Atrial Giant Cell Myocarditis as a Cause of Heart Failure: Diagnostic Pathway and Successful Treatment.

We present a patient with acute heart failure and new onset atrial fibrillation secondary to giant cell myocarditis with lone atrial involvement. The diagnosis was managed with cardiac magnetic resonance and confirmed by interventionally guided biopsy. In the future, diagnosis could be managed noninvasively for this rare entity as the gold standard. (Level of Difficulty: Advanced.).

Fast-Strain Encoded Cardiac Magnetic Resonance During Vasodilator Perfusion Stress Testing.

Background: Cardiac magnetic resonance perfusion imaging during vasodilator stress is an established modality in patients with suspected and known coronary artery disease (CAD). Aim: This study aimed to evaluate the performance of fast-Strain-Encoded-MRI (fast-SENC) for the diagnostic classification and risk stratification of patients with ischemic heart disease. Methods: Perfusion and fast-SENC cardiac magnetic resonance (CMR) images were retrospectively analyzed in 111 patients who underwent stress CMR. The average myocardial perfusion score index, global and segmental longitudinal and circumferential strain (GLS and GCS and SLS and SCS, respectively), were measured at rest and during stress. The combination of SLS and SCS was referred to as segmental aggregate strain (SAS). Segments exhibiting perfusion defects or SAS impairment during stress were defined as "ischemic." All-cause mortality, non-fatal infarction, and urgent revascularization were deemed as our combined clinical endpoint. Results: During adenosine stress testing, 44 of 111 (39.6%) patients exhibited inducible perfusion abnormalities. During a mean follow-up of 1.94 ± 0.65 years, 25 (22.5%) patients reached the combined endpoint (death in n = 2, infarction in n = 3 and urgent revascularization in n = 20). Inducible perfusion defects were associated with higher number of segments with inducible SAS reduction ≥6.5% (χ2 = 37.8, AUC = 0.79, 95% CI = 0.71-0.87, p < 0.001). In addition, patients with inducible perfusion defects or SAS impairment exhibited poorer outcomes (AUCPerf = 0.81 vs. AUCSAS = 0.74, p = NS vs. each other, and χ2 = 30.8, HR = 10.3 and χ2 = 9.5, HR = 3.5, respectively, p < 0.01 for both). Conclusion: Purely quantitative strain analysis by fast-SENC during vasodilator stress was related to the diagnosis of ischemia by first-pass perfusion and is non-inferior for the risk stratification of patients with ischemic heart disease. This may bear clinical implications, especially in patients with contraindications for contrast agent administration.

Relationship Between Quality of Life Indicators and Cardiac Status Indicators in Chemotherapy Patients.

AIM: With the aim of improving personalized treatment of patients on chemotherapy, the objective of the study was to assess the degree of association between selected Quality of life (QoL) indicators and both clinical and imaging cardiac status indicators when detecting deterioration in QoL of these patients. METHODS: In a cohort clinical study in Hamburg, from August 2017 through October 2020, 59 cancer patients, aged 18-80 years, were evaluated before chemotherapy, and at several follow-ups, using EQ-5D and SF-36 QoL questionnaires, fast strain-encoded (fast-SENC) cardiac magnetic resonance (CMR), conventional CMR, and echocardiography, and further received a clinical and biomarker examination. Data was analyzed using survival analyses. A decline of more than 5% in each observed QoL metric value was defined as the observed event. Patient were separated into groups according to the presentation of cardiotoxicity as per its clinical definition, the establishment of the indication for cardioprotective therapy initiation, and by a worsening in the value of each observed imaging metric by more than 5% in the previous follow-up compared to the corresponding pre-chemotherapy baseline value. RESULTS: Among clinical cardiac status indicators, the indication for cardioprotective therapy showed statistically good association with QoL scores (EQ-5D p=0.028; SF-36 physical component p=0.016; SF-36 mental component p=0.012). In terms of imaging metrics, the MyoHealth segmental myocardial strain score was the only one demonstrating consistently good QoL score association (EQ-5D p=0.005; SF-36 physical component p=0.056; SF-36 mental component p=0.002). CONCLUSIONS: Established fast-SENC CMR scores are capable of highlighting patients with reduced QoL, who require more frequent/optimal management.

Multiparametric Early Detection and Prediction of Cardiotoxicity Using Myocardial Strain, T1 and T2 Mapping, and Biochemical Markers: A Longitudinal Cardiac Resonance Imaging Study During 2 Years of Follow-Up.

BACKGROUND: Our goal was to evaluate the ability of cardiovascular magnetic resonance for detecting and predicting cardiac dysfunction in patients receiving cancer therapy. Left ventricular ejection fraction, global and regional strain utilizing fast-strain-encoded, T1 and T2 mapping, and cardiac biomarkers (troponin and BNP [brain natriuretic peptide]) were analyzed. METHODS: Sixty-one patients (47 with breast cancer, 11 with non-Hodgkin lymphoma, and 3 with Hodgkin lymphoma) underwent cardiovascular magnetic resonance scans at baseline and at regular intervals during 2 years of follow-up. The percentage of all left ventricular myocardial segments with strain ≤-17% (normal myocardium [%]) was analyzed. Clinical cardiotoxicity (CTX) and sub-CTX were defined according to standard measures. RESULTS: Nine (15%) patients developed CTX, 26 (43%) had sub-CTX. Of the 35 patients with CTX or sub-CTX, 24 (69%) were treated with cardioprotective medications and showed recovery of cardiac function. The amount of normal myocardium (%) exhibited markedly higher accuracy for the detection of CTX and sub-CTX compared with left ventricular ejection fraction, T1, and T2 mapping as well as troponin I (Δareas under the curve=0.20, 0.24, and 0.46 for normal myocardium (%) versus left ventricular ejection fraction, troponin I, and T1 mapping, P<0.001 for all). In addition, normal myocardium (%) at baseline accurately identified patients with subsequent CTX (P<0.001), which was not achieved by any other markers. CONCLUSIONS: Normal myocardium (%) derived by fast-strain-encoded cardiovascular magnetic resonance, is an accurate and sensitive tool that can establish cardiac safety in patients with cancer undergoing cardiotoxic chemotherapy not only for the early detection but also for the prediction of those at risk of developing CTX. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03543228.

Use of drug-eluting stents in acute myocardial infarction with persistent ST-segment elevation: results of the ALKK PCI-registry.

BACKGROUND: Drug-eluting stents (DES) reduce the rate of in-stent restenosis (ISR) and target vessel revascularization significantly when compared with bare metal stents (BMS). Their beneficial effects have been demonstrated in patients with acute myocardial infarction also, but the use of DES in the latter population seems to be still limited in clinical practice. METHODS AND RESULTS: From January 2006 to December 2011, 25,424 patients with ST-elevation myocardial infarction were enrolled in the German ALKK PCI-registry. In 5,467 patients (21.5 %), a DES was implanted in the culprit segment, in 16,911 patients (66.5 %) a BMS, and 2,959 patients (11.6 %) received neither DES nor BMS. The rates of DES for typical subgroups were 31.7 % in patients with diabetes, 36.6 % in unprotected left main stenosis, 32.4 % in ostial lesions, 32.0 % for a stent length >15 mm, 26.2 % for a stent diameter ≤3 mm, and 58.5 % for ISR. There was a wide range in the use of DES between the different ALKK hospitals with a minimum of 2.3 % and a maximum of 58.3 % for the total study period (median 22.0 %, quartiles 14.6 and 37.5 %). CONCLUSIONS: Despite convincing data for the use of DES in patients with STEMI, there is still an underuse of DES in this clinical setting in Germany. This is particularly worrying for the subgroups of patients and lesions with a high risk of restenosis. Further efforts are needed to reduce the skepticism about DES and to improve guideline adherent treatment.

Age-related differences in antithrombotic therapy, success rate and in-hospital mortality in patients undergoing percutaneous coronary intervention: results of the quality control registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte (ALKK).

INTRODUCTION: This analysis examines the influence of age on antithrombotic therapy, success rate of percutaneous coronary intervention (PCI) and in-hospital mortality in patients with Acute Coronary Syndrome (ACS) and elective PCI. METHODS: We analysed data of 26,795 unselected patients with ST-elevation myocardial infarction (STEMI), non-ST-elevation myocardial infarction (NSTEMI), unstable Angina (UA) and elective PCI from the ALKK-PCI Registry 2006, a German prospective, multicentre registry. RESULTS: Elderly patients (>75) with ACS were significantly less often treated with acetylsalicylic acid intravenously and a clopidogrel loading dose of 600 mg. Moreover, the administration of GP IIb/IIIa antagonists was significantly lower in these patients. The rate of successful PCI (indicated as TIMI 3 flow) is comparable in younger and elderly patients with elective PCI, UA and NSTEMI, whereas there were more unsuccessful interventions in elderly patients with STEMI (13.2 vs. 11.0%, p < 0,033). In all indications elderly patients showed increased in-hospital mortality. CONCLUSION: In clinical practice, elderly patients with ACS undergoing PCI receive significantly less intensive antithrombotic treatment. In terms of successful PCI, there was no significant difference between the age groups in patients with elective PCI, UA and NSTEMI. The higher in-hospital mortality of the elderly in all patient groups is most likely due to a higher rate of comorbidities.

Guideline-recommended secondary prevention drug therapy after acute myocardial infarction: predictors and outcomes of nonadherence.

BACKGROUND: Guideline-recommended pharmacotherapy after myocardial infarction (MI) has been shown to reduce cardiovascular morbidity and mortality. Our objectives were to determine factors of, and to measure outcomes associated with nonadherence after MI. DESIGN: Multicentre, prospective, observational study (Acute Coronary Syndromes Registry). METHODS: We analyzed data of 11,823 consecutive hospital survivors of acute MI and evaluated their discharge medication with the five following drugs: acetyl salicylic acid, clopidogrel, ß-blocker, angiotensin-converting enzyme inhibitor/sartan and statin. Patients receiving less than four drugs (group 1, n=3439, 29.1%) were compared with those receiving 4-5 drugs (group 2, n=8384, 70.9%). The impact of clinical, demographic and treatment factors on not prescribing each of these five drugs at discharge was investigated by using multiple logistic regression models. RESULTS: Patients of group 1 were older, had more comorbidities, more frequently suffered a nonST elevation MI and less often received reperfusion therapy. In the multivariate analysis, group 1 was associated with an increased risk for death at 1-year follow-up [odds ratio (OR): 1.6, 95% confidence interval (CI): 1.4-1.9]. After adjustment for confounding variables chronic oral anticoagulation was the strongest predictor for not receiving acetyl salicylic acid (OR: 19.6, 95% CI: 15.9-24.0) at discharge, no percutaneous coronary intervention within 48 h for not receiving statin (OR: 2.1, 95% CI: 1.9-2.4) and clopidogrel (OR: 10.4, 95% CI: 9.4-11.5), chronic obstructive lung disease for not receiving ß-blocker (OR: 4.2, 95% CI: 3.6-4.9) and chronic renal insufficiency for not receiving angiotensin-converting enzyme inhibitor/sartan (OR: 2.8, 95% CI: 2.2-3.5). CONCLUSION: In clinical practice guideline-adherent secondary prevention drug therapy is linked with an improved 1-year survival. Comorbidities and no interventional treatment were strong negative predictors for guideline-adherent discharge medication.

Enoxaparin in patients with primary percutaneous coronary intervention for acute ST segment elevation myocardial infarction.

The inhibition of thrombin plays a key role as adjunct therapy in the management of patients with primary percutaneous coronary intervention for ST elevation myocardial infarction. Enoxaparin provides a more predictable and constant level of anticoagulation compared with the current standard unfractionated heparin. The available data from smaller studies and prospective registries suggest that enoxaparin is associated with a reduction in the rate of death and nonfatal reinfarction after primary percutaneous coronary intervention without an increase in bleeding complications. Thus, a large randomized trial is warranted to further evaluate the role of enoxaparin in these patients.

Quantification of free total plasma DNA and minimal residual disease detection in the plasma of children with acute lymphoblastic leukemia.

The analysis of total plasma DNA and the monitoring of leukemic clone-specific immunoglobulin and/or T-cell receptor gene rearrangements for the evaluation of minimal residual disease (MRD) in the plasma may be useful tools for prognostic purposes or for early detection of subclinical disease recurrence in children with acute lymphoblastic leukemia (ALL). The aim of this paper is to establish reference ranges for total plasma DNA concentrations and to test the feasibility of MRD measurements employing plasma DNA from children with ALL by using real-time quantitative (RQ)-PCR. Despite wide inter-individual variation, the median concentrations of total plasma DNA for 12 healthy donors (57 ng/ml), 21 children with ALL after day 4 of treatment initiation (62 ng/ml) and 13 children with other malignancies (76 ng/ml) were similar. However, ALL patients had significantly higher concentrations at diagnosis (277 ng/ml) and on treatment day 3 (248 ng/ml) before returning to normal afterwards. Early plasma DNA MRD kinetics could be established for 15 ALL patients and showed good concordance with bone marrow MRD. Plasma DNA was higher in children with ALL at diagnosis but returned to normal within the first four treatment days. Despite low concentrations of DNA, it is feasible to measure MRD kinetics in plasma DNA during ALL induction therapy by adapted real-time PCR methodologies.

Light scattering of human lens vesicles in vitro.

In passing through the lens, light crosses thousands of cell membranes. To explore the possible contribution of lipids to the scattering properties of the lens, we have carried out in vitro studies with lipids extracted from human lenses 1-90 years of age. Sphingomyelin and human lens lipids were extruded into large unilamellar vesicles (LUVs). The intensity of light scattered by human lens LUVs increased with age and lipid hydrocarbon chain order. Hydrocarbon chain order also correlated with light scattering intensity by sphingomyelin LUVs. Light scattered by LUVs composed of sphingomyelin (1-30 mg ml(-1)) was 20 to 100 times more intense than that scattered by the same concentration of alpha-crystallin in aqueous media. Increased lipid hydrocarbon chain order as well as variations in the headgroup and interfacial region of bilayers resulting from lipid compositional changes can influence membrane light scattering properties. In vitro measurements suggest that the contribution to light scattering by lipids may be significant and should not be disregarded in the investigation of factors and components that lead to the increase in light scattering by human lenses with age and cataract.

31P NMR quantification and monophasic solvent purification of human and bovine lens phospholipids.

Most lipid extraction procedures [Folch, J., Lees, M., and Sloane-Stanley, G.H. (1957) A Simple Method for the Isolation and Purification of Total Lipids from Animal Tissues, J. Biol. Chem. 226, 497-509; Bligh, E.G., and Dyer, W.J. (1959) A Rapid Method of Total Lipid Extraction and Purification, Can. J. Biochem. Physiol. 37, 911-917] employ biphasic solvent mixtures designed to dissolve the lipids in an organic phase and remove impurities in an aqueous phase. However, when applying these protocols to biological matrices such as that of the ocular lens, the formation of an emulsion layer between the organic and aqueous phases causes poor reproducibility in extraction yields and gives only a small amount of the lipid-containing chloroform phase. In this study, we quantified phospholipids at each step of the Folch et al. extraction protocol and compared the yield of human and bovine lens phospholipids obtained by the Folch-based approach and a novel monophasic methanol extraction method designed to circumvent the problems associated with biphasic extraction protocols. A monophasic methanol extraction coupled with 31P NMR spectroscopy was found to be the simplest, quickest, and most effective method for quantifying the phospholipid content of the lens.