Diagnostic value of left ventricular layer strain and specific regional strain patterns in cardiac amyloidosis and Fabry disease.

Aims: Layer-specific left ventricular (LV) strain alterations have been suggested as a specific finding in Fabry disease (FD). Our study aimed to assess the diagnostic value of layer-specific radial strain (RS) indices compared to the established LV regional strain pattern in cardiac amyloidosis (CA) and FD, i.e. apical sparing and posterolateral strain deficiency (PLSD). Methods and results: We retrospectively analysed the global, subendocardial, subepicardial LV radial strain, the corresponding strain gradient, as well as the regional and global longitudinal strain. The diagnostic accuracy of the diverse LV strain analyses was comparatively assessed using receiver operating characteristic curve and multivariable regression analyses. In 40 FD and 76 CA patients, CA featured more reduced layer strain values [global RS -12.3 (-15.6 to -9.6) in CA vs. -16.7 (-20.0 to -13.6) in FD; P < 0.001; subendocardial RS -22.3 (-27.4 to -15.9) vs. -28.3 (-31.8 to -23.6), P < 0.001; subepicardial RS -6.6 (-8.6 to -4.7) in CA vs. -8.9 (-11.7 to - 6.5) in FD; P < 0.001]. Global radial and longitudinal strain held an area under the curve (AUC) of 0.75 (0.66-0.84) and AUC 0.73 (0.63-0.83). While the apical sparing and PLSD strain pattern showed the highest accuracy as single parameters [AUC 0.87 (0.79-0.95) and 0.81 (0.72-0.89), P < 0.001], the combination of subendocardial RS and the apical sparing pattern featured the highest diagnostic accuracy [AUC 0.92 (0.87-0.97)]. Conclusion: Combining radial strain-derived parameters to the established strain pattern apical sparing and PLSD improve the diagnostic accuracy in the echocardiographic assessment in suspected storage disease.

Neurological affection and serum neurofilament light chain in wild type transthyretin amyloidosis.

In contrast to inherited transthyretin amyloidosis (A-ATTRv), neuropathy is not a classic leading symptom of wild type transthyretin amyloidosis (A-ATTRwt). However, neurological symptoms are increasingly relevant in A-ATTRwt as well. To better understand the role of neurological symptoms in A-ATTRwt, A-ATTRwt patients were prospectively characterized at Amyloidosis Center Charité Berlin (ACCB) between 2018 and 2023 using detailed neurological examination, quality of life questionnaires, and analysis of age- and BMI-adapted serum neurofilament light chain (NFL) levels. 16 out of 73 (21.9%) patients presented with a severe neuropathy which we defined by a Neuropathy Impairment Score (NIS) of 20 or more. In this group, quality of life was reduced, peripheral neuropathy was more severe, and spinal stenosis and joint replacements were frequent. Age- and BMI matched serum NFL levels were markedly elevated in patients with a NIS ≥ 20. We therefore conclude that highly abnormal values in neuropathy scores such as the NIS occur in A-ATTRwt, and have an important impact on quality of life. Both peripheral neuropathy and spinal canal stenosis are likely contributors. Serum NFL may serve as a biomarker for neurological affection in patients with A-ATTRwt. It will be important to consider neurological aspects of A-ATTRwt for diagnosis, clinical follow-up, and future treatment development.

Patient satisfaction with coronary CT angiography versus invasive coronary angiography: results of a single-center randomized trial.

OBJECTIVE: Because there is evidence for a clinical benefit of using coronary computed tomography (CT) angiography instead of invasive coronary angiography (ICA) in patients with suspected coronary artery disease (CAD), we ascertained if patient satisfaction could represent an important barrier to implementation of coronary CT in clinical practice. MATERIALS AND METHODS: A total of 329 patients with suspected CAD and clinical indication for ICA were randomly assigned to undergo either CT or ICA for guiding treatment. Satisfaction for both groups was assessed by patient questionnaire completed twice, ≥24 h after CT or ICA, and at follow-up after a median of 3.7 years. Assessment included preparation, concern, comfort, helplessness, pain, willingness to undergo tests again, overall satisfaction, and preference. Pearson's chi-square test and Wilcoxon rank-sum test were used. RESULTS: Overall, 91% of patients undergoing CT (152/167) and 86% undergoing ICA completed assessment (140/162, p = 0.19). Patients reported being significantly better prepared for CT, less concerned about the test, and felt less helpless than during ICA (all: p < 0.001). Subjective pain (horizontal nonmarked visual analogue scale) was significantly lower for CT (6.9 ± 14.7) than for ICA (17.1 ± 22.7; p < 0.001). At follow-up, significantly more patients in the CT group reported very good satisfaction with communication of findings compared with the ICA group (p < 0.001) and 92% would recommend the institution to someone referred for the same examination. CONCLUSIONS: Results from our single-center randomized study show very good satisfaction with coronary CT compared to ICA. Thus, superior acceptance of CT should be considered in shared decision-making. CLINICAL RELEVANCE STATEMENT: This evaluation of patient satisfaction in a randomized study shows that patients' preference is in line with the clinical benefit provided by CT and also suggests to prefer a CT-first strategy in suspected coronary artery disease. KEY POINTS: • Subjective pain was significantly lower for coronary CT angiography than for invasive coronary angiography and patients felt better prepared and less concerned about CT. • Patients were overall more satisfied with coronary CT angiography than invasive coronary angiography in a randomized controlled trial. • After a median follow-up of 3.7 years, more patients in the CT group indicated very good satisfaction with the communication of findings and with the examination itself.

Right heart and left atrial strain to differentiate cardiac amyloidosis and Fabry disease.

Echocardiographic differentiation of cardiac amyloidosis (CA) and Fabry disease (FD) is often challenging using standard echocardiographic parameters. We retrospectively analyzed the diagnostic accuracy of right heart and left atrial strain parameters to discriminate CA from FD using receiver operating characteristic curve analyses and logistic regression models. A total of 47 FD and 88 CA patients with left ventricular wall thickening were analyzed. The comparison of both cardiomyopathies revealed significantly reduced global and free wall longitudinal right ventricular strain (RVS; global RVS: CA - 13 ± 4%, n = 67, vs. FD - 18 ± 4%, n = 39, p < 0.001) as well as right atrial strain (RAS; reservoir RAS: CA 12 ± 8%, n = 70, vs. FD 26 ± 9%, n = 40, p < 0.001) and left atrial strain (LAS) in CA patients. Individually, global RVS as well as phasic LAS and RAS showed the highest diagnostic accuracy to distinguish CA and FD. The best diagnostic accuracy was achieved by combining the age, basal RV diameter, global RVS, and reservoir and conduit RAS (area under the curve 0.96 [95% CI 0.90-1.00]). Differential echocardiographic diagnostic work-up of patients with suspected CA or FD can be improved by integrating structural and functional parameters of the right heart and the left atrium.Trial registration: DRKS00027403.

Coronary microevaginations characterize culprit plaques and their inflammatory microenvironment in a subtype of acute coronary syndrome with intact fibrous cap: results from the prospective translational OPTICO-ACS study.

AIMS: Coronary microevaginations (CMEs) represent an outward bulge of coronary plaques and have been introduced as a sign of adverse vascular remodelling following coronary device implantation. However, their role in atherosclerosis and plaque destabilization in the absence of coronary intervention is unknown. This study aimed to investigate CME as a novel feature of plaque vulnerability and to characterize its associated inflammatory cell-vessel-wall interactions. METHODS AND RESULTS: A total of 557 patients from the translational OPTICO-ACS study programme underwent optical coherence tomography imaging of the culprit vessel and simultaneous immunophenotyping of the culprit lesion (CL). Two hundred and fifty-eight CLs had a ruptured fibrous cap (RFC) and one hundred had intact fibrous cap (IFC) acute coronary syndrome (ACS) as an underlying pathophysiology. CMEs were significantly more frequent in CL when compared with non-CL (25 vs. 4%, P < 0.001) and were more frequently observed in lesions with IFC-ACS when compared with RFC-ACS (55.0 vs. 12.7%, P < 0.001). CMEs were particularly prevalent in IFC-ACS-causing CLs independent of a coronary bifurcation (IFC-ICB) when compared with IFC-ACS with an association to a coronary bifurcation (IFC-ACB, 65.4 vs. 43.7%, P = 0.030). CME emerged as the strongest independent predictor of IFC-ICB (relative risk 3.36, 95% confidence interval 1.67-6.76, P = 0.001) by multivariable regression analysis. IFC-ICB demonstrated an enrichment of monocytes in both culprit blood analysis (culprit ratio: 1.1 ± 0.2 vs. 0.9 ± 0.2, P = 0.048) and aspirated culprit thrombi (326 ± 162 vs. 96 ± 87 cells/mm2, P = 0.017), while IFC-ACB confirmed the accumulation of CD4+ T cells, as recently described. CONCLUSION: This study provides novel evidence for a pathophysiological involvement of CME in the development of IFC-ACS and provides first evidence for a distinct pathophysiological pathway for IFC-ICB, driven by CME-derived flow disturbances and inflammatory activation involving the innate immune system. TRIAL REGISTRATION: Registration of the study at clinicalTrials.gov (NCT03129503).

Diagnostic value of papillary muscle hypertrophy and mitral valve thickness to discriminate cardiac amyloidosis and Fabry disease.

BACKGROUND: Cardiac amyloidosis (CA) and Fabry disease (FD) cause myocardial damage but may also affect the valvular and subvalvular apparatus. We aimed to evaluate the diagnostic accuracy of new echocardiographic indices including mitral valve thickness and papillary muscle (PM) hypertrophy to differentiate CA and FD. METHODS: In patients with confirmed CA and FD, a detailed assessment of valvular function, mitral valve leaflet thickness and PM area as well as PM left ventricular area ratio (PM/LV-ratio) was performed in offline analyses. Receiver operating characteristic curve analyses were conducted to determine the diagnostic accuracy of mitral valve thickness, PM hypertrophy, and PM/LV-ratio to distinguish CA from FD. RESULTS: We retrospectively analyzed a cohort of 129 patients (FD n = 49, CA n = 80). CA patients showed significantly more thickened mitral valve leaflets (4.1 ± 1.3 mm vs. 2.9 ± 1.1 mm, p < 0.001) and a higher PM area [4.0 (3.1-4.6) mm2 vs. 2.8 (2.1-4.6) mm2, p = 0.009] with a comparable PM/LV-ratio in both groups. Mitral valve thickness showed the highest diagnostic accuracy to discriminate CA [AUC 0.77 (95% CI 0.67-0.87)]. The prevalence of aortic, tricuspid, and pulmonary valve regurgitation was significantly higher in CA (aortic regurgitation ≥ II° 13% vs. 4%, tricuspid regurgitation≥ II° 19% vs. 8%, p < 0.001). CONCLUSION: Our results suggest that the assessment of mitral valve thickness may be a new useful echocardiographic parameter to differentiate CA and FD, whereas papillary muscle hypertrophy and PM/LV-ratio showed a limited diagnostic performance to discriminate CA. German clinical trials registry: DRKS00027403.

Cholesterol crystals at the culprit lesion in patients with acute coronary syndrome are associated with worse cardiovascular outcomes at two years follow up - results from the translational OPTICO-ACS study program.

BACKGROUND: Cholesterol crystals (CCs) represent a feature of advanced atherosclerotic plaque and may be assessed by optical coherence tomography (OCT). Their impact on cardiovascular outcomes in patients presenting with acute coronary syndromes (ACS) is yet unknown. METHODS: The culprit lesion (CL) of 346 ACS-patients undergoing preintervention OCT imaging were screened for the presence of CCs and divided into two groups accordingly. The primary end-point was the rate of major adverse cardiac events plus (MACE+) consisting of cardiac death, myocardial infarction, target vessel revascularization and re-hospitalization due to unstable or progressive angina at two years. RESULTS: Among 346 patients, 57.2% presented with CCs at the CL. Patients with CCs exhibited a higher prevalence of ruptured fibrous caps (RFC-ACS) (79.8% vs. 56.8%; p < 0.001) and other high-risk features such as thin cap fibroatheroma (80.8% vs. 64.9%; p = 0.001), presence of macrophages (99.0% vs. 85.1%; p < 0.001) as well as a greater maximum lipid arc (294.0° vs. 259.3°; p < 0.001) at the CL as compared to patients without CCs. MACE+ at two years follow-up occurred more often in CC-patients (29.2% vs. 16.1%; p = 0.006) as compared to patients without CCs at the culprit site. Multivariable cox regression analysis identified CCs as independent predictor of MACE+ (HR 1.705; 1.025-2.838 CI, p = 0.040). CONCLUSIONS: CCs were associated with conventional high-risk plaque features and associated with increased MACE+-rates at two years follow up. The identification of CCs might be useful as prognostic marker in patients with ACS and assist "precision prevention" in the future.

Impact of body mass index on worsening of diastolic function and impairment of left atrial strain in the general female urban population: a subanalysis of the Berlin female risk evaluation echocardiography follow-up study.

Background: The association of body mass index (BMI) with diastolic dysfunction (DD) is well described in the literature. However, there is conflicting evidence and long-term follow-up data regarding effects of BMI on preclinical DD and left atrial (LA) function are scarce, highlighting the importance of early detection tools, such as myocardial strain. Purpose: The aim of our study was to prospectively analyze the impact of clinical and demographic parameters, especially of BMI, on worsening of diastolic function and left atrial strain (LAS) in an urban population of women with a low prevalence of cardiovascular risk factors. Methods and Results: An extensive clinical and echocardiographic assessment comprising the analysis of phasic LAS using two-dimensional speckle-tracking echocardiography (2D STE) was performed in 258 participants of the Berlin Female Risk Evaluation (BEFRI) trial between October 2019 and December 2020 after a mean follow-up period of 6.8 years. We compared clinical and echocardiographic parameters stratifying women by BMI < or ≥25 kg/m2, and we analyzed the impact of demographic characteristics on the worsening of DD and LA mechanics in the longer-term follow-up using univariate and multivariate regression analyses. 248 women were suitable for echocardiographic analysis of LAS using 2D STE. After a mean follow-up time of 6.8 years, LA reservoir strain (LASr) and LA conduit strain (LAScd) were significantly reduced in participants with a BMI ≥25 kg/m2 compared with women with a BMI <25 kg/m2 at baseline (30 ± 8% vs. 38 ± 9%, p < 0.0001; -14 ± 7% vs. -22 ± 8%, p < 0.0001). 28% of the overweighted women presented a deterioration of diastolic function at the time of follow-up in contrast with only 7% of the group with a BMI <25 kg/m2 (p < 0.0001). BMI remained significantly associated with LAS reductions after adjustment for other risk factors in multivariate regression analyses. Conclusion: Overweight and obesity are related to impaired LAS and to a worsening of diastolic function after a long-term follow-up in a cohort of randomly selected women.

Determinants of myocardial work indices in women.

OBJECTIVE: By incorporating myocardial deformation and afterload, novel echocardiographic myocardial work indices appear to be advantageous compared to load-dependent left ventricular (LV) deformation analyses. As such, these indices may provide a more accurate and, above all, load-independent estimation of LV function in patients with chronically increased afterload. To date however, data on the relation of these indices to clinical and conventional echocardiographic parameters are scarce. PURPOSE: Our aim was to evaluate the relationship between myocardial work indices and age, body mass index (BMI), NTproBNP, the clinical history of arterial hypertension and diastolic dysfunction as well as selected conventional echocardiographic parameters in women. METHODS: We analyzed echocardiographic data of women included in the Berlin Female Risk Evaluation (BEFRI) trial. Global Work Index (GWI), Global Constructive Work (GCW), Global Wasted Work (GWW) and Global Work Efficiency (GWE) were calculated using commercially available software based on noninvasive pressure-strain loops. The impact of selected clinical and echocardiographic characteristics on myocardial work parameters was investigated by uni- and multivariate regression analyses. RESULTS: A total of 224 women were included in the final analysis. 155 of them were normotensive and 69 had a history of arterial hypertension. Diastolic dysfunction was more prevalent in subjects with arterial hypertension. Study participants with arterial hypertension showed higher GWI and GCW whereas GWW and GWE did not significantly differ between groups. GCW and GWW were lower and GWE higher in the presence of normal diastolic function. In multivariate regression analyses, arterial hypertension, LV GLS, and interventricular septal thickness were significantly associated with GWI. GCW showed significant associations with the clinical history of arterial hypertension, LV GLS, age and IVRT. Similarly, LV GLS, IVRT and mitral inflow E wave deceleration time were identified to be significant determinants of GWW and GWE. CONCLUSION: Our data confirm that, in a randomly selected sample of the general urban female population, myocardial work parameters are predominantly determined by LV GLS. In addition, the presence of arterial hypertension was identified to be a significant determinant of GWI and GCW, but not for GWW and GWE. Finally, a prolonged LV relaxation time was significantly associated with GWW and GWE, suggesting more wasted myocardial work and lower GWE values with increasing LV relaxation time.

Spotty calcium deposits within acute coronary syndrome (ACS)-causing culprit lesions impact inflammatory vessel-wall interactions and are associated with higher cardiovascular event rates at one year follow-up: Results from the prospective translational OPTICO-ACS study program.

BACKGROUND AND AIMS: Spotty calcium deposits (SCD) represent a vulnerable plaque feature which seems to result - as based on recent invitro studies - from inflammatory vessel-wall interactions. SCD can be reliably assessed by optical coherence tomography (OCT). Their prognostic impact is yet unknown. Therefore, the aims of this translational study were to comprehensively characterize different plaque calcification patterns, to analyze the associated inflammatory mechanisms in the microenvironment of acute coronary syndrome (ACS)-causing culprit lesions (CL) and to investigate the prognostic significance of SCD in a large cohort of ACS-patients. METHODS: CL of the first 155 consecutive ACS-patients from the translational OPTICO-ACS-study program were investigated by OCT-characterization of the calcium phenotype at ACS-causing culprit lesions. Simultaneous immunophenotyping by flow-cytometric analysis and cytokine bead array technique across the CL gradient (ratio local/systemic levels) was performed and incidental major adverse cardiovascular events plus (MACE+) at 12 months after ACS were assessed. RESULTS: SCD were observed within 45.2% of all analyzed ACS-causing culprit lesions (CL). Culprits containing spotty calcium were characterized by an increased culprit ratio of innate effector cytokines interleukin (IL)-8 [2.04 (1.24) vs. 1.37 (1.10) p < 0.05], as well as TNF (tumor necrosis factor)-α [1.17 (0.93) vs. 1.06 (0.89); p < 0.05)] and an increased ratio of circulating neutrophils [0.96 (0.85) vs. 0.91 (0.77); p < 0.05] as compared to culprit plaques without SCD. Total monocyte levels did not differ between the two groups (p = n.s.). However, SCD-containing CLs were characterized by an increased culprit ratio of intermediate monocytes [(1.15 (0.81) vs. 0.96 (0.84); p < 0.05)] with an enhanced surface expression of the integrin receptor CD49d as compared to intermediate monocytes derived from SCD-free CLs [(1.06 (0.94) vs. 0.97 (0.91)] p < 0.05. Finally, 12 months rates of MACE+ were higher in patients with, as compared to patients without SCD at CL (16.4% vs. 5.3%; p < 0.05). CONCLUSIONS: This study for the first time identified a specific inflammatory profile of CL with SCD, with a predominance of neutrophils, intermediate monocytes and their corresponding effector molecules. Hence, this study advances our understanding of ACS-causing CL and provides the basis for future personalized anti-inflammatory, therapeutic approaches to ACS.

Consensus recommendations on holistic care in hereditary ATTR amyloidosis: an international Delphi survey of patient advocates and multidisciplinary healthcare professionals.

BACKGROUND: Hereditary transthyretin-mediated amyloidosis is a rare, progressive and potentially life-limiting multisystem disease, affecting every aspect of a patient's life. OBJECTIVES: This online international Delphi survey aimed to evolve clinical-patient-led practical guidance, to inspire and encourage a holistic approach to care that is managed in specialist settings by multidisciplinary teams and supported by allied healthcare professionals (HCPs) and patient advocacy groups (PAGs). DESIGN: A 14-member joint patient advocate-HCP primary panel was convened including representation from PAGs and key clinical specialties (neurology, cardiology, internal medicine, physiotherapy, clinical psychology, dietetics and specialist nursing). Guidance evolved on the care provision needed to support seven core goals: early diagnosis and treatment; disease monitoring and organisation of care; maintenance of physical and mental health; family-centred care and caregiver support; patient-doctor dialogue; access to social support and social networking. PARTICIPANTS: From June to October 2022, 252 HCPs and 51 PAG representatives from 27 countries were invited to participate in a Delphi survey. Of the 122 respondents who answered at least one survey question, most were HCPs (100, 82%) from specialist centres; the remainder were PAG representatives (22, 18%). MAIN OUTCOME MEASURE: Both level of agreement and feasibility in practice of each recommendation was tested by two anonymised online Delphi voting rounds. RESULTS: Based on an a priori threshold for consensus of ≥75% agreement, the clinical-patient community endorsed all but one recommendation. However, only 17/49 (35%) recommendations were identified by most HCPs as a core part of routine care; the remainder (32/49 (65%)) were identified as part of core care by <50% of HCPs respondents, or as largely achievable by 30%-45% of HCPs. By comparison, PAGs recorded lower implementation levels. CONCLUSIONS: Further consideration is needed on how to evolve multidisciplinary services (supported by allied HCPs and PAGs) to address the complex needs of those affected by this disease.

Prevalence, one-year-incidence and predictors of carcinoid heart disease.

BACKGROUND: Carcinoid heart disease (CHD) caused by neuroendocrine tumours (NET) is associated with an increased morbidity and mortality due to valvular dysfunction and right sided heart failure. The present study aimed to assess the prevalence and one-year-incidence of CHD in NET patients. Tumour characteristics, laboratory measurements, and echocardiographic findings were evaluated to identify predictors of CHD manifestation. METHODS: The study was an investigator-initiated, monocentric, prospective trial. Patients with NET without previously diagnosed CHD were included and underwent comprehensive gastroenterological and oncological diagnostics. Echocardiographic examinations were performed at baseline and after one year. RESULTS: Forty-seven NET patients were enrolled into the study, 64% of them showed clinical features of a carcinoid syndrome (CS). Three patients presented with CHD at baseline and three patients developed cardiac involvement during the follow-up period corresponding to a prevalence of 6% at baseline and an incidence of 6.8% within one year. Hydroxyindoleacetic acid (5-HIAA) was identified to predict the occurrence of CHD (OR, 1.004; 95% CI, 1.001-1.006 for increase of 5-HIAA), while chromogranin A (CgA), and Kiel antigen 67 (Ki 67%) had no predictive value. Six patients with CHD at twelve-month follow-up revealed a tendency for larger right heart diameters and increased values of myocardial performance index (MPEI) at baseline compared to NET patients. CONCLUSION: The prevalence at baseline and one-year-incidence of CHD was 6-7%. 5-HIAA was identified as the only marker which predict the development of CHD.

A comprehensive echocardiographic analysis during simulated hypovolaemia: An observational study.

BACKGROUND: Peri-operative and critically ill patients often experience mild to moderate hypovolaemic shock with preserved mean arterial pressure (MAP), heart rate (HR) and decreased stroke volume index (SVI). OBJECTIVES: The aim of this study was to evaluate echocardiographic parameters during simulated mild to moderate central hypovolaemia. DESIGN: This was a prospective preclinical study. SETTING: Laboratory trial performed in Charité-Universitätsmedizin Berlin, Germany. PATIENTS AND METHODS: Thirty healthy male volunteers underwent graded central hypovolaemia using a lower body negative pressure (LBNP) chamber with a stepwise decrease to simulate a mild (-15 mmHg), mild-to-moderate (-30 mmHg), and moderate state of hypovolaemic shock (-45 mmHg). During every stage, a transthoracic echocardiography examination (TTE) was performed by a certified examiner. MAIN OUTCOME MEASURES: Systolic and diastolic myocardial performance markers, as well as cardiac volumes were recorded during simulated hypovolaemia and compared to baseline values. RESULTS: During simulated hypovolaemia via LBNP, SVI decreased progressively at all stages, whereas MAP and HR did not consistently change. Left ventricular (LV) ejection fraction decreased at -30 and -45 mmHg. Simultaneously with SVI decline, LV global longitudinal strain (LV GLS), tricuspid annular plain systolic excursion (TAPSE), and right ventricular RV S' and left-atrial end-systolic volume (LA ESV) decreased compared to baseline at all stages. CONCLUSIONS: In this study, simulated central hypovolaemia using LBNP did not induce consistent changes in MAP and HR. SVI decreased and was associated with deteriorated right- and left-ventricular function, observed with echocardiography. The decreased filling status was characterised by decreased LA ESV. CLINICAL TRIAL NUMBER: ClinicalTrials.gov Identifier: NCT03481855.

Culprit plaque morphology determines inflammatory risk and clinical outcomes in acute coronary syndrome.

AIMS: Rupture of the fibrous cap (RFC) and erosion of an intact fibrous cap (IFC) are the two predominant mechanisms causing acute coronary syndromes (ACS). It is uncertain whether clinical outcomes are different following RFC-ACS vs. IFC-ACS and whether this is affected by a specific inflammatory response. The prospective, translational OPTIcal-COherence Tomography in Acute Coronary Syndrome study programme investigates the impact of the culprit lesion phenotype on inflammatory profiles and prognosis in ACS patients. METHODS AND RESULTS: This analysis included 398 consecutive ACS patients, of which 62% had RFC-ACS and 25% had IFC-ACS. The primary endpoint was a composite of cardiac death, recurrent ACS, hospitalization for unstable angina, and target vessel revascularization at 2 years [major adverse cardiovascular events (MACE+)]. Inflammatory profiling was performed at baseline and after 90 days. Patients with IFC-ACS had lower rates of MACE+ than those with RFC-ACS (14.3% vs. 26.7%, P = 0.02). In 368-plex proteomic analyses, patients with IFC-ACS showed lower inflammatory proteome expression compared with those with RFC-ACS, including interleukin-6 and proteins associated with the response to interleukin-1ß. Circulating plasma levels of interleukin-1ß decreased from baseline to 3 months following IFC-ACS (P < 0.001) but remained stable following RFC-ACS (P = 0.25). Interleukin-6 levels decreased in patients with RFC-ACS free of MACE+ (P = 0.01) but persisted high in those with MACE+. CONCLUSION: This study demonstrates a distinct inflammatory response and a lower risk of MACE+ following IFC-ACS. These findings advance our understanding of inflammatory cascades associated with different mechanisms of plaque disruption and provide hypothesis generating data for personalized anti-inflammatory therapeutic allocation to ACS patients, a strategy that merits evaluation in future clinical trials.

Phasic left atrial strain to predict worsening of diastolic function: Results from the prospective Berlin Female Risk Evaluation follow-up trial.

Purpose: The predictive value of maximum left atrial volume index (LAVI), phasic left atrial strain (LAS) and other standard echocardiographic parameters assessing left ventricular (LV) diastolic function to discriminate a future worsening of diastolic function (DD) in patients at risk is unclear. We aimed to prospectively assess and compare the clinical impact of these parameters in a randomly selected study sample of the general urban female population. Methods and results: A comprehensive clinical and echocardiographic evaluation was performed in 256 participants of the Berlin Female Risk Evaluation (BEFRI) trial after a mean follow up time of 6.8 years. After an assessment of participants' current DD status, the predictive impact of an impaired LAS on the course of DD was assessed and compared with LAVI and other DD parameters using receiver operating characteristic (ROC) curve and multivariate logistic regression analyses. Subjects with no DD (DD0) who showed a decline of diastolic function by the time of follow-up showed a reduced LA reservoir (LASr) and conduit strain (LAScd) compared to subjects who remained in the healthy range (LASr 28.0% ± 7.0 vs. 41.9% ± 8.5; LAScd -13.2% ± 5.1 vs. -25.4% ± 9.1; p < 0.001). With an area under the curve (AUC) of 0.88 (95%CI 0.82-0.94) and 0.84 (95%CI 0.79-0.89), LASr and LAScd exhibited the highest discriminative value in predicting worsening of diastolic function, whereas LAVI was only of limited prognostic value [AUC 0.63 (95%CI 0.54-0.73)]. In logistic regression analyses, LAS remained a significant predictor for a decline of diastolic function after controlling for clinical and standard echocardiographic DD parameters, indicating its incremental predictive value. Conclusion: The analysis of phasic LAS may be useful to predict worsening of LV diastolic function in DD0 patients at risk for a future DD development.GRAPHICAL ABSTRACT.

[Alternative treatment strategies for atrial fibrillation : Benefits from yoga?] / Alternative Behandlungsverfahren bei Vorhofflimmern : Was bringt Yoga?

Atrial fibrillation, the most common sustained cardiac arrhythmia, is associated with significant morbidity, mortality, and healthcare utilization. Since the procedures used to treat atrial fibrillation have a number of limitations and risks, there is a growing interest in alternative treatment strategies for patients with atrial fibrillation. One such option is yoga. To date, only a few studies are available on its effect on atrial fibrillation. However, these suggest that yoga may indeed be able to reduce the frequency of the arrhythmia and its progression. The risk factors for atrial fibrillation and quality of life in affected patients are also positively affected. As adverse effects and complications are extremely rare with competent guidance, yoga may already be recommended now. However, further clinical studies are needed to provide recommendations that meet evidence-based criteria.

Valve embolization during transcatheter aortic valve implantation: Incidence, risk factors and follow-up by computed tomography.

Background: In most cases of transcatheter valve embolization and migration (TVEM), the embolized valve remains in the aorta after implantation of a second valve into the aortic root. There is little data on potential late complications such as valve thrombosis or aortic wall alterations by embolized valves. Aims: The aim of this study was to analyze the incidence of TVEM in a large cohort of patients undergoing transcatheter aortic valve implantation (TAVI) and to examine embolized valves by computed tomography (CT) late after TAVI. Methods: The patient database of our center was screened for cases of TVEM between July 2009 and July 2021. To identify risk factors, TVEM cases were compared to a cohort of 200 consecutive TAVI cases. Out of 35 surviving TVEM patients, ten patients underwent follow-up by echocardiography and CT. Results: 54 TVEM occurred in 3757 TAVI procedures, 46 cases were managed percutaneously. Horizontal aorta (odds ratio [OR] 7.51, 95% confidence interval [CI] 3.4-16.6, p < 0.001), implantation of a self-expanding valve (OR 4.63, 95% CI 2.2-9.7, p < 0.01) and a left ventricular ejection fraction < 40% (OR 2.94, 95% CI 1.1-7.3, p = 0.016) were identified as risk factors for TVEM. CT scans were performed on average 26.3 months after TAVI (range 2-84 months) and detected hypoattenuated leaflet thickening (HALT) in two patients as well as parts of the stent frame protruding into the aortic wall in three patients. Conclusion: TVEM represents a rare complication of TAVI. Follow up-CT detected no pathological findings requiring intervention.

Frequently Used Patient-Reported Outcome Measures of General Physical Function Were Highly Correlated With a Multitask Performance Outcome Test Battery.

OBJECTIVES: This study aimed to determine the relationship between frequently used patient-reported outcome (PRO) measures and a multitask performance outcome (PerfO) measure of general physical function (PF) and to examine the association of these measures with depressive mood, pain, and age. METHODS: Frequently used PRO measures of general PF (Patient-Reported Outcomes Measurement Information System [PROMIS] PF item bank, PROMIS PF Short Form 20a, Short Form 36 Physical Function Scale) and a PerfO test battery, namely, the Physical Performance Test (PPT), were administered to 78 adult patients from 3 inpatient clinics (cardiology and angiology, rheumatology and clinical immunology, and psychosomatic medicine) at Charité - Universitätsmedizin Berlin. Pearson correlations were used to investigate the associations between PRO measures and the PPT. To explore the predictive value of age, depressive symptoms, and pain intensity, we conducted multiple linear regression analysis for each PF measure. RESULTS: We found strong linear relationships between PRO measures and PPT sum scores. Correlations between PPT sum scores and PROMIS PF T-scores were r > 0.75. For all PRO and PerfO measures, age was a predictor of general PF whereas depressive mood was not found to be a relevant predictor. Moreover, pain intensity was found to be a significant predictor of PRO measures but not for PPT sum scores. CONCLUSIONS: Our findings suggest that frequently used PRO measures and a multitask PerfO measure of general PF can be used to measure a common PF construct. Nevertheless, PF scores based on PRO measures should ideally be controlled for self-rated pain intensity.