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Background: Elevated pulmonary vascular resistance (PVR) is broadly accepted as an imminent risk factor for mortality after heart transplantation (HTx). However, no current HTx recipient risk score includes PVR or other hemodynamic parameters. This study examined the utility of various hemodynamic parameters for risk stratification in a contemporary HTx population., Methods: Patients from seven German HTx centers undergoing HTx between 2011 and 2015 were included retrospectively. Established risk factors and complete hemodynamic datasets before HTx were analyzed. Outcome measures were overall all-cause mortality, 12-month mortality, and right heart failure (RHF) after HTx., Results: The final analysis included 333 patients (28% female) with a median age of 54 (IQR 46-60) years. The median mean pulmonary artery pressure was 30 (IQR 23-38) mm Hg, transpulmonary gradient 8 (IQR 5-10) mm Hg, and PVR 2.1 (IQR 1.5-2.9) Wood units. Overall mortality was 35.7%, 12-month mortality was 23.7%, and the incidence of early RHF was 22.8%, which was significantly associated with overall mortality (log-rank HR 4.11, 95% CI 2.47-6.84; log-rank p < .0001). Pulmonary arterial elastance (Ea) was associated with overall mortality (HR 1.74, 95% CI 1.25-2.30; p < .001) independent of other non-hemodynamic risk factors. Ea values below a calculated cutoff represented a significantly reduced mortality risk (HR 0.38, 95% CI 0.19-0.76; p < .0001). PVR with the established cutoff of 3.0 WU was not significant. Ea was also significantly associated with 12-month mortality and RHF., Conclusions: Ea showed a strong impact on post-transplant mortality and RHF and should become part of the routine hemodynamic evaluation in HTx candidates., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Aim: Presepsin is a sensitive biomarker for the diagnosis and estimation of prognosis in septic patients. The prognostic role of presepsin in patients undergoing transcatheter aortic valve implantation (TAVI) has never been investigated. Patients, materials & methods: In 343 patients, presepsin and N-terminal pro-B-type natriuretic peptide were measured before TAVI. One-year all-cause mortality was used as outcome measure. Results: Patients with high presepsin levels were more likely to succumb than patients with low presepsin values (16.9% vs 12.3%; p = 0.015). Elevated presepsin remained a significant predictor of 1-year all-cause mortality (odds ratio: 2.2 [95% CI: 1.12-4.29]; p = 0.022) after adjustment. N-terminal pro-B-type natriuretic peptide did not predict 1-year all-cause mortality. Conclusion: Elevated baseline presepsin levels are an independent predictor of 1-year mortality in TAVI patients.

Background: Activation of inflammatory pathways during acute myocardial infarction contributes to infarct size and left ventricular (LV) remodeling. The present prospective randomized clinical trial was designed to test the efficacy and safety of broad-spectrum anti-inflammatory therapy with a mammalian target of rapamycin (mTOR) inhibitor to reduce infarct size., Design: Controlled-Level EVERolimus in Acute Coronary Syndrome (CLEVER-ACS, clinicaltrials.gov NCT01529554) is a phase II randomized, double-blind, multi-center, placebo-controlled trial on the effects of a 5-day course of oral everolimus on infarct size, LV remodeling, and inflammation in patients with acute ST-elevation myocardial infarction (STEMI). Within 5 days of successful primary percutaneous coronary intervention (pPCI), patients are randomly assigned to everolimus (first 3 days: 7.5 mg every day; days 4 and 5: 5.0 mg every day) or placebo, respectively. The primary efficacy outcome is the change from baseline (defined as 12 hours to 5 days after pPCI) to 30-day follow-up in myocardial infarct size as measured by cardiac magnetic resonance imaging (CMRI). Secondary endpoints comprise corresponding changes in cardiac and inflammatory biomarkers as well as microvascular obstruction and LV volumes assessed by CMRI. Clinical events, laboratory parameters, and blood cell counts are reported as safety endpoints at 30 days., Conclusion: The CLEVER-ACS trial tests the hypothesis whether mTOR inhibition using everolimus at the time of an acute STEMI affects LV infarct size following successful pPCI., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Left ventricular (LV) longitudinal, circumferential, and radial motion can be measured using feature tracking of cardiac magnetic resonance (CMR) images. The aim of our study was to detect differences in LV mechanics between patients with dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) who were matched using a propensity score-based model. Between April 2017 and October 2019, 1224 patients were included in our CMR registry, among them 141 with ICM and 77 with DCM. Propensity score matching was used to pair patients based on their indexed end-diastolic volume (EDVi), ejection fraction (EF), and septal T1 relaxation time (psmatch2 module L Feature tracking provided six parameters for global longitudinal, circumferential, and radial strain with corresponding strain rates in each group. Strain parameters were compared between matched pairs of ICM and DCM patients using paired t tests. Propensity score matching yielded 72 patients in each group (DCM mean age 58.6 ± 11.6 years, 15 females; ICM mean age 62.6 ± 13.2 years, 11 females, p = 0.084 and 0.44 respectively; LV-EF 32.2 ± 13.5% vs. 33.8 ± 12.1%, p = 0.356; EDVi 127.2 ± 30.7 ml/m 2 vs. 121.1 ± 41.8 ml/m 2 , p = 0.251; native T1 values 1165 ± 58 ms vs. 1167 ± 70 ms, p = 0.862). There was no difference in global longitudinal strain between DCM and ICM patients (- 10.9 ± 5.5% vs. - 11.2 ± 4.7%, p = 0.72), whereas in DCM patients there was a significant reduction in global circumferential strain (- 10.0 ± 4.5% vs. - 12.2 ± 4.7%, p = 0.002) and radial strain (17.1 ± 8.51 vs. 21.2 ± 9.7%, p = 0.039). Our data suggest that ICM and DCM patients have inherently different myocardial mechanics, even if phenotypes are similar. Our data show that GCS is significantly more impaired in DCM patients. This feature may help in more thoroughly characterizing cardiomyopathy patients., (© 2021. The Author(s).)

The aim of this study was to evaluate the cartilage intermediate layer protein 1 (CILP1) as a biomarker of right ventricular dysfunction in patients with ischemic cardiomyopathy (ICM). CILP1 plasma concentrations were measured in 98 patients with ICM and 30 controls without any cardiac abnormalities. All participants underwent cardiac magnetic resonance imaging. Median CILP1 concentrations were higher in ICM than in controls. In the tertile analysis, low right ventricular ejection fraction (RVEF) and high right ventricular end-systolic volume index and N-terminal pro-brain natriuretic peptide (NT-proBNP) were associated with higher CILP1 levels in ICM. However, there were no associations between CILP1 concentrations and left ventricular (LV) parameters in this group. In receiver-operating characteristic (ROC) analysis CILP1 was a good predictor of RVEF < 40% with an optimal cut-off value of 3545 pg/ml in ICM, whereas it was not predictive of LV ejection fraction (LVEF) < 40% (area under the curve [AUC] = 0.57) There was no significant difference between the ROC curves of CILP1 (AUC = 0.72) and NT-proBNP (AUC = 0.77) for RVEF < 40% ( p  = 0.42). In multivariable regression analysis, RVEF was the only independent predictor of elevated CILP1. CILP1 and LVEF were the only independent predictors of RVEF < 40% in ICM. Our analysis demonstrates the potential role of CILP1 as a novel cardiac biomarker of prognostically relevant RV dysfunction in patients with ICM., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Pulmonary Circulation published by Wiley Periodicals LLC on behalf of the Pulmonary Vascular Research Institute.)

The main aim of this study was to assess the prognostic utility of TAPSE/PASP as an echocardiographic parameter of maladaptive RV remodeling in cardiomyopathy patients using cardiac magnetic resonance (CMR) imaging. Furthermore, we sought to compare TAPSE/PASP to TAPSE. The association of the echocardiographic parameters TAPSE/PASP and TAPSE with CMR parameters of RV and LV remodeling was evaluated in 111 patients with ischemic and non-ischemic cardiomyopathy and cut-off values for maladaptive RV remodeling were defined. In a second step, the prognostic value of TAPSE/PASP and its cut-off value were analyzed regarding mortality in a validation cohort consisting of 221 patients with ischemic and non-ischemic cardiomyopathy. A low TAPSE/PASP (<0.38 mm/mmHg) and TAPSE (<16 mm) were associated with a lower RVEF and a long-axis RV global longitudinal strain (GLS) as well as higher RVESVI, RVEDVI and NT-proBNP. A low TAPSE/PASP, but not TAPSE, was associated with a lower LVEF and long-axis LV GLS, and a higher LVESVI, LVEDVI and T1 relaxation time at the interventricular septum and the RV insertion points. Furthermore, in the validation cohort, low TAPSE/PASP was associated with a higher mortality and TAPSE/PASP was an independent predictor of mortality. TAPSE/PASP is a predictor of maladaptive RV and LV remodeling associated with poor outcomes in cardiomyopathy patients.

Background: Cardiac amyloidosis (CA) is an infiltrative disease characterised by accumulation of amyloid deposits in the extracellular space of the myocardium-comprising transthyretin (ATTR) and light chain (AL) amyloidosis as the most frequent subtypes. Histopathological proof of amyloid deposits by endomyocardial biopsy (EMB) is the gold standard for diagnosis of CA. Cardiovascular magnetic resonance (CMR) allows non-invasive workup of suspected CA. We conducted a multi-centre study to assess the diagnostic value of CMR in comparison to EMB for the diagnosis of CA., Methods: We studied N = 160 patients characterised by symptoms of heart failure and presence of left ventricular (LV) hypertrophy of unknown origin who presented to specialised cardiomyopathy centres in Germany and underwent further diagnostic workup by both CMR and EMB. If CA was diagnosed, additional subtyping based on EMB specimens and monoclonal protein studies in serum was performed. The CMR protocol comprised cine- and late-gadolinium-enhancement (LGE)-imaging as well as native and post-contrast T1-mapping (in a subgroup)-allowing to measure extracellular volume fraction (ECV) of the myocardium., Results: An EMB-based diagnosis of CA was made in N = 120 patients (CA group) whereas N = 40 patients demonstrated other diagnoses (CONTROL group). In the CA group, N = 114 (95%) patients showed a characteristic pattern of LGE indicative of CA. In the CONTROL group, only 1/40 (2%) patient showed a "false-positive" LGE pattern suggestive of CA. In the CA group, there was no patient with elevated T1-/ECV-values without a characteristic pattern of LGE indicative of CA. LGE-CMR showed a sensitivity of 95% and a specificity of 98% for the diagnosis of CA. The combination of a characteristic LGE pattern indicating CA with unremarkable monoclonal protein studies resulted in the diagnosis of ATTR-CA (confirmed by EMB) with a specificity of 98% [95%-confidence interval (CI) 92-100%] and a positive predictive value (PPV) of 99% (95%-CI 92-100%), respectively. The EMB-associated risk of complications was 3.13% in this study-without any detrimental or persistent complications., Conclusion: Non-invasive CMR shows an excellent diagnostic accuracy and yield regarding CA. When combined with monoclonal protein studies, CMR can differentiate ATTR from AL with high accuracy and predictive value. However, invasive EMB remains a safe invasive gold-standard and allows to differentiate CA from other cardiomyopathies that can also cause LV hypertrophy.

Background: Primary coronary slow-flow phenomenon (CSFP) is defined as delayed opacification of contrast media in at least 1 coronary vessel in the absence of obstructive epicardial coronary artery disease (CAD) during coronary angiography. Epicardial fat tissue (EFT) surrounding coronary vessels provides paracrine effects. Released cytokines diffusing in the vessel wall may induce local inflammatory reactions that potentially result in endothelial dysfunction. The latter is thought to be the underlying cause of primary CSFP. However, to date, there are no data describing an association between EFT and CSFP. Therefore, the aim of the present study was to compare EFT thickness, clinical parameters, and outcomes in patients with and without CSFP., Methods: Coronary angiograms with primary CSFP obtained during a 10-year period were included in the analysis. EFT was measured in the 2-dimensional echocardiographic records. Clinical and diagnostic data were compared with non-CSFP patients who were matched for age, sex, and body mass index. Long-term follow-up was conducted by telephone interview., Results: A total of 48 CSFP patients (90% male; mean age, 64 ± 11.4 years) were identified, resulting in a prevalence of 0.13%. CSFP was observed in 87.5% in the left anterior descending artery, 50% in the right coronary artery, and 20.8% in the circumflex artery. Almost half of all patients showed CSFP in >1 vessel. There were no differences in baseline characteristics between CSFP patients and matched controls except for smoking history (31% vs 13%; P=.03). Median EFT thickness was significantly different between patients with and without CSFP (4.9 mm [interquartile range, 4.0-6.1 mm] vs 3.9 mm [interquartile range, 3.1-4.9 mm], respectively; P<.01). No differences in outcomes were observed., Conclusion: EFT is thicker in CSFP patients than in matched controls, but this appears to have no impact on long-term outcomes. Further studies are needed to elucidate the role of EFT in CSFP.

Background: Previous publications about the association between fatty-acid binding protein 4 (FABP4) and cardiac remodeling have reported different, both beneficial and harmful, associations. Aim of the present investigation was to evaluate the association of FABP4 with parameters of myocardial remodeling defined by cardiac magnetic resonance imaging (CMR)., Methods: We investigated plasma FABP4 levels in 331 patients (71% men, mean age 63±13 years) with preserved left ventricular ejection fraction (LVEF ≥ 55%) who underwent a CMR examination. We used linear cox regression to investigate associations between FABP4 and left ventricular end-diastolic diameter (LVEDD), right ventricular end-diastolic diameter (RVEDD), relative wall thickness (RWT), left ventricular mass index (LVMI), and LVEF (unadjusted and adjusted for age, sex, body mass index, cardiac biomarkers, and comorbidities)., Results: FABP4 levels were associated with lower LVMI and higher NT-proBNP levels in an adjusted model. The inverse association between FABP4 and LVMI was more pronounced in lower FABP4 levels, whereas the positive association between FABP4 and NT-proBNP was more pronounced in relatively high NT-proBNP levels., Conclusions: Possible beneficial and harmful associations between FABP4 and left ventricular size have been reported. Our results suggest a beneficial association with LVMI (more pronounced in lower FABP4 levels) but a harmful association with NT-proBNP (more pronounced in higher FABP4 levels). Therefore, our results might indicate a potential dose-dependent association of FABP4, but this observation needs further investigation in larger study samples.