >15–30 mg/dL, >30–60 mg/dL, and >60 mg/dL). Multivessel disease was significantly more common in patients with Lp(a) >60 mg/dL (p Central Figure Conclusion Lp(a) levels at time of ACS were neither associated with cardiovascular nor with total mortality. Although Lp(a) has been shown to be associated with incidence of coronary artery disease, this study does not support any role of Lp(a) as a risk factor after ACS. This should be taken into account for development of outcome studies for agents targeting Lp(a) plasma levels.

Background/Introduction Cardiac amyloidosis (CA) is a rare and complex condition with poor prognosis. Novel therapies have been shown to improve outcome, however, most of the affected individuals remain undiagnosed, mainly due to a lack in awareness among clinicians. One approach to overcome this issue is to use automated diagnostic algorithms that act based on routinely available laboratory results. Purpose We tested the performance of flexible machine learning and traditional statistical prediction models for non-invasive CA diagnosis based on routinely collected laboratory parameters. Since laboratory routines vary between hospitals or other health care providers, special attention has been taken to adaptive and dynamic parameter selection, and to dealing with the frequent occurrence of missing values. Methods Our cohort consisted of 376 clinically accepted patients with various types of heart failure. Of these, 69 were diagnosed with CA via endomyocardial biopsy (positives), and 307 had unrelated cardiac disorders (negatives). A total of 63 routine laboratory parameters were collected from these patients, with a high incidence of missing values (on average 60% of patients for each parameter). We tested the performance of two prediction models: logistic regression, and extreme gradient boosting with regression trees. To deal with missing values we adopted two strategies: a) finding an optimal overlap of parameters and deleting all patients with missing values (reduction of parameters and samples), and b) retaining all features and imputing missing values with parameter-wise means. To fairly assess the performance of prediction models we employed a 10-fold cross validation (stratified to preserve sample class ratio). Finally, area under curve for receiver-operator characteristic (ROC AUC) was used as our final performance measure. Results A complex machine learning model based on forests of regression trees proved to be the most performant (ROC AUC 0.94±4%) and robust to missing values. The best regression model was obtained with the 25 most frequent variables and patient deletion in case of missing values (ROC AUC 0.82±0.8%). While progressive inclusion of predictor variables worsened the performance of the logistic regression, it increased that of the machine learning approach. Conclusions Extreme gradient boosting of regression trees by routine laboratory parameters achieved staggering accuracy results for the automated diagnosis of CA. Our data suggest that implementations of such algorithms as independent interpreters of routine laboratory results may help to establish or suggest the diagnosis of CA in patients with heart failure symptoms, even in the absence of specialized experts.

Aims. Two thirds of patients with heart failure and preserved ejection fraction (HFpEF) have an indication for oral anticoagulation (OAC) to prevent thromboembolic events. However, evidence regarding the safety of OAC in HFpEF is limited. Therefore, our aim was to describe bleeding events and to find predictors of bleeding in a large HFpEF cohort. Methods and Results. We recorded bleeding events in a prospective HFpEF cohort. Out of 328 patients (median age 71 years (interquartile range (IQR) 67&ndash, 77)), 64.6% (n = 212) were treated with OAC. Of those, 65.1% (n = 138) received vitamin-K-antagonists (VKA) and 34.9% (n = 72) non-vitamin K oral anticoagulants (NOACs). During a median follow-up time of 42 (IQR 17&ndash, 63) months, a total of 54 bleeding events occurred. Patients on OAC experienced more bleeding events (n = 49 (23.1%) versus n = 5 (4.3%), p &lt, 0.001). Major drivers of events were gastrointestinal (GI) bleeding (n = 18 (36.7%)]. HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly) score (hazard ratios (HR) of 2.15 (95% confidence interval (CI) 1.65&ndash, 2.79, p &lt, 0.001)) was the strongest independent predictor for overall bleeding. In the subgroup of GI bleeding, mean right atrial pressure (mRAP: HR of 1.13 (95% CI 1.03&ndash, 1.25, p = 0.013)) and HAS-BLED score (HR of 1.74 (95% CI 1.15&ndash, 2.64, p = 0.009)] remained significantly associatiated with bleeding events after adjustment. mRAP provided additional prognostic value beyond the HAS-BLED score with an improvement from 0.63 to 0.71 (95% CI 0.58&ndash, 0.84, p for comparison 0.032), by C-statistic. This additional prognostic value was confirmed by significant improvements in net reclassification index (61.3%, p = 0.019) and integrated discrimination improvement (3.4%, p = 0.015). Conclusion. OAC-treated HFpEF patients are at high risk of GI bleeding. High mRAP as an indicator of advanced stage of disease was predictive for GI bleeding events and provided additional risk stratification information beyond that obtained by HAS-BLED score.

Background: Reduced left ventricular function (LVF) is a predictor for stent-thrombosis. In advanced heart failure (characterized by high NT-proBNP) with an activated coagulation system, coronary events clinically perceived as sudden death or death from heart failure may be more common in patients treated by percutaneous coronary intervention (PCI) than in patients treated by coronary artery bypass grafting (CABG). Our study analyses (1) if patients with reduced LVF who require coronary revascularization will have a better survival benefit with CABG or PCI, and (2) if the survival benefit is predicted by NT-proBNP. Methods: This observational retrospective study included patients from the coronary catheter laboratory database of the Medical University of Vienna (CCLD-MUW). Multivariate Cox regression analyses were performed to test the hypothesis that there is an interaction in the risk of death between those with lower or elevated NT-proBNP levels and the revascularization procedure (PCI or CABG). The relative risk of PCI compared to CABG as reference was calculated for patients with low and elevated NT-proBNP levels. Results: In the entire study population with 398 patients (340 PCI and 58 CABG) the revascularization procedure had no predictive value. When the revascularization procedure*NTproBNP interaction was forced into the Cox regression model, this term was an independent predictor of death. The relative risk of PCI compared to CABG was similar in patients with lower NT-proBNP&mdash, 1.01 (95% confidence interval (CI), 0.45&ndash, 2.24), but was significantly increased in patients with elevated NT-proBNP&mdash, 1.58 (95% CI, 1.07&ndash, 2.33). Conclusion: Death is associated to the revascularization procedure, but only in those patients with elevated NT-proBNP levels. NT-proBNP is a predicting factor for the revascularization procedure: elevated levels showed an increased risk of death after PCI compared to CABG, whereas lower levels were associated with a similar risk after both revascularization procedures.

Aims Accumulation of extracellular matrix (ECM) is known to play a crucial role in the pathophysiology of heart failure (HF). However, its prognostic relevance is poorly investigated. Methods and results A total of 73 HF patients who underwent LV endomyocardial biopsy were enrolled in our study. ECM area was quantified by TissueFAXS and ImageJ software. Patients were followed-up at 6-month intervals. The study endpoint was defined as hospitalization for a cardiac reason and/or cardiac death. Furthermore, the influence of the ECM on invasively measured haemodynamic parameters was tested. During a median follow-up period of 9.0 months, 34 patients (46.6%) reached the combined endpoint. Median ECM area was 30.5%. Patients with ECM area ≥30.5% experienced significantly more events (67.6% vs. 25.0%, P < 0.001) in comparison with patients with an ECM area

Die koronare Herzkrankheit (KHK; Synonym: coronary artery disease – CAD; stable ischemic heart disease – SIHD) ist definiert als Manifestation der arteriellen Verschlusskrankheit in den Herzkranzgefasen. Durch den Prozess der Arteriosklerose kommt es zur Bildung sogenannter Plaques, wodurch es zur Einengung des Gefaslumens kommt. Dies hat eine Minderdurchblutung des Herzmuskels zur Folge und fuhrt zu einem in Relation zum Sauerstoffverbrauch verminderten Sauerstoffangebot der Herzmuskelzelle. Man unterscheidet zwischen einer stabilen KHK, welche typischerweise durch das Leitsymptom der Angina pectoris (AP) charakterisiert ist, und der instabilen KHK, welche als akutes koronares Syndrom (Abb. 1) bezeichnet wird und den akuten Myokardinfarkt (ST-Elevations-Infarkt: STEMI, nicht-ST-Elevations-Infarkt: NSTEMI) bis zur instabilen Angina pectoris inkludiert. Open image in new window Abb. 1 Akutes Koronarsyndrom. (Kuch B. et al. J Kardiologie. 2003;10(3):103–6) Koronare Herzkrankheit: Erkrankung der arteriosklerotisch veranderten Koronargefase In der folgenden Ubersicht soll die stabile KHK abgehandelt werden. Es wird in der folgenden Ubersicht immer wieder auf Guidelines bzw. Klassen der Empfehlung und Evidenzlevels von diagnostischen Hilfsmitteln, Interventionen und Therapien eingegangen. Hier eine kurze Beschreibung: Klasse I: wird empfohlen Klasse IIa: Evidenz und Expertenmeinung widerspruchlich, Sachlage spricht aber eher fur Nutzen und Wirksamkeit Klasse IIb: wird eher nicht empfohlen Klasse III: wird nicht empfohlen, moglicherweise schadlich Evidenzlevel A: Daten aus mehreren randomisierten, klinischen Studien Evidenzlevel B: Daten aus einer einzigen randomisierten, klinischen Studie Evidenzlevel C: Expertenmeinung, Fallstudien, retrospektive Studien

Subcutaneous implantable cardioverter-defibrillators (S-ICD) are an innovative and less invasive alternative to transvenous ICD (TV-ICD) in selected patients. We aimed to investigate the underlying diseases and the specific indications for implanting S-ICD in clinical practice, as well as the prevalence of shock delivery and complications.From December 2012, data of 236 patients (30,5% female; age 48,6±16,8years) were gathered from 12 centres in Austria. Follow-up data over a period of 1,7±1,1years were available for 231 patients (in total 359,2 patient-years). Predominant underlying diseases were ischemic cardiomyopathy (iCMP; 32,0%), idiopathic ventricular fibrillation (22,6%) and dilated cardiomyopathy (dCMP; 17,3%). The most frequent indications for implantation were sudden cardiac death survival (27,4%), primary prevention for iCMP (23,9%) and for dCMP (12,8%), and previous explantation of TV-ICD (12,4%). Appropriate shocks were documented in 16 patients (6,9%), iCMP being the predominant underlying disease. Arrhythmia conversion was successful in all patients, efficacy of the first shock was 96%. Inappropriate shock rate was 5,2%, predominantly caused by oversensing of T wave or artefacts. A device upgrade to an ICD system with pacing function was necessary in1%. Clinical complications needing surgical revision occurred in 8 patients (3,5%).S-ICD were mostly implanted for primary prevention, one fourth of our cases were sudden death survivors. Clinical and functional complication rate was relatively low. In conclusion, S-ICD is a safe and efficient alternative in a larger population of ICD candidates, when no cardiac pacing is needed. EC-number: C-136-17.

INTRODUCTION Since proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were introduced to the market, the interest in PCSK9 metabolism has increased dramatically. OBJECTIVES We investigated prospectively the influence of long-term physical activity on PCSK9, highand low-density lipoprotein cholesterol (HDL-C and LDL-C, respectively), and lipoprotein(a) levels [Lp(a)]. PATIENTS AND METHODS A total of 109 participants were recruited and instructed to increase their sport pensum by 75 min/wk of vigorous-intensity or 150 min/wk of moderate-intensity endurance training (or a mixture) within the calculated training pulse for 8 months. Stress tests were performed at baseline and at the end of the study to prove and quantify the performance gain. PCSK9 levels were measured at baseline and after 2, 6, and 8 months by an enzyme-linked immunosorbent assay. HDL-C, LDL-C, and Lp(a) levels were measured at baseline and every 2 months. RESULTS The final study sample included 79 subjects, who showed a mean performance gain of 11.4%. Mean (SD) PCSK9 and HDL-C levels increased significantly from 224.7 (66.8) ng/ml to 243.4 (84.0) ng/ml (P = 0.04) and 58.3 (18.4) mg/dl to 61.1 (18.5) mg/dl (P = 0.014), respectively. Mean (SD) LDL-C levels decreased significantly from 115.0 (33.4) mg/dl to 109.8 (31.7) mg/dl (P = 0.04), but there was no significant change in mean (SD) Lp(a) levels: 37.9 (51.9) nmol/l to 43.3 (60.6) nmol/l; P = 0.218. CONCLUSIONS Our study showed a decrease in LDL-C levels induced by a long-term physical activity with a simultaneous increase in PCSK9 levels. PCSK9 is essential in lipid metabolism and should not be basically considered as harmful. It is possible that a certain amount of PCSK9 is beneficial to ensure an adequate lipid supply.

INTRODUCTION Since proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were introduced to the market, the interest in PCSK9 metabolism has increased dramatically. OBJECTIVES We investigated prospectively the influence of long-term physical activity on PCSK9, highand low-density lipoprotein cholesterol (HDL-C and LDL-C, respectively), and lipoprotein(a) levels [Lp(a)]. PATIENTS AND METHODS A total of 109 participants were recruited and instructed to increase their sport pensum by 75 min/wk of vigorous-intensity or 150 min/wk of moderate-intensity endurance training (or a mixture) within the calculated training pulse for 8 months. Stress tests were performed at baseline and at the end of the study to prove and quantify the performance gain. PCSK9 levels were measured at baseline and after 2, 6, and 8 months by an enzyme-linked immunosorbent assay. HDL-C, LDL-C, and Lp(a) levels were measured at baseline and every 2 months. RESULTS The final study sample included 79 subjects, who showed a mean performance gain of 11.4%. Mean (SD) PCSK9 and HDL-C levels increased significantly from 224.7 (66.8) ng/ml to 243.4 (84.0) ng/ml (P = 0.04) and 58.3 (18.4) mg/dl to 61.1 (18.5) mg/dl (P = 0.014), respectively. Mean (SD) LDL-C levels decreased significantly from 115.0 (33.4) mg/dl to 109.8 (31.7) mg/dl (P = 0.04), but there was no significant change in mean (SD) Lp(a) levels: 37.9 (51.9) nmol/l to 43.3 (60.6) nmol/l; P = 0.218. CONCLUSIONS Our study showed a decrease in LDL-C levels induced by a long-term physical activity with a simultaneous increase in PCSK9 levels. PCSK9 is essential in lipid metabolism and should not be basically considered as harmful. It is possible that a certain amount of PCSK9 is beneficial to ensure an adequate lipid supply.

Two thirds of patients with heart failure and preserved ejection fraction (HFpEF) suffer from atrial fibrillation (AF). However, current evidence regarding safety of OAC in HFpEF is limited. We recorded bleeding events in a prospective HFpEF cohort over 8 years. Out of 328 patients (median age 71

Approximately 50% of patients presenting with clinical signs of heart failure are diagnosed with heart failure with preserved ejection fraction (HFpEF) [(1)][1]. Pulmonary hypertension (PH) is a common feature of HFpEF and predicts poor outcome. According to the diastolic pressure gradient (DPG)

Background Recent studies suggest that reduced right ventricular function is an important predictor of outcome in patients with heart failure and preserved ejection fraction (HFpEF). Because affected patients suffer from a broad spectrum of non-cardiac co-morbidities, it remains unclear, whether they actually die from right heart failure (RHF) or as a consequence of other conditions. Methods Consecutive patients with a confirmed diagnosis of HFpEF were enrolled in this prospective registry. Local and external medical records, as well as telephone interviews with relatives were used to ascertain modes of death. RHF was accepted as a mode of death, if the following criteria were met: 1. right ventricular dysfunction assessed by transthoracic echocardiography, and 2. clinical signs of right heart decompensation at the time of death. Results Out of 230 patients with complete follow-up, 16.5% ( n =38) died after a mean of 30±17months. 60.5% deaths were classified as cardiovascular and 34.2% as non-cardiovascular. In 5.3% patients, the reason for death remained unknown. Of the cardiovascular cases ( n =23), 91.4% of deaths were attributed to RHF, 4.3% died from stroke and 4.3% from sudden cardiac death. Of the non-cardiovascular deaths ( n =13), 46.2% of deaths were attributed to major infections and 38.4% deaths were related to cancer. Other reasons for death included ileus (7.7%) and major bleeding (7.7%). Conclusion In our well-characterised HFpEF cohort, more than half of all deaths could directly be attributed to RHF. The right ventricle seems to be a meaningful therapeutic target in a subset of patients.

Background Everolimus-eluting bioresorbable vascular scaffolds (BVS) represent an innovative treatment option for coronary artery disease. Clinical and angiographic results seem promising, however, data on its immediate procedural performance are still scarce. The aim of our study was to assess the mechanical properties of BVS by Optical Coherence Tomography (OCT) in clinical routine. Methods Post-implantation OCT images of 40 BVS were retrospectively compared to those of 40 metallic everolimus-eluting stents (EES). Post-procedural device related morphological features were assessed. This included incidences of gross underexpansion and the stent eccentricity index (SEI, minimum/maximum diameter) as a measure for focal radial strength. Results Patients receiving BVS were younger than those with EES (54.0 ± 11.2 years versus 61.7 ± 11.4 years, p = 0.012), the remaining baseline, vessel and lesion characteristics were comparable between groups. Lesion pre-dilatation was more frequently performed and inflation time was longer in the BVS than in the EES group (n = 34 versus n = 23, p = 0.006 and 44.2 ± 12.8 versus 25.6 ± 8.4 seconds, p

Patients with heart failure with preserved ejection fraction have functional impairment resulting in reduced quality of life. Specific pathological mechanisms underlying symptoms have not yet been defined.The aim of this study was to identify hemodynamic and other patient-related variables that are associated with New York Heart Association (NYHA) functional class and to analyze functional class in perspective with other clinical, laboratory, imaging, and hemodynamic parameters with respect to its influence on outcomes.Between January 2011 and February 2015, 193 patients with confirmed heart failure with preserved ejection fraction were enrolled.Those in more advanced NYHA functional classes (III and IV; n = 136) were older (p = 0.008), had higher body mass indexes (p = 0.004), and had higher levels of N-terminal pro-brain natriuretic peptide (p = 0.001) compared with less symptomatic patients (NYHA class II; n = 57). Furthermore, parameters reflecting left ventricular diastolic dysfunction were more pronounced in advanced NYHA classes (early mitral inflow velocity/early diastolic mitral annular velocity; p = 0.023) as well as parameters reflecting right ventricular afterload (diastolic pulmonary artery pressure; p 0.001). By multivariate regression analysis, age (p = 0.007), body mass index (p = 0.002), N-terminal pro-brain natriuretic peptide (p 0.001), early mitral inflow velocity/mitral peak velocity of late filling (p = 0.031), and diastolic pulmonary artery pressure (p 0.001) were independently associated with advanced NYHA class. After 21.9 months of follow-up, 64 patients (33.2%) reached the combined endpoint, defined as hospitalization for heart failure and/or cardiac death. By multivariate Cox analysis, NYHA functional class was independently associated with outcome (hazard ratio: 2.133; p = 0.040), as well as N-terminal pro-brain natriuretic peptide (hazard ratio: 1.655; p 0.001) and impaired right ventricular function (hazard ratio: 2.360; p = 0.001).Symptoms of breathlessness in patients with heart failure with preserved ejection fraction are multifactorial and largely related to body mass index, left ventricular diastolic function, and the pulmonary vasculature. Clinically meaningful therapeutic interventions should target body weight, left ventricular stiffness, and concomitant pulmonary vascular disease.