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SummaryThe prevalence and significance of cardiac amyloidosis have been considerably underestimated in the past; however, the number of patients diagnosed with cardiac amyloidosis has increased significantly recently due to growing awareness of the disease, improved diagnostic capabilities and demographic trends. Specific therapies that improve patient prognosis have become available for certain types of cardiac amyloidosis. Thus, the earliest possible referral of patients with suspicion of cardiac amyloidosis to an experienced center is crucial to ensure rapid diagnosis, early initiation of treatment, and structured patient care. This requires intensive collaboration across several disciplines, and between resident physicians and specialized centers. The aim of this consensus statement is to provide guidance for the rapid and efficient diagnosis and treatment of light-chain amyloidosis and transthyretin amyloidosis, which are the most common forms of cardiac amyloidosis.

Background In heart failure with preserved ejection fraction (HFpEF), echocardiographic studies suggest that global longitudinal strain (GLS) has an impact on survival. Feature-tracking cardiovascular MRI also allows for strain analysis; however, to the knowledge of the authors, little is known about its prognostic value and whether it reflects severity of diffuse fibrosis, as assessed by cardiovascular MRI T1 mapping. Purpose To investigate the association between myocardial strain at cardiovascular MRI with extracellular volume by T1 mapping and outcome in participants with HFpEF. Materials and Methods In this secondary analysis of a prospective study (NCT03405987), consecutive participants with HFpEF underwent cardiovascular MRI between July 2012 and March 2018, including T1 mapping and three-dimensional strain analysis. Extracellular volume and strain results were assessed to determine if there was a correlation between these two factors. Cox regression was performed to determine the prognostic relevance of MRI-derived myocardial strain for a combined end point (events) of heart failure hospitalizations and cardiovascular death. Results In total, 206 consecutive participants with HFpEF (mean age, 71 years ± 8 [standard deviation]; 69% women) were included. Median myocardial global longitudinal strain (GLS) at MRI was -8.5% and showed low correlation with extracellular volume (r = 0.28; P = .003). A total of 109 events (53%) were recorded during a follow-up of 38 months ± 29. Participants with a GLS above the median had higher event rates (log-rank test, P < .001). By multivariable Cox regression analysis, GLS remained independently associated with outcome (hazard ratio, 1.06 per 1% strain increase; 95% confidence interval: 1.01, 1.11; P = .03) when corrected for risk factors including age, diabetes, renal function, N-terminal pro-b-type natriuretic peptide serum concentration, and right ventricular size and function. Conclusion In participants with heart failure with preserved ejection fraction, global longitudinal strain at cardiovascular MRI was correlated with extracellular volume by T1 mapping and was associated with cardiovascular events. © RSNA, 2020 Online supplemental material is available for this article.

The percutaneous coronary intervention (PCI) for chronic total occlusions (CTO) remains debated. Therefore the aim of this large-scale observational multi-center registry was to compare the long-term outcome of CTO patients undergoing different therapeutic approaches comparing successful CTO revascularization either by PCI or coronary artery bypass graft (CABG), failed CTO-PCI and optimal medical therapy (OMT) alone.A total of 6630 CTO patients were enrolled from two high-volume centers to compare different treatment strategies. All procedures were performed by high-volume CTO operators in tertiary university hospital. Successful CTO-PCI was performed in 3906 patients, failed CTO-PCI in 1479 patients, 412 patients underwent CABG surgery and 833 patients were treated with OMT. During the 5-year follow-up period, 1019 (15%) patients died. Kaplan-Meier analysis unveiled a significantly improved long-term outcome for CTO patients undergoing revascularization either by PCI or by CABG compared to patients with failed CTO-PCI or OMT alone (log-rank P 0.001). In the multivariate Cox-regression analysis successful CTO-PCI was associated with significantly improved long-term outcome compared to patients under OMT (adj. HR 0.39, 95%CI 0.33-0.45, P 0.001) or CABG (adj. HR 0.68, 95%CI 0.53-0.86, P = 0.002) independent of clinical confounders encompassing age, BMI, diabetes, kidney function and left ventricular function.This study showed an improved long-term outcome for CTO revascularization compared to optimal medical therapy, independent from revascularization mode, with the highest survival rate in patients undergoing successful CTO-PCI.

Aims Concomitant cardiac amyloidosis (CA) in severe aortic stenosis (AS) is difficult to recognize, since both conditions are associated with concentric left ventricular thickening. We aimed to assess type, frequency, screening parameters, and prognostic implications of CA in AS. Methods and results A total of 191 consecutive AS patients (81.2 ± 7.4 years; 50.3% female) scheduled for transcatheter aortic valve replacement (TAVR) were prospectively enrolled. Overall, 81.7% underwent complete assessment including echocardiography with strain analysis, electrocardiography (ECG), cardiac magnetic resonance imaging (CMR), 99mTc‐DPD scintigraphy, serum and urine free light chain measurement, and myocardial biopsy in immunoglobulin light chain (AL)‐CA. Voltage/mass ratio (VMR; Sokolow–Lyon index on ECG/left ventricular mass index) and stroke volume index (SVi) were tested as screening parameters. Receiver operating characteristic curve, binary logistic regression, and Kaplan–Meier curve analyses were performed. CA was found in 8.4% of patients (n = 16); 15 had transthyretin (TTR)‐CA and one AL‐CA. While global longitudinal strain by echo did not reliably differentiate AS from CA‐AS [area under the curve (AUC) 0.643], VMR as well as SVi showed good discriminative power (AUC 0.770 and 0.773, respectively), which was comparable to extracellular volume by CMR (AUC 0.756). Also, VMR and SVi were independently associated with CA by multivariate logistic regression analysis (P = 0.016 and P = 0.027, respectively). CA did not significantly affect survival 15.3 ± 7.9 months after TAVR (P = 0.972). Conclusion Both TTR‐ and AL‐CA can accompany severe AS. Parameters solely based on ECG and echocardiography allow for the identification of the majority of CA‐AS. In the present cohort, CA did not significantly worsen prognosis 15.3 months after TAVR.

Objectives The aim of the present long-term study was to assess the incidence and mode of valve hemodynamic deterioration (VHD) of bioprosthetic aortic valves, as well as associated factors. Background Modern definitions of bioprosthetic valve deterioration recommend the use of echocardiography for the assessment of transprosthetic gradients and valvular regurgitation. Methods A total of 466 consecutive patients (mean age 73.5 ± 7.5 years, 56.0% women) underwent surgical bioprosthetic aortic valve replacement between 1994 and 2014. Clinical assessment, transthoracic echocardiography, and laboratory testing were performed at baseline and follow-up. VHD was defined as mean transprosthetic gradient ≥30 mm Hg and/or at least moderate valvular regurgitation on echocardiography. Patient-prosthesis mismatch was defined as an effective orifice area indexed to body surface area ≤0.8 cm2/m2. Results Patients were followed for a median of 112.3 months (interquartile range: 57.7 to 147.7 months). Among patients with complete follow-up (n = 383), 70 subjects (18.3%; 4.8% per valve-year) developed VHD after a median of 32.4 months (interquartile range: 12.9 to 87.2 months; stenosis, n = 45; regurgitation, n = 16; both, n = 9). Factors associated with VHD by multivariate regression analysis were serum creatinine >2.1 mg/dl (hazard ratio [HR]: 4.143; 95% confidence interval [CI]: 1.740 to 9.866; p = 0.001), porcine tissue valves (HR: 2.241; 95% CI: 1.356 to 3.706; p = 0.002), arterial hypertension (HR: 3.022; 95% CI: 1.424 to 6.410; p = 0.004), and patient-prosthesis mismatch (HR: 1.931; 95% CI: 1.102 to 3.384; p = 0.022). By Kaplan-Meier analysis, elderly subjects showed faster development of VHD (age 80 years, 100.3 months [95% CI: 63.6 to 136.9 months]; p = 0.023). By multivariate Cox regression, age, diabetes, concomitant coronary artery bypass grafting, creatinine, and VHD (p Conclusions On the basis of echocardiography, every fifth patient developed VHD after surgical bioprosthetic heart valve replacement. VHD was associated with renal impairment, the use of porcine tissue valves, arterial hypertension, and patient-prosthesis mismatch. Patients younger than 70 years were not affected by faster VHD.

Background Left atrial (LA) function is related with outcome in heart failure with preserved ejection fraction (HFpEF). However, how LA function contributes to outcome in the context of atrial fibrillation (AF) versus sinus rhythm (SR) remains unclear. Purpose To determine the prognostic impact of LA size and phasic function in patients with HFpEF in SR vs. AF. Methods We enrolled consecutive HFpEF patients and assessed indexed LA volumes (LAVi) and emptying fractions (LA-EF) on cardiac magnetic resonance (CMR) imaging. We prospectively followed patients and used Cox regression models to determine the association of LA size and function with a composite endpoint of heart failure hospitalization and cardiovascular death. Results A total of 188 patients (71% female, 70±8 y/o) were included of whom 92 (49%) were in persistent AF (Figure 1A). Patients in persistent AF were older (p=0.017) and had a worse NYHA functional class (p=0.003). Compared to SR, peak and minimal LAVi were increased and LA-EF impaired (each p A total of 65 patients reached the combined endpoint during a follow-up of 31 (9–57) months. Multivariate Cox regression adjusted for established risk factors revealed that LA-EF was significantly associated with outcome in patients in SR (adj.HR 2.14; 95% CI [1.32–3.47] per 1-SD decline, p=0.002). In persistent AF, however, no LA imaging parameter was related to outcome (Figure 1B). By receiver operating characteristic curve and restricted cubic spline- analyses, we identified an LA-EF ≥40% as best indicator for favorable outcomes in patients with HFpEF and SR (Figure 2B). Persistent AF carried a similar risk for adverse outcome compared to impaired LA-EF ( Conclusions In HFpEF patients in SR, impaired LA-EF is independently associated with worse cardiovascular outcome, which is similar to persistent AF. With disease progression including development of persistent AF, LA parameters lose their prognostic ability and thus, are not helpful for further risk stratification. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Patients with transthyretin cardiac amyloidosis (TTR CA) suffer from impaired exercise capacity, have a poor quality of life (QoL), and approved treatments are lacking. Stimulators of the soluble guanylate cyclase are promising new pharmaceuticals in the treatment armamentarium of heart failure patients. The aim of the present study was to report on the safety and efficacy of riociguat administration in patients with TTR CA. TTR CA patients received riociguat for 4–6 months within the frames of a national named patient use (NPU) program. Parameters of interest included changes in submaximal exercise capacity, invasive hemodynamic parameters, and QoL. Between March 2012 and June 2017, 86 CA patients were screened for the NPU program, of whom 13 TTR CA patients were eligible for participation. In our study cohort, riociguat had an acceptable tolerability profile. At follow-up, we could detect slight improvements in median 6-min walk distance (396 m [interquartile range (IQR) = 340–518] vs. 400 m [IQR = 350–570], P = 0.045), New York Heart Association class ≥ III (n = 7 [53.9%] vs. n = 0 [0.0%], P = 0.031), cardiac output (4.3 L/min [IQR = 3.9–5.1] vs. 4.5 L/min [IQR = 4.2–5.1], P = 0.022), diastolic pressure gradient (1.0 mmHg [IQR = −1.5–3.0) vs. −1.0 mmHg [IQR = −3.0–1.0], P = 0.049), and QoL (50.0% [IQR = 40.0–58.0] vs. 60.0% [IQR = 50.0–75.0], P = 0.021). Pulmonary arterial pressures were not altered. The present case series of TTR CA patients indicates that riociguat administration was safe and associated with minor clinical as well as hemodynamic improvements.

Aims Increased afterload to the right ventricle (RV) has been shown to induce myocardial fibrosis at the RV insertion points (RVIPs). Such changes can be discrete but potentially detected by cardiac magnetic resonance (CMR) T1-mapping. Whether RVIP fibrosis is associated with prognosis in heart failure with preserved ejection fraction (HFpEF) is unknown. Methods and results We prospectively investigated 167 consecutive HFpEF patients, a population frequently suffering from post-capillary pulmonary hypertension, who underwent CMR including T1-mapping. About 92.8% also underwent right heart catheterization for haemodynamic assessment. Native T1 times were 995 ± 73 ms at the anterior and 1040 ± 90 ms at the inferior RVIP. By Spearman’s rank order testing, RVIP T1 times were significantly correlated with pulmonary artery pressure (mean PAP, r = 0.313 and 0.311 for anterior and inferior RVIP), pulmonary artery wedge pressure (r = 0.301 and 0.251) and right atrial pressure (r = 0.245 and 0.185; P for all Conclusion Interstitial expansion of the anterior RVIP as detected by CMR T1-mapping reflects haemodynamic alterations, and is independently related with prognosis in HFpEF.

The renin-angiotensin system plays an important role in the development and progression of heart failure (HF). In addition to the classical renin-angiotensin pathway, an alternative pathway produces Angs (angiotensins), which counteract the negative effects of Ang II. We hypothesized that Ang profiling could provide insights into the pathogenesis and prognosis of HF with preserved ejection fraction. We aimed to investigate the effects of Angs on outcome in HF with preserved ejection fraction. Consecutive patients were included into a prospective single-center registry. Clinical, laboratory, and imaging parameters were assessed and serum samples were taken at baseline and measured by mass spectroscopy. Serum equilibrium levels were analyzed in regard to the combined clinical end point of cardiovascular death or HF hospitalization. In total, 155 patients were included during a median follow-up time of 22.5 (interquartile range, 4.0–61.0) months, 52 individuals (34%) reached the combined end point. We identified higher levels of Ang 1–7 and Ang 1–5 as predictors for poor outcome. After adjusting for potential confounding factors, Ang 1–5 remained predictive for poor outcome. In addition to Ang 1–7 and Ang 1–5, the novel ACE (angiotensin-converting enzyme) independent Ang composite marker [Ang 1–7+Ang 1–5] was shown to predict adverse events. We conclude that Angs of the alternative renin-angiotensin system seem to play a role in HF with preserved ejection fraction and are linked to outcome in patients with HF and preserved ejection fraction. Ang 1–5 and the alternative renin-angiotensin system composite marker [Ang 1–7+Ang 1–5] are independent predictors of outcome.

Objectives This study investigated the diagnostic and prognostic value of cardiac magnetic resonance (CMR) imaging in chronic aortic regurgitation (AR). Background Accurate quantification of AR severity by echocardiography frequently remains difficult. CMR is recommended as the complementary method; however, its accuracy and prognostic utility remain unknown. Methods A total of 232 consecutive patients (34.5% were females 55.5 ± 19.8 years of age) with chronic AR (including 40 with moderate to severe and 44 with severe AR on echocardiography) underwent CMR within 4 weeks of echocardiography. CMR included phase-contrast velocity-encoded imaging for the measurement of regurgitant volume and fraction at the sinotubular junction and assessment of holodiastolic retrograde flow (HRF) in the descending aorta. Significant AR was defined as the presence of HRF on CMR. Patients were followed prospectively, and multivariate Cox regression was applied for outcome analysis using a combination of heart failure, hospitalization, and cardiovascular death as primary endpoint. Results AR severity on the basis of echo was reclassified in a significant number of patients according to CMR: 6.8% with mild AR on echo had HRF on CMR, whereas 34.1% with severe AR on echo did not have HRF on CMR and were reclassified as having nonsignificant AR. In 40 patients with uncertain AR severity (moderate to severe) on echo, 45.0% had HRF on CMR, indicating severe AR. Patients were followed for 35.3 ± 26.6 months. During that period, 63 patients (27.2%) reached the combined endpoint, including 43 (18.5%) with heart failure hospitalizations and 20 (8.6%) with cardiovascular deaths. By multivariate regression analysis, including clinical as well as imaging parameters, only N-terminal pro–B-type natriuretic peptide concentration (hazard ratio: 2.184 [95% confidence interval: 1.468 to 3.248]; p Conclusions In chronic AR, CMR has the potential to add important diagnostic and prognostic information.

The complex anatomy and physiology of the right ventricle (RV) is a major limitation of visual echocardiographic gradation of RV systolic function (RVF). The aim of this study was to compare visual assessment (“eyeballing”) of RVF with gold standard magnetic resonance imaging (MRI)-derived right ventricular ejection fraction (RVEF). Medical professionals from a range of clinical settings and with varying degrees of echocardiography experience were recruited via an online ultrasound teaching platform. In an anonymized web-based test, participants graded RVF in 10 patients with varying degrees of RVF via “eyeballing” of an RV-focused four-chamber view. Two skills were evaluated: (1) ability to differentiate between normal and reduced RVF; and (2) ability to determine the correct degree of RV systolic dysfunction. A total of 868 participants from 99 countries were included. For detection of reduced RVF (MRI-RVEF 40% of cases. In the present cohort, “eyeballing” was associated with excellent sensitivity but poor specificity in terms of differentiation between normal and abnormal RVF. Even among experts, classification of the degree of RV dysfunction was imprecise. In accordance with current guidelines, the present data suggest that “eyeballing” should be combined with evaluation of other echocardiographic parameters of RVF.

Objectives Decision making in severe aortic stenosis (AS) requires a comprehensive pre-operative evaluation of the risk-to-benefit ratio. The aim of this study was to assess whether certain pre-operative symptoms are associated with outcome after surgical aortic valve replacement (SAVR). Background The cardinal symptoms of AS indicating a need for intervention are angina, symptoms of heart failure, and syncope. Nevertheless, it remains unknown whether the presence of these more advanced symptoms conveys an increased risk after SAVR and whether the detection of early symptoms in patients with asymptomatic AS should be emphasized more in routine clinical practice. Methods A total of 625 patients with isolated severe AS undergoing elective SAVR were prospectively enrolled in this long-term observational study. Results Patients experiencing syncope had significantly smaller left ventricular diameters (p = 0.02), left atrial diameters (p = 0.043), right ventricular diameters (p = 0.04), and right atrial diameters (p = 0.001), smaller aortic valve areas (p = 0.048), and lower indexed stroke volumes (p = 0.043) compared with patients without syncope. Syncope conveyed an increased risk for mortality after SAVR that persisted after multivariate adjustment for a bootstrap-selected confounder model, with an adjusted hazard ratio of 2.27 (95% confidence interval: 1.04 to 4.95; p = 0.04) for 1-year short-term mortality and an adjusted hazard ratio of 2.11 (95% confidence interval: 1.39 to 3.21; p Conclusions This long-term observational study in a large contemporary cohort of patients with AS for the first time demonstrates that syncope represents an underestimated threat in aortic stenosis, associated with poor prognosis after SAVR. Importantly, other primary indications for SAVR (i.e., dyspnea, angina, and decreased left ventricular function) were associated with significantly better post-operative outcomes than syncope. Patients experiencing syncope displayed a specific pathophysiologic phenotype characterized by a smaller aortic valve area, smaller cardiac cavities, and lower stroke volumes.

Aim: Peak oxygen uptake (peakVO2) is one of the strongest predictors of survival in patients with valvular heart disease. The purpose of this study was to determine whether endurance training improves peakVO2 and endurance capacity in patients with moderate-severe aortic and mitral valve disease.Methods: 30 patients with moderate-severe valvular heart disease were randomly assigned to 12 weeks of endurance training (TG) (n = 16) or standard care (SC) (n = 14). PeakVO2 and maximum working capacity (Wattmax) were assessed by cardiopulmonary exercise testing, as well as submaximal endurance test at 80% of peakVO2 at baseline and after 12 weeks.Results: There was a significant improvement in peakVO2 from 27.2 ± 5.9 ml/kg to 30.4 ± 6.3 ml/kg (P < 0.001) in TG compared to the SC (peakVO2 from 24.6 ± 4.4 to 24.7 ± 3.8) and in the Wattmax from 151.8 ± 41.0 Watt to 171.2 ± 49.7 Watt in the TG compared to the SC (152.9 ± 35.6 Watt to 149.2 ± 28.4 Watt). The endurance capacity increased significantly from 17.0 ± 9.4 min to 32.8 ± 16.8 min (p = 0.003) in the TG compared to the SC (11.7 ± 6.2 min to 11.2 ± 7.6 min). The heart rate during the endurance test decreased in the TG from 154 ± 14 b/min to 142 ± 20 b/min for the same workload. No changes could be seen in the SC.Conclusion: Endurance training in patients with moderate to severe valvular heart disease increased significantly the peakVO2 as well as the endurance capacity.

Background: Left ventricular (LV) dilatation is a key compensatory feature in patients with chronic aortic regurgitation (AR). However, sex-differences in LV remodeling and outcomes in chronic AR have been poorly investigated so far. Methods: We performed cardiovascular magnetic resonance imaging (CMR) including phase-contrast velocity-encoded imaging for the measurement of regurgitant fraction (RegF) at the sinotubular junction, in consecutive patients with at least mild AR on echocardiography. We assessed LV size (end-diastolic volume indexed to body surface area, LVEDV/BSA) and investigated sex differences between LV remodeling and increasing degrees of AR severity. Cox-regression models were used to test differences in outcomes between men and women using a composite of heart failure hospitalization, unscheduled AR intervention, and cardiovascular death. Results: 270 consecutive patients (59.6% male, 59.8 &plusmn, 20.8 y/o, 59.6% with at least moderate AR on echocardiography) were included. On CMR, mean RegF was 18.1 &plusmn, 17.9% and a total of 65 (24.1%) had a RegF &ge, 30%. LVEDV/BSA was markedly closer related with AR severity (RegF) in men compared to women. Each 1-SD increase in LVEDV/BSA (mL/m2) was associated with a 9.7% increase in RegF in men and 5.9% in women, respectively (p-value for sex-interaction &lt, 0.001). Based on previously published reference values, women&mdash, in contrast to men&mdash, frequently had a normal LV size despite severe AR (e.g., for LVEDV/BSA on CMR: 35.3% versus 8.7%, p &lt, 0.001). In a Cox-regression model adjusted for age, LVEDV/BSA and RegF, women were at significantly higher risk for the composite endpoint when compared to men (adj. HR 1.81 (95%CI 1.09&ndash, 3.03), p = 0.022). Conclusion: In patients with chronic AR, LV remodeling is a hallmark feature in men but not in women. Severity of AR may be underdiagnosed in female patients in the absence of LV dilatation. Future studies need to address the dismal prognosis in female patients with chronic AR.

Background Right ventricular (RV) function is strongly associated with outcome in heart failure. Whether it also adds important prognostic information in patients undergoing transcatheter aortic valve implantation (TAVI) is unknown. Methods We consecutively enrolled patients with severe aortic stenosis (AS) scheduled for TAVI and preprocedural cardiac magnetic resonance (CMR) imaging. Kaplan-Meier estimates and multivariate Cox regression analyses were used to identify factors associated with outcome. A composite of heart failure hospitalization and/or cardiovascular death was selected as primary study endpoint. Results 423 consecutive patients (80.7±7.3 years; 48% female) were prospectively included, 201 (48%) underwent CMR imaging. 55 (27%) patients presented with RV systolic dysfunction (RVSD) defined by RV ejection fraction (RVEF) A total of 51 events (37 deaths, 14 hospitalizations for heart failure) occurred during follow-up (9.8±9 months). While LVSD (LVEF Conclusions RVSD rather than LVSD, as determined on CMR, is an important predictor of outcome in patients undergoing TAVI. RV function might thus add useful prognostic information on top of established risk factors. Figure 1. Kaplan-Meier survival curves 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

Aims Right ventricular dysfunction (RVD) on echocardiography has been shown to predict outcomes in patients undergoing transcatheter aortic valve replacement (TAVR). However, a comparison with the gold standard, RV ejection fraction (EF) on cardiovascular magnetic resonance (CMR), has never been performed. Methods and results Consecutive patients scheduled for TAVR underwent echocardiography and CMR. RV fractional area change (FAC), tricuspid annular plane systolic excursion, RV free-lateral-wall tissue Doppler (S’), and strain were assessed on echocardiography, and RVEF on CMR. Patients were prospectively followed. Adjusted regression analyses were used to report the strength of association per 1-SD decline for each RV function parameter with (i) N-terminal prohormone of brain natriuretic peptide (NT-proBNP) levels, (ii) prolonged in-hospital stay (>14 days), and (iii) a composite of heart failure hospitalization and death. Two hundred and four patients (80.9 ± 6.6 y/o; 51% female; EuroSCORE-II: 6.3 ± 5.1%) were included. At a cross-sectional level, all RV function parameters were associated with NT-proBNP levels, but only FAC and RVEF were significantly associated with a prolonged in-hospital stay [adjusted odds ratio 1.86, 95% confidence interval (CI) 1.07–3.21; P = 0.027 and 2.29, 95% CI 1.43–3.67; P = 0.001, respectively]. A total of 56 events occurred during follow-up (mean 13.7 ± 9.5 months). After adjustment for the EuroSCORE-II, only RVEF was significantly associated with the composite endpoint (adjusted hazard ratio 1.70, 95% CI 1.32–2.20; P Conclusion RVD as defined by echocardiography is associated with an advanced disease state but fails to predict outcomes after adjustment for pre-existing clinical risk factors in TAVR patients. In contrast, RVEF on CMR is independently associated with heart failure hospitalization and death.

Aims Cardiac amyloidosis (CA) leads to signs and symptoms of heart failure (HF). The mechanisms of biventricular dysfunction and their impact on outcome in subtypes of CA are poorly understood. Our aim was to compare right ventricular (RV) and left ventricular (LV) parameters in patients with light chain (AL) and wild-type transthyretin amyloidosis (ATTRw) and evaluate their ability to predict cardiac outcome. Methods and results We included patients with CA into a prospective registry. Baseline assessment included biventricular 2D speckle tracking imaging parameters. Patients were followed-up in regular intervals. The composite endpoint was defined as cardiovascular death, heart transplantation or ventricular assist device implantation, and HF hospitalization. We included 122 patients with CA. Sixty-two of these patients (50.8%) were diagnosed with ATTRw and 60 (49.2%) with AL. In ATTRw, parameters of RV size and function correlated well with symptom severity and only morphological and functional parameters of the RV predicted outcome. RV free wall strain was the only independent predictor of outcome with a hazard ratio (HR) of 1.185 [95% confidence interval (CI) 1.047-1.342, P = 0.007]. In AL on the other hand, RV function correlated well with symptoms but was not associated with outcome. In contrast, global longitudinal strain of the LV (LV-GLS) was predictive for outcome. After adjusting in a multivariable model, LV-GLS remained predictive with a HR of 1.180 (95% CI 1.032-1.348, P = 0.015). Conclusion Our data suggest that mechanisms underlying HF differ between ATTRw and AL. This may have substantial implications in particular in light of emerging therapies for both subtypes of CA.

Purpose Cardiovascular disease and foremost coronary heart disease (CHD) are the worldwide leading causes of death. The aim of this study was to use non-invasive, multimodel retinal imaging to define microvascular features in patients with and without coronary angiography (CA)-confirmed CHD. Methods In this prospective, cross-sectional pilot study we included adult patients who presented to a tertiary referral center for elective CA due to suspected CHD. All patients underwent widefield fundus photography for retinopathy grading. Optical coherence tomography angiography was used to measure vessel density (VD) of the individual capillary plexuses in 6 × 6-mm macular volume scans. Adaptive optics imaging was performed to assess the first-order arteriolar lumen diameter (LD), total diameter (TD), wall-to-lumen ratio (WLR), and wall cross-section area, as well as to qualitatively describe vessel morphology. Results Of the included 45 patients (13 females; 65 ± 10 years old), 27 were confirmed with CHD in elective CA. The most prevalent retinal vascular pathologies were arteriovenous nickings, focal arterial narrowings, and microaneurysms. VD in the superficial capillary plexus, deep capillary plexus, and choriocapillaris was lower in CHD patients, although the odds ratios were not significantly different from 1 (P = 0.06-0.92). Median arterial LD, TD, and WLR values were 98.3 µm (interquartile range [IQR] = 13.0), 122.9 µm (IQR = 17.6), and 0.26 µm (IQR = 0.07), respectively, with a trend toward a higher WLR in CHD patients. Conclusions In a cardiovascular risk population, high-resolution quantitative and qualitative microvascular phenotyping in the retina may provide valuable subclinical indicators for coronary artery impairment, although larger clinical trials are needed. Translational relevance Subclinical retinal microvascular changes may serve as non-invasive, cost-effective biomarkers for risk stratification of patients with CHD.

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.

Impaired left atrial (LA) function is a hallmark of heart failure with preserved ejection fraction (HFpEF) ([1][1]). However, how the various phases of LA function (reservoir, conduit, and booster pump function) ([Figure 1][2]) contribute to hemodynamic changes and cardiovascular outcomes in HFpEF

In cardiac amyloidosis (CA), extracellular deposition of amyloid fibrils within the myocardium significantly expands the extracellular volume (ECV). Affected patients develop severe heart failure and face a dismal prognosis. Cardiac magnetic resonance (CMR) T1 mapping allows ECV measurement [(1)][1

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.

Background Pericardial and pleural effusion are common findings in patients with cardiac amyloidosis (CA). While this might be suggestive of a sign of right heart failure, it is not known, whether effusions correlate with right ventricular (RV) function in patients with CA. Furthermore, data on the prognostic significance of pleural and pericardial effusion in CA is scarce. Methods Patients with cardiac transthyretin (ATTR) and light chain (AL) amyloidosis were included in a clinical registry at our dedicated CA outpatient clinic. CA was diagnosed according to current guidelines. All patients underwent a comprehensive transthoracic echocardiography (TTE) exam at the time of study inclusion. The TTE protocol included standard and advanced parameters describing left ventricular and RV function, including speckle-tracking imaging to assess global longitudinal left ventricular and RV free wall (RV-FW) strain. The presence of pericardial and pleural effusion was determined in every patient and was verified by cardiac magnetic resonance imaging when present. The size of pericardial effusion was measured at the point of its maximum extension. The clinical endpoint was defined as all-cause death. Results Between March 2012 and February 2019, 177 patients were included in our CA registry, however, TTE image quality was only sufficient for analysis in 143 patients. Of these, 83 patients (59.4%) were diagnosed with ATTR and 60 patients (42.0%) with AL. In total, 23 patients (16.1%) presented with isolated pericardial effusion and 36 (25.2%) with isolated pleural effusion. In 17 patients (11.9%) both pericardial and pleural effusion were found and in 66 patients (46.2%) no effusion was present at baseline. Overall, there was no significant difference in the type of effusion between patients with AL and ATTR. In general, pericardial effusions were small (median diameter 7.1 mm (IQR 5.2–9.7) and none were hemodynamically compromising. Interestingly, the presence of pleural effusion correlated well with poor RV function, measured by RV-FW strain (p=0.034). However, no such correlation could be found for pericardial effusion and RV-FW strain (p=0.319). Kaplan Meier analysis showed that patients presenting with pleural effusion had a worse prognosis compared to patients with pericardial effusion alone or no effusion at baseline (p=0.001, Figure 1). Figure 1 Conclusion More than 50% of patients with CA presented with pleural and/or pericardial effusions. While pleural effusion was clearly associated with poor RV function, we were not able to detect this association with pericardial effusion. In addition, patients with pleural effusions had an exceptionally poor prognosis compared to patients with pericardial effusions or no effusion at baseline.

Background Intracardiac filling and pulmonary arterial pressures play a central role in various heart failure entities, as they are strong predictors of outcome. However, their role in patients with cardiac amyloidosis (CA) is less clear. Purpose We aimed to characterize hemodynamic profiles of CA patients and assess their association with outcomes. Methods The present study was conducted within a prospective, national CA registry. Patients underwent invasive hemodynamic, clinical, laboratory, and echocardiography assessment, as well cardiac magnetic resonance imaging with T1-mapping. The main outcome measure was a combined endpoint consisting of hospitalization for heart failure or cardiovascular death. Results Between March 2012 and October 2018, 63 consecutively recruited CA patients underwent invasive hemodynamic profiling. Of those, 36 had cardiac transthyretin amyloidosis (ATTR) and 25 cardiac light-chain amyloidosis (AL). In two patients amyloid subtyping was not possible. Median age of the study population was 74.0 years and the majority were male (61.9%). Almost half of the patients were in New York Heart Association (NYHA) class ≥III (47.6%) and showed elevated N-terminal prohormone of brain natriuretic peptides (NT-proBNP) with a median of 3222 pg/mL. In comparison to AL, cardiac TTR patients were older (75.0 years versus 69.0 years, p=0.004), more often male (80.6% versus 40.0%, p=0.001), less symptomatic (NYHA class ≥III: 38.9% versus 64.0%, p=0.021), and had lower NT-proBNP values (2324pg/mL versus 5151pg/mL, p=0.004). Hemodynamic profiling revealed significantly increased intracardiac as well as pulmonary arterial pressures (PAP). On an average, pulmonary artery wedge pressure was 20.0mmHg [interquartile range (IQR): 17.0–25.0], mean PAP (mPAP) was 30.0mmHg (IQR: 25.0–37.0), and mean right atrial pressure (mRAP) was 11.0mmHg (IQR: 7.0–16.0). No differences between ATTR and AL patients could be detected (p=0.148, p=0.398, p=0.620). During a median follow-up of 63.0 weeks, 28 study participants (44.4%) reached the combined endpoint. Moreover, cardiac AL patients had significantly more events as their ATTR counterparts (72.0% versus 27.8%, p=0.001). In cardiac ATTR patients, mPAP was significantly associated with outcome [hazard ratio (HR): 1.083, p=0.034, Figure 1A], which was not the case in the AL group (HR: 1.024, p=0.186, Figure 1B). Cardiac output and pulmonary vascular resistance were not associated with outcome. Neither in the ATTR (p=0.144; p=0.063) nor in AL cohort (p=0.420; p=0.115). Figure 1 Conclusion Despite differences in the severity of symptoms between cardiac AL and cardiac ATTR patients, no differences with regards to hemodynamic profiles could be detected. Furthermore, intracardiac filling and pulmonary arterial pressures seem to be of greater clinical importance in cardiac ATTR as compared to cardiac AL, as these parameters were associated with outcome in the first, but not the latter group.

Background Transthyretin amyloid cardiomyopathy (ATTR-CA) is caused by deposition of amyloid fibrils in the myocardium. The deposition occurs when transthyretin (TTR) becomes unstable and misfolds. Tafamidis is a kinetic stabilizer of TTR that prevents tetramer dissociation and amyloidogenesis by TTR. Methods Eighteen patients with diagnosis of ATTR-CA (hATTR or wtATTR) from our national amyloidosis registry were treated with 20 mg of tafamidis for a period of six months. In our explorative analysis we aimed to evaluate the effects of tafamdis by changes from baseline of the serum NT-proBNP concentration, 6-minute walking distance, as well as cardiac structure and function. Results The exploratory analysis showed a decrease in serum NT-proBNP concentration in tafamidis treated patients, compared to increase in untreated patients (median difference, −481.0 pg/mL). Tafamidis improved the walking distance during the 6-minute walk test at month six, compared to baseline (mean, 31.25 m). Echocardiographic findings revealed an improvement of the global longitudinal strain (mean, 0.77%), a decrease in left atrial size (mean, −1.65 mm) and a decrease in left ventricular size (mean, −4.13 mm) in tafamidis treated patients compared to untreated patients. Due to insufficient power the results did not differ significantly between tafamidis treated patients and untreated patients. Change from baseline Tafamidis No treatment Treatment Difference p-value Cardiac Biomarkers n=18 n=15 NT-proBNP, ng/L Baseline, median 2740.0 2835.0 CFB to 6 months, median −207.0 274.0 −481.0 0.329 Functional Status n=8 n=7 6MWT, m Baseline, mean 441.00 420.50 CFB to 6 months, mean 31.25 −16.50 +47.75 0.373 Echocardiogram n=17 n=15 LA, mm Baseline, mean 63.41 61.33 CFB to 6 months, mean −1.65 0.60 −2.25 LV, mm Baseline, mean 44.13 41.80 CFB to 6 months, mean −4.13 0.33 −4.46 0.075 LV wall thickness, mm Baseline, mean 22.06 18.47 CFB to 6 months, mean 0.68 −0.60 +1.28 0.055 Longitudinal strain, % Baseline, mean −10.66 −12.42 CFB to 6 months, mean 0.77 −1.03 +1.80 0.652 MRI n=7 n=6 ECV, % Baseline, mean 52.26 44.22 CFB to 6 months, mean 0.81 3.70 − 2.89 0.493 LV mass, g Baseline, mean 187.71 170.33 CFB to 6 months, mean 24.29 19,67 +4.62 0.612 Conclusion Treatment with tafamidis for a period of six months in patients with ATTR-CA leads to positive effects on NT-proBNP level, 6-minute walking distance, as well as cardiac structure and function compared to untreated patients.

Background Global left atrial (LA) size and function have been shown to be associated with adverse events in heart failure with preserved ejection fraction (HFpEF). The machanism of coupling from left heart failure to pulmonary circulation is still controversially discussed. Purpose To study the prognostic most relevant determinant of LA size and function and its backward and forward interplay. Methods 188 HFpEF patients were prospectively enrolled and underwent baseline clinical assessment, cardiac magnetic resonance imaging (CMR) and invasive hemodynamic assessment. Coronary artery disease was ruled out by coronary angiography. 92 patients were in atrial fibrillation (AF), 96 in sinus rhythm. LA size and function were assessed by CMR including LA strain imaging by myocardial feature tracking (Figure 1A & B). Results Patients in AF had more pronounced dilatation of all phasic LA volumes and reduction of all phasic LA functions when compared to sinus rhythm (each p After 31 (9–57) months 66 patients reached the combined endpoint defined as combination from hospitalization due to heart failure and cardiovascular death. In AF no atrial functional or volume parameter was correlated to outcome. In contrast in sinus rhythm several phasic LA volume and functional parameters were associated with outcome. After multivariate cox regression analysis only reduced total LA ejection fraction and conduit strain rate were still predictive for worse outcome (p=0.031 and Conclusion Total LA ejection fraction plays a key role in the prognosis of HFpEF. This effect seems to be mainly related to its LA conduit function but not to LA booster pump function. LA conduit function correlates to impaired 6MWD, sPAP and PVR.

Background Increased afterload to the right ventricle (RV) has been shown to induce myocardial fibrosis at the RV insertion points (RVIPs). Such changes can be discrete but potentially detected by cardiac magnetic resonance (CMR) T1-mapping. Whether RVIP fibrosis is associated with prognosis in heart failure with preserved ejection fraction (HFpEF) is unknown. Methods We prospectively investigated 167 consecutive HFpEF patients, a population frequently suffering from postcapillary pulmonary hypertension (PH), who underwent CMR including T1-mapping. 92,8% also underwent right heart catheterization for hemodynamic assessment. Kaplan–Meier analysis, cox regression analysis and Spearman's rank order correlation were applied as statistical methods. The parameter with the strongest discriminative power of each group (clinical, hemodynamic and CMR) by receiver operating curve analysis was selected to the enter the multivariate cox model. Results Native T1 times were 995±73 ms at the anterior and 1040±90 ms at the inferior RVIP. By Spearman's rank order testing, RVIP T1 times were significantly correlated with pulmonary artery pressure (mean PAP, r=0.313 and 0.311 for anterior and inferior RVIP, respectively), pulmonary artery wedge pressure (r=0.301 and 0.251) and right atrial pressure (r=0.245 and 0.185; p for all Kaplan Meier Curve Conclusions Interstitial expansion of the anterior RVIP as detected by CMR T1-mapping reflects hemodynamic alterations, and is independently related with prognosis in HFpEF.

Background Apical sparing describes a reduced longitudinal strain in the basal segments and preserved or supranormal longitudinal strain in the apical segments of the left ventricular (LV) myocardium. This pattern has been described as a typical finding in patients with cardiac amyloidosis (CA) and restrictive cardiomyopathy. However, apical sparing is not a quantitative parameter and is fairly subjective to the echocardiographer's judgement. It is not known, if a certain degree of apical sparing is also present in patients with only mild LV hypertrophy and diastolic dysfunction such as it is present in heart failure with preserved ejection fraction (HFpEF). Methods Patients with cardiac transthyretin and light chain amyloidosis and patients with HFpEF were included in a clinical registry at our outpatient clinic. CA was diagnosed according to current guidelines. All patients underwent a comprehensive transthoracic echocardiography (TTE) exam at the time of study inclusion. The TTE protocol included standard and speckle-tracking imaging to assess the presence of apical sparing as well as the basal to apical strain gradient. Patients with known coronary artery disease were excluded. Results In total 115 patients were included in this study. Of these, 87 (75.7%) were diagnosed with CA and 28 (24.3%) with HFpEF. Not surprisingly, apical sparing was found in a majority (86.2%) of patients with CA, however mild forms of this phenomenon were also present in 67.9% of patients with HFpEF (p=0.029, Figure 1). Median basal longitudinal strain was significantly more impaired in patients with CA (p Figure 1 Conclusion Mild forms of apical sparing can be found in patients without CA. Gradual reduction in strain from base to apex could be an unspecific pathophysiologic mechanism which is remarkably pronounced in patients with CA.

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.

Background Cardiac magnetic resonance (CMR) provides the gold standard for the assessment of ventricular volumes and mass. However, data on right ventricular systolic dysfunction (RVSD) and its prognostic significance on outcome in patients undergoing transcatheter aortic valve replacement (TAVR) are lacking. Methods We consecutively enrolled patients with severe aortic stenosis scheduled for TAVR who underwent preprocedural CMR. Kaplan-Meier estimates and multivariate Cox-regression analysis were used to identify factors associated with outcome, including RVSD. A composite of heart failure hospitalization and/or cardiovascular death was selected as primary study endpoint. Results 145 consecutive patients (80.5±7.6 years; 51.7% female) were prospectively included, 25 (17.2%) of which had RVSD defined as RV ejection fraction (RVEF) Conclusions RVSD rather than LVSD, as determined by CMR, is an important predictor of outcome in patients undergoing TAVR. RV function might thus add useful prognostic information on top of established risk factors.

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.

Purpose of the present cohort study was the determination of lower body function and rotation in patients with symptomatic component mal-rotation after total knee arthroplasty using instrumented 3D gait analysis. A consecutive series of 12 patients (61.3 years ± 11.4 years) were included suffering under remaining pain or limited range of motion at least six months after total knee arthroplasty. A CT-scan according to the protocol of Berger et al. and instrumented 3D gait analysis were carried out including clinical examination, videotaping, and kinematic analysis using a Plug-in Gait model. Outcome variables were temporospatial parameters as well as kinematics in sagittal and transversal plane. Data for reference group were collected retrospectively and matched by age and gender. Temporospatial parameters of the study group showed decreased velocity, cadence, and step length as well as increased step time. Single limb support was reduced for the affected limb. In sagittal plane, maximum knee flexion during swing phase was reduced for the replaced knee joint. In transverse plane, there was hardly any difference between affected and non-affected limb. Compared to the reference group, both limbs show significant increased internal ankle rotation and external hip rotation. There were significant strong linear correlations between ankle rotation and hip rotation as well as ankle rotation and radiological tibial mal-rotation. Patients with symptomatic component mal-rotation after total knee arthroplasty showed typically functional deficits. The affected and non-affected limb showed significant increased internal ankle rotation and external hip rotation, while only the affected, replaced knee showed reduced internal knee rotation. Identification of rotational abnormalities of hip and ankle joints seems to be mandatory in TKA to identify the patient group with external hip rotation, internal ankle rotation, and an elevated risk for symptomatic rotational TKA component mal-alignment.

Background Atrial fibrillation (AF) is a frequent finding in HFpEF. However, its association with invasive haemodynamics, imaging parameters and outcome in HFpEF is not well established. Furthermore, the relevance of AF subtype with regard to outcome is unclear. This study sought to investigate the prognostic impact of paroxysmal and persistent AF in a well‐defined heart failure with preserved ejection fraction (HFpEF) population. Materials and methods Between 2010 and 2016, 254 HFpEF patients were prospectively enrolled. All patients underwent echocardiography as well as left and right heart catheterization. Patients without contraindications underwent CMR including T1 mapping. Follow‐up and outcome data were collected. Patients with significant coronary artery disease were excluded. Results A total of 153 patients (60%) suffered from AF, 119 (47%) had persistent and 34 (13%) had paroxysmal AF. By multiple logistic regression analysis, persistent AF was independently associated with NT‐proBNP (P = .003), NYHA functional class (P = .040), left and right atrial size (P = .022 and

Background/Aims: Heart failure (HF) is a main cause of mortality of hemodialysis (HD) patients. While HF with reduced ejection fraction (HFrEF) is known to only affect a minority of patients, little is known about the prevalence, associations with clinical characteristics and prognosis of HF with preserved ejection fraction (HFpEF). Methods: We included 105 maintenance HD patients from the Medical University of Vienna into this prospective single-center cohort study and determined the prevalence of HFpEF (per the 2013 criteria of the European Society of Cardiology) and HFrEF (EF Results: All but 4 patients (96%) had evidence of diastolic dysfunction. 70% of the entire cohort fulfilled HF criteria (81% HFpEF, 19% HFrEF). Age, female sex, body mass index, blood pressure and dialysis vintage were predictive of HFpEF (sensitivity 86%, specificity 63%; AUC 0.87), while age, female sex, NT pro-BNP, history of coronary artery disease and atrial fibrillation were predictive of HFrEF (sensitivity 85%, specificity 90%; AUC 0.95). Compared to patients without HF, those with HFpEF and HFrEF had a higher risk of hospitalization for cardiovascular reason and/or cardiac death (adjusted HR 4.31, 95% CI 0.46-40.03; adjusted HR 3.24, 95% CI 1.08-9.75, respectively). Conclusion: Diastolic dysfunction and HFpEF are highly prevalent in HD patients while HFrEF only affects a minority. Distinct patient-specific characteristics predict diagnosis of either entity with good accuracy.

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

Background: Concomitant left main coronary artery (LMCA) disease in patients with chronic total occlusions (CTO) commonly results in referral for coronary artery bypass grafting, although the impact of LMCA in CTO patients remains largely unknown. Nevertheless, patient selection for percutaneous coronary intervention of CTOs (CTO-PCI) or alternative revascularization strategies should be based on precise evaluation of the coronary anatomy to anticipate those patients that most likely benefit from a procedure and not on strict adherence to perpetual clinical practice. Therefore, the aim of this study was to assess the impact of LMCA disease on long-term outcomes in patients undergoing percutaneous coronary intervention for CTO. Methods: We enrolled 3860 consecutive patients undergoing PCI for at least one CTO lesion and investigated the predictive value of concomitant LMCA disease. All-cause mortality was defined as the primary study endpoint. Results: We observed that LMCA disease is significantly associated with mortality. In the Cox regression analysis, we observed a crude hazard ratio (HR) 1.59 (95% confidence interval (CI) 1.23&ndash, 2.04, p &lt, 0.001) for patients with LMCA disease as compared to patients without. Results remained unchanged after bootstrap- or clinical confounder-based adjustment. Conclusion: LMCA disease is associated with excess mortality in CTO patients. Specifically, anatomical features such as CTO of the circumflex artery represent a high risk patient population.

Current European guidelines classify heart failure (HF) patients according to left ventricular ejection fraction (LVEF) as reduced, mid-range, and preserved subtypes [(1)][1]. Although this is reasonable clinically, several aspects limit the use of LVEF as sole indicator for the severity of HF.