Right Heart Structure and Function after Electrical Cardioversion for Atrial Fibrillation.

INTRODUCTION: Atrial fibrillation (AF) adversely impacts right ventricular (RV) and right atrial (RA) structure and function. There are limited data on these changes after electrical cardioversion (ECV) and the relative contribution of heart rate to evaluate the immediate (1-2 h) and short-term (4-6 weeks) changes in right cardiac chamber dimensions and RV function after ECV in patients with persistent AF. METHODS: Right cardiac chamber dimensions and RV function were measured in 64 patients using transthoracic echocardiography 1-2 h before, immediately after, and 4-6 weeks after ECV. Associations between changes in right-heart measures and rhythm status at follow-up were assessed using linear regression models. RESULTS: For patients who remained in sinus rhythm 4-6 weeks after ECV (n = 48), median fractional area change (FAC) at baseline, immediately after ECV, and 4-6 weeks after ECV were 39 (Q1:35, Q3:42) %, 42 (Q1:39, Q3:46) %, 46 (Q1:43, Q3:49) % (p < 0.01); median tricuspid annular plane systolic excursion (TAPSE) values at the same time points were 18 (Q1:17, Q3:20) mm, 20 (Q1:18, Q3:23) mm, and 24 (Q1:22, Q3:26) mm (p < 0.01), respectively. There was no significant difference in RV end systolic area and RA volume index before and after ECV. However, RV end systolic area and RA volume index decreased significantly after 4-6 weeks from a median of 10 (Q1:8, Q3:13) cm2 to 8 (Q1:7, Q3:10) cm2 (p < 0.01), and from a median of 30 (Q1:24, Q3:36) mL/m2 to 24 (Q1:20, Q3:27) mL/m2 (p < 0.01). Changes in TAPSE were significantly associated with sinus rhythm at follow-up (p = 0.027), changes in FAC showed a strong trend to association with sinus rhythm (p = 0.053), and this was not true for RA measures (p = 0.64). CONCLUSIONS: Among AF patients who remained in sinus rhythm after ECV, RV function improved immediately after ECV with further improvement at 4-6 weeks following sinus rhythm restoration.

Ultrasound Molecular Imaging of Atherosclerosis With Nanobodies: Translatable Microbubble Targeting Murine and Human VCAM (Vascular Cell Adhesion Molecule) 1.

OBJECTIVE: Contrast-enhanced ultrasound molecular imaging (CEUMI) of endothelial expression of VCAM (vascular cell adhesion molecule)-1 could improve risk stratification for atherosclerosis. The microbubble contrast agents developed for preclinical studies are not suitable for clinical translation. Our aim was to characterize and validate a microbubble contrast agent using a clinically translatable single-variable domain immunoglobulin (nanobody) ligand. Approach and Results: Microbubble with a nanobody targeting VCAM-1 (MBcAbVcam1-5) and microbubble with a control nanobody (MBVHH2E7) were prepared and characterized in vitro. Attachment efficiency to VCAM-1 under continuous and pulsatile flow was investigated using activated murine endothelial cells. In vivo CEUMI of the aorta was performed in atherosclerotic double knockout and wild-type mice after injection of MBcAbVcam1-5 and MBVHH2E7. Ex vivo CEUMI of human endarterectomy specimens was performed in a closed-loop circulation model. The surface density of the nanobody ligand was 3.5×105 per microbubble. Compared with MBVHH2E7, MBcAbVcam1-5 showed increased attachment under continuous flow with increasing shear stress of 1-8 dynes/cm2 while under pulsatile flow attachment occurred at higher shear stress. CEUMI in double knockout mice showed signal enhancement for MBcAbVcam1-5 in early (P=0.0003 versus MBVHH2E7) and late atherosclerosis (P=0.007 versus MBVHH2E7); in wild-type mice, there were no differences between MBcAbVcam1-5 and MBVHH2E7. CEUMI in human endarterectomy specimens showed a 100% increase in signal for MBcAbVcam1-5versus MBVHH2E7 (20.6±27.7 versus 9.6±14.7, P=0.0156). CONCLUSIONS: CEUMI of the expression of VCAM-1 is feasible in murine models of atherosclerosis and on human tissue using a clinically translatable microbubble bearing a VCAM-1 targeted nanobody.

Von Willebrand Factor Interacts with Surface-Bound C1q and Induces Platelet Rolling.

Premature atherosclerosis and thrombotic complications are major causes of morbidity and mortality in patients with systemic lupus erythematosus (SLE). However, the high incidence of these complications cannot be explained by traditional risk factors alone, suggesting direct effects of an activated immune system on hemostasis. The unexpected nucleotide sequence homology between SLE patient-derived autoantibodies against complement C1q (Fab anti-C1q) and von Willebrand factor (VWF) led us to investigate a potential interaction between the complement and hemostatic systems on the level of initiating molecules. VWF was found to bind to surface-bound C1q under static conditions. The binding could specifically be inhibited by Fab anti-C1q and C1q-derived peptides. Under shear stress the C1q-VWF interaction was enhanced, resembling the binding of VWF to collagen I. Additionally, we could show that C1q-VWF complexes induced platelet rolling and firm adhesion. Furthermore, we observed VWF binding to C1q-positive apoptotic microparticles and cholesterol crystals, as well as increased VWF deposition in C1q-positive glomeruli of SLE patients compared with control nephropathy. We show, to our knowledge for the first time, binding of VWF to C1q and thus a direct interaction between starter molecules of hemostasis and the classical pathway of complement. This direct interaction might contribute to the pathogenic mechanisms in complement-mediated, inflammatory diseases.

Conventional versus 3-D Echocardiography to Predict Arrhythmia Recurrence After Atrial Fibrillation Ablation.

BACKGROUND: Arrhythmia recurrence after atrial fibrillation (AF) ablation remains high and requires repeat interventions in a substantial number of patients. We assessed the value of conventional and 3-D echocardiography to predict AF recurrence. METHODS AND RESULTS: Consecutive patients undergoing AF ablation by means of pulmonary vein isolation were included in a prospective registry. Echocardiograms were obtained prior to the ablation procedure, and analyzed offline in a standardized manner, including 3-D left atrial (LA) volumetry and determination of LA function and sphericity. The primary endpoint, AF recurrence (>30 seconds) between 3 to 12 months after AF ablation, was independently adjudicated. We included 276 patients (73% male, mean age 59.9 ± 9.9 years). Paroxysmal and persistent AF were present in 178 (64%) and 98 (36%) patients, respectively. Mean left ventricular ejection fraction and indexed LA volume in 3-D (LAVI) were 52 ± 12% and 42 ± 13 mL/m2 , respectively. AF recurrence was observed in 110 (40%) patients after a single procedure. Median (interquartile range) time to AF recurrence was 123 (92; 236) days. In multivariable Cox regression models, the only predictors for AF recurrence were the minimal, maximal, and indexed 3-D LA volumes, P = 0.024, P = 0.016, and P = 0.014, respectively. Quartile specific analysis of 3-D LAVI showed an HR of 1.885 (95%CI 1.066-3.334; P for trend = 0.015) for the highest compared to the lowest quartile. CONCLUSION: Our results show the important role of LA volume for the long-term freedom from arrhythmia after AF ablation. These data also highlight the potential of 3-D echocardiography in this context and may facilitate patient selection for AF ablation.

Isolated double-orifice mitral valve: a case report.

BACKGROUND: Double-orifice mitral valve is an extremely rare cardiac anomaly possibly originating from insufficient endocardial fusion in embryogenesis. Severe concomitant cardiac anomalies and malfunction of the valve usually lead to an early diagnosis in childhood. Therefore the prevalence of isolated double-orifice mitral valve in adulthood is not known. CASE PRESENTATION: We present the case of a 63 years old, female Caucasian patient with isolated double-orifice mitral valve diagnosed in routine echocardiographic evaluation after chemotherapy presenting without clinical symptoms. CONCLUSION: Trans-thoracic echocardiography is a suitable modality to diagnose and further assess anatomical and functional properties of the anomaly. In the presence of double-orifice mitral valve concomitant cardiac anomalies and valvular stenosis or regurgitation must be excluded. If an isolated double-orifice mitral valve with no functional abnormalities is present, no further follow-up is necessary.

Transapical Transcatheter Aortic Valve Implantation Using the JenaValve: A One-Year Follow-up.

OBJECTIVE: Since the first transcatheter aortic valve implantation (TAVI) in 2002, TAVI technique has gained an increasing popularity especially in high-risk patients. In this study, we present the first echocardiographic midterm outcome with the second-generation transapical JenaValve TAVI system (JenaValve Technology GmbH, Munich, Germany) in patients with aortic stenosis (AS). METHODS: Between November 2011 and November 2012, a total of 28 patients received transapical TAVI using the JenaValve. Primary endpoint was a combined efficacy endpoint after 1 year, which included all-cause mortality after more than 30 days, failure of current therapy for AS requiring hospitalization for symptoms of valve-related cardiac decompensation or prosthetic heart valve dysfunction. Moreover, we analyzed secondary endpoints after 3 and 12 months including cardiovascular mortality; major stroke; and life-threatening, disabling, or major bleeding. Mean echocardiographic follow-up was 471.35 ± 102.72 days. RESULTS: Mean age was 80.43 ± 6.03 years and EuroSCORE II was 8.80 ± 7.21%. Successful implantation was accomplished in 100% (n = 28). Median transvalvular aortic mean pressure gradient was 44.5 mm Hg (interquartile range [IQR]: 34.5; 55.5) preoperatively, 12 mm Hg (IQR: 9; 16) postoperatively, and 11 mm Hg (IQR: 8; 16) after 1 year. After 12 months, no paravalvular leakage was seen in 52.38% of the patients and grade 1 paravalvular leakage was seen in 47.62% of the patients. There was no grade 2 or 3 leakage detected. Stroke, valve thrombosis or dislocation, myocardial infarction, or bleeding was also not observed. However, criteria for the combined efficacy endpoint after 1 year were met in five patients (17.86%). Thirty-day mortality was 14.29% (n = 4) and all-cause mortality after 1 year was 21.43% (n = 6). CONCLUSION: The JenaValve transapical TAVI system is a safe and feasible procedure with low peri- and postoperative complications and convincing midterm performance of the prosthesis.

Ultrasound imaging for risk assessment in atherosclerosis.

Atherosclerosis and its consequences like acute myocardial infarction or stroke are highly prevalent in western countries, and the incidence of atherosclerosis is rapidly rising in developing countries. Atherosclerosis is a disease that progresses silently over several decades before it results in the aforementioned clinical consequences. Therefore, there is a clinical need for imaging methods to detect the early stages of atherosclerosis and to better risk stratify patients. In this review, we will discuss how ultrasound imaging can contribute to the detection and risk stratification of atherosclerosis by (a) detecting advanced and early plaques; (b) evaluating the biomechanical consequences of atherosclerosis in the vessel wall;

Interaction between pulmonary hypertension and diastolic dysfunction in an elderly heart failure population.

BACKGROUND: Pulmonary hypertension due to left heart disease is very common. Our aim was to investigate the relationship of the severity of left ventricular diastolic dysfunction with precapillary and postcapillary pulmonary hypertension (PH) in an elderly heart failure (HF) population. METHODS AND RESULTS: A post hoc analysis of the Trial of Intensified Medical Therapy in Elderly Patients With Congestive Heart Failure data was done. Baseline transthoracic echocardiography was used to categorize diastolic function, estimate pulmonary artery pressure and pulmonary capillary wedge pressure, and calculate the transpulmonary pressure gradient (TPG). Among 392 HF patients, PH was present in 31% of patients with grade 1, in 37% of patients with grade 2, and in 65% of patients with grade 3 diastolic dysfunction; 54% of all HF patients with PH had a TPG >12 mm Hg, suggesting not only a postcapillary but also an additional precapillary component of PH. Survival was not related to the severity of diastolic dysfunction, but was worse in patients with PH (hazard ratio 1.63, 95% confidence interval 1.07-2.51; P = .024). CONCLUSIONS: Our data indicate that HF patients with even mild diastolic dysfunction often have PH. Echocardiographic assessment suggest that the presence of PH might not simply be due to increased PCWP, but in part due to a precapillary component.

Molecular imaging reveals rapid reduction of endothelial activation in early atherosclerosis with apocynin independent of antioxidative properties.

OBJECTIVE: Antioxidative drugs continue to be developed for the treatment of atherosclerosis. Apocynin is an nicotinamide adenine dinucleotide phosphate oxidase inhibitor with anti-inflammatory properties. We used contrast-enhanced ultrasound molecular imaging to assess whether short-term apocynin therapy in atherosclerosis reduces vascular oxidative stress and endothelial activation APPROACH AND RESULTS: Genetically modified mice with early atherosclerosis were studied at baseline and after 7 days of therapy with apocynin (4 mg/kg per day IP) or saline. Contrast-enhanced ultrasound molecular imaging of the aorta was performed with microbubbles targeted to vascular cell adhesion molecule 1 (VCAM-1; MB(V)), to platelet glycoprotein Ibα (MB(Pl)), and control microbubbles (MB(Ctr)). Aortic vascular cell adhesion molecule 1 was measured using Western blot. Aortic reactive oxygen species generation was measured using a lucigenin assay. Hydroethidine oxidation was used to assess aortic superoxide generation. Baseline signal for MBV (1.3 ± 0.3 AU) and MB(Pl )(1.5 ± 0.5 AU) was higher than for MBCtr (0.5 ± 0.2 AU; P<0.01). In saline-treated animals, signal did not significantly change for any microbubble agent, whereas short-term apocynin significantly (P<0.05) reduced vascular cell adhesion molecule 1 and platelet signal (MBV: 0.3 ± 0.1; MBPl: 0.4 ± 0.1; MBCtr: 0.3 ± 0.2 AU; P=0.6 between agents). Apocynin reduced aortic vascular cell adhesion molecule 1 expression by 50% (P<0.05). However, apocynin therapy did not reduce reactive oxygen species content, superoxide generation, or macrophage content. CONCLUSIONS: Short-term treatment with apocynin in atherosclerosis reduces endothelial cell adhesion molecule expression. This change in endothelial phenotype can be detected by molecular imaging before any measurable decrease in macrophage content and is not associated with a detectable change in oxidative burden.

Propionibacterium acnes prosthetic valve endocarditis with abscess formation: a case report.

BACKGROUND: Endocarditis due to Propionibacterium acnes is a rare disease. Scant data on treatment of these infections is available and is based on case reports only. If the disease is complicated by abscess formation, surgical intervention combined with an antibiotic therapy might improve clinical outcome. In some cases, cardiac surgeons are reluctant to perform surgery, since they consider the intervention as high risk. Therefore, a conservative therapy is required, with little, if any evidence to choose the optimal antibiotic. We report the first case of a successfully treated patient with P. acnes prosthetic valve endocarditis without surgery. CASE PRESENTATION: We report the case of a 29-year-old patient with a prosthetic valve endocarditis and composite graft infection with abscess formation of the left ventricular outflow tract due to P. acnes. Since cardiac surgery was considered as high risk, the patient was treated intravenously with ceftriaxone 2 g qd and rifampin 600 mg bid for 7 weeks and was switched to an oral therapy with levofloxacin 500 mg bid and rifampin 600 mg bid for an additional 6 months. Two sets of blood cultures collected six weeks after completion of treatment remained negative. The patient is considered to be cured based on absence of clinical signs and symptoms, normal laboratory parameters, negative radiology scans and negative blood cultures, determined at site visits over two years after completion of treatment. CONCLUSION: To our knowledge, this is the first successfully managed patient with P. acnes prosthetic valve endocarditis with abscess formation of the left ventricular outflow tract who was treated with antibiotics alone without a surgical intervention. A six month treatment with a rifampin and levofloxacin combination was chosen, based on the excellent activity against stationary-phase and adherent bacteria.

Implementing focused echocardiography and AI-supported analysis in a population-based survey in Lesotho: implications for community-based cardiovascular disease care models.

In settings where access to expert echocardiography is limited, focused echocardiography, combined with artificial intelligence (AI)-supported analysis, may improve diagnosis and monitoring of left ventricular hypertrophy (LVH). Sixteen nurses/nurse-assistants without prior experience in echocardiography underwent a 2-day hands-on intensive training to learn how to assess parasternal long axis views (PLAX) using an inexpensive hand-held ultrasound device in Lesotho, Southern Africa. Loops were stored on a cloud-drive, analyzed using deep learning algorithms at the University Hospital Basel, and afterwards confirmed by a board-certified cardiologist. The nurses/nurse-assistants obtained 756 echocardiograms. Of the 754 uploaded image files, 628 (83.3%) were evaluable by deep learning algorithms. Of those, results of 514/628 (81.9%) were confirmed by a cardiologist. Of the 126 not evaluable by the AI algorithm, 46 (36.5%) were manually evaluable. Overall, 660 (87.5%) uploaded files were evaluable and confirmed. Following short-term training of nursing cadres, a high proportion of obtained PLAX was evaluable using AI-supported analysis. This could be a basis for AI- and telemedical support in hard-to-reach areas with minimal resources.

Diagnosis of acute aortic syndromes with ultrasound and d-dimer: the PROFUNDUS study.

BACKGROUND: In patients complaining common symptoms such as chest/abdominal/back pain or syncope, acute aortic syndromes (AAS) are rare underlying causes. AAS diagnosis requires urgent advanced aortic imaging (AAI), mostly computed tomography angiography. However, patient selection for AAI poses conflicting risks of misdiagnosis and overtesting. OBJECTIVES: We assessed the safety and efficiency of a diagnostic protocol integrating clinical data with point-of-care ultrasound (POCUS) and d-dimer (single/age-adjusted cutoff), to select patients for AAI. METHODS: This prospective study involved 12 Emergency Departments from 5 countries. POCUS findings were integrated with a guideline-compliant clinical score, to define the integrated pre-test probability (iPTP) of AAS. If iPTP was high, urgent AAI was requested. If iPTP was low and d-dimer was negative, AAS was ruled out. Patients were followed for 30 days, to adjudicate outcomes. RESULTS: Within 1979 enrolled patients, 176 (9 %) had an AAS. POCUS led to net reclassification improvement of 20 % (24 %/-4 % for events/non-events, P < 0.001) over clinical score alone. Median time to AAS diagnosis was 60 min if POCUS was positive vs 118 if negative (P = 0.042). Within 941 patients satisfying rule-out criteria, the 30-day incidence of AAS was 0 % (95 % CI, 0-0.41 %); without POCUS, 2 AAS were potentially missed. Protocol rule-out efficiency was 48 % (95 % CI, 46-50 %) and AAI was averted in 41 % of patients. Using age-adjusted d-dimer, rule-out efficiency was 54 % (difference 6 %, 95 % CI, 4-9 %, vs standard cutoff). CONCLUSIONS: The integrated algorithm allowed rapid triage of high-probability patients, while providing safe and efficient rule-out of AAS. Age-adjusted d-dimer maximized efficiency. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT04430400.

Cardiovascular management of cancer patients with chemotherapy-associated left ventricular systolic dysfunction in real-world clinical practice.

BACKGROUND: Chemotherapy-induced left ventricular systolic dysfunction (LVSD) may limit survival in cancer patients and therefore should be treated timely with appropriate heart failure medication. This study aimed to evaluate quality of cardiac care in cancer patients with documented chemotherapy-induced LVSD in real-world clinical practice. METHODS: Using an institutional echo database, we screened 1,520 cancer patients for first documentation of chemotherapy-associated LVSD, defined as left ventricular ejection fraction (LVEF) ≤45%. Hospital charts of all 63 patients meeting inclusion criteria were reviewed regarding patient characteristics and frequency of heart failure medication prescription. RESULTS: Patients were 61 (interquartile range [IQR], 50-70) years old, mostly symptomatic, and had an average LVEF of 34 ± 8%. Most patients received anthracyclines (73%) and/or alkylating agents (73%) as part of their chemotherapeutic regimen. Median time from cancer diagnosis to first documentation of LVSD was 2.2 (0.7-5.2) years. Fewer than two-thirds of patients received guideline-recommended heart failure medication, and only one-half of patients received cardiology consult. Cardiology consultation was associated with a significantly higher frequency of heart failure medication prescription (100% vs. 52% for angiotensin-converting enzyme inhibitor or angiotensin receptor blocker (P < .0001); 94% vs. 41% for beta-blocker (P < .0001) and better survival (71% vs. 41%; P < .05). CONCLUSIONS: Chemotherapy-associated LVSD is insufficiently treated in cancer patients. Cardiology consultation improves rates of heart failure medication and therefore should be advocated in all patients with chemotherapy-induced LVSD.

Complement C1q and von Willebrand factor interaction in atherosclerosis of human carotid artery.

Atherosclerosis is an inflammatory disease of the vessel wall, with cholesterol crystal (CC) deposition being a hallmark of the disease. As evidence for a cross-talk between complement activation and hemostasis on CC surfaces has been limited to in vitro data, the aim of this study was to demonstrate the presence of C1q-vWF complexes in human atherosclerosis ex vivo. We used immunofluorescence staining and a proximity ligation assay (PLA, Duolink®) to examine the presence, localization, and co-localization of C1q and vWF in frozen sections of human carotid arteries with atherosclerosis or without atherosclerotic changes as well as material from thrombendarteriectomy. We observed significantly higher levels of C1q and vWF in healthy tissue compared to diseased material and greater co-localization in the PLA in healthy samples than in diseased samples. In diseased samples, fluorescence signals were highest in locations encompassing atheroma and foam cells. While there was overall reduced signal in areas with CCs, the staining was spotty, and there was evidence of co-localization on individual CCs. Thus, we demonstrate the presence of C1q-vWF complexes in human carotid arteries ex vivo, which was most abundant in healthy endothelial and subendothelial space and reduced in diseased tissue. C1q-vWF interaction can also be demonstrated on the CC surface.

Renal dysfunction and outcome in left ventricular non-compaction.

BACKGROUND: While renal function has been observed to inversely correlate with clinical outcome in other cardiomyopathies, its prognostic significance in patients with left ventricular non-compaction cardiomyopathy (LVNC) has not been investigated. The aim of this study was to determine the prognostic value of renal function in LVNC patients. METHODS: Patients with isolated LVNC as diagnosed by echocardiography and/or magnetic resonance imaging in 4 Swiss centers were retrospectively analyzed for this study. Values for creatinine, urea, and estimated glomerular filtration rate (eGFR) as assessed by the CKD-EPI 2009 formula were collected and analyzed by a Cox regression model for the occurrence of a composite endpoint (death or heart transplantation). RESULTS: During the median observation period of 7.4 years 23 patients reached the endpoint. The ageand gender-corrected hazard ratios (HR) for death or heart transplantation were: 1.9 (95% confidence interval [CI] 1.4-2.6) for each increase over baseline creatinine level of 30 µmol/L (p < 0.001), 1.6 (95% CI 1.2-2.2) for each increase over baseline urea level of 5 mmol/L (p = 0.004), and 3.6 (95% CI 1.9-6.9) for each decrease below baseline eGFR level of 30 mL/min (p ≤ 0.001). The HR (log2) for every doubling of creatinine was 7.7 (95% CI 3-19.8; p < 0.001), for every doubling of urea 2.5 (95% CI 1.5-4.3; p < 0.001), and for every bisection of eGFR 5.3 (95% CI 2.4-11.6; p < 0.001). CONCLUSIONS: This study provides evidence that in patients with LVNC impairment in renal function is associated with an increased risk of death and heart transplantation suggesting that kidney function assessment should be standard in risk assessment of LVNC patients.

Liraglutide Lowers Endothelial Vascular Cell Adhesion Molecule-1 in Murine Atherosclerosis Independent of Glucose Levels.

The authors determined the effect of the GLP-1 receptor agonist liraglutide on endothelial surface expression of vascular cell adhesion molecule (VCAM)-1 in murine apolipoprotein E knockout atherosclerosis. Contrast-enhanced ultrasound molecular imaging using microbubbles targeted to VCAM-1 and control microbubbles showed a 3-fold increase in endothelial surface VCAM-1 signal in vehicle-treated animals, whereas in the liraglutide-treated animals the signal ratio remained around 1 throughout the study. Liraglutide had no influence on low-density lipoprotein cholesterol or glycated hemoglobin, but reduced TNF-α, IL-1ß, MCP-1, and OPN. Aortic plaque lesion area and luminal VCAM-1 expression on immunohistology were reduced under liraglutide treatment.

Hypertensive Heart Disease-The Imaging Perspective.

Hypertensive heart disease (HHD) develops in response to the chronic exposure of the left ventricle and left atrium to elevated systemic blood pressure. Left ventricular structural changes include hypertrophy and interstitial fibrosis that in turn lead to functional changes including diastolic dysfunction and impaired left atrial and LV mechanical function. Ultimately, these changes can lead to heart failure with a preserved (HFpEF) or reduced (HFrEF) ejection fraction. This review will outline the clinical evaluation of a patient with hypertension and/or suspected HHD, with a particular emphasis on the role and recent advances of multimodality imaging in both diagnosis and differential diagnosis.

Echocardiographic pattern of left ventricular function recovery in tachycardia-induced cardiomyopathy patients.

AIMS: Tachycardia-induced cardiomyopathy (TCM) represents a partially reversible type of cardiomyopathy (CM) that is often underdiagnosed and cardiac chamber remodelling in TCM remains incompletely understood. We aim to explore differences in the dimensions of the left ventricle and functional recovery in patients with TCM compared with patients with other forms of CM. METHODS AND RESULTS: We identified patients with reduced ejection fraction (≤50%) and/or atrial fibrillation or flutter with a left ventricular ejection fraction that improved from baseline (≥15% in left ventricular ejection fraction at follow-up or normalization of cardiac function with at least 10% improvement). Patients were then divided into two groups: (A) TCM patients and (B) patients with other forms of CM (controls). Two hundred thirty-eight patients were included (31% female, 70 years median age), 127 patients had TCM, and 111 had other forms of CM. Patients with TCM did not significantly improve indexed left ventricular volume (LVEDVI) after treatment (60 [45, 84] mL/m2 versus 56 [45, 70] mL/m2 , P = ns) compared with controls (67 [54, 81] mL/m2 versus 52 [42, 69] mL/m2 , P < 0.001). Patients with TCM patients had significantly worse fractional shortening at baseline than controls (15.5 [12, 23] vs. 20 [13, 30], P = 0.01) and higher indexed left atrial volume (LAVI) at baseline than controls (48 [37, 58] vs. 41 [33, 51], P = 0.01) that remained dilated at follow-up (follow-up LAVI 41 [33, 52] mL/m2 ). Good predictors of TCM were: normal LVEDVI (LVEDVI < 58 mL/m2 (M) and < 52 mL/m2 (F)) (odds ratio [OR] 5.2; 95% confidence interval [CI] 2.2-13.3, P < 0.001), fractional shortening < 30% (OR 3.5; 95% CI 1.4-9.2, P = 0.009), LAVI >40 mL/m2 (OR 3.4; 95% CI 1.6-7.3, P = 0.001) and normal wall thickness left ventricle (OR 3.2; 95% CI 1.4-7.8, P = 0.008). 54% of patients with TCM demonstrated diastolic dysfunction at follow-up, without differences from controls (54% vs. 43%, P = ns). 21% of patients with TCM showed persistent heart failure symptoms at follow-up compared with 4.5% of controls, P = 0.004. CONCLUSIONS: TCM patients have a specific pattern of functional recovery with persistent remodelling of the left atria and left ventricle. Several echocardiographic parameters might help identify TCM before treatment.

Biomarkers associated with rhythm status after cardioversion in patients with atrial fibrillation.

Biomarkers may help to improve our knowledge about the complex pathophysiology of atrial fibrillation (AF). In this study we sought to identify significant changes in biomarkers and clinical measures in patients with and without AF recurrence after electrical cardioversion. We measured 21 conventional and new biomarkers before and 30 days after electrical cardioversion and assessed the associations of changes in biomarker levels with rhythm status at follow-up. Significant between-group changes were observed for bone morphogenetic protein 10 (BMP10), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and total bilirubin. Their respective changes were - 10.4%, - 62.0% and - 25.6% in patients with sinus rhythm, and 3.1%, 1.1% and - 9.4% in patients with recurrent AF, for a between-group difference of - 13.5% (95% confidence interval [CI] - 19.3% to - 7.6%; P < 0.001), - 63.1% (95% CI - 76.6% to - 49.6%; P < 0.001) and - 16.3% (95% CI - 27.9% to - 4.7%; P = 0.007). In multivariable models, the reductions of BMP10 and NT-proBNP were significantly associated with follow-up rhythm status (ß coefficient per 1 - SD decrease, - 3.85; 95% CI - 6.34 to - 1.35; P = 0.003 for BMP10 and - 5.84; 95% CI - 10.22 to - 1.47; P = 0.009 for NT-proBNP. In conclusion, changes in BMP10 und NT-proBNP levels were independently associated with rhythm status after cardioversion, suggesting that these markers may be dependent on the actual heart rhythm.

NOX1 mediates metabolic heart disease in mice and is upregulated in monocytes of humans with diastolic dysfunction.

AIMS: Microvascular inflammation plays an important role in the pathogenesis of diastolic dysfunction (DD) and metabolic heart disease. NOX1 is expressed in vascular and immune cells and has been implicated in the vascular pathology of metabolic disease. However, its contribution to metabolic heart disease is less understood. METHODS AND RESULTS: NOX1-deficient mice (KO) and male wild-type (WT) littermates were fed a high-fat high-sucrose diet (HFHS) and injected streptozotocin (75 mg/kg i.p.) or control diet (CTD) and sodium citrate. Despite similar weight gain and increase in fasting blood glucose and insulin, only WT-HFHS but not KO-HFHS mice developed concentric cardiac hypertrophy and elevated left ventricular filling pressure. This was associated with increased endothelial adhesion molecule expression, accumulation of Mac-2-, IL-1ß-, and NLRP3-positive cells and nitrosative stress in WT-HFHS but not KO-HFHS hearts. Nox1 mRNA was solidly expressed in CD45+ immune cells isolated from healthy mouse hearts but was negligible in cardiac CD31+ endothelial cells. However, in vitro, Nox1 expression increased in response to lipopolysaccharide (LPS) in endothelial cells and contributed to LPS-induced upregulation of Icam-1. Nox1 was also upregulated in mouse bone marrow-derived macrophages in response to LPS. In peripheral monocytes from age- and sex-matched symptomatic patients with and without DD, NOX1 was significantly higher in patients with DD compared to those without DD. CONCLUSIONS: NOX1 mediates endothelial activation and contributes to myocardial inflammation and remodelling in metabolic disease in mice. Given its high expression in monocytes of humans with DD, NOX1 may represent a potential target to mitigate heart disease associated with DD.