Time course of eosinophilic myocarditis visualized by CMR

We report the diagnostic potential of cardiovascular magnetic resonance (CMR) to visualize the time course of eosinophilic myocarditis upon successful treatment. A 50-year-old man was admitted with a progressive heart failure. Endomyocardial biopsies were taken from the left ventricle because of a white blood cell count of 17000/mm3 with 41% eosinophils. Histological evaluation revealed endomyocardial eosinophilic infiltration and areas of myocyte necrosis. The patient was diagnosed with hypereosinophilic myocarditis due to idiopathic hypereosinophilic syndrome. CMR-studies at presentation and a follow-up study 3 weeks later showed diffuse subendocardial LGE in the whole left ventricle. Upon treatment with steroids, CMR-studies revealed marked reduction of subendocardial LGE after 3 months in parallel with further clinical improvement. This case therefore highlights the clinical importance of CMR to visualize the extent of endomyocardial involvement in the diagnosis and treatment of eosinophilic myocarditis

Skeletal muscle alterations in tachycardia-induced heart failure are linked to deficient natriuretic peptide signalling and are attenuated by RAS-/NEP-inhibition

Background Heart failure induced cachexia is highly prevalent. Insights into disease progression are lacking. Methods Early state of left ventricular dysfunction (ELVD) and symptomatic systolic heart failure (HF) were both induced in rabbits by tachypacing. Tissue of limb muscle (LM) was subjected to histologic assessment. For unbiased characterisation of early and late myopathy, a proteomic approach followed by computational pathway-analyses was performed and combined with pathway-focused gene expression analyses. Specimen of thoracic diaphragm (TD) served as control for inactivity-induced skeletal muscle alterations. In a subsequent study, inhibition of the renin-angiotensin-system and neprilysin (RAS-/NEP) was compared to placebo. Results HF was accompanied by loss of protein content (8.7±0.4% vs. 7.0±0.5%, mean±SEM, control vs. HF, p<0.01) and a slow-to-fast fibre type switch, establishing hallmarks of cachexia. In ELVD, the enzymatic set-up of LM and TD shifted to a catabolic state. A disturbed malate-aspartate shuttle went well with increased enzymes of glycolysis, forming the enzymatic basis for enforced anoxic energy regeneration. The histological findings and the pathway analysis of metabolic results drew the picture of suppressed PGC-1α signalling, linked to the natriuretic peptide system. In HF, natriuretic peptide signalling was desensitised, as confirmed by an increase in the ratio of serum BNP to tissue cGMP (57.0±18.6pg/ml/nM/ml vs. 165.8±16.76pg/ml/nM/ml, p<0.05) and a reduced expression of natriuretic peptide receptor-A. In HF, combined RAS-/NEP-inhibition prevented from loss in protein content (8.7±0.3% vs. 6.0±0.6% vs. 8.3±0.9%, Baseline vs. HF-Placebo vs. HF-RAS/NEP, p<0.05 Baseline vs. HF-Placebo, p = 0.7 Baseline vs. HF-RAS/NEP). Conclusions Tachypacing-induced heart failure entails a generalised myopathy, preceding systolic dysfunction. The characterisation of “pre-cachectic” state and its progression is feasible. Early enzymatic alterations of LM depict a catabolic state, rendering LM prone to futile substrate metabolism. A combined RAS-/NEP-inhibition ameliorates cardiac-induced myopathy independent of systolic function, which could be linked to stabilised natriuretic peptide/cGMP/PGC-1α signalling

Less major bleeding and higher hemoglobin after left atrial appendage closure in high‐risk patients: Data from a long‐term, longitudinal, two‐center observational study

Background Left atrial appendage closure (LAAC) is a mechanical alternative for stroke prevention in patients at risk who cannot tolerate oral anticoagulation (OAC). Hypothesis Our hypothesis was that the reduction of anticoagulation following LAAC results in a decrease of bleeding events and a rise in serum hemoglobin in a high-risk collective of patients with atrial fibrillation (AF). Methods Bleeding events, use of erythrocyte concentrates, anticoagulation, embolic events, and serum hemoglobin levels before and following LAAC were compared over more than 4 years. Results Seventy-five patients (CHA₂DS₂-VASc score 4.4 ± 1.7, HAS-BLED score 4.6 ± 1.1) were analyzed. Before LAAC (observation period 1.8 ± 1.8 years), 67 patients experienced 1.8 ± 1.4 bleeding events (0.9 ± 1.3 major) per year resulting in 0.7 ± 1.3 transfusions per year. After LAAC (2.6 ± 2.0 years), 26 patients (p < .0001 vs. before) had 0.6 ± 2.1 bleeding events (p < .0001), 0.2 ± 0.6 major bleedings (p < .0001) and received 0.6 ± 1.9 transfusions per year (p = .671). Fourteen patients had stroke before and 3 after LAAC (p = .008). Serum hemoglobin increased from initially 9.9 ± 3.0 to 11.9 ± 2.3 g/dL until the end of follow-up (p = .0005). Adverse embolic events did not differ before and after LAAC in our collective. Conclusion In this clinical relevant cohort of AF patients with high risk for stroke and intolerance to OAC, we show that LAAC was able to reduce the rate of stroke and bleeding events, which translated into a rising serum hemoglobin concentration

N-acetyl-b-D-glucosaminidase: A potential cardiorenal biomarker with a relevant impact on ICD shock therapies and mortality

Aims Chronic heart failure may lead to chronic kidney disease. Previous studies suggest tubular markers N-acetyl-b-D-glucosaminidase (NAG) and Kidney-injury-molecule-1 (KIM-1) as potential markers for the cardiorenal syndrome (CRS). The prognostic value of NAG and KIM-1 regarding implantable cardioverter defibrillator (ICD) shock therapies is unknown. Methods We included 314 patients with an ICD and collected plasma and urine samples. Urine-values of NAG and KIM-1 got related to urinary creatinine. Outcomes of interest were sustained adequate shock therapies and a combined endpoint of all-cause mortality, rehospitalisation due to congestive heart failure and adequate shock therapies. Follow up time was 32 months (IQR 6-35 months). Results KIM-1 and NAG were positively correlated with NT-proBNP (KIM-1:r= .34,P < .001; NAG:r= .47,P < .001). NAG was significantly elevated in patients with primary prevention compared with secondary prevention ICD indication (P= .003). According to Kaplan Meier analysis, NAG as well as NT-proBNP were significant predictors for adequate ICD shock therapies and for the combined endpoint (eachP < .001). Elevated KIM-1 showed no significant differences (eachP= n.s.). In multivariate cox regression analysis, NAG as well as NT-proBNP were both independent predictors for adequate ICD shock therapies as well as the combined endpoint, beside ejection fraction <35% (eachP < .05). Diabetes, primary prevention ICD indication, coronary artery disease, eGFR and age were no significant predictors for both endpoints (eachP= n.s.). Conclusion Similar to NT-proBNP, NAG showed promising value for overall prognostication in ICD patients. Especially, NAG seems to incorporate an additional prognostic value regarding occurrence of ICD shock therapies

MR-IMPACT II: Magnetic Resonance Imaging for Myocardial Perfusion Assessment in Coronary artery disease Trial: perfusion-cardiac magnetic resonance vs. single-photon emission computed tomography for the detection of coronary artery disease: a comparative multicentre, multivendor trial

Aims Perfusion-cardiac magnetic resonance (CMR) has emerged as a potential alternative to single-photon emission computed tomography (SPECT) to assess myocardial ischaemia non-invasively. The goal was to compare the diagnostic performance of perfusion-CMR and SPECT for the detection of coronary artery disease (CAD) using conventional X-ray coronary angiography (CXA) as the reference standard. Methods and results In this multivendor trial, 533 patients, eligible for CXA or SPECT, were enrolled in 33 centres (USA and Europe) with 515 patients receiving MR contrast medium. Single-photon emission computed tomography and CXA were performed within 4 weeks before or after CMR in all patients. The prevalence of CAD in the sample was 49%. Drop-out rates for CMR and SPECT were 5.6 and 3.7%, respectively (P = 0.21). The primary endpoint was non-inferiority of CMR vs. SPECT for both sensitivity and specificity for the detection of CAD. Readers were blinded vs. clinical data, CXA, and imaging results. As a secondary endpoint, the safety profile of the CMR examination was evaluated. For CMR and SPECT, the sensitivity scores were 0.67 and 0.59, respectively, with the lower confidence level for the difference of +0.02, indicating superiority of CMR over SPECT. The specificity scores for CMR and SPECT were 0.61 and 0.72, respectively (lower confidence level for the difference: −0.17), indicating inferiority of CMR vs. SPECT. No severe adverse events occurred in the 515 patients. Conclusion In this large multicentre, multivendor study, the sensitivity of perfusion-CMR to detect CAD was superior to SPECT, while its specificity was inferior to SPECT. Cardiac magnetic resonance is a safe alternative to SPECT to detect perfusion deficits in CA

Incremental value of high-sensitive troponin T in addition to the revised cardiac index for peri-operative risk stratification in non-cardiac surgery

Aims We aimed to evaluate the incremental value of high-sensitive troponin T (hsTnT) for risk prediction prior to non-cardiac surgery in comparison with the established revised cardiac index. Methods and results In this prospective, international multicentre observational study, 979 patients prior to non-cardiac surgery were enrolled. The endpoints were in-hospital mortality, the combination of death, acute myocardial infarction, cardiac arrest, cardio-pulmonary resuscitation, and acute decompensated heart failure. Twenty-five patients (2.6%) deceased and 36 (3.7%) of the patients experienced the combined endpoint. Cardiac markers were elevated in those patients who died when compared with survivors (hsTnT: 21 ng/L vs. 7 ng/L; P < 0.001; NT-proBNP: 576 pg/mL vs. 166 pg/mL; P < 0.001). Applying a cut-off for hsTnT of 14 ng/L and for NT-proBNP of 300 pg/mL, those patients with elevated hsTnT had a mortality of 6.9 vs. 1.2% (P < 0.001) and with elevated NT-proBNP 4.8 vs. 1.4% (P = 0.002). The highest AUC of the ROC curve was found for hsTnT as a predictor for mortality of 0.809. In a multivariate Cox regression analyses, hsTnT was the strongest independent predictor for the combined endpoint [HR 2.6 (95% CI: 1.3-5.3); P = 0.01]. Conclusion High-sensitive troponin T provides strong prognostic information in patients undergoing non-cardiac surgery incremental to the widely accepted revised cardiac inde

Eplerenone prevents salt-induced vascular stiffness in Zucker diabetic fatty rats: a preliminary report

Background Aldosterone levels are elevated in a rat model of type 2 diabetes mellitus, the Zucker Diabetic fatty rat (ZDF). Moreover blood pressure in ZDF rats is salt-sensitive. The aim of this study was to examine the effect of the aldosterone antagonist eplerenone on structural and mechanical properties of resistance arteries of ZDF-rats on normal and high-salt diet. Methods After the development of diabetes, ZDF animals were fed either a normal salt diet (0.28%) or a high-salt diet (5.5%) starting at an age of 15 weeks. ZDF rats on high-salt diet were randomly assigned to eplerenone (100 mg/kg per day, in food) (ZDF+S+E), hydralazine (25 mg/kg per day) (ZDF+S+H), or no treatment (ZDF+S). Rats on normal salt-diet were assigned to eplerenone (ZDF+E) or no treatment (ZDF). Normoglycemic Zucker lean rats were also divided into two groups receiving normal (ZL) or high-salt diet (ZL+S) serving as controls. Systolic blood pressure was measured by tail cuff method. The experiment was terminated at an age of 25 weeks. Mesenteric resistance arteries were studied on a pressurized myograph. Specifically, vascular hypertrophy (media-to-lumen ratio) and vascular stiffness (strain and stress) were analyzed. After pressurized fixation histological analysis of collagen and elastin content was performed. Results Blood pressure was significantly higher in salt-loaded ZDF compared to ZDF. Eplerenone and hydralazine prevented this rise similarily, however, significance niveau was missed. Media-to-lumen ratio of mesenteric resistance arteries was significantly increased in ZDF+S when compared to ZDF and ZL. Both, eplerenone and hydralazine prevented salt-induced vascular hypertrophy. The strain curve of arteries of salt-loaded ZDF rats was significantly lower when compared to ZL and when compared to ZDF+S+E, but was not different compared to ZDF+S+H. Eplerenone, but not hydralazine shifted the strain-stress curve to the right indicating a vascular wall composition with less resistant components. This indicates increased vascular stiffness in salt-loaded ZDF rats, which could be prevented by eplerenone but not by hydralazine. Collagen content was increased in ZL and ZDF rats on high-salt diet. Eplerenone and hydralazine prevented the increase of collagen content. There was no difference in elastin content. Conclusion Eplerenone and hydralazine prevented increased media-to-lumen ratio in salt-loaded ZDF-rats, indicating a regression of vascular hypertrophy, which is likely mediated by the blood pressure lowering-effect. Eplerenone has additionally the potential to prevent increased vascular stiffness in salt-loaded ZDF-rats. This suggests an effect of the specific aldosterone antagonist on adverse vascular wall remodelling

Effects of percutaneous coronary intervention on dyspnea in stable coronary artery disease

Background Dyspnea is a frequent symptom in patients with stable coronary artery disease (CAD) and is recognized as a possible angina equivalent. Objectives This study was to assess the impact of percutaneous coronary intervention (PCI) on dyspnea, quality of life, and angina pectoris in patients with stable CAD. Methods The prospective, multi-center PLA-pCi-EBO-pilot trial included 144 patients with symptomatic stable CAD and successful PCI. The prespecified endpoints angina pectoris (Seattle Angina Questionnaire–SAQ) and dyspnea (NYHA scale) were assessed 6 months after PCI. Predictors for symptomatic improvement were assessed with uni- and multivariable logistic regression analyses. Results Patients with concomitant dyspnea had worse SAQ physical limitation scores at baseline (49.5 ± 21.0 vs 58.9 ± 22.0, p = 0.013) but showed no difference for angina frequency or quality of life. Overall, symptomatic burden of angina pectoris and dyspnea was alleviated by PCI. However, patients with concomitant dyspnea had markedly worse scores for physical limitation (78.9 ± 25.0 vs 94.3 ± 10.6, p < 0.001), angina frequency (77.9 ± 22.8 vs 91.1 ± 12.4, p < 0.001), and quality of life (69.4 ± 24.1 vs 82.5 ± 14.4, p < 0.001) after PCI. The prevalence of dyspnea (NYHA class ≥ 2) declined from 73% before PCI to 54%. Of 95 initially dyspneic patients, 57 (60%) improved at least one NYHA class 6 months after PCI. In a multivariable logistic regression analysis, “atypical angina pectoris” was associated with improved NYHA class, whereas “diabetes mellitus” had a negative association. Conclusion PCI effectively reduced dyspnea, which is a frequent and demanding symptom in patients with CAD. The German Clinical Trials Register registration number is DRKS0001752 (www.drks.de)

Natriuretic peptides and integrated risk assessment for cardiovascular disease. an individual-participant-data meta-analysis

BACKGROUND: Guidelines for primary prevention of cardiovascular diseases focus on prediction of coronary heart disease and stroke. We assessed whether or not measurement of N-terminal-pro-B-type natriuretic peptide (NT-proBNP) concentration could enable a more integrated approach than at present by predicting heart failure and enhancing coronary heart disease and stroke risk assessment. METHODS: In this individual-participant-data meta-analysis, we generated and harmonised individual-participant data from relevant prospective studies via both de-novo NT-proBNP concentration measurement of stored samples and collection of data from studies identified through a systematic search of the literature (PubMed, Scientific Citation Index Expanded, and Embase) for articles published up to Sept 4, 2014, using search terms related to natriuretic peptide family members and the primary outcomes, with no language restrictions. We calculated risk ratios and measures of risk discrimination and reclassification across predicted 10 year risk categories (ie, <5%, 5% to <7·5%, and ≥7·5%), adding assessment of NT-proBNP concentration to that of conventional risk factors (ie, age, sex, smoking status, systolic blood pressure, history of diabetes, and total and HDL cholesterol concentrations). Primary outcomes were the combination of coronary heart disease and stroke, and the combination of coronary heart disease, stroke, and heart failure. FINDINGS: We recorded 5500 coronary heart disease, 4002 stroke, and 2212 heart failure outcomes among 95 617 participants without a history of cardiovascular disease in 40 prospective studies. Risk ratios (for a comparison of the top third vs bottom third of NT-proBNP concentrations, adjusted for conventional risk factors) were 1·76 (95% CI 1·56-1·98) for the combination of coronary heart disease and stroke and 2·00 (1·77-2·26) for the combination of coronary heart disease, stroke, and heart failure. Addition of information about NT-proBNP concentration to a model containing conventional risk factors was associated with a C-index increase of 0·012 (0·010-0·014) and a net reclassification improvement of 0·027 (0·019-0·036) for the combination of coronary heart disease and stroke and a C-index increase of 0·019 (0·016-0·022) and a net reclassification improvement of 0·028 (0·019-0·038) for the combination of coronary heart disease, stroke, and heart failure. INTERPRETATION: In people without baseline cardiovascular disease, NT-proBNP concentration assessment strongly predicted first-onset heart failure and augmented coronary heart disease and stroke prediction, suggesting that NT-proBNP concentration assessment could be used to integrate heart failure into cardiovascular disease primary prevention